humulin-s and Diabetes-Mellitus--Type-2

Although advances in insulin therapy and delivery have been made, global evidence indicates sub-optimal glycemic management in people on insulin therapy with either type 1 diabetes (T1D) or type 2 diabetes (T2D). In this review, we discuss connected insulin pens that include tracking insulin pens (TIPs) and smart insulin pens (SIPs) and caps, as approaches to improving mean glucose or time in range while minimizing exposure to hypoglycemia or time below range (TBR) in people with diabetes (PwD) on multiple daily injection (MDI) therapy. We discuss various factors offered by SIPs that can facilitate precision insulin management, that is, delivering the right dose at the right time. These factors include the automatic recording of insulin dose size and delivery time; differentiating prime from therapy doses; active insulin tracking; dose calculators that provide individualized dosing recommendations; alerts for missed doses (ie, rapid-acting or long-acting insulin), insulin temperature, and insulin age monitoring; and integrated data reports for the clinical care team. A data-driven approach to care is critical to precision insulin management and includes helping PwD make informed choices regarding their preferred method of insulin delivery and ensuring insulin delivery technology tools are configured for their personal therapy plan. The data-driven approach involves developing a plan for ongoing collaborative use of the resulting data with their care team that may include adjusting insulin regimen and optimizing the care plan on a timely basis. We conclude with a list of practice protocols that are needed to support data-driven precision insulin management. This review includes a summary of research including various stages of connected insulin pens and caps.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Insulin, Regular, Human

Insulin treatment is an essential hormone replacement therapy for the survival of people with type 1 diabetes and is often used for treatment in type 2 diabetes, particularly as the disease progresses. Advances in insulin therapy have been made since its discovery, including production of human insulin and development of insulin analogs with improved efficacy and safety profiles. The different types of available insulin formulations allow health care professionals to personalize treatment to an individual's needs. Generally, insulin requires parenteral administration via subcutaneous injection owing to very low oral bioavailability.. This article reviews the human, technological, economical, and regulatory factors affecting the performance of insulin pens and the relationship between them. Opportunities and challenges that insulin pen injections may encounter in the future are also considered.. Insulin delivery devices, together with other factors, influence dose accuracy, convenience, and quality of life, contributing to easier medication administration with high efficacy and safety. For patients, ease of use, fast and accurate drug delivery, and painless injection are the most valuable features of an insulin injection device. For manufacturers, technological feasibility and economic viability also need to be considered when developing injection devices.. Insulin pen injectors are generally preferred over vial and syringe, although access may be limited in some health care systems. Insulin pen injectors can adapt to different insulin regimens and formulations and have the potential to acquire dosing data in real time.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin, Regular, Human; Quality of Life; Syringes

To compare the clinical efficacy and safety of glargine-U100 (Lantus/Gla-100) with glargine-U300 (Toujeo/Gla-300) in adult patients with type 2 diabetes (T2D) and type 1 diabetes (T1D).. A literature search on Gla-300/Gla-100 in diabetes management was conducted using the MEDLINE/Embase/Cochrane databases from inception to 10 January 2021. Eligible studies considered for inclusion were parallel-design, randomized controlled trials (RCTs). The Cochrane risk-of-bias tool was used to evaluate the quality of the included studies. The random-effects model was applied for interpretation of the results.. Of 5348 records screened, 592 were assessed for eligibility and 15 RCTs were considered for data extraction and meta-analysis (T2D [N = 10; n = 7082]; T1D [N = 5; n = 2222]). In patients with T1D, all safety parameters were comparable between Gla-100 and Gla-300. In T2D, statistically significant differences were observed in favour of Gla-300 over Gla-100 for nocturnal and total hypoglycaemia. For efficacy parameters, a statistically and clinically significant difference favouring Gla-100 in basal insulin dose requirement was observed for both T2D and T1D. Change in HbA1c showed a statistically but not clinically significant reduction with Gla-100 compared with Gla-300 in T1D. Statistically significant but clinically less relevant differences favoured Gla-300 for control of body weight in T1D and T2D and Gla-100 for fasting blood glucose in T2D.. Gla-100 and Gla-300 had comparable efficacy and safety profiles in both T1D and T2D populations. Gla-300 showed a lower risk of nocturnal and total hypoglycaemia, significant in insulin-experienced/exposed patients with T2D. Patients on Gla-300 required significantly more units of insulin daily than the Gla-100 group to achieve equivalent efficacy.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Regular, Human; Treatment Outcome

Alzheimer's disease (AD) is the main type of dementia and is a disease with a profound socioeconomic burden due to the lack of effective treatment. In addition to genetics and environmental factors, AD is highly associated with metabolic syndrome, defined as the combination of hypertension, hyperlipidemia, obesity and type 2 diabetes mellitus (T2DM). Among these risk factors, the connection between AD and T2DM has been deeply studied. It has been suggested that the mechanism linking both conditions is insulin resistance. Insulin is an important hormone that regulates not only peripheral energy homeostasis but also brain functions, such as cognition. Insulin desensitization, therefore, could impact normal brain function increasing the risk of developing neurodegenerative disorders in later life. Paradoxically, it has been demonstrated that decreased neuronal insulin signalling can also have a protective role in aging and protein-aggregation-associated diseases, as is the case in AD. This controversy is fed by studies focused on neuronal insulin signalling. However, the role of insulin action on other brain cell types, such as astrocytes, is still unexplored. Therefore, it is worthwhile exploring the involvement of the astrocytic insulin receptor in cognition, as well as in the onset and/or development of AD.

Topics: Alzheimer Disease; Brain; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Metabolic Syndrome; Risk Factors

The metabolic syndrome is a cluster of overlapping conditions resulting in an increased incidence of type 2 diabetes, cardiovascular disease, and cancer. In the last few decades, prevalence of the metabolic syndrome in the Western world has reached epidemic proportions and this is likely due to alterations in diet and the environment as well as decreased physical activity. This review discusses how the Western diet and lifestyle (Westernization) has played an important etiological role in the pathogenesis of the metabolic syndrome and its consequences by exerting negative effects on activity of the insulin-insulin-like growth factor-I (insulin-IGF-I) system. It is further proposed that interventions that normalize/reduce activity of the insulin-IGF-I system may play a key role in the prevention and treatment of the metabolic syndrome. For successful prevention, limitation, and treatment of the metabolic syndrome, the focus should be primarily on changing our diets and lifestyle in accordance with our genetic make-up, formed in adaptation to Paleolithic diets and lifestyles during a period of several million years of human evolution. Translating this insight into clinical practice, however, requires not only individual changes in our food and lifestyle, starting in pediatric populations at a very young age, but also requires fundamental changes in our current health systems and food industry. Change is needed: primary prevention of the metabolic syndrome should be made a political priority. New strategies and policies should be developed to stimulate and implement behaviors encouraging the sustainable use of healthy diets and lifestyles to prevent the metabolic syndrome before it develops.

Topics: Child; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin-Like Growth Factor I; Insulin, Regular, Human; Metabolic Syndrome; Signal Transduction

The use of continuous subcutaneous insulin infusion (CSII) via insulin pumps is today considered standard of care for type 1 diabetes (T1D). Closed-loop systems combining continuous glucose monitoring with automated algorithm-driven insulin delivery have been shown to be safe and efficacious in randomized controlled trials and real-life studies in both paediatric and adult participants with T1D. Implementation of hybrid closed-loop (HCL) systems has shown incremental effectiveness, with further reduction of hypoglycaemia and hyperglycaemia. Although less extensively studied in type 2 diabetes (T2D), insulin pumps have demonstrated their effectiveness in glucose control, along with a reduction in need for insulin and a neutral effect on weight. Recent studies have also shown promising results with the use of HCL systems in T2D. Cost-effectiveness studies in both T1D and T2D have shown that pump use is cost-effective in several countries, leading to improvements in quality-adjusted life-years. Insulin pumps are currently reimbursed for T1D in many European countries, but in only a few for individuals with T2D. HCL systems are to be evaluated in future trials performed in T2D to compare their incremental efficacy and cost-effectiveness in comparison with available intensification tools which include multiple daily insulin injections, metformin, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. There is a need for updated guidelines for the use of CSII and HCL in individuals living with T2D based on the emerging evidence, with identification of and recommendations for the people who would benefit the most, which would eventually form a basis for reimbursement and health policies.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Child; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Insulin, Regular, Human; Sodium-Glucose Transporter 2 Inhibitors; Technology

Glucose monitoring has evolved from self-monitoring of blood glucose to glycated hemoglobin, and the latest continuous glucose monitoring (CGM). A key challenge to adoption of CGM for management of diabetes in Asia is the lack of regional CGM recommendations. Hence, thirteen diabetes-specialists from eight Asia-Pacific (APAC) countries/regions convened to formulate evidence-based, APAC-specific CGM recommendations for individuals with diabetes. We defined CGM metrics/targets and developed 13 guiding-statements on use of CGM in: (1) people with diabetes on intensive insulin therapy, and (2) people with type 2 diabetes on basal insulin with/without glucose lowering drugs. Continual use of CGM is recommended in individuals with diabetes on intensive insulin therapy and suboptimal glycemic control, or at high risk of problematic hypoglycemia. Continual/intermittent CGM may also be considered in individuals with type 2 diabetes on basal insulin regimen and with suboptimal glycemic control. In this paper, we provided guidance for optimizing CGM in special populations/situations, including elderly, pregnancy, Ramadan-fasting, newly diagnosed type 1 diabetes, and comorbid renal disease. Statements on remote CGM, and stepwise interpretation of CGM data were also developed. Two Delphi surveys were conducted to rate the agreement on statements. The current APAC-specific CGM recommendations provide useful guidance for optimizing use of CGM in the region.

Topics: Aged; Blood Glucose; Blood Glucose Self-Monitoring; Consensus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Pregnancy

To compare the efficacy and safety of insulin glargine-300 once daily (Gla-300) with insulin degludec/aspart (IDegAsp) once daily in patients with type 2 diabetes (T2D) inadequately controlled on oral anti-diabetic drugs (OADs).. A systematic literature review of randomized controlled trials was followed by an indirect treatment comparison of studies involving insulin naïve adults, inadequately controlled [glycated haemoglobin (HbA1c) ≥7.0%] on OADs, who received Gla-300 or IDegAsp once daily. Outcomes of interest were change in HbA1c, blood glucose, weight and insulin dose, as well as incidence and event rate of hypoglycaemia and other adverse events.. Four trials with broadly similar baseline patient characteristics were included in the meta-analyses and indirect treatment comparison. At 24-28 weeks, the indirect comparison of Gla-300 to IDegAsp once daily estimated no statistically significant difference for change in HbA1c (%) from baseline [mean difference of 0.10% (95% CI: -0.20, 0.39; p = .52)]; a statistically significant mean difference of -1.31 kg (95% CI: -1.97, -0.65; p < .05) for change in body weight from baseline; statistically significant odds ratios of 0.62 (95% CI: 0.41, 0.93; p < .05) for incidence of any hypoglycaemia; and 0.47 (95% CI: 0.25, 0.87; p < .05) for incidence of anytime confirmed hypoglycaemia (plasma glucose <3.0-3.1 mmol/L). No significant differences were observed for insulin dose and adverse events.. In insulin-naïve patients with T2D inadequately controlled on OADs, commencing Gla-300 shows a comparable HbA1c reduction, but with significantly less weight gain and a lower incidence of any and confirmed hypoglycaemia compared with commencing IDegAsp.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Regular, Human

Basal insulin treatment for type 2 diabetes is usually initiated on a background of oral glucose-lowering medications (OGLM). We wanted to examine the influence of various OGLMs on fasting plasma glucose (FPG) and hemoglobin A

Topics: Diabetes Mellitus, Type 2; Glucose; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Metformin; Sulfonylurea Compounds

Physiologic insulin secretion consists of an oscillating pattern of secretion followed by distinct trough periods that stimulate ligand and receptor activation. Apart from the large postprandial bolus release of insulin, β cells also secrete small amounts of insulin every 4-8 min independent of a meal. Insulin resistance is associated with a disruption in the normal cyclical pattern of insulin secretion. In the case of type-2 diabetes, β-cell mass is reduced due to apoptosis and β cells secrete insulin asynchronously. When ligand/receptors are constantly exposed to insulin, a negative feedback loop down regulates insulin receptor availability to insulin, creating a relative hyperinsulinemia. The relative excess of insulin leads to insulin resistance (IR) due to decreased receptor availability. Over time, progressive insulin resistance compromises carbohydrate metabolism, and may progress to type-2 diabetes (T2D). In this review, we discuss insulin resistance pathophysiology and the use of dynamic exogenous insulin administration in a manner consistent with more normal insulin secretion periodicity to reverse insulin resistance. Administration of insulin in such a physiologic manner appears to improve insulin sensitivity, lower HgbA1c, and, in some instances, has been associated with the reversal of end-organ damage that leads to complications of diabetes. This review outlines the rationale for how the physiologic secretion of insulin orchestrates glucose metabolism, and how mimicking this secretion profile may serve to improve glycemic control, reduce cellular inflammation, and potentially improve outcomes in patients with diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Ligands

Numerous studies have demonstrated the clinical benefits of continuous glucose monitoring (CGM) in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) who are treated with intensive insulin regimens. Based on this evidence, CGM is now a standard of care for individuals within these diabetes populations and widely covered by commercial and public insurers. Moreover, recent clinical guidelines from the American Diabetes Association and American Association of Clinical Endocrinology now endorse CGM use in individuals treated with nonintensive insulin regimens. However, despite increasing evidence supporting CGM use for individuals treated with less-intensive insulin therapy or noninsulin medications, insurance coverage is limited or nonexistent. This narrative review reports key findings from recent randomized, observational, and retrospective studies investigating use of CGM in T2D individuals treated with basal insulin only and/or noninsulin therapies and presents an evidence-based rationale for expanding access to CGM within this population.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Retrospective Studies

Type 2 diabetes mellitus (T2DM) is the world's most common metabolic disease. The development of T2DM is mainly caused by a combination of two factors: the failure of insulin secretion by the pancreatic β-cells and the inability of insulin-sensitive tissues to respond to insulin (insulin resistance); therefore, the disease is indicated by a chronic increase in blood glucose. T2DM patients can be treated with mono- or combined therapy using oral antidiabetic drugs and insulin-replaced agents; however, the medication often leads to various discomforts, such as abdominal pain, diarrhea or constipation, nausea and vomiting, and hypersensitivity reactions. A biguanide drug, metformin, has been used as a first-line drug to reduce blood sugar levels. Sulfonylureas work by blocking the ATP-sensitive potassium channel, directly inducing the release of insulin from pancreatic β-cells and thus decreasing blood glucose concentrations. However, the risk of the failure of sulfonylurea as a monotherapy agent is greater than that of metformin or rosiglitazone (a thiazolidinedione drug). Sulfonylureas are used as the first-line drug of choice for DM patients who cannot tolerate metformin therapy. Other antidiabetic drugs, thiazolidinediones, work by activating the peroxisome proliferator-activated receptor gamma (PPARγ), decreasing the IR level, and increasing the response of β-cells towards the glucose level. However, thiazolidines may increase the risk of cardiovascular disease, weight gain, water retention, and edema. This review article aims to discuss case reports on the use of metformin, sulfonylureas, and thiazolidinediones in DM patients. The literature search was conducted on the PubMed database using the keywords 'metformin OR sulfonylureas OR thiazolidinediones AND case reports', filtered to 'free full text', 'case reports', and '10 years publication date'. In some patients, metformin may affect sleep quality and, in rare cases, leads to the occurrence of lactate acidosis; thus, patients taking this drug should be monitored for their kidney status, plasma pH, and plasma metformin level. Sulfonylureas and TZDs may cause a higher risk of hypoglycemia and weight gain or edema due to fluid retention. TZDs may be associated with risks of cardiovascular events in patients with concomitant T2DM and chronic obstructive pulmonary disease. Therefore, patients taking these drugs should be closely monitored for adverse effects.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Metformin; Sulfonylurea Compounds; Thiazolidinediones

One of the greatest barriers to the treatment of T2DM is nonadherence which particularly applies to insulin therapy. There is a need for a comprehensive overview of all factors associated with nonadherence to insulin therapy. The aim of this study was to identify factors associated with adherence or nonadherence to insulin therapy among adults with T2DM.. A scoping review was conducted in accordance with the PRISMA 2020 statement. A systematic search was performed in PubMed, Cinahl, and Web of Science (January 2013 to March 2023).. A final sample of 48 studies was included in the scoping review. The synthesis revealed 30 factors associated with adherence or nonadherence. The factors were grouped into 6 themes: demographics, attitude and perceptions, management of diabetes, impact on daily living, disease and medication, and healthcare system.. The most prominent factors identified were age, cost of healthcare, personal beliefs towards insulin therapy, social stigma, patient education, complexity of diabetes treatment, impact of insulin therapy on daily life, and fear of side effects. The results indicate a need for further research to determine threshold values for the factors associated with adherence or nonadherence.

Topics: Adult; Diabetes Mellitus, Type 2; Drug-Related Side Effects and Adverse Reactions; Humans; Insulin; Insulin, Regular, Human; Medication Adherence

To summarize the evidence of recently published randomized controlled trials (RCTs) studying efficacy, in terms of glycaemic control, and safety of the newly developed once-weekly basal insulin analogues.. A systematic literature search was conducted through Medline (via PubMed), Cochrane Library and Google Scholar until June 30, 2023. Double-independent study selection, data extraction and quality assessment were performed. Results were summarized with random-effects meta-analysis.. A total of 3962 patients with type 2 diabetes mellitus (T2DM) among nine RCTs were analysed. All RCTs had low risk of bias according to the Cochrane Collaboration risk-of-bias tool (RoB2). Once-weekly insulins demonstrated better efficacy in glycated haemoglobin (HbA1c) reduction (mean difference [MD] -0.13%, 95% confidence interval [CI] -0.23, -0.03; P = 0.08) and a significantly greater time in range compared with once-daily insulin analogues (MD 3.54%, 95% CI 1.56, 5.53; P = 0.005). Based on subgroup analyses, the reduction in HbA1c and the odds of achieving an end-of-treatment HbA1c <6.5% were significantly greater for icodec compared to the once-daily insulin (MD -0.18%, 95% CI -0.27, -0.09 [P < 0.001] and odds ratio [OR] 1.75, 95% CI 1.34, 2.29 [P < 0.001], respectively). Once-weekly insulins were associated with higher odds of level 1 hypoglycaemia during the 24-hour period (OR 1.3, 95% CI 1.04, 1.64; P = 0.02) but were safer in terms of level 2 or 3 nocturnal hypoglycaemic events (OR 0.74, 95% CI 0.56, 0.97; P = 0.03). No difference was observed regarding serious adverse events between the two groups.. The once-weekly basal insulin analogues seem to be at least equally efficient in glycaemic management and safe compared to once-daily injections in people with T2DM. Phase 4 RCTs are expected to shed further light on the effectiveness and safety of once-weekly insulin therapy over the long term.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

Despite enormous global efforts within clinical research and medical practice to reduce cardiovascular disease(s) (CVD), it still remains the leading cause of death worldwide. While genetic factors clearly contribute to CVD etiology, the preponderance of epidemiological data indicate that a major common denominator among diverse ethnic populations from around the world contributing to CVD is the composite of Western lifestyle cofactors, particularly Western diets (high saturated fat/simple sugar [particularly high fructose and sucrose and to a lesser extent glucose] diets), psychosocial stress, depression, and altered sleep/wake architecture. Such Western lifestyle cofactors are potent drivers for the increased risk of metabolic syndrome and its attendant downstream CVD. The central nervous system (CNS) evolved to respond to and anticipate changes in the external (and internal) environment to adapt survival mechanisms to perceived stresses (challenges to normal biological function), including the aforementioned Western lifestyle cofactors. Within the CNS of vertebrates in the wild, the biological clock circuitry surveils the environment and has evolved mechanisms for the induction of the obese, insulin-resistant state as a survival mechanism against an anticipated ensuing season of low/no food availability. The peripheral tissues utilize fat as an energy source under muscle insulin resistance, while increased hepatic insulin resistance more readily supplies glucose to the brain. This neural clock function also orchestrates the reversal of the obese, insulin-resistant condition when the low food availability season ends. The circadian neural network that produces these seasonal shifts in metabolism is also responsive to Western lifestyle stressors that drive the CNS clock into survival mode. A major component of this natural or Western lifestyle stressor-induced CNS clock neurophysiological shift potentiating the obese, insulin-resistant state is a diminution of the circadian peak of dopaminergic input activity to the pacemaker clock center, suprachiasmatic nucleus. Pharmacologically preventing this loss of circadian peak dopaminergic activity both prevents and reverses existing metabolic syndrome in a wide variety of animal models of the disorder, including high fat-fed animals. Clinically, across a variety of different study designs, circadian-timed bromocriptine-QR (quick release) (a unique formulation of micronized bromocriptine-a dopamine D2 receptor

Topics: Animals; Brain; Bromocriptine; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dopamine; Dopamine Agonists; Insulin; Insulin Resistance; Insulin, Regular, Human; Metabolic Syndrome

A daily habit of yogic practice or walking, along with an oral hypoglycemic agent (OHA) could be beneficial for better control of type 2 diabetes mellitus (T2DM). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to find out the efficiency of yoga or walking on glycemic control in T2DM.. The present systematic review and meta-analysis were completed according to the PRISMA guidelines. The risk of bias in included studies was evaluated, by using the revised Cochrane risk-of-bias tool for randomized trials. Meta-analysis was implemented using RevMan software. Forest plots were used to illustrate the study findings and meta-analysis results.. Sixteen studies were included in this systematic review, where 1820 participants were allocated to one of the following interventions: yoga, walking, and without any regular exercise (control group). Participants were between 17-75 years of age. Compared to the control group, the yoga group had a significant reduction in fasting blood glucose (FBG) by 31.98 mg/dL (95% CI = -47.93 to -16.03), postprandial blood glucose (PPBG) by 25.59 mg/dL (95% CI = -44.00 to -7.18], glycosylated hemoglobin (HbAlc) by 0.73% (95% CI = -1.24 to -0.22), fasting insulin by 7.19 μIU/mL (95% CI = -12.10 to -2.28), and homeostatic model assessment for insulin resistance (HOMA-IR) by 3.87 (95% CI = -8.40 to -0.66). Compared to the control group, the walking group had a significant reduction in FBG by 12.37 mg/dL (95% CI = -20.06 to -4.68) and HbA1c by 0.35% (95% CI = -0.70 to -0.01). Compared to the walking group, the yoga group had a significant reduction in FBG by 12.07 mg/dL (95% CI = -24.34 to - 0.20), HbA1c by 0.20% (95% CI = -0.37 to -0.04), fasting insulin by 10.06 μIU/mL (95% CI = -23.84 to 3.71) and HOMA-IR by 5.97 (95% CI = -16.92 to 4.99).. Yoga or walking with OHA has positive effects on glycemic control. For the management of T2DM, yoga has relatively more significant effects on glycemic control than walking.Review registration number: PROSPERO registration number CRD42022310213.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Walking; Yoga

The evolution of basal insulin therapy over the past 100 years since the discovery of insulin is a testimony to the biomedical bench-to-bedside process, wherein incremental advances in the basic sciences are progressively translated over time into a series of enhancements in clinical care, each building upon the success of its predecessors. The emergence of recombinant DNA technology and the resultant biosynthesis of human insulin in the 1980s provided the critical capacity to bioengineer designer insulin analogues with pharmacokinetic and pharmacodynamic properties that can better mimic, although not fully replicate, the effects of endogenous insulin secretion. Through these efforts, basal insulin therapy has progressed over this time from first-generation analogues (glargine U-100, detemir) to second-generation analogues (glargine U-300, degludec) to ultra-long-acting formulations that are suitable for administration once weekly (icodec). Each iteration in this progression has represented a step closer towards the goal of replicating the continuous secretion of insulin that normally comprises the basal output of the pancreatic beta-cells between meals, during episodes of fasting and overnight. However, it may be that we may have reached the achievable limit in the context of an "open-loop" approach, such that only with the addition of closed loop control will we be able to achieve physiologic basal insulin replacement. In this review, we will examine the evolution of basal insulin therapy over the past 100 years and its implications for patient care and outcomes in current practice and the future.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Insulin, Regular, Human

In the 1950's, Dr. I. Arthur Mirsky first recognized the possible importance of insulin degradation changes to the pathogenesis of type 2 diabetes. While this mechanism was ignored for decades, insulin degradation is now being recognized as a possible factor in diabetes risk. After Mirsky, the relative importance of defects in insulin release and insulin resistance were recognized as risk factors. The hyperbolic relationship between secretion and sensitivity was introduced, as was the relationship between them, as expressed as the disposition index (DI). The DI was shown to be affected by environmental and genetic factors, and it was shown to be differentiated among ethnic groups. However, the importance of differences in insulin degradation (clearance) on the disposition index relationship remains to be clarified. Direct measure of insulin clearance revealed it to be highly variable among even normal individuals, and to be affected by fat feeding and other physiologic factors. Insulin clearance is relatively lower in ethnic groups at high risk for diabetes such as African Americans and Hispanic Americans, compared to European Americans. These differences exist even for young children. Two possible mechanisms have been proposed for the importance of insulin clearance for diabetes risk: in one concept, insulin resistance per se leads to reduced clearance and diabetes risk. In a second and new concept, reduced degradation is a primary factor leading to diabetes risk, such that lower clearance (resulting from genetics or environment) leads to systemic hyperinsulinemia, insulin resistance, and beta-cell stress. Recent data by Chang and colleagues appear to support this latter hypothesis in Native Americans. The importance of insulin clearance as a risk factor for metabolic disease is becoming recognized and may be treatable.

Topics: Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 2; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin-Secreting Cells; Insulin, Regular, Human

Prevalence of type 2 diabetes increased from 2.5% of the US population in 1990 to 10.5% in 2018. This creates a major public health problem, due to increases in long-term complications of diabetes, including neuropathy, retinopathy, nephropathy, skin ulcers, amputations, and atherosclerotic cardiovascular disease. In this review, we evaluated the scientific basis that supports the use of physiologic insulin resensitization. Insulin resistance is the primary cause of type 2 diabetes. Insulin resistance leads to increasing insulin secretion, leading to beta-cell exhaustion or burnout. This triggers a cascade leading to islet cell destruction and the long-term complications of type 2 diabetes. Concurrent with insulin resistance, the regular bursts of insulin from the pancreas become irregular. This has been treated by the precise administration of insulin more physiologically. There is consistent evidence that this treatment modality can reverse the diabetes-associated complications of neuropathy, diabetic ulcers, nephropathy, and retinopathy, and that it lowers HbA1c. In conclusion, physiologic insulin resensitization has a persuasive scientific basis, significant treatment potential, and likely cost benefits.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin Resistance; Insulin Secretion; Insulin, Regular, Human; Pancreas

Diabetes mellitus is a common disease state among older people, with type 2 diabetes making up most cases. As the disease progresses, many patients will need to transition to insulin therapy. Pharmacists can play a pivotal role in the care of older people with diabetes by providing recommendations related to insulin therapy. Senior care pharmacists need to be knowledgeable about the pharmacokinetics, dosing, adverse effects, and cost concerns related to insulin therapy.

Topics: Aged; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Pharmacists

The health and economic burden of type 2 diabetes is of global significance. Many people with type 2 diabetes eventually need insulin to help reduce their risk of serious associated complications. However, barriers to the initiation and/or optimization of insulin expose people with diabetes to sustained hyperglycemia. In this review, we investigated how new and future technologies may provide opportunities to help overcome these barriers to the initiation and/or optimization of insulin.. A focused literature search of PubMed and key scientific congresses was conducted. Software tools and devices developed to support the initiation and/or optimization of insulin were identified by manually filtering >300 publications and conference abstracts.. Most software tools have been developed for smartphone platforms. At present, published data suggest that the use of these technologies is associated with equivalent or improved glycemic outcomes compared with standard care, with additional benefits such as reduced time burden and improved knowledge of diabetes among health care providers. However, there remains paucity of good-quality evidence. Most new devices to support insulin therapy help track the dose and timing of insulin.. New digital health tools may help to reduce barriers to optimal insulin therapy. An integrated solution that connects glucose monitoring, dose recording, and titration advice as well as records comorbidities and lifestyle factors has the potential to reduce the complexity and burden of treatment and may improve adherence to titration and treatment, resulting in better outcomes for people with diabetes.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

Rapid-acting insulins (RAIs) have been instrumental in the management of diabetes because of their improved postprandial glucose (PPG) control compared with regular human insulin. However, their absorption rate and time action following subcutaneous administration still falls short of the normal physiological response to meal consumption, increasing the risk of early postmeal hyperglycaemia and late postmeal hypoglycaemia. Increased demand for faster acting insulins, which can quickly control PPG excursions without increasing the risk of late hypoglycaemia, led to the development of ultra-rapid-acting insulins, including ultra-rapid lispro (URLi). URLi is a novel formulation of insulin lispro with accelerated absorption driven by two excipients: treprostinil, which increases local vasodilation, and citrate, which increases local vascular permeability. Clinical pharmacology studies consistently showed an earlier onset and shorter duration of action with URLi compared with Lispro. In a head-to-head study with Faster aspart, Aspart and Lispro, URLi was absorbed faster, provided earlier insulin action, and more closely matched physiological glucose response than the other insulins tested. URLi's unique pharmacokinetic properties increase its potential for improved PPG control beyond that achieved with RAIs. Indeed, in pivotal phase 3 trials, URLi was superior to Lispro for PPG control both at 1 and 2 hours after a meal in type 1 and type 2 diabetes with multiple daily injections, and in type 1 diabetes with continuous subcutaneous insulin infusion. This was achieved without increasing the risk of hypoglycaemia. In this review, we focus on the clinical and pharmacological evidence for URLi in the treatment of diabetes and discuss the potential benefits and considerations with URLi compared with RAIs.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Lispro; Insulin, Regular, Human; Insulin, Short-Acting

Recent data suggests that (pre)diabetes onset is preceded by a period of hyperinsulinemia. Consumption of the "modern" Western diet, over-nutrition, genetic background, decreased hepatic insulin clearance, and fetal/metabolic programming may increase insulin secretion, thereby causing chronic hyperinsulinemia. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, polycystic ovarian syndrome, and Alzheimer's disease. Recent data suggests that the onset of prediabetes and diabetes are preceded by a variable period of hyperinsulinemia. Emerging data suggest that chromic hyperinsulinemia is also a driving force for increased activation of the hypothalamic-adrenal-pituitary (HPA) axis in subjects with the metabolic syndrome, leading to a state of "functional hypercortisolism". This "functional hypercortisolism" by antagonizing insulin actions may prevent hypoglycemia. It also disturbs energy balance by shifting energy fluxes away from muscles toward abdominal fat stores. Synergistic effects of hyperinsulinemia and "functional hypercortisolism" promote abdominal visceral obesity and insulin resistance which are core pathophysiological components of the metabolic syndrome. It is hypothesized that hyperinsulinemia-induced increased activation of the HPA axis plays an important etiological role in the development of the metabolic syndrome and its consequences. Numerous studies have demonstrated reversibility of hyperinsulinemia with lifestyle, surgical, and pharmaceutical-based therapies. Longitudinal studies should be performed to investigate whether strategies that reduce hyperinsulinemia at an early stage are successfully in preventing increased activation of the HPA axis and the metabolic syndrome.

Topics: Cushing Syndrome; Diabetes Mellitus, Type 2; Humans; Hypothalamo-Hypophyseal System; Insulin; Insulin, Regular, Human; Metabolic Syndrome; Obesity; Pituitary-Adrenal System

Alzheimer's disease (AD) is a global concern and has become a major public health event affecting human health. Insulin is a metabolic hormone secreted mainly by the peripheral tissue pancreas. In recent years, more and more evidence has proved that insulin regulates various functions of the brain. The hippocampus, one of the earliest brain regions affected by AD, is widely distributed with insulin receptors. Studies have shown that type 2 diabetes mellitus, characterized by insulin resistance, is closely related to AD, which has drawn extensive attention to the relationship between hippocampal insulin signaling and AD. Therefore, we provide an overview of intranasal insulin administration on memory and its underlying mechanism. We also highlight the molecular link between hippocampal insulin resistance and AD and provide a theoretical basis for finding new therapeutic targets for AD in clinical practice.

Topics: Alzheimer Disease; Diabetes Mellitus, Type 2; Hippocampus; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human

Alzheimer's disease (AD) and type 2 diabetes (T2D) are chronic diseases that share several pathological mechanisms, including insulin resistance and impaired insulin signalling. Their shared features have prompted the evaluation of the drugs used to manage diabetes for the treatment of AD. Insulin delivery itself has been utilized, with promising effects, in improving cognition and reducing AD related neuropathology. The most recent clinical trial involving intranasal insulin reported no slowing of cognitive decline; however, several factors may have impacted the trial outcomes. Long-acting and rapid-acting insulin analogues have also been evaluated within the context of AD with a lack of consistent outcomes. This narrative review provided insight into how targeting insulin signalling in the brain has potential as a therapeutic target for AD and provided a detailed update on the efficacy of insulin, its analogues and the outcomes of human clinical trials. We also discussed the current evidence that warrants the further investigation of the use of the mimetics of insulin for AD. These small molecules may provide a modifiable alternative to insulin, aiding in developing drugs that selectively target insulin signalling in the brain with the aim to attenuate cognitive dysfunction and AD pathologies.

Topics: Alzheimer Disease; Brain; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin, Regular, Human

The goal of diabetes care is to achieve and maintain good glycemic control over time, so as to prevent or delay the development of micro- and macrovascular complications in type 1 (T1D) and type 2 diabetes (T2D). However, numerous barriers hinder the achievement of this goal, first of all the frequent episodes of hypoglycemia typical in patients treated with insulin as T1D patients, or sulphonylureas as T2D patients. The prevention strategy and treatment of hypoglycemia are important for the well-being of patients with diabetes. Hypoglycemia is strongly associated with an increased risk of cardiovascular disease in diabetic patients, due probably to the release of inflammatory markers and prothrombotic effects triggered by hypoglycemia. Treatment of hypoglycemia is traditionally based on administration of carbohydrates or of glucagon via intramuscular (IM) or subcutaneous injection (SC). The injection of traditional glucagon is cumbersome, such that glucagon is an under-utilized drug. In 1983, it was shown for the first time that intranasal (IN) glucagon increases blood glucose levels in healthy volunteers, and in 1989-1992 that IN glucagon is similar to IM glucagon in resolving hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. IN glucagon was developed in 2010 and continued in 2015; in 2019 IN glucagon obtained approval in the US, Canada, and Europe for severe hypoglycemia in children and adults. In the 2010s, two ready-to-use injectable formulations, a stable non-aqueous glucagon solution and the glucagon analog dasiglucagon, were developed, showing an efficacy similar to traditional glucagon, and approved in the US in 2020 and in 2021, respectively, for severe hypoglycemia in adults and in children. Fast-acting glucagon (nasal administration and injected solutions) appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both adults and children. It is anticipated that the availability of fast-acting glucagon will expand the use of glucagon, improve overall metabolic control, and prevent hypoglycemia-related complications, in particular cardiovascular complications and cognitive impairment.

Topics: Administration, Intranasal; Adult; Child; Critical Care; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucagon; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin, Regular, Human; Powders; Sulfonylurea Compounds; Treatment Outcome

Initiating insulin therapy with a basal insulin analogue has become a standard of care in the treatment of type 2 diabetes mellitus (T2DM). Despite increasing choices in pharmacological approaches, intensified glucose monitoring and improvements in quality of care, many patients do not achieve the desired level of glycaemic control. Although insulin therapy, when optimized, can help patients reach their glycaemic goals, there are barriers to treatment initiation on both the side of the patient and provider. Providers experience barriers based on their perceptions of patients' capabilities and concerns. They may lack the confidence to solve the practical problems of insulin therapy and avoid decisions they perceive as risky for their patients. In this study, we review recommendations for basal insulin initiation, focussing on glycaemic targets, titration, monitoring, and combination therapy with non-insulin anti-hyperglycaemic medications. We provide practical advice on how to address some of the key problems encountered in everyday clinical practice and give recommendations where there are gaps in knowledge or guidelines. We also discuss common challenges faced by people with T2DM, such as weight gain and hypoglycaemia, and how providers can address and overcome them.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

Evidence suggests a major contribution of postprandial glucose (PPG) excursions to the increased risk of micro- and macro-vascular complications in individuals with type 2 diabetes mellitus (T2DM). Administration of bolus insulin remains a very effective therapeutic option for PPG control. The aim of this expert group recommendation document was to provide practical and easy-to-execute guidelines for physicians on the appropriate use of bolus insulin in the management of T2DM. A panel of key opinion leaders from India reviewed and discussed the available clinical evidence and guideline recommendations on the following topics: (1) optimum control of PPG; (2) choice of bolus insulin; and (3) special situations and practical considerations. The expert panel critically analyzed the current literature and clinical practice guidelines and factored their rich clinical experience to develop a set of nine expert group recommendations for the effective use of bolus insulin. These recommendations will not only result in a more evidence-based application of bolus insulin in the clinical setting but also trigger further research and provide a valuable base for the development of future guidelines on the use of bolus insulin in the management of individuals with T2DM.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Postprandial Period

Throughout history, up to the early part of the 20th century, diabetes has been a devastating disorder, particularly when diagnosed in childhood when it was usually fatal. Consequently, the successful pancreatic extraction of insulin in 1921 was a miraculous, life-changing advance. In this review, the truly transformative effect that insulin has had on the lives of people with type 1 diabetes and on those with type 2 diabetes who are also dependent on insulin is described, from the time of its first successful use to the present day. We have highlighted in turn how each of the many facets of improvements over the last century, from advancements in the properties of insulin and its formulations to the evolution of different methods of delivery, have led to continued improvement in clinical outcomes, through the use of illustrative stories from history and from our own clinical experiences. This review concludes with a brief look at the current challenges and where the next century of technological innovation in insulin therapy may take us.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin, Regular, Human

New concentrated insulins (exceeding 100 units/mL) and dedicated devices have recently become available, offering new treatment options for people with diabetes, for basal and prandial insulin supplementation. The concentrated insulin formulations range from 2-fold concentration (insulin lispro 200 units/mL) with rapid-acting prandial action to 5-fold concentration (human regular insulin, 500 units/mL) with basal and short-acting prandial actions. Long-acting basal insulins include degludec 200 units/mL and glargine 300 units/mL. Concentrated insulins have been developed with the goal of easing insulin therapy by reducing the volume and number of injections and in some cases making use of altered pharmacokinetic and pharmacodynamic properties. This review summarizes the unique characteristics of each concentrated insulin to help healthcare providers and people with diabetes understand how to best use them.

