Incidence Of Severe Hypoglycemia Research Articles

Safety of Empagliflozin: An Individual Participant-Level Data Meta-Analysis from Four Large Trials.

Empagliflozin is a sodium-glucose co-transporter-2 inhibitor used to treat type 2 diabetes (T2D) to improve glycemic control, reduce risk of cardiovascular death in patients with T2D, and treat patients with symptomatic chronic heart failure (HF) and chronic kidney disease (CKD). The safety profile of empagliflozin is well documented, although adverse events (AEs) remain of interest to clinicians. This study provides an up-to-date safety evaluation of empagliflozin. Data were pooled from four long-term trials which included: patients with T2D and established cardiovascular disease (EMPA-REG OUTCOME), patients with HF, with/without diabetes (EMPEROR-Reduced and EMPEROR-Preserved), and patients with CKD, with/without diabetes (EMPA-KIDNEY). Since three of the four trials evaluated empagliflozin 10mg, the meta-analysis was restricted to this dose. Total trial medication exposure was 19,727 patient-years for patients who received empagliflozin (n = 10,472) and 19,447 patient-years for placebo (n = 10,461). The percentages of patients with serious AEs, fatal AEs, and AEs leading to discontinuation were similar for both groups. The incidences of serious urinary tract infection and serious pyelonephritis or urosepsis were similar for both groups but higher for women taking empagliflozin versus placebo. Serious genital infections were not increased with empagliflozin versus placebo. There was a slight increase in ketoacidosis and serious volume depletion in patients who received empagliflozin versus placebo. The occurrence of serious acute kidney injury was lower with empagliflozin versus placebo. Empagliflozin was not associated with an increased incidence of severe hypoglycemia, bone fractures, or lower limb amputations. Empagliflozin is therefore considered safe in people without diabetes, the elderly, patients with very low estimated glomerular filtration rate, low body mass index, and HF. Safety is unaltered by blood pressure, concomitant medication for hypertension, HF, and immunosuppression. This meta-analysis of long-term safety data extends current knowledge and confirms the safety and tolerability of empagliflozin.

IGlarLixi for type 2 diabetes: a systematic review and meta-analysis.

To assess the efficacy and tolerability of iGlarLixi-a novel, fixed-ratio, soluble combination of insulin glargine and lixisenatide-for the treatment of type 2 diabetes (T2D). The PubMed, Embase, Cochrane Library and ClinicalTrials.gov databases were searched from inception to November 15, 2023 to identify randomized controlled trials (RCTs) comparing iGlarLixi with a placebo or any other antidiabetic agent in adults with T2D. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated to evaluate the outcomes. A total of 10 trials enrolling 6071 T2D patients were included. Compared with placebos or other antidiabetic agents, iGlarLixi exerted beneficial effects on changes in HbA1c, the percentage of patients who achieved an HbA1c < 7%, the percentage of patients who achieved an HbA1c < 6.5%, the percentage of patients who achieved an HbA1c < 7.0% without weight gain and/or without severe or blood glucose-confirmed hypoglycemic episodes, changes in fasting plasma glucose, and changes in self-measured plasma glucose. Regarding safety, iGlarLixi did not increase the incidence of severe hypoglycemia or serious adverse events but did increase the incidence of gastrointestinal adverse events, symptomatic hypoglycemia, and adverse events (e.g., nausea, vomiting, diarrhea). iGlarLixi showed improved efficacy and safety in patients with T2D. Additional large, multicenter RCTs are warranted to obtain deeper insights into the efficacy and safety of iGlarLixi, thereby providing guidance for clinical treatment decisions.

