humulin-s and Diabetes-Mellitus

Innovations in syringe and pen needle (PN) technology over the last 100 years have led to important advances in insulin delivery for people with diabetes, paralleling the strides made in developing recombinant DNA human insulin and insulin analogs with varying onset and duration of action. In this review, the history of advances in insulin delivery is described, focusing on progress in syringe, needle, and PN technologies. The early glass and metal syringes that required sterilization by boiling have been replaced by disposable, single-use syringes or pens with clear labeling for precise insulin dosing. The early needles ranging in length from 19 to 26 mm that required manual sharpening against a whetstone have been replaced by syringe needles of 6 mm and PNs of 4 mm in length as slender as 34 gauge. Imaging studies using ultrasound and computed tomography measured the thickness of skin and subcutaneous tissue layers to show feasibility of targeted insulin administration with shorter needles. These developments, coupled with innovations in needle/PN wall and tip structure, have led to improved injection experience for people with diabetes. It is also important to acknowledge the role of injection technique education, together with these advances in injection technology, for improving clinical outcomes and patient satisfaction. With continued projected growth of diabetes prevalence, particularly in developing countries where expensive and complex insulin delivery systems may not be practical, insulin syringes and pens will continue to serve as reliable and cost-effective means of insulin delivery for people with diabetes.

Topics: Diabetes Mellitus; Humans; Injections, Subcutaneous; Insulin; Insulin, Regular, Human; Patient Satisfaction; Skin

A decrease in the activity of the insulin signaling system of the brain, due to both central insulin resistance and insulin deficiency, leads to neurodegeneration and impaired regulation of appetite, metabolism, endocrine functions. This is due to the neuroprotective properties of brain insulin and its leading role in maintaining glucose homeostasis in the brain, as well as in the regulation of the brain signaling network responsible for the functioning of the nervous, endocrine, and other systems. One of the approaches to restore the activity of the insulin system of the brain is the use of intranasally administered insulin (INI). Currently, INI is being considered as a promising drug to treat Alzheimer's disease and mild cognitive impairment. The clinical application of INI is being developed for the treatment of other neurodegenerative diseases and improve cognitive abilities in stress, overwork, and depression. At the same time, much attention has recently been paid to the prospects of using INI for the treatment of cerebral ischemia, traumatic brain injuries, and postoperative delirium (after anesthesia), as well as diabetes mellitus and its complications, including dysfunctions in the gonadal and thyroid axes. This review is devoted to the prospects and current trends in the use of INI for the treatment of these diseases, which, although differing in etiology and pathogenesis, are characterized by impaired insulin signaling in the brain.

Topics: Administration, Intranasal; Alzheimer Disease; Brain; Brain Injuries; Cerebral Infarction; Diabetes Mellitus; Emergence Delirium; Humans; Insulin; Insulin, Regular, Human

Glucose oxidase (GOx) has attracted a lot of attention in the field of diabetes diagnosis and treatment in recent years owing to its inherent biocompatibility and glucose-specific catalysis. GOx can effectively catalyze the oxidation of glucose in the blood to hydrogen peroxide (H

Topics: Blood Glucose; Diabetes Mellitus; Glucose; Glucose Oxidase; Humans; Hydrogen Peroxide; Insulin; Insulin, Regular, Human; Nanocomposites

Over the last four decades, vanadium compounds have been extensively studied as potential antidiabetic drugs. With the present review, we aim at presenting a general overview of the most promising compounds and the main results obtained with in vivo studies, reported from 1899-2023. The chemistry of vanadium is explored, discussing the importance of the structure and biochemistry of vanadate and the impact of its similarity with phosphate on the antidiabetic effect. The spectroscopic characterization of vanadium compounds is discussed, particularly magnetic resonance methodologies, emphasizing its relevance for understanding species activity, speciation, and interaction with biological membranes. Finally, the most relevant studies regarding the use of vanadium compounds to treat diabetes are summarized, considering both animal models and human clinical trials. An overview of the main hypotheses explaining the biological activity of these compounds is presented, particularly the most accepted pathway involving vanadium interaction with phosphatase and kinase enzymes involved in the insulin signaling cascade. From our point of view, the major discoveries regarding the pharmacological action of this family of compounds are not yet fully understood. Thus, we still believe that vanadium presents the potential to help in metabolic control and the clinical management of diabetes, either as an insulin-like drug or as an insulin adjuvant. We look forward to the next forty years of research in this field, aiming to discover a vanadium compound with the desired therapeutic properties.

Topics: Animals; Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Vanadium; Vanadium Compounds

Since diabetes was first described over 3,000 years ago, clinicians and scientists alike have sought ever improving treatments en route to a cure. As we approach the 100th anniversary of insulin's first therapeutic use, this article will recount the glorious history associated with research surrounding insulin's isolation, purification, cloning, and subsequent modification. The discovery path we will relate tells the story of many relentless and passionate investigators pursuing ground-breaking research. The fruits of their labor include several Nobel Prizes, new technology, and, more importantly, ever improving treatments for one of humankind's greatest medical scourges.

Topics: Diabetes Mellitus; History, 20th Century; Humans; Insulin; Insulin, Regular, Human; Nobel Prize; Research Personnel

Diabetes is a chronic metabolic disease characterized by lack of insulin in the body leading to failure of blood glucose regulation. Diabetes patients usually need frequent insulin injections to maintain normal blood glucose levels, which is a painful administration manner. Long-term drug injection brings great physical and psychological burden to diabetic patients. In order to improve the adaptability of patients to use insulin and reduce the pain caused by injection, the development of oral insulin formulations is currently a hot and difficult topic in the field of medicine and pharmacy. Thus, oral insulin delivery is a promising and convenient administration method to relieve the patients. However, insulin as a peptide drug is prone to be degraded by digestive enzymes. In addition, insulin has strong hydrophilicity and large molecular weight and extremely low oral bioavailability. To solve these problems in clinical practice, the oral insulin delivery nanosystems were designed and constructed by rational combination of various nanomaterials and nanotechnology. Such oral nanosystems have the advantages of strong adaptability, small size, convenient processing, long-lasting pharmaceutical activity, and drug controlled-release, so it can effectively improve the oral bioavailability and efficacy of insulin. This review summarizes the basic principles and recent progress in oral delivery nanosystems for insulin, including physiological absorption barrier of oral insulin and the development of materials to nanostructures for oral insulin delivery nanosystems.