Topics: Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Compounding; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Insulin, Regular, Human; Insulins

To conduct a review in order to assess the safety of intranasal human insulin in clinical studies as well as the temporal stability of nasal insulin sprays.. An electronic search was performed using MEDLINE. We selected original research on intranasal human insulin without further additives in humans. The studies included could be of any design as long as they used human intranasal insulin as their study product. All outcomes and adverse side effects were extracted.. A total of 38 studies in 1092 individuals receiving acute human intranasal insulin treatment and 18 studies in 832 individuals receiving human intranasal insulin treatment lasting between 21 days and 9.7 years were identified. No cases of symptomatic hypoglycaemia or severe adverse events (AEs) were reported. Transient local side effects in the nasal area were frequently experienced after intranasal insulin and placebo spray, while other AEs were less commonly reported. There were no reports of participants being excluded as a result of AEs. No instances of temporal stability of nasal insulin were reported in the literature. Tests on insulin that had been repacked into spray flasks showed that it had a chemical stability of up to 57 days.. Our retrospective review of published studies on intranasal insulin did not reveal any safety concerns; however, there were insufficient data to ensure the long-term safety of this method of chronic insulin administration. Improved insulin preparations that cause less nasal irritation would be desirable for future treatment.

Topics: Administration, Intranasal; Aerosols; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Compounding; Drug Stability; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin, Regular, Human; Protein Stability; Recombinant Proteins

Diabetes during pregnancy may lead to maternal, fetal and neonatal complications. In order to limit unwarranted outcomes, strict glycemic control is essential. In the past, human insulin was the only insulin formulation administered in pregnancy. However, insulin analogues have also been used for this indication in recent years.. This article reviews the published data regarding the safety of insulin analogue use during pregnancy. We present the qualities, advantages and pitfalls of insulin analogue use in pregnancy compared with human insulin. Insulins lispro, aspart and detemir are safe in pregnant women with type 1 diabetes. Correspondingly, they were reclassified for the treatment of pregnant women with diabetes from category C to category B. For insulin glargine use in pregnancy, most studies are small and retrospective. Yet, no major safety concerns were reported. Insulin glulisine and degludec have not been studied in pregnancy.. Insulin analogues are viable therapeutic options for diabetes in pregnancy, specifically lispro, aspart and detemir. Though data in limited, their safety and efficacy are comparable with human insulin. Remarkably, the analogues are superior to human insulin regarding hypoglycaemia risk. More data, specifically for their use in pregnancies complicated by gestational diabetes or type 2 diabetes, is needed.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Infant, Newborn; Insulin, Regular, Human; Insulins; Pregnancy

Insulin remains the most effective and consistent means of controlling blood glucose levels in diabetes. Since 1946, neutral protamine Hagedorn (NPH) has been the predominant basal insulin in clinical use. However, absorption is variable due to the need for resuspension and the time-action profile (peak activity 4-6 h after subcutaneous administration) confers an increased propensity for between-meal and nocturnal hypoglycaemia. In the 1980s, recombinant DNA technology enabled modifications to the insulin molecule resulting in the soluble long-acting insulin analogues, glargine and detemir. Both exhibit a lower risk of hypoglycaemia compared with neutral protamine Hagedorn due to improved time-action profiles and reduced day-to-day glucose variability. Glargine is indicated for administration once daily and detemir once or twice daily. Degludec is the latest prolonged-acting insulin which forms long subcutaneous multi-hexamers that delay absorption. Recent phase III trials in type 1 and type 2 diabetes show that degludec was non-inferior to comparators (predominantly glargine) with a minimal although inconsistent reduction in overall hypoglycaemia and a small absolute difference in nocturnal hypoglycaemia. Newer developmental agents include LY2605541 and glargine U300. LY2605541 comprises insulin lispro combined with polyethylene glycol, thereby increasing its hydrodynamic size and retarding absorption from the subcutaneous tissue. Glargine U300 is a new formulation of glargine resulting in a flatter and more prolonged time-action profile than its predecessor. This article reviews recent advances in basal insulin analogues, including a critical appraisal of the degludec trials.

Topics: Animals; Chemistry, Pharmaceutical; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drugs, Investigational; Humans; Hypoglycemic Agents; Insulin, Long-Acting; Insulin, Regular, Human; Recombinant Proteins

The rise in prevalence of obesity and diabetes has created a challenge in managing increasing numbers of patients who require high doses of insulin. This article reviews the published literature on the properties of U-500 insulin and its use in clinical practice. U-500 insulin is likely to have a longer time to peak effect and a longer duration of action than similar doses of U-100 insulin. Evidence for its use in clinical practice rests on retrospective case series, which suggests that the use of U-500 insulin either by multiple daily injections or a continuous subcutaneous insulin infusion is effective in improving glycaemic control. To prevent insulin dosing and administration errors, great care must be taken in providing staff and patient education, and in developing policies for the management of patients on U-500 insulin who are admitted to hospital.

Topics: Blood Glucose; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Evidence-Based Medicine; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Infusion Systems; Insulin Resistance; Insulin, Regular, Human; Male; Obesity; Patient Education as Topic; Treatment Outcome

The aim of this review is to summarize the clinical efficacy, tolerability and safety data of insulin detemir, and compare its use with that of neutral protamine Hagedorn (NPH) insulin in randomized controlled trials in people with type 1 or type 2 diabetes. A literature search was conducted with PubMed using predefined search terms. Studies were included if they met the following criteria: randomized, controlled trial, comparison of insulin detemir with NPH insulin, non-hospitalized adults aged ≥18 years with either type 1 or type 2 diabetes, and study duration of ≥12 weeks. The following types of studies were excluded: non-randomized controlled trials, studies of mixed cohorts of patients with type 1 or type 2 diabetes that did not report results separately, pharmacokinetic/pharmacodynamic studies, reviews, pooled or meta-analyses or health-economic analyses. Fourteen publications met the inclusion criteria. Nine studies in people with type 1 diabetes and three studies in people with type 2 diabetes, using insulin detemir in a basal-bolus regimen were included. Two studies were in people with type 2 diabetes using insulin detemir with oral antidiabetes medicines. In 14 studies of people with type 1 or type 2 diabetes, insulin detemir treatment provided similar or better glycaemic control, lower within-subject variability, similar or lower frequency of hypoglycaemia and less weight gain when compared with NPH insulin.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Randomized Controlled Trials as Topic; Weight Gain

Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin. Insulin glulisine is a short acting analogue with a rapid onset of action. The antiapoptotic property, mediated through insulin substrate receptor-2 has a favourable protective action on beta cells. Insulin detemir is a long acting analogue, soluble at neutral pH, which reversibly binds to albumin in plasma, prolonging its action. Its lower affinity for insulin receptors necessitates higher doses compared to human insulin. The reduction in body weight is an additional advantage of detemir. A major concern about all newer insulin analogues is their altered mitogenic properties and resultant risk of carcinogenicity on long term use. Albulin is a latest addition of insulin analogue which is under various in vitro and in vivo studies. Inhaled insulin in powder form (Exubera) is recently approved by FDA and appears promising.

Topics: Administration, Inhalation; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Long-Acting; Insulin, Regular, Human; Serum Albumin; Serum Albumin, Human

To assess the safety and efficacy of multiple daily doses of oral insulin (ORMD-0801) in subjects with type 2 diabetes (T2DM) over 12 weeks.. Participants with T2DM on metformin or combination oral therapy with glycated haemoglobin (HbA1c) levels ≥ 7.5% (58 mmol/mol) were randomized to receive ORMD-0801 8 mg or 16 mg once (QD) or twice (BID) daily, or 32 mg QD, BID or three times daily (TID) over a 12-week period.. A total of 373 subjects were randomized to active treatment or placebo (~60% male, age ~ 56 years, HbA1c 9%-9.8%; 75-84 mmol/mol). Placebo-adjusted HbA1c changes from baseline to Week 12 were observed with ORMD-0801 8 mg BID (-7.15 ± 3.57 mmol/mol [-0.65% ± 0.33%]; P = 0.046). However, a significant site interaction was observed in two sites. After excluding these, HbA1c reduction was observed with 8 mg QD (-0.81 ± 0.37%; -8.89 ± 4.01 mmol/mol; P = 0.028, n = 15), 8 mg BID (-0.82 ± 0.37%; -8.95 ± 4.08 mmol/mol; P = 0.029, n = 17), 32 mg QD (-0.54 ± 0.26%; -5.89 ± 2.78 mmol/mol;P = 0.036, n = 69) and 32 mg BID (-0.53 ± 0.26%; -5.80 ± 2.83 mmol/mol; P = 0.042, n = 68). No effect was observed with 16 mg QD (0.25 ± 0.37%; 2.76 ± 3.99 mmol/mol; P = 0.48, n = 18), 16 mg BID (-0.36 ± 0.40%; -3.97 ± P = 0.36, n = 15) or 32 mg TID (-0.45 ± 0.27%, -4.89 ± 2.90 mmol/mol; P = 0.093, n = 69). Continuous glucose monitor and serum glucose measurements showed similar trends but were not significant. ORMD-0801 was safe, well tolerated and not associated with weight gain or hypoglycaemia.. Oral insulin (ORMD-0801) induced greater reductions in HbA1c when compared to placebo, and was safe and well tolerated in individuals with uncontrolled T2DM. The efficacy and safety findings support continued development of the 8-mg dose at bedtime, which is currently being evaluated in two Phase 3 trials.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Male; Middle Aged

To compare the pharmacodynamic properties of different doses of regular human insulin administered in capsule form twice daily in a randomised twelve-week open-label study.. A total of 100 individuals (48 males, 52 females) with type 2 diabetes on metformin completed the study according to the protocol. The mean (SD) age was 48.5 (6.7) years, body mass index 25.7 (2.8) kg/m. The study met its primary clinical endpoint of a decrease in HbA1c of 0.5% or higher (least square mean decrease 0.52%; P = .004, median decrease 0.6%) in the dose group receiving 150 iu BD. In a subset of this population, with starting HbA1c values of 9% to 9.5%, an average decrease of 1.575% was observed. In the total population, least square mean decreases in HbA1c for the 75 and 300 iu BD groups were -0.11% and -0.42%, respectively. Mean change in FPG in the 150 iu BD dose group was -18.8 mg/dl (P = .017) and -14.8 and -2.7 mg/dl for the 75 and 300 iu BD groups, respectively. A decrease of 20% for triglycerides (-40 mg/dl) was observed in the 150 iu BD dose group. No significant increases in body weight were observed, and significant decreases in systolic blood pressure were seen in all groups. No serious treatment-related adverse events were recorded, and no incidence of hypoglycaemia was reported throughout the entire 12-week study period.. Capsulin oral insulin administered twice per day at a dose of 150 iu per capsule is safe, with no confirmed treatment-linked hypoglycaemic events, and results in significant decreases from baseline in HbA1c, FPG and triglycerides.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Male; Middle Aged; Treatment Outcome

The cardiorenal benefits of adding sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy for patients on insulin, particularly those on intensive regimens that include short-acting (SA) insulin, have not been explored.. In Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomized to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular (CV), renal, metabolic, and safety outcomes with dapagliflozin versus placebo by insulin dose and regimen were studied with Cox regression models.. The study included 7,013 insulin users at baseline, with 4,650 (66.3%) patients on regimens including SA insulin. Insulin doses varied, with 2,443 (34.8%) patients receiving <0.5 IU/kg, 2,795 (39.9%) 0.5 to ≤1 IU/kg, and 1,339 (19.1%) >1 IU/kg. Dapagliflozin reduced CV death/hospitalization for heart failure among overall insulin users (hazard ratio [HR] 0.82 [95% CI 0.69-0.97]) and consistently in patients on insulin regimens with or without SA insulin (0.83 [0.67-1.03] and 0.78 [0.57-1.07], respectively, Pinteraction = 0.75). No heterogeneity was observed by insulin dose (Pinteraction = 0.43). The HR for major adverse CV events with dapagliflozin among insulin users (0.84 [0.74-0.97]) was similar irrespective of regimen or dose (Pinteraction = 0.75 and 0.07). Dapagliflozin reduced the rate of adverse renal outcomes overall and consistently across subgroups of insulin users. Decreases in HbA1c, weight, and systolic blood pressure with dapagliflozin were seen regardless of insulin dose or regimen. The known safety profile of dapagliflozin was unchanged in patients on intensive insulin regimens.. The benefits and safety of dapagliflozin were maintained in high-risk patients receiving high-dose or intensive insulin regimens including SA insulin.

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Glucosides; Humans; Insulin; Insulin, Regular, Human; Sodium-Glucose Transporter 2 Inhibitors

To determine the effectiveness and safety of early combination of insulin glargine with intravenous (IV) insulin infusion compared with IV insulin infusion alone in the management of diabetic ketoacidosis (DKA).. This was a single-centre, open-label, randomized controlled trial of adults aged 18 years or older diagnosed with DKA. The 'early glargine' group was given subcutaneous insulin glargine 0.3 units/kg within the first 3 hours of DKA diagnosis, in addition to the standard IV insulin infusion. The control group received standard IV insulin treatment only. The primary outcome was the time to DKA resolution. The other outcomes included rebound hyperglycaemia, mortality, hypoglycaemia and hypokalaemia, as well as the length of hospital stay (LOS).. A total of 60 patients (30 patients per group) were enrolled. Most patients (76.7%) had type 2 diabetes. Both groups were similar in baseline characteristics, except for higher serum beta-hydroxybutyrate and lower pH levels in the early glargine group. The mean ± standard deviation time to DKA resolution in the early glargine group was significantly faster than the control group (9.89 ± 3.81 vs. 12.73 ± 5.37 hours; P = .022). The median (interquartile range) LOS was significantly shorter in the early glargine group than in the control group (4.75 [3.53-8.96] vs. 15.25 [5.71-26.38] days; P = .024). The incidence of rebound hyperglycaemia, all-cause mortality, hypoglycaemia and hypokalaemia was similar between the groups.. Early combination of insulin glargine with IV insulin infusion led to a faster DKA resolution and a shorter LOS, without increasing hypoglycaemia and hypokalaemia.

Topics: Adult; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Hypokalemia; Insulin; Insulin Glargine; Insulin, Regular, Human

Continuous glucose monitoring (CGM) can guide treatment for people with type 1 (T1D) and type 2 diabetes (T2D). The ANSHIN study assessed the impact of non-adjunctive CGM use in adults with diabetes using intensive insulin therapy (IIT).. This single-arm, prospective, interventional study enrolled adults with T1D or T2D who had not used CGM in the prior 6 months. Participants wore blinded CGMs (Dexcom G6) during a 20-day run-in phase, with treatment based on fingerstick glucose values, followed by a 16-week intervention phase and then a randomized 12-week extension phase with treatment based on CGM values. The primary outcome was change in HbA1c. Secondary outcomes were CGM metrics. Safety endpoints were the number of severe hypoglycaemic (SH) and diabetic ketoacidosis (DKA) events.. Of the 77 adults enrolled, 63 completed the study. Those enrolled had mean (SD) baseline HbA1c of 9.8% (1.9%), 36% had T1D, and 44% were ≥65 years old. Mean HbA1c decreased by 1.3, 1.0 and 1.0 percentage points for participants with T1D, T2D or age ≥65, respectively (p < .001 for each). CGM-based metrics including time in range also improved significantly. SH events decreased from the run-in period (67.3 per 100 person-years) to the intervention period (17.0 per 100 person-years). Three DKA events unrelated to CGM use occurred during the total intervention period.. Non-adjunctive use of the Dexcom G6 CGM system improved glycaemic control and was safe for adults using IIT.

Topics: Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Prospective Studies

To evaluate the efficacy and safety of empagliflozin in combination with insulin ± oral antidiabetic drugs (OADs) over 24 weeks, in Chinese patients with type 2 diabetes (T2D) who had insufficient glycaemic control.. This was a randomized, double-blind, placebo-controlled, parallel group, multicentre phase III study. Adult patients with T2D and insufficient glycaemic control who received insulin ± up to two OADs were randomized (1:1:1) to receive empagliflozin 10 or 25 mg, or placebo for 24 weeks. The primary endpoint was change from baseline in HbA1c at week 24.. Of 219 randomized patients, 73 patients were in each treatment group; baseline characteristics were comparable among the groups. There was a significantly larger decrease from baseline in HbA1c (adjusted mean treatment difference -0.99 and -0.98 for in the empagliflozin 10 and 25 mg groups, respectively; P < .0001) with both doses of empagliflozin than with placebo. There were also significantly larger decreases from baseline in fasting plasma glucose, 2-hour postprandial glucose and body weight with both empagliflozin doses than with placebo. Among patients in the empagliflozin 10 mg, 25 mg and placebo groups, 17.8%, 9.6% and 11.0% reported confirmed hypoglycaemic events, respectively (nominal P = .2422 and .7661 in the empagliflozin 10 and 25 mg groups, respectively), and no Clinical Events Committee-confirmed diabetic ketoacidosis events were reported.. In Chinese patients with T2D, empagliflozin combined with insulin ± OADs improved glycaemic control and was well tolerated, without an increased risk of hypoglycaemia.

Topics: Adult; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; East Asian People; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Treatment Outcome

Basal insulin Fc (BIF) (insulin efsitora alfa; LY3209590), a fusion protein combining a novel single-chain insulin variant with a human IgG Fc domain, is designed for once-weekly basal insulin administration. This phase 2 study assessed the safety and efficacy of BIF versus degludec in insulin-naive patients with type 2 diabetes (T2D) previously treated with oral antihyperglycemic medications.. During this randomized, parallel, open-label study, 278 insulin-naive patients with T2D were randomly assigned (1:1) to receive BIF once weekly or degludec once daily over the 26-week treatment period. Both groups were titrated to fasting glucose of 80-100 mg/dL (4.4 to <5.6 mmol/L). The primary end point was HbA1c change from baseline to week 26 (noninferiority margin 0.4%). Secondary end points included fasting blood glucose (FBG), six-point glucose profiles, and rate of hypoglycemia.. After 26 weeks of treatment, BIF demonstrated a noninferior HbA1c change from baseline versus degludec, with a treatment difference of 0.06% (90% CI -0.11, 0.24; P = 0.56). Both BIF and degludec treatment led to significant reductions in FBG from baseline. At week 26, the between-treatment difference for BIF versus degludec was 4.7 mg/dL (90% CI 0.1, 9.3; P = 0.09). The rate of level 2 hypoglycemia was low and not significantly different between treatment groups (BIF 0.22 events/patient/year, degludec 0.15 events/patient/year; P = 0.64); there was no severe hypoglycemia. The occurrence of treatment-emergent adverse events was also similar between BIF and degludec.. Once-weekly BIF achieved excellent glycemic control similar to degludec, with no concerning hypoglycemia or other safety findings.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glucose; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human

To evaluate the efficacy of iGlarLixi in the Asian Pacific (AP) population with type 2 diabetes (T2D) using derived time-in-ranges calculated from seven-point self-measured blood glucose.. Two phase III trials were analysed. LixiLan-O-AP was performed in insulin-naive T2D patients (n = 878) randomized to iGlarLixi, glargine 100 units/mL (iGlar) or lixisenatide (Lixi). LixiLan-L-CN was performed in insulin-treated T2D patients (n = 426) randomized to iGlarLixi or iGlar. Changes in derived time-in-ranges from baseline to end-of-treatment (EOT) and estimated treatment differences (ETDs) were analysed. The proportions of patients achieving 70% or higher derived time-in-range (dTIR), 5% or higher dTIR improvement, and the composite triple target (≥ 70% dTIR, < 4% derived time-below-the-range [dTBR] and < 25% derived time-above-the-range [dTAR]) were calculated.. The changes from baseline to EOT in dTIR with iGlarLixi were greater versus iGlar (ETD. iGlarLixi achieved greater improvements in dTIR parameters versus iGlar or Lixi in insulin-naïve and insulin-experienced AP people with T2D.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human

To address the need for noninvasive alternatives to metabolic surgery or duodenal exclusion devices for the management of type 2 diabetes (T2D) and obesity by developing an orally administered therapeutic polymer, GLY-200, designed to bind to and enhance the barrier function of mucus in the gastrointestinal tract to establish duodenal exclusion noninvasively.. A Phase 1, randomized, double-blind, placebo-controlled, single- (SAD) and multiple-ascending-dose (MAD) healthy volunteer study was conducted. In the SAD arm, four cohorts received a single dose of 0.5 g up to 6.0 g GLY-200 or placebo, while in the MAD arm, four cohorts received 5 days of twice-daily or three-times-daily dosing (total daily dose 2.0 g up to 6.0 g GLY-200 or placebo). Assessments included safety and tolerability (primary) and exploratory pharmacodynamics, including serum glucose, insulin, bile acids and gut hormones.. No safety signals were observed; tolerability signals were limited to mild to moderate dose-dependent gastrointestinal events. In the MAD arm (Day 5), reductions in glucose and insulin and increases in bile acids, glucagon-like peptide-1, peptide YY and glicentin, were observed following a nonstandardized meal in subjects receiving twice-daily dosing of 2.0 g GLY-200 (N = 9) versus those receiving placebo (N = 8).. GLY-200 is safe and generally well tolerated at doses of ≤2.0 g twice daily. Pharmacodynamic results mimic the biomarker signature observed after Roux-en-Y gastric bypass and duodenal exclusion devices, indicating a pharmacological effect in the proximal small intestine. This study represents the first clinical demonstration that duodenal exclusion can be achieved with an oral drug and supports further development of GLY-200 for the treatment of obesity and/or T2D.

Topics: Bile Acids and Salts; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Glucose; Humans; Insulin; Insulin, Regular, Human; Obesity

Fast acting insulin analogues are known to improve arterial stiffness. The combination of metformin with insulin represents a widely used therapeutic strategy in diabetes. We hypothesized that insulin treatment in patients with type 2 diabetes (T2D) with long-acting, fast-acting or basal bolus insulin as an add-on to metformin would provide additional improvement of arterial stiffness.. The INSUlin Regimens and VASCular Functions (INSUVASC) study is a pilot, randomized, open label three-arms study that included 42 patients with type 2 diabetes (T2D) in primary prevention, after a failure to oral antidiabetic agents. Arterial stiffness measurements were performed at fasting and after a standardized breakfast. During the first visit (V1) pre-randomization, participants took only metformin to perform the tests. The same tests were repeated after 4 weeks of insulin treatment during the second visit (V2).. Data were available for final analysis in 40 patients, with a mean age of 53.6±9.7 years and a mean duration of diabetes of 10.6±5.6 years. Twenty-one were females (52.5%), hypertension and dyslipidemia were present in 18 (45%) and 17 patients (42.5%), respectively. After insulin treatment, the metabolic control was associated to a decrease in oxidative stress and improvement of endothelial functions, with a post prandial diastole duration increased and a decrease of the peripheral arterial stiffness, with a better post prandial pulse pressure ratio and ejection duration after insulin. In hypertensive patients, insulin treatment provided positive effects by decreasing the pulse wave velocity and improving reflection time.. A short time treatment by insulin in addition to metformin improved myocardial perfusion. Moreover, insulin treatment in hypertensive patients provides a better hemodynamic profile in large arteries.

Topics: Adult; Diabetes Mellitus, Type 2; Diastole; Female; Humans; Insulin; Insulin, Regular, Human; Male; Metformin; Middle Aged; Pulse Wave Analysis

To investigate the benefits of using the Personalized Treatment Tool (PTT), a web-based clinical decision support tool assisting the diabetologist in the evaluation of patient's clinical characteristics and SMBG data, in the management of patients with non-insulin treated type 2 diabetes and inadequate glucose control.. We conducted a single-center, 16-week, cluster-randomized controlled trial.. Eighty-two patients with 64.3 ± 9.4 years of age, disease duration 13.2 ± 9.1 years and HbA1c 7.8 ± 0.6%, 41 in the PTT group and 41 in the control group, completed the study. At follow-up, changes in indicators of glucose control and variability were not statistically different between the two groups. However, when considering the subgroup of patients on a single anti-diabetes drug at baseline (9 in the PTT group, 14 in the control group), changes in HbA1c and CGM-derived TIR 70-140 mg/dl, 24-hour MSG, GRADE, and HBGI were significantly improved in the PTT group compared to the control group.. When performed in a structured manner and used to modify the diabetes therapy through an algorithm-driven digital tool, SMBG can lead to significant improvements of glycemic control and variability in patients with type 2 diabetes not treated with insulin.

Topics: Adolescent; Adult; Blood Glucose; Blood Glucose Self-Monitoring; Child; Child, Preschool; Decision Making; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Pilot Projects; Young Adult

To investigate the association between continuous glucose monitoring (CGM) metrics and perinatal outcomes in insulin-treated diabetes mellitus in pregnancy.. In a post-hoc analysis of the GlucoMOMS randomized controlled trial, we investigated the association between the metrics of an offline, intermittent CGM, glycated haemoglobin (HbA1c) and perinatal outcomes per trimester in different types of diabetes (type 1, 2 or insulin-treated gestational diabetes mellitus [GDM]). Data were analysed using multivariable binary logistic regression. Outcomes of interest were neonatal hypoglycaemia, pre-eclampsia, preterm birth, large for gestational age (LGA) and Neonatal Intensive Care Unit (NICU) admission. The glucose target range was defined as 3.5-7.8 mmol/L (63-140 mg/dL).. Of the 147 participants (N = 50 type 1 diabetes, N = 94 type 2 diabetes/insulin-treated GDM) randomized to the CGM group of the GlucoMOMS trial, 115 participants had CGM metrics available and were included in the current study. We found that, in pregnancies with type 1 diabetes, a higher second trimester mean glucose was associated with LGA (odds ratio 2.6 [95% confidence interval 1.1-6.2]). In type 2 and insulin-treated gestational diabetes, an increased area under the curve above limit was associated with LGA (odds ratio 10.0 [95% confidence interval 1.4-72.8]). None of the CGM metrics were associated with neonatal hypoglycaemia, pre-eclampsia, shoulder dystocia, preterm birth and NICU admission rates for pregnancies complicated by any type of diabetes.. In this study, in type 2 diabetes or insulin-treated GDM, the glucose increased area under the curve above limit was associated with increased LGA. In type 1 diabetes, the mean glucose was the major determinant of LGA. Our study found no evidence that other CGM metrics determined adverse pregnancy outcomes.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose; Humans; Hypoglycemia; Infant, Newborn; Insulin; Insulin, Regular, Human; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth

Optimizing insulin therapy for patients with type 2 diabetes can be challenging given the need for frequent dose adjustments. Most patients receive suboptimal doses and do not achieve glycemic control.. To examine whether a voice-based conversational artificial intelligence (AI) application can help patients with type 2 diabetes titrate basal insulin at home to achieve rapid glycemic control.. In this randomized clinical trial conducted at 4 primary care clinics at an academic medical center from March 1, 2021, to December 31, 2022, 32 adults with type 2 diabetes requiring initiation or adjustment of once-daily basal insulin were followed up for 8 weeks. Statistical analysis was performed from January to February 2023.. Participants were randomized in a 1:1 ratio to receive basal insulin management with a voice-based conversational AI application or standard of care.. Primary outcomes were time to optimal insulin dose (number of days needed to achieve glycemic control), insulin adherence, and change in composite survey scores measuring diabetes-related emotional distress and attitudes toward health technology and medication adherence. Secondary outcomes were glycemic control and glycemic improvement. Analysis was performed on an intent-to-treat basis.. The study population included 32 patients (mean [SD] age, 55.1 [12.7] years; 19 women [59.4%]). Participants in the voice-based conversational AI group more quickly achieved optimal insulin dosing compared with the standard of care group (median, 15 days [IQR, 6-27 days] vs >56 days [IQR, >29.5 to >56 days]; a significant difference in time-to-event curves; P = .006) and had better insulin adherence (mean [SD], 82.9% [20.6%] vs 50.2% [43.0%]; difference, 32.7% [95% CI, 8.0%-57.4%]; P = .01). Participants in the voice-based conversational AI group were also more likely than those in the standard of care group to achieve glycemic control (13 of 16 [81.3%; 95% CI, 53.7%-95.0%] vs 4 of 16 [25.0%; 95% CI, 8.3%-52.6%]; difference, 56.3% [95% CI, 21.4%-91.1%]; P = .005) and glycemic improvement, as measured by change in mean (SD) fasting blood glucose level (-45.9 [45.9] mg/dL [95% CI, -70.4 to -21.5 mg/dL] vs 23.0 [54.7] mg/dL [95% CI, -8.6 to 54.6 mg/dL]; difference, -68.9 mg/dL [95% CI, -107.1 to -30.7 mg/dL]; P = .001). There was a significant difference between the voice-based conversational AI group and the standard of care group in change in composite survey scores measuring diabetes-related emotional distress (-1.9 points vs 1.7 points; difference, -3.6 points [95% CI, -6.8 to -0.4 points]; P = .03).. In this randomized clinical trial of a voice-based conversational AI application that provided autonomous basal insulin management for adults with type 2 diabetes, participants in the AI group had significantly improved time to optimal insulin dose, insulin adherence, glycemic control, and diabetes-related emotional distress compared with those in the standard of care group. These findings suggest that voice-based digital health solutions can be useful for medication titration.. ClinicalTrials.gov Identifier: NCT05081011.

Topics: Adult; Aged; Artificial Intelligence; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Male; Middle Aged

We studied a smart insulin pen cap that can be plugged to several brand of insulin pens, to track insulin administration via smart-phone Bluetooth technology, with alarm/reminder system aiming.. This pilot randomized, cross-over design study assessed the use of a smart insulin pen cap in improving adherence, glycemic control and patient satisfaction in insulin-treated patients with poorly controlled type 2 diabetes. Eighty patients on basal insulin ± oral agents with hemoglobin A1C (HbA1c) between 7.0% and 12.0% were randomized to a 12-week active phase receiving alarms/reminders and a 12-week control/masked phase without feedback. We assessed differences between groups on treatment adherence, insulin omission, and mistiming of insulin injections, HbA1c, treatment satisfaction (using Diabetes Treatment Satisfaction Questionnaire Status).. Compared to the control/masked phase, the active phase resulted in lower mean daily blood glucose (147.0 ± 34 vs 157.6 ± 42 mg/dL,. The results of this pilot study indicates that this smart insulin pen cap was effective in improving glycemic control with overall good satisfaction in insulin treated patients with type 2 diabetes. Future studies are needed to confirm its potential for improving care in insulin treated patients with diabetes.

Topics: Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Pilot Projects

Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes.. Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30-5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin-angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%.. Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia.. Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.

Topics: Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Insulin; Insulin, Regular, Human; Male; Naphthyridines; Renal Insufficiency, Chronic

To investigate whether an increased bolus: basal insulin ratio (BBR) with liver-targeted bolus insulin (BoI) would increase BoI use and decrease hypoglycaemic events (HEv).. We enrolled 52 persons (HbA1c 6.9% ± 0.12%, mean ± SEM) with type 1 diabetes using multiple daily injections. Hepatic-directed vesicle (HDV) was used to deliver 1% of peripheral injected BoI to the liver. A 90-day run-in period was used to introduce subjects to unblinded continuous glucose monitoring and optimize standard basal insulin (BaI) (degludec) and BoI (lispro) dosing. At 90 days, BoI was changed to HDV-insulin lispro and subjects were randomized to an immediate 10% or 40% decrease in BaI dose.. At 90 days postrandomization, total insulin dosing was increased by ~7% in both cohorts. The -10% and -40% BaI cohorts were on 7.7% and 13% greater BoI with 6.9% and 30% (P = .02) increases in BBR, respectively. Compared with baseline at randomization, nocturnal level 2 HEv were reduced by 21% and 43%, with 54% and 59% reductions in patient-reported HEv in the -10% and -40% BaI cohorts, respectively.. Our study shows that liver-targeted BoI safely decreases HEv and symptoms without compromising glucose control. We further show that with initiation of liver-targeted BoI, the BBR can be safely increased by significantly lowering BaI dosing, leading to greater BoI usage.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Insulin, Regular, Human; Liver

To compare the efficacy and safety of basal insulin glargine 100 units/ml (Gla) + 2-3 oral antihyperglycaemic drugs (OADs) with twice-daily premixed insulin aspart 70/30 (Asp30) + metformin (MET) after short-term intensive insulin therapy in adults with type 2 diabetes in China.. This open-label trial enrolled insulin-naïve adults with type 2 diabetes and an HbA1c of 7.5%-11.0% (58-97 mmol/mol) despite treatment with 2-3 OADs. All participants stopped previous OADs except MET, then received short-term intensive insulin therapy during the run-in period, when those with a fasting plasma glucose of less than 7.0 mmol/L and 2-hour postprandial glucose of less than 10.0 mmol/L were randomized to Gla + MET + a dipeptidyl peptidase-4 inhibitor or twice-daily Asp30 + MET. If HbA1c was more than 7.0% (>53 mmol/mol) at week 12, participants in the Gla group were added repaglinide or acarbose, at the physician's discretion, and participants in the Asp30 group continued to titrate insulin dose. The change in HbA1c from baseline to week 24 was assessed in the per protocol (PP) population (primary endpoint).. There were 384 enrollees (192 each to Gla and Asp30); 367 were included in the PP analysis. The threshold for non-inferiority of Gla + OADs versus Asp30 + MET was met, with a least squares mean change from baseline in HbA1c of -1.72% and -1.70% (-42.2 and -42.1 mmol/mol), respectively (estimated difference -0.01%; 95% CI -0.20%, 0.17% [-0.1 mmol/mol; 95% CI -2.2, 1.9]). Achievement of HbA1c less than 7.0% (<53 mmol/mol) was comparable between the groups (60% vs. 57%). The proportion of participants with any (24% vs. 38%; P = .003), symptomatic (19% vs. 31%; P = .007) or confirmed hypoglycaemia (18% vs. 33%; P < .001) was lower in the Gla + OADs group.. Compared with Asp30 + MET, Gla + 2-3 OADs showed similar efficacy but a lower hypoglycaemia risk in Chinese individuals with type 2 diabetes who had undergone short-term intensive insulin therapy.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human; Metformin

Administration of supplemental sliding scale insulin for correction of hyperglycemia in non-intensive care unit (ICU) patients with type 2 diabetes is frequently used with basal-bolus insulin regimens. In this noninferiority randomized controlled trial we tested whether glycemic control is similar with and without aggressive sliding scale insulin treatment before meals and bedtime in patients treated with basal-bolus insulin regimens.. Patients with type 2 diabetes with admission blood glucose (BG) 140-400 mg/dL treated with basal-bolus insulin were randomized to intensive (correction for BG >140 mg/dL, n = 108) or to nonintensive (correction for BG >260 mg/dL, n = 107) administration of rapid-acting sliding scale insulin before meals and bedtime. The groups received the same amount of sliding scale insulin for BG >260 mg/dL. Primary outcome was difference in mean daily BG levels between the groups during hospitalization.. Mean daily BG in the nonintensive group was noninferior to BG in the intensive group with equivalence margin of 18 mg/dL (intensive 172 ± 38 mg/dL vs. nonintensive 173 ± 43 mg/dL, P = 0.001 for noninferiority). There were no differences in the proportion of target BG readings of 70-180 mg/dL, <70 or <54 mg/dL (hypoglycemia), or >350 mg/dL (severe hyperglycemia) or total, basal, or prandial insulin doses. Significantly fewer subjects received sliding scale insulin in the nonintensive (n = 36 [34%]) compared with the intensive (n = 98 [91%] [P < 0.0001]) group with no differences in sliding scale insulin doses between the groups among those who received sliding scale insulin (intensive 7 ± 4 units/day vs. nonintensive 8 ± 4 units/day, P = 0.34).. Among non-ICU patients with type 2 diabetes on optimal basal-bolus insulin regimen with moderate hyperglycemia (BG <260 mg/dL), a less intensive sliding scale insulin treatment did not significantly affect glycemic control.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human

To compare the effect of an isocaloric multifactorial diet with a diet rich in monounsaturated fatty acids (MUFA) and similar macronutrient composition on pancreatic fat (PF) and postprandial insulin response in type 2 diabetes (T2D).. According to a randomized controlled parallel-group design, 39 individuals with T2D, 35-75 years old, in satisfactory blood glucose control, were assigned to an 8 week isocaloric intervention with a multifactorial diet rich in MUFA, polyunsaturated fatty acids, fiber, polyphenols, and vitamins (n = 18) or a MUFA-rich diet (n = 21). Before/after the intervention, PF content was measured by the proton-density fat fraction using a three-dimensional mDIXON MRI sequence, and plasma insulin and glucose concentrations were measured over a 4 h test meal with a similar composition as the assigned diet.. After 8 weeks, PF significantly decreased after the multifactorial diet (from 15.7 ± 6.5% to 14.1 ± 6.3%; P = 0.024), while it did not change after the MUFA diet (from 17.1 ± 10.1% to 18.6 ± 10.6%; P = 0.139) with a significant difference between diets (P = 0.014). Postprandial glucose response was similar in the two groups. Early postprandial insulin response (incremental postprandial areas under the curve [iAUC0-120]) significantly increased with the multifactorial diet (from 36,340 ± 34,954 to 44,138 ± 31,878 pmol/L/min; P = 0.037), while it did not change significantly in the MUFA diet (from 31,754 ± 18,446 to 26,976 ± 12,265 pmol/L/min; P = 0.178), with a significant difference between diets (P = 0.023). Changes in PF inversely correlated with changes in early postprandial insulin response (r = -0.383; P = 0.023).. In patients with T2D, an isocaloric multifactorial diet, including several beneficial dietary components, markedly reduced PF. This reduction was associated with an improved postprandial insulin response.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Diet; Fatty Acids, Monounsaturated; Glucose; Humans; Insulin; Insulin, Regular, Human; Middle Aged; Postprandial Period; Triglycerides

The efficacy and safety of continuous glucose monitoring (CGM) in adjusting inpatient insulin therapy have not been evaluated.. This randomized trial included 185 general medicine and surgery patients with type 1 and type 2 diabetes treated with a basal-bolus insulin regimen. All subjects underwent point-of-care (POC) capillary glucose testing before meals and bedtime. Patients in the standard of care (POC group) wore a blinded Dexcom G6 CGM with insulin dose adjusted based on POC results, while in the CGM group, insulin adjustment was based on daily CGM profile. Primary end points were differences in time in range (TIR; 70-180 mg/dL) and hypoglycemia (<70 mg/dL and <54 mg/dL).. There were no significant differences in TIR (54.51% ± 27.72 vs. 48.64% ± 24.25; P = 0.14), mean daily glucose (183.2 ± 40 vs. 186.8 ± 39 mg/dL; P = 0.36), or percent of patients with CGM values <70 mg/dL (36% vs. 39%; P = 0.68) or <54 mg/dL (14 vs. 24%; P = 0.12) between the CGM-guided and POC groups. Among patients with one or more hypoglycemic events, compared with POC, the CGM group experienced a significant reduction in hypoglycemia reoccurrence (1.80 ± 1.54 vs. 2.94 ± 2.76 events/patient; P = 0.03), lower percentage of time below range <70 mg/dL (1.89% ± 3.27 vs. 5.47% ± 8.49; P = 0.02), and lower incidence rate ratio <70 mg/dL (0.53 [95% CI 0.31-0.92]) and <54 mg/dL (0.37 [95% CI 0.17-0.83]).. The inpatient use of real-time Dexcom G6 CGM is safe and effective in guiding insulin therapy, resulting in a similar improvement in glycemic control and a significant reduction of recurrent hypoglycemic events compared with POC-guided insulin adjustment.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Glucose; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

Sodium-glucose cotransporter-2 inhibitors (SGLT2is), such as empagliflozin, lower blood glucose in type 2 diabetes mellitus and improve cardiorenal outcomes regardless of diabetes presence. Whether SGLT2is exert any effects on the brain's metabolism has not been studied. We conducted a single-arm clinical trial to investigate the effects of once daily administration of oral empagliflozin (25 mg) for 14 days on systemic and brain metabolism in 21 non-diabetics aged 55 years old or older. Empagliflozin lowered circulating insulin and elevated β-hydroxybutyrate over 34-h periods, both following its first administration and after 14 days of daily administration, with minor alterations in glucose homeostasis. Levels of phosphorylated insulin-like growth factor-1 receptor (pIGF-1R), phosphorylated insulin receptor (pIR), phosphorylated-in-tyrosine insulin receptor substrate-1 (pY-IRS-1), and phosphorylated protein kinase B or AKT (pAKT) were increased in extracellular vesicles enriched for neuronal origin (NEVs) following the first empagliflozin administration, but not after 14 days. Our finding of IGF-1R upregulation in NEVs is promising because several post-mortem and epidemiological studies support the idea that upregulation of IGF signaling may protect against Alzheimer's disease (AD). Moreover, our finding showing activation of insulin signaling and, in particular, the canonical pathway (pIR, pY-IRS-1, pAKT) in NEVs is important because such changes have been repeatedly associated with neuronal survival. Using brain magnetic resonance spectroscopy (MRS), we detected decreased concentrations of the excitatory neurotransmitter glutamate and its precursor glutamine after empagliflozin administration. This finding is also encouraging since glutamatergic excitotoxicity has long been implicated in AD pathology. Overall, our findings may motivate the repurposing of SGLT2is for use in AD and other, related diseases that are characterized by downregulation of IGF-1/insulin signaling in neurons and excitotoxicity.

