humulin-s and Hyperglycemia

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

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

This study performed a systematic review and meta-analysis on glycemic control and pregnancy outcomes in women with type 1 diabetes mellitus (T1DM) treated with lispro (LP) versus regular insulin (RI) since before pregnancy.. We performed a MEDLINE and EMBASE search. Abstracts (and full articles when appropriate) were reviewed by two independent researchers. Inclusion criteria were patients with T1DM, data on women treated with RI and LP since before pregnancy until delivery in the same article, at least five pregnancies in each group, and information on at least one pregnancy outcome. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort studies.. Outcome data were summarized with Revman version 5.0 (ims.cochrane.org/revman/download [The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark]), applying a random effects model. Two hundred sixty-seven abstracts were identified, and four full articles fulfilled inclusion criteria, all of them corresponding to observational studies. Baseline characteristics were similar in women treated with LP or RI. Regarding outcome data, no differences between LP and RI groups were observed in hemoglobin A1c, gestational age at birth, birth weight, and rate of diabetic ketoacidosis, pregnancy-induced hypertension, pre-eclampsia, spontaneous miscarriages, interruptions, total abortions, cesarean section, preterm birth, macrosomia, small-for gestational-age newborns, stillbirth, neonatal and perinatal mortality, neonatal hypoglycemia, and major malformations. The rate of large-for-gestational age newborns was higher in the LP group (relative risk 1.38; 95% confidence interval 1.14-1.68).. In relation to women with T1DM treated with RI, those treated with LP display similar baseline characteristics and no differences in metabolic control or perinatal outcome with the exception of a higher rate of large-for-gestational-age newborns.

Topics: Adult; Birth Weight; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Lispro; Insulin, Regular, Human; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome

Various studies have evaluated the safety and efficacy of using insulin pumps during Ramadan; some of them demonstrated favorable outcomes in reducing hypoglycemia and hyperglycemia. However, there is no consensus on the recommendations for basal insulin adjustments and the utilization of technical features of insulin pumps to improve glycemic control.. We aimed to investigate the effects of different insulin pump settings on time in range in patients with type 1 diabetes during Ramadan.. In this randomized pilot study, 30 patients classified to have low to moderate risk for fasting were assigned to either a control group to receive basal insulin adjustments only or an intervention group to use the temporary basal rate and extended bolus features in addition to the basal insulin modifications. The percentage of time spent at different glucose ranges was measured by continuous glucose monitoring.. Incorporating technological approaches of pump therapy with clinical practice guidelines could improve glycemic control during Ramadan.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Regular, Human; Islam; Pilot Projects

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

To investigate changes in cardiac repolarization abnormalities (heart rate-corrected QT [QT. In a randomized crossover study, 24 individuals with type 1 diabetes underwent two experimental clamps with three steady-state phases during electrocardiographic monitoring: (1) a 45-minute euglycaemic phase (5-8 mmol/L), (2) a 60-minute insulin-induced hypoglycaemic phase (2.5 mmol/L), and (3) 60-minute recovery in either hyperglycaemia (20 mmol/L) or euglycaemia (5-8 mmol/L).. All measured markers of arrhythmic risk indicated increased risk during hypoglycaemia. These findings were accompanied by a decrease in vagal tone during both hyperglycaemia and euglycaemia clamps. Compared with baseline, the QT. In people with type 1 diabetes, insulin-induced hypoglycaemia prolongs cardiac repolarization, which is sustained during a 60-minute recovery period independently of recovery to hyperglycaemia or euglycaemia. Thus, vulnerability to serious cardiac arrhythmias and sudden cardiac death may extend beyond a hypoglycaemic event, regardless of hyperglycaemic or euglycaemic recovery.

Topics: Arrhythmias, Cardiac; Cross-Over Studies; Diabetes Mellitus, Type 1; Heart Rate; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin, Regular, Human; Long QT Syndrome

Bayesian adaptive trial design has the potential to create more efficient clinical trials. However, a barrier to the uptake of bayesian adaptive designs for confirmatory trials is limited experience with how they may perform compared with a frequentist design.. To compare the performance of a bayesian and a frequentist adaptive clinical trial design.. This prospective cohort study compared 2 trial designs for a completed multicenter acute stroke trial conducted within a National Institutes of Health neurologic emergencies clinical trials network, with individual patient-level data, including the timing and order of enrollments and outcome ascertainment, from 1151 patients with acute stroke and hyperglycemia randomized to receive intensive or standard insulin therapy. The implemented frequentist design had group sequential boundaries for efficacy and futility interim analyses at 90 days after randomization for 500, 700, 900, and 1100 patients. The bayesian alternative used predictive probability of trial success to govern early termination for efficacy and futility with a first interim analysis at 500 randomized patients and subsequent interims after every 100 randomizations.. The main outcome was the sample size at end of study, which was defined as the sample size at which each of the studies stopped accrual of patients.. Data were collected from 1151 patients. As conducted, the frequentist design passed the futility boundary after 936 participants were randomized. Using the same sequence and timing of randomization and outcome data, the bayesian alternative crossed the futility boundary approximately 3 months earlier after 800 participants were randomized.. Both trial designs stopped for futility before reaching the planned maximum sample size. In both cases, the clinical community and patients would benefit from learning the answer to the trial's primary question earlier. The common feature across the 2 designs was frequent interim analyses to stop early for efficacy or for futility. Differences between how these analyses were implemented between the 2 trials resulted in the differences in early stopping.