Assessing glycemic variability in critically ill patients: A prospective cohort study comparing insulin infusion therapy with insulin sliding scale

Glycemic variability (GV) has been associated with an increased mortality rate among critically ill patients. The clinical outcomes of having less GV even with slight hyperglycemia are better than those having tight glycemic control but higher GV. Insulin infusion remains the preferred method to control stress hyperglycemia in critically ill patients. However, its impacts on GV and clinical outcomes in critically ill patients still need further investigation. This study intended to evaluate the impact of insulin infusion therapy (IIT) compared to the insulin sliding scale (ISS) on the extent of GV and explore its impact on the clinical outcomes for critically ill patients. A prospective, single-center observational cohort study was conducted at a tertiary academic hospital in Saudi Arabia between March 2021 and November 2021. The study included adult patients admitted to ICUs who received insulin for stress hyperglycemia management. Patients were categorized into two groups based on the regimen of insulin therapy during ICU stay (IIT versus ISS). The primary outcome was the GV between the two groups. Secondary outcomes were ICU mortality, the incidence of hypoglycemia, and ICU length of stay (LOS). A total of 381 patients were screened; out of them, eighty patients met the eligibility criteria. The distribution of patients having diabetes and a history of insulin use was similar between the two groups. The GV was lower in the IIT group compared to the ISS group using CONGA (− 0.65, 95% CI [− 1.16, − 0.14], p-value = 0.01). Compared with ISS, patients who received IIT had a lower incidence of hypoglycemia that required correction (6.8% vs 2.77%; p-value = 0.38). In contrast, there were no significant differences in ICU LOS and ICU mortality between the two groups. Our study demonstrated that the IIT is associated with decreased GV significantly in critically ill patients without increasing the incidence of severe hypoglycemia. There is no survival benefit with the use of the IIT. Further studies with larger sample size are required to confirm our findings and elaborate on IIT's potential effect in reducing ICU complications in critically ill patients.

Mitigating Severe Hypoglycemia in Users of Advanced Diabetes Technologies: Impaired Awareness of Hypoglycemia and Unhelpful Hypoglycemia Beliefs as Targets for Interventions.

Objective: A subgroup analysis of the Hypoglycemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycemia persisting despite optimized care (HARPdoc) trial was conducted to explore the impact of Blood Glucose Awareness Training (BGAT, a hypoglycemia awareness training program) and the HARPdoc (a psychoeducation addressing unhelpful hypoglycemia beliefs) in reducing severe hypoglycemia (SH) in individuals using advanced diabetes technologies (ADTs). Methods: Data from trial participants who utilized ADTs, including continuous glucose monitors or automated insulin delivery systems, were extracted. Generalized linear mixed-effects models with Poisson distribution or linear mixed-effects models were used to evaluate SH incidence, and Gold questionnaire, Attitudes to Awareness of Hypoglycemia (A2A), Problem Areas in Diabetes (PAID), Hospital Anxiety and Depress Scale (HADS)-anxiety, and HADS-depression scores as measures of hypoglycemia awareness, unhelpful hypoglycemia beliefs, diabetes distress, and anxiety and depression symptoms, respectively. Results: In the 45 participants using ADTs, the BGAT and HARPdoc interventions both reduced SH incidence by more than 50% (P < 0.0001) and yielded improvements in hypoglycemia awareness (P < 0.05). HARPdoc outperformed BGAT in reducing SH at month 24 (P = 0.01). HARPdoc also mitigated unhelpful hypoglycemia beliefs (P < 0.0001), diabetes distress (P < 0.05), and anxiety symptoms (P < 0.05); BGAT demonstrated no significant impacts in these respects. Neither HARPdoc nor BGAT had significant effects on depression symptoms. Conclusion: Psychoeducation (BGAT and HARPdoc) was effective in reducing SH in people using ADTs. HARPdoc may also provide greater long-term SH reduction and improves psychological well-being in this patient group.

Real-world effectiveness and safety of insulin glargine 100 U/mL plus lixisenatide in adults with type 2 diabetes: An international, multicentre, 12-month, prospective observational study.