Topics: Alzheimer Disease; Blood Glucose; Brain; Diabetes Mellitus, Type 2; Female; Glutamic Acid; Humans; Insulin; Insulin-Like Growth Factor I; Insulin, Regular, Human; Ketosis; Middle Aged; Neurons; Neurotransmitter Agents; Placenta Growth Factor; Receptor, Insulin; Signal Transduction; Sodium-Glucose Transporter 2 Inhibitors

Antipsychotics (APs) are the cornerstone of treatment for schizophrenia (SCZ) but are unfortunately associated with serious metabolic adverse effects including weight gain and type 2 diabetes. The pathophysiology of AP-induced metabolic dysfunction is largely undetermined. Brain insulin resistance has been posited to be at the cross-roads of many cognitive and metabolic disorders, and disruption of central insulin action has emerged as a possible explanatory mechanism underlying AP induced metabolic dysfunction. Previous studies suggest that change in neuroimaging-based parameters with intranasal insulin administration can be leveraged to investigate brain insulin resistance. In this proof-of-concept study, we will utilize neural signatures of insulin action in the brain to examine if APs disrupt brain insulin signaling. It is hypothesized that: 1) intranasal insulin (INI), but not intranasal placebo (INP), will change cerebral blood flow and resting state connectivity, as well as increase glutamate levels in the striatum and dorsolateral prefrontal cortex; 2) oral olanzapine (OLA), but not oral placebo (PL), will inhibit the effect of INI on these parameters. Thirty-two healthy volunteers will undergo a single blind, cross-over design, wherein all participants receive the following four treatment combinations, 2-6 weeks apart, in a random sequence: INP + PL, INP + OLA, INI + PL, and INI + OLA. Participants will undergo an MRI-based assay of brain insulin resistance 15 minutes after administering 160 IU INI or INP. The scanning protocol includes resting and task-based functional MRI, arterial spin labelling, and proton magnetic resonance spectroscopy. Demonstrating that OLA can acutely induce brain insulin resistance is clinically relevant to metabolic health in SCZ. Evidence of brain insulin resistance induced by acute AP dosing can inform the early use of adjunctive insulin sensitizers for the treatment of metabolic comorbidities associated with AP treatment in severe mental illness. Trial registration ClinicalTrials.gov Registration: NCT03741478.

Topics: Antipsychotic Agents; Brain; Cross-Over Studies; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Magnetic Resonance Imaging; Olanzapine; Single-Blind Method

Insulin is an essential medicine in the management of diabetes. When stored at high temperatures(HTs), its efficacy could rapidly decline. Therefore, appropriate storage of in-use insulin is necessary to achieve its maximum therapeutic effects. However, the ambient temperature in tropical countries is normally relatively high. This study aimed to compare the efficacies of basal insulin in a pen previously kept at 37°C for 21 days and basal insulin in a refrigerated pen (2°C-8°C). Continuous glucose monitoring (CGM) was used to evaluate daily mean glucose levels (MGLs).. This randomized controlled, crossover, equivalence trial recruited adults with type 2 diabetes mellitus and glycated hemoglobin levels <8% who had used insulin glargine for >3 months. Subjects were randomized for sequential use of refrigerated basal insulin followed by basal insulin kept at HT, with a 2-week washout between phases. The HT insulin pens were stored in a 37°C incubator for 21 days before use, while the refrigerated insulin pens were stored at 2°C-8°C. Study patients received 7-day CGM. The primary outcome was the difference in the groups' MGLs. The secondary outcome parameters were glucose variability represented by the standard deviation (SD), mean amplitude of glycemic excursion (MAGE), and percentage of time in range (TIR). The remaining quantity of insulin was evaluated by ultrahigh-performance liquid chromatography (UHPLC) assay.. HT basal insulin pens retain their potency and have biological activity comparable to that of refrigerated pens.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Long-Acting; Insulin, Regular, Human; Temperature

To better understand outcomes in people with type 2 diabetes at high risk of hypoglycemia, we conducted post hoc analyses in subgroups of participants from the real-world ACHIEVE Control study (NCT02451137) with ≥1 hypoglycemia risk factor.. Insulin-naive adults with type 2 diabetes and A1c ≥8% were randomized 1:1 to insulin glargine 300 U/mL (Gla-300) or standard-of-care basal insulin (SOC-BI). Participants had documented history of ≥1 risk factors for hypoglycemia: chronic kidney disease, cardiovascular disease, dementia or blindness, age ≥65 years, or history of hypoglycemia. Outcomes included individualized A1c target attainment without documented symptomatic hypoglycemia (blood glucose [BG] ≤3.9 mmol/L or <3.0 mmol/L) or severe hypoglycemia, A1c target attainment, and absence of documented symptomatic or severe hypoglycemia at 6 and 12 months.. Within subgroups, odds ratios generally showed trends favoring Gla-300 versus SOC-BI, particularly for hypoglycemia avoidance in participants ≥65 years of age (BG ≤3.9 mmol/L; odds ratio, 1.52; 95% confidence interval, 1.14-2.03) and those with chronic kidney disease (BG ≤3.9 mmol/L; odds ratio, 2.28; 95% confidence interval, 1.26-4.12). Results were consistent with the overall population.. These data suggest potential benefit of Gla-300 versus SOC-BI for avoiding hypoglycemia in participants with ≥1 hypoglycemia risk factor.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human

To test the hypothesis that the addition of periodic courses of short-term intensive insulin therapy (IIT) could enhance the effect of metformin (MET) maintenance therapy on preservation of beta-cell function following induction IIT.. In this multicentre, randomized controlled trial, 108 adults with type 2 diabetes (median 1.3 years' duration; HbA1c 6.6% ± 0.6%) were randomized to 3 weeks of induction IIT (glargine, lispro) followed by MET maintenance, either with or without periodic 2-week courses of IIT every 3 months for 2 years. Beta-cell function was assessed by the Insulin Secretion Sensitivity Index-2 (ISSI-2) at an oral glucose tolerance test every 3 months.. In both arms, induction IIT increased ISSI-2, improved whole-body insulin sensitivity and reduced hepatic insulin resistance (all P ≤ .0004). The primary outcome of baseline-adjusted ISSI-2 at 2 years was not improved by the addition of intermittent IIT (MET + IIT) and was slightly higher in the MET arm (baseline-adjusted difference -35 [95% CI: -66, -3]), with three additional beta-cell measures showing no significant differences. Baseline-adjusted HbA1c at 2 years did not differ between MET and MET + IIT (6.3% ± 0.1% vs. 6.4% ± 0.1%, P = .46), with 32.6% of participants in each arm maintaining HbA1c of 6.0% or less at 2 years.. Although initial induction IIT induces metabolic improvement, subsequent repeat courses of IIT every 3 months do not further enhance the effect of MET maintenance therapy on beta-cell function.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human; Metformin

Insulin icodec is a novel, long-acting insulin analog designed to cover basal insulin requirements with once-weekly subcutaneous administration. Here we describe the molecular engineering and the biological and pharmacological properties of insulin icodec.. A number of in vitro assays measuring receptor binding, intracellular signaling as well as cellular metabolic and mitogenic responses were used to characterize the biological properties of insulin icodec. To evaluate the pharmacological properties of insulin icodec in individuals with type 2 diabetes, a randomized, double-blind, double-dummy, active-controlled, multiple-dose, dose escalation trial was conducted.. The long half-life of insulin icodec was achieved by introducing modifications to the insulin molecule aiming to obtain a safe, albumin-bound circulating depot of insulin icodec, providing protracted insulin action and clearance. Addition of a C20 fatty diacid-containing side chain imparts strong, reversible albumin binding, while three amino acid substitutions (A14E, B16H and B25H) provide molecular stability and contribute to attenuating insulin receptor (IR) binding and clearance, further prolonging the half-life. In vitro cell-based studies showed that insulin icodec activates the same dose-dependent IR-mediated signaling and metabolic responses as native human insulin (HI). The affinity of insulin icodec for the insulin-like growth factor-1 receptor was proportionately lower than its binding to the IR, and the in vitro mitogenic effect of insulin icodec in various human cells was low relative to HI. The clinical pharmacology trial in people with type 2 diabetes showed that insulin icodec was well tolerated and has pharmacokinetic/pharmacodynamic properties that are suited for once-weekly dosing, with a mean half-life of 196 hours and close to even distribution of glucose-lowering effect over the entire dosing interval of 1 week.. The molecular modifications introduced into insulin icodec provide a novel basal insulin with biological and pharmacokinetic/pharmacodynamic properties suitable for once-weekly dosing.. NCT02964104.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Long-Acting; Insulin, Regular, Human

To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM).. To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test.. No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes.. LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes.

Topics: Asymptomatic Diseases; Biosimilar Pharmaceuticals; Cross Reactions; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Hypersensitivity; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Immunogenetic Phenomena; Incidence; Insulin Antibodies; Insulin Glargine; Insulin, Regular, Human; Recombinant Proteins

To compare metabolic control under lispro and recombinant regular human insulin (RHI) in people with diet-unresponsive type 2 diabetes mellitus (T2DM) and compensated non-alcoholic liver disease (CLD).. 108 people with T2DM and CLD were randomly allocated to RHI or lispro according to a 12+12 week cross-over protocol. A 1-week continuous glucose monitoring (CGM) session was performed at the end of each treatment period followed by a standard meal test with a 12IU lispro or RHI shot ahead.. CGM showed higher glycemic excursions under RHI than under lispro (p<0.01) with lower glucose levels in the late post-absorption phase (p<0.05) and even more during the night (p<0.01). Post-challenge incremental areas under the curve (ΔAUC) were undistinguishable for insulin but lower for glucose, while insulin peaked higher and earlier and glycemic excursions were lower with lispro than with RHI (0.05

Topics: Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Regular, Human; Liver Cirrhosis; Male; Middle Aged; Postprandial Period

The present study was to compare the efficacy and safety of subject-driven and investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID).. In this 20-week, randomized, open-label, two-group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self-mixed human insulin were randomized 1:1 to subject-driven or investigator-driven titration of BIAsp 30 BID, in combination with metformin and/or α-glucosidase inhibitors. Dose adjustment was decided by patients in the subject-driven group after training, and by investigators in the investigator-driven group.. Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA1c) reduction was 14.5 mmol/mol (1.33%) in the subject-driven group and 14.3 mmol/mol (1.31%) in the investigator-driven group. Non-inferiority of subject-titration vs investigator-titration in reducing HbA1c was confirmed, with estimated treatment difference -0.26 mmol/mol (95% confidence interval -2.05, 1.53) (-0.02%, 95% confidence interval -0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self-measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient-year) was reported in the subject-driven (1.10) and investigator-driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA1c <53.0 mmol/mol (7.0%), and 51.2 and 45.9% patients achieving the HbA1c target without confirmed hypoglycemia throughout the trial in the subject-driven and investigator-driven groups, respectively.. Subject-titration of BIAsp 30 BID was as efficacious and well-tolerated as investigator-titration. The present study supported patients to self-titrate BIAsp 30 BID under physicians' supervision.

Topics: Adult; Asian People; Biphasic Insulins; Blood Glucose; China; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Regular, Human; Male; Middle Aged; Research Personnel; Research Subjects

To compare the effects of the neutral protamine Hagedorn (NPH) recombinant human insulin formulations Gansulin and Humulin N® on the glycemic control of patients with type 2 diabetes mellitus (T2DM).. Prospective, double-blind, randomized, parallel, single-center study of 37 individuals with T2DM treated with NPH insulin formulations. The Tukey-Kramer test for multiple comparisons, the Wilcoxon paired comparison test and the Chi-Square test were used for the statistical analyses. The significance level was set at 5% (p < 0.05).. The NPH insulin formulations Humulin and Gansulin similarly reduced the HbA1c levels observed at the end of the study compared with the values obtained at the beginning of the study. In the Humulin group, the initial HbA1c value of 7.91% was reduced to 6.56% (p < 0.001), whereas in the Gansulin group, the reduction was from 8.18% to 6.65% (p < 0.001). At the end of the study, there was no significant difference between the levels of glycated hemoglobin (p = 0.2410), fasting plasma glucose (FG; p = 0.9257) and bedtime plasma glucose (BG; p = 0.3906) between the two insulin formulations. There was no nt difference in the number of hypoglycemic events between the two insulin formulations, and no severe hyp episodes were recorded.. This study demonstrated similar glycemic control by NPH insulin Gansulin compared with human insulin Humulin N® in patients with T2DM.

Topics: Adult; Blood Glucose; Chemistry, Pharmaceutical; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Regular, Human; Isophane Insulin, Human; Male; Middle Aged; Prospective Studies; Recombinant Fusion Proteins; Statistics, Nonparametric; Treatment Outcome

Initiation and titration of human regular U-500 insulin (U-500R) with a dosing algorithm of either thrice daily (TID) or twice daily (BID) improved glycemic control with fewer injections in patients with type 2 diabetes treated with high-dose, high-volume U-100 insulin. The objective of this analysis was to compare patient-reported outcomes between U-500R TID and BID treatment groups in this titration-to-target randomized, clinical trial.. In this 24-week, open-label, parallel trial, 325 patients were randomized to TID (n = 162) or BID (n = 163) U-500R after a 4-week lead-in period (screening). The Treatment Related Impact Measure-Diabetes (TRIM-D) and EQ-5D-5L questionnaires were administered at screening, baseline/randomization, and endpoint (24 weeks). The Visual Analog Scale-Injection Site Pain (VAS-ISP) was assessed at baseline/randomization, 12 weeks, and endpoint.. The TRIM-D showed statistically significant improvements in overall scores from baseline to endpoint for both BID and TID groups, most domains in the TID group, and all domains in the BID group. The BID group achieved better scores than the TID patients in overall and in treatment burden, daily life, and compliance domains (p < .05). EQ-5D-5L index scores showed no statistically significant differences for TID and BID groups (and no differences between TID and BID groups) from baseline to endpoint. VAS-ISP scores improved for both treatment groups (-5.60 TID; -6.47 BID; p < .05 for both) from baseline to endpoint.. U500 can be successfully titrated for improved glycemic control using BID and TID regimens with diabetes-specific Patient-Reported Outcomes showing improvements in both arms; however, BID had better scores than TID in overall, treatment burden, daily life, and compliance domains.. These secondary analyses are based on the study first received January 22, 2013 and reported in Clinical Trial Registry No.: NCT01774968 .

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Insulin, Regular, Human; Male; Medication Adherence; Middle Aged; Patient Reported Outcome Measures; Quality of Life

To compare the efficacy and safety of 2 dosing regimens for human regular U-500 insulin (U-500R, 500 units/mL) replacing high-dose U-100 insulins with or without oral antihyperglycemic drugs in patients with inadequately controlled type 2 diabetes (T2D).. We conducted a 24-week, open-label, parallel trial in 325 patients (demographics [means]: age, 55.4 years; diabetes duration, 15.2 years; body mass index, 41.9 kg/m(2); glycated hemoglobin [HbA1c], 8.7%; U-100 insulin dose, 287.5 units administered in 5 injections/day [median; range, 2 to 10]). Patients were randomized to thrice-daily (TID, n = 162) or twice-daily (BID, n = 163) U-500R after a 4-week lead-in period. The primary outcome was HbA1c change from baseline.. After 24 weeks, both treatments demonstrated significant HbA1c reductions (TID, -1.12%; BID, -1.22%; both, P<.001) and clinical equivalence (difference, -0.10%; 95% confidence interval, -0.33 to 0.12%; noninferiority margin, 0.4%). Comparable increases in total daily U-500R dose (TID, 242.7 to 343.1 units; BID, 249.0 to 335.0 units) were observed. Incidence and rate of documented symptomatic hypoglycemia (≤70 mg/dL) were lower for TID versus BID (P = .003 and P = .02, respectively); severe hypoglycemia was similar between treatments. Weight gain was similar in both groups (TID, 5.4 kg; BID, 4.9 kg).. Initiation and titration of U-500R using either algorithm (TID or BID) improves glycemic control effectively and safely with fewer injections in patients with T2D treated with high-dose/high-volume U-100 insulin. These results provide clinicians with a practical framework for using U-500R in severely insulin-resistant patients with suboptimally controlled T2D.

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin Resistance; Insulin, Regular, Human; Male; Middle Aged; Treatment Outcome

Hyperglucagonemia is a characteristic feature of type 2 diabetes (T2DM) that has been postulated to be due to β-cell dysfunction and the resultant loss of insulin-mediated α-cell suppression. When administered in early T2DM, short-term intensive insulin therapy (IIT) can improve β-cell function, resulting in reduced glycemic variability.. To evaluate the impact of IIT on hyperglucagonemia and its associations with β-cell function and glycemic variability. Design/Setting/Participants/Intervention: Sixty-two patients with T2DM of mean 3.0 ± 2.1 years duration and glycated hemoglobin of 6.8 ± 0.7% underwent 4 weeks of IIT, consisting of basal detemir and premeal insulin aspart.. Glucagon response was measured by area under the glucagon curve (AUCglucagon) on oral glucose tolerance test at baseline and 1 day post-IIT. β-Cell function before and after IIT was assessed by Insulin Secretion-Sensitivity Index-2 and ΔISR0-120/Δglucose0-120*Matsuda index (where ISR is the prehepatic insulin secretion rate determined by C-peptide deconvolution). Glucose variability was assessed in both the first and last weeks by the coefficient of variation of capillary glucose on daily six-point self-monitoring profiles.. Both Insulin Secretion-Sensitivity Index-2 and ΔISR0-120/Δglucose0-120*Matsuda index demonstrated improvement in β-cell function after IIT (both P ≤ .02), accompanied by reduced glycemic variability (P = .05). There was a marked reduction in AUCglucagon after IIT, as compared to baseline (P < .001). However, the decrease in AUCglucagon was not associated with the change in either β-cell measure (both P ≥ .34) or glucose variability (P = .37).. Short-term IIT can reduce post-challenge hyperglucagonemia in early T2DM, but this effect does not appear to be due to improved β-cell function.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Insulin, Regular, Human; Male; Middle Aged; Pancreatic Diseases; Up-Regulation

Few randomized studies have focused on the optimal management of non-intensive care unit patients with type 2 diabetes in Latin America. We compared the safety and efficacy of a basal-bolus regimen with analogues and human insulins in general medicine patients admitted to a University Hospital in Asunción, Paraguay.. In a prospective, open-label trial, we randomized 134 nonsurgical patients with blood glucose (BG) between 140 and 400 mg/dL to a basal-bolus regimen with glargine once daily and glulisine before meals (n = 66) or Neutral Protamine Hagedorn (NPH) twice daily and regular insulin before meals (n = 68). Major outcomes included differences in daily BG levels and frequency of hypoglycemic events between treatment groups.. There were no differences in the mean daily BG (157 ± 37 mg/dL versus 158 ± 44 mg/dL; P = .90) or in the number of BG readings within target <140 mg/dL before meals (76% versus 74%) between the glargine/glulisine and NPH/regular regimens. The mean insulin dose in the glargine/glulisine group was 0.76 ± 0.3 units/kg/day (glargine, 22 ± 9 units/day; glulisine, 31 ± 12 units/day) and was not different compared with NPH/regular group (0.75 ± 0.3 units/kg/day [NPH, 28 ± 12 units/day; regular, 23 ± 9 units/day]). The overall prevalence of hypoglycemia (<70 mg/dL) was similar between patients treated with NPH/regular and glargine/glulisine (38% versus 35%; P = .68), but more patients treated with human insulin had severe (<40 mg/dL) hypoglycemia (7.6% versus 25%; P = .08). There were no differences in length of hospital stay or mortality between groups.. The basal-bolus regimen with insulin analogues resulted in equivalent glycemic control and frequency of hypoglycemia compared to treatment with human insulin in hospitalized patients with diabetes.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human; Male; Middle Aged; Outcome Assessment, Health Care; Paraguay

To investigate the efficacy and safety of prandial Technosphere inhaled insulin (TI), an inhaled insulin with a distinct time action profile, in insulin-naïve type 2 diabetes (T2D) inadequately controlled on oral antidiabetes agents (OADs).. Subjects with T2D with HbA1c levels ≥7.5% (58.5 mmol/mol) and ≤10.0% (86.0 mmol/mol) on metformin alone or two or more OADs were randomized to add-on prandial TI (n = 177) or prandial Technosphere inhaled placebo (TP) (n = 176) to their OAD regimen in this double-blind, placebo-controlled trial. Primary end point was change in HbA1c at 24 weeks.. TI significantly reduced HbA1c by -0.8% (-9.0 mmol/mol) from a baseline of 8.3% (66.8 mmol/mol) compared with TP -0.4% (-4.6 mmol/mol) (treatment difference -0.4% [95% CI -0.57, -0.23]; P < 0.0001). More TI-treated subjects achieved an HbA1c ≤7.0% (53.0 mmol/mol) (38% vs. 19%; P = 0.0005). Mean fasting plasma glucose was similarly reduced in both groups. Postprandial hyperglycemia, based on 7-point glucose profiles, was effectively controlled by TI. Mean weight change was 0.5 kg for TI and -1.1 kg for the TP group (P < 0.0001). Mild, transient dry cough was the most common adverse event, occurring similarly in both groups (TI, 23.7%; TP, 19.9%) and led to discontinuation in only 1.1% of TI-treated and 3.4% of TP-treated subjects. There was a small decline in forced expiratory volume in 1 s in both groups, with a slightly larger decline in the group receiving TI (TI, -0.13 L; TP, -0.04 L). The difference resolved after treatment discontinuation.. Prandial TI added to one or more OADs in inadequately controlled T2D is an effective treatment option. Mild, transient dry cough was the most common adverse event.

Topics: Administration, Inhalation; Adult; Aged; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin, Regular, Human; Male; Metformin; Microspheres; Middle Aged; Placebos; Powders; Treatment Outcome

To assess β-cell function and insulin sensitivity following improvement in glycemic control in severely insulin-resistant patients with poorly controlled type 2 diabetes (T2D).. A subset of patients in a 24-week, open-label, randomized trial comparing thrice-daily (n = 14/162) versus twice-daily (n = 11/163) human regular U-500 insulin (U-500R) underwent mixed meal tolerance testing at baseline and endpoint. Baseline characteristics were similar between treatment groups (combined means: age, 54.0 years; diabetes duration, 13.6 years; body mass index, 38.8 kg/m(2); glycated hemoglobin [HbA1c], 8.3%; U-100 insulin dose, 287.6 units/day, 2.6 units/kg/day). Primary outcome measure was ratio of area under the curve (AUC) for C-peptide to glucose (AUCC-peptide/AUCglucose) at 24-week endpoint.. Change from baseline HbA1c, daily U-500R dose, and weight were -1.17% (P = .0002), +80.8 units (P = .0003), and +5.9 kg (P = .33), respectively. β-Cell function significantly improved after 24 weeks of U-500R therapy in combined treatment groups. The AUCC-peptide/AUCglucose increased 34.0% (ratio of least-squares geometric mean, 1.34; 95% confidence interval, 1.18 to 1.52; P = .0001). Integral of total insulin secretion rate increased from 27.0 to 33.7 nmol/m(2), and glucose sensitivity improved from 18.3 to 24.0 pmol/min/m(2)/mM (both, P = .02). Matsuda index improved from 0.8 to 1.3 (P = .008).. Despite long-standing diabetes and poor glycemic control at baseline, functional recovery of β-cells was observed with improved glycemic control in these severely insulin-resistant patients with T2D, possibly due to alleviation of glucotoxicity.

Topics: Adult; Aged; Blood Glucose; Calibration; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Dosage Calculations; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Insulin-Secreting Cells; Insulin, Regular, Human; Male; Middle Aged; Severity of Illness Index; Time Factors

Premixed insulin is a commonly prescribed formulation for the outpatient management of patients with type 2 diabetes. The safety and efficacy of premixed insulin formulations in the hospital setting is not known.. In a prospective, open-label trial, we randomized general medicine and surgery patients to receive a basal-bolus regimen with glargine once daily and glulisine before meals (n = 33) or premixed human insulin (30% regular insulin and 70% NPH insulin) twice daily (n = 39). Major outcomes included differences in daily blood glucose (BG) levels and frequency of hypoglycemic events (<70 mg/dL) between treatment groups.. At the first prespecified interim analysis, the study was stopped early because of an increased frequency of hypoglycemia >50% in patients treated with premixed human insulin. A total of 64% of patients treated with premixed insulin experienced one or more episodes of hypoglycemia compared with 24% in the basal-bolus group (P < 0.001). There were no differences in mean daily BG level after the first day of insulin treatment (175 ± 32 vs. 179 ± 43 mg/dL, P = 0.64) between groups. A BG target between 80 and 180 mg/dL before meals was achieved in 55.9% of BG readings in the basal-bolus group and 54.3% of BG readings in the premixed insulin group (P = 0.23). There was no difference in the length of hospital stay or mortality between treatment groups.. Inpatient treatment with premixed human insulin resulted in similar glycemic control but in significantly higher frequency of hypoglycemia compared with treatment with basal-bolus insulin regimen in hospitalized patients with diabetes.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Regular, Human; Male; Middle Aged; Prospective Studies

OBJECTIVE Increased glycemic variability has been reported to be associated with the risk of hypoglycemia and possibly diabetes complications and is believed to be due to β-cell dysfunction. However, it is not known whether improvement in β-cell function can reduce glycemic variability. Because short-term intensive insulin therapy (IIT) can improve β-cell function in early type 2 diabetes (T2DM), our objective was to determine whether the β-cell functional recovery induced by this therapy is associated with decreased glycemic variability. RESEARCH DESIGN AND METHODS Sixty-one patients with T2DM of 3.0 years mean duration underwent 4 weeks of IIT, which consisted of basal insulin detemir and premeal insulin aspart. Glucose variability was assessed in both the first and the last week by the coefficient of variation of capillary glucose on daily 6-point self-monitoring profiles. β-Cell function before and after IIT was assessed with the Insulin Secretion-Sensitivity Index-2 (ISSI-2). RESULTS Between the first and the last week on IIT, 55.7% of patients had a reduction in glucose variability. Change in glucose variability was negatively correlated with the change in β-cell function (ISSI-2) (r = -0.34, P = 0.008). On multiple linear regression analyses, percentage change in ISSI-2 emerged as the only factor independently associated with the change in glucose variability (standardized β = -0.42, P = 0.03). Moreover, patients with an increase in ISSI-2 ≥25% experienced a reduction in glucose variability compared with their peers who had almost no change (-0.041 ± 0.06 vs. -0.0002 ± 0.04, respectively; P = 0.006). CONCLUSIONS In early T2DM, glycemic variability is a modifiable parameter that can be reduced by improving β-cell function with short-term IIT.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin-Secreting Cells; Insulin, Regular, Human; Male; Middle Aged

Diabetes remission is frequent after biliopancreatic diversion (BPD) in morbidly obese patients with type 2 diabetes (T2D). Data, mechanisms, and clinical indications in nonobese T2D patients are scanty.. The objective of the study was to assess remission and investigate insulin sensitivity and β-cell function after BPD in nonobese patients with long-standing T2D.. This was a clinical research study comparing 15 T2D patients (aged 55 ± 1 years, duration of 16 ± 2 years, body mass index of 28.3 ± 0.6 kg/m², glycosylated hemoglobin 8.6% ± 1.3%) with 15 gender-, age-, and body mass index-matched nondiabetic controls. Before surgery and 2 months and 1 year later, a 3-hour oral glucose tolerance test, a 5-hour mixed-meal test, and a 3-hour euglycemic clamp were performed.. The intervention included a BPD (distal gastrectomy, proximal ileum anastomosed to remaining stomach, biliopancreatic limb anastomosed to ileum 50 cm from the ileocecal valve).. Glycemia improved in all patients, but remission (glycosylated hemoglobin < 6.5% and normal oral glucose tolerance test) occurred in 6 of 15 patients. Insulin resistance (19.8 ± 0.8 μmol · min⁻¹ · kg(ffm)⁻¹, P < .001 vs 40.9 ± 5.3 of controls) resolved already at 2 months (34.2 ± 2.8) and was sustained at 1 year (34.7 ± 1.6), although insulin-mediated suppression of endogenous glucose production remained impaired. In contrast, β-cell glucose sensitivity (19 [12] pmol · min⁻¹ · m⁻² · mM⁻¹ vs 96 [73] of controls, P < .0001) rose (P = .02) only to 31 [26] at 1 year and was lower in nonremitters (16 [18]) than remitters (46 [33]).. In nonobese patients with long-standing T2D, BPD improves metabolic control but induces remission in only approximately 40% of patients. Peripheral insulin sensitivity is restored early after surgery and similarly in remitters and nonremitters, indicating a weight-independent effect of the operation. The initial extent of β-cell incompetence is the main predictor of the metabolic outcome.

Topics: Bariatric Surgery; Biliopancreatic Diversion; Body Mass Index; Diabetes Mellitus, Type 2; Female; Gluconeogenesis; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Insulin, Regular, Human; Italy; Liver; Male; Middle Aged; Overweight; Recombinant Proteins; Remission Induction; Weight Loss

Short-term intensive insulin therapy (IIT) can improve pancreatic β-cell function when administered early in the course of type 2 diabetes mellitus (T2DM). However, the degree of improvement in response to this therapy varies between patients. Thus, we sought to characterize the determinants of improvement in β-cell function in response to short-term IIT in early T2DM. Sixty-three patients with mean 3.0 ± 2.1 yr duration of T2DM and Hb A1c of 6.8 ± 0.8% underwent 4 wk of IIT consisting of basal insulin detemir and premeal insulin aspart, with oral glucose tolerance test administered at baseline and 1 day post-IIT. β-Cell function before and after IIT was assessed by Insulin Secretion Sensitivity Index-2 (ISSI-2). Reversibility of β-cell dysfunction was defined as percentage change in ISSI-2 of ≥25%. Overall, the study population experienced an increase in ISSI-2 from baseline to post-IIT (P = 0.01), with one-third of participants achieving ≥25% improvement in ISSI-2. Compared with their peers, those with increases in ISSI-2 of ≥25% had greater decrements in fasting glucose (P < 0.0001), Hb A1c (P = 0.001), ALT (P = 0.04), AST (P = 0.02), and HOMA-IR (P < 0.0001). On logistical regression analysis, baseline Hb A1c (OR = 2.83, 95% CI 1.16-6.88, P = 0.02) and change in HOMA-IR (OR = 0.008, 95%CI 0.0004-0.16, P = 0.001) emerged as independent predictors of reversibility of β-cell dysfunction. Indeed, reversibility of β-cell dysfunction was achieved in only those participants in whom IIT yielded an improvement in HOMA-IR. In conclusion, decline in HOMA-IR may be a key determinant of improvement of β-cell function in response to short-term IIT, suggesting a fundamental contribution of insulin resistance to the reversible component of β-cell dysfunction in early T2DM.

Topics: Adult; Diabetes Mellitus, Type 2; Disease Progression; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin-Secreting Cells; Insulin, Long-Acting; Insulin, Regular, Human; Male; Middle Aged; Prognosis; Treatment Outcome

In type 2 diabetic patients, insulin detemir (B29Lys(ε-tetradecanoyl),desB30 human insulin) induces less weight gain than NPH insulin. Due to the proposed reduction of tubular action by insulin detemir, type 2 diabetic patients should have increased urinary sodium excretion, thereby reducing extracellular volume and body weight when changed from NPH insulin to insulin detemir.. In a randomised, open-labelled, two-way crossover study of 24 patients with type 2 diabetes, patients were first treated with NPH insulin or insulin detemir for 8 weeks. Thereafter, they were changed to the other insulin for 8 weeks. In a third 1 week period, they were changed back to the first insulin.. At the end of 8 weeks, body weight was reduced by 0.8 ± 0.2 kg (mean ± SEM) on insulin detemir compared with NPH insulin (p < 0.01). After insulin detemir treatment, we also observed a significant reduction of lean body mass (0.8 ± 0.2 kg, p < 0.05) and a non-significant reduction of extracellular volume (0.8 ± 0.5 l/1.73 m², p = 0.14). The weight loss occurred after as early as 1 week (0.8 ± 0.2 kg, p < 0.001), with a simultaneous and transient increase of urinary sodium excretion (p = 0.07).. Insulin detemir induces significant and sustained weight loss, which is first observed at 1 week after changing from NPH insulin. The initial weight loss seems to be related to changes in fluid volume and may reflect changed insulin action in the kidneys.