Topics: Bayes Theorem; Humans; Hyperglycemia; Insulin; Insulin, Regular, Human; Prospective Studies; Stroke; United States

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

The objective of this study was to compare acute effects of prolonged sitting, prolonged standing and sitting interrupted with regular activity breaks on vascular function and postprandial glucose metabolism. In a randomized cross-over trial, 18 adults completed: 1. Prolonged Sitting; 2. Prolonged Standing and 3. Sitting with 2-min walking (5 km/h, 10% incline) every 30 min (Regular Activity Breaks). Flow mediated dilation (FMD) was measured in the popliteal artery at baseline and 6 h. Popliteal artery hemodynamics, and postprandial plasma glucose and insulin were measured over 6 h. Neither raw nor allometrically-scaled FMD showed an intervention effect (p = 0.285 and 0.159 respectively). Compared to Prolonged Sitting, Regular Activity Breaks increased blood flow (overall effect of intervention p<0.001; difference = 80%; 95% CI 34 to 125%; p = 0.001) and net shear rate (overall effect of intervention p<0.001; difference = 72%; 95% CI 30 to 114%; p = 0.001) at 60 min. These differences were then maintained for the entire 6 h. Prolonged Standing increased blood flow at 60 min only (overall effect of intervention p<0.001; difference = 62%; 95% CI 28 to 97%; p = 0.001). Regular Activity Breaks decreased insulin incremental area under the curve (iAUC) when compared to both Prolonged Sitting (overall effect of intervention P = 0.001; difference = 28%; 95% CI 14 to 38%; p<0.01) and Prolonged Standing (difference = 19%; 95% CI 4 to 32%, p = 0.015). There was no intervention effect on glucose iAUC or total AUC (p = 0.254 and 0.450, respectively). In normal-weight participants, Regular Activity Breaks induce increases in blood flow, shear stress and improvements in postprandial metabolism that are associated with beneficial adaptations. Physical activity and sedentary behaviour messages should perhaps focus more on the importance of frequent movement rather than simply replacing sitting with standing.

Topics: Adult; Area Under Curve; Arterial Pressure; Blood Glucose; Cross-Over Studies; Exercise; Female; Glucose; Hemodynamics; Humans; Hyperglycemia; Insulin; Insulin, Regular, Human; Male; Postprandial Period; Sedentary Behavior; Sitting Position; Standing Position; Triglycerides; Walking

Healthy pancreatic β-cells secrete the hormones insulin and amylin in a fixed ratio. Both hormones are lacking in type 1 diabetes, and postprandial glucose control using insulin therapy alone is difficult. This study tested the pharmacodynamic effects of the amylin analog pramlintide and insulin delivered in a fixed ratio over a 24-h period.. Patients with type 1 diabetes were stabilized on insulin pump therapy with insulin lispro before a randomized, single-masked, two-way crossover, 24-h inpatient study in which regular human insulin was administered with pramlintide or placebo using separate infusion pumps in a fixed ratio (9 μg/unit). Meal content and timing and patient-specific insulin doses were the same with each treatment. The primary outcome measure was change in mean glucose by continuous glucose monitoring (CGM). Profiles of laboratory-measured glucose, insulin, glucagon, and triglycerides were also compared.. Mean 24-h glucose measured by CGM was lower with pramlintide versus placebo (8.5 vs. 9.7 mmol/L, respectively;. Coadministration of fixed-ratio pramlintide and regular human insulin for 24 h improved postprandial hyperglycemia and glycemic variability in patients with type 1 diabetes. Longer studies including dose titration under daily conditions are needed to determine whether this regimen could provide long-term improvement of glycemic control.

Topics: Adolescent; Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Combinations; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Infusion Systems; Insulin, Regular, Human; Islet Amyloid Polypeptide; Male; Meals; Middle Aged; Single-Blind Method; Young Adult

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 aim of this multicenter, prospective, randomized, crossover trial is to compare, in critical care patients receiving insulin infusion therapy (IIT), the pharmacodynamic of Humulin insulin (Hlin), currently used as "standard of care," and Humalog insulin (Hlog), a shorter acting insulin formulation. This was measured as extent and duration of the carryover effect of insulin treatment, with the latter calculated as ratio between blood glucose concentration (BGC) reduction during and after IIT.. Twenty-eight patients treated in an intensive care unit and receiving full nutritional support were randomly assigned to Hlin or Hlog as first treatment. Insulin was infused at a constant rate in patients presenting with BGC greater than or equal to 180 mg/dL (0.04 U/kg per hour) and was discontinued when BGC was less than or equal to 140 mg/dL (therapeutic BGC drop). Further reductions in BGC after discontinuation of insulin infusion were recorded (postinfusional BGC drop). During the study period, whole blood BGC was measured every 30 minutes. A minimal 6-hour washout interval was maintained between treatments with the 2 types of insulin. The primary end point was the extent (calculated as ratio between the therapeutic BGC drop and the postinfusional BGC drop) and duration of the carryover effect.. Treatment with Hlog, as compared with Hlin, was associated with a less profound carryover effect as well as a briefer duration of carryover (median, 0.40 vs 0.62; P < .001; median, 1 vs 1.5 hours; P < .001).. The use of constant Hlog infusion for IIT, when compared with Hlin at the same dose, is associated with a less profound carryover effect on BGC after discontinuation of IIT, a briefer duration of carryover, a faster BGC drop during infusion, and a quicker BGC rise after discontinuation. These characteristics suggest that Hlog IIT may be preferable for use in critically ill patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Critical Care; Cross-Over Studies; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Regular, Human; Intensive Care Units; Male; Middle Aged; Prospective Studies; Single-Blind Method; Young Adult