Topics: Administration, Oral; Blood Glucose; Diabetes Mellitus; Drug Delivery Systems; Humans; Insulin; Insulin, Regular, Human; Nanostructures; Pharmaceutical Preparations

Subcutaneous and inhaled insulins are associated with needle phobia, lipohypertrophy, lipodystrophy, and cough in diabetes treatment. Oral nanoinsulin has been developed, reaping the physiologic benefits of peroral administration. This review profiles intestinal receptors exploitable in targeted delivery of oral nanoinsulin. Intestinal receptor targeting improves oral insulin bioavailability and sustains blood glucose-lowering response. Nonetheless, these studies are conducted in small animal models with no optimization of insulin dose, targeting ligand type and content, and physicochemical and molecular biologic characteristics of nanoparticles against the in vivo/clinical diabetes responses as a function of the intestinal receptor population characteristics with diabetes progression. The interactive effects between nanoinsulin and antidiabetic drugs on intestinal receptors, including their up-/downregulation, are uncertain. Sweet taste receptors upregulate SGLT-1, and both have an undefined role as new intestinal targets of nanoinsulin. Receptor targeting of oral nanoinsulin represents a viable approach that is relatively green, requiring an in-depth development of the relationship between receptors and their pathophysiological profiles with physicochemical attributes of the oral nanoinsulin. SIGNIFICANCE STATEMENT: Intestinal receptor targeting of oral nanoinsulin improves its bioavailability with sustained blood glucose-lowering response. Exploring new intestinal receptor and tailoring the design of oral nanoinsulin to the pathophysiological state of diabetic patients is imperative to raise the insulin performance to a comparable level as the injection products.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Glucose; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Nanoparticles

The year 2021 marks the 100th anniversary of the discovery of insulin, which has greatly changed the lives of people with diabetes and become a cornerstone of advances in medical science. A rapid bench-to-bedside application of the lifesaving pancreatic extract and its immediate commercialization was the result of a promising idea, positive drive, perseverance, and collaboration of Banting and colleagues. As one of the very few proteins isolated in a pure form at that time, insulin also played a key role in the development of important methodologies and in the beginning of various fields of modern science. Since its discovery, insulin has evolved continuously to optimize the care of people with diabetes. Since the 1980s, recombinant DNA technology has been employed to engineer insulin analogs by modifying their amino acid sequence, which has resulted in the production of insulins with various profiles that are currently used. However, unmet needs in insulin treatment still exist, and several forms of future insulins are under development. In this review, we discuss the past, present, and future of insulin, including a history of ceaseless innovations and collective intelligence. We believe that this story will be a solid foundation and an unerring guide for the future.

Topics: Amino Acid Sequence; Diabetes Mellitus; Humans; Insulin; Insulin, Regular, Human; Insulins

The discovery of insulin a century ago changed the lives of millions of individuals suffering from diabetes, paving the way for long-term survival. While the availability of recombinant insulin for hormone replacement therapy has served extremely well to help control blood glucose in diabetes, there remains significant room for further improvements for an ultimate "cure" for diabetes patients. In this review, we celebrate the 100th anniversary of the discovery of insulin and consolidate the key milestones and advances in the development of recombinant human insulin. We then summarize recent and current technological developments in terms of insulin gene- and cell-replacement therapies that are promising in greater therapeutic potential. We envision that the next era of insulin replacement therapies will effectively treat diabetes and serve our patients even better for the next century to come.

Topics: Blood Glucose; Diabetes Mellitus; Genetic Therapy; Humans; Insulin; Insulin, Regular, Human

In June 2019, the Leona M. and Harry B. Helmsley Charitable Trust and JDRF International (JDRF) co-sponsored the Healthcare Professional Resource Workshop in San Francisco, California. The workshop convened stakeholders in the diabetes field in order to: [1] review information and resources created for healthcare professionals (HCPs) caring for people with diabetes on intensive insulin therapy; [2] share knowledge to scale and decentralize diabetes care; [3] identify synergies across the leading diabetes information resources; and [4] determine the areas of unmet need for HCPs caring for people with diabetes on intensive insulin therapy. Here, we summarize the conclusions and recommendations from the workshop.

Topics: Diabetes Mellitus; Health Personnel; Health Resources; Humans; Insulin, Regular, Human; Telemedicine

As patients with diabetes continue to have greater problems with obesity, the need for more medications and higher doses of insulin has increased. Some patients are so insulin resistant that they require U-500 insulin.. All insulins carry the risk of hypoglycemia. Despite being the most potent insulin available, the methodology for describing U-500 insulin administration varies. This paper examines the properties of U-500 insulin and suggests a unified method of defining how it is administered.. A literature search for English language articles that reference U-500 insulin was performed. The 51 articles, and additional websites as applicable, were independently reviewed.. Now that U-500 insulin has a specific syringe and a pen, all patients who use this should be converted to one of these two devices. The insulin dose should be described as the number of units administered.. U-500 insulin is a potent formulation and carries the risk of hypoglycemia. A unified method of administration is now available, and the description of its use should reflect the number of units administered.

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Injections; Insulin Resistance; Insulin, Regular, Human; Medication Errors; Obesity; Patient Education as Topic

Obesity confers paradoxical survival benefits in heart failure with preserved ejection fraction (HFpEF). The purpose of this study was to examine the impact of DM and insulin treatment status on the associations of body mass index (BMI) with the death risks in HFpEF patients.. HFpEF patients from the TOPCAT trial were included. Cox regression model was constructed to assess the relationship of BMI with the risks of all-cause death and cardiovascular death. Restricted cubic splines were used to characterize the dose-response associations of BMI with risks of death.. Compared with normal weight, hazard ratios of all-cause death in overweight and class I obesity were 0.62 (0.45-0.85), 0.67 (0.47-0.94) in no DM HFpEF patients, and 0.48 (0.25-0.91), 0.41 (0.22-0.79) in non-insulin-treated DM patients. However, insulin treatment removed this beneficial effect. Consistent results were found when modeling for time-updated BMI. Cubic spline analyses suggested a linear trend of increased death risk with higher BMI in insulin-treated DM patients.. The "obesity paradox" was present in HFpEF patients without DM or with non-insulin-treated DM but absent in those with insulin-treated DM. Insulin treatment may be a crucial confounder of the obesity paradox in HFpEF patients.. URL: https://clinicaltrials.gov. Unique identifier: NCT00094302.