Topics: Aged; Body Composition; Cross-Over Studies; Diabetes Mellitus, Type 2; Extracellular Fluid; Fluid Shifts; Glomerular Filtration Rate; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Middle Aged; Outpatient Clinics, Hospital; Patient Dropouts; Sodium; Time Factors; Water-Electrolyte Balance; Weight Loss

Coinjection of hyaluronidase has been shown to accelerate insulin absorption in healthy volunteers and patients with type 1 diabetes mellitus. This study was undertaken to compare the postprandial glycemic response of patients with type 2 diabetes mellitus (T2DM) administered insulin lispro with and without recombinant human hyaluronidase (rHuPH20) and regular human insulin (RHI) with rHuPH20.. This double-blind three-way crossover study compared the insulin pharmacokinetics and glucodynamic response to a standardized liquid meal (80 g of carbohydrate) in 21 patients with T2DM who received subcutaneous injections of individually optimized doses of lispro±rHuPH20 and RHI+rHuPH20. The optimum dose (targeting postprandial glucose [PPG] of 70-140 mg/dL) of each preparation was selected by the investigator following a fixed-dose escalation procedure in three dose-finding meals.. Co-injection of lispro+rHuPH20 accelerated pharmacokinetics relative to lispro alone (time to peak insulin concentration, 43 vs. 74 min; P=0.0045) with increased exposure in the first hour (184% of control; P<0.0001) and reduced exposure after 2 h (67% of control; P=0.0001). These accelerated pharmacokinetics improved both total hyperglycemic excursions (area under the curve for 0-4 h >140 mg/dL, 56% of control; P=0.048) and hypoglycemic excursions (area under the curve for 0-8 h <70 mg/dL, 34% of control; P=0.033), allowing over three times as many patients to reach the American Diabetes Association's target of peak PPG <180 mg/dL without requiring glucose treatment for hypoglycemia. The mean optimum dose of lispro was reduced 8% from 0.275 U/kg without rHuPH20 to 0.254 U/kg with rHuPH20 (P=0.04). RHI+rHuPH20 had responses and optimum doses comparable to insulin lispro alone. All insulin preparations were well tolerated.. Lispro+rHuPH20 provided superior control of glycemic excursion compared with lispro alone, with lower insulin requirements and reduced hypoglycemic excursions.

Topics: Adolescent; Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hyaluronoglucosaminidase; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Lispro; Insulin, Regular, Human; Male; Middle Aged; Postprandial Period; Treatment Outcome; United States; Young Adult

To examine the effect of intensive glycemic control therapy (IT) on insulin sensitivity and β-cell function in newly diagnosed type 2 diabetic patients compared with subjects with normal glucose tolerance (NGT) and those with impaired glucose tolerance (IGT).. Forty-eight newly diagnosed type 2 diabetic patients were randomly assigned to IT for 2 weeks and followed up for 1 year. Intravenous glucose tolerance tests were conducted in NGT, IGT, and diabetic subjects. Blood glucose and insulin were measured before and after IT and at the 1-year follow-up.. IT lowered the homeostasis model assessment (HOMA) for insulin resistance (IR) significantly, from 3.12 ± 1.4 (mean ± SD) to 1.72 ± 0.8, a level comparable to the IGT (1.96 ± 1.1) and NGT (1.37 ± 0.6) subjects in the remission group; however, no HOMA-IR improvement was observed in nonremission subjects. HOMA-β in the remission group was improved (mean, interquartile range) from 18.4 (8.3-28.5) to 44.6 (32.1-69.1) and acute insulin response of insulin (AIRins) from 1.50 ± 0.22 to 1.83 ± 0.19 μIU/mL after IT, but was still significantly lower than those in NGT individuals (HOMA-β: 86.4 [56.7-185.2], P < 0.01; AIRins: 2.54 ± 0.39 μIU/mL, P < 0.01). After IT and at 1 year, the hyperbolic relationship between HOMA-β and HOMA sensitivity of remission subjects shifted close to that of IGT subjects.. IT in newly diagnosed type 2 diabetes not only partially restored β-cell function but also greatly restored insulin sensitivity. Compared with IGT and NGT subjects, β-cell function was less restored than insulin sensitivity after IT in the remission subjects.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin-Secreting Cells; Insulin, Isophane; Insulin, Regular, Human; Isophane Insulin, Human; Male; Middle Aged

This study set out to define relationships between changes in plasma leptin and changes in body weight, plasma insulin and blood glucose control during a 12-month crossover study of once-daily Ultratard or twice-daily Insulatard insulin.. Fasting plasma leptin and insulin were measured during a multicentre cross-over study involving 60 subjects with type 2 diabetes (fasting glucose > 8 mM). After a 2-month run-in, there were two 6-month periods of treatment with Insulatard or Ultratard insulin.. Mean plasma leptin increased significantly in both groups after insulin therapy was instigated (12.8 +/- 8.1 to 22.9 +/- 13.1 ng/ml in the Insulatard group; 12.1 +/- 7.2 to 19.2 +/- 12.3 ng/ml in the Ultratard group). Weight also increased significantly in both groups (82.4 +/- 14.3 kg to 88.8 +/- 14.3 kg and 82.2 +/- 15.3 kg to 85.3 +/- 15.2 kg respectively). The increase in plasma leptin correlated well with the increase in weight (R = 0.416, p = 0.001), and this correlation continued after the crossover point. Plasma leptin correlated with BMI throughout the study (R = 0.540, p = 0.000).. The sustained rise in body weight despite a substantial increase in plasma leptin suggests that either resistance to the hypothalamic action of leptin develops when insulin therapy is begun in type 2 diabetes, or that resetting of the set point for body weight occurs such that a larger body mass is tolerated for a given level of plasma leptin.

Topics: Body Mass Index; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Insulin; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Leptin; Male; Middle Aged

My Diabetes My Way (MDMW) is Scotland's interactive website and mobile app for people with diabetes and their caregivers. It contains multimedia resources for diabetes education and offers access to electronic personal health records. This study aims to assess the cost-utility of MDMW compared with routine diabetes care in people with type 2 diabetes who do not use insulin.. Analysis used the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model 2. Clinical parameters of MDMW users (n = 2576) were compared with a matched cohort of individuals receiving routine care alone (n = 11 628). Matching criteria: age, diabetes duration, sex, and socioeconomic status. Impact on life expectancy, quality-adjusted life years (QALYs), and costs of treatment and complications were simulated over ten years, including a 10% sensitivity analysis.. MDMW cohort: 1670 (64.8%) men; average age 64.3 years; duration of diabetes 5.5 years. 906 (35.2%) women: average age 61.6 years; duration 4.7 years. The cumulative mean QALY (95% CI) gain: 0.054 (0.044-0.062) years. Mean difference in cost: -£118.72 (-£150.16 to -£54.16) over ten years. Increasing MDMW costs (10%): -£50.49 (-£82.24-£14.14). Decreasing MDMW costs (10%): -£186.95 (-£218.53 to -£122.51).. MDMW is "dominant" over usual care (cost-saving and life improving) in supporting self-management in people with type 2 diabetes not treated with insulin. Wider use may result in significant cost savings through delay or reduction of long-term complications and improved QALYs in Scotland and other countries. MDMW may be among the most cost-effective interventions currently available to support diabetes.

Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Education, Distance; Female; Health Records, Personal; Humans; Insulin; Insulin, Regular, Human; Male; Middle Aged; Prospective Studies; Quality-Adjusted Life Years

INSULIA is an insulin-titration app developed for patients with type 2 diabetes treated with basal insulin as part of a basal insulin-supported oral therapy (BOT). The app uses patient-logged fasting blood glucose (FBG) values and a titration plan defined by the treating physician to provide basal insulin dosing recommendations. Physicians use the web portal to monitor their patients' therapy progress and, if necessary, adjust therapy. The aim of this study was to assess the app, specifically its features, handling and impact on diabetes treatment and self-management in Germany.. This German retrospective pilot study included physicians (diabetologists, general practitioners, and internists) and patients with type 2 diabetes who either receive or start BOT using the app. Both groups completed group-specific questionnaires between December 2018 and June 2019.. Overall, 10 physicians and 34 patients with type 2 diabetes completed their respective questionnaires. Physicians perceived their app-using patients to be more involved and more confident in managing their insulin therapy than patients not using the app. The majority of patients considered the app as a tool that assists with safer insulin treatment. The physicians perceived that due to the app use, FBG and HbA. The titration app seems to have a positive impact on BOT patients' FBG and HbA

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human; Mobile Applications; Pilot Projects; Retrospective Studies; Smartphone

To examine the impact of real-time continuous glucose monitoring (rtCGM) on psychosocial outcomes in adults with insulin-using type 2 diabetes (T2D).. A total of 174 insulin-using adults with T2D completed questionnaires assessing diabetes distress, hypoglycemic confidence, hypoglycemic fear, device-related emotional burden, and device-related trust before and after a six-month trial of rtCGM. Hemoglobin A1c (HbA1c) was assessed at the same time points; impaired hypoglycemic awareness (IAH) was assessed at baseline. Change in psychosocial outcomes was examined with. Respondents were predominantly male (57.5%) and non-Hispanic white (67.8%). Significant improvement over the trial was observed in hypoglycemic fear (. Introduction of rtCGM in adults with insulin-using T2D was associated with significant improvements in diabetes-related psychosocial outcomes over six months. Gains were significantly greater among participants reporting IAH and those with higher HbA1c at baseline, thus providing the first evidence regarding which users might more likely benefit.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Male

The aim of this study was to develop a predictive model to classify people with type 2 diabetes (T2D) into expected levels of success upon bolus insulin initiation.. Machine learning methods were applied to a large nationally representative insurance claims database from the United States (dNHI database; data from 2007 to 2017). We trained boosted decision tree ensembles (XGBoost) to assign people into Class 0 (never meeting HbA1c goal), Class 1 (meeting but not maintaining HbA1c goal), or Class 2 (meeting and maintaining HbA1c goal) based on the demographic and clinical data available prior to initiating bolus insulin. The primary objective of the study was to develop a model capable of determining at an individual level, whether people with T2D are likely to achieve and maintain HbA1c goals. HbA1c goal was defined at <8.0% or reduction of baseline HbA1c by >1.0%.. Of 15 331 people with T2D (mean age, 53.0 years; SD, 8.7), 7800 (50.9%) people met HbA1c goal but failed to maintain that goal (Class 1), 4510 (29.4%) never attained this goal (Class 0), and 3021 (19.7%) people met and maintained this goal (Class 2). Overall, the model's receiver operating characteristic (ROC) was 0.79 with greater performance on predicting those in Class 2 (ROC = 0.92) than those in Classes 0 and 1 (ROC = 0.71 and 0.62, respectively). The model achieved high area under the precision-recall curves for the individual classes (Class 0, 0.46; Class 1, 0.58; Class 2, 0.71).. Predictive modeling using routine health care data reasonably accurately classified patients initiating bolus insulin who would achieve and maintain HbA1c goals, but less so for differentiation between patients who never met and who did not maintain goals. Prior HbA1c was a major contributing parameter for the predictions.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Middle Aged

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; France; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Retrospective Studies

To assess the efficacy and safety of analog insulins in comparison with human insulins for hyperglycemia in hospitalized patients with acute stroke.. In this single-center, open-label, randomized trial, 102 patients (age 59.4 ± 11.7 years, 54 women) admitted with acute stroke (52 ischemic, 50 hemorrhagic) and hyperglycemia were assigned to analog insulin (n = 52) or human insulin (n = 50) group during February to June 2021. Insulin was initiated and titrated according to the predefined standard protocol. The capillary blood glucose (BG) level was monitored by standardized glucometers. The primary outcomes were mean daily BG and the number of hypoglycemic events.. Between the 2 treatment groups, there was no significant difference in the mean daily BG (P >.05 for all days) or in the frequency of hypoglycemic episodes (P =.727). Four participants experienced severe hypoglycemia; all were receiving human insulin (P =.054). In the analog insulin group, there was a tendency toward lower daily total requirement for insulin (P =.053). The difference in bolus insulin dose was significantly lower in the analog insulin group (P =.029), but the difference in basal insulin dose was similar (P =.167). Between the 2 groups, there were no significant differences in the hospital mortality rate, modified Rankin Scale score on outcome, or length of hospital stay (P =.729,.658, and.918, respectively).. Hospitalized patients acute stroke and hyperglycemia exhibited similar mean BG but a trend of lower incidence of severe hypoglycemia when treated with analog insulins in comparison with human insulin.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Middle Aged; Stroke

To assess the diurnal patterns of postprandial glucose tolerance and insulin sensitivity, 19 subjects with type 2 diabetes (8 women; 60 ± 11 years; BMI 32 ± 5 kg/m2) and 19 anthropometrically matched subjects with no diabetes (ND; 11 women; 53 ± 12 years; BMI 29 ± 5 kg/m2) were studied during breakfast (B), lunch (L), and dinner (D) with identical mixed meals (75 g carbohydrates) on 3 consecutive days in a randomized Latin square design. Three stable isotopes of glucose were ustilized to estimate meal fluxes, and mathematical models were used in estimating indices of insulin action and β-cell function. Postmeal glucose excursions were higher at D versus B and at D versus L in type 2 diabetes (P < 0.05), while in ND they were higher at D versus B (P = 0.025) and at L versus B (P = 0.04). The insulin area under the curve was highest at B compared with L and D in type 2 diabetes, while no differences were observed in ND. Disposition index (DI) was higher at B than at L (P < 0.01) and at D (P < 0.001) in ND subjects, whereas DI was low with unchanging pattern across B-L-D in individuals with type 2 diabetes. Furthermore, between-meal differences in β-cell responsivity to glucose (F) and insulin sensitivity (SI) were concurrent with changes in the DI within groups. Fasting and postmeal glucose, insulin, and C-peptide concentrations, along with estimates of endogenous glucose production (EGP), Rd, SI, F, hepatic extraction of insulin, insulin secretion rate, extracted insulin, and DI, were altered in type 2 diabetes compared with ND (P < 0.011 for all). The data show a diurnal pattern of postprandial glucose tolerance in overweight otherwise glucose-tolerant ND individuals that differs from overweight individuals with type 2 diabetes. The results not only provide valuable insight into management strategies for better glycemic control in people with type 2 diabetes, but also improved understanding of daytime glucose metabolism in overweight individuals without impaired glucose tolerance or overt diabetes.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucose; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Meals; Middle Aged; Overweight

The objective of the study was to determine the clinical factors associated with knowledge and self-care practice among adults living with type 2 diabetes mellitus.. Descriptive cross-sectional design.. A convenience sample of 330 participants was recruited over 3-months in 2018 and data were collected using a structured instrument.. Participants on insulin treatment modality had four times higher odds of knowledge on diabetes (B = 4.17, p = 0.023) while those on combined therapy (both oral hypoglycaemic agent and insulin) had 7.26 times higher odds of knowledge (B = 7.26, p < 0.001). Participants without medically confirmed diabetic complications had 3.66 higher odds of knowledge of diabetes (B = 3.66, p = 0.002). Participants on insulin treatment modality had a 1.4-fold higher odds of self-care practice (B = 1.4, p = 0.028). It was revealed that participants with hypertension and diabetic foot had lower odds of self-care practice (B = -1.13, p = 0.021).. In particular, participants who were on insulin and combined therapy (tablet and insulin) had higher knowledge and better self-care practice. Self-care was significantly influenced among those with, than those without diabetic foot and hypertension as complications.

Topics: Adult; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Foot; Humans; Hypertension; Insulin; Insulin, Regular, Human; Self Care

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

To investigate changes in the pattern of drugs used to treat type 2 diabetes in Denmark from 2005 to 2021.. A nationwide, population-based drug utilization study based on medical databases covering the Danish population was conducted. We assessed incident and prevalent use patterns among all 441 205 individuals initiating at least one non-insulin, glucose-lowering drug.. The rate of new users of non-insulin, glucose-lowering drugs increased from 2005, peaked in 2011, decreased to stable levels during 2013 to 2019, then increased dramatically during 2020-2021. The prevalence of use increased from 2.1% (in 2005) to 5.0% (in 2021) of the entire adult population. In 2021, metformin comprised 39% of all glucose-lowering drug consumption, followed by insulin (17%), sodium-glucose co-transporter-2 inhibitors (SGLT-2is) (17%), glucagon-like peptide-1 receptor agonists (GLP-1RAs) (16%) and dipeptidyl peptidase-4 inhibitors (7.5%). Overall, 56% of users were on monotherapy, 28% used dual therapy, while 13% and 2.8% used three and four drug classes, respectively. Both the intensity and diversity of therapies increased substantially over time, with 15 different treatment regimens each covering more than 1% of users in 2021. General practitioners prescribed 88% of all glucose-lowering drugs. Marked shifts towards GLP-1RA initiation by general practitioners and SGLT-2i initiation by specialists were observed, and changing user profiles suggested increasing use for non-diabetes indications.. The rate of new users of non-insulin, glucose-lowering drugs has increased in recent years and the prevalence of glucose-lowering drug use increases steadily. Glucose-lowering drugs are mainly prescribed by general practitioners, and the intensity, diversity and indications of glucose-lowering treatment are increasing.

Topics: Adult; Denmark; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Sodium-Glucose Transporter 2 Inhibitors

To assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of basal insulin Fc (BIF; LY3209590), a fusion protein combining a novel single-chain insulin variant together with human IgG2 Fc domain, following single and multiple once-weekly BIF administration.. The single ascending dose, 15-day study assessed four BIF doses (5-35 mg) in healthy participants and people with type 2 diabetes (T2D). In the 6-week multiple ascending dose study, people with T2D, previously treated with basal insulin, received insulin glargine daily or a one-time loading dose of BIF followed by 5 weeks of once-weekly dosing (1-10 mg). Safety, tolerability and PK and glucose PD were examined.. Mean ages of people with T2D (N = 57) and healthy participants (N = 16) in the single-dose study were 58.4 and 35.8 years, respectively; mean body mass index values were 29.5 and 26.1 kg/m. BIF was well tolerated and the PK/PD profile enabled once-weekly dosing with minimal variation in exposure in a treatment interval of 1 week. The findings suggest BIF is suitable for further development as a weekly basal insulin in people with diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Glucose; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human

To conduct a study on glycemic control improvement by appropriate re-education on the self-injection technique (SIT) in patients with diabetes mellitus undergoing insulin therapy.. Patients who received appropriate SIT and were treated with insulin for more than a year were re-educated. For the observation period of six months, the subjects' SIT was checked, and hemoglobin A1c (HbA1c) levels were measured at each visit. HbA1c levels, insulin doses, and behavioral changes in SIT were investigated at baseline and at the end of the observation period.. In the per-protocol set population, the HbA1c level decreased by 0.2 % (2.0 mmol/mol) on average, showing a significant difference (p = 0.009). No significant difference was observed in the proportion of subjects with decreased HbA1c levels, changes in total daily insulin doses, or blood glucose levels. Four of the six SIT items covered by re-education were improved.. Providing re-education on insulin SIT was considered effective in reducing HbA1c levels and improving adherence to proper SIT.

Topics: Blood Glucose; COVID-19; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Pandemics; Self Administration

To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method.. This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets.. Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia.. Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human; Male

To compare outcomes in adults with type 2 diabetes (T2D) suboptimally controlled with basal insulin who initiated treatment with iGlarLixi or premixed insulin.. This retrospective real-world analysis was conducted using data from adults (age ≥ 18 years) with T2D in the US Optum Clinformatics database who had previously received basal insulin and newly initiated iGlarLixi or premixed insulin. Cohorts were propensity-score matched on baseline characteristics using a greedy nearest neighbour-matching algorithm, and outcomes were assessed at 12 months. Subgroup analyses were performed for those aged 65 years or older and those with a baseline HbA1c of 9% or higher. The primary endpoint was treatment persistence in the overall population. Secondary endpoints were treatment adherence, healthcare resource utilization (HRU), costs, hypoglycaemia events and change in HbA1c from baseline.. Each cohort comprised 834 participants. In the overall population, treatment persistence at 12 months was statistically significantly higher for iGlarLixi versus premixed insulin: 42.5% versus 39.1%; hazard ratio 0.88; 95% confidence interval 0.778-0.998; P = .0465. Adherence and HbA1c reduction were similar between groups, whereas hypoglycaemia events, HRU and costs were numerically lower for iGlarLixi. Outcomes in both the age 65 years or older subgroup and in those with an HbA1c of 9% or higher were consistent with those for the overall population.. In this observational study in people with T2D suboptimally controlled on basal insulin, once-daily iGlarLixi was an effective treatment alternative to premixed insulin with significantly higher treatment persistence, similar adherence and HbA1c reduction, and numerically lower hypoglycaemia events, HRU and costs, regardless of age or baseline HbA1c.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human; Retrospective Studies

The optimal treatment of prednisolone-associated hyperglycaemia is unclear, but guidelines recommend using a body weight-based daily insulin dose. This study evaluated how clinical variables were associated with insulin requirements in hospitalised patients with prednisolone-associated hyperglycaemia.. In this prospective study, fifty adult inpatients who were taking prednisolone ≥20 mg/day and experienced hyperglycaemia were prescribed a 24-h intravenous insulin infusion. The daily insulin dose required to attain a mean glucose of 8 mmol/L was calculated. The associations between daily insulin dose and clinical variables were assessed.. The participants age was 69 ± 10 years, daily prednisolone dose was 34 ± 10 mg, HbA1c was 7.7 ± 2.0 % (61 ± 10 mmol/mol), 77 % had known type 2 diabetes and 30 % were female. In univariate analysis, weight was associated with daily insulin dose (r. In patients with prednisolone-associated hyperglycaemia, calculating insulin doses based on sex, HbA1c, diabetes status and regular diabetes treatment and weight may improve glycaemic control compared to weight-based dosing.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Male; Middle Aged; Prednisolone; Prospective Studies

High-throughput proteomics allows researchers to simultaneously explore the roles of thousands of biomarkers in the pathophysiology of diabetes. We conducted proteomic association studies of incident type 2 diabetes and physiologic responses to an intravenous glucose tolerance test (IVGTT) to identify novel protein contributors to glucose homeostasis and diabetes risk. We tested 4,776 SomaScan proteins measured in relation to 18-year incident diabetes risk in participants from the Cardiovascular Health Study (N = 2,631) and IVGTT-derived measures in participants from the HERITAGE Family Study (N = 752). We characterize 51 proteins that were associated with longitudinal diabetes risk, using their respective 39, 9, and 8 concurrent associations with insulin sensitivity index (SI), acute insulin response to glucose (AIRG), and glucose effectiveness (SG). Twelve of the 51 diabetes associations appear to be novel, including β-glucuronidase, which was associated with increased diabetes risk and lower SG, suggesting an alternative pathway to insulin for glucose disposal; and plexin-B2, which also was associated with increased diabetes risk, but with lower AIRG, and not with SI, indicating a mechanism related instead to pancreatic dysfunction. Other novel protein associations included alcohol dehydrogenase-1C, fructose-bisphosphate aldolase-B, sorbitol dehydrogenase with elevated type 2 diabetes risk, and a leucine-rich repeat containing protein-15 and myocilin with decreased risk.. Plasma proteins are associated with the risk of incident diabetes in older adults independent of various demographic, lifestyle, and biochemical risk factors. These same proteins are associated with subtle differences in measures of glucose homeostasis earlier in life. Proteins that are associated with lower insulin sensitivity in individuals without diabetes tend to be associated with appropriate compensatory mechanisms, such as a stronger acute insulin response or higher glucose effectiveness. Proteins that are associated with future diabetes risk, but not with insulin insensitivity, tend to be associated with lower glucose effectiveness and/or impaired acute insulin response.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Glucose; Homeostasis; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Proteomics

Automated insulin delivery (AID) has rarely been studied in adults with type 2 diabetes. We tested the feasibility of using AID for type 2 diabetes with the Omnipod 5 System in a multicenter outpatient trial.. Participants previously were using either basal-only or basal-bolus insulin injections, with or without the use of a continuous glucose monitor (CGM), and had a baseline HbA1c ≥8% (≥64 mmol/mol). Participants completed 2 weeks of CGM sensor data collection (blinded for those not previously using CGM) with their standard therapy (ST), then transitioned to 8 weeks of AID. Participants who previously used basal-only injections used the AID system in manual mode for 2 weeks before starting AID. Antihyperglycemic agents were continued at clinician discretion. Primary safety outcomes were percentage of time with sensor glucose ≥250 mg/dL and <54 mg/dL during AID. Additional outcomes included HbA1c and time in target range (TIR) (70-180 mg/dL).. Participants (N = 24) had a mean (± SD) age of 61 ± 8 years, baseline HbA1c of 9.4% ± 0.9% (79 ± 10 mmol/mol), and diabetes duration of 19 ± 9 years. Percentage of time with sensor glucose ≥250 mg/dL decreased with AID by 16.9% ± 16.2% (P < 0.0001), whereas percentage of time at <54 mg/dL remained low during both ST and AID (median [interquartile range] 0.0% [0.00%, 0.06%] vs. 0.00% [0.00%, 0.03%]; P = 0.4543). HbA1c (± SD) decreased by 1.3% ± 0.7% (14 ± 8 mmol/mol; P < 0.0001) and TIR increased by 21.9% ± 15.2% (P < 0.0001) without a significant change in total daily insulin or BMI with AID.. Findings from this feasibility trial of AID in adults with type 2 diabetes with suboptimal glycemic outcomes justify further evaluation of this technology in this population.

Topics: Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Insulin, Regular, Human; Middle Aged

We conducted a Mendelian randomization (MR) study to examine the associations of type 2 diabetes and glycemic traits with gastrointestinal diseases (GDs).. Uncorrelated genetic variants associated with type 2 diabetes (n = 231), fasting insulin (n = 38), fasting glucose (n = 71), and hemoglobin A1c (n = 75) at the genome-wide significance were selected as instrument variables. Genetic associations with 23 common GDs were obtained from the FinnGen and UK Biobank studies and other large consortia.. Genetic liability to type 2 diabetes was associated with the risk of 12 GDs. Per 1-unit increase in the log-transformed odds ratio (OR) of type 2 diabetes, the OR was 1.06 (95% CI, 1.03-1.09) for gastroesophageal reflux disease, 1.12 (95% CI, 1.07-1.17) for gastric ulcer, 1.11 (95% CI, 1.03-1.20) for acute gastritis, 1.07 (95% CI, 1.01-1.13) for chronic gastritis, 1.08 (95% CI, 1.03-1.12) for irritable bowel syndrome, 1.04 (95% CI, 1.01-1.07) for diverticular disease, 1.08 (95% CI, 1.02-1.14) for acute pancreatitis, 1.09 (95% CI, 1.05-1.12) for cholelithiasis, 1.09 (95% CI, 1.05-1.13) for cholelithiasis with cholecystitis, 1.29 (95% CI, 1.17-1.43) for nonalcoholic fatty liver disease, 1.12 (95% CI, 1.03-1.21) for liver cirrhosis, and 0.93 (95% CI, 0.89-0.97) for ulcerative colitis. Genetically predicted higher levels of fasting insulin and glucose were associated with six and one GDs, respectively.. Associations were found between genetic liability to type 2 diabetes and an increased risk of a broad range of GDs, highlighting the importance of GD prevention in patients with type 2 diabetes.

Topics: Acute Disease; Blood Glucose; Cholelithiasis; Diabetes Mellitus, Type 2; Gastritis; Genome-Wide Association Study; Glucose; Humans; Insulin; Insulin, Regular, Human; Mendelian Randomization Analysis; Pancreatitis; Polymorphism, Single Nucleotide; Risk Factors

To determine the benefit of starting continuous glucose monitoring (CGM) in adult-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) with regard to longer-term glucose control and serious clinical events.. A retrospective observational cohort study within the Veterans Affairs Health Care System was used to compare glucose control and hypoglycemia- or hyperglycemia-related admission to an emergency room or hospital and all-cause hospitalization between propensity score overlap weighted initiators of CGM and nonusers over 12 months.. CGM users receiving insulin (n = 5,015 with T1D and n = 15,706 with T2D) and similar numbers of nonusers were identified from 1 January 2015 to 31 December 2020. Declines in HbA1c were significantly greater in CGM users with T1D (-0.26%; 95% CI -0.33, -0.19%) and T2D (-0.35%; 95% CI -0.40, -0.31%) than in nonusers at 12 months. Percentages of patients achieving HbA1c <8 and <9% after 12 months were greater in CGM users. In T1D, CGM initiation was associated with significantly reduced risk of hypoglycemia (hazard ratio [HR] 0.69; 95% CI 0.48, 0.98) and all-cause hospitalization (HR 0.75; 95% CI 0.63, 0.90). In patients with T2D, there was a reduction in risk of hyperglycemia in CGM users (HR 0.87; 95% CI 0.77, 0.99) and all-cause hospitalization (HR 0.89; 95% CI 0.83, 0.97). Several subgroups (based on baseline age, HbA1c, hypoglycemic risk, or follow-up CGM use) had even greater responses.. In a large national cohort, initiation of CGM was associated with sustained improvement in HbA1c in patients with later-onset T1D and patients with T2D using insulin. This was accompanied by a clear pattern of reduced risk of admission to an emergency room or hospital for hypoglycemia or hyperglycemia and of all-cause hospitalization.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Retrospective Studies; Veterans Health

To describe clinical characteristics, treatment patterns and glucagon-like peptide-1 receptor agonist (GLP-1 RA) persistence in individuals with type 2 diabetes (T2D) initiating their first GLP-1 RA.. A real-world analysis of adults with T2D initiating GLP-1 RA therapy between 2007 and June 2020 from the multicentre Diabetes Prospective Follow-Up (DPV) Registry, stratified by antidiabetes therapy at the time of GLP-1 RA initiation: oral antidiabetic drugs (OAD), insulin ± OAD or lifestyle modification (LM). GLP-1 RA treatment persistence in individuals with ≥12 months follow-up was determined by Kaplan-Meier analysis.. Overall, 15 111 individuals with T2D initiating GLP-1 RA therapy (55% men) were identified; median [interquartile range (IQR)] age [58.7 (50.6-66.7) years], diabetes duration [8.5 (3.6-14.7) years], glycated haemoglobin [HbA1c; 8.2 (7.1-9.8)%]. Median (95% confidence interval) GLP-1 RA persistence in eligible individuals (n = 5189) was 11 (10-12) months; OAD 12 (11-14) months (n = 2453); insulin ± OAD 11 (9-12) months (n = 2204); and LM 7 (5-9) months (n = 532). Median treatment persistence tended to increase from 2007-2012 to 2017-2020. Median (IQR) HbA1c decreased from baseline [8.2 (7.1-9.8)%] to discontinuation [7.5 (6.6-8.7)%], with a greater decrease observed in individuals with persistence >12 months versus ≤12 months. Individuals who discontinued GLP-1 RA therapy predominantly switched to insulin (if not already using) or dipeptidyl peptidase-4 inhibitors.. Real-world registry data revealed improved outcomes with longer median GLP-1 RA persistence; ~50% of patients overall achieved HbA1c <7% at 12 months. Persistence was highest with baseline OAD and/or insulin, and tended to increase over the period 2007-2020.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Male; Middle Aged; Prospective Studies; Retrospective Studies

Type 2 diabetes (T2DM) is a leading cause of mortality in South Africa and resistance to the use of insulin is common. This study aimed to explore factors that influence the initiation of insulin in patients with T2DM in primary care facilities in Cape Town, South Africa.. An exploratory descriptive qualitative study was conducted. Seventeen semi-structured interviews were held with patients eligible for insulin, on insulin and primary care providers. Participants were selected by maximum variation purposive sampling. Data were analysed using the framework method in Atlas-ti.. Factors related to the health system, service delivery, clinical care and patients. Systemic issues related to the required inputs of workforce, educational materials, and supplies. Service delivery issues related to workload, poor continuity and parallel coordination of care. Clinical issues related to adequate counselling. Patient factors included a lack of trust, concerns about injections, impact on lifestyle and disposal of needles.. Although resource constraints are likely to remain, district and facility managers can improve supplies, educational materials, continuity and coordination. Counselling must be improved and may require innovative alternative approaches to support clinicians who face high number of patients. Alternative approaches using group education, telehealth and digital solutions should be considered.Contribution: This study identified key factors influencing insulin initiation in patients with T2DM in primary care. These can be addressed by those responsible for clinical governance, service delivery and in further research.

Topics: Diabetes Mellitus, Type 2; Humans; Insulin; Insulin, Regular, Human; Primary Health Care; South Africa

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Insulin, Regular, Human

Prior studies provided evidence that low-density lipoprotein (LDL)-cholesterol-lowering statins reduce cardiovascular events while conveying an increased risk of type 2 diabetes. The aim of this study was to investigate the association between LDL levels and both insulin sensitivity and insulin secretion in a cohort of 356 adult first-degree relatives of patients with type 2 diabetes.. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp and first-phase insulin secretion was measured by both intravenous glucose tolerance test (IVGTT) and OGTT.. LDL-cholesterol levels were not independently associated with insulin-stimulated glucose disposal. After adjusting for several potential confounders, LDL-cholesterol concentration exhibited a positive independent association with acute insulin response (AIR) during IVGTT and with the OGTT derived Stumvoll first-phase insulin secretion index. When insulin release was adjusted for the underlying degree of insulin sensitivity, using the disposition index (AIR × insulin-stimulated glucose disposal), β-cell function was significantly associated with LDL-cholesterol levels, even after further adjusting for several potential confounders.. The present results suggest that LDL cholesterol is a positive modulator of insulin secretion. The deterioration in glycemic control observed during treatment with statins might thus be explained by an impairment in insulin secretion due to the cholesterol-lowering effect of statins.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Glucose; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Insulin Resistance; Insulin, Regular, Human; Lipoproteins, LDL

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; France; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Retrospective Studies

Type 2 diabetes mellitus (T2DM) affects 25% of adults over age 65. Nevertheless, few clinical trials include patients over age 75.. This case series reports retrospective data on a cohort of 85 patients aged 80 and over (mean 88.1, range 80-104) with T2DM, managed by a single endocrinologist. The practice's computerized data base was searched for all patients 80 years of age and older with a diagnosis of T2DM.. The major observations were the significant decrease in the use of agents associated with hypoglycemia (sulfonylureas and insulin), and the beneficial and well-tolerated use of glucagon like peptide-1 receptor analogues (GLP-1 RA). The mean A1c in the entire cohort dropped from 7.6% to 6.6% over a mean of 9 months. Nearly one-half of the cohort were treated with GLP1-RA, reflecting studies demonstrating the safety and efficacy of this class of drugs in less elderly patients. At presentation, 75% were on sulfonylurea and/or insulin; this number was reduced to 27%. Furthermore, none of the patients required short-acting (bolus) insulin to achieve the individualized A1c target.. Patients with T2DM aged 80 and over respond well to GLP1-RA drugs, drastically reducing the need for agents associated with hypoglycemia. The important question, which will require larger and prospective studies, is whether the lowering of A1c, as shown in this paper, and the use of GLP-1 RA specifically, are associated with improved morbidity and mortality in the very elderly.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Prospective Studies; Retrospective Studies; Sulfonylurea Compounds

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Insulin, Regular, Human

Type 2 diabetes (T2D) is a metabolic disorder characterized by loss of pancreatic β-cell function, decreased insulin secretion and increased insulin resistance, that affects more than 537 million people worldwide. Although several treatments are proposed to patients suffering from T2D, long-term control of glycemia remains a challenge. Therefore, identifying new potential drugs and targets that positively affect β-cell function and insulin secretion remains crucial. Here, we developed an automated approach to allow the identification of new compounds or genes potentially involved in β-cell function in a 384-well plate format, using the murine β-cell model Min6. By using MALDI-TOF mass spectrometry, we implemented a high-throughput screening (HTS) strategy based on the automation of a cellular assay allowing the detection of insulin secretion in response to glucose, i.e., the quantitative detection of insulin, in a miniaturized system. As a proof of concept, we screened siRNA targeting well-know β-cell genes and 1600 chemical compounds and identified several molecules as potential regulators of insulin secretion and/or synthesis, demonstrating that our approach allows HTS of insulin secretion in vitro.

Topics: Animals; Diabetes Mellitus, Type 2; Glucose; High-Throughput Screening Assays; Humans; Insulin; Insulin Secretion; Insulin, Regular, Human; Mice; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

To determine the potential impact of the cross-reactivity of insulin glargine U-100 and its metabolites on insulin sensitivity and β-cell measures in people with type 2 diabetes.. Using liquid chromatography-mass spectrometry (LC-MS), we measured concentrations of endogenous insulin, glargine and its two metabolites (M1 and M2) in fasting and oral glucose tolerance test-stimulated plasma from 19 participants and fasting specimens from another 97 participants 12 months after randomization to receive the insulin glargine. The last dose of glargine was administered before 10:00 PM the night before testing. Insulin was also measured on these specimens using an immunoassay. We used fasting specimens to calculate insulin sensitivity (Homeostatic Model Assessment 2 [HOMA2]-S%; QUICKI index; PREDIM index) and β-cell function (HOMA2-B%). Using specimens following glucose ingestion, we calculated insulin sensitivity (Matsuda ISI[comp] index) and β-cell response (insulinogenic index [IGI], and total incremental insulin response [iAUC] insulin/glucose).. In plasma, glargine was metabolized to form the M1 and M2 metabolites that were quantifiable by LC-MS; however, the analogue and its metabolites cross-reacted by less than 100% in the insulin immunoassay. This incomplete cross-reactivity resulted in a systematic bias of fasting-based measures. By contrast, because M1 and M2 did not change following glucose ingestion, a bias was not observed for IGI and iAUC insulin/glucose.. Despite glargine metabolites being detected in the insulin immunoassay, dynamic insulin responses can be used to assess β-cell responsiveness. However, given the cross-reactivity of the glargine metabolites in the insulin immunoassay, fasting-based measures of insulin sensitivity and β-cell function are biased.

Topics: Blood Glucose; Chromatography, Liquid; Diabetes Mellitus, Type 2; Glucose; Humans; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Regular, Human; Mass Spectrometry

To investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission.. Retrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression.. In total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment.. Hospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA.

