Insulin Analogs and the Mode of Insulin Delivery: Recent Advances and Challenges.

Diabetes is a medical condition associated with impaired glucose regulation caused either due to insufficient insulin production or resistance to insulin (Type 2 diabetes, gestational diabetes) or the absence of insulin through the selective killing of beta cells in the pancreas (Type 1 diabetes). Irregular insulin production leads to various health complications. To prevent such complications, patients must adhere to medical recommendations before availing of any advanced insulin therapy(ies), considered productive for the treatment. Natural insulin, although highly effective in controlling blood glucose levels, patients are often at risk of developing hypoglycemia and many other complications. This has led to the development of insulin analogs, the modified variants of natural insulin having a minimal risk of causing hypoglycemia. Besides the development of analogs, the mode of insulin delivery is also considered critical in achieving better glycemic control in diabetic patients. Until recently, various exogenous insulin delivery methods were practiced, but effective glycemic control without any associated risk and ease of delivery remains a subject of paramount concern. It countered attenuation or delayed onset of diabetes-associated complications without a permanent cure, raising an unmet demand for insulin formulations and delivery methods that offer stability, biocompatibility, reproducibility, precision dosing, non-immunogenicity, and safety. The current practice utilizes non-physiological delivery methods with less invasive administration routes, offering glycemic stability and therapeutic effectiveness. This review focuses on the recent advances made and future perspectives envisioned about newer insulin therapies and delivery methods that tend to improve the management of diabetes by inculcating ideas to reduce the disease's severity and improve the quality of life.

Impact of empagliflozin on insulin needs in patients with heart failure and diabetes: An EMPEROR-Pooled analysis.

AIM: To assess the effect of empagliflozin on patients with comorbid heart failure (HF) and diabetes with or without baseline insulin, and to study the impact of empagliflozin on insulin requirements over time. MATERIALS AND METHODS: We performed a post-hoc analysis of pooled patient-level data from two cardiovascular outcomes trials of empagliflozin in HF (EMPEROR-Reduced and EMPEROR-Preserved trials). We undertook a subgroup analysis stratified by baseline insulin use, including all patients with diabetes. The studied endpoints included the primary composite endpoint of first hospitalization for HF or cardiovascular death, rate of decline of estimated glomerular filtration rate, composite renal outcome and rates of sustained insulin initiation. RESULTS: Among 4794 patients with diabetes, 1333 (658 in empagliflozin, 675 in placebo) were using insulin at baseline. The treatment effect of empagliflozin on the primary endpoint was consistent irrespective of insulin use [no insulin, hazard ratio 0.74, 95% confidence interval (CI) 0.63-0.86; using insulin, hazard ratio 0.81, 95% CI 0.66-1.00, pinteraction = .49], as was the effect on the rate of decline of the estimated glomerular filtration rate (pinteraction = .75). There was no effect of empagliflozin on the composite renal outcome in patients using or not using insulin (pinteraction = .30). Among patients not using insulin at baseline, those randomized to empagliflozin initiated insulin less frequently throughout the follow-up period compared with those receiving placebo (2.6% vs. 3.8%, odds ratio 0.66, 95% CI 0.50-0.88). CONCLUSIONS: Empagliflozin exerts a consistent benefit on cardiovascular outcomes and renal function decline, irrespective of baseline insulin use, and reduces the need for sustained insulin initiation in patients with HF and diabetes.

C-peptide index at 2 h post-meal is a useful predictor of endogenous insulin secretory capacity and withdrawal from insulin therapy in subjects with type 2 diabetes.