Prandial treatment with human regular insulin for diabetes may result in early postprandial hyperglycaemia and late hypoglycaemia due to its slow onset and long duration of action. This study compared injections of recombinant human insulin (rHI) formulated with recombinant human hyaluronidase [rHuPH20] (INSULIN-PH20) to insulin lispro for prandial treatment in subjects with type 1 diabetes (T1D).. After a 1-month run-in period using twice-daily insulin glargine (or usual basal insulin therapy for pump users) with prandial lispro, 46 subjects with T1D (42 ± 13 years; body mass index: 26 ± 4 kg/m(2); A1c: 6.8 ± 0.5%) were assigned to INSULIN-PH20 or lispro in a random sequence for two consecutive, 12-week periods as the prandial insulin in an intensive treatment regimen.. The mean glycaemic excursion for INSULIN-PH20 (0.96 ± 2.00 mmol/l) was comparable (p = 0.322) to lispro (0.80 ± 1.95 mmol/l). The 8-point self-monitored blood glucose profiles were also comparable in the two groups. Good glycaemic control (A1c) was maintained for both treatments at 12 weeks (INSULIN-PH20: 7.0 ± 0.5%; lispro: 6.9 ± 0.6%). Overall rates of hypoglycaemia (≤ 3.9 mmol/l) were 24 events per patient per 4 weeks for INSULIN-PH20 and 22 events for lispro. There were no significant differences in adverse events or immunogenicity between treatments and both treatments were well tolerated.. Unlike commercially available formulations of regular human insulin, a formulation of rHI with rHuPH20 was comparable to lispro for postprandial glucose excursions in a basal-bolus treatment regimen for T1D patients. Glycaemic control, safety and tolerability profiles were comparable for both treatments.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Humans; Hyaluronoglucosaminidase; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Lispro; Insulin, Regular, Human; Male; Meals; Postprandial Period; Treatment Outcome

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

Optimal inpatient glycemic management targets a blood glucose (BG) of 140-180 mg/dL and is an important safety measure for hospitalized patients with hyperglycemia. Traditional barriers to appropriate insulin administration include incorrect timing of prandial insulin administration, failure to administer basal insulin to persons with insulin deficiency/type 1 diabetes mellitus (DM), and inaccurate insulin dosing or timing resulting in hypoglycemia. Given the ongoing rapid assimilation of technology to manage our patients with DM, we investigated the use of continuous glucose monitoring (CGM) in the inpatient setting as a potential solution to traditional barriers to optimal hyperglycemia management for inpatient care. In this study, we evaluated the efficacy of use of inpatient CGM for insulin dosing in comparison with current standard of care and whether CGM could aid in minimizing hypoglycemic events.. This study evaluated the use of Abbott professional (blinded) Freestyle Libre CGMs in participants treated with basal bolus insulin administered with subcutaneous insulin (basal bolus therapy [BBT]: n = 20) or on intravenous insulin (IVI) infusions (n =16) compared with standard point of care (POC) BG measurements. All participants on IVI were admitted with a diagnosis of diabetic ketoacidosis (DKA). The CGM data was not available in real time. Sensors were removed at the time of discharge and data uploaded to Libre View. Continuous BG data were aggregated for each subject and matched to POC BG or lab chemistry values within five minutes. The POC BG results were assessed for comparability (CGM vs standard BG testing). Data were further analyzed for clinical decision-making for correction insulin.. These results suggest that the use of inpatient CGM arrives at similar correction insulin dosing. The routine use of CGM for inpatients would consistently underestimate the BG compared with POC BG and could aid in minimizing and predicting hypoglycemia in the hospital setting. Our data support that the model of adoption of real-time inpatient CGM technology is anticipated to have significant impact in the clinical setting in efforts to maintain adequate glycemic control targeting BG 140-180 mg/dL while minimizing the frequency of hypoglycemic events.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Glucose; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin, Regular, Human; Reproducibility of Results; Standard of Care

During COVID-19 pandemic, several studies have demonstrated a strong link between SARS-CoV-2 infection and diabetes mellitus. Hyperglycaemia is a frequent event during the infection, also in patients without a history of diabetes. Furthermore, several cases of diabetic ketoacidosis during COVID-19 disease have been described. No data are available about the effects of SARS-CoV-2 infection on glycaemic control in pancreas transplant patients.. A 45-year-old woman affected by type 1 diabetes mellitus was treated with kidney-pancreas transplantation in 2015, 6 years before COVID-19 infection. After transplantation, insulin therapy was stopped with a good glycaemic control during the following years.After SARS-CoV-2 infection, she developed severe hyperglycaemia requiring insulin therapy again. During the acute phase of the infection, the detection of antibodies against islet cells (ICA) and against glutamic acid decarboxylase (GAD) was found positive.. The onset of hyperglycaemia after SARS-CoV-2 infection might be the result of a direct virus-induced toxicity or the effect of a virus-mediated activation of autoimmunity.