Topics: Adult; COVID-19; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Hospitalization; Hospitals; Humans; Hyperglycemia; Hyperglycemic Hyperosmolar Nonketotic Coma; Insulin; Insulin, Regular, Human; Middle Aged; Retrospective Studies; United Kingdom

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin Infusion Systems; Insulin, Regular, Human; Pregnancy

We examined the associations of GAD antibodies (GADA) and C-peptide (CP) with insulin initiation, glycemic responses, and severe hypoglycemia in type 2 diabetes (T2D).. In 5,230 Chinese patients (47.6% men) with T2D (mean ± SD age: 56.5 ± 13.9 years; median diabetes duration: 6 [interquartile range 1, 12] years), enrolled consecutively in 1996-2012 and prospectively observed until 2019, we retrospectively measured fasting CP and GADA in stored serum and examined their associations with aforementioned outcomes.. At baseline, 28.6% (n = 1,494) had low CP (<200 pmol/L) and 4.9% (n = 257) had positive GADA (GADA+). In the low-CP group, 8.0% had GADA+, and, in the GADA+ group, 46.3% had low CP. The GADA+ group had an adjusted hazard ratio (aHR) of 1.46 (95% CI 1.15-1.84, P = 0.002) for insulin initiation versus the GADA- group, while the low-CP group had an aHR of 0.88 (0.77-1.00, P = 0.051) versus the high-CP group. Following insulin initiation, the GADA+ plus low-CP group had the largest decrements in HbA1c (-1.9% at month 6; -1.5% at month 12 vs. -1% in the other three groups). The aHR of severe hypoglycemia was 1.29 (95% CI 1.10-1.52, P = 0.002) in the low-CP group and 1.38 (95% CI 1.04-1.83, P = 0.024) in the GADA+ group.. There is considerable heterogeneity in autoimmunity and β-cell dysfunction in T2D with GADA+ and high CP associated with early insulin initiation, while GADA+ and low CP, increased the risk of severe hypoglycemia. Extended phenotyping is warranted to increase the precision of classification and treatment in T2D.

Topics: Adult; Aged; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Humans; Hypoglycemia; Insulin; Insulin, Regular, Human; Male; Middle Aged; Retrospective Studies

The Rare and Atypical Diabetes Network (RADIANT) will perform a study of individuals and, if deemed informative, a study of their family members with uncharacterized forms of diabetes.. The protocol includes genomic (whole-genome [WGS], RNA, and mitochondrial sequencing), phenotypic (vital signs, biometric measurements, questionnaires, and photography), metabolomics, and metabolic assessments.. Among 122 with WGS results of 878 enrolled individuals, a likely pathogenic variant in a known diabetes monogenic gene was found in 3 (2.5%), and six new monogenic variants have been identified in the SMAD5, PTPMT1, INS, NFKB1, IGF1R, and PAX6 genes. Frequent phenotypic clusters are lean type 2 diabetes, autoantibody-negative and insulin-deficient diabetes, lipodystrophic diabetes, and new forms of possible monogenic or oligogenic diabetes.. The analyses will lead to improved means of atypical diabetes identification. Genetic sequencing can identify new variants, and metabolomics and transcriptomics analysis can identify novel mechanisms and biomarkers for atypical disease.

Topics: Diabetes Mellitus, Type 2; Family; High-Throughput Nucleotide Sequencing; Humans; Insulin; Insulin, Regular, Human; PTEN Phosphohydrolase

The benefits of the newer antidiabetic agents available for managing type 2 diabetes mellitus (T2DM) remain indisputable, but many patients will require insulin therapy in the disease course. Given the limited access to newer antidiabetic agents, insulin remains a standard treatment modality in T2DM in South Africa. Early, multifactorial intervention remains ideal, but glucose, blood pressure and cholesterol values remain above target in many countries. Barriers to achieving glucose control in South Africa include the healthcare provider's being unfamiliar with the practicalities of insulin administration, initiation and titration. This article highlights these gaps and offers pragmatic solutions to overcome them.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; South Africa

We assess the incidence and economic burden of severe and non-severe hypoglycemia in insulin-treated diabetes type 1 and 2 patients in Switzerland.. We developed a health economic model to assess the incidence of hypoglycemia, the subsequent medical costs, and the production losses in insulin-treated diabetes patients. The model distinguishes between severity of hypoglycemia, type of diabetes, and type of medical care. We used survey data, health statistics, and health care utilization data extracted from primary studies.. The number of hypoglycemic events in 2017 was estimated at 1.3 million in type 1 diabetes patients and at 0.7 million in insulin-treated type 2 diabetes patients. The subsequent medical costs amount to 38 million Swiss Francs (CHF), 61 % of which occur in type 2 diabetes. Outpatient visits dominate costs in both types of diabetes. Total production losses due to hypoglycemia amount to CHF 11 million. Almost 80 % of medical costs and 39 % of production losses are due to non-severe hypoglycemia.. Hypoglycemia leads to substantial socio-economic burden in Switzerland. Greater attention to non-severe hypoglycemic events and to severe hypoglycemia in type 2 diabetes could have a major impact on reducing this burden.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin, Regular, Human; Switzerland

Diabetes self-management education and support (DSMES) is a critical component of diabetes care, but time for it is often limited. Digital tools, such as mobile applications (apps), show promise in extending efforts and supporting self-management education, but have not been fully used. Objectives of this multi-phase study were to (1) evaluate an app designed to support patients with insulin therapy and (2) examine provider perspectives on DSMES apps.. Phase 1: Thirty-two adult patients with type 2 diabetes new to or having difficulties with insulin therapy were introduced to the BD. Phase 1: Patients reported satisfaction with the app, and significant improvements in HbA1c and diabetes distress were observed. Phase 2: Most providers viewed apps as adjuncts to diabetes education. Only 33% had previous app experience; however, 100% would consider recommending apps to their patients. Most would spend 5-15 minutes introducing apps to patients. All respondents agreed that the following DSMES app features-evidence-based educational content, data logging and tracking features, customizable user experience, digital coaching via goal setting or reminders, and ability to share data with providers-are key components to consider.. Findings suggest DSMES apps can play a role in self-management support and provide guidance on factors to consider when introducing digital tools into clinical practice.. Clinicaltrials.gov, #NCT03999268.

Topics: Adult; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin; Insulin, Regular, Human; Mobile Applications; Patient Outcome Assessment; Self-Management

To explore determinants of excessive weight gain after initiation of insulin therapy in type 2 diabetes mellitus (T2DM), in particular variables identified in the pre-insulin phase.. We performed a retrospective observational intervention cohort study, by means of a new user design/ inception cohort concerning n = 5086 patients. We studied determinants of excessive weight gain (5 kg or more) in the first year after initiation of insulin therapy, using both visualization and logistic regression analysis with subsequent receiver operation characteristic (ROC) analyses. Potential determinants pre-, at- and post-insulin initiation were included.. One out of 10 patients (10.0%) gained 5 kg weight or more. The earliest determinants of excessive weight gain were weight change (inversely) and HbA1c change in the two years prior to insulin therapy (p < 0.001). Patients that lost weight parallel with HbA1c rise in the two-years pre-insulin, showed the most pronounced weight gain. Of these patients, roughly one out of five (20.3%) gained 5 kg weight or more.. Clinicians and patients should be alert for excessive weight gain after initiation of insulin, in the case of weight loss prior to insulin therapy initiation, particularly with increasing and prolonged high HbA1c at (and after) insulin initiation.

Topics: Cohort Studies; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Retrospective Studies; Weight Gain

This study characterized incidence, patient profiles, risk factors and outcomes of in-hospital diabetic ketoacidosis (DKA) in patients with COVID-19 compared with influenza and pre-pandemic data.. This study consisted of 13 383 hospitalized patients with COVID-19 (March 2020-July 2022), 19 165 hospitalized patients with influenza (January 2018-July 2022) and 35 000 randomly sampled hospitalized pre-pandemic patients (January 2017-December 2019) in Montefiore Health System, Bronx, NY, USA. Primary outcomes were incidence of in-hospital DKA, in-hospital mortality, and insulin use at 3 and 6 months post-infection. Risk factors for developing DKA were identified.. The overall incidence of DKA in patients with COVID-19 and influenza, and pre-pandemic were 2.1%, 1.4% and 0.5%, respectively (p < .05 pairwise). Patients with COVID-19 with DKA had worse acute outcomes (p < .05) and higher incidence of new insulin treatment 3 and 6 months post-infection compared with patients with influenza with DKA (p < .05). The incidence of DKA in patients with COVID-19 was highest among patients with type 1 diabetes (12.8%), followed by patients with insulin-dependent type 2 diabetes (T2D; 5.2%), non-insulin dependent T2D (2.3%) and, lastly, patients without T2D (1.3%). Patients with COVID-19 with DKA had worse disease severity and higher mortality [odds ratio = 6.178 (4.428-8.590), p < .0001] compared with those without DKA. Type 1 diabetes, steroid therapy for COVID-19, COVID-19 status, black race and male gender were associated with increased risk of DKA.. The incidence of DKA was higher in COVID-19 cohort compared to the influenza and pre-pandemic cohort. Patients with COVID-19 with DKA had worse outcomes compared with those without. Many COVID-19 survivors who developed DKA during hospitalization became insulin dependent. Identification of risk factors for DKA and new insulin-dependency could enable careful monitoring and timely intervention.

Topics: COVID-19; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Humans; Incidence; Influenza, Human; Insulin; Insulin, Regular, Human; Male; Pandemics; Retrospective Studies; Risk Factors

To describe glucose-lowering drugs prescribing pattern in a large population of older diabetics from 2010 to 2021.. Using linkable administrative health databases, we included patients aged 65-90 years treated with glucose-lowering drugs. Prevalence rate of drugs was collected within each study year. A stratified analysis by gender, age and coexistence of cardiovascular disease (CVD) was conducted.. A total of 251 737 and 308 372 patients were identified in 2010 and 2021, respectively. Use of metformin (68.4% to 76.6%), DPP-4i (1.6% to 18.4%), GLP-1-RA (0.4% to 10.2%), SGLT2i (0.6% to 11.1%) increased, while sulfonylureas (53.6% to 20.7%) and glinides (10.5% to 3.5%) decreased over time. Metformin, glitazones, GLP1-RA, SGLT2i and DPP4i (except for 2021) usage decreased with aging, in contrast to sulfonylureas, glinides and insulin. The coexistence of CVD was associated with a higher prescription of glinides, insulin, DPP-4i, GLP1-RA and SGLT2i, particularly in 2021.. We found a significant increase in the prescriptions of GLP-1 RA and SGLT2i in older diabetics, mainly in those with CVD. However, drugs without CV benefits including sulfonylureas and DPP-4i continued to be highly prescribed in older patients. There is still room to improve the management in this population according to recommendations.

Topics: Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Metformin; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Treatment Outcome

The effects of diabetes medications on COVID-19 hospitalization outcomes have not been consistent. We sought to determine the effect of metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), and insulin on admission to the intensive care unit (ICU), need for assisted ventilation, development of renal insufficiency, and mortality in patients admitted with COVID-19 infection after controlling for clinical variables and other relevant diabetes-related medications in patients with type 2 diabetes mellitus (DM).. This was a retrospective study of patients hospitalized with COVID-19 from a single hospital system. Univariate and multivariate analyses were performed that included demographic data, glycated hemoglobin, kidney function, smoking status, insurance, Charlson comorbidity index, number of diabetes medications, and use of angiotensin-converting enzyme inhibitors and statin prior to admission and glucocorticoids during admission.. A total of 529 patients with type 2 DM were included in our final analysis. Neither metformin nor DPP4i prescription was associated with ICU admission, need for assisted ventilation, or mortality. Insulin prescription was associated with increased ICU admission but not with need for assisted ventilation or mortality. There was no association of any of these medications with development of renal insufficiency.. In this population, limited to type 2 DM and controlled for multiple variables that have not been consistently studied (such as a measure of general health, glycated hemoglobin, and insurance status), insulin prescription was associated with increased ICU admission. Metformin and DPP4i prescriptions did not have an association with the outcomes.

Topics: COVID-19; Diabetes Mellitus, Type 2; Dipeptidases; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Hospitals; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Metformin; Renal Insufficiency; Retrospective Studies

Evidence of an increased dementia risk with insulin use in type 2 diabetes is weakened by confounding by indication and disease severity. Herein we reassess this association, while accounting for confounding through design and analysis.. Using administrative health care data from British Columbia, Canada, we identified patients diagnosed with type 2 diabetes in 1998-2016. To adjust for confounding by diabetes severity through design, we compared new users of insulin to new users of a noninsulin class, both from a restricted cohort of those who previously received two noninsulin antihyperglycemic classes. We further adjusted for confounding using 1) conventional multivariable adjustment and 2) inverse probability of treatment weighting (IPTW) based on the high-dimensional propensity score algorithm. The hazard ratio [HR] (95% CI) of dementia was estimated using cause-specific hazards models with death as a competing risk.. The analytical comparative cohort included 7,863 insulin versus 25,230 noninsulin users. At baseline, insulin users were more likely to have worse health indicators. A total of 78 dementia events occurred over a median (interquartile range) follow-up of 3.9 (5.9) years among insulin users, and 179 events occurred over 4.6 (4.4) years among noninsulin users. The HR (95% CI) of dementia for insulin use versus noninsulin use was 1.68 (1.29-2.20) before adjustment and 1.39 (1.05-1.86) after multivariable adjustment, which was further attenuated to 1.14 (0.81-1.60) after IPTW.. Among individuals with type 2 diabetes previously exposed to two noninsulin antihyperglycemic medications, no significant association was observed between insulin use and all-cause dementia.

Topics: Cohort Studies; Dementia; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

This study investigated the ethnic differences in glycaemic levels and clinical characteristics among insulin-naïve people with type 2 diabetes (T2D) initiating biphasic insulin aspart 30/70 (BIAsp 30) in primary practice in England.. Retrospective, observational cohort study utilizing data from the Clinical Practice Research Datalink Aurum database, including White, South Asian, Black and Chinese insulin-naïve adults with T2D, initiating BIAsp 30. The index date was that of the first BIAsp 30 prescription. Endpoints included change in glycated haemoglobin (HbA1c) and body mass index (BMI) 6 months post index.. In total, 11 186 eligible people were selected (9443 White, 1116 South Asian, 594 Black, 33 Chinese). HbA1c decreased across all subgroups 6 months post index: estimated %-point changes [95% CI of -2.32 (-2.36; -2.28) (White); -1.91 (-2.02; -1.80) (South Asian); -2.55 (-2.69; -2.40) (Black); and -2.64 (-3.24; -2.04) (Chinese)]. The BMI increased modestly 6 months post index in all subgroups [estimated changes (95% CI) kg/m. Among insulin-naïve people with T2D initiating BIAsp 30, clinically meaningful HbA1c reductions in all ethnicities were observed. Some ethnic groups had larger reductions than others, but differences were small. In all groups, small BMI increases were seen, with small differences observed between groups. Hypoglycaemia rates were low.

Topics: Adult; Biphasic Insulins; Cohort Studies; Diabetes Mellitus, Type 2; England; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Insulin, Regular, Human; Retrospective Studies; Treatment Outcome

To assess the risk of major congenital malformations with metformin versus insulin in pregnancies with type 2 diabetes.. This cohort study used four Nordic countries' nationwide registers of live and stillborn infants exposed to metformin or insulin during first trimester organogenesis. Main exclusion criteria were type 1 diabetes, polycystic ovary syndrome, fertility treatment, and exposure to other diabetes drugs. Adjusted risk ratios (RRs) and 95% CIs were estimated for any and cardiac malformations.. Of 3,734,125 infants in the source population, 25,956 were exposed to metformin or insulin in the first trimester, and 4,023 singleton infants were included. A malformation was diagnosed in 147 (4.7%) of 3,145 infants with exposure to any metformin (alone or in addition to insulin) and 50 (5.7%) of 878 infants with exposure to insulin alone (RR 0.84, 95% CI 0.46-1.54). Among 2,852 infants exposed to metformin alone and 293 infants exposed to metformin in addition to insulin 127 (4.4%) and 20 (6.8%), respectively, had a malformation. The adjusted risk was not increased for either metformin alone (0.83, 0.44-1.58) or both metformin and insulin (0.98, 0.56-1.69) versus insulin alone. Corresponding RRs for cardiac malformations were 1.01 (0.55-1.84) for any metformin, 0.92 (0.47-1.81) for metformin alone, and 1.72 (0.76-3.91) for both metformin and insulin.. No evidence of an increased malformation risk with metformin versus insulin in the first trimester was found. Results should be interpreted with caution since information on glycemic control was missing.

Topics: Abnormalities, Drug-Induced; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin, Regular, Human; Metformin; Pregnancy

There is limited research regarding insulin dosing changes following adoption of plant-based diets. We conducted a nonrandomized crossover trial utilizing two plant-based diets (Dietary Approaches to Stop Hypertension, or DASH, and Whole Food, Plant-Based, or WFPB) to assess acute changes in insulin requirements and associated markers among individuals with insulin-treated type 2 diabetes.. Participants (n = 15) enrolled in a 4-week trial with sequential, one-week phases: Baseline, DASH 1, WFPB, and DASH 2. Each diet was ad libitum and meals were provided.. Compared to baseline, daily insulin usage was 24%, 39%, and 30% lower after DASH 1, WFPB, and DASH 2 weeks respectively (all p < 0.01). Insulin resistance (HOMA-IR) was 49% lower (p < 0.01) and the insulin sensitivity index was 38% higher (p < 0.01) at the end of the WFPB week before regressing toward baseline during DASH 2. Total, LDL, and HDL cholesterol, leptin, urinary glucose, and hsCRP decreased to a nadir at the end of the WFPB week before increasing during DASH 2.. Adopting a DASH or WFPB diet can result in significant, rapid changes in insulin requirements, insulin sensitivity, and related markers among individuals with insulin-treated type 2 diabetes, with larger dietary changes producing larger benefits.

Topics: Diabetes Mellitus, Type 2; Diet; Diet, Vegetarian; Dietary Approaches To Stop Hypertension; Humans; Hypertension; Insulin; Insulin Resistance; Insulin, Regular, Human

Successful management of type 2 diabetes mellitus (T2DM), a complex and chronic disease, requires a combination of anti-hyperglycemic and anti-inflammatory agents. Here, we have conceptualized and tested an integrated "closed-loop mimic" in the form of a glucose-responsive microgel (GRM) based on chitosan, comprising conventional insulin (INS) and curcumin-laden nanoparticles (nCUR) as a potential strategy for effective management of the disease. In addition to mimicking the normal, on-demand INS secretion, such delivery systems display an uninterrupted release of nCUR to combat the inflammation, oxidative stress, lipid metabolic abnormality, and endothelial dysfunction components of T2DM. Additives such as gum arabic (GA) led to a fivefold increased INS loading capacity compared to GRM without GA. The GRMs showed excellent in vitro on-demand INS release, while a constant nCUR release is observed irrespective of glucose concentrations. Thus, this study demonstrates a promising drug delivery technology that can simultaneously, and at physiological/pathophysiological relevance, deliver two drugs of distinct physicochemical attributes in the same formulation.

Topics: Chitosan; Curcumin; Diabetes Mellitus, Type 2; Glucose; Humans; Insulin; Insulin, Regular, Human; Microgels; Nanoparticles

SARS-CoV-2 infection increases the risk of diabetes and diabetic ketoacidosis (DKA) in both adults and children. We investigated the clinical course of new-onset type 2 diabetes in youth presenting with DKA during the COVID-19 pandemic.. This single-center retrospective cohort study included 148 subjects with obesity aged 10 to 21 years, admitted with DKA from January 2018 to January 2022. Groups were defined by the presence of DKA precipitant: any infection (n = 38, 26%), which included the SARS-CoV-2 (n = 10, 7%) and other infection (n = 28, 19%) groups, and no infection (n = 110, 74%). The primary outcome was insulin discontinuation within a 12-month follow-up.. The mean age was 14.9 years (IQR, 13.8-16.5), and age-adjusted body mass index (%) was 99.1 (IQR, 98.0-99.5) with 85.8% identifying as Black or Hispanic. There were no differences in DKA severity among groups. The incidence of DKA was higher during the pandemic (March 2020-January 2022, n = 117) than in the prepandemic period (January 2018-February 2020, n = 31). Within the first year after the acute DKA episode, 46 patients discontinued all insulin within 9 months (IQR, 4-14). Sixteen subjects restarted insulin 10 months (IQR, 6.5-11.0) after insulin discontinuation. Infection with SARS-CoV-2 at diagnosis was not associated with the likelihood (P =.57) or timing (P =.27) of discontinuing all insulin within 1 year, nor was having any infection.. The incidence of DKA at the onset of type 2 diabetes was higher during the SARS-CoV-2 pandemic than in the prepandemic period. SARS-CoV-2 infection was not associated with DKA severity or insulin discontinuation within the first year of diagnosis in youth with new-onset type 2 diabetes and DKA.

Topics: Adolescent; Adult; Child; COVID-19; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Humans; Insulin; Insulin, Regular, Human; Pandemics; Retrospective Studies; SARS-CoV-2

Short-term (2 weeks to 3 months) insulin intensive therapy using continuous subcutaneous insulin infusion (CSII) can improve islet beta cell function and prolong glycemic remission in patients with newly diagnosed type 2 diabetes mellitus (T2DM). However, the total daily insulin dose (TDD, IU/kg/d) required to achieve near-normoglycemic control with CSII still needs to be frequently adjusted based on blood glucose monitoring. Although real-time continuous glucose monitoring (rtCGM), which measures the interstitial fluid glucose concentration continuously without much difficulty, facilitates the adjustment of insulin dosage, its adoption in the T2DM population is strictly limited by insurance coverage and lack of awareness of rtCGM among clinicians. Thus, it is of clinical significance to identify easy-to-use parameters that may allow a more rapid and accurate prediction of TDD requirement. This study aimed to explore the association between hand grip strength (HGS) and TDD requirement in patients with T2DM receiving CSII therapy.. A total of 180 eligible patients with T2DM were enrolled in the study and divided into three groups based on their HGS: low (L), medium (M), and high (H). The TDD requirement was calculated on day 7 or 8 of CSII treatment. Anthropometric parameters, including HGS, skeletal muscle mass, skeletal muscle index (SMI) and 6-m gait speed, and laboratory data, were collected on the morning of the second day after admission, within the first 24 h of CSII therapy. These parameters were used to identify significant predictors of TDD requirement using Pearson or Spearman correlation test, and stepwise multiple regression analysis.. There were no significant differences in age, duration of T2DM, waist-to-hip ratio (WHR), body mass index (BMI), blood pressure, liver function, estimated glomerular filtration rate, triglyceride, total cholesterol, glycosylated hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of beta cell function (HOMA-β) among the groups. The H group had higher body muscle mass-to-fat ratio (BMFR), skeletal muscle mass-to-fat ratio (SMFR), SMI, 6-m gait speed, and lower TDD requirement than the M and L groups. The HGS negatively correlated with TDD requirement (r = -0.33,. Lower HGS is associated with an increased TDD requirement in T2DM patients. HGS may facilitate the prediction of TDD requirement in T2DM patients receiving CSII therapy.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Hand Strength; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

Insulin-stimulated glucose uptake in skeletal muscle is mediated by the glucose transporter GLUT4. The small GTPase Rac1 acts as a switch of signal transduction that regulates GLUT4 translocation to the plasma membrane following insulin stimulation. However, it remains obscure whether signaling cascades upstream and downstream of Rac1 in skeletal muscle are impaired by obesity that causes insulin resistance and type 2 diabetes. In an attempt to clarify this point, we investigated Rac1 signaling in the leptin-deficient (

Topics: Animals; Diabetes Mellitus, Type 2; Glucose; Glucose Transporter Type 4; Insulin; Insulin, Regular, Human; Leptin; Mice; Mice, Obese; Monomeric GTP-Binding Proteins; Muscle, Skeletal; rac1 GTP-Binding Protein; Signal Transduction

Although insulin mediated glucose uptake in skeletal muscle is a major mechanism ensuring glucose disposal in humans, glucose effectiveness, i.e., the ability of glucose itself to stimulate its own uptake independent of insulin, accounts for roughly half of the glucose disposed during an oral glucose tolerance test. Both insulin dependent and insulin independent skeletal muscle glucose uptake are however reduced in individuals with diabetes. We here show that AMPK activator O304 stimulates insulin independent glucose uptake and utilization in skeletal muscle and heart in vivo, while preventing glycogen accumulation. Combined glucose uptake and utilization requires an increased metabolic demand and we show that O304 acts as a mitochondrial uncoupler, i.e., generates a metabolic demand. O304 averts gene expression changes associated with metabolic inflexibility in skeletal muscle and heart of diabetic mice and reverts diabetic cardiomyopathy. In Type 2 diabetes, insulin resistance elicits compensatory insulin hypersecretion, provoking β-cell stress and eventually compensatory failure. In db/db mice O304 preserves β-cell function by preventing decline in insulin secretion, β-cell mass, and pancreatic insulin content. Thus, as a dual AMPK activator and mitochondrial uncoupler O304 mitigates two central defects of T2D; impaired glucose uptake/utilization and β-cell failure, which today lack effective treatment.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Glucose; Humans; Hyperglycemia; Insulin; Insulin, Regular, Human; Mice; Muscle, Skeletal

To elucidate how proinsulin synthesis and insulin was affected by metformin under conditions of nutrient overstimulation.. Isolated human pancreatic islets from seven donors were cultured at 5.5 mmol/L glucose and 0.5 mmol/L palmitate for 12, 24 or 72 h. Metformin (25 μmol/L) was introduced after initial 12 h with palmitate. Proinsulin and insulin were measured. Expression of prohormone convertase 1/3 (PC1/3) and carboxypeptidase E (CPE), was determined by western blot. Adolescents with obesity, treated with metformin and with normal glucose tolerance (n = 5), prediabetes (n = 14), or type 2 diabetes (T2DM; n = 7) were included. Fasting proinsulin, insulin, glucose, 2-h glucose and glycated haemoglobin were measured. Proinsulin/insulin ratio (PI/I) was calculated.. In human islets, palmitate treatment for 12 and 24 h increased proinsulin and insulin proportionally. After 72 h, proinsulin but not insulin continued to increase which was coupled with reduced expression of PC1/3 and CPE. Metformin normalized expression of PC1/3 and CPE, and proinsulin and insulin secretion. In adolescents with obesity, before treatment, fasting proinsulin and insulin concentrations were higher in subjects with T2DM than with normal glucose tolerance. PI/I was reduced after metformin treatment in subjects with T2DM as well as in subjects with prediabetes, coupled with reduced 2-h glucose and glycated haemoglobin.. Metformin normalized proinsulin and insulin secretion after prolonged nutrient-overstimulation, coupled with normalization of the converting enzymes, in isolated islets. In adolescents with obesity, metformin treatment was associated with improved PI/I, which was coupled with improved glycaemic control.

Topics: Adolescent; Carboxypeptidase H; Diabetes Mellitus, Type 2; Glucose; Glycated Hemoglobin; Humans; Insulin; Insulin, Regular, Human; Islets of Langerhans; Metformin; Palmitates; Pediatric Obesity; Prediabetic State; Proinsulin

Diabetes mellitus (DM) is the leading cause of premature death and disability. Despite a significant number of drugs, the effectiveness of therapy aimed at normalizing the level of glycemia and preventing complications does not fully satisfy doctors and patients. Therefore, the search for new approaches for the prevention and treatment of DM and its complications continues. Significant resources are used to develop new drugs, but recently the possibility of using «old» widely available drugs with newly discovered pleiotropic properties has been substantiated. These may include preparations of gammaaminobutyric acid (GABA) and agents that directly or indirectly activate GABAergic transmission, which have a pronounced pancreatic protective effect, which has been widely discussed in foreign literature over the past 10-15 years. However, there are few such publications in the domestic literature.It has been established that the content of GABA in β-cells in patients with type 1 and type 2 diabetes is reduced and this correlates with the severity of the disease. Genetic suppression of GABA receptors causes a significant decrease in the mass of β-cells and glucose-stimulated insulin secretion, which confirms the importance of GABA in ensuring glucose homeostasis and the advisability of replenishing the GABA deficiency in DM with its additional administration. It has been established that in animals with DM, GABA suppresses apoptosis and stimulates the regeneration of β-cells, increases β-cell mass and insulin production.Experimental data have been obtained indicating a synergistic effect of GABA when combined with glucagon-like peptide-1 (GLP-1) receptor agonists, DPP-4 inhibitors and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, when a more pronounced pancreoprotective effect is observed, due to decrease in oxidative and nitrosative stress, inflammation, increase in the level of Klotho protein, Nrf-2 activity and antioxidant defense enzymes, suppression of NF-kB activity and expression of pro-inflammatory cytokines. As a result, all this leads to a decrease in apoptosis and death of β-cells, an increase in β-cell mass, insulin production and, at the same time, a decrease in glucagon levels and insulin resistance.The review substantiates the feasibility of using GABA and drugs with a positive GABAeric effect in combination with new generation antidiabetic agents: GLP-1 receptor agonists, DPP-4 inhibitors and SGLT-2 inhibitors in order to increase their an

Topics: Animals; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; gamma-Aminobutyric Acid; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Sodium

Among adults with insulin- and/or secretagogue-treated diabetes in the United States, very little is known about the real-world descriptive epidemiology of iatrogenic severe (level 3) hypoglycaemia. Addressing this gap, we collected primary, longitudinal data to quantify the absolute frequency of events as well as incidence rates and proportions.. iNPHORM is a US-wide, 12-month ambidirectional panel survey (2020-2021). Adults with type 1 diabetes mellitus (T1DM) or insulin- and/or secretagogue-treated type 2 diabetes mellitus (T2DM) were recruited from a probability-based internet panel. Participants completing ≥1 follow-up questionnaire(s) were analysed.. Among 978 respondents [T1DM 17%; mean age 51 (SD 14.3) years; male: 49.6%], 63% of level 3 events were treated outside the health care system (e.g. by family/friend/colleague), and <5% required hospitalization. Following the 12-month prospective period, one-third of individuals reported ≥1 event(s) [T1DM 44.2% (95% CI 36.8%-51.8%); T2DM 30.8% (95% CI 28.7%-35.1%), p = .0404, α = 0.0007]; and the incidence rate was 5.01 (95% CI 4.15-6.05) events per person-year (EPPY) [T1DM 3.57 (95% CI 2.49-5.11) EPPY; T2DM 5.29 (95% CI 4.26-6.57) EPPY, p = .1352, α = 0.0007]. Level 3 hypoglycaemia requiring non-transport emergency medical services was more common in T2DM than T1DM (p < .0001, α = 0.0016). In total, >90% of events were experienced by <15% of participants.. iNPHORM is one of the first long-term, prospective US-based investigations on level 3 hypoglycaemia epidemiology. Our results underscore the importance of participant-reported data to ascertain its burden. Events were alarmingly frequent, irrespective of diabetes type, and concentrated in a small subsample.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Male; Middle Aged; Prospective Studies; Secretagogues; United States

Insulin lispro 100 units/mL Jr KwikPen is the first prefilled, disposable, half-unit insulin pen that delivers 0.5-30 units in increments of 0.5 units for the treatment of patients with diabetes. This study describes the profile of patients in Spain who initiated insulin therapy with Jr KwikPen in a real-world setting.. This retrospective, observational study based on IQVIA's electronic medical records database included patients with Type 1 (T1D) or Type 2 (T2D) diabetes who initiated therapy with Jr KwikPen between May 2018 and December 2020. Sociodemographic, clinical, and treatment characteristics at treatment initiation were analysed descriptively.. The profile of patients who initiated therapy with Jr KwikPen in routine practice was broad with many patients being adults. Most of these patients had T1D, inadequate glycemic control, and multiple associated comorbidities. These results suggest that Jr KwikPen is prescribed in patients who may benefit from finer insulin dose adjustments, namely children, adolescents, adults, older individuals, or pregnant women with T1D or T2D.

Topics: Adolescent; Adult; Aged; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Male; Middle Aged; Pregnancy; Retrospective Studies; Spain; Young Adult

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

Diabetes may feature impaired insulin kinetics, which could be aggravated by altered hepatic metabolism and glycemic control. Thus, we examined insulin clearance and its possible determinants in individuals with recent-onset diabetes.. Participants of the German Diabetes Study (GDS) with type 1 diabetes (T1D) (n = 306), type 2 diabetes (T2D) (n = 489), or normal glucose tolerance (control [CON]) (n = 167) underwent hyperinsulinemic-euglycemic clamps for assessment of whole-body insulin sensitivity (M value) and insulin clearance (ICCLAMP). Insulin clearance rates were further calculated during intravenous glucose tolerance tests (ICIVGTT) and mixed-meal tests (ICMMT). Hepatocellular lipid content (HCL) was quantified with 1H-MRS.. Both T1D and T2D groups had lower ICCLAMP (0.12 ± 0.07 and 0.21 ± 0.06 vs. 0.28 ± 0.14 arbitrary units [a.u.], respectively, all P < 0.05) and ICMMT (0.71 ± 0.35 and 0.99 ± 0.33 vs. 1.20 ± 0.36 a.u., all P < 0.05) than CON. In T1D, ICCLAMP, ICIVGTT, and ICMMT correlated negatively with HbA1c (all P < 0.05). M value correlated positively with ICIVGTT in CON and T2D (r = 0.199 and r = 0.178, P < 0.05) and with ICMMT in CON (r = 0.176, P < 0.05). HCL negatively associated with ICIVGTT and ICMMT in T2D (r = -0.005 and r = -0.037) and CON (r = -0.127 and r = -0.058, all P < 0.05). In line, T2D or CON subjects with steatosis featured lower ICMMT than those without steatosis (both P < 0.05).. Insulin clearance is reduced in both T1D and T2D within the first year after diagnosis but correlates negatively with liver lipid content rather in T2D. Moreover, insulin clearance differently associates with glycemic control and insulin sensitivity in each diabetes type, which may suggest specific mechanisms affecting insulin kinetics.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycemic Control; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Lipids; Liver

This study examined the impact of insulin products donated by a pharmaceutical manufacturer and dispensed by Dispensary of Hope-partnered pharmacies on medication access and treatment outcomes among uninsured patients with type 2 diabetes (T2D).. This was a pilot, single-center, retrospective observational study.. Uninsured patients with diabetes who were newly established with Ascension Medical Group clinics for the treatment of T2D were included in this study. Participants were prescribed insulin glargine, insulin isophane, or insulin isophane/insulin regular insulin therapy between March 2020 and August 2021. A retrospective chart review was conducted. Information collected included participants' hemoglobin A1c (HbA1c) level at baseline, 3 months, and 6 months; change in HbA1c level; insulin prescribed; fill history; whether they had been referred to a patient assistance program; and whether they were seen by a pharmacist under a collaborative practice agreement.. Thirty-eight participants were assessed, and 22 met criteria for the primary outcome. The mean HbA1c level decreased from 11.2% at baseline to 8.9% at 3 months and 8.8% at 6 months, resulting in a mean change in HbA1c of -2.4 percentage points (P = .033). Eleven participants (50%) had an HbA1c level of less than 9% at 6 months. The mean proportion of days covered was 76%. The mean monthly savings for insulin ranged from $183.74 (insulin isophane) to $253.84 (insulin glargine) per participant.. Our results showed a significant improvement in glycemic control among participants, demonstrating the substantial impact that pharmacies partnered with charitable medication distributors such as the Dispensary of Hope can have on individuals with insulin-treated T2D.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Regular, Human; Medically Uninsured; Retrospective Studies

Insulin-positive (+) cells (IPCs), detected in multiple organs, are of great interest as a probable alternative to ameliorate pancreatic beta-cells dysfunction and insulin deficiency in diabetes. Liver is a potential source of IPCs due to it common embryological origin with pancreas. We previously demonstrated the presence of IPCs in the liver of healthy and diabetic rats, but detailed description and analysis of the factors, which potentially can induced ectopic hepatic expression of insulin in type 1 (T1D) and type 2 diabetes (T2D), were not performed. In present study we evaluate mass of hepatic IPCs in the rat models of T1D and T2D and discuss factors, which may stimulate it generation: glycaemia, organ injury, involving of hepatic stem/progenitor cell compartment, expression of transcription factors and inflammation. Quantity of IPCs in the liver was up by 1.7-fold in rats with T1D and 10-fold in T2D compared to non-diabetic (ND) rats. We concluded that ectopic hepatic expression of insulin gene is activated by combined action of a number of factors, with inflammation playing a decision role.

Topics: Animals; Cell Differentiation; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Inflammation; Insulin; Insulin-Secreting Cells; Insulin, Regular, Human; Liver; Rats

Telemedicine can increase access to endocrinology care for people with type 2 diabetes (T2D), but patterns of use and outcomes of telemedicine specialty care for adults with T2D beyond initial uptake in 2020 are not known.. To evaluate patterns of telemedicine use and their association with glycemic control among adults with varying clinical complexity receiving endocrinology care for T2D.. Retrospective cohort study in a single large integrated US health system. Participants were adults who had a telemedicine endocrinology visit for T2D from May to October 2020. Data were analyzed from June 2022 to October 2023.. Patients were followed up through May 2022 and assigned to telemedicine-only, in-person, or mixed care (both telemedicine and in-person) cohorts according to visit modality.. Multivariable regression models were used to estimate hemoglobin A1c (HbA1c) change at 12 months within each cohort and the association of factors indicating clinical complexity (insulin regimen and cardiovascular and psychological comorbidities) with HbA1c change across cohorts. Subgroup analysis was performed for patients with baseline HbA1c of 8% or higher.. Of 11 498 potentially eligible patients, 3778 were included in the final cohort (81 Asian participants [2%], 300 Black participants [8%], and 3332 White participants [88%]); 1182 used telemedicine only (mean [SD] age 57.4 [12.9] years; 743 female participants [63%]), 1049 used in-person care (mean [SD] age 63.0 [12.2] years; 577 female participants [55%]), and 1547 used mixed care (mean [SD] age 60.7 [12.5] years; 881 female participants [57%]). Among telemedicine-only patients, there was no significant change in adjusted HbA1c at 12 months (-0.06%; 95% CI, -0.26% to 0.14%; P = .55) while in-person and mixed cohorts had improvements of 0.37% (95% CI, 0.15% to 0.59%; P < .001) and 0.22% (95% CI, 0.07% to 0.38%; P = .004), respectively. Patients with a baseline HbA1c of 8% or higher had a similar pattern of glycemic outcomes. For patients prescribed multiple daily injections vs no insulin, the 12-month estimated change in HbA1c was 0.25% higher (95% CI, 0.02% to 0.47%; P = .03) for telemedicine vs in-person care. Comorbidities were not associated with HbA1c change in any cohort.. In this cohort study of adults with T2D receiving endocrinology care, patients using telemedicine alone had inferior glycemic outcomes compared with patients who used in-person or mixed care. Additional strategies may be needed to support adults with T2D who rely on telemedicine alone to access endocrinology care, especially for those with complex treatment or elevated HbA1c.