Topics: Body Mass Index; Diabetes Mellitus; Heart Failure; Humans; Insulin; Insulin, Regular, Human; Obesity; Stroke Volume

Rapid-acting insulin analogues are generally preferred over regular human insulin because of their more immediate onset of action and shorter time-action profile. However, these analogues may not always be tolerated by or universally available for people with insulin-requiring diabetes. Jet injection has been demonstrated to facilitate faster insulin absorption. We determined whether administration of regular human insulin by jet injection achieves the same pharmacological properties as that of a rapid-acting insulin analogue.. Twenty healthy volunteers received regular human insulin (0.2units/kg) by jet injection. Glucose 20% was infused intravenously to maintain euglycaemia over six hours. The glucose infusion rates (GIR) were determined to compare pharmacological profiles. These profiles were compared with data from two other studies in which a similar dose of insulin aspart was administered by conventional pen.. Jet-injected regular human insulin had a pharmacological profile that was essentially not dissimilar from that of aspart insulin administered by conventional pen, and can therefore be used as an alternative for conventionally administered rapid-acting insulin analogues.

Topics: Adolescent; Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucose Clamp Technique; Healthy Volunteers; Humans; Hypoglycemic Agents; Injections, Jet; Injections, Subcutaneous; Insulin Aspart; Insulin, Regular, Human; Male; Young Adult

The purpose of this study was to develop and test a new Clinic Tool to assist health care professionals with clinical care of persons with diabetes using the Control-IQ system.. A Clinic Tool was iteratively developed with input from diabetes clinicians, which outlined a systematic process for assessing data, reviewing insulin settings, providing education, and documenting the encounter. Diabetes clinicians were recruited to trial the Clinical Tool in up to five clinical encounters (in-person, telehealth, or telephone). Quantitative surveys and free-text responses, including a knowledge quiz and the System Usability Scale (SUS), were administered to determine clinician satisfaction, confidence, knowledge, and implications for practice.. Twenty-nine clinicians (43% endocrinologists, mean 10.7 years in practice) enrolled in the study and completed 89 encounters using the Control-IQ Clinic Tool. Participants spent an average of 10 minutes using the Tool and reported excellent SUS scores within the 90%-95% percentile for usability. Knowledge quiz scores increased in 42% of participants. Both familiarity with Control-IQ and confidence providing clinical care to Control-IQ users significantly improved (. The Control-IQ Clinical Tool is highly usable and impacted clinical care delivery to Control-IQ users. Tools that serve to improve clinician confidence in delivery of care to diabetes device users should be expanded, leveraged, and studied to assess the impact on adherence and glycemic control for persons with diabetes.

Topics: Diabetes Mellitus; Humans; Insulin; Insulin, Regular, Human; Surveys and Questionnaires; Telemedicine

Topics: Blood Glucose; Cross-Over Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Insulin Lispro; Insulin, Regular, Human; Pilot Projects

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

Topics: Adult; Blood Glucose; Diabetes Mellitus; Glycemic Control; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human

Diabetic ketoacidosis (DKA) is a well-known, potentially fatal complication of diabetes. The American Diabetes Association hyperglycemic crises guidelines suggest the use of intravenous insulin in patients presenting with DKA, along with a recommended rate of glucose reduction of 50-75 mg/dL/h. However, no specific guidance is provided regarding how to best achieve this rate of glucose decline.. Is there a difference in time to DKA resolution between a variable intravenous insulin infusion strategy and a fixed infusion strategy in the absence of an institutional protocol?. Single-center, retrospective cohort study of DKA patient encounters in 2018.. Insulin infusion strategy was considered to be variable if the infusion rate changed within the first 8 hours of therapy or was considered fixed if the rate remained unchanged for the same period. The primary outcome was time to resolution of DKA. Secondary outcomes were hospital length of stay, intensive care unit length of stay, hypoglycemia, mortality, and DKA recurrence.. The median time to resolution of DKA was 9.3 hours in the variable infusion group compared with 7.8 hours in the fixed infusion group (HR, 0.82; 95% CI, 0.43-1.5, P = 0.5360). Severe hypoglycemia was observed in 13% of patients in the variable infusion group and in 50% of patients in the fixed infusion group ( P = 0.006).. In this analysis, insulin infusion strategy (variable vs. fixed) was not associated with a significant difference in the time to resolution of DKA in the absence of an institutional protocol. The fixed infusion strategy was associated with a higher incidence of severe hypoglycemia.

Topics: Diabetes Mellitus; Diabetic Ketoacidosis; Glucose; Humans; Hypoglycemia; Insulin; Insulin, Regular, Human; Retrospective Studies

This study uses 2021 National Health Interview Survey data to examine the prevalence of insulin rationing among adults younger than 65 years in the US by demographic characteristics.

Topics: Adult; Diabetes Mellitus; Drug Costs; Health Care Rationing; Humans; Insulin; Insulin, Regular, Human; Middle Aged; Prevalence; United States; Young Adult

This Medical News article discusses recent announcements of price caps on some insulins.

Topics: Diabetes Mellitus; Humans; Insulin; Insulin, Regular, Human; Patients

Diabetes is a combination of heterogeneous disorders presenting with episodes of hyperglycemia and glucose intolerance, as a result of lack of insulin, defective insulin action, or both. There are more than 387 million people with Diabetes Mellitus (DM) and the number is likely to reach 592 million by 2035. The prevalence of DM is 9.1% in India. With increasing incidence of diabetes worldwide, evaluation of diabetes knowledge, attitude and practice (KAP) has become crucial for guiding behavioral changes for persons with diabetes and individuals at risk. KAP-related studies are important in tailoring a health programme to help curb the threats caused by the disease. Adequate information helps the public understand the risks of diabetes and its complications, seeks treatment of existing disease, takes preventive measures and develops proactive attitude towards health. This was an interventional study where patients of either gender with ≥1-year history of DM were enrolled into the study after obtaining the consent. A total of 200 patients were included in this study. The p-value (<0.0001) showed that there was significant improvement in the KAP score of intervention group patients from baseline to follow up compared to that of control group. This study shows that improvement in knowledge of the disease has positive impact on Attitude and Practice of the subjects, thus improving their glycemic control.