Topics: COVID-19; Diabetes Mellitus, Type 1; Female; Humans; Hyperglycemia; Insulin; Insulin, Regular, Human; Middle Aged; Pancreas Transplantation; Pandemics; SARS-CoV-2

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

Patients hospitalized with COVID-19 and hyperglycemia require frequent glucose monitoring, usually performed with glucometers. Continuous glucose monitors (CGMs) are common in the outpatient setting but not yet approved for hospital use. We evaluated CGM accuracy, safety for insulin dosing, and CGM clinical reliability in 20 adult patients hospitalized with COVID-19 and hyperglycemia.. Study patients were fitted with a remotely monitored CGM. CGM values were evaluated against glucometer readings. The CGM sensor calibration was performed if necessary. CGM values were used to dose insulin, without glucometer confirmation.. CGM accuracy against glucometer, expressed as mean absolute relative difference (MARD), was calculated using 812 paired glucometer-CGM values. The aggregate MARD was 10.4%. For time in range and grades 1 and 2 hyperglycemia, MARD was 11.4%, 9.4%, and 9.1%, respectively, with a small variation between medical floors and intensive care units. There was no MARD correlation with mean arterial blood pressure levels, oxygen saturation, daily hemoglobin levels, and glomerular filtration rates. CGM clinical reliability was high, with 99.7% of the CGM values falling within the "safe" zones of Clarke error grid. After CGM placement, the frequency of glucometer measurements decreased from 5 to 3 and then 2 per day, reducing nurse presence in patient rooms and limiting viral exposure.. With twice daily, on-demand calibration, the inpatient CGM use was safe for insulin dosing, decreasing the frequency of glucometer fingersticks. For glucose levels >70 mg/dL, CGMs showed adequate accuracy, without interference from vital and laboratory values.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; COVID-19; Diabetes Mellitus, Type 1; Humans; Hyperglycemia; Insulin; Insulin, Regular, Human; Reproducibility of Results; Tertiary Care Centers

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

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

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

Insulin infusion site (IIS) failures are a weakness in insulin pump therapy. We examined experience with IIS failures among U.S. individuals with diabetes on insulin pump through survey distributed to the T1D Exchange Online Community. Demographic factors, IIS characteristics, and diabetes-related perceptions were assessed by logistic regression to determine odds of higher (≥1 per month) or lower (<1 per month) reported IIS failure frequency. IIS failures were common; 41.4% reported ≥1 per month. IIS failure is usually detected through development of hyperglycemia rather than pump alarm. No assessed demographic factor or IIS characteristic was predictive; however, higher odds of ≥1 failure per month were associated with feelings of burnout (odds ratios [OR] 1.489 [1.024, 2.165]) and considering pump discontinuation (OR 2.233 [1.455, 3.427]). IIS failures are frequent and unpredictable, typically require hyperglycemia for detection, and are associated with negative perceptions. More should be done toward preventing IIS failures and/or detecting them sooner.

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

Genetic modification of non-β-cells to produce insulin is a promising therapeutic strategy for type 1 diabetes; however, it is associated with issues, including biosafety and precise regulation of insulin supply. In this study, a glucose-activated single-strand insulin analog (SIA) switch (GAIS) was constructed to achieve repeatable pulse activation of SIA secretion in response to hyperglycemia. In the GAIS system, the conditional aggregation domain-furin cleavage sequence-SIA fusion protein was encoded by the intramuscularly delivered plasmid and temporarily kept in the endoplasmic reticulum (ER) because it binds to the GRP78 protein; then, upon hyperglycemia, the SIA was released and secreted into the blood. In vitro and in vivo experiments systematically demonstrated the effects of the GAIS system, including glucose-activated and repeatable SIA secretion, long-term precise blood glucose control, recovered HbA1c levels, improved glucose tolerance, and ameliorated oxidative stress. Additionally, this system offers sufficient biosafety, as evidenced by the assays of immunological and inflammatory safety, ER stress, and histological evaluation. Compared with the viral delivery/expression system, the ex vivo implantation of engineered cells, and the exogenous inducer system, the GAIS system combines the advantages of biosafety, effectiveness, persistence, precision, and convenience, providing therapeutic potential for the treatment of type 1 diabetes.. We undertook this study to establish a glucose-responsive single-strand insulin analog (SIA) self-supply system in vivo. We sought to determine whether the endoplasmic reticulum (ER) can serve as a safe and temporary repository to store designed fusion proteins and release SIAs under hyperglycemic conditions for efficient blood glucose regulation. The intramuscularly expressed plasmid-encoded conditional aggregation domain-furin cleavage sequence-SIA fusion protein can be temporarily stored in the ER, and the SIA can be released under the stimulation of hyperglycemia, resulting in efficient and long-term regulation of stable blood glucose in mice with type 1 diabetes (T1D). The glucose-activated SIA switch system provides applicable potential for T1D therapy, integrating regulation and monitoring of blood glucose levels.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 1; Furin; Glucose; Hyperglycemia; Insulin; Insulin-Secreting Cells; Insulin, Regular, Human; Mice