Topics: Adult; Cohort Studies; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Insulin, Regular, Human; Middle Aged; Retrospective Studies; Telemedicine

This study compared the outcomes between intensive and nonintensive insulin regimens and assessed the predictive factors for failing to achieve the glycated hemoglobin (A1C) goals in type-2-diabetes-mellitus (T2DM) patients requiring insulin therapy.. A single-center, retrospective assessment of the medical records of 125 T2DM patients undergoing intensive (46 patients) and nonintensive insulin therapy (79 patients) were conducted.. No significant differences were found when the intensive and nonintensive insulin therapy groups were compared in terms of the percentage decreases of glucose and A1C levels. The mean A1C levels of the nonintensive and intensive groups declined from 11.15% and 11.30% to 7.97% and 8.06%, respectively.. Both intensive and nonintensive insulin therapies improved the baseline glycemic parameters but being overweight or obese and/or being reluctant to dietary recommendations led to treatment failures regardless of the insulin regimen.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin; Insulin, Regular, Human; Retrospective Studies

Finger prick blood glucose (BG) monitoring remains a mainstay of management in people with type 2 diabetes (T2DM) who take sulphonylurea (SU) drugs or insulin. We recently examined patient experience of BG monitoring in people with type 1 diabetes (T1DM). There has not been any recent comprehensive assessment of the performance of BG monitoring strips or the patient experience of BG strips in people with T2DM in the UK.. An online self-reported questionnaire containing 44 questions, prepared following consultation with clinicians and patients, was circulated to people with T2DM. 186 responders provided completed responses (25.5% return rate). Fixed responses were coded numerically (eg not confident = 0 fairly confident = 1).. Of responders, 84% were treated with insulin in addition to other agents. 75% reported having had an HbA1c check in the previous 6 months. For those with reported HbA1c ≥ 65 mmol/mol, a majority of people (70%) were concerned or really concerned about the shorter term consequences of running a high HbA1c This contrasted with those who did not know their recent HbA1c, of whom only 33% were concerned/really concerned and those with HbA1c <65 mmol/mol of whom 35% were concerned. Regarding BG monitoring/insulin adjustment, only 25% of responders reported having sufficient information with 13% believing that the accuracy and precision of their BG metre was being independently checked. Only 9% recalled discussing BG metre accuracy when their latest metre was provided and only 7% were aware of the International Standardisation Organisation (ISO) standards for BG metres. 77% did not recall discussing BG metre performance with a healthcare professional.. The group surveyed comprised engaged people with T2DM but even within this group there was significant variation in (a) awareness of shorter term risks, (b) confidence in their ability to implement appropriate insulin dosage (c) awareness of the limitations of BG monitoring technology. There is clearly an area where changes in education/support would benefit many.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin; Insulin, Regular, Human

Some guidelines allow for the use of either insulin or noninsulin antidiabetic agents for gestational diabetes, but only insulin is recommended for pregnant women with preexisting type 2 diabetes mellitus (T2DM). We aimed to document treatment patterns in routine care for women with preexisting T2DM.. We identified pregnancy cohorts within 2 US claims databases for publicly and privately insured individuals: the Medicaid Analytical eXtract (2000-2014) and OptumClinformatics (2004-2014). T2DM was classified with a validated algorithm using ICD-9-CM and CPT codes. We assessed medication usage over the years of the study, and changes in medication use before and after the beginning of pregnancy, using prescription fills as a proxy for the use of insulin, metformin, sulphonylureas and other noninsulin antidiabetic agents before pregnancy and during each trimester.. Among 12,631 women with T2DM, insulin use in pregnancy was stable over the study years (55%-60% in the 2nd trimester), but 2nd trimester use of metformin increased from <5% to 20%. Over the study period, 41% of women filled a prescription for metformin before pregnancy, 37% in the 1st trimester and 17% in the 2nd trimester. By the 2nd trimester, few women used sulphonylureas (11%) or other noninsulin antidiabetic agents (1%). Of the women on metformin only before pregnancy, 36% switched to insulin only by 2nd trimester, 11% added insulin and 16% continued on metformin only. Of the women on metformin and insulin before pregnancy, 61% switched to insulin only by 2nd trimester, 22% continued with metformin and insulin and <5% used only metformin.. The use of insulin-metformin combinations and other noninsulin antidiabetic drugs during pregnancy has increased. Safety studies for these medication regimens are needed.

Topics: Diabetes Mellitus, Type 2; Female; Glucose; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Male; Metformin; Pregnancy; Sulfonylurea Compounds; United States

Continuous glucose monitoring (CGM) is indicated in poorly controlled insulin-treated patients with type 2 diabetes (T2D) to improve glycemic control and reduce the risk of hypoglycemia, but the benefits of CGM for lower risk patients have not been well studied. Among 17,422 insulin-treated patients with T2D with hemoglobin A1c (HbA1c) <8% and no recent severe hypoglycemia (based on emergency room visits or hospitalizations), CGM initiation occurred in 149 patients (17,273 noninitiators served as reference). Changes in HbA1c and severe hypoglycemia rates for the 12 months before and after CGM initiation were calculated. CGM initiation was associated with decreased HbA1c (-0.06%), whereas noninitiation was associated with increased HbA1c (+0.32%); a weighted adjusted difference-in-difference model of change in HbA1c yielded a net benefit of -0.30%; 95% CI -0.50%, -0.10%;

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

The purpose of this study was to identify the psychological phenotypes of persons with type 2 diabetes (T2D) on insulin therapy to better inform personalized diabetes education strategies to improve self-management behaviors.. Q-methodology, a research approach combining the quantitative rigor of statistical analysis with qualitative data on perception of diabetes self-management by persons with T2D on insulin therapy, was used. The Summary of Diabetes Self-Care Activity measure and A1C in the past 6 months were used to further describe self-management behaviors of each P-sample, Q-sorter. Of 160 statements, 33 Q-sample statements were selected as Q-set. Then, 37 P-samples (24 men; 13 women) were recruited from a university-affiliated diabetes clinic in South Korea. Data obtained from each P-sample with a Q-set and a Q-sorting table, a forced-choice normal distribution table, were analyzed using varimax rotation.. Forty-one percent of the variance was explained with 5 factors represented by 27 Q-sorters, explaining variance ranging from 5% to 17% for each factor: Factor A (n = 6): those showing self-management education need but possessing inadequate health literacy; Factor B (n = 4): those valuing lifestyle modification to control diabetes; Factor C (n = 5): those valuing antidiabetic medication to control diabetes; Factor D (n = 6): carpe diem, accepting diabetes as destiny; and Factor E (n = 6): those overestimating their competencies to control diabetes. Ten Q-sorters fell into either confounded or nonsignificant.. Tailoring messages and educational approaches based on patients' psychological phenotypes are necessary to promote optimal self-management behaviors.

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Male; Patient-Centered Care; Self-Management

The high-dose large-volume insulin injections that may become necessary during pregnancy due to marked pregnancy-induced insulin resistance may result in suboptimal therapeutic effectiveness. Use of U-500 insulin, a concentrated insulin formulation, has been suggested during pregnancy. However, the pharmacokinetic properties of U-500 insulin monotherapy can impede achievement of strict pregnancy glycemic targets. We propose a novel regimen for treatment of severe pregnancy-induced insulin resistance that enables precise delivery of U-500 basal insulin therapy through continuous subcutaneous insulin infusion (CSII) while maintaining the desired kinetics of prandial rapid-acting U-100 insulin therapy. This combination approach, guided by continuous glucose monitoring data, enabled achievement of pregnancy glycemic targets while reducing basal insulin requirements by approximately one-third. We report our method for (1) conversion to U-500 insulin delivery through CSII during pregnancy and (2) conversion from U-500 basal insulin delivery through CSII to U-100 intravenous insulin infusion therapy at delivery, to offer clinicians who encounter similar challenging scenarios a novel approach to diabetes management during pregnancy in the setting of marked insulin resistance.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Infusion Systems; Insulin Resistance; Insulin, Regular, Human; Prediabetic State; Pregnancy

Insulin therapy forms a cornerstone of pharmacological management of diabetes mellitus (DM). However, there remains a lack of acceptance and adherence to insulin, thereby contributing to poor DM control. This study aimed to determine the impact of patients' beliefs about insulin on acceptance and adherence to insulin therapy.. This was a qualitative study using grounded theory approach. The study took place from September 2019 to January 2021 at a cluster of primary healthcare clinics in Singapore. Maximum variation sampling was used to recruit adult patients with type 2 DM on basal or premixed insulin for at least 6 months. Semistructured in-depth interviews were conducted using a topic guide and audio recorded. Data collection continued until saturation. Data analysis utilised a constant comparison procedure and a synthesis approach.. Twenty-one participants (mean age 61 years) were interviewed for this study. Data analyses showed that there were 6 main themes that emerged. Four themes influenced both insulin acceptance and adherence. These were concerns about insulin being a lifelong treatment, physical fear of insulin injection, erroneous beliefs about insulin, and perceived fear of DM complications. Two additional themes influenced adherence to insulin therapy. These were socioeconomic concerns, and concerns about side effects of insulin.. Patients' beliefs about insulin impact on the acceptance and adherence to insulin therapy. Health care providers need to elicit and address these beliefs during counselling to improve acceptance and adherence to insulin therapy.

Topics: Adult; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin, Regular, Human; Middle Aged; Primary Health Care; Qualitative Research

Insulin deficiency (ID) and resistance (IR) contribute to progression from normal glucose tolerance to diabetes to insulin requirement although their relative contributions in young-onset diabetes is unknown.. We examined the associations of HOMA2 using fasting plasma glucose and C-peptide in Chinese aged 20-50 years with (1) progression to type 2 diabetes (T2D) in participants without diabetes in a community-based cohort (1998-2013) and (2) glycaemic deterioration in patients with T2D in a clinic-based cohort (1995-2014). We defined ID as HOMA2-%B below median and insulin IR as HOMA2-IR above median.. During 10-year follow-up, 62 (17.9%) of 347 community-dwelling participants progressed to T2D. After 8.6 years, 291 (48.1%) of 609 patients with T2D had glycaemic deterioration. At baseline, progressors for T2D had higher HOMA2-IR, while in patients with T2D, progressors for glycaemic deterioration had higher HOMA2-IR and lower HOMA2-%B than non-progressors. The non-ID/IR group and the ID/IR group had an adjusted odds ratios of 2.47 (95% CI: 1.28, 4.94) and 5.36 (2.26, 12.79), respectively, for incident T2D versus the ID/non-IR group. In patients with T2D, 50% of the ID/IR group required insulin at 6.7 years versus around 11 years in the non-ID/IR or ID/non-IR, and more than 15 years in the non-ID/non-IR group. Compared with the latter group, the adjusted hazard ratios were 2.74 (1.80, 4.16) in the ID/non-IR, 2.73 (1.78, 4.19) in the non-ID/IR and 4.46 (2.87, 6.91) in the ID/IR group (p-interaction = 0.049).. In young Chinese adults, IR and ID contributed to progression to T2D and glycaemic deterioration.

Topics: Adult; Blood Glucose; China; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Middle Aged

Insulin-stimulated muscle glucose uptake is a key process in glycemic control. This process depends on the redistribution of glucose transporters to the surface membrane, a process that involves regulatory proteins such as TBC1D1 and TBC1D4. Accordingly, a TBC1D4 loss-of-function mutation in human skeletal muscle is associated with an increased risk of type 2 diabetes, and observations from carriers of a TBC1D1 variant associate this protein to a severe obesity phenotype. Here, we identified interactors of the endogenous TBC1D4 protein in human skeletal muscle by an unbiased proteomics approach. We detected 76 proteins as candidate TBC1D4 interactors. The binding of 12 of these interactors was regulated by insulin, including proteins known to be involved in glucose metabolism (e.g., 14-3-3 proteins and α-actinin-4 [ACTN4]). TBC1D1 also coprecipitated with TBC1D4 and vice versa in both human and mouse skeletal muscle. This interaction was not regulated by insulin or exercise in young, healthy, lean individuals. Similarly, the exercise- and insulin-regulated phosphorylation of the TBC1D1-TBC1D4 complex was intact. In contrast, we observed an altered interaction as well as compromised insulin-stimulated phosphoregulation of the TBC1D1-TBC1D4 complex in muscle of obese individuals with type 2 diabetes. Altogether, we provide a repository of TBC1D4 interactors in human and mouse skeletal muscle that serve as potential regulators of TBC1D4 function and, thus, insulin-stimulated glucose uptake in human skeletal muscle.

Topics: Animals; Diabetes Mellitus, Type 2; Glucose; GTPase-Activating Proteins; Humans; Insulin; Insulin, Regular, Human; Lighting; Mice; Muscle, Skeletal; Phosphorylation

Kidney insulin clearance, proposed to be the main route of extra-hepatic insulin clearance, occurs in tubular cells following glomerular filtration and peritubular uptake, a process that may be impaired in people with type 2 diabetes (T2D) and/or impaired kidney function. Human studies that investigated kidney insulin clearance are limited by the invasive nature of the measurement. Instead, we evaluated relationships between whole-body insulin clearance, and gold-standard measured kidney function and insulin sensitivity in adults with T2D and normal kidney function.. We determined insulin, inulin/iohexol and para-aminohippuric acid (PAH) clearances during a hyperinsulinemic-euglycemic clamp to measure whole-body insulin clearance and kidney function. Insulin sensitivity was expressed by glucose infusion rate (M value). Associations between whole-body insulin clearance, kidney function and insulin sensitivity were examined using univariable and multivariable linear regressions models.. We investigated 44 predominantly male (77%) T2D adults aged 63 ± 7, with fat mass 34.5 ± 9 kg, lean body mass 63.0 ± 11.8 kg, and HbA1c 7.4 ± 0.6%. Average whole-body insulin clearance was 1188 ± 358 mL/min. Mean GFR was 110 ± 22 mL/min, mean ERPF 565 ± 141 mL/min, and M value averaged 3.9 ± 2.3 mg/min. Whole-body insulin clearance was positively correlated with lean body mass, ERPF and insulin sensitivity, but not with GFR. ERPF explained 6% of the variance when entered in a nested multivariable linear regression model op top of lean body mass (25%) and insulin sensitivity (15%).. In adults with T2D and normal kidney function, whole-body insulin clearance was predicted best by lean body mass and insulin sensitivity, and to a lesser extent by ERPF. GFR was not associated with whole-body insulin clearance. In contrast to prior understanding, this suggests that in this population kidney insulin clearance may not play such a dominant role in whole-body insulin clearance.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Kidney; Male; Renal Plasma Flow

In folklore, Heritiera fomes (H. fomes) has been extensively used in treatment of various ailments such as diabetes, cardiac and hepatic disorders. The present study aimed to elucidate the antidiabetic actions of hot water extract of H. fomes (HWHF), including effects on insulin release from BRIN BD11 cells and isolated mouse islets as well as glucose homeostasis in high-fat-fed rats. Molecular mechanisms underlying anti-diabetic activity along with isolation of active compounds were also evaluated. Non-toxic concentrations of HWHF stimulated concentration-dependent insulin release from isolated mouse islets and clonal pancreatic β-cells. The stimulatory effect was potentiated by glucose and isobutyl methylxanthine (IBMX), persisted in presence of tolbutamide or a depolarizing concentration of KCl but was attenuated by established inhibitors of insulin release such as diazoxide, verapamil, and Ca2+ chelation. HWHF caused depolarization of the β-cell membrane and increased intracellular Ca2+. The extract also enhanced glucose uptake and insulin action in 3T3-L1 differentiated adipocytes cells and significantly inhibited in a dose-dependent manner starch digestion, protein glycation, DPP-IV enzyme activity, and glucose diffusion in vitro. Oral administration of HWHF (250 mg/5ml/kg b.w.) to high-fat fed rats significantly improved glucose tolerance and plasma insulin responses and it inhibited plasma DPP-IV activity. HWHF also decreased in vivo glucose absorption and intestinal disaccharidase activity while increasing gastrointestinal motility and unabsorbed sucrose transit. Compounds were isolated from HWHF with similar molecular weights to quercitrin (C21 H20 O11) ranging from 447.9 to 449.9 Da which stimulated the insulin release in vitro and improved both glucose tolerance and plasma insulin responses in mice. In conclusion, H. fomes and its water-soluble phytochemicals such as quercitrin may exert antidiabetic actions mediated through a variety of mechanisms which might be useful as dietary adjunct in the management of type 2 diabetes.

Topics: Animals; Blood Glucose; Calcium; Coriolaceae; Diabetes Mellitus, Type 2; Glucose; Hypoglycemic Agents; Imidazoles; Insulin; Insulin Secretion; Insulin, Regular, Human; Islets of Langerhans; Malvaceae; Mice; Plant Bark; Rats; Sulfonamides; Thiophenes; Water

Several risk factors for severe hypoglycaemia (SH) are associated with insulin-treated diabetes. This study explored potential risk factors in adults with insulin-treated type 2 diabetes mellitus (T2DM).. In this case-control study, adults with T2DM initiating insulin were identified in the IQVIA PharMetrics® Plus database. The index date was the date of the first SH event (cases). Using incidence-density sampling, controls were selected from those who had been exposed 'at risk' of SH for the same amount of time as each case. After exact-matching on the well-established factors, previously unreported risk factors were evaluated through conditional logistic regression.. In 3153 case-control pairs, pregnancy [odds ratios (OR) = 3.20, p = .0003], alcohol abuse (OR = 2.43, p < .0001), short-/rapid-acting insulin (OR = 2.22/1.47, p < .0001), cancer (OR = 1.87, p < .0001), dementia/Alzheimer's disease (OR = 1.73, p = .0175), peripheral vascular disease (OR = 1.59, p < .0001), antipsychotics (OR = 1.59; p = .0059), anxiolytics (OR = 1.51, p = .0012), paralysis/hemiplegia/paraplegia (OR = 1.51, p = .0416), hepatitis (OR = 1.50, p = .0303), congestive heart failure (OR = 1.47, p = .0002), adrenergic-corticosteroid combinations (OR = 1.45, p = .0165), β-adrenoceptor agonists (OR = 1.40, p = .0225), opioids (OR = 1.38, p < .0001), corticosteroids (OR = 1.35, p = .0159), cardiac arrhythmia (OR = 1.29. p = .0065), smoking (OR = 1.28, p = .005), Charlson Comorbidity Index score 2 (OR = 1.28, p = .0026), 3 (OR = 1.41, p = .0016) or ≥4 (OR = 1.57, p = .0002), liver/gallbladder/pancreatic disease (OR = 1.26, p = .0182) and hypertension (OR = 1.19, p = .0164) were independently associated with SH.. Although all people with insulin-treated diabetes are at risk of SH, these results have identified some previously unrecognized risk factors and sub-groups of insulin-treated adults with T2DM at greater risk. Scrutiny of current therapies and comorbidities are advised as well as additional glucose monitoring and education, when identifying and managing SH in vulnerable populations.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Case-Control Studies; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Risk Factors

The aim of this study was to define the relationship between time in range (TIR) and hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM).. The glycemic profile of 999 Japanese patients was analyzed with FreeStyle Libre Pro Continuous Glucose Monitoring (FLP-CGM) while they continued their prescribed glucose-lowering medications. FLP-CGM data recorded over 8 consecutive days were analyzed.. The regression model for HbA1c on TIR was HbA1c = 9.4966-0.0309 × TIR. The predicted HbA1c level for TIR of 70% was 7.33% and is higher than reports subjecting mostly T1DM. The TIR corresponding to HbA1c 7.0% was 80.64%. The patients with low TIR tended to have long duration of diabetes, used high dose of daily insulin, high body mass index, high HbA1c, liver dysfunction and high triglyceride. Relatively higher percentages of patients of this group used sulfonylureas, glucagon like peptide-1 receptor agonists and insulin.. Our data showed predicted HbA1c corresponding to TIR is largely depends on study population, thus is not uniform. Our results provide new insights on the management of T2DM. However, caution should be exercised in extending the HbA1C-TIR relationship using FLP-CGM to any other sensors since there could be a risk of hypoglycemia in doing so.

Topics: Benchmarking; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucose; Glycated Hemoglobin; Humans; Insulin; Insulin, Regular, Human

People living with diabetes in low-resource settings may be at increased hypoglycemia risk due to food insecurity and limited access to glucose monitoring. We aimed to assess hypoglycemia risk associated with sulphonylurea (SU) and insulin therapy in people living with type 2 diabetes in a low-resource sub-Saharan African setting.. This study was conducted in the outpatients' diabetes clinics of two hospitals (one rural and one urban) in Uganda. We used blinded continuous glucose monitoring (CGM) and self-report to compare hypoglycemia rates and duration in 179 type 2 diabetes patients treated with sulphonylureas (n=100) and insulin (n=51) in comparison with those treated with metformin only (n=28). CGM-assessed hypoglycemia was defined as minutes per week below 3mmol/L (54mg/dL) and number of hypoglycemic events below 3.0 mmol/L (54 mg/dL) for at least 15 minutes.. CGM recorded hypoglycemia was infrequent in SU-treated participants and did not differ from metformin: median minutes/week of glucose <3 mmol/L were 39.2, 17.0 and 127.5 for metformin, sulphonylurea and insulin, respectively (metformin vs sulphonylurea, p=0.6). Hypoglycemia risk was strongly related to glycated haemoglobin (HbA1c) and fasting glucose, with most episodes occurring in those with tight glycemic control. After adjusting for HbA1c, time <3 mmol/L was 2.1 (95% CI 0.9 to 4.7) and 5.5 (95% CI 2.4 to 12.6) times greater with sulphonylurea and insulin, respectively, than metformin alone.. In a low-resource sub-Saharan African setting, hypoglycemia is infrequent among people with type 2 diabetes receiving sulphonylurea treatment, and the modest excess occurs predominantly in those with tight glycemic control.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin, Regular, Human; Metformin; Sulfonylurea Compounds

Drug errors pose a major health hazard to a number of patient populations. However, patients with type 2 diabetes mellitus seem especially vulnerable to this risk as diabetes mellitus is usually concomitant with various comorbidities and polypharmacy, which present significant risk factors for the occurrence of drug errors. Despite this fact, there is little data on drug errors from patients' perspective. The present survey aimed to examine the viewpoints of patients with type 2 diabetes mellitus regarding their experiences with medication errors, the overall treatment satisfaction, and their perceptions on how a medication error was handled in daily hospital routine.. Inpatients at the Department of Endocrinology and Diabetology of the University Hospital of Graz were included in the survey. Out of 100 patients, one-half had insulin therapy before hospitalization while the other half had no insulin therapy prior to admission. After giving informed consent, patients filled out a questionnaire with 22 items.. Independent of their preexisting therapy, 25% of patients already suffered at least one drug error, whereby prescribing a wrong dose seemed to be the most common type of error. Furthermore, 26% of patients in the non-insulin versus 50% in the insulin group (p = 0.084) were convinced that drug errors were addressed honestly by the medical staff, while 54% in the non-insulin versus 80% in the insulin-group (p = 0.061) assumed that adequate measures were taken to prevent drug errors. Finally, 9 out of 10 patients seemed satisfied with their treatment regardless of their diabetes therapy.. The results of the survey clearly showed that patients experienced at least one medication error during hospitalization. However, these errors only rarely led to patient harm. The survey also revealed the value of an honest and respectful doctor-patient relationship regarding patient perception of medication errors and general complaints. Increasing patient awareness on the existing in-hospital error management systems could eliminate treatment-related concerns and create a climate of trust that is essential for effective treatment.

Topics: Diabetes Mellitus, Type 2; Humans; Insulin; Insulin, Regular, Human; Medication Errors; Physician-Patient Relations

We investigated trends in the proportion of diabetes treatment and glycemic control, which may be altered by recent advances in insulin and non-insulin drugs, in Japanese patients with type 2 diabetes.. A serial cross-sectional study was performed using a multicenter large-population database from the Japan Diabetes Clinical Data Management study group. Patients with type 2 diabetes who attended clinics belonging to the study group between 2002 and 2018 were included to examine trends in glycated hemoglobin A1c (HbA1c) by treatment group using multivariable non-linear regression model.. The proportion of patients with insulin only decreased from 15.0% to 3.6%, patients with insulin+non-insulin drugs increased from 8.1% to 15.1%, patients with non-insulin drugs increased from 50.8% to 67.0%, and those with no drugs decreased from 26.1% to 14.4% from 2002 to 2018, respectively. The HbA1c levels of each group, except for no drugs, continued to decrease until 2014 (unadjusted mean HbA1c (%) from 2002 to 2014: from 7.89 to 7.45 for insulin only, from 8.09 to 7.63 for insulin+non-insulin, and from 7.51 to 6.98 for non-insulin) and remained unchanged thereafter. Among insulin-treated patients, use of human insulin decreased, use of long-acting analog insulin increased, and concomitant use of non-insulin drugs increased (from 35.1% in 2002 to 80.9% in 2018), which included increased use of dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists, and the persistently high use of metformin.. During the past two decades, combined use of insulin and non-insulin drugs increased and glycemic control improved and leveled off after 2014 in Japanese patients with type 2 diabetes. Further studies of the trend in association with age and factors related to metabolic syndrome are necessary to investigate strategies aiming at personalized medicine in diabetes care.

Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Japan

Though many trials had examined the effectiveness of taking insulin with or without oral agents, there are limited real-world data, particularly among patients with type 2 diabetes mellitus (T2DM) in the resource limited settings. This study aimed to examine level of glycemic control among patients with T2DM after initiation of insulin and factors associated with poor glycemic control.. An analysis of retrospective medical records of patients with T2DM who initiated insulin due to uncontrolled hyperglycemia by oral agents was conducted from 2015-2020 in the University of Gondar Comprehensive Specialized Hospital. Difference in median fasting plasma glucose (FPG) before and after insulin initiations was examined by a Wilcoxon signed-rank test. Kruskal Wallis test was performed to explore difference in the median level of FPG among treatment groups. A logistic regression model was also used to identify associated factors of poor glycemic control after insulin initiation. Statistical significance was declared at p < 0.05.. Of 424 enrolled patients with T2DM, 54.7% were males and the mean age was 59.3±9.3 years. A Wilcoxon signed-rank test showed that there was significant deference in FPG before and after insulin initiation (P < 0.001). A declining trend of blood glucose was observed during the 1-year follow-up period of post-initiation. However, majority of the participants did not achieve target glucose levels. Participants who had higher FPG and systolic blood pressure (SBP) before insulin initiation were found more likely to have poor glycemic control after insulin initiation. Similarly, patients who received atorvastatin compared with simvastatin were found to have poor glycemic control in the post-period of initiation (P = 0.04). Premixed insulin was associated with a lower likelihood of poor glycemic control than neutral protamine Hagedorn (NPH) insulin (P < 0.001).. Following insulin initiation, a significant change in glycemic level and declining trend of FPG was observed during a 1-year follow-up period. However, the majority of patients still had a poorly controlled glycemic level. Appropriate management focusing on predictors of glycemic control would be of a great benefit to achieve glycemic control.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Ethiopia; Female; Follow-Up Studies; Glycated Hemoglobin; Glycemic Control; Hospitals, University; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Insulin, Regular, Human; Male; Middle Aged; Retrospective Studies

Coronavirus disease 2019 (COVID-19) is thought to contribute to diabetic ketoacidosis (DKA) and worse outcomes in patients with diabetes. This study compared the cumulative insulin dose required to achieve DKA resolution in the intensive care unit among patients with type 2 diabetes and COVID-19 infection versus without COVID-19 infection.. This retrospective cohort study evaluated 100 patients-50 patients with COVID-19 in cohort 1 and 50 patients without COVID-19 in cohort 2-treated with insulin infusions for DKA at a tertiary care teaching hospital. The primary outcome was to compare the cumulative insulin dose required to achieve DKA resolution in each cohort. The secondary outcomes included time to DKA resolution, mean insulin infusion rate, and mean weight-based cumulative insulin infusion dose required to achieve DKA resolution. All endpoints were adjusted for confounders.. The mean cumulative insulin dose was 190.3 units in cohort 1 versus 116.4 units in cohort 2 (P = .0038). Patients receiving steroids had a mean time to DKA resolution of 35.9 hours in cohort 1 versus 15.6 hours in cohort 2 (P = .0014). In cohort 1 versus cohort 2, the mean insulin infusion rate was 7.1 units/hour versus 5.3 units/hour (P = .0025), whereas the mean weight-based cumulative insulin infusion dose was 2.1 units/kg versus 1.5 units/kg (P = .0437), respectively.. COVID-19-infected patients required a significantly larger cumulative insulin dose, longer time to DKA resolution, higher insulin infusion rate, and higher weight-based insulin infusion dose to achieve DKA resolution versus non-COVID-19-infected patients with type 2 diabetes.

Topics: COVID-19; COVID-19 Drug Treatment; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Retrospective Studies

To assess the change in HbA1c after initiation of biosimilar follow-on insulin (Basaglar) or reference insulin (Lantus) among patients with type 2 diabetes. We also compared treatment adherence, safety events and costs at 1 year after initiation of insulin.. Using claims data from a large US health plan during 2016-2020, we identified adults with type 2 diabetes who initiated either Basaglar or Lantus. Generalized linear regression modelling assessed the differences in outcomes between the two groups. A 0.4% margin was used to determine non-inferiority for HbA1c.. The study included 1136 Basaglar users and 6304 Lantus users. Both Lantus and Basaglar groups showed more than 1% reduction in HbA1c over 6 months and over 12 months. Reduction in HbA1c with Basaglar was similar (non-inferior) to that with Lantus, with an adjusted difference of Basaglar to Lantus of 0.14% (95% CI -0.02 to 0.30) over 6 months and 0.17% (95% CI 0.02 to 0.32) over 12 months. Rates of adverse events were similar for both hypoglycaemia and vascular events. The Basaglar group showed higher adherence in terms of proportion of days covered (adjusted difference 0.06, 95% CI 0.04 to 0.08). Medical costs were similar, but the cost of Basaglar was lower (adjusted mean cost difference -$462, 95% CI -$556 to -$363) after adjustment.. In patients with type 2 diabetes, Basaglar provided similar glycaemic control compared with Lantus, had a similar safety profile and lower drug costs, and showed more favourable adherence.

Topics: Adult; Biosimilar Pharmaceuticals; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Regular, Human; Treatment Adherence and Compliance

Non-adherence to insulin therapy is a major global public health issue that has a causal relationship with increased diabetic complications that leads to further increase in the health care cost. However, adherence to insulin therapy and associated factors among diabetic mellitus (DM) patients are still not studied adequately in Ethiopia.. To assess the adherence to insulin therapy and associated factors among type 1 and type 2 diabetic patients on follow-up at Madda Walabu University-Goba Referral Hospital, South East Ethiopia.. An institution-based, cross-sectional study was employed among 311 both type 1 and type 2 diabetic patients, Madda Walabu University-Goba Referral Hospital from March 4 to April 30, 2020. Study participants were recruited with simple random sampling method. Adherence to insulin therapy was measured by 8-item Morisky medication adherence scale. Therefore from these 8-items, those who score 6 or more are considered as adherent to insulin therapy. The data were collected through interviewer administered questionnaires by trained graduating class nurse students. The data were entered to Epidata version 3.1, and analyzed with SPSS version 25. Bivariate and multivariable logistic regression analyses were used to identify factors associated with adherence to insulin therapy. Statistical significance were declared at p <0.05.. A total of 311 patients participate in the study with response rate of 100%. Among these only 38.9% of them were adherent to insulin therapy with a CI of [33.5, 44.3]. Having glucometer (AOR = 3.88; 95% CI [1.46, 10.35]), regular hospital follow-up (AOR = 3.13; 95% CI [1.12, 8.70]), being knowledgeable (AOR = 3.36; 95% CI [1.53, 7.37]), and favorable attitudes (AOR = 4.55; 95%CI [1.68, 12.34]) were the factor associated with adherence to insulin therapy.. This study concluded that adherence to insulin therapy was low in the study area. Having glucometer, regular hospital follow-up, being knowledgeable, and favorable attitudes were the factor associated with adherence to insulin therapy. Attention should be paid to help diabetic patients on acquiring knowledge regarding the need of consistent adherence to insulin therapy and its complications.

Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Ethiopia; Follow-Up Studies; Hospitals, University; Humans; Insulin; Insulin, Regular, Human; Medication Adherence; Referral and Consultation; Universities

Insulin resistance is a metabolic disorder characterized by the decreased response to insulin in muscle, liver, and adipose cells. This condition remains a complex phenomenon that involves several genetic defects and environmental stresses. In the present study, we investigated the mechanism of known phytochemical constituents of Tinospora crispa and its interaction with insulin-resistant target proteins by using network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Tinoscorside A, Makisterone C, Borapetoside A and B, and β sitosterol consider the main phytoconstituents of Tinospora crispa by its binding with active sites of main protein targets of insulin resistance potential therapy. Moreover, Tinoscorside A was revealed from the docking analysis as the ligand that binds most strongly to the target protein, PI3K. This finding was strengthened by the results of MD simulation, which stated that the conformational stability of the ligand-protein complex was achieved at 15 ns and the formation of hydrogen bonds at the active site. In conclusion, Tinospora crispa is one of the promising therapeutic agent in type 2 diabetes mellitus management. Regulation in glucose homeostasis, adipolysis, cell proliferation, and antiapoptosis are predicted to be the critical mechanism of Tinospora crispa as an insulin sensitizer.

Topics: Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Ligands; Molecular Docking Simulation; Molecular Dynamics Simulation; Network Pharmacology; Plant Extracts; Tinospora

Mendelian randomization (MR) suggests that postprandial hyperinsulinemia (unadjusted for plasma glucose) increases BMI, but its impact on cardiometabolic disease, a leading cause for mortality and morbidity in people with obesity, is not established. Fat distribution i.e., increased centripetal and/or reduced femoro-gluteal adiposity, is causally associated with and better predicts cardiometabolic disease than BMI. We therefore undertook bidirectional MR to assess the effect of corrected insulin response (CIR) (insulin 30 min after a glucose challenge adjusted for plasma glucose) on BMI, waist-to-hip ratio (WHR), leg fat, type 2 diabetes (T2D), triglyceride (TG), HDL, liver fat, hypertension (HTN), and coronary artery disease (CAD) in people of European descent. Inverse variance-weighted MR suggests a potential causal association between increased CIR and increased BMI (b = 0.048 ± 0.02, P = 0.03), increased leg fat (b = 0.029 ± 0.012, P = 0.01), reduced T2D (b = -0.73 ± 0.15, P = 6 × 10-7, odds ratio [OR] 0.48 [95% CI 0.36-0.64]), reduced TG (b = -0.07 ± 0.02, P = 0.003), and increased HDL (b = 0.04 ± 0.01, P = 0.006) with some evidence of horizontal pleiotropy. CIR had neutral effects on WHR (b = 0.009 ± 0.02, P = 0.69), liver fat (b = -0.08 ± 0.04, P = 0.06), HTN (b = -0.001 ± 0.004, P = 0.7, OR 1.00 [95% CI 0.99-1.01]), and CAD (b = -0.002 ± 0.002, P = 0.48, OR 0.99 [95% CI 0.81-1.21]). T2D decreased CIR (b -0.22 ± 0.04, P = 1.3 × 10-7), with no evidence that BMI, TG, HDL, liver fat, HTN, and CAD modulate CIR. In conclusion, we did not find evidence that increased CIR increases cardiometabolic disease. It might increase BMI with favorable fat distribution, reduce T2D, and improve lipids.

Topics: Blood Glucose; Body Mass Index; Coronary Artery Disease; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Glucose; Humans; Insulin; Insulin, Regular, Human; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors; Triglycerides

To investigate the baseline demographic and clinical characteristics of patients with type 1 diabetes mellitus (T1DM) newly treated with a sodium-glucose cotransporter 2 inhibitor (SGLT2i) as an add-on to insulin, or treated with insulin alone or in combination with oral anti-diabetic drugs other than an SGLT2i.. Retrospective study using data from the JMDC database (December 21, 2018, to October 31, 2020). Included patients with T1DM treated with an SGLT2i (add-on to insulin) (n = 1027) or with insulin (n = 4320). Baseline demographic and clinical characteristics were summarized, and change in insulin dose and efficacy outcomes, including hemoglobin A1c (HbA1c) and body mass index (BMI), before and after the first SGLT2i or insulin prescription were evaluated.. The SGLT2i add-on group had higher HbA1c and BMI than the insulin group. Daily insulin doses decreased from immediately before to after the first SGLT2i prescription. HbA1c and BMI improved from baseline to after the first SGLT2i prescription.. This large real-world study reported the baseline demographic and clinical characteristics of patients with T1DM newly treated with an SGLT2i in Japan. The findings may guide the appropriate use of SGLT2i and support large-scale database studies in T1DM research.