To assess the impact of insulin glargine (100 U/mL) and lixisenatide (iGlarLixi) fixed-ratio combination therapy on the overall management of glycaemia in patients with type 2 diabetes (T2D), previously inadequately controlled with oral antidiabetic drugs ± basal insulin or glucagon-like peptide-1 receptor agonists (GLP-1 RAs). This 12-month, international, multicentre, prospective, observational study included patients (age ≥ 18 years) with T2D who had initiated iGlarLixi within 1 month prior to study inclusion. Data were collected at study inclusion, month 3, month 6 and month 12 from patient diaries, self-measured plasma glucose, and questionnaires. The primary endpoint was change in HbA1c from baseline to month 6. Of the 737 eligible participants (mean age: 57.8 [standard deviation: 11.2] years; male: 49%), 685 had baseline and post-baseline HbA1c data available. The least squares mean change in HbA1c from baseline to month 6 was -1.4% (standard error [95% confidence interval (CI)]: 0.05 [-1.5, -1.3]). The absolute change from baseline at month 12 was -1.7% ± 1.9% (95% CI: -1.9, -1.5). There were 72 hypoglycaemia events reported during the study period, with a very low incidence of severe hypoglycaemia (two participants [rate: 0.003 events per patient-year]). This real-world observational study shows that initiation of iGlarLixi in people with T2D inadequately controlled on oral antidiabetic drugs ± basal insulin or GLP-1 RAs improves glycaemic control with a low incidence of hypoglycaemia.

Burden of impaired awareness of hypoglycemia in people with diabetes undergoing hemodialysis

IntroductionImpaired awareness of hypoglycemia (IAH) refers to a diminished capacity to detect hypoglycemia. IAH can result in severe and even life-threatening outcomes for individuals with diabetes, especially those in advanced...

Evaluating the clinical effectiveness and safety of insulin glargine 300 U/mL in individuals with type 2 diabetes uncontrolled on basal insulin: A real-world evidence study from Saudi Arabia (EVOLUTION).

To evaluate the effectiveness and safety profile of switching to insulin glargine 300 U/mL (Gla-U300) in patients with uncontrolled type 2 diabetes (T2D) on basal insulin in Saudi Arabia. We conducted a multicentre retrospective study that retrieved the medical records of adult T2D patients switched to Gla-U300 because of poor glycaemic control on their basal insulin. Data covering 6 months ± 30 days before and after the switch were retrieved. Data from 718 patients were analysed. The mean HbA1c decreased significantly 6 months after switching to Gla-U300, with a mean reduction of 0.7% (95% confidence interval [CI] 0.6%-0.9%; P < .001). The percentage of patients with HbA1c levels of less than 7% increased from 6.4% before switching to 10.3% after switching to Gla-U300. The percentage of patients achieving the predefined individualized HbA1c goal increased from 8.6% before switching to 17.3% after switching to Gla-U300. The mean daily insulin dose decreased from a baseline level of 32.2 (± 14.7) to 31.0 (± 15) U (P = .09). About 36.1 of the patients required adjustment to the initial dose. Gla-300 was well tolerated; 4.5% of the patients experienced overall confirmed or symptomatic hypoglycaemia, compared with 15.3% before switching to Gla-U300. The incidence of severe hypoglycaemia after switching was 0.6% (n = 4 patients), compared with 1% before switching. Real-world evidence supports the effectiveness of switching to Gla-U300 from first-generation basal insulin in T2D in Saudi Arabia.