AIMS: To evaluate the correlation between C-peptide index (CPI) at 2 h post-meal and endogenous insulin secretory capacity and to develop clinical models to predict the possibility of withdrawal from insulin therapy in patients with type 2 diabetes. METHOD: This was a single-centre retrospective study of patients with type 2 diabetes admitted to our hospital. Patients were divided into a withdrawal group (n = 72) and a non-withdrawal group (n = 75) based on whether they were able to withdraw from insulin therapy at discharge, and the correlation between CPI at 2 h after meal and diabetes-related parameters was evaluated. In addition, we created two clinical models to predict the possibility of withdrawal from insulin therapy using machine learning. RESULTS: The glycated haemoglobin values of the study participants were 87.8 ± 22.6 mmol/mo. The CPI at 2 h post-meal was 1.93 ± 1.28 in the non-withdrawal group and 2.97 ± 2.07 in the withdrawal group (p < 0.001). CPI at 2 h post-meal was an independent predictor of withdrawal from insulin therapy. In addition, CPI at 2 h post-meal was a better predictor than fasting CPI. Six factors associated with insulin therapy withdrawal (age, duration of diabetes, creatinine, alanine aminotransferase, insulin therapy until hospitalization, and CPI at 2 h post-meal) were used to generate two clinical models by machine learning. The accuracy of the generated clinical models ranged from 78.3% to 82.6%. CONCLUSION: The CPI at 2 h post-meal is a clinically useful measure of endogenous insulin secretory capacity under non-fasting conditions.

Barriers to the Use of Insulin Therapy and Potential Solutions: A Narrative Review of Perspectives from the Asia-Pacific Region.

The rising prevalence of type 2 diabetes (T2D) is posing major challenges for the healthcare systems of many countries, particularly in the Asia-Pacific Region, in which T2D can present at younger ages and lower body mass index when compared with Western nations. There is an important role for insulin therapy in the management of T2D in these nations, but available evidence suggests that insulin is under-utilized and often delayed, to the detriment of patient prognosis. The authors of this article gathered as an advisory panel (representative of some of the larger Asia-Pacific nations) to identify their local barriers to insulin use in T2D, and to discuss ways in which to address these barriers, with their outputs summarized herein. Many of the key barriers identified are well-documented issues of global significance, including a lack of healthcare resources or of an integrated structure, insufficient patient education, and patient misconceptions about insulin therapy. Barriers identified as more innate to Asian countries included local inabilities of patients to afford or gain access to insulin therapy, a tendency for some patients to be more influenced by social media and local traditions than by the medical profession, and a willingness to switch care providers and seek alternative therapies. Strategies to address some of these barriers are provided, with hypothetical illustrative case histories.

The IDEAL (Insulin therapy DE-intensificAtion with iglarLixi) Randomised Controlled Trial-Study Design and Protocol.

INTRODUCTION: Multiple daily injection insulin regimen (MDI) represents the most intensive insulin regimen used in the management of people with type 2 diabetes (PwT2D). Its efficacy regarding glycaemic control is counterbalanced by the increased risk of hypoglycaemia, frequently observed tendency to weight gain and necessity for frequent glucose monitoring. Recent introduction of novel antidiabetic medications with pleiotropic effects reaching far beyond the reduction of glycaemia (HbA1c), such as the glucagon-like peptide 1 receptor agonist (GLP-1 RA), has significantly widened the therapeutic options available for management of T2D. Consequently, there is currently a substantial number of PwT2D for whom the MDI regimen was initiated at a time when no other options were available. Yet, in present times, these individuals could benefit from simplified insulin regimens ideally taking advantage of the beneficial effects of the novel classes of antidiabetic medications. iGlarLixi (Suliqua®) is a once-daily fixed-ratio combination of basal insulin analogue glargine 100 U/ml and a GLP-1 RA lixisenatide. METHODS: Insulin therapy DE-intensificAtion with iglarLixi (IDEAL) is a six-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period examining the efficacy and safety of MDI regimen de-intensification with once-daily administration of iGlarLixi versus MDI regimen continuation in PwT2D on a backgroud therapy with metformin ± sodium-glucose cotransporter 2 inhibitor. PLANNED OUTCOMES: The primary objective is to compare the effects of MDI therapy de-intensification with iGlarLixi versus MDI regimen continuation regarding glycaemic control (HbA1c). Secondary objectives include detailed evaluation of the effects of MDI regimen de-intensification with iGlarLixi on glycaemic control using standardised continuous glucose monitoring (CGM) metrics and self-monitoring of plasma glucose. Furthermore, body weight and body composition analysis, quality of life and safety profile are evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04945070.