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

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

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

To describe the clinical and sociodemographic characteristics of pregnant women diagnosed with gestational diabetes mellitus (GDM) and to assess factors potentially associated with out-of-target glycemic control and the need for insulin.. Retrospective descriptive cohort. Women with GDM delivered at a reference hospital between January 2018 and September 2020 were included; women delivered in a different institution were excluded. Measured variables were age, body mass index (BMI) at the start of pregnancy, family history of diabetes, gestational age at the time of diagnosis, blood glucose levels at baseline and following oral glucose tolerance test, fructosamine, Hba1c, and insulin therapy use. A descriptive exploratory analysis of factors associated with poor glycemic control was conducted using uni and multivariate analyses.. Of the patients with GDM, 44 % were out of target for blood glucose with lifestyle and dietary measures. The exploratory analyses revealed a potential increase in the risk of poor glycemic control associated with initial blood glucose level on OGTT (raw OR: 3.57; 95 % CI: 2.1 - 6.1), BMI > 25 kg/m2 (OR: 1.97, 95 % CI: 1.15 - 3.34), and more advanced gestational age at the time of diagnosis as a protective factor against the need for insulin therapy (OR: 0.45, 95 % CI: 0.27- 0.75). However, these associations were not confirmed in the multivariate analysis.. A baseline blood glucose value greater than 95 mg/dl and BMI of more than 25 kg/m2 could be associated with poor glycemic control in women with GDM. Studies that assess these variables and control for confounding factors are needed in order to identify the factors associated with insulin requirement in pregnant women.. describir las características clínicas y sociodemográficas de las gestantes con diagnóstico de diabetes mellitus gestacional (DMG) y evaluar posibles factores asociados al control glucémico fuera de objetivo y requerimiento de insulina.. cohorte retrospectiva descriptiva. Se incluyeron mujeres con DMG atendidas en un hospital de referencia entre enero de 2018 y septiembre de 2020; se excluyeron mujeres con parto realizado en otra Institución. Las variables medidas fueron edad, índice de masa corporal al inicio del embarazo, antecedentes familiares de diabetes, edad gestacional al diagnóstico, glucemia basal y glucemia post prueba de tolerancia oral a la glucosa, fructosamina, Hba1c, y uso de insulinoterapia. Se realizó un análisis descriptivo y exploratorio de los factores asociados al mal control glucémico por medio del análisis uni y multivariado.. el 44 % de las pacientes con DMG presentaron control glucémico fuera de objetivo con medidas higiénico-dietéticas. El análisis exploratorio mostró que podría haber un incremento en el riesgo del mal control glucémico asociado al valor inicial de la glucemia durante la PTOG (OR crudo: 3,57, IC 95 %: 2,1 - 6,1), el IMC > 25 kg/m2 (OR: 1,97, IC 95 %: 1,15 - 3,34) y la mayor edad gestacional al momento del diagnóstico como factor protector del requerimiento de la insulinoterapia (OR: 0,45, IC 95 %: 0,27 - 0,75). Sin embargo, estas asociaciones no se confirmó en el análisis multivariado.. el valor de la glucemia basal mayor a 95 mg/dl, el IMC mayor a 25 kg/m2 podrían estar asociadas al mal control glucémico en las mujeres con DMG. Se necesitan estudios que evalúen estas variables con control de los factores de confusión para determinar los factores que indican el uso de insulina en mujeres gestantes.

Topics: Argentina; Blood Glucose; Diabetes, Gestational; Female; Hospitals; Humans; Hyperglycemia; Insulin; Insulin, Regular, Human; Pregnancy; Retrospective Studies; Risk Factors

To assess the efficacy and safety of faster aspart (FIAsp) in paediatric population with type 1 diabetes mellitus (T1DM) and insulin pumps in real-world settings.. Of 44 patients, 20 used FIAsp, 16 of which switched from aspart to FIAsp and 24 used aspart/lispro. We performed within-groups and between-groups analyses in three time points for anthropometric data, % of 24-h time in range of 70-180 mg/dl (TIR), time < 70 mg/dl and <54 mg/dl and time > 180 mg/dl and >250 mg/dl, bolus and basal insulins doses (units/kg/day and %), total daily dose (TDD, units/kg/day), glycaemic variability, frequency of set changes, sensor wear per week and meals per day.. Use of FIAsp over time increased TIR (P = 0.002) and TDD (P = 0.008 and P = 0.004, respectively for three months after the switch and recent use) and decreased time in hyperglycaemia (>180 P = 0.003 and > 250 mg/dl, P = 0.004). Frequency of set changes differ in the first 3 months (P = 0.042). Patients with FIAsp consumed more meals per day compared to those with aspart/lispro (P = 0.032).. Real-world data confirm that use of FIAsp in insulin pumps in paediatric populations improves glycaemic control long-term.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Humans; Hyperglycemia; Insulin; Insulin Lispro; Insulin, Regular, Human