Topics: Diabetes Mellitus; Health Knowledge, Attitudes, Practice; Humans; Hyperglycemia; Insulin; Insulin, Regular, Human

Traditionally, the care of critically ill patients with diabetes or stress hyperglycemia in the intensive care unit (ICU) demands the use of continuous intravenous insulin (CII) therapy to achieve narrow glycemic targets. To reduce the risk of iatrogenic hypoglycemia and to achieve glycemic targets during CII, healthcare providers (HCP) rely on hourly point-of-care (POC) arterial or capillary glucose tests obtained with glucose monitors. The burden of this approach, however, was evident during the beginning of the pandemic when the immediate reduction in close contact interactions between HCP and patients with COVID-19 was necessary to avoid potentially life-threatening exposures. Taking advantage of the advancements in current diabetes technologies, including continuous glucose monitoring (CGM) devices integrated with digital health tools for remote monitoring, HCP implemented novel protocols in the ICU to care for patients with COVID-19 and hyperglycemia. We provide an overview of research conducted in the ICU setting with the use of initial CGM technology to current devices and summarize our recent experience in the ICU.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; COVID-19; Diabetes Mellitus; Humans; Hyperglycemia; Insulin; Insulin, Regular, Human; Intensive Care Units

Integration of insulin dosing data into the electronic health record (EHR), combined with other patient-generated health care data, would facilitate the use of wirelessly connected insulin delivery systems, including smart insulin pens, insulin pumps, and advanced hybrid closed-loop systems. In 2022, Diabetes Technology Society developed the Integration of Continuous Glucose Monitoring Data into the EHR (iCoDE) Project, which is the first consensus standard for integrating data from a wearable device into the EHR. The iCoDE Standard is a comprehensive guide for any health care delivery organization or hospital for automatically integrating continuous glucose monitoring data into the EHR. Diabetes Technology Society is following iCoDE with the Integration of Connected Diabetes Device Data into the EHR (iCoDE-2) Project, to similarly provide guidance for integrating insulin delivery data into the EHR alongside continuous glucose monitoring data.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus; Electronic Health Records; Humans; Insulin; Insulin, Regular, Human

The management of insulin injections and insulin pumps before 18F-fluorodeoxyglucose-positron emission tomography integrated computerized tomography (FDG-PET/CT) scans is an important area to investigate given the rising rate of diabetes, the significant association between diabetes and cancer, and the complex relationship among glucose, insulin, and FDG tumor uptake. The purpose of this study was to determine the recommendations around subcutaneous insulin administration, insulin pumps, and hybrid closed-loop systems before FDG-PET scans.. We examined the websites of 100 hospitals selected from the 2022 US News and World Report top cancer hospitals for specific strategies around diabetes medication management before FDG-PET/CT scans.. Of the 100 hospital websites, 61 had instructions addressing patients with diabetes. Of the 61 hospitals, 47.5% (n = 29) referred patients to their provider for further instructions, 18% (n = 11) referred patients to their own internal radiology department for further instructions, 16.4% (n = 10) had instructions on oral diabetic medications, 23% (n = 14) had instructions on insulin, and 3.3% (n = 2) had instructions on insulin pump management. Most commonly, instructions were to stop insulin 3 to 4 hours before the study and direct patients to their referring provider for more detailed instructions (n = 7).. There is a lack of guidance and consensus among US cancer hospitals on managing insulin and continuous subcutaneous insulin infusions before FDG-PET/CT studies and a majority rely on referring providers to advise patients. However, society guidelines offer inconsistent recommendations and little research has been carried out to help guide referring providers. A multidisciplinary panel of specialists could help to guide practitioners on optimal management.

Topics: Diabetes Mellitus; Fluorodeoxyglucose F18; Humans; Insulin; Insulin, Regular, Human; Neoplasms; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals

The mechanisms behind reported decreases in plasma insulin and glucagon during hemodialysis (HD) are not clear. Here, we investigated these mechanisms during HD treatment and the characteristics of insulin and glucagon removal when using two super high-flux membranes. In an experimental study, clearance, adsorption rates, and reduction rates of insulin and glucagon were investigated when using cellulose triacetate (CTA) and polysulfone (PS) membranes in a closed circuit using bovine blood. In a clinical study, 20 diabetes patients with end-stage kidney disease who were stable on HD were randomly selected for two HD sessions with two different membranes. At 1 h after the initiation of HD, insulin and glucagon clearance were measured, and the reduction rates were also investigated. In the experimental study, the PS membrane showed significantly higher clearance, adsorption rates, and reduction rates of insulin and glucagon compared with the CTA membrane. Although glucagon was detected in the ultrafiltration fluids in both membranes, insulin was absent in the PS membrane. In the clinical study, both membranes showed significant reductions in plasma insulin and glucagon at each time point. The PS membrane showed significantly higher insulin clearance and reduction rates compared with the CTA membrane. The two membranes showed no significant difference in glucagon clearance, but the glucagon reduction rate was significantly higher with the PS membrane. Our findings show that HD with the two super high-flux membranes used removes significant amounts of glucoregulatory peptide hormones from plasma in patients with diabetes and end-stage kidney disease, potentially affecting their glucose metabolism.

Topics: Animals; Cattle; Diabetes Mellitus; Glucagon; Humans; Insulin; Insulin, Regular, Human; Kidney Failure, Chronic; Kinetics; Membranes, Artificial; Renal Dialysis

Prior studies suggested that metformin may be associated with reduced dementia incidence, but associations may be confounded by disease severity and prescribing trends. Cessation of metformin therapy in people with diabetes typically occurs due to signs of kidney dysfunction but sometimes is due to less serious adverse effects associated with metformin.. To investigate the association of terminating metformin treatment for reasons unrelated to kidney dysfunction with dementia incidence.. This cohort study was conducted at Kaiser Permanente Northern California, a large integrated health care delivery system, among a cohort of metformin users born prior to 1955 without history of diagnosed kidney disease at metformin initiation. Dementia follow-up began with the implementation of electronic health records in 1996 and continued to 2020. Data were analyzed from November 2021 through September 2023.. A total of 12 220 early terminators, individuals who stopped metformin with normal estimated glomerular filtration rate (eGFR), were compared with routine metformin users, who had not yet terminated metformin treatment or had terminated (with or without restarting) after their first abnormal eGFR measurement. Early terminators were matched with routine users of the same age and gender who had diabetes for the same duration.. The outcome of interest was all-cause incident dementia. Follow-up for early terminators and their matched routine users was started at age of termination for the early terminator. Survival models adjusted for sociodemographic characteristics and comorbidities at the time of metformin termination (or matched age). Mediation models with HbA1c level and insulin usage 1 and 5 years after termination tested whether changes in blood glucose or insulin usage explained associations between early termination of metformin and dementia incidence.. The final analytic sample consisted of 12 220 early terminators (5640 women [46.2%]; mean [SD] age at start of first metformin prescription, 59.4 [9.0] years) and 29 126 routine users (13 582 women [46.6%]; mean [SD] age at start of first metformin prescription, 61.1 [8.9] years). Early terminators had 1.21 times the hazard of dementia diagnosis compared with routine users (hazard ratio, 1.21; 95% CI, 1.12 to 1.30). In mediation analysis, contributions to this association by changes in HbA1c level or insulin use ranged from no contribution (0.00 years; 95% CI, -0.02 to 0.02 years) for insulin use at 5 years after termination to 0.07 years (95% CI, 0.02 to 0.13 years) for HbA1c level at 1 year after termination, suggesting that the association was largely independent of changes in HbA1c level and insulin usage.. In this study, terminating metformin treatment was associated with increased dementia incidence. This finding may have important implications for clinical treatment of adults with diabetes and provides additional evidence that metformin is associated with reduced dementia risk.