Reduction in Diabetes-Related Hospitalizations and Medical Costs After Dexcom G6 Continuous Glucose Monitor Initiation in People with Type 2 Diabetes Using Intensive Insulin Therapy.

INTRODUCTION: Some people with type 2 diabetes (T2D) require intensive insulin therapy to manage their diabetes. This can increase the risk of diabetes-related hospitalizations. We hypothesize that initiation of real-time continuous glucose monitoring (RT-CGM), which continuously measures a user's glucose values and provides threshold- and trend-based alerts, will reduce diabetes-related emergency department (ED) and inpatient hospitalizations and concomitant costs. METHODS: A retrospective analysis of US healthcare claims data using Optum's de-identified Clinformatics® Data Mart database was performed. The cohort consisted of commercially insured, CGM-naïve individuals with T2D who initiated Dexcom G6 RT-CGM system between August 1, 2018, and March 31, 2021. Twelve months of continuous health plan enrollment before and after RT-CGM initiation was required to capture baseline and follow-up rates of diabetes-related hospitalizations and associated healthcare resource utilization (HCRU) costs. Analyses were performed for claims with a diabetes-related diagnosis code in either (1) any position or (2) first or second position on the claim. RESULTS: A total of 790 individuals met the inclusion criteria. The average age was 52.8 (10.5) [mean (SD)], 53.3% were male, and 76.3% were white. For claims with a diabetes-related diagnosis code in any position, the number of individuals with ≥ 1 ED visit decreased by 30.0% (p = 0.01) and with ≥ 1 inpatient visit decreased by 41.5% (p < 0.0001). The number of diabetes-related visits and average number of visits per person similarly decreased by at least 31.4%. Larger relative decreases were observed for claims with a diabetes-related diagnosis code in the first or second position on the claim. Total diabetes-related costs expressed as per-person-per-month (PPPM) decreased by $341 PPPM for any position and $330 PPPM for first or second position. CONCLUSION: Initiation of Dexcom G6 among people with T2D using intensive insulin therapy was associated with a significant reduction in diabetes-related ED and inpatient visits and related HCRU costs. Expanded use of RT-CGM could augment these benefits and result in further cost reductions.

Role of nutritional therapy on dietary habits and glycemic control in insulin-treated kidney transplant patients with diabetes.

AIMS: To evaluate the effect of nutritional therapy on glycemic compensation and key cardio-renal risk markers in patients with diabetes and kidney transplant, on insulin treatment by Multiple Daily Injection (MDI) or Continuous Subcutaneous Insulin Infusion (CSII). METHODS: 34 patients with diabetes on insulin treatment and kidney transplant recipients were enrolled;12 participated in the structured nutritional program (intervention group), 22 patients (control group) did not receive nutritional protocol. Both groups were then divided into subgroups according to the method of insulin administration (MDI and CSII). RESULTS: Statistically significant reduction in fasting blood glucose values, glycosylated hemoglobin (HbA1c) and glycosuria were observed in both groups at the end of the study. The intervention group, significantly reduced total cholesterolemia and the glycemic index, together with reduced dietary intake of lipids, cholesterol, soluble carbohydrates and increased consumption of carbohydrates and fiber. These improvements were even more pronounced in patients treated with CSII. CONCLUSIONS: A proper nutritional approach optimize glycometabolic outcomes and contribute significantly to the reduction of the major cardiovascular risk factors in renal transplant patients.

Exogenous Insulin Therapy Is Associated with the Risk of Advanced Colorectal Adenoma in Patients with Diabetes Mellitus.