141-LB: Cost-Effectiveness of Real-Time Continuous Glucose Monitoring (rt-CGM) vs. Intermittent-Scanning Continuous Glucose Monitoring (is-CGM) from a U.S. Payer Perspective in Patients with Type 2 Diabetes on Multiple Daily Injections of Insulin (PwT2D on MDI)

Diabetes management for PwT2D on MDI requires access to timely glucose readings to inform treatment decisions and avoid acute events like severe hypoglycemia (SHE) and Diabetic Ketoacidosis (DKA). CGM systems have different features that can impact glycemic outcomes and disease complications and costs. There is a gap in the literature on the cost-effectiveness of rt-CGM vs is-CGM systems. We conducted lifetime projections of disease outcomes and costs from a US payer perspective using the IQVIA Core Diabetes Model v9.5+. Cohort characteristics and clinical inputs were sourced from the DIAMOND T2D and REPLACE RCTs. Applying Bucher's adjusted indirect comparison method resulted in an HbA1c effect of -0.33 favoring rt-CGM, SHE incidence rates of 0.014 and 0 Per Person-Year (PPY) for is-CGM and rt-CGM, respectively, and DKA rates were estimated using Time-Above-Range (0.0313 and 0 PPY, respectively). The cost of both CGM systems is based on Medicare pricing and 80% reimbursement (HCPCS code A4239). A utility for fear of hypoglycemia (FoH) reduction was applied from the ALERTT1 RCT. The model associates rt-CGM use with reduced eye (-5.64%), renal (-7.42%), neural (-4.08%), and cardiovascular (-2.56%) complications compared to is-CGM. It projects rt-CGM users to have higher quality-adjusted life years (QALYs) by 0.454 with cost savings of -$1,355, and an incremental cost-effectiveness ratio of -$2,983/QALY. Rt-CGM remained cost-effective under the $50,000 willingness-to-pay threshold even when its cost was increased by 70% (+$1,713). Scenario analysis with 50% lower FoH utility, SHE, and DKA rates reduced QALYs gained to 0.264. Our analysis suggests that rt-CGM is cost-saving and cost-effective vs is-CGM in PwT2D on MDI in the US and can inform US payers of the economic value of different CGM systems. Disclosure H. Alshannaq: Employee; Dexcom, Inc., Other Relationship; Vertex Pharmaceuticals Incorporated. G. J. Norman: Employee; Dexcom, Inc. P. M. Lynch: Employee; Dexcom, Inc., Stock/Shareholder; Dexcom, Inc.

139-LB: Use of Digital Diabetes Solution Is Associated with Improved Glycemic Control without Increased Risk of Severe Hypoglycemia in Adults with Type 2 Diabetes Mellitus in the United States—Retrospective Cohort Study

Background: Dario Diabetes Solution (DDS) is a digital health application (app) that combines blood glucose (BG) monitoring system with a smartphone app, allowing tracking of BG levels in real time. This study assessed effects of DDS on HbA1c levels in adults with type 2 diabetes mellitus (T2DM) with baseline (BL) HbA1c ≥8% and on severe hypoglycemia (SH). Methods: This retrospective cohort analysis included adults with T2DM who used DDS (users) and nonusers from 1JAN2017 to 31OCT2021. BL period was 1 year before index date (users, first DDS registration; nonusers, first claim date in the quarter); follow up was 6 months. DDS users and nonusers were sequentially matched 1:3 using exact and propensity score matching. Secondary endpoints included SH (event requiring medical intervention) rates for all patients (pts) and for pts with BL HbA1c ≥8% who achieved predefined target HbA1c &amp;lt;8%. SH incidence in users vs nonusers was examined. Results: Overall cohort included 568 DDS users and 1699 nonusers: mean age, 57.5±11.3 years; mean BL HbA1c, 9.14±1.83%; oral antidiabetic drugs, 51%; insulin, 6%. BL SH was rare (users, 7/568; nonusers, 12/1699). There were 387 users and 1089 nonusers with BL HbA1c ≥8% (mean BL HbA1c, 10.0±1.7%). In this subgroup, HbA1c &amp;lt;8% was achieved by 9% more DDS users (174/387 [45%]) vs nonusers (393/1089 [36%]) at 6 months; P=0.002. At 6 months, overall SH rate was 38.8 (users) vs 10.6 (nonusers) events/1000 pts per year (incidence rate ratio, 0.9; P=0.9). No observed increase in SH risk was associated with DDS in this population. SH was rare in pts who achieved HbA1c &amp;lt;8% (users, 1/174; nonusers, 3/393). Conclusions: In this retrospective study, a larger proportion of adults with uncontrolled T2DM (BL HbA1c ≥8%) achieved HbA1c &amp;lt;8% after using DDS vs nonusers, with no increased risk of SH. Disclosure N. Thingalaya: None. F. Lee: Employee; Sanofi, Stock/Shareholder; Sanofi. D. Kerr: Consultant; Sanofi-Aventis U. S. P. Potukuchi: None. L. Wilson: Employee; Sanofi. K. C. Lee: Employee; Sanofi. E. K. Han-burgess: Employee; Sanofi. A. Edwards: Employee; Symphony Health, an ICON plc company, Other Relationship; Sanofi. X. Yu: None. A. Kennedy: None. Funding Sanofi