Topics: Adult; Child; Cohort Studies; Death; Dementia; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Incidence; Insulin; Insulin, Regular, Human

During 1921 to 1922, a team effort by Banting, Macleod, Collip and Best isolated and purified insulin and demonstrated its life-giving properties, giving rise to the birth of insulin therapy. In the early years (1922-1950), priorities revolved around the manufacture of insulin to meet demand, improving purity to avoid allergic reactions, establishing insulin standards and increasing its duration of action to avoid multiple daily injections. Shortly after the emergence of insulin, Joslin and Allen advocated the need to achieve and maintain good glycaemic control to realize its full potential. Although this view was opposed by some during a dark period in the history of insulin, it was subsequently endorsed some 60 years later endorsed by the Diabetes Control and Complications Trial and United Kingdom Prospective Diabetes Study. Major scientific advances by the Nobel Laureates Sanger, Hodgkin, Yalow and Gilbert and also by Steiner have revolutionized the understanding of diabetes and facilitated major advances in insulin therapy. The more recent advent of recombinant technology over the last 40 years has provided the potential for unlimited source of insulin, and the ability to generate various insulin 'analogues', in an attempt to better replicate normal insulin secretory patterns. The emerging biosimilars now provide the opportunity to improve availability at a lower cost.

Topics: Biosimilar Pharmaceuticals; Diabetes Mellitus; Drug Development; History, 20th Century; History, 21st Century; Humans; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Prospective Studies

To date, identification of nonislet-specific transcriptional factors in the regulation of insulin gene expression has been little studied. Here, we report that the expression level of the transcription factor YY1 is increased dramatically in both human and mouse pancreatic β-cells after birth. Nevertheless, the physiological role of YY1 during β-cell development and its regulatory mechanism in β-cell function remain largely unknown. After β-cell ablation of Yy1, we observed rapid onset of hyperglycemia, impaired glucose tolerance, and reduced β-cell mass in neonatal and adult mice. These mice also had hypoinsulinemia with normal insulin sensitivity compared with their wild-type littermates, manifesting as a type 1 diabetic phenotype. Mechanistically, genome-wide RNA sequencing has defined dysregulated insulin signaling and defective glucose responsiveness in β-cells devoid of YY1. Integrative analyses coupled with chromatin immunoprecipitation assays targeting YY1, and histone modifications, including H3K4me1, H3K27ac, and H3K27me3, have further identified Ins1 and Ins2 as direct gene targets of YY1. Luciferase reporter assays and loss- and gain-of-function experiments also demonstrated that YY1 binds to the enhancer regions in exon 2 of Ins1 and Ins2, activating insulin transcription and, therefore, proinsulin and insulin production in pancreatic β-cells. YY1 also directly interacts with RNA polymerase II, potentially stabilizing the enhancer-promoter interaction in the multiprotein-DNA complex during transcription initiation. Taken together, our findings suggest a role for YY1 as a transcriptional activator of insulin gene expression, assisting β-cell maturation and function after birth. These analyses may advance our understanding of β-cell biology and provide clinically relevant insights targeting the pathophysiological origins of diabetes.

Topics: Animals; Diabetes Mellitus; Glucose; Homeostasis; Insulin; Insulin-Secreting Cells; Insulin, Regular, Human; Mice; YY1 Transcription Factor

A growing body of evidence suggests that intrapancreatic fat is associated with diabetes, but whether distribution of intrapancreatic fat across the regions of the pancreas has a pathophysiologic role is unknown. The aim of this study was to investigate the differences in intrapancreatic fat deposition between the head, body, and tail of the pancreas, as well as the relationship between regional intrapancreatic fat deposition and diabetes status and insulin traits. A total of 368 adults from the general population underwent MRI on a 3 Tesla scanner, and intrapancreatic fat was manually quantified in duplicate. Statistical models included adjustment for age, sex, ethnicity, BMI, and liver fat. Intrapancreatic fat deposition in the head, body, and tail of the pancreas did not differ significantly in adjusted models in either the overall cohort or the three subgroups based on diabetes status. HOMA of insulin resistance and fasting insulin were significantly positively associated with fat in the tail and body of the pancreas. There was no significant association between regional intrapancreatic fat and HOMA of β-cell function. The association of increased intrapancreatic fat deposition in the tail and body regions with increased insulin resistance may have an important role in the early identification of patients at risk for developing insulin resistance and diseases that stem from it.

Topics: Adult; Diabetes Mellitus; Humans; Insulin; Insulin Resistance; Insulin, Regular, Human; Pancreas

Standard diabetic ketoacidosis care in the US includes intravenous insulin treatment in the intensive care unit. Subcutaneous (SQ) insulin could decrease intensive care unit need, but the data are limited.. To assess outcomes after implementation of an SQ insulin protocol for treating diabetic ketoacidosis.. This cohort study is a retrospective evaluation of a prospectively implemented SQ insulin protocol. The study was conducted at an integrated health care system in Northern California. Participants included hospitalized patients with diabetic ketoacidosis at 21 hospitals between January 1, 2010, and December 31, 2019. The preimplementation phase was 2010 to 2015, and the postimplementation phase was 2017 to 2019. Data analysis was performed from October 2020 to January 2022.. An SQ insulin treatment protocol for diabetic ketoacidosis.. Difference-in-differences evaluation of the need for intensive care, mortality, readmission, and length of stay at a single intervention site using an SQ insulin protocol from 2017 onward compared with 20 control hospitals using standard care.. A total of 7989 hospitalizations for diabetic ketoacidosis occurred, with 4739 (59.3%) occurring before and 3250 (40.7%) occurring after implementation. The overall mean (SD) age was 42.3 (17.7) years, with 4137 hospitalizations (51.8%) occurring among female patients. Before implementation, SQ insulin was the first insulin used in 40 intervention (13.4%) and 651 control (14.7%) hospitalizations. After implementation, 98 hospitalizations (80.3%) received SQ insulin first at the intervention site compared with 402 hospitalizations (12.8%) at control sites. The adjusted rate ratio for intensive care unit admission was 0.43 (95% CI, 0.33-0.56) at the intervention sites, a 57% reduction compared with control sites, and was 0.50 (95% CI, 0.25-0.99) for 30-day hospital readmission, a 50% reduction. There were no significant changes in hospital length of stay and rates of death.. These findings suggest that a protocol based on SQ insulin for diabetic ketoacidosis treatment was associated with significant decreases in intensive care unit need and readmission, with no evidence of increases in adverse events.