BACKGROUND/AIMS: Exogenous insulin therapy increases systemic exposure to insulin which may promote the development of colorectal neoplasia. We sought to evaluate the association between exogenous insulin therapy and the incidence of advanced adenoma in type 2 diabetes mellitus. METHODS: A retrospective cohort study was conducted from January 1, 2007, to January 1, 2018, in a regional health system serving the United States Philadelphia metropolitan area, Central New Jersey, and South Central Pennsylvania. Study patients consisted of a random sample of patients with type 2 diabetes mellitus aged 40-80 years who had undergone two rounds of colonoscopy examinations. The exposure was cumulative duration of insulin therapy (i.e., no use, 1-365 days and > 365 days). The outcome was time to incident advanced adenoma. RESULTS: Of the 975 eligible patients, 184 patients accumulated > 365 days of insulin therapy before the follow-up colonoscopy. The mean (standard deviation) duration between the two rounds of colonoscopy examination was 5.1 (2.9) years among the insulin users and 5.3 (3.9) years among non-users. Compared to no insulin exposure, receiving > 365 days of insulin therapy was associated with an increased incidence of advanced adenoma (adjusted hazard ratio [aHR] 4.84, 95% confidence interval [CI] 2.82-8.30), right-sided advanced adenoma (aHR 5.48, 95% CI 2.90-10.35), and 3 or more adenomas (aHR 2.61, 95% CI 1.46-4.69) at the follow-up colonoscopy examination. CONCLUSION: Insulin therapy is associated with an increased risk of advanced adenoma and may serve as a novel risk-stratification factor to enhance the efficiency of existing colorectal cancer screening and surveillance programs.

Rapid improvement of severe fatty liver in a case of fulminant type 1 diabetes following insulin treatment.

A 36-year-old woman presented to the emergency room with a consciousness disorder after developing abdominal pain with diarrhea for 2 days. She presented with marked hyperglycemia, ketoacidosis, and increased serum free fatty acid (FFA) levels; however, no elevation in the glycated hemoglobin (HbA1c) levels was observed. Based on the marked depletion of insulin secretion, the patient was diagnosed as diabetic ketoacidosis attributed to fulminant type 1 diabetes (FT1D). Computed tomography on admission revealed severe fatty liver (FL), which improved 17 h following insulin treatment. Insulin treatment also suppressed the serum FFA levels. Some cases of FT1D with FL and liver dysfunction have been reported previously; however, its pathogenesis and clinical course remain unclear. Compared to previous reports, this case reported the shortest time for FL improvement. In this case, rapid and severe insulin deficiency led to a markedly high FFA level and significant accumulation of triglycerides in the hepatocytes, resulting in severe FL. A rapid and large dose of insulin was administered when systemic insulin sensitivity was nearly maximal owing to insulin deficiency, increased insulin efficacy, early reduction of FFA, suppressed triglyceride accumulation in the hepatocytes, and increased triglyceride excretion from the liver. All these factors could have contributed to the rapid improvement in FL.

Real-World Outcomes of Individualized Targeted Therapy with Insulin Glargine 300 Units/mL in Insulin-Naïve Korean People with Type 2 Diabetes: TOBE Study.

INTRODUCTION: The TOujeo BEyond glucose control (TOBE) study evaluated clinical outcomes with insulin glargine 300 units/mL (Gla-300) in insulin-naïve Korean people with type 2 diabetes mellitus (T2DM) in a real-world setting. METHODS: This 24-week, prospective, non-interventional, multicenter, open-label, single-arm, observational study included adults aged ≥ 20 years with T2DM suboptimally controlled with oral hypoglycemic agents and/or glucagon-like peptide 1 receptor agonists who require basal insulin. Eligible participants were assigned to either general target glycated hemoglobin (HbA1c < 7%) or individualized target groups as per physician's discretion considering guidelines and participants' characteristics. The primary endpoint was the proportion of participants achieving the HbA1c target (individualized or general) at 24 weeks. RESULTS: Among 369 participants, 19.5% (72/369) of participants achieved the HbA1c target at week 24; 37.5% (33/88) in the individualized and 13.9% (39/281) in the general target group. In both target groups, similar reductions in fasting plasma glucose and body weight were observed, with low incidence of hypoglycemia, and T2DM duration was significantly shorter in participants who did versus those who did not achieve the target HbA1c (individualized target group: 9.6 ± 8.0 versus 13.1 ± 8.4 years, P = 0.0454; general target group: 10.2 ± 8.6 versus 12.8 ± 7.4 years, P = 0.0378). CONCLUSIONS: This study showed that initiation of insulin therapy with Gla-300 in people with T2DM using an individualized approach is more effective in achieving an HbA1c target. Moreover, earlier initiation of insulin therapy in people with suboptimally controlled T2DM may increase the success rate of glycemic control. A graphical abstract is available with this article.