3-OR: Severe Hypoglycemia among Older Adults with Diabetes (iNPHORM, USA)

Despite an aging US diabetes population, little is known about the real-world frequency of iatrogenic severe hypoglycemia (SH) among older adults. We analyzed iNPHORM data to address this gap. People ≥60-year-old with T1DM or T2DM on insulin and/or secretagogues were recruited from a probability-based internet panel. Data on SH were obtained via a screener, baseline, and 12 monthly follow-ups. Crude SH incidence rates (IRs) and proportions (IPs) were calculated overall, and by diabetes type, medication type, and mode of SH recovery. N=307 were analyzed (T1DM: 8.5%; age: 67.5 [SD:5.5] years; male: 54.1%; retention rate: 81.8%). Among T2DM respondents, 39.9% used insulin without secretagogues, 50.2% secretagogues without insulin, and 10.0% insulin and secretagogues. The overall IP of SH was 19.9 (95%CI: 15.8-24.7)%, and the IR was 0.89 (95%CI: 0.62-1.27) events per person-year (EPPY). People with T1DM had a higher total IP (42.3 [95%CI: 25.5-61.1]%) and IR (2.07 [95%CI: 0.98-4.38] EPPY) than those with T2DM (IP: 17.8 [95%CI: 13.8-22.7]%; IR: 0.78 [95%CI: 0.52-1.15] EPPY), including insulin without secretagogue users (1.09 [95%CI: 0.66-1.80] vs. 0.61 [95%CI: 0.26 to 1.45] [insulin with secretagogues] and 0.50 [95%CI: 0.23 to 1.05] [secretagogues without insulin] EPPY). Emergency care and hospitalization constituted 3.6% (T1DM: 0%; T2DM: 6.7%) and 1.8% (T1DM: 0%; T2DM: 2.2%) of SH (n=224), respectively. Paramedical/hospital-based SH was more common in T2DM (0.06 [95%CI: 0.02-0.19]) than T1DM (0 EPPY) with IRs highest among insulin without secretagogue users (0.11 [95%CI: 0.03-0.47] EPPY). This is the first US prospective study on SH frequency in older adults with diabetes. Most (96.4%) events occurred at-home, underscoring the need for self-reported SH capture. Overall IPs and IRs were greater in T1DM than T2DM; but those with T2DM had more healthcare-based events. To mitigate undue health and economic costs, it is imperative clinicians remain vigilant to preventing SH in this vulnerable and growing population. Disclosure A.Ratzki-leewing: Consultant; Novo Nordisk, Eli Lilly and Company, Research Support; Sanofi. J.E.Black: None. G.Zou: None. B.L.Ryan: None. S.B.Harris: Advisory Panel; Bayer Inc., AstraZeneca, Eli Lilly and Company, Dexcom, Inc., Novo Nordisk A/S, Novo Nordisk Canada Inc., Sanofi, Consultant; Abbott Diabetes, Janssen Pharmaceuticals, Inc., Other Relationship; American Diabetes Association, Research Support; Abvance Therapeutics, Canadian Institutes of Health Research. Funding Sanofi Global

A Comparison of Variable Versus Fixed Insulin Infusion Rate on Resolution of Diabetic Ketoacidosis.