Topics: Adult; Cohort Studies; Diabetes Mellitus; Diabetic Ketoacidosis; Female; Hospitals; Humans; Insulin; Insulin, Regular, Human; Length of Stay; Retrospective Studies

We study the efficacy of a glucagon-like peptide-1 (GLP-1) and estrogen dual agonist (GLP1-E2) in pancreatic islet protection. GLP1-E2 provides superior protection from insulin-deficient diabetes induced by multiple low-dose streptozotocin (MLD-STZ-diabetes) and by the Akita mutation in mice than a GLP-1 monoagonist. GLP1-E2 does not protect from MLD-STZ-diabetes in estrogen receptor-α (ERα)-deficient mice and fails to prevent diabetes in Akita mice following GLP-1 receptor (GLP-1R) antagonism, demonstrating the requirement of GLP-1R and ERα for GLP1-E2 antidiabetic actions. In the MIN6 β cell model, GLP1-E2 activates estrogen action following clathrin-dependent, GLP-1R-mediated internalization and lysosomal acidification. In cultured human islet, proteomic bioinformatic analysis reveals that GLP1-E2 amplifies the antiapoptotic pathways activated by monoagonists. However, in cultured mouse islets, GLP1-E2 provides antiapoptotic protection similar to monoagonists. Thus, GLP1-E2 promotes GLP-1 and E2 antiapoptotic signals in cultured islets, but

Topics: Animals; Diabetes Mellitus; Estrogen Receptor alpha; Estrogens; Glucagon-Like Peptide 1; Insulin; Insulin, Regular, Human; Islets of Langerhans; Mice; Proteomics; Streptozocin

Diabetes, a global health concern, requires insulin therapy. As insulin demand and prices rise dramatically, insulin affordability has increasingly become an issue facing patients with diabetes worldwide. To cut insulin costs, many patients ration their supply, which may have dire health consequences. This particularly affects lower-income populations, who are often forced to choose between purchasing their medications or paying for other necessities. Nutrition might be one solution for this. This commentary aims to provide comprehensive insight with historical context into intersectional components of diabetes in the global arena through analyses of insulin affordability, coupled with the critical role of nutrition intervention after searching the PubMed for relevant articles. More studies in personalized nutrition, supplementations, and dietary behaviors may develop evidence-based nutrition interventions to control diabetes. We argue that alongside price regulation, a greater focus to nutrition to address issues of food insecurity and food assistance programs may help to improve insulin affordability.

Topics: Costs and Cost Analysis; Diabetes Mellitus; Food Assistance; Humans; Insulin; Insulin, Regular, Human

Intravenous (IV) insulin infusion is the standard of care for treating diabetic ketoacidosis (DKA) worldwide. Subcutaneous (SC) insulin aspart could decrease the use of health care resources.. To compare the cost-effectiveness of mild uncomplicated DKA management with SC insulin aspart vs IV insulin infusion among pediatric patients from the perspective of a public health care payer using clinical data.. This economic evaluation included children aged 2 to 14 years presenting to the emergency department of a single academic medical center with mild DKA between January 1, 2015, and March 15, 2020. The medical records for DKA treatment course and its associated hospitalization costs were reviewed. Data were analyzed from January 1, 2015, to March 15, 2020.. Subcutaneous insulin aspart vs IV regular insulin infusion.. The incremental cost-effectiveness ratio (US dollars per hour), duration of DKA treatment, and length of hospital stay.. A total of 129 children with mild DKA episodes (mean [SD] age, 9.9 [3.1] years; 72 girls [55.8%]) were enrolled in the study. Seventy children received SC insulin aspart and 59 received IV regular insulin. Overall, the length of hospital stay in the SC insulin group was reduced (mean, 16.9 [95% CI, -31.0 to -2.9] hours) compared with the IV insulin group (P = .005). The mean (SD) cost of hospitalization in the SC insulin group (US $1071.99 [US $523.89]) was less than that in the IV insulin group (US $1648.90 [US $788.03]; P = .001). The incremental cost-effectiveness ratio was -34.08 (95% CI, -25.97 to -129.82) USD/h. The use of SC insulin aspart was associated with a lower likelihood of prolonged hospital stay (β = -17.22 [95% CI, -32.41 to -2.04]; P = .03) than IV regular insulin when controlling for age and sex.. Findings of this economic evaluation suggest that SC insulin aspart is dominant vs IV regular insulin in the management of mild uncomplicated DKA in children.

Topics: Child; Cost-Benefit Analysis; Diabetes Mellitus; Diabetic Ketoacidosis; Female; Humans; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin, Regular, Human

Topics: Abdomen; Diabetes Mellitus; Insulin; Insulin, Regular, Human; Pancreas

Topics: Abdomen; Diabetes Mellitus; Insulin; Insulin, Regular, Human; Pancreas

There have been major advances in insulin delivery and formulations over the past several decades. It is unclear whether these changes have resulted in improved glycemic control for patients with diabetes.. To characterize trends and disparities in glycemic control and severe hyperglycemia in US adults with diabetes using insulin.. This serial population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) between 1988-1994 and 1999-2020. Participants were nonpregnant US adults aged 20 years or older who had a diagnosis of diabetes and were currently using insulin.. Diabetes diagnosis and use of insulin.. Trends in glycemic control (glycated hemoglobin [HbA1c] level <7%) and severe hyperglycemia (HbA1c level >10%; to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01; to convert to millimoles per mole, multiply by 10.93 and subtract by 23.50) overall and by age, race and ethnicity, and indicators of socioeconomic status were evaluated using logistic regression. Analyses incorporated sample weights to account for oversampling of certain populations and survey nonresponse.. There were 2482 participants with diabetes using insulin included in the analyses (mean [SD] age, 59.8 [0.4] years); 51.3% were men, 7.0% were Mexican American individuals, 17.9% were non-Hispanic Black individuals, and 65.2% were non-Hispanic White individuals. From 1988-1994 to 2013-2020, the proportion of patients with diabetes who received insulin and achieved glycemic control did not significantly change, from 29.2% (95% CI, 22.6%-36.8%) to 27.5% (95% CI, 21.7%-34.2%). Mexican American adults who received insulin were less likely than non-Hispanic White adults to achieve glycemic control, and disparities increased during the study period. The proportion of adults with severe hyperglycemia did not significantly change and was 14.6% (95% CI, 12.0-17.5) in 2013-2020. Adults who were Mexican American or non-Hispanic Black, were uninsured, or had low family income had the highest prevalence of severe hyperglycemia.. In this population-based cross-sectional study of NHANES data over the past 3 decades, glycemic control stagnated and racial and ethnic disparities increased among US adults with diabetes who received insulin. Efforts to improve access to insulin may optimize glycemic control and reduce disparities in this population.