Despite various efforts in managing diabetes, individuals with type 2 diabetes mellitus (T2DM) encounter numerous challenges to achieve good glycemic control. The major cause is failure to initiate insulin therapy in a timely manner, primarily because of the fear of hypoglycemia. Insulin glargine 300 units/mL (Gla-300) has smooth and prolonged activity resulting in stable and sustained glycemic control, thus reducing the risk of hypoglycemia. Studies on efficacy and safety of Gla-300 in various populations have been published globally. However, there are limited real-world studies in Asian populations. This study evaluated effectiveness and safety of Gla-300 in Korean people with T2DM who were not on insulin prior to this study but were taking oral glucose-lowering medications. The participants were assigned to two groups: general glycated hemoglobin (HbA1c) target (HbA1c < 7%) and individualized HbA1c target according to the participant's characteristics. Results showed that Gla-300 helped to achieve the glycemic target more effectively using an individualized approach. In both groups, similar reductions in fasting plasma glucose and body weight were observed, with low incidence of hypoglycemia. People who achieve glycemic target had a shorter duration of T2DM than those who did not achieve their glycemic target. This suggests that earlier insulin initiation may be a better approach and may increase the success rate of insulin therapy.

A short-term economic evaluation of early insulin therapy compared to oral anti-diabetic drugs in order to reduce the major adverse events in type 2 diabetes patients in Iran.

OBJECTIVE: While there are some recommendations about early insulin therapy in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients, there is not sufficient evidence on this strategy's cost-effectiveness. This study compared early insulin therapy versus oral anti-diabetic drugs (OADs) for managing T2DMusing a cost-effectiveness analysis approach in Iran. METHODS: In this economic evaluation, a decision analytic model was designed. The target population was newly diagnosed type 2 diabetic patients, and the study was carried out from the perspective of Iran's healthcare system with a one-year time horizon. Basal insulin, Dipeptidyl peptidase-4 (DPP-4) inhibitors, and Thiazolidinediones (TZDs) were compared in this evaluation. The main outcome for assessing the effectiveness of each intervention was the reduction in the occurrence of diabetes complications. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and deterministic and probabilistic sensitivity analyses were carried out. RESULTS: The DPP-4 inhibitors strategy was the dominant strategy with the highest effectiveness and the lowest cost. Early insulin therapy was dominated (ICER: $-53,703.18), meaning that it was not cost-effective. The sensitivity analyses consistently affirmed the robustness of the base case findings. The probabilistic sensitivity analysis indicated probabilities of 77%, 22%, and 1% for DPP-4 inhibitors, TZDs strategies, and early insulin therapy, respectively, in terms of being cost-effective. CONCLUSION: In terms of cost-effectiveness, early insulin therapy was not cost-effective compared to OADs for managing newly diagnosed T2DM patients. Future studies in this regard, utilizing more comprehensive evidence, can yield more accurate results.

The effect of bolus advisors on glycaemic parameters in adults with diabetes on intensive insulin therapy: A systematic review with meta-analysis.