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.

Metabolic Control, Diabetic Complications and Drug Therapy in a Cohort of Patients with Type 1 and Type 2 Diabetes in Secondary and Tertiary Care between 2004 and 2019.

Retrospective cross-sectional analysis of four single-centre cohorts between 2004 and 2019. All patients with T1DM or T2DM in secondary care (n = 5571) or tertiary care (n = 2001) were included. Statistical analyses were performed using linear mixed models. Diabetes duration increased in both patients with T1DM and T2DM in secondary care and tertiary care (p < 0.001). Patients in secondary care consistently showed good glycaemic control, while patients in tertiary care showed inadequate glycaemic control. All four cross-sectional cohorts showed a significant increase in the prevalence of nephropathy over time and three out of four cohorts (T1DM and T2DM in secondary care and T2DM in tertiary care) showed an increase in the prevalence of neuropathy (all p < 0.001). The incidence of severe hypoglycaemia was consistently low. The use of insulin pumps and insulin analogues in the therapy of T1DM increased significantly. The increased prevalence of complications is likely due to older age and longer diabetes duration. Low rates of hypoglycaemia, lower limb amputations and good glycaemic control in secondary care patients indicate a good structure of patient care.

Clinical trial validation of the STAR-3D glycemic control framework

Glycemic control (GC) to regulate dysglycemia in critically ill patients is associated with improved outcomes. However, it has been hard to achieve safely due to metabolic variability. Protocol design is critical to provide safe, effective control to all patients. STAR is a unique model-based, patient-specific, and risk-based glycemic control framework accounting for inter- and intra- patient variability using a clinically validated digital twin model. This study presents the first clinical trial results of STAR with a new 3D stochastic model, which was shown to improve predictions of patient-specific insulin sensitivity variability and value in validated virtual trials, and can thus potentially improve glycemic control outcomes.In total, 616 patients are considered in this analysis, totaling 37489 hours of control. Overall, 77% of blood glucose (BG) measurements were in target, with a median BG of 6.7 mmol/L. There was no incidence of severe hypoglycemia (BG < 2.2 mmol/L) and only 0.3% of mild hypoglycemia (BG < 4.0 mmol/L). These results were achieved with a median [25th 75th percentiles] of 4.0 [2.0 6.0] U/h of insulin, and nutrition rates with median 100 [83 100] % of goal feed. These results were consistent when considering per-patient statistics.Using this new tri-variate stochastic model in the STAR glycemic control framework successfully provided extremely safe, effective GC for all patients, with high nutrition intake, despite targeting normoglycemic ranges. High safety from hypoglycemia, high %BG in normoglycemia, and high nutrition delivery are all associated with improved outcome in ICU patients.

Adverse Physiological and Biochemical Effects of Synthetic Human Insulin in Diabetic Type-2 Patients, A Comparative Clinical Study