Topics: Adult; Cross-Sectional Studies; Diabetes Mellitus; Female; Glycated Hemoglobin; Glycemic Control; Humans; Hyperglycemia; Insulin; Insulin, Regular, Human; Male; Middle Aged; Nutrition Surveys

Differences in risk profiles for individuals with early- (<40 years old) vs. later-onset (≥40 years old) diabetes were examined.. A nested case-comparison study design using 30-year longitudinal data from the Coronary Artery Risk Development in Young Adults (CARDIA) study was used. Survey data (socio-demographics, family history, medical records, and lifestyle behaviors), obesity-related measures (body mass index, weight), blood pressure, and laboratory data (insulin, fasting glucose, 2-h glucose, and lipids) were used to examine progression patterns of diabetes development in those with early-onset vs. later-onset diabetes.. Of 605 participants, 120 were in early-onset group while 485 were in later-onset group. Early-onset group had a lower A Priori Diet Quality Score, but not statistically significant at baseline; however, the between-group difference became significant at the time that diabetes was first detected (p = 0.026). The physical activity intensity score consistently decreased from baseline to the development of diabetes in both the early- and later-onset groups. Early-onset group showed more dyslipidemia at baseline and at the time that diabetes was first detected, and rapid weight gain from baseline to the development of diabetes.. Emphases on lifestyle modification and risk-based diabetes screening in asymptomatic young adults are necessary for early detection and prevention.

Topics: Adult; Coronary Vessels; Diabetes Mellitus; Exercise; Humans; Insulin; Insulin, Regular, Human; Young Adult

Topics: Blood Glucose; Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Insulin, Regular, Human

Topics: Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Insulin, Regular, Human

Topics: Diabetes Mellitus; Humans; Insulin; Insulin, Regular, Human

There are 150 million people with diabetes worldwide who require insulin replacement therapy, and the prevalence of diabetes is rising the fastest in middle- and low-income countries. The current formulations require costly refrigerated transport and storage to prevent loss of insulin integrity. This study shows the development of simple "drop-in" amphiphilic copolymer excipients to maintain formulation integrity, bioactivity, pharmacokinetics, and pharmacodynamics for over 6 months when subjected to severe stressed aging conditions that cause current commercial formulation to fail in under 2 weeks. Further, when these copolymers are added to Humulin R (Eli Lilly) in original commercial packaging, they prevent insulin aggregation for up to 4 days at 50 °C compared to less than 1 day for Humulin R alone. These copolymers demonstrate promise as simple formulation additives to increase the cold chain resilience of commercial insulin formulations, thereby expanding global access to these critical drugs for treatment of diabetes.

Topics: Diabetes Mellitus; Excipients; Humans; Insulin; Insulin, Regular, Human; Refrigeration

Many patient decision aids (PDAs) are developed in academic settings by academic researchers. Academic settings are different from public health clinics where the focus is on clinical work. Thus, research on implementation in public health settings will provide insights to effective implementation of PDA in real-world settings. This study explores perceived factors influencing implementation of an insulin PDA in five public health clinics.. This study adopted a comparative case study design with a qualitative focus to identify similarities and differences of the potential barriers and facilitators to implementing the insulin PDA across different sites. Focus groups and individual interviews were conducted with 28 healthcare providers and 15 patients from five public health clinics under the Ministry of Health in Malaysia. The interviews were transcribed verbatim and analysed using the thematic approach.. Five themes emerged which were: 1) time constraint; 2) PDA costs; 3) tailoring PDA use to patient profile; 4) patient decisional role; and 5) leadership and staff motivation. Based on the interviews and drawing on observations and interview reflection notes, time constraint emerged as the common prominent factor that cut across all the clinics, however, tailoring PDA use to patient profile; patient decisional role; leadership and staff motivation varied due to the distinct challenges faced by specific clinics. Among clinics from semi-urban areas with more patients from limited education and lower socio-economic status, patients' ability to comprehend the insulin PDA and their tendency to rely on their doctors and family to make health decisions were felt to be a prominent barrier to the insulin PDA implementation. Staff motivation appeared to be stronger in most of the clinics where specific time was allocated to diabetes team to attend to diabetes patients and this was felt could be a potential facilitator, however, a lack of leadership might affect the insulin PDA implementation even though a diabetes team is present.. This study found time constraint as a major potential barrier for PDA implementation and effective implementation of the insulin PDA across different public health clinics would depend on leadership and staff motivation and, the need to tailor PDA use to patient profile. To ensure successful implementation, implementers should avoid a 'one size fits all' approach when implementing health innovations.

Topics: Academic Medical Centers; Adult; Aged; Case-Control Studies; Decision Making; Decision Support Techniques; Diabetes Mellitus; Female; Focus Groups; Humans; Insulin, Regular, Human; Interviews as Topic; Malaysia; Male; Middle Aged; Qualitative Research

Current therapy fails to emulate rapid (first-phase) insulin release in relation to a meal, a key defect in types 1 and 2 diabetes. We aimed to quantify the pharmacokinetic (PK) and pharmacodynamic (PD) profile of insulin tregopil, an enterically-absorbed insulin analog that restores the normal distribution of insulin between the hepatic portal and peripheral circulations.. The PK and PD profiles of insulin tregopil were studied in overnight-fasted, catheterized, conscious canines using four approaches: (1) equimolar intraportal infusions of tregopil vs human insulin; (2) escalating doses of oral tregopil; (3) identical, consecutive enteric doses of tregopil; and (4) comparison of oral tregopil to inhaled and subcutaneous human insulin administration.. Equimolar intraportal infusions of tregopil and human insulin resulted in very similar PK profiles and PD profiles were nearly identical. Enteric delivery of tregopil brought about rapid absorption with t. Enterically delivered tregopil is rapidly absorbed and restores a portal-to-peripheral vascular distribution. These characteristics should improve postprandial hyperglycaemia in types 1 and 2 diabetes.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dogs; Female; Glucose; Humans; Insulin; Insulin, Regular, Human; Male