AIM: To conduct a systematic review with meta-analysis to provide a comprehensive synthesis of randomized controlled trials (RCTs) and prospective cohort studies investigating the effects of currently available bolus advisors on glycaemic parameters in adults with diabetes. MATERIALS AND METHODS: An electronic search of PubMed, Embase, CINAHL, Cochrane Library and ClinicalTrials.gov was conducted in December 2022. The risk of bias was assessed using the revised Cochrane Risk of Bias tool. (Standardized) mean difference (MD) was selected to determine the difference in continuous outcomes between the groups. A random-effects model meta-analysis and meta-regression were performed. This systematic review was registered on PROSPERO (CRD42022374588). RESULTS: A total of 18 RCTs involving 1645 adults (50% females) with a median glycated haemoglobin (HbA1c) concentration of 8.45% (7.95%-9.30%) were included. The majority of participants had type 1 diabetes (N = 1510, 92%) and were on multiple daily injections (N = 1173, 71%). Twelve of the 18 trials had low risk of bias. The meta-analysis of 10 studies with available data on HbA1c showed that the use of a bolus advisor modestly reduced HbA1c compared to standard treatment (MD -011%, 95% confidence interval -0.22 to -0.01; I2 = 0%). This effect was accompanied by small improvements in low blood glucose index and treatment satisfaction, but not with reductions in hypoglycaemic events or changes in other secondary outcomes. CONCLUSION: Use of a bolus advisor is associated with slightly better glucose control and treatment satisfaction in people with diabetes on intensive insulin treatment. Future studies should investigate whether personalizing bolus advisors using artificial intelligence technology can enhance these effects.

Epidemiological parameters and monitoring of analysis of treatment of children and adolescents with type 1 diabetes mellitus in insulin pump therapy with modified educational program.

OBJECTIVE: Aim: The aim of the present published work is efficacy evaluation of the modified educational program in achieving the target levels of glycemia in children and adolescents with type 1 diabetes mellitus in pump insulin therapy in Almaty.. PATIENTS AND METHODS: Materials and Methods: This study involved 125 children and adolescents with type 1 DM and evaluated the effectiveness of a modified educational program at the School of Type 1 Diabetes Mellitus. Participants were divided into subgroups based on their method of glycemia evaluation. The program's effectiveness was assessed through pre-and post-training questionnaires and measurement of glycohemoglobin levels. Statistical analysis was conducted using the Statistica application. RESULTS: Results: The study evaluated the effectiveness of a modified educational program for children and adolescents with type 1 DM. The results indicated that those who participated in the modified program demonstrated significant improvements in their knowledge and ability to manage their diabetes. They were able to correctly answer 80-90% of the questionnaire questions six months to a year after the training. Additionally, those in the modified program exhibited better carbohydrate metabolism rates and achieved higher rates of their individual treatment goals, especially when using the FreeStyle Libre system for continuous monitoring of blood glucose levels. These findings suggest that a modified educational approach can significantly enhance diabetes management and treatment outcomes in children and adolescents. CONCLUSION: Conclusions: The study concluded that a modified educational program leads to better target therapy levels in children and adolescents with type 1 diabetes mellitus, highlighting the importance of motivated parents and frequent blood glycemia measurements.

Glucagon-like peptide-1 receptor agonists as a possible intervention to delay the onset of type 1 diabetes: A new horizon.

Type 1 diabetes (T1D) is a chronic autoimmune condition that destroys insulin-producing beta cells in the pancreas, leading to insulin deficiency and hyper-glycemia. The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels. However, this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells. Recent research has explored the potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as a novel intervention to modify the disease course and delay the onset of T1D. GLP-1RAs are medications initially developed for treating type 2 diabetes. They exert their effects by enhancing glucose-dependent insulin secretion, suppressing glucagon secretion, and slowing gastric emptying. Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D. This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D, possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells. This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification, which should open new avenues for preventing and treating T1D, improving the quality of life and long-term outcomes for individuals at risk of T1D.

Temporal trends in the starting of insulin therapy in type 2 diabetes in Italy: data from the AMD Annals initiative.