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

Model predictive control (MPC) has become one of the most popular control strategies for automated insulin delivery (AID) in type 1 diabetes (T1D). These algorithms rely on a prediction model to determine the best insulin dosing every sampling time. Although these algorithms have been shown to be safe and effective for glucose management through clinical trials, managing the ever-fluctuating relationship between insulin delivery and resulting glucose uptake (aka insulin sensitivity, IS) remains a challenge. We aim to evaluate the effect of informing an AID system with IS on the performance of the system.. The University of Virginia (UVA) MPC control-based hybrid closed-loop (HCL) and fully closed-loop (FCL) system was used. One-day simulations at varying levels of IS were run with the UVA/Padova T1D Simulator. The AID system was informed with an estimated value of IS obtained through a mixed meal glucose tolerance test. Relevant controller parameters are updated to inform insulin dosing of IS. Performance of the HCL/FCL system with and without information of the changing IS was assessed using a novel performance metric penalizing the time outside the target glucose range.. Feedback in AID systems provides a certain degree tolerance to changes in IS. However, IS-informed bolus and basal dosing improve glycemic outcomes, providing increased protection against hyperglycemia and hypoglycemia according to the individual's physiological state.. The proof-of-concept analysis presented here shows the potentially beneficial effects on system performance of informing the AID system with accurate estimates of IS. In particular, when considering reduced IS, the informed controller provides increased protection against hyperglycemia compared with the naïve controller. Similarly, reduced hypoglycemia is obtained for situations with increased IS. Further tailoring of the adaptation schemes proposed in this work is needed to overcome the increased hypoglycemia observed in the more resistant cases and to optimize the performance of the adaptation method.

Topics: Algorithms; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Glucose; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Insulin Resistance; Insulin, Regular, Human

To determine the optimal insulin-to-steroid dose ratio for the attainment of glycemic control in hospitalized patients.. We retrospectively studied data collected from the electronic health records within an academic medical center from 18 599 patient-days where patients were treated concurrently with insulin and steroids. Multivariate logistic regression analyses, which included demographic and clinical variables, were performed to assess the relationships between the exposures of total and basal insulin-to-steroid ratios and the outcomes of glycemic control (all blood glucose readings on the following patient-day were >70 and ≤180 mg/dL) and hypoglycemia within 3 subgroups of steroid dosing: low (≤10-mg prednisone equivalent dose [PED]), medium (from >10-mg to ≤40-mg PED), and high (>40-mg PED).. Increased insulin-to-steroid ratio was associated with increased odds of both glycemic control and hypoglycemia. The optimal total insulin-to-steroid ratio for attaining glycemic control was 0.294 U/kg/10-mg PED in the low-dose subgroup, 0.257 U/kg/10-mg PED in the medium-dose subgroup, and 0.085 U/kg/10-mg PED in the high-dose subgroup. The optimal basal insulin-to-steroid ratio was 0.215 U/kg/10-mg PED in the low-dose subgroup, 0.126 U/kg/10-mg PED in the medium-dose subgroup, and 0.036 U/kg/10-mg PED in the high-dose subgroup.. Increasing insulin-to-steroid ratios are positively associated with glycemic control and hypoglycemia. Our study suggests that approximately 0.3 U/kg/10-mg PED is an optimal dose for low- and medium-dose steroids, whereas approximately 0.1 U/kg/10-mg PED is an optimal dose for high-dose steroids. Further prospective studies are needed to identify insulin regimens that will optimize glycemic control in steroid-treated patients while minimizing the risk of hypoglycemia.

Topics: Blood Glucose; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin, Regular, Human; Retrospective Studies; Steroids

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

To face the rapid spread of SARS-CoV2 coronavirus pandemic, home lockdown in Spain was decreed on 15th March 2020. The main objective of this study is to evaluate the impact of this constraint on glycemic control in children and adolescents with type 1 diabetes mellitus (T1D).. Observational, retrospective study in children and adolescents with T1D users of interstitial glucose monitoring systems. The following information corresponding to the last 2 weeks of lockdown was collected for subsequent comparison with data of 2 weeks prior to quarantine: daily insulin needs, mean interstitial glucose, estimated HbA1c, coefficient of variation (CV), time in range (70-180mg/dl), hypoglycemia (<70 and <54mg/dl) and hyperglycemia (>180 and> 250mg/dl), sensor use and number of blood glucose measurements. Data about meal routines, physical exercise, need for adjustments in therapy, acute complications and lockdown of caregivers were assessed via a survey.. 80 patients were studied (mean age 12.61±3.32 years, mean time of evolution of the disease 5.85±3.92 years), 66.2% treated with an insulin pump, users of following glucose monitoring systems: Guardian 3 (65%), FreeStyle Libre (18.8%) and Dexcom G6 (16.2%). Time in range in the cohort increased significantly during confinement (72.1±10.5 vs 74.8±10.5%; P=0.011) with lower time in hypoglycemia both <70mg/dl (4.6±3.2 vs 3.2±2.7%; P<0.001) and <54mg/dl (1.2±1.6 vs 0.7±1.2%; P<0.001) and hyperglycemia >250mg/dl (4.6±3.9 vs 3.7±3.7%; P=0.038). CV also decreased (35.8±6.3 vs 33.1±6.1%; P<0.001). Patients treated with multiple doses of insulin and poorer baseline glycemic control experienced greatest improvement. Daily insulin requirements remained stable. Regular practice of physical exercise and caregivers' confinement did not have a significant impact.. Glycemic control in children and adolescents with T1D improved during quarantine, particularly in those with worse baseline control.