The Follow-Up Study of patients previously enrolled in Exubera controlled clinical trials (FUSE) was designed to evaluate whether patients previously treated with Exubera (EXU; insulin human [rDNA origin], inhaled powder) in controlled clinical trials died because of incident primary lung cancer at a substantially higher rate than patients treated with a comparator.. FUSE is a hybrid, randomized, controlled trial/cohort study including participants of 17 prior EXU clinical trials. Pooled patient data from these trials were used, and the subset of patients enrolled in the follow-up cohort study was followed prospectively for 2 years in order to evaluate the incidence of fatal and nonfatal primary lung cancers and all-cause mortality.. There were 24,409 person-years (PY) of observation among 7,439 trial patients, with 4,017 PY (16.5%) from the period after the trials but before the prospective follow-up and 5,299 PY (21.7%) from the prospective follow-up. Just over half of the 2,631 patients (51.6%) in the prospective follow-up were randomized to EXU in the original trial. The incidence density ratio was 2.8 (95% CI 0.5, 28.5) for lung cancer-related mortality and 3.7 (95% CI 1.0, 20.7) for incident primary lung cancer. The hazard ratio for all-cause mortality was 0.81 (95% CI 0.60, 1.10).. These data cannot exclude an increased risk of lung cancer-related mortality associated with EXU use. If real, the absolute increased risk of lung cancer-related mortality was small (0.48 cases per 1,000 PY). For all-cause mortality-the most reliably measured end point with the clearest interpretation-EXU users did not experience an excess all-cause death rate (relative or absolute) compared with users of other diabetes treatments over the study period.

Topics: Administration, Inhalation; Adult; Cohort Studies; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin, Regular, Human; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Randomized Controlled Trials as Topic

Topics: Diabetes Mellitus; Drug Administration Schedule; Drug Compounding; Excipients; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Insulin, Regular, Human; Osmolar Concentration; Recombinant Proteins

Diabetes in neonates usually has a monogenic aetiology; however, the cause remains unknown in 20-30%. Heterozygous INS mutations represent one of the most common gene causes of neonatal diabetes mellitus.. Clinical and functional characterisation of a novel homozygous intronic mutation (c.187+241G>A) in the insulin gene in a child identified through the Monogenic Diabetes Registry (http://monogenicdiabetes.uchicago.edu).. The proband had insulin-requiring diabetes from birth. Ultrasonography revealed a structurally normal pancreas and C-peptide was undetectable despite readily detectable amylin, suggesting the presence of dysfunctional β cells. Whole-exome sequencing revealed the novel mutation. In silico analysis predicted a mutant mRNA product resulting from preferential recognition of a newly created splice site. Wild-type and mutant human insulin gene constructs were derived and transiently expressed in INS-1 cells. We confirmed the predicted transcript and found an additional transcript created via an ectopic splice acceptor site.. Dominant INS mutations cause diabetes via a mutated translational product causing endoplasmic reticulum stress. We describe a novel mechanism of diabetes, without β cell death, due to creation of two unstable mutant transcripts predicted to undergo nonsense and non-stop-mediated decay, respectively. Our discovery may have broader implications for those with insulin deficiency later in life.

Topics: Diabetes Mellitus; Humans; Infant; Insulin, Regular, Human; Introns; Mutation; Sequence Analysis, DNA

Recent guidelines recommend a physiologic approach to non-intensive care unit (ICU) inpatient glucose management utilizing basal-bolus with correctional (BBC) insulin over traditional sliding-scale insulin monotherapy. Unfortunately, few studies exist using a BBC approach restricted to human insulins (regular and neutral protamine Hagedorn [NPH]). This study evaluated changes in provider prescribing patterns, effects on blood glucose, and safety with implementation of hospital order sets for BBC using human insulins.. Order sets were developed for non-ICU inpatients, consisting of basal, prandial, and correctional insulin using NPH and regular human insulins. Evaluation compared a 4-month period before (admissions, n = 274) with a 4-month period after order set availability (n = 302). Primary outcome was change in insulin prescribing patterns. Secondary outcomes included use of nonpreferred diabetes treatments, hemoglobin A1c testing, mean daily blood glucose, and incidence of hypoglycemia.. Use of BBC insulin regimen increased from 10.6 to 27.5% after order set implementation (P<.001). Use of oral antihyperglycemic agents decreased from 24.1 to 14.9% after implementation (P = .006). Hemoglobin A1c testing rose from 50.0 to 62.3% after (P = .003). Mean daily blood glucose improved, with an estimated mean difference of 14.4 mg/dL (95% confidence interval, 2.2 to 26.5 mg/dL) over hospital days 3 through 9 (P = .02). There was no significant change in the incidence of moderate or severe hypoglycemia.. Implementation of hospital-wide human insulin order sets led to improvements in prescribing practices and blood glucose control, without increasing the incidence of hypoglycemia. These order sets may be useful for facilities limited by formulary and cost considerations to the use of older human insulins.

Topics: Aged; Diabetes Mellitus; Drug Prescriptions; Female; Hospitals, Rural; Humans; Hypoglycemic Agents; Inpatients; Insulin, Regular, Human; Male; Middle Aged; Outcome Assessment, Health Care

Neonatal diabetes mellitus (DM) is a rare condition that can be either transient or permanent. In this case report, we describe a novel mutation (p.L30Q) in the INS gene resulting in permanent DM in a four-month-old female who presented with polyphagia, polyuria, irritability, and hyperglycemia with glucosuria and ketonuria without acidosis.

Topics: Diabetes Mellitus; Female; Humans; Hyperglycemia; Hyperphagia; Hypoglycemic Agents; Infant; Insulin; Insulin, Isophane; Insulin, Regular, Human; Isophane Insulin, Human; Mosaicism; Mothers; Mutation, Missense; Polyuria; Treatment Outcome

Topics: Developmental Disabilities; Diabetes Mellitus; Diet; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin Resistance; Insulin, Regular, Human; Male; Metformin; Middle Aged

Topics: Diabetes Mellitus; Humans; Immunologic Techniques; Insulin Antibodies; Insulin, Regular, Human