AIMS: Opportunities and needs for starting insulin therapy in Type 2 diabetes (T2D) have changed overtime. We evaluated clinical characteristics of T2D subjects undergoing the first insulin prescription during a 15-year-observation period in the large cohort of the AMD Annals Initiative in Italy. METHODS: Data on clinical and laboratory variables, complications and concomitant therapies and the effects on glucose control after 12 months were evaluated in T2D patients starting basal insulin as add-on to oral/non-insulin injectable agents, and in those starting fast-acting in add-on to basal insulin therapy in three 5-year periods (2005-2019). RESULTS: We evaluated data from 171.688 T2D subjects who intensified therapy with basal insulin and 137.225 T2D patients who started fast-acting insulin. Overall, intensification with insulin occurred progressively earlier over time in subjects with shorter disease duration. Moreover, the percentage of subjects with HbA1c levels > 8% at the time of basal insulin initiation progressively decreased. The same trend was observed for fast-acting formulations. Clinical characteristics of subjects starting insulin did not change in the three study-periods, although all major risk factors improved overtime. After 12 months from the starting of basal or fast-acting insulin therapy, mean HbA1c levels decreased in all the three investigated time-periods, although mean HbA1c levels remained above the recommended target. CONCLUSIONS: In this large cohort of T2D subjects, a progressively earlier start of insulin treatment was observed during a long observation period, suggesting a more proactive prescriptive approach. However, after 12 months from insulin prescription, in many patients, HbA1c levels were still out-of-target.

Decreased circulating dipeptidyl peptidase-4 activity after short-term intensive insulin therapy predicts clinical outcomes in patients with newly diagnosed type 2 diabetes.

Background: This study aims to investigate the changes in circulating dipeptidyl peptidase-4 (DPP-4) activity following short-term intensive insulin therapy (SIIT) in newly diagnosed type 2 diabetes (T2D) patients and to assess its potential in predicting long-term remission. Methods: Ninety-five patients underwent SIIT for 2-3 weeks to attain and sustain near-normal glycemia. Insulin was then discontinued, and patients were followed for a year to evaluate glycemic outcomes. Biochemical tests, serum DPP-4 activity, and mixed meal tolerance tests were conducted at baseline, post-SIIT, and the 3-month follow-up. Results: DPP-4 activity decreased from 44.08 ± 9.58 to 40.53 ± 8.83 nmol/min/mL after SIIT (P<0.001). After three months post-SIIT, DPP-4 activity remained stable in the remission group (39.63 ± 8.53 nmol/L) but increased in the non-remission group (42.34 ± 6.64 nmol/L). This resulted in a more pronounced decrease in DPP-4 activity from baseline in the remission group (-3.39 ± 8.90 vs. -1.10 ± 8.95, P = 0.035). Logistic regression analyses showed that patients with greater DPP-4 activity reduction had a higher likelihood of 1-year remission (70% vs. 51.1%, OR: 7.939 [1.829, 34.467], P = 0.006 in the fully adjusted model). A non-linear relationship between △DPP-4 and 1-year remission rate was observed, with a clear threshold and saturation effect. Conclusion: Circulating DPP-4 activity significantly decreases after SIIT. The change in circulating DPP-4 activity during the 3-month post-treatment phase has the potential to predict long-term remission.

Errors in diabetic insulin therapy and the vitality of proper precautions in Bangladesh: Real-life insights from the developing world.

Background: Insulin therapy errors can have life-threatening consequences in patients with diabetes. Given the increasing prevalence of diabetes and insulin therapy in Bangladesh, it is crucial to identify and prevent these errors. This study uses case-based clinical experiences to thematically analyze insulin therapy errors and propose preventive measures. The study aims to provide valuable insights into the challenges faced in managing insulin therapy in a developing country setting and the importance of involving various stakeholders. Materials and Methods: This is a qualitative research that used a case study approach to identify and analyze errors in insulin therapy in diabetic patients who had experienced adverse clinical consequences. The cases were thematically analyzed to generate insights into current global health problems resulting from erroneous insulin therapy. Results: The two case studies highlight potential risks of errors in insulin therapy, including poor glycemic control, complications, and death. The analysis also highlights the importance of careful monitoring, checks, and communication among health-care providers, patients, and pharmacists to prevent such errors. In addition, it emphasizes the need for education and awareness among patients and health-care providers to ensure safe and effective insulin therapy. Conclusion: Accurate insulin therapy is crucial for diabetes management and preventing adverse outcomes. Identified themes emphasize improved communication, education, and monitoring to minimize therapy errors. Insights from this study can inform policies and practices for better patient outcomes. Further research can identify the root causes and develop interventions to prevent errors, leading to improved quality of life for diabetics.