Topics: Demography; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucose; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Japan; Retrospective Studies; Sodium; Sodium-Glucose Transporter 2 Inhibitors

To establish cut-points and thresholds for elevated diabetes distress; document change over time; and define minimal clinically important differences (MCID) using the new Type 2 Diabetes Distress Assessment System (T2-DDAS).. A national sample of adults with type 2 diabetes completed the T2-DDAS CORE distress scale and the 7 T2-DDAS SOURCE distress scales at baseline and 6-months. Scores were computed separately for insulin- and non-insulin users. Spline regression models defined CORE cut-points and SEM formulas defined MCID. A rational "threshold" approach defined elevated SOURCE scores.. 471 participants (205 insulin, 266 non-insulin) completed both assessments. Analyses yielded ≥2.0 as the cut-point for both elevated CORE and elevated SOURCE. Prevalence of elevated CORE was 61.8 % (69.9 % over 6 months). Elevated SOURCE scores varied from 30.6 % (Stigma/Shame) to 76.4 % (Management); 87.5 % indicated at least 1 elevated SOURCE score. Most (77.1 %) reported multiple elevated SOURCES. 81.8 % with elevated CORE distress at baseline remained elevated at 6 months. MCID analyses yielded +/- 0.25 as significant change. Few differences between insulin- and non-insulin users occurred.. Elevated CORE distress is highly prevalent and persistent over time; most participants reported multiple SOURCES of distress. Findings highlight the need for comprehensive assessment of diabetes distress.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin, Regular, Human; Prevalence

Background: The liver has the capacity to regulate glucose metabolism by altering the insulin clearance rate (ICR). The decreased fasting insulin concentrations and enhanced prandial hyperinsulinemia after Roux-en-Y gastric-bypass (GB) surgery and sleeve gastrectomy (SG) are well documented. Here, we investigated the effect of GB or SG on insulin kinetics in the fasting and fed states. Method: ICR was measured (i) during a mixed-meal test (MMT) in obese non-diabetic GB (n = 9) and SG (n = 7) subjects and (ii) during a MMT combined with a hyperinsulinemic hypoglycemic clamp in the same GB and SG subjects. Five BMI-matched and non-diabetic subjects served as age-matched non-operated controls (CN). Results: The enhanced ICR during the fasting state after GB and SC compared with CN (p < 0.05) was mainly attributed to augmented hepatic insulin clearance rather than non-liver organs. The dose-response slope of the total insulin extraction rate (InsExt) of exogenous insulin per circulatory insulin value was greater in the GB and SG subjects than in the CN subjects, despite the similar peripheral insulin sensitivity among the three groups. Compared to the SG or the CN subjects, the GB subjects had greater prandial insulin secretion (ISR), independent of glycemic levels. The larger post-meal ISR following GB compared with SG was associated with a greater InsExt until it reached a plateau, leading to a similar reduction in meal-induced ICR among the GB and SG subjects. Conclusions: GB and SG alter ICR in the presence or absence of meal stimulus. Further, altered ICR after bariatric surgery results from changes in hepatic insulin clearance and not from a change in peripheral insulin sensitivity.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Gastrectomy; Gastric Bypass; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Obesity, Morbid

Mutations in HNF1A cause Maturity Onset Diabetes of the Young (HNF1A-MODY). To understand mechanisms of β-cell dysfunction, we generated stem cell-derived pancreatic endocrine cells with hypomorphic mutations in HNF1A. HNF1A-deficient β-cells display impaired basal and glucose stimulated-insulin secretion, reduced intracellular calcium levels in association with a reduction in CACNA1A expression, and accumulation of abnormal insulin granules in association with SYT13 down-regulation. Knockout of CACNA1A and SYT13 reproduce the relevant phenotypes. In HNF1A deficient β-cells, glibenclamide, a sulfonylurea drug used in the treatment of HNF1A-MODY patients, increases intracellular calcium, and restores insulin secretion. While insulin secretion defects are constitutive in β-cells null for HNF1A, β-cells heterozygous for hypomorphic HNF1A (R200Q) mutations lose the ability to secrete insulin gradually; this phenotype is prevented by correction of the mutation. Our studies illuminate the molecular basis for the efficacy of treatment of HNF1A-MODY with sulfonylureas, and suggest promise for the use of cell therapies.

Topics: Calcium; Diabetes Mellitus, Type 2; Hepatocyte Nuclear Factor 1-alpha; Humans; Insulin; Insulin, Regular, Human; Stem Cells; Synaptotagmins

Gut microbiome studies have documented depletion of butyrate-producing taxa in type 2 diabetes. We analyzed associations between butyrate-producing taxa and detailed measures of insulin homeostasis, whose dysfunction underlies diabetes in 224 non-Hispanic Whites and 129 African Americans, all of whom completed an oral glucose tolerance test. Stool microbiome was assessed by whole-metagenome shotgun sequencing with taxonomic profiling. We examined associations among 36 butyrate-producing taxa (n = 7 genera and 29 species) and insulin sensitivity, insulin secretion, disposition index, insulin clearance, and prevalence of dysglycemia (prediabetes plus diabetes, 46% of cohort), adjusting for age, sex, BMI, and race. The genus Coprococcus was associated with higher insulin sensitivity (β = 0.14; P = 0.002) and disposition index (β = 0.12; P = 0.012) and a lower rate of dysglycemia (odds ratio [OR] 0.91; 95% CI 0.85-0.97; P = 0.0025). In contrast, Flavonifractor was associated with lower insulin sensitivity (β = -0.13; P = 0.004) and disposition index (β = -0.11; P = 0.04) and higher prevalence of dysglycemia (OR 1.22; 95% CI 1.08-1.38; P = 0.0013). Species-level analyses found 10 bacteria associated with beneficial directions of effects and two bacteria with adverse associations on insulin homeostasis and dysglycemia. Although most butyrate producers analyzed appear to be metabolically beneficial, this is not the case for all such bacteria, suggesting that microbiome-directed therapeutic measures to prevent or treat diabetes should be targeted to specific butyrate-producing taxa rather than all butyrate producers.

Topics: Blood Glucose; Butyrates; Diabetes Mellitus, Type 2; Homeostasis; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Microbiota

Glycaemic control associates with better outcomes for hospitalised patients. Whether GLP-1 receptor agonists (GLP-1 RA) are suitable and effective drugs for inpatients is unclear.. A retrospective, single centre, observational study using data from the electronic health record. Patients admitted using GLP-1 RA as outpatients, from 2016 to 2019, were identified. Outcomes were compared to those admitted using twice-daily (BD) mixed insulin. Capillary glucose, medication use, creatinine, and demographic data were collected. As drugs may be discontinued/not administered in hospital, days when GLP-1 RA was administered were 'GLP-1 RA active' and, for insulin, 'insulin active'. The primary comparison was rate of hypoglycaemia (<4 mmol/L) and severe hypoglycaemia (<3 mmol/L). A logistic regression model examined variables for hypoglycaemia.. GLP-1 RA comprised n = 262 admissions and BD insulin n = 166. The 'insulin active' cohort (n = 957 patient days) had higher risk of hypoglycaemia than 'GLP-1 RA active' (n = 806 days); occurring on 14.7% of days; 95% confidence interval [CI] 12.6-17.1 versus 9.9% days; 95% CI 8.0-12.2; p = 0.002, and severe hypoglycaemia 4.0% of days (95% CI 2.8-5.4) versus 2.0% (95% CI 1.1%-3.2%; p = 0.005). Daily glucose (mean ± standard deviation) was 10.8 ± 5.2 mmol/L in insulin active versus 9.6 ± 4.7 mmol/L in GLP-1 RA active; p < 0.001. Insulin use, age, and acute admissions predicted hypoglycaemia. The odds ratio for hypoglycaemia was 2.15 times greater (95% CI, 1.14-4.08; p = 0.019) with insulin than with GLP-1 RA.. GLP-1 RA provided better glycaemic control than BD mixed insulin and should be continued during hospitalisation unless there is a clear indication for cessation.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucose; Glycated Hemoglobin; Glycemic Control; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Retrospective Studies

There have been numerous studies in humans and rodents substantiating the role of the gastrointestinal microbiome in the pathogenesis and progression of both type 1 and type 2 diabetes mellitus. Diabetes mellitus is a common endocrinopathy in dogs; however, little is known about the composition of the gut microbiome during the development and treatment of diabetes in this species. The objective of this pilot study was to characterize the gastrointestinal microbiome of dogs with diabetes mellitus at the time of diagnosis and over the first 12 weeks of insulin therapy and identify associations with glycemic control. Rectal swabs and serum for fructosamine measurement were collected from 6 newly diagnosed diabetic dogs at 2-week intervals for 12 weeks. Rectal samples were sequenced using 16S, ITS, and archaeal primers. Measures of alpha and beta diversity were assessed for changes over time; associations between absolute sequence variant (ASV) relative abundances and time and fructosamine concentration were identified using a microbiome-specific, multivariate linear effects model. No statistically significant changes over time were noted in alpha diversity and samples significantly grouped by dog rather than by time in the beta diversity analysis. However, multiple ASVs were negatively (Clostridium sensu stricto 1, Romboutsia, Collinsella) and positively (Streptococcus, Bacteroides, Ruminococcus gauveauii, Peptoclostridium) associated with time and two ASVs were positively associated with fructosamine (Enterococcus, Escherichia-Shigella). These changes in gastrointestinal microbial composition warrant further investigation of how they may relate to diabetes mellitus progression or control in dogs.

Topics: Animals; Diabetes Mellitus, Type 2; Dogs; Fructosamine; Gastrointestinal Microbiome; Humans; Insulin; Insulin, Regular, Human; Pilot Projects; RNA, Ribosomal, 16S

South Asian women have a higher risk of type 2 diabetes after gestational diabetes mellitus (GDM) than Nordic women; however, the mechanisms behind this difference remain unclear. We investigated insulin sensitivity, β-cell function, and hepatic insulin clearance in 179 South Asian and 108 Nordic women ∼17 months after GDM (mean age 35.3 years, BMI 29.1 kg/m2) by oral glucose tolerance test using deconvolution of C-peptide kinetics. Thirty-one percent of South Asian and 53% of Nordic participants were normoglycemic at the time of measurement. South Asian women had higher areas under the curve (AUCs) for glucose, prehepatic insulin, and peripheral insulin and lower insulin sensitivity, disposition index, and fasting hepatic insulin clearance than Nordic women. In the group with prediabetes or diabetes, South Asian women had similar AUCs for glucose and prehepatic insulin but a higher AUC for peripheral insulin, lower disposition index, and lower fasting hepatic insulin clearance than Nordic women. The waist-to-height ratio mediated ∼25-40% of the ethnic differences in insulin sensitivity in participants with normoglycemia. Overall, our novel data revealed that South Asian women with normoglycemia after GDM showed lower insulin secretion for a given insulin resistance and lower hepatic insulin clearance than Nordic women. South Asian women are at high risk of developing type 2 diabetes after GDM, and preventive efforts should be prioritized.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Kinetics; Pregnancy

Glycemic control immediately after hospital admission is difficult. This study aimed to develop an algorithm-based approach to initiate insulin therapy on admission.. Patients with history of diabetes mellitus admitted at UC Davis medical center, with any blood glucose (BG) value ≥ 180 mg/dL, or who received any insulin within the first 24 h of hospitalization were selected for a retrospective chart review.. Total of 315 patient records were studied. Patients prescribed insulin prior to admission had higher 24-hour average BG and higher corrected total daily dose of insulin (CxTDD), compared with the patients who were not prescribed insulin prior to admission. For the patients not receiving home insulin and not given new glucocorticoids, first BG upon presentation correlated with the risk of first 24-hour average BG > 180 mg/dL. Factors associated with CxTDD were first BG, weight, oral intake, and glucocorticoid dose. Home insulin daily dose, opiate/intravenous pain medication and systemic inflammatory response syndrome were associated with CxTDD only in the patients receiving home insulin.. A subgroup of patients can be given correction insulin as a sole initial treatment on admission. For patients requiring basal-bolus insulin, several factors associated with the initial insulin requirements are identified.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glucocorticoids; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Opiate Alkaloids; Retrospective Studies

We aimed to determine if severe hypoglycemia (SH) independently increases the risk of hospitalization for heart failure (hHF) in type 2 diabetes, regardless of the prevalent or incident cardiovascular disease (CVD).. This was a nationwide population-based propensity score-matched study using Korean National Health Insurance Service data (2002-2018). The hazards of hHF were compared in individuals who experienced SH (n = 8,965) and 1:3 matched controls, among adults with diabetes using oral anti-diabetes medications (OADs) with or without insulin and without previous hHF at baseline.. During 236,417 person-years, 1,189 cases of hHF occurred. The hazard of hHF was higher in individuals with SH compared to matched controls (adjusted hazard ratio [aHR] 1.503, 95 % confidence interval [CI] 1.324-1.707). The increase in aHR remained significant when excluding participants with prevalent or incident major adverse cardiovascular events (MACE; aHR 1.352, 95 % CI 1.228-1.622) and any CVD (aHR 1.342, 95 % CI 1.025-1.756). Two or more SH events were associated with further increase in hHF risk.. SH was associated with increased risks of hHF among adults with diabetes using OAD with or without insulin. The increased risk was attenuated but remained significant in those without prevalent or incident MACE or CVDs.

Topics: Adult; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Heart Failure; Hospitalization; Humans; Hypoglycemia; Insulin; Insulin, Regular, Human; Risk Factors

Though initiation of insulin results in a significant change in glycemic levels, treating patients without significant hypoglycemic events remains difficult in diabetes patients initiated with different insulin-based regimens. This study assessed the association of hypoglycemic incidence and glycemic control between NPH and premixed insulin regimens in patients with type 2 diabetes mellitus (T2DM).. This was a retrospective observational study in patients with T2DM who were treated with insulin-based therapy from 2015 to 2020 at the University of Gondar Comprehensive Specialized hospital. Average fasting blood glucose (FBG) between NPH and premixed insulin regimens was compared using an independent t-test. The Association of NPH and premixed insulin regimens with hypoglycemic incidences and glycemic control was examined by a logistic regression model. P < 0.05 was statistically significant.. From 405 participants, more than half (55.3%) were males with a mean age of 59.2(±9.1) years. Baseline mean HbA1C and FBG levels were 12.73(±1.1) % and 347.7(±48.5) mg/dl, respectively. Within a one-year follow-up period of insulin initiation, the rate of hypoglycemia was 13.1%. The incidence of hypoglycemia was significantly higher in patients initiated with premixed insulin compared with NPH insulin regimens (P < 0.001). After one year of insulin initiation, HbA1C decreased from 12.7 to 7.6 and from 12.8 to 7.3% and FBG levels decreased from 347.5 to 160.7 and from 348.2 to 147.3 mg/dl following initiation of NPH and premixed insulin, respectively. Patients treated with premixed-based insulin were found more likely to achieve target FBG compared with patients treated with NPH insulin regimens after one year of initiation (P = 0.02).. Premixed insulin-based regimen has found to have a higher hypoglycemic incidence, but a better level of glycemic control compared to NPH insulin-based therapy. Therefore, patients initiated with premixed insulin need to be highly vigilant and motivated to recognize the symptoms of hypoglycemia.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Ethiopia; Female; Glycated Hemoglobin; Glycemic Control; Hospitals; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Insulin, Regular, Human; Male; Middle Aged

Type 2 diabetes may affect the humoral immune response after vaccination, but data concerning coronavirus disease 19 (COVID-19) vaccines are scarce. We evaluated the impact of diabetes on antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in older residents of long-term care facilities (LTCFs) and tested for differences according to antidiabetic treatment.. For this analysis, 555 older residents of LTCFs participating in the GeroCovid Vax study were included. SARS-CoV-2 trimeric S immunoglobulin G (anti-S IgG) concentrations using chemiluminescent assays were tested before the first dose and after 2 and 6 months. The impact of diabetes on anti-S IgG levels was evaluated using linear mixed models, which included the interaction between time and presence of diabetes. A second model also considered diabetes treatment: no insulin therapy (including dietary only or use of oral antidiabetic agents) and insulin therapy (alone or in combination with oral antidiabetic agents).. The mean age of the sample was 82.1 years, 68.1% were women, and 25.2% had diabetes. In linear mixed models, presence of diabetes was associated with lower anti-S IgG levels at 2 (β = -0.20; 95% CI -0.34, -0.06) and 6 months (β = -0.22; 95% CI -0.37, -0.07) after the first vaccine dose. Compared with those without diabetes, residents with diabetes not using insulin had lower IgG levels at 2- and 6-month assessments (β = -0.24; 95% CI -0.43, -0.05 and β = -0.30; 95% CI -0.50, -0.10, respectively), whereas no differences were observed for those using insulin.. Older residents of LTCFs with diabetes tended to have weaker antibody response to COVID-19 vaccination. Insulin treatment might buffer this effect and establish humoral immunity similar to that in individuals without diabetes.

Topics: Aged; Aged, 80 and over; Antibody Formation; COVID-19; COVID-19 Vaccines; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Immunoglobulin G; Insulin; Insulin, Regular, Human; Long-Term Care; Male; SARS-CoV-2; Vaccination

Recent joint American Diabetes Association and European Association for the Study of Diabetes guidelines recommend routine islet autoantibody testing in all adults newly diagnosed with type 1 diabetes. We aimed to assess the impact of routine islet autoantibody testing in this population.. We prospectively assessed the relationship between islet autoantibody status (GADA, IA-2A, and ZNT8A), clinical and genetic characteristics, and progression (annual change in urine C-peptide-to-creatinine ratio [UCPCR]) in 722 adults (≥18 years old at diagnosis) with clinically diagnosed type 1 diabetes and diabetes duration <12 months. We also evaluated changes in treatment and glycemia over 2 years after informing participants and their clinicians of autoantibody results.. Of 722 participants diagnosed with type 1 diabetes, 24.8% (179) were autoantibody negative. This group had genetic and C-peptide characteristics suggestive of a high prevalence of nonautoimmune diabetes: lower mean type 1 diabetes genetic risk score (islet autoantibody negative vs. positive: 10.85 vs. 13.09 [P < 0.001] [type 2 diabetes 10.12]) and lower annual change in C-peptide (UCPCR), -24% vs. -43% (P < 0.001).After median 24 months of follow-up, treatment change occurred in 36.6% (60 of 164) of autoantibody-negative participants: 22.6% (37 of 164) discontinued insulin, with HbA1c similar to that of participants continuing insulin (57.5 vs. 60.8 mmol/mol [7.4 vs. 7.7%], P = 0.4), and 14.0% (23 of 164) added adjuvant agents to insulin.. In adult-onset clinically diagnosed type 1 diabetes, negative islet autoantibodies should prompt careful consideration of other diabetes subtypes. When routinely measured, negative antibodies are associated with successful insulin cessation. These findings support recent recommendations for routine islet autoantibody assessment in adult-onset type 1 diabetes.

Topics: Adolescent; Adult; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glutamate Decarboxylase; Humans; Insulin; Insulin, Regular, Human

Topics: Developing Countries; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin, Regular, Human

Defects in the pancreatic β-cell's secretion system are well-described in type 2 diabetes (T2D) and include impaired proinsulin processing and a deficit in mature insulin-containing secretory granules; however, the cellular mechanisms underlying these defects remain poorly understood. To address this, we used an in situ fluorescent pulse-chase strategy to study proinsulin trafficking. We show that insulin granule formation and the appearance of nascent granules at the plasma membrane are decreased in rodent and cell culture models of prediabetes and hyperglycemia. Moreover, we link the defect in insulin granule formation to an early trafficking delay in endoplasmic reticulum (ER) export of proinsulin, which is independent of overt ER stress. Using a ratiometric redox sensor, we show that the ER becomes hyperoxidized in β-cells from a dietary model of rodent prediabetes and that addition of reducing equivalents restores ER export of proinsulin and insulin granule formation and partially restores β-cell function. Together, these data identify a critical role for the regulation of ER redox homeostasis in proinsulin trafficking and suggest that alterations in ER redox poise directly contribute to the decline in insulin granule production in T2D. This model highlights a critical link between alterations in ER redox and ER function with defects in proinsulin trafficking in T2D. Hyperoxidation of the ER lumen, shown as hydrogen peroxide, impairs proinsulin folding and disulfide bond formation that prevents efficient exit of proinsulin from the ER to the Golgi. This trafficking defect limits available proinsulin for the formation of insulin secretory granules during the development of T2D.

Topics: Diabetes Mellitus, Type 2; Endoplasmic Reticulum; Homeostasis; Humans; Insulin; Insulin-Secreting Cells; Insulin, Regular, Human; Oxidation-Reduction; Prediabetic State; Proinsulin

Metformin is often used as a first-line therapy for type 2 diabetes; however, frequent discontinuation with reduced kidney function and increased disease severity indicates that a comparison with any other group (eg, nonusers or insulin users) must address significant residual confounding concerns.. To examine the potential for residual confounding in a commonly used observational study design applied to metformin and to propose a more robust study design for future observational studies of metformin.. This retrospective cohort study with a prevalent user design was conducted using an administrative claims database for Medicare Advantage beneficiaries in the US. Participants were categorized into 2 distinct cohorts: 404 458 individuals with type 2 diabetes and 81 791 individuals with prediabetes. Clinical history was observed in 2018, and end points were observed in 2019. Statistical analyses were conducted between May and December 2021.. Prevalent use (recent prescription and history of use on at least 90 of the preceding 365 days) of metformin or insulin but not both at the start of the observation period.. Total inpatient admission days in 2019 and total medical spending (excluding prescription drugs) in 2019. Each of these measures was treated as a binary outcome (0 vs >0 inpatient days and top 10% vs bottom 90% of medical spending).. The study included 404 458 adults with type 2 diabetes (mean [SD] age, 74.5 [7.5] years; 52.7% female). A strong metformin effect estimate was associated with reduced inpatient admissions (odds ratio, 0.60; 95% CI, 0.58-0.62) and reduced medical expenditures (odds ratio, 0.57; 95% CI, 0.55-0.60). However, implementation of additional robust design features (negative control outcomes and a complementary cohort) revealed that the estimated beneficial effect was attributable to residual confounding associated with individuals' overall health, not metformin itself.. These findings suggest that common observational study designs for studies of metformin in a type 2 diabetes population are at risk for consequential residual confounding. By performing 2 additional validation checks, the study design proposed here exposes residual confounding that nullifies the initially favorable claim derived from a common study design.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Insulin, Regular, Human; Male; Medicare Part C; Metformin; Retrospective Studies; United States

A queueing theory based model of mTOR complexes impact on Akt-mediated cell response to insulin is presented in this paper. The model includes several aspects including the effect of insulin on the transport of glucose from the blood into the adipocytes with the participation of GLUT4, and the role of the GAPDH enzyme as a regulator of mTORC1 activity. A genetic algorithm was used to optimize the model parameters. It can be observed that mTORC1 activity is related to the amount of GLUT4 involved in glucose transport. The results show the relationship between the amount of GAPDH in the cell and mTORC1 activity. Moreover, obtained results suggest that mTORC1 inhibitors may be an effective agent in the fight against type 2 diabetes. However, these results are based on theoretical knowledge and appropriate experimental tests should be performed before making firm conclusions.

Topics: Adipocytes; Diabetes Mellitus, Type 2; Glucose; Glucose Transporter Type 4; Humans; Insulin; Insulin, Regular, Human; Mechanistic Target of Rapamycin Complex 1; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases

To determine the extent to which the presence of acanthosis nigricans confers additional risk for insulin resistance, in addition to obesity alone (body mass index, BMI) within a young, overweight, UK population.. Retrospective data were collected to compare the degree of insulin resistance within a sample of 94 young people with acanthosis nigricans, and a matched cohort of 94 participants with obesity alone. Insulin resistance was assessed by fasting glucose, fasting insulin and Homeostatic Model Assessment of insulin resistance (HOMA-IR) score (a mathematical model derived to measure insulin resistance).. The acanthotic and control group were well matched for age, BMI, BMI SDS and sex, although the groups were not matched for ethnicity. The acanthotic group showed a significantly greater median fasting insulin (215 pmol/L), mean fasting glucose (4.7 mmol/L) and median HOMA-IR score (6.4), compared with the control group (126 pmol/L, 4.5 mmol/L and 3.7, respectively). The presence of acanthosis nigricans as an indicator of insulin resistance was found to have a positive predictive value of 81% (within this study population).. Individuals with both acanthosis nigricans and obesity had significantly greater degrees of insulin resistance than individuals with obesity alone. The findings support the potential for acanthosis nigricans as a visible marker of type 2 diabetes in young people.

Topics: Acanthosis Nigricans; Case-Control Studies; Diabetes Mellitus, Type 2; Glucose; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Obesity; Overweight; Retrospective Studies; United Kingdom

Pancreatic and duodenal homeobox factor-1 (. HOMA-beta (homeostatic model assessment beta-cell function) was significantly lower in the high-risk group than in the low-risk group for all subjects (72.9±54.2% vs 107.0±63.5%, p<0.05). Glucose levels and glucose area under the curve (AUC) were not significantly different between both the risk groups. The insulin levels at 60 and 120 min and the insulin AUC after MTT were remarkably lower in the high-risk group than those in the low-risk group for all subjects (AUC 75.7±36.7 vs 112.7±59.5, p<0.05). High-risk subjects with type 2 diabetes had significantly lower insulin levels at 30 and 60 min and insulin AUC than low-risk subjects. Non-diabetic high-risk subjects depicted significantly lower insulin levels at 120 and 180 min. There were negligible differences in insulin resistance between the risk groups.. These results suggest that the

Topics: Diabetes Mellitus, Type 2; East Asian People; Genes, Homeobox; Genome-Wide Association Study; Glucose; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin, Regular, Human; Polymorphism, Genetic

Hyperglycemic crises (ie, diabetic ketoacidosis [DKA] and hyperglycemic hyperosmolar state [HHS]) are life-threatening acute complications of diabetes. Efforts to prevent these events at the population level have been hindered by scarce granular data and difficulty in identifying individuals at highest risk.. To assess sociodemographic, clinical, and treatment-related factors associated with hyperglycemic crises in adults with type 1 or type 2 diabetes in the US from 2014 to 2020.. This retrospective cohort study analyzed administrative claims and laboratory results for adults (aged ≥18 years) with type 1 or type 2 diabetes from the OptumLabs Data Warehouse from January 1, 2014, through December 31, 2020.. Rates of emergency department or hospital visits with a primary diagnosis of DKA or HHS (adjusted for age, sex, race/ethnicity, and region, and for year when calculating annualized rates) were calculated separately for patients with type 1 diabetes and type 2 diabetes. The associations of sociodemographic factors (age, sex, race/ethnicity, region, and income), clinical factors (comorbidities), and treatment factors (glucose-lowering medications, hemoglobin A1c) with DKA or HHS in patients with type 1 or type 2 diabetes were assessed using negative binomial regression.. Among 20 156 adults with type 1 diabetes (mean [SD] age, 46.6 [16.5] years; 51.2% male; 72.6% White race/ethnicity) and 796 382 with type 2 diabetes (mean [SD] age, 65.6 [11.8] years; 50.3% female; 54.4% White race/ethnicity), adjusted rates of hyperglycemic crises were 52.69 per 1000 person-years (95% CI, 48.26-57.12 per 1000 person-years) for type 1 diabetes and 4.04 per 1000 person-years (95% CI, 3.88-4.21 per 1000 person-years) for type 2 diabetes. In both groups, factors associated with the greatest hyperglycemic crisis risk were low income (≥$200 000 vs <$40 000: type 1 diabetes incidence risk ratio [IRR], 0.61 [95% CI, 0.46-0.81]; type 2 diabetes IRR, 0.69 [95% CI, 0.56-0.86]), Black race/ethnicity (vs White race/ethnicity: type 1 diabetes IRR, 1.33 [95% CI, 1.01-1.74]; type 2 diabetes IRR, 1.18 [95% CI, 1.09-1.27]), high hemoglobin A1c level (≥10% vs 6.5%-6.9%: type 1 diabetes IRR, 7.81 [95% CI, 5.78-10.54]; type 2 diabetes IRR, 7.06 [95% CI, 6.26-7.96]), history of hyperglycemic crises (type 1 diabetes IRR, 7.88 [95% CI, 6.06-9.99]; type 2 diabetes IRR, 17.51 [95% CI, 15.07-20.34]), severe hypoglycemia (type 1 diabetes IRR, 2.77 [95% CI, 2.15-3.56]; type 2 diabetes IRR, 4.18 [95% CI, 3.58-4.87]), depression (type 1 diabetes IRR, 1.62 [95% CI, 1.37-1.92]; type 2 diabetes IRR, 1.46 [95% CI, 1.34-1.59]), neuropathy (type 1 diabetes IRR, 1.64 [95% CI, 1.39-1.93]; type 2 diabetes IRR, 1.25 [95% CI, 1.17-1.34]), and nephropathy (type 1 diabetes IRR, 1.22 [95% CI, 1.01-1.48]; type 2 diabetes IRR, 1.23 [95% CI, 1.14-1.33]). Age had a U-shaped association with hyperglycemic crisis risk in patients with type 1 diabetes (compared with patients aged 18-44 years: 45-64 years IRR, 0.72 [95% CI, 0.59-0.87]; 65-74 years IRR, 0.62 [95% CI, 0.47-0.80]; ≥75 years IRR, 0.96 [95% CI, 0.66-1.38]). In type 2 diabetes, risk of hyperglycemic crises decreased progressively with age (45-64 years IRR, 0.57 [95% CI, 0.51-0.63]; 65-74 years IRR, 0.44 [95% CI, .39-0.49]; ≥75 years IRR, 0.41 [95% CI, 0.36-0.47]). In patients with type 2 diabetes, higher risk was associated with sodium-glucose cotransporter 2 inhibitor therapy (IRR, 1.30; 95% CI, 1.14-1.49) and insulin dependency (compared with regimens with bolus insulin: regimens with basal insulin only, IRR, 0.69 [95% CI, 0.63-0.75]; and without any insulin, IRR, 0.36 [95% CI, 0.33-0.40]).. In this cohort study, younger age, Black race/ethnicity, low income, and poor glycemic control were associated with an increased risk of hyperglycemic crises. The findings suggest that multidisciplinary interventions focusing on groups at high risk for hyperglycemic crises are needed to prevent these dangerous events.

Topics: Adolescent; Adult; Age Factors; Cohort Studies; Demography; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Ethnicity; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin, Regular, Human; Insurance Claim Review; Male; Middle Aged; Poverty; Retrospective Studies; Risk Factors; Social Class; United States; Young Adult

Topics: Aged; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Drug Interactions; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Regular, Human; Insurance Claim Review; Male; Middle Aged; Secretagogues; United States

Topics: Diabetes Mellitus, Type 2; Humans; Insulin; Insulin, Regular, Human; Republic of Korea

Topics: Animals; Blood Glucose; Boronic Acids; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Liberation; Glucose Oxidase; Humans; Hydrogen Peroxide; Injections, Subcutaneous; Insulin, Regular, Human; Oxidation-Reduction; Rats

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Insulin; Insulin, Regular, Human

Type 2 diabetes (T2D) is a common metabolic disease. Variants in human IGF2 mRNA binding protein 2 (IMP2/IGF2BP2) are associated with increased risk of T2D. IMP2 contributes to T2D susceptibility primarily through effects on insulin secretion. However, the underlying mechanism is not known.. To understand the role of IMP2 in insulin secretion and T2D pathophysiology, we generated Imp2 pancreatic β-cell specific knockout mice (βIMP2KO) by recombining the Imp2. The deletion of IMP2 in pancreatic β-cells leads to reduced compensatory β-cell proliferation and function. Mechanically, IMP2 directly binds to Pdx1 mRNA and stimulates its translation in an m6A dependent manner. Moreover, IMP2 orchestrates IGF2-AKT-GSK3β-PDX1 signaling to stable PDX1 polypeptides. In human EndoC-βH1 cells, the over-expression of IMP2 is capable to enhance cell proliferation, PDX1 protein level and insulin secretion.. Our work therefore reveals IMP2 as a critical regulator of pancreatic β-cell proliferation and function; highlights the importance of posttranscriptional gene expression in T2D pathology.

Topics: Adenosine; Animals; Cell Line; Cell Proliferation; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Gene Knockout Techniques; Homeodomain Proteins; Humans; Insulin Secretion; Insulin-Secreting Cells; Insulin, Regular, Human; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Promoter Regions, Genetic; Rats; RNA-Binding Proteins; RNA, Messenger; Signal Transduction; Trans-Activators; Transfection

Organic anion transporter 3 (OAT3) plays an important role in the disposition of various anionic drugs which impacts the pharmacokinetics and pharmacodynamics of the therapeutics, thus influencing the pharmacological effects and toxicity of the drugs. In this study, we investigated the effect of insulin on the regulation of OAT3 function, expression, and SUMOylation. We demonstrated that insulin induced an increase in OAT3 transport activity through a dose- and time-dependent manner in COS-7 cells. The insulin-induced elevation in OAT3 function was blocked by PKA inhibitor H89, which correlated well with OAT3 protein expression. Moreover, both PKA activator Bt2-cAMP-induced increase and insulin-induced increase in OAT3 function were blocked by PKB inhibitor AKTi1/2. To further investigate the involvement of SUMOylation, we treated OAT3-expressing cells with insulin in presence or absence of H89 or AKTi1/2 followed by examining OAT3 SUMOylation. We showed that insulin enhanced OAT3 SUMOylation, and such enhancement was abrogated by H89 and AKTi1/2. Lastly, insulin increased OAT3 function and SUMOylation in rat kidney slice. In conclusion, our investigations demonstrated that insulin regulated OAT3 function, expression, and SUMOylation through PKA/PKB signaling pathway. Graphical abstract.

Topics: Animals; Chlorocebus aethiops; COS Cells; Cyclic AMP-Dependent Protein Kinases; Diabetes Mellitus, Type 2; Estrone; Humans; Insulin, Regular, Human; Isoquinolines; Kidney; Models, Animal; Organic Anion Transporters, Sodium-Independent; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Rats; Recombinant Proteins; Signal Transduction; Sulfonamides; Sumoylation

Severely insulin-resistant type 2 diabetes (T2D) patients face unique treatment challenges. Humulin R U-500 (U-500R) as insulin monotherapy with both basal/bolus properties addresses these challenges, although it remains understudied. This retrospective study compared real-world patient characteristics, treatment patterns, and outcomes before and after U-500R initiation.. Adults with T2D on dispensed doses of >180 units/d U-500R monotherapy (index date=first fill) with ≥9-month continuous enrollment both pre- and post-index date and ≥180 units/d insulin pre-index were identified using Veterans Health Administration data (January 1, 2014-January 30, 2017). Overall group was further stratified into elderly and 201 to 300 units dispensed total daily dose (dTDD) subgroups. Syringe and KwikPen users were separately analyzed as subcohorts. Treatment patterns (dTDD), insulin dosage (units/kg), proportion of days covered (PDC) with insulins, and outcomes (HbA1c and hypoglycemic events) were descriptively evaluated, with regression models used to confirm associations between exposure and outcomes.. Among 951 U-500R initiators (overall group), mean dTDD (248.5 vs 392.1), percentage of patients with insulin dosage >2 units/kg (38.6% vs 88.1%), and mean PDC (73% vs 77%) significantly increased from the pre- to post-index periods (all P<.001). Changes in HbA1c (9.3% vs 8.5%; P<.0001) and hypoglycemia events per patient per year (2.1 vs 3.1, P<.0001) were statistically significant and confirmed by regression models (P<.0001). Subgroups (elderly, 492; 201 to 300 units, 148) and device subcohorts (syringe, 714; KwikPen, 244) showed similar trends.. U-500R initiation was associated with significantly improved treatment compliance patterns and glycemic control, with modest increase in hypoglycemia events.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Retrospective Studies; United States

Topics: Algorithms; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Regular, Human

A dedicated Humulin R U-500 (U-500R) prefilled disposable insulin pen (KwikPen) became available in 2016, yet limited evidence exists on treatment patterns and outcomes of U-500R via KwikPen (U500-KP).. This is a retrospective observational study among adults with ≥2 claims for type 2 diabetes initiating U500-KP (index date: first claim) identified in Veterans Health Administration database. Treatment patterns and outcomes were evaluated in 9-month pre- and post-index periods, including dispensed total daily insulin dosage derived from claims expressed in units (dTDD) and units/kg, HbA1c, symptomatic hypoglycemia, and body weight. Multivariable modeling was used to confirm the associations between U500-KP initiation and outcomes.. A total of 647 U500-KP initiators were identified. The mean age was 64 years, and mean Quan-Charlson Comorbidity-index score was 3.8. Before U500-KP initiation, 62% of patients had dTDD ≤ 200 units with mean A1c 9.5%. Mean dTDD increased from 188.2 to 269.9 units after U500-KP initiation with mean A1c decreased by 0.83% (SD = 1.67) and mean weight gain of 1.5 kg (SD = 6.74). Hypoglycemia events increased from 4.3 to 5.3 (p < 0.05) per person per year.. Initiation of U500-KP brought significant improvement in dispensed insulin dose and glycemic control accompanied by moderate increases in hypoglycemia and weight.