Topics: Adolescent; Blood Glucose; Blood Glucose Self-Monitoring; Child; Communicable Disease Control; COVID-19; Diabetes Mellitus, Type 1; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin, Regular, Human; Retrospective Studies; RNA, Viral; SARS-CoV-2

Long-term glucagon receptor (GCGR) agonism is associated with hyperglycemia and glucose intolerance, while acute GCGR agonism enhances whole-body insulin sensitivity and hepatic AKTSer473 phosphorylation. These divergent effects establish a critical gap in knowledge surrounding GCGR action. mTOR complex 2 (mTORC2) is composed of seven proteins, including RICTOR, which dictates substrate binding and allows for targeting of AKTSer473. We used a liver-specific Rictor knockout mouse (RictorΔLiver) to investigate whether mTORC2 is necessary for insulin receptor (INSR) and GCGR cross talk. RictorΔLiver mice were characterized by impaired AKT signaling and glucose intolerance. Intriguingly, RictorΔLiver mice were also resistant to GCGR-stimulated hyperglycemia. Consistent with our prior report, GCGR agonism increased glucose infusion rate and suppressed hepatic glucose production during hyperinsulinemic-euglycemic clamp of control animals. However, these benefits to insulin sensitivity were ablated in RictorΔLiver mice. We observed diminished AKTSer473 and GSK3α/βSer21/9 phosphorylation in RictorΔLiver mice, whereas phosphorylation of AKTThr308 was unaltered in livers from clamped mice. These signaling effects were replicated in primary hepatocytes isolated from RictorΔLiver and littermate control mice, confirming cell-autonomous cross talk between GCGR and INSR pathways. In summary, our study reveals the necessity of RICTOR, and thus mTORC2, in GCGR-mediated enhancement of liver and whole-body insulin action.

Topics: Animals; Glucose; Glucose Intolerance; Homeostasis; Hyperglycemia; Insulin; Insulin Resistance; Insulin, Regular, Human; Liver; Mechanistic Target of Rapamycin Complex 2; Mice; Mice, Inbred C57BL; Mice, Knockout; Proto-Oncogene Proteins c-akt; Rapamycin-Insensitive Companion of mTOR Protein; Receptor, Insulin; Receptors, Glucagon; TOR Serine-Threonine Kinases

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

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

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

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

Insulin has a narrow therapeutic index, reflected in a small margin between a dose that achieves good glycemic control and one that causes hypoglycemia. Once injected, the clearance of exogenous insulin is invariant regardless of blood glucose, aggravating the potential to cause hypoglycemia. We sought to create a "smart" insulin, one that can alter insulin clearance and hence insulin action in response to blood glucose, mitigating risk for hypoglycemia. The approach added saccharide units to insulin to create insulin analogs with affinity for both the insulin receptor (IR) and mannose receptor C-type 1 (MR), which functions to clear endogenous mannosylated proteins, a principle used to endow insulin analogs with glucose responsivity. Iteration of these efforts culminated in the discovery of MK-2640, and its in vitro and in vivo preclinical properties are detailed in this report. In glucose clamp experiments conducted in healthy dogs, as plasma glucose was lowered stepwise from 280 mg/dL to 80 mg/dL, progressively more MK-2640 was cleared via MR, reducing by ∼30% its availability for binding to the IR. In dose escalations studies in diabetic minipigs, a higher therapeutic index for MK-2640 (threefold) was observed versus regular insulin (1.3-fold).

Topics: Animals; Animals, Inbred Strains; Binding, Competitive; CHO Cells; Cricetulus; Diabetes Mellitus, Type 1; Dogs; Dose-Response Relationship, Drug; Drug Design; Drug Evaluation, Preclinical; Half-Life; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin, Regular, Human; Lectins, C-Type; Ligands; Male; Mannose Receptor; Mannose-Binding Lectins; Metabolic Clearance Rate; Receptor, Insulin; Receptors, Cell Surface; Recombinant Proteins; Swine; Swine, Miniature

Topics: Absorption, Physiological; Animals; Blood Glucose; Dogs; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drugs, Investigational; Energy Metabolism; Gluconeogenesis; Glucose Clamp Technique; Glycosylation; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Infusions, Intravenous; Insulin, Regular, Human; Liver; Male; Metabolic Clearance Rate; Random Allocation; Somatostatin