Future of Time-in-Range Goals in the Era of Advanced Hybrid Closed-Loop Automated Insulin Delivery Systems.

The concept of maintaining blood glucose levels within the 70-180 mg/dL range, known as time-in-range, has raised questions regarding its representation of true physiological euglycemia. Some have speculated that focusing on the time spent within the 70-140 mg/dL range, introduced as time in tight range (TITR) through the International Consensus statement, could serve as a more precise metric for assessing normoglycemia in individuals with type 1 diabetes. This article delves into the current status of TITR as an emerging marker and explores how advanced hybrid closed-loop systems may offer a promising avenue for achieving this higher level of glycemic control.

Insulin Pump Therapy vs Multiple Daily Insulin Injections for Glycemic Control in Children With Type 1 Diabetes: A Systematic Review and Meta-Analysis.

Type 1 diabetes mellitus (T1DM), characterized by the autoimmune destruction of pancreatic beta cells and consequent insulin deficiency, leads to various complications. Management primarily focuses on optimal glycemic control through intensive insulin therapy, either via multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) using insulin pumps, which offer flexibility and improved basal insulin delivery. Despite the benefits of insulin pumps, such as reduced hypoglycemia risk and better mealtime insulin management, they pose challenges such as complexity in site changes and potential ketoacidosis due to tubing issues. This systematic review adheres to PRISMA guidelines and compares CSII with MDI in children and adolescents with T1DM, concentrating on outcomes such as glycemic control measured with HbA1c and glucose levels. The review includes studies meeting stringent criteria, encompassing a broad range of methodologies and geographies. The findings of this meta-analysis indicate the differences in glycemic control with CSII compared to MDI. However, significant heterogeneity in results and methodological variations across studies necessitate cautious interpretation. The study underscores the potential of CSII in offering better control for some patients, supporting a more personalized approach to T1DM management. It highlights the need for further research to understand the long-term effects and to refine treatment protocols, considering the variations in healthcare systems, treatment approaches, and patient demographics globally.

A case-control study to evaluate irisin levels in patients with type 1 diabetes mellitus.

BACKGROUND: Irisin is a precious hormone-like myokine that plays a key role in glucose/energy expenditure and metabolic regulation This paper aimed to determine the irisin levels in patients with type 1 diabetes mellitus and their correlation with insulin therapy and glycaemic control. METHODS: Ninety type 1 diabetes mellitus patients were collected. The patients were subdivided into two groups: group I (37) newly diagnosed type 1 diabetes mellitus and group II (53) T1DM (on insulin injection); for comparison, 30 healthy individuals were included as control. The serum levels of irisin were estimated using ELISA. FSG and lipid profile were measured through spectrophotometrically. Glycated hemoglobin was determined using High-performance liquid chromatography. RESULT: Serum levels of irisin were significantly lower (P = 0.01), as compared to the control group. Also irisin level was significantly lower in group I compared to group II. Fasting serum glucose, glycated hemoglobin, and lipid profile were significantly elevated in patient groups compared to the control group. Serum irisin was negatively correlated to fasting serum glucose, and glycated hemoglobin, whereas it positively correlated to serum lipid profile. In multiple stepwise regression, only glycated hemoglobin (ß = - 0.600, P = 0.040) was determined as an independent predictor for predicting the irisin levels. The AUC was excellent (AUC = 0.996, P = 0.0001), with high diagnostic accuracy (88.2) in differentiating newly diagnosed type 1 diabetes mellitus from the healthy subject group. CONCLUSION: We demonstrated low irisin levels in type 1 diabetes mellitus and the association of the highest irisin amounts to an insulin therapy and a better glycaemic control. Furthermore, the measurement of irisin levels could be useful as laboratory markers to monitor type 1 diabetes mellitus severity and therapy response.