Background: The use of Synthetic human insulin in diabetic individuals may develop number of serious medical complications in population like Hypoglycemia, Weight gain, Little Skin Depression and Dementia. Aims and Objectives: The aims and objects of current study were to provide awareness about the recent Biochemical and Physiological side effects of Artificial Insulin Therapy for Type 2 Diabetes Mellitus to the people. Study Design: A comparative clinical study. Place and Duration: Present study was conducted in Lahore Medical &amp; Dental College Lahore, The university of Lahore, Lahore, Suleman Roshan medical college Tando Adam Sindh and Allama Iqbal Medical College Lahore Pakistan from March 2021 June 2022. Methodology: Total 450 diabetic type- 2 patients of age 40-60 years were selected for present study and they were divided into three different groups regarding injected units of synthetic insulin. In Group-A 100 male and 50 female were taking 20 units twice a day, whereas 100 male and 50 female individuals with diabetes type-2 of Group-B were injected 30 units twice a day while 80 male and 40 female of Group-C were taking 45 units twice a day respectively. Fasting and Random glucose levels, Body mass index (BMI), levels of Dementia and Skin Depression parameters of each individual were measured and compared group wise. Results: A remarkable significant changes (P≤0.05) in Fasting glucose levels, Random glucose levels after 2 hour of meal, Random glucose levels after 3 hour of meal, Random glucose levels after 4 hour of meal, Body mass index, body mass index after 6 month, body mass index after 12 month, Incidence of severe hypoglycemia of male and female were concluded in group-B and group-C as compared with group-A, because 20 units of insulin created less hypoglycemic effects as compared with 30 and 45 units which were injected in Group-B and Group-C comparatively. Practical implication: Awareness about side effects of artificial Insulin therapy for Type 2 Diabetes Mellitus to the people is so important and helpful for quality of life and safety. Conclusion: The findings of present study were indicated that long term insulin therapy develop hypoglycemia and significant changes (P≤0.05) in BMI in patients with diabetes type-2. It was concluded that a significant (P≤0.05) weight gain in regular user of synthetic insulin diabetic type-2 patients was very common. Keywords: Hypoglycemia, Synthetic insulin, Body mass index, Diabetes Mellitus

ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes.

ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes.

Efficacy and Safety of Analog Insulin in Comparison With Human Insulin for Hyperglycemia in Hospitalized Patients With Acute Stroke: A Randomized, Open-Label, Single-Center Trial

ObjectiveTo assess the efficacy and safety of analog insulins in comparison with human insulins for hyperglycemia in hospitalized patients with acute stroke. MethodsIn 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. ResultsBetween 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). ConclusionHospitalized 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.

External validation and clinical application of the predictive model for severe hypoglycemia.

ObjectiveAn internally validated, one-year risk prediction model for severe hypoglycemia (SH) in type 2 diabetes was evaluated in a general hospital setting to externally verify and validate its performance.Research design and methodsBetween December 2017 to December 2019, 2,645 adult patients with type 2 diabetes who visited the diabetes center were enrolled. The receiver operating characteristics curve and Harrell C-statistics were compared to identify the discrimination of the model. The predicted and actual incidence of SH for one year in the development and validation cohorts were compared by ranking participants by deciles of predicted risk.ResultsThe concordance index was 0.878 in the external validation cohort. The sensitivity and specificity of the predictive model were 0.833 and 0.847, respectively. Based on the predicted risk, we stratified the groups into four categories: low (<0.05%), intermediate (0.05% to <0.5%), high (0.5% to <2.0%), and very high-risk group (≥2.0%). The actual annual incidence of SH gradually increased with the increased risk score level for the decile group (P for trend <0.001). The actual annual SH incidence significantly increased with increase in SH risk scores, which proportionately increased with age, duration of diabetes, glycated hemoglobin, and albuminuria and decreased with body mass index, renal function (p for trends <0.001 for all) in type 2 diabetes.ConclusionOn external validation, the novel one-year SH prediction model showed excellent discrimination in participants with type 2 diabetes and can effectively screen high-risk patients for SH, even in the general hospital setting.

Who are the Best Candidate Patients with Diabetes for Tirzepatide?