To compare intraperitoneal (IP) to subcutaneous (SC) insulin delivery in an artificial pancreas (AP).. Ten adults with type 1 diabetes participated in a non-randomized, non-blinded sequential AP study using the same SC glucose sensing and Zone Model Predictive Control (ZMPC) algorithm adjusted for insulin clearance. On first admission, subjects underwent closed-loop control with SC delivery of a fast-acting insulin analogue for 24 hours. Following implantation of a DiaPort IP insulin delivery system, the identical 24-hour trial was performed with IP regular insulin delivery. The clinical protocol included 3 unannounced meals with 70, 40 and 70 g carbohydrate, respectively. Primary endpoint was time spent with blood glucose (BG) in the range of 80 to 140 mg/dL (4.4-7.7 mmol/L).. Percent of time spent within the 80 to 140 mg/dL range was significantly higher for IP delivery than for SC delivery: 39.8 ± 7.6 vs 25.6 ± 13.1 ( P = .03). Mean BG (mg/dL) and percent of time spent within the broader 70 to 180 mg/dL range were also significantly better for IP insulin: 151.0 ± 11.0 vs 190.0 ± 31.0 ( P = .004) and 65.7 ± 9.2 vs 43.9 ± 14.7 ( P = .001), respectively. Superiority of glucose control with IP insulin came from the reduced time spent in hyperglycaemia (>180 mg/dL: 32.4 ± 8.9 vs 53.5 ± 17.4, P = .014; >250 mg/dL: 5.9 ± 5.6 vs 23.0 ± 11.3, P = .0004). Higher daily doses of insulin (IU) were delivered with the IP route (43.7 ± 0.1 vs 32.3 ± 0.1, P < .001) with no increased percent time spent <70 mg/dL (IP: 2.5 ± 2.9 vs SC: 4.1 ± 5.3, P = .42).. Glycaemic regulation with fully-automated AP delivering IP insulin was superior to that with SC insulin delivery. This pilot study provides proof-of-concept for an AP system combining a ZMPC algorithm with IP insulin delivery.

Topics: Adult; Algorithms; Blood Glucose; Diabetes Mellitus, Type 1; Female; France; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Infusions, Parenteral; Infusions, Subcutaneous; Insulin Infusion Systems; Insulin Lispro; Insulin, Regular, Human; Male; Middle Aged; Pancreas, Artificial; Pilot Projects; Proof of Concept Study

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

The objective of the present study was to prepare and characterize low molecular weight chitosan (LMWC) with different molecular weight and degrees of deacetylation (DDA) and to optimize their use in oral insulin nano delivery systems. Water in oil nanosized systems containing LMWC-insulin polyelectrolyte complexes were constructed and their ability to reduce blood glucose was assessed in vivo on diabetic rats. Upon acid depolymerization and testing by viscosity method, three molecular weights of LMWC namely, 1.3, 13 and 18 kDa were obtained. As for the DDA, three LMWCs of 55%, 80% and 100% DDA were prepared and characterized by spectroscopic methods for each molecular weight. The obtained LMWCs showed different morphological and in silico patterns. Following complexation of LMWCs with insulin, different aggregation sizes were obtained. Moreover, the in vivo tested formulations showed different activities of blood glucose reduction. The highest glucose reduction was achieved with 1.3 kDa LMWC of 55% DDA. The current study emphasizes the importance of optimizing the molecular weight along with the DDA of the incorporated LMWC in oral insulin delivery preparations in order to ensure the highest performance of such delivery systems.

Topics: Acetylation; Administration, Oral; Animals; Blood Glucose; Chitosan; Diabetes Mellitus, Experimental; Drug Compounding; Drug Delivery Systems; Electrolytes; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin, Regular, Human; Male; Molecular Weight; Nanoparticles; Particle Size; Random Allocation; Rats, Sprague-Dawley; Recombinant Proteins; Surface Properties; Viscosity

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

There are an estimated 1000 children with diabetes in Tanzania. Recently, the first two pediatric endocrinologists, trained in the European Society for Paediatric Endocrinology (ESPE)/International Society for Paediatric and Adolescent Diabetes (ISPAD) program in Nairobi, Kenya, entered practice. The purpose of this study was to prospectively assess the impact of a 6-month diabetes management and education program on glycemic control and acute complications in children and adolescents in Tanzania.. Eighty-one patients aged 3-19 yr were enrolled. All were on split-dose Insulatard (Neutral Protamine Hagedorn) and Actrapid (soluble, regular) insulin, and were given three glucose test strips per week. Children were seen in clinic an average of six times over 6 months and received 3 h of diabetes education. A structured questionnaire evaluated social demographic data and acute complications.. Despite regular clinic attendance, diabetes education, and provision of insulin, hemoglobin A1c (HbA1c) levels did not improve. Four children (5%) had HbA1c 7.5%, 22 (28%) HbA1c 7.5-10%, 9 (24%) HbA1c 11-12.5%, and 36 (44%) HbA1c >12.5%. There was a substantial reduction in severe hypoglycemia, with 17% of subjects experiencing this acute complication compared to 52% in the 6 months prior to study enrolment. Six children were admitted in diabetic ketoacidosis during the study compared to three during the previous 6 months. Twenty-six children (36%) reported missing >6 doses of insulin (but only two lacked insulin).. Diabetes education significantly reduced the risk of severe hypoglycemia, but better glycemic control of diabetes was not attained. Further study is needed to explore factors to improve glycemic control including increased testing, or perhaps different insulin regimens.

Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Therapy, Combination; Family; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin, Isophane; Insulin, Regular, Human; Insulin, Regular, Pork; Isophane Insulin, Human; Male; Medication Adherence; Outpatient Clinics, Hospital; Patient Education as Topic; Prospective Studies; Tanzania

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

Topics: Diabetes Mellitus, Type 1; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Lispro; Insulin, Regular, Human; Pregnancy; Pregnancy in Diabetics

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