Topics: Adult; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Regular, Human; Middle Aged; Retrospective Studies; Veterans

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

Topics: Aged; Cresols; Dermatitis, Allergic Contact; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Injection Site Reaction; Insulin, Regular, Human; Isophane Insulin, Human; Preservatives, Pharmaceutical

The comparative cardiovascular safety of analogue and human insulins in adults with type 2 diabetes who initiate insulin therapy in usual care settings has not been carefully evaluated using machine learning and other rigorous analytic methods.. To examine the association of analogue vs human insulin use with mortality and major cardiovascular events.. This retrospective cohort study included 127 600 adults aged 21 to 89 years with type 2 diabetes at 4 health care delivery systems who initiated insulin therapy from January 1, 2000, through December 31, 2013. Machine learning and rigorous inference methods with time-varying exposures were used to evaluate associations of continuous exposure to analogue vs human insulins with mortality and major cardiovascular events. Data were analyzed from September 1, 2017, through June 30, 2018.. On the index date (first insulin dispensing), participants were classified as using analogue insulin with or without human insulin or human insulin only.. Overall mortality, mortality due to cardiovascular disease (CVD), myocardial infarction (MI), stroke or cerebrovascular accident (CVA), and hospitalization for congestive heart failure (CHF) were evaluated. Marginal structural modeling (MSM) with inverse probability weighting was used to compare event-free survival in separate per-protocol analyses. Adjusted and unadjusted hazard ratios and cumulative risk differences were based on logistic MSM parameterizations for counterfactual hazards. Propensity scores were estimated using a data-adaptive approach (machine learning) based on 3 nested covariate adjustment sets. Sensitivity analyses were conducted to address potential residual confounding from unmeasured differences in risk factors across delivery systems.. The 127 600 participants (mean [SD] age, 59.4 [12.6] years; 68 588 men [53.8%]; mean [SD] body mass index, 32.3 [7.1]) had a median follow-up of 4 quarters (interquartile range, 3-9 quarters) and experienced 5464 deaths overall (4.3%), 1729 MIs (1.4%), 1301 CVAs (1.0%), and 3082 CHF hospitalizations (2.4%). There were no differences in adjusted hazard ratios for continuous analogue vs human insulin exposure during 10 quarters for overall mortality (1.15; 95% CI, 0.97-1.34), CVD mortality (1.26; 95% CI, 0.86-1.66), MI (1.11; 95% CI, 0.77-1.45), CVA (1.30; 95% CI, 0.81-1.78), or CHF hospitalization (0.93; 95% CI, 0.75-1.11).. Insulin-naive adults with type 2 diabetes who initiate and continue treatment with human vs analogue insulins had similar observed rates of major cardiovascular events, CVD mortality, and overall mortality.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Heart Failure; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Retrospective Studies; Risk Factors; Stroke; Young Adult

This study was conducted to evaluate existing burden and unmet needs related to mealtime insulin (MTI) injection timing among adult Japanese patients with type 1 (T1D) and type 2 (T2D) diabetes. It also aimed to evaluate if a novel MTI could reduce this burden.. This study comprised of a qualitative pilot study facilitating development of an online survey; followed by an online quantitative survey involving T1D, young T2D (yT2D) and elderly T2D (eT2D) patients to assess burden of current MTI timings in Japan.. Overall, 38% patients (amongst T1D, yT2D and eT2D groups) reported injecting MTI just before start or during meal in the past month. Experiencing lower glucose level/hypoglycemic condition before the meal and forgetting were the main reasons for injecting during/after meal in T1D and T2D patients respectively. Patients reported moderate-to-severe burden in multiple aspects of their lives, associated with current MTI timing. Most patients perceived that this burden would remain the same if a faster acting MTI was available.. Substantial burden reported by Japanese patients regarding the current MTI timings suggests the need for new MTI products that could achieve optimal post-prandial glucose control at different timings to meet patients' needs in Japan.

Topics: Aged; Cost of Illness; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Insulin, Regular, Human; Japan; Male; Meals; Middle Aged; Pilot Projects; Surveys and Questionnaires

With increased duration of type 2 diabetes, most people have a growing need of glucose-lowering medication and eventually might require insulin. Presumptive evidence is reported that early detection (eg, by population-based screening) and treatment of hyperglycemia will postpone the indication for insulin treatment. A treatment legacy effect of population-based screening for type 2 diabetes of about 3 years is estimated. Therefore, we aim to compare insulin prescription and glycemic control in people with screen-detected type 2 diabetes after 10 years with data from people diagnosed with type 2 diabetes seven (treatment legacy effect) and 10 years before during care-as-usual.. Three cohorts were compared: one screen-detected cohort with 10 years diabetes duration (Anglo-Danish-Dutch study of Intensive Treatment in People with Screen-Detected Diabetes in Primary care (ADDITION-NL): n=391) and two care-as-usual cohorts, one with 7-year diabetes duration (Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) and Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC): n=4473) and one with 10-year diabetes duration (GIANTT and ZODIAC: n=2660). Insulin prescription (primary outcome) and hemoglobin A1c (HbA1c) of people with a known diabetes duration of 7 years or 10 years at the index year 2014 were compared using regression analyses.. Population-based screen-detected type 2 diabetes is associated with less need for insulin after 10 years compared with people diagnosed during care-as-usual. Glycemic control was better after screen detection but on average good in all groups.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Insulin, Regular, Human

Therapies for treatment of type 2 diabetes (T2D) involve a variety of medications, depending on the stage of T2D progression. It is now an accepted knowledge that in silico trials can help to accelerate drug development and support treatment optimization. A T2D simulator (T2DS), consisting of a model of the glucose-insulin system and an in silico population describing glucose-insulin dynamics in T2D subjects, has been recently developed based on early-stage T2D data, studied with sophisticated experimental techniques. This limits the domain of validity of the simulator to this specific sub-population of T2D. Here we proposed a method for tuning the T2DS to any desired T2D target population, e.g. insulin-naïve (i.e., not experienced with insulin) patients, without the need to resort to complex and expensive clinical studies. This will allow to use the T2DS for testing treatments in the target population. To illustrate the methodology, we used a case study: extending the T2DS to reproduce the behavior of insulin-naïve T2D subjects. The methodology described here can be extended to other stages of T2D, allowing an extensive in silico testing phase of different treatments before human trials.

Topics: Blood Glucose; Cloning, Molecular; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin, Regular, Human

Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin, Regular, Human

To evaluate multiple determinants of the longitudinal change in insulin clearance (IC) in subjects at high risk for type 2 diabetes (T2D).. Adults (n=492) at risk for T2D in the Prospective Metabolism and Islet Cell Evaluation cohort, a longitudinal observational cohort, had four visits over 9 years. Values from oral glucose tolerance tests collected at each assessment were used to calculate the ratios of both fasting C peptide-to-insulin (IC. IC declined by 20% over the 9-year follow-up period (p<0.05). Primary GEE results indicated that non-European ethnicity, as well as increases in baseline measures of waist circumference, white cell count, and alanine aminotransferase, was associated with declines in IC. Our findings suggest that non-European ethnicity and components of the metabolic syndrome, including central obesity, non-alcoholic fatty liver disease, and subclinical inflammation, may be related to longitudinal declines in IC.

Topics: Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin Resistance; Insulin, Regular, Human; Islets of Langerhans; Longitudinal Studies; Male; Middle Aged; Prediabetic State; Prognosis; Prospective Studies

Topics: Adult; Cost Savings; Diabetes Mellitus, Type 2; Drug Costs; Drug Substitution; Glycated Hemoglobin; Humans; Insulin; Insulin, Regular, Human; Medication Adherence; Retrospective Studies; Treatment Outcome

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin, Regular, Human; Medicare; United States

Prices for newer analogue insulin products have increased. Lower-cost human insulin may be effective for many patients with type 2 diabetes.. To evaluate the association between implementation of a health plan-based intervention of switching patients from analogue to human insulin and glycemic control.. A retrospective cohort study using population-level interrupted times series analysis of members participating in a Medicare Advantage and prescription drug plan operating in 4 US states. Participants were prescribed insulin between January 1, 2014, and December 31, 2016 (median follow-up, 729 days). The intervention began in February 2015 and was expanded to the entire health plan system by June 2015.. Implementation of a health plan program to switch patients from analogue to human insulin.. The primary outcome was the change in mean hemoglobin A1c (HbA1c) levels estimated over three 12-month periods: preintervention (baseline) in 2014, intervention in 2015, and postintervention in 2016. Secondary outcomes included rates of serious hypoglycemia or hyperglycemia using ICD-9-CM and ICD-10-CM diagnostic codes.. Over 3 years, 14 635 members (mean [SD] age: 72.5 [9.8] years; 51% women; 93% with type 2 diabetes) filled 221 866 insulin prescriptions. The mean HbA1c was 8.46% (95% CI, 8.40%-8.52%) at baseline and decreased at a rate of -0.02% (95% CI, -0.03% to -0.01%; P <.001) per month before the intervention. There was an association between the start of the intervention and an overall HbA1c level increase of 0.14% (95% CI, 0.05%-0.23%; P = .003) and slope change of 0.02% (95% CI, 0.01%-0.03%; P < .001). After the completion of the intervention, there were no significant differences in changes in the level (0.08% [95% CI, -0.01% to 0.17%]) or slope (<0.001% [95% CI, -0.008% to 0.010%]) of mean HbA1c compared with the intervention period (P = .09 and P = 0.81, respectively). For serious hypoglycemic events, there was no significant association between the start of the intervention and a level (2.66/1000 person-years [95% CI, -3.82 to 9.13]; P = .41) or slope change (-0.66/1000 person-years [95% CI, -1.59 to 0.27]; P = .16). The level (1.64/1000 person-years [95% CI, -4.83 to 8.11]; P = .61) and slope (-0.23/1000 person-years [95% CI, -1.17 to 0.70]; P = .61) changes in the postintervention period were not significantly different compared with the intervention period. The baseline rate of serious hyperglycemia was 22.33 per 1000 person-years (95% CI, 12.70-31.97). For the rate of serious hyperglycemic events, there was no significant association between the start of the intervention and a level (4.23/1000 person-years [95% CI, -8.62 to 17.08]; P = .51) or slope (-0.51/1000 person-years [95% CI, -2.37 to 1.34]; P = .58) change.. Among Medicare beneficiaries with type 2 diabetes, implementation of a health plan program that involved switching patients from analogue to human insulin was associated with a small increase in population-level HbA1c.

Topics: Aged; Diabetes Mellitus, Type 2; Drug Costs; Female; Glycated Hemoglobin; Health Expenditures; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Regular, Human; Kaplan-Meier Estimate; Male; Medicare Part C; Middle Aged; Retrospective Studies; United States

Purpose The purpose of this article is to provide recommendations to the diabetes educator/expert prescriber team for the use of human regular U-500 insulin (U-500R) in patients with severely insulin-resistant type 2 diabetes, including its initiation and titration, by utilizing dosing charts and teaching materials translated from a recent U-500R clinical trial. Conclusions Clinically relevant recommendations and teaching materials for the optimal use and management of U-500R in clinical practice are provided based on the efficacy and safety results of and lessons learned from the U-500R clinical trial by Hood et al, current standards of practice, and the authors' clinical expertise. This trial was the first robustly powered, randomized, titration-to-target trial to compare twice-daily and three-times-daily U-500R dosing regimens. Modifications were made to the initiation and titration dosing algorithms used in this trial to simplify dosing strategies for the clinical setting and align with current glycemic targets recommended by the American Diabetes Association. Leveraging the expertise, resources, and patient interactions of the diabetes educator who can provide diabetes self-management education and support in collaboration with the multidisciplinary diabetes team is strongly recommended to ensure patients treated with U-500R receive the timely and comprehensive care required to safely and effectively use this highly concentrated insulin.

Topics: Adult; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Health Educators; Humans; Hypoglycemic Agents; Insulin Resistance; Insulin, Regular, Human; Male; Patient Care Team; Patient Education as Topic; Randomized Controlled Trials as Topic; Translational Research, Biomedical

Topics: Diabetes Mellitus, Type 2; Fees, Pharmaceutical; Humans; Hypoglycemic Agents; Injections; Insulin; Insulin, Regular, Human

The aim of this study was to compare the changes in the total daily dose (TDD) of insulin of patients on U-500 insulin; before hospitalization, during hospitalization and six weeks after discharge.. A retrospective chart review of veterans with type 2 diabetes receiving U-500 insulin in the ambulatory setting and who were admitted between 2012 and 2015 was performed. During hospitalization, patients were transitioned to receive U-100 insulin (detemir or glargine for basal and aspart for bolus). Paired t-tests were conducted to compare TDD of insulin during hospitalization to prior to admission and at six week of follow-up.. We showed that patients received significantly less total daily insulin while hospitalized compared to their insulin doses in the ambulatory setting, and we demonstrate that patients receiving U-500 insulin can be safely transitioned to U-100 insulin while hospitalized, with minimal hypoglycemia.

Topics: Aged; Diabetes Mellitus, Type 2; Drug Monitoring; Follow-Up Studies; Glycated Hemoglobin; Hospitals, Veterans; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin, Regular, Human; Length of Stay; Male; Medical Records; Middle Aged; Nebraska; Retrospective Studies; Risk; Severity of Illness Index

Insulin human inhalation powder, a rapid-acting inhaled insulin, was approved by the FDA in June 2014 for patients with type 1 or type 2 diabetes. For patients reluctant to start insulin therapy because of fear of injections, insulin human inhalation powder may be an alternative. This article discusses appropriate dosing, use, and monitoring.

Topics: Administration, Inhalation; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

OBJECTIVE Several studies have been published in 2009 suggesting a possible association between insulin glargine and increased risk of malignancies, including breast cancer. The objective of this study was to assess the relation between the individual insulins (glargine, aspart, lispro, and human insulin) and development of breast cancer. RESEARCH DESIGN AND METHODS Seven hundred seventy-five incident cases of primary invasive or in situ carcinoma breast cancer occurring in women with diabetes from 92 centers in the U.K., Canada, and France were matched to a mean of 3.9 diabetic community control subjects (n = 3,050; recruited from 580 general practices) by country, age, recruitment date, and diabetes type and management. The main risk model was a multivariate conditional logistic regression model with case/control status as the dependent variable and individual insulin use, 8 years preceding the index date, as the independent variable, controlling for past use of any insulin, oral antidiabetes drugs, reproductive factors, lifestyle, education, hormone replacement therapy and history of contraceptive use, BMI, comorbidities, diabetes duration, and annual number of physician visits. Glargine was also compared with every other insulin by computing all ratios using the variance-covariance matrix of logistic model parameters. RESULTS Adjusted odds ratios of breast cancer for each type of insulin versus no use of that insulin were 1.04 (95% CI 0.76-1.44) for glargine, 1.23 (0.79-1.92) for lispro, 0.95 (0.64-1.40) for aspart, and 0.81 (0.55-1.20) for human insulin. Two-by-two comparisons found no difference between glargine and the different types of insulins. Insulin dosage or duration of use and tumor stage did not change the results. CONCLUSIONS This international study found no difference in the risk of developing breast cancer in patients with diabetes among the different types of insulin with short- to mid-term duration of use. Longer-term studies would be of interest.

Topics: Aged; Breast Neoplasms; Canada; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; France; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Insulin, Regular, Human; Insulins; Middle Aged; Risk Factors; United Kingdom

Whether human insulin can induce bladder cancer is rarely studied.. The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the entry date in Taiwan) was not included in the calculation of follow-up. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, duration of therapy and cumulative dose) were calculated and the hazard ratios were estimated by Cox regression.. There were 87,940 ever-users and 697,294 never-users, with respective numbers of incident bladder cancer of 454 (0.52%) and 3,330 (0.48%), and respective incidence of 120.49 and 94.74 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) indicated a significant association with insulin in the age-sex-adjusted models [1.238 (1.122-1.366)], but not in the model adjusted for all covariates [1.063 (0.951-1.187)]. There was also a significant trend for the hazard ratios for the different categories of the dose-response parameters in the age-sex-adjusted models, which became insignificant when all covariates were adjusted.. This study relieves the concern of a bladder cancer risk associated with human insulin. Appropriate adjustment for confounders is important in the evaluation of cancer risk associated with a medication.

Topics: Adult; Age Factors; Aged; Databases, Factual; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin, Regular, Human; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Sex Factors; Taiwan; Urinary Bladder; Urinary Bladder Neoplasms

To investigate the risk of macro- and microvascular complications in patients with type 2 diabetes receiving rapid-acting insulin analogues (IA) or human regular insulin (HI).General practice diabetes patients with continuous prescription of any IA or HI for ≥3 years were selected from the German Disease Analyzer database (IMS Health). Logistic and Cox regression models were applied to analyze the incidence and time to onset of vascular outcomes (IA vs. HI).2764 patients on IA (insulin lispro, glulisine, aspart) and 4193 patients on HI were included (age, mean [SD]: 61.0 [11.3] and 64.7 [10.5] years, follow-up [Q1,Q3]: 4.6 [3.7,6.1] and 4.7 [3.7,5.9] years). No significant differences were detected between IA and HI regarding the incidence of vascular complications (OR [95%CI]: macrovascular 0.92 [0.72-1.18], microvascular 0.95 [0.77-1.17]) or regarding time to their onset, after adjustment for sex, age, comorbidities and time on IA/HI, or by propensity-score-based matching. However, in an additional short-term analysis (median [Q1,Q3] follow-up (IA 2.9 [1.2,4.6], HI 2.4 [0.8,4.4] years) of a larger sample (no continuous insulin treatment required) with more comorbidities, time to onset of macrovascular complications was significantly longer for AI than HI (HR 0.88 [0.81-0.97], p=0.009; microvascular complications: no difference).After long-term continuous treatment with IA or HI under real-life conditions, there was no different risk of macro- or microvascular complications, contradicting previous short-term analyses. Further prospective studies are needed to clarify whether selection bias may have been introduced by using strict entry criteria.

Topics: Adult; Age Factors; Aged; Databases, Factual; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin, Regular, Human; Insulin, Short-Acting; Male; Microcirculation; Middle Aged; Retrospective Studies; Sex Factors

Whether human insulin therapy may increase thyroid cancer risk in patients with type 2 diabetes mellitus (T2DM) has not been investigated.. The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the Bureau of National Health Insurance. The entry date was set at 1 January 2004, and 968,384 patients with T2DM were followed up for thyroid cancer incidence until the end of 2009. Ever-users, never-users and subgroups of human insulin exposure (using tertile cut-offs of time since starting insulin, duration of therapy and cumulative dose) at entry date were calculated for thyroid cancer incidence. Insulin glargine was not marketed until after the entry date. Therefore, to exclude the potential contamination of insulin glargine, patients who happened to use insulin glargine were censored at the time of its initiation when calculating the period of follow-up. Hazard ratios were estimated by Cox regression.. There were 111,121 ever-users and 857,263 never-users of human insulin, with respective numbers of incident thyroid cancer of 118 (0·11%) and 1047 (0·12%), and respective incidences of 23·9 and 23·8 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) did not show a significant association with human insulin in either the age-sex-adjusted or the fully adjusted model: 0·942 (0·778-1·141) and 1·096 (0·888-1·353), respectively. When categorized into tertiles of the dose-response parameters, none of the hazard ratios was significant.. This study does not support the role of human insulin therapy in increasing the risk of thyroid cancer in patients with T2DM.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Humans; Hypoglycemic Agents; Insulin, Regular, Human; Male; Middle Aged; Retrospective Studies; Risk Factors; Thyroid Neoplasms

The relationship between hypoglycemia and the dose of insulin used in patients with type 2 diabetes mellitus was investigated by continuous glucose monitoring (CGM).. In total, 83 CGM studies were performed in 70 outpatients with type 2 diabetes receiving treatment by subcutaneous insulin injection.. The total dose of insulin, bolus insulin dose, and basal insulin dose used in the subjects were 32±18 units, 19±13 units, and 13±8 units, respectively. The proportion of time in the hypoglycemic range (blood glucose<3.9 mmol/L) during CGM was positively correlated with the bolus insulin ratio (bolus/total insulin dose, r=0.22, P=0.04), although it was not associated with the total dose of insulin or the hemoglobin A1c (HbA1c) level. It was negatively correlated with the mean blood glucose (r=-0.38, P<0.01), whereas it was not associated with the SD or the mean amplitude of glycemic excursions (MAGE). The proportion of time in the hypoglycemic range was significantly greater in the subjects with a bolus insulin ratio of ≥0.6 (3.2±4.4%, n=42) than a ratio of <0.6 (1.2±3.0%, n=41), although the HbA1c level, total dose of insulin, mean blood glucose, SD, and MAGE were not significantly different between the two groups.. An excessive dose of bolus insulin might increase the duration of hypoglycemia, independently from the HbA1c levels, in patients with type 2 diabetes mellitus receiving subcutaneous insulin injection.

Topics: Aged; Biphasic Insulins; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Extracellular Fluid; Female; Glucose; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin, Long-Acting; Insulin, Regular, Human; Insulin, Short-Acting; Male; Middle Aged; Monitoring, Ambulatory; Recombinant Proteins; Time Factors

Topics: Diabetes Mellitus, Type 2; Drug Overdose; Humans; Insulin, Regular, Human; Male; Medication Errors; Pharmacy Service, Hospital

Topics: Diabetes Mellitus, Type 2; Drug Overdose; Humans; Insulin, Regular, Human; Male; Medication Errors; Pharmacy Service, Hospital

To add to the evidence on comparative long-term effects of insulin analog glargine versus human NPH insulin on the risk for cancer.. We identified cohorts of initiators of glargine and human NPH without an insulin prescription during the prior 19 months among patients covered by the Inovalon Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) between January 2003 and December 2010. Patients were required to have a second prescription of the same insulin within 180 days and to be free of cancer. We balanced cohorts on risk factors for cancer outcomes based on comorbidities, comedication, and health care use during the prior 12 months using inverse probability of treatment weighting. Incident cancer was defined as having two claims for cancer (any cancer) or the same cancer (breast, prostate, colon) within 2 months. We estimated adjusted hazard ratios (HRs) and their 95% CI using weighted Cox models censoring for stopping, switching, or augmenting insulin treatment, end of enrollment, and mortality.. More patients initiated glargine (43,306) than NPH (9,147). Initiators of glargine (NPH) were followed for 1.2 (1.1) years and 50,548 (10,011) person-years; 993 (178) developed cancer. The overall HR was 1.12 (95% CI 0.95-1.32). Results were consistent for breast cancer, prostate cancer, and colon cancer; various durations of treatment; and sensitivity analyses.. Patients initiating insulin glargine rather than NPH do not seem to be at an increased risk for cancer. While our study contributes significantly to our evidence base for long-term effects, this evidence is very limited mainly based on actual dynamics in insulin prescribing.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Male; Middle Aged; Neoplasms; Probability; Proportional Hazards Models; Registries; Risk Factors

Few studies are available evaluating the impact of rapid-acting insulin analogues on long-term diabetes outcomes. Our aim was to compare the use of rapid-acting insulin analogues versus human regular insulin in relation to the occurrence of diabetic complications in a cohort of diabetic patients through the analysis of administrative databases.. A population-based cohort study was conducted using administrative data from four local health authorities in the Abruzzo Region (900,000 inhabitants). Diabetic patients free of macrovascular disease at baseline and treated either with human regular insulin or rapid-acting insulin analogues were followed for a maximum of 3 years. The incidence of diabetic complications was ascertained by hospital discharge claims. Hazard ratios (HRs) and 95% CIs of any diabetic complication and macrovascular, microvascular and metabolic complications were estimated separately using Cox proportional hazard models adjusted for patients' characteristics and anti-diabetic drug use. Propensity score matching was also used to adjust for significant difference in the baseline characteristics between the two treatment groups.. A total of 2,286 patients were included: 914 receiving human regular insulin and 1,372 rapid-acting insulin analogues. During the follow-up, 286 (31.3%) incident events occurred in the human regular insulin group and 235 (17.1%) in the rapid-acting insulin analogue group. After propensity score-based matched-pair analyses, rapid-acting insulin analogues users had a HR of 0.73 (0.58-0.92) for any diabetes-related complication and HRs of 0.73 (0.55-0.93) and 0.55 (0.32-0.96) for macrovascular and metabolic complications respectively, as compared with human regular insulin users. No difference between the two groups was found for microvascular complications.. Our findings suggest that the use of rapid-acting insulin analogues is associated with a lower risk of cardiovascular and metabolic complications compared with human regular insulin use.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin, Regular, Human; Insulin, Short-Acting; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies

Topics: Aged, 80 and over; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Diabetes Mellitus, Type 2; Female; Graves Disease; Graves Ophthalmopathy; Humans; Hypoglycemia; Hypoglycemic Agents; Immunosuppressive Agents; Insulin, Regular, Human; Methimazole; Prednisone; Recombinant Proteins; Treatment Outcome

Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with an increased risk of cancer in a large population-based cohort study.. Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. In a cohort of incident users of insulin, the association between insulin glargine and other insulin analogues, respectively, and cancer was analysed in comparison with human insulin using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant. The first hospital admission with a primary diagnosis of cancer was considered as the main outcome; secondary analyses were performed with specific cancers as outcomes.. Of the 19,337 incident insulin users enrolled, 878 developed cancer. Use of insulin glargine was associated with a lower risk of malignancies in general in comparison with human insulin (HR 0.75, 95% CI 0.71, 0.80). In contrast, an increased risk was found for breast cancer (HR 1.58, 95% CI 1.22, 2.05). Dose-response relationships could not be identified.. Users of insulin glargine and users of other insulin analogues had a lower risk of cancer in general than those using human insulin. Both associations might be a consequence of residual confounding, lack of adherence or competing risk. However, as in previous studies, we demonstrated an increased risk of breast cancer in users of insulin glargine in comparison with users of human insulin.

Topics: Breast Neoplasms; Cohort Studies; Community Pharmacy Services; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Electronic Health Records; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Long-Acting; Insulin, Regular, Human; Male; Medical Record Linkage; Middle Aged; Neoplasms; Netherlands; Patient Admission; Proportional Hazards Models; Risk

A number of observational studies have linked insulin glargine (A21Gly,B31Arg,B32Arg human insulin) with a putative increased cancer risk, particularly breast cancer, but many of these 'first generation' studies had study design and analysis flaws, and were inconclusive. A small number of 'second generation' studies are now emerging in which the applied pharmaco-epidemiological principles are more robust. For example, when Ruitar and colleagues (Diabetologia DOI: 10.1007/s00125-011-2312-4 ) focused specifically on breast cancer rather than all incident cancer risk, they were able to show a positive association with insulin glargine for breast cancer although there was no association with all incident cancer risk. A list of preferred qualities for pharmaco-epidemiological studies is presented.

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Insulin, Regular, Human; Male; Neoplasms

In this rodent study, we compared the effects of early versus late intensive insulin therapy on diabetic nephropathy and potential causal mechanisms. Diabetes was induced in rats by high-fat diet and low-dose streptozotocin. Intensive insulin therapy was initiated in the early intensive insulin therapy groups as soon as diabetes was confirmed and lasted for 8 (8wEI group) and 16 weeks (16wEI group). In the late insulin therapy group (LI group), intensive insulin treatment was initiated 8 weeks later and lasted for 8 weeks. Age-matched diabetic rats (8wDM group and 16wDM group) and non-diabetic rats (8wNC group and 16wNC group) served as controls. Histological analysis, real-time PCR, and western blot were performed in renal cortex specimens. Glomerular hypertrophy and mesangial matrix expansion were prominent in the 16wDM and LI groups while the EI groups remained normal and similar to the 16wNC group. Western blots revealed that p38 MAPK activities in the EI groups decreased significantly, whereas the level in the LI group was markedly higher than the 16wEI group, and not different from the DM groups. Activities of MKK3/6, CREB and MKP-1 proteins as well as CREB and MKP-1 mRNA showed a similar pattern. Therefore, we concluded that early intensive insulin treatment and attainment of good glycemic control counteracted some renal molecular pathways associated with epigenetic metabolic memory to minimize risk of diabetic nephropathy. However, late insulin therapy did not abrogate the increased renal cortical p38 MAPK pathway activation in diabetic rats and led to glomerular hypertrophy and extracellular matrix expansion.

Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Gene Expression Regulation; Glomerular Mesangium; Humans; Hypertrophy; Hypoglycemic Agents; Insulin, Isophane; Insulin, Regular, Human; Isophane Insulin, Human; Kidney Cortex; Kidney Glomerulus; Male; MAP Kinase Signaling System; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Protein Processing, Post-Translational; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Time Factors

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin, Long-Acting; Insulin, Regular, Human; Male; Neoplasms

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin, Long-Acting; Insulin, Regular, Human; Male; Neoplasms

Topics: Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Follow-Up Studies; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Regular, Human; Postprandial Period; Randomized Controlled Trials as Topic

Modifications made to medication-use processes after an overdose of U-500 regular insulin are described.. After a medication error occurred with U-500 regular insulin, a multidisciplinary team of physicians, nurses, advanced-practice nurses, and pharmacists was created to review and improve the ordering, dispensing, and administration processes associated with U-500 regular insulin. The group determined that current safety practices for managing insulin were inadequate. New safety processes specific to U-500 regular insulin were developed and implemented. Vials of U-500 regular insulin are no longer dispensed to nursing units and are stored only in the pharmacy and separated from other insulins. The ordering of U-500 regular insulin is limited to the endocrinology service, and all orders are written using a specialized U-500 regular insulin order set. The option for i.v. administration for U-500 regular insulin was removed from the pharmacy order-entry system; thus, only the subcutaneous route is entered by the pharmacist. In addition, patient-specific doses of U-500 regular insulin are prepared in the pharmacy using only tuberculin syringes that require a double check by two pharmacists. These syringes are delivered to patient care areas in a bag distinguishing the medication as "high alert." One last safety check involving a two-nurse check at the bedside to confirm correct medication administration is performed. Lastly, patient education material specifically for U-500 regular insulin is available online.. A multidisciplinary team recommended modifications to the medication-use system regarding U-500 regular insulin after review of a medication error. No errors involving U-500 regular insulin have been reported since implementation of the changes.

Topics: Aged; Diabetes Mellitus, Type 2; Drug Overdose; Humans; Insulin, Regular, Human; Male; Medication Errors; Patient Care Team; Pharmacy Service, Hospital

Despite the occurrence of a severe allergic reaction including an anaphylactic shock, a drug may remain essential and impossible to replace. This may be the case of insulin in a diabetic patient. We describe the case of an anaphylactic shock to human insulin in whom a desensitization protocol was successfully achieved.. A 50-year-old type 2 diabetic man presented one year after initiation of the insulin therapy an anaphylactic shock following the subcutaneous administration of a human insulin containing protamine (Insulatard®). A desensitization protocol to human insulin was performed and allowed to use two human insulin analogues containing no protamine (asparte and glargine), with a two-year event-free follow-up. Positive skin tests with insulin and protamine, and the presence of insulin specific IgE were evidenced of an IgE-mediated mechanism. Desensitization was monitored by skin tests, Maunsell's test, measurement of specific IgE and IgG4, and the basophil activation test. The decrease of basophil sensitivity to insulin is an early marker for tolerance induction.. The effectiveness of the desensitization to human insulin underlines the importance to define the modalities of such desensitization protocol and of the monitoring of the tolerance induction.

Topics: Anaphylaxis; Basophil Degranulation Test; Basophils; Biomarkers; Desensitization, Immunologic; Diabetes Mellitus, Type 2; Humans; Immunoglobulin E; Immunoglobulin G; Injections, Subcutaneous; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Intradermal Tests; Isophane Insulin, Human; Male; Middle Aged; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Skin Tests; Treatment Outcome

To assess the safety and efficacy of insulin analogues versus human insulin in pregnant women with pregestational diabetes.. We collected data on pregnant women with type 1 or type 2 diabetes who were attended at the Diabetes and Pregnancy Unit between January 1998 and April 2008 (N=351). Two hundred and forty one patients were treated with regular insulin and NPH and 110 were treated with different combinations of insulins including an insulin analogue (most of them with NPH and lispro).. There was no significant difference in terms of congenital malformation rate between groups (3.3% and 3.6%). The group on insulin analogue had slightly higher mean HbA1c during the first trimester than the group on human insulin (6.6 [1.0]% vs 6.9 [1.1]%; P=0,022) and needed smaller insulin doses during whole pregnancy. Severe hypoglycaemia was significantly less frequent among women treated with a rapid insulin analogue (2.3 vs 10.0%; P=0,025). Neonatal hypoglycaemia was significantly more frequent in the group treated with a rapid insulin analogue (34.9 vs 23.6%; P=0.043) due to the concomitant use of an insulin pump. Other obstetric and neonatal variables were not different between the two groups.. Our study shows that insulin analogues are safe during pregnancy in women with pregestational diabetes mellitus. Overall, glycaemic control, maternal and foetal outcome were similar to those with human insulin. The main advantage with respect to human insulin was to importantly reduce maternal severe hypoglycaemia.

Topics: Abnormalities, Drug-Induced; Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Lispro; Insulin, Isophane; Insulin, Regular, Human; Logistic Models; Pregnancy; Pregnancy in Diabetics; Retrospective Studies

Type 2 diabetes has become a worldwide pandemic and the problem continues to grow. As the disease progresses, the majority of patients will require insulin therapy within 6 years of diagnosis. During the therapy, evaluation and intensification of the current treatment is required in order to achieve the good glycaemic state. In patients who are taking basal insulin or premix OD but failing to achieve the recommended glycaemic targets of HbA1c <6.5%-7%, one option is to intensify to a modern premixed insulin BID or TID. Its formulations have both basal and short or rapid-acting insulin capabilities, enabling them to cover both fasting and postprandial blood glucose levels. Other strategy is known as basal-plus method, basal plus 1 and then basal plus 2. This strategy is used by adding OD short-acting or rapid-acting insulin (analog) before having largest portion meal or before meal when blood glucose before the next meal is high. It is very important for clinicians to have the capability of choosing the right regimen based on individual's need and applying the right strategy to intensify the insulin therapy for their patients.

Topics: Algorithms; Ambulatory Care; Clinical Protocols; Diabetes Mellitus, Type 2; Disease Progression; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin, Regular, Human; Outpatients; Risk Factors; Treatment Failure

To determine the relative contributions of basal hyperglycemia (BHG) versus postprandial hyperglycemia (PPHG) before and after treatment intensification in patients with glycated hemoglobin A(1c) (A1C) >7.0% while on prior oral therapy.. Self-measured, plasma-referenced glucose profiles and A1C values were evaluated from participants in six studies comparing systematically titrated insulin glargine with an alternative regimen (adding basal, premixed, or prandial insulin, or increasing oral agents). Hyperglycemic exposure (>100 mg/dL [5.6 mmol/L]) as a result of BHG versus PPHG was calculated.. On prior oral therapy, 1,699 participants (mean age 59 years, diabetes duration 9 years) had mean fasting plasma glucose (FPG) of 194 mg/dL (10.8 mmol/L), and mean A1C was 8.7%. BHG contributed an average of 76-80% to hyperglycemia over the observed range of baseline A1C levels. Adding basal insulin for 24 or 28 weeks lowered mean FPG to 117 mg/dL (6.5 mmol/L), A1C to 7.0%, and BHG contribution to 32-41%. Alternative regimens reduced FPG to 146 mg/dL (8.1 mmol/L), A1C to 7.1%, and the contribution of BHG to 64-71%. BHG contributions for patients with A1C averaging 7.6-7.7% were 76% at baseline and 34 and 68% after adding basal insulin or other therapies, respectively.. When A1C is >7.0% despite oral therapy, BHG routinely dominates exposure. Intensified therapy reduces A1C and changes this relationship, but BHG amenable to further intervention still accounts for one-third of total hyperglycemia after basal insulin treatment and two-thirds after alternative methods.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diagnosis, Differential; Drug Eruptions; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Intradermal Tests; Isophane Insulin, Human; Male; Middle Aged; Urticaria

Inhaled human insulin (Exubera((R)) [insulin human (rDNA origin)] Inhalation Powder) has recently been approved in the EU and the US for preprandial use in adult patients with diabetes mellitus. This formulation of insulin has a more rapid onset, but similar duration, of glucose-lowering activity compared with subcutaneously administered regular human insulin.Preprandial inhaled human insulin provided glycemic control that was comparable to preprandial subcutaneous regular insulin when added to long- or intermediate-acting subcutaneous basal insulin in patients with type 1 diabetes. Inhaled human insulin is also effective when administered alone, when combined with oral antihyperglycemic therapy, or when combined with basal subcutaneous insulin in patients with type 2 diabetes. Comparable rates of hypoglycemia occurred in patients treated with inhaled human insulin and in those treated with subcutaneous regular human insulin. Patients treated with inhaled human insulin demonstrated a greater decline in pulmonary function (forced expiratory volume in 1 second, carbon monoxide diffusing capacity) than patients treated with comparator antihyperglycemic agents; the mean difference between the treatment groups that favored the comparators was noted within the first several weeks of treatment, and did not change over a 2-year treatment period. This agent has also been associated with significant improvements in some quality-of-life and treatment satisfaction scores, especially when compared with subcutaneous mealtime insulin regimens.

Topics: Administration, Inhalation; Carbon Monoxide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin, Regular, Human

To determine current and potential patterns of prescription of human insulins and insulin analogs in patients with diabetes mellitus in hospitals and general/specialist practice in France.. This was a survey of diabetologists and endocrinologists working in hospital and/or private practice in France. The clinicians answered a six-part questionnaire during a face-to-face interview at the clinician's practice regarding current and potential patterns of use of human insulin and insulin analogs.. A total of 80 French clinicians were interviewed. The majority of clinicians prescribed insulin analogs to their diabetic patients, with human insulin being prescribed in a minority of patients. When asked their opinions on switching from a regimen involving human insulin to one involving insulin analogs, clinicians generally recommended a treatment regimen that involved very little change. Most clinicians recommended that basal insulin analogs replace NPH human insulin, rapid-acting insulin analogs replace rapid-acting (regular) human insulin, and premix insulin analogs replace human premix insulins, with little change in the recommended number of injections or the dose of the insulin. Precaution was recommended in the elderly, pregnant patients, those of certain ethnicities, and those at risk of hypoglycemia.. Insulin analogs are currently prescribed by the majority of diabetologists and endocrinologists in this survey in France. When switching from a regimen involving human insulin to one involving insulin analogs, clinicians generally recommend a treatment program that involves very little change.

Topics: Diabetes Mellitus, Type 2; France; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Surveys and Questionnaires