Background: Tirzepatide is a dual receptor agonist of the 2 incretin hormones: Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon- Like Peptide-1 (GLP-1) which is was recently approved for treatment of type 2 diabetes. Objective: To define the most appropriate patients that may benefit from tirzepatide. Methods: Pubmed search until August 10, 2022. Search terms were GLP- 1, GIP, tirzepatide, efficacy, safety, obesity. Clinical trials and pertinent animal studies and reviews were included. Results: Tirzepatide was more effective in lowering hemoglobin A1c (HbA1c) levels and body weight than submaximal doses of semaglutide (1.0 mg once-weekly), dulaglutide (1.5 mg once-weekly), insulin degludec (mean daily dose 48.8 U) and insulin glargine (mean daily dose 43.5 U). In patients with type 2 diabetes and Non-Alcoholic Fatty Liver Disease (NAFLD), tirzepatide significantly decreased Liver Fat Content (LVC). Safety profile of tirzepatide was generally similar to that of GLP-1 agonists, but frequency of Gastrointestinal (GI) adverse effects are slightly higher with tirzepatide. Incidence of severe hypoglycemia (blood glucose &lt; 54 mg/dl) is also slightly higher with tirzepatide than semaglutide and dulaglutide, but much lower than insulin degludec and glargine. Drug discontinuation rates due to adverse effects were higher with tirzepatide compared with semaglutide, dulaglutide, and insulin. Conclusions: Tirzepatide may be most appropriate for patients with type 2 diabetes who are obese, as alternative to GLP-1 agonists or basal insulin, and in patients with NAFLD.

Risky self-management behaviors in adolescents with type 1 diabetes: Measurement validation for the Diabetes-Specific Risk-Taking Inventory.

Among persons with type 1 diabetes (T1D), adolescents often experience the greatest challenge achieving optimal treatment engagement and glycemic targets. Risk-taking behaviors often increase during adolescence and may interfere with engagement in T1D care. We developed the Diabetes-Specific Risk-Taking Inventory (DSRI) to assess risky T1D self-management behaviors in adolescents with T1D. In the current study, we aimed to examine the DSRI's psychometric properties. We surveyed a national sample of 224 adolescents from the T1D Exchange registry (M age=16.9 ± 1.1, 49% female, M A1c=8.5% ± 1.3, 76.8% on insulin pumps) in a cross-sectional design. Participants completed the DSRI and measures of engagement, general risk-taking, and executive functioning and reported on incidence of severe hypoglycemia and diabetic ketoacidosis over the past year. The DSRI demonstrated reliability (internal consistency: α=0.89; test-retest reliability: r=0.86, p < 0.01). Concurrent validity was demonstrated through significant associations between the DSRI and T1D engagement (r=-0.75), general risk-taking (r=0.57), executive dysfunction (r=0.34), and report of severe hypoglycemia over the past year (r=0.22). The DSRI accounted for unique variance in adolescents' most recent glycated hemoglobin, above and beyond other variables, indicating its incremental validity. Overall, initial psychometrics suggest the DSRI is a reliable and valid measure of risks that adolescents may take with their T1D care. This innovative self-report measure has potential to be an actionable clinical tool to screen for high-risk behaviors not routinely assessed in T1D clinical care.

Effect of Different Glucose Monitoring Methods on Bold Glucose Control: A Systematic Review and Meta-Analysis.

Objective To evaluate the effectiveness of different glucose monitoring methods on blood glucose control and the incidence of adverse events among patients with type 1 diabetes mellitus. Methods Using the method of literature review, the databases PubMed, Cochrane, and Embase were retrieved to obtain relevant research literature, and the selected studies were analyzed and evaluated. This study used Cochrane software RevMan5.4 to statistically analyze all the data. Results A total of 15 studies were included in this study, including 10 randomized controlled trials and 5 crossover design trials, with a total of 2071 patients. Meta-analysis results showed that continuous blood glucose monitoring (CGM) could significantly reduce the HbA1c level of patients, weighted mean difference (WMD) = −2.69, 95% confidence interval (CI) (-4.25, -1.14), and P < 0.001 compared with self-monitoring of blood glucose (SMBG). Meanwhile, the incidence of severe hypoglycemia in the CGM group was significantly decreased, risk ratio (RR) = 0.52, 95% CI 0.35-0.77, and P = 0.001. However, there was no statistical difference in the probability of diabetic ketoacidosis between CGM and SMBG groups, RR = 1.34, 95% CI 0.57-3.15, and P = 0.5. Conclusion Continuous blood glucose monitoring is associated with lower blood glucose levels than the traditional blood glucose self-test method.