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.

Fracture risk revisited: Bone mineral density T-score and fracture risk in type 2 diabetes.

AIM: To study the association between femoral neck (FN) bone mineral density (BMD) T-score and fracture risk in individuals with and without type 2 diabetes (T2D). MATERIALS AND METHODS: We performed a single-centre retrospective cohort study using the Danish National Health Service. BMD of the FN was measured by dual-energy X-ray absorptiometry. Cox proportional hazards regression models were used to study the association between FN BMD T-score and fractures in individuals with and without T2D separately, adjusted for age, comorbidities and comedication. The results from this analysis were used to estimate the 10-year absolute fracture risk. RESULTS: In total, there were 35,129 women (2362 with T2D) and 7069 men (758 with T2D). The FN BMD T-score was significantly associated with risk of any, hip and major osteoporotic fracture in men and women with [adjusted hazard risk ratios (aHR) women, hip: 1.57; 95% confidence interval (CI) 1.24-2.00, incidence rate (IR) 8.7; aHR men, hip: 1.55; 95% CI 1.01-2.36, IR 4.6] and without T2D (aHR women, hip: 1.75; 95% CI 1.64-1.87, IR 7.0; aHR men, hip: 1.97, 95% CI 1.73-2.25, IR 6.3), and its ability to predict fracture risk was similar. Fracture IRs were not significantly different for individuals with or without T2D, nor was the estimated cumulative 10-year fracture risk. CONCLUSIONS: The FN BMD T-score was significantly associated with hip, non-spine and major osteoporotic fracture risk in men and women with and without T2D. Fracture risk for a given T-score and age was equal in individuals with and without T2D, as was the ability of the FN BMD T-score to predict fracture risk.

Efficacy and safety of once-weekly insulin icodec versus once-daily basal insulin in Japanese individuals with type 2 diabetes: A subgroup analysis of the ONWARDS 1, 2 and 4 trials.

AIM: To explore the efficacy and safety of once-weekly insulin icodec (icodec) in Japanese adults (≥20 years old) with type 2 diabetes from the global ONWARDS 1, 2 and 4 trials. MATERIALS AND METHODS: Insulin-naive (ONWARDS 1) and insulin-experienced (ONWARDS 2 and 4) individuals were randomized to icodec or a once-daily insulin comparator: insulin glargine U100 [ONWARDS 1 (basal insulin only) and 4 (basal-bolus regimen)] or insulin degludec [ONWARDS 2 (basal insulin only)]. The primary outcome was change in glycated haemoglobin from baseline to end of treatment (EOT) (ONWARDS 1: Week 52; ONWARDS 2 and 4: Week 26). Here, we present the Japanese subgroup results. RESULTS: Similar reductions in glycated haemoglobin from baseline to EOT were observed in each trial for icodec and comparators. The proportion of time in range (blood glucose 3.9-10.0 mmol/L) at EOT was also comparable across treatment groups (time in range: 58%-68%), as was time spent with blood glucose below 3.0 mmol/L (<1.0%). Combined clinically significant (blood glucose <3.0 mmol/L) or severe (requiring external assistance for recovery) hypoglycaemia rates were low, with no severe events (ONWARDS 1 and 2) or a single severe event (ONWARDS 4; icodec group) reported. These results generally aligned with findings from the respective global populations. No new safety issues were identified. CONCLUSIONS: Icodec improved glycaemic control to a similar degree as once-daily basal insulin comparators while maintaining low levels of clinically significant or severe hypoglycaemia. The findings support icodec use in Japanese individuals with different levels of type 2 diabetes progression.

Detection of hypoglycaemia in type 1 diabetes through breath volatile organic compound profiling using gas chromatography-ion mobility spectrometry.

AIM: To evaluate the relationship between breath volatile organic compounds (VOCs) and glycaemic states in individuals with type 1 diabetes (T1D), focusing on identifying specific VOCs as biomarkers for hypoglycaemia to offer a non-invasive diabetes-monitoring method. MATERIALS AND METHODS: Ten individuals with T1D underwent induced hypoglycaemia in a clinical setting. Breath samples, collected every 10-15 minutes, were analysed using gas chromatography-ion mobility spectrometry (GC-IMS). Correlation analysis and machine learning models, including Partial Least Squares Discriminant Analysis (PLS-DA) and Support Vector Machine classifiers, were used to classify glycaemic states based on VOC profiles. RESULTS: Statistical analysis revealed moderate correlations between specific VOCs (e.g. isoprene, acetone) and venous blood glucose levels. Machine learning models showed high accuracy in classifying glycaemic states, with the best performance achieved by a two-class PLS-DA model showing an accuracy of 93%, sensitivity of 92% and specificity of 94%. Key biomarkers identified included isoprene, acetone, 2-butanone, methanol, ethanol, 2-propanol and 2-pentanone. CONCLUSIONS: This study shows the potential of breath VOCs to accurately classify glycaemic states in individuals with T1D. While key biomarkers such as isoprene, acetone and 2-butanone were identified, the analysis emphasizes the importance of using overall VOC patterns rather than individual compounds, which can be markers for multiple conditions. Machine learning models leveraging these patterns achieved high accuracy, sensitivity and specificity. These findings suggest that breath analysis using GC-IMS could be a viable non-invasive method for monitoring glycaemic states and managing diabetes.

Diabetes mellitus and adverse clinical events in patients with atrial fibrillation: A report from the GLORIA-AF registry phase III.

AIMS: Atrial fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations have not been fully elucidated, particularly with concomitant insulin use. This study aimed to analyse the associations between adverse events and DM, as well as adverse events and sole insulin use. MATERIALS AND METHODS: Our analysis included individuals with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-year follow-up. Outcomes included all-cause death, major bleeding, cardiovascular (CV) death, myocardial infarction (MI), stroke, thromboembolism and major adverse cardiovascular events (MACE). RESULTS: A total of 15 861 AF individuals were included (age 70.0 ± 10.2 years; 55% male, 20% Asian), of whom, 3666 had DM (age 70.0 ± 9.5 years ; 59% male, 21% Asian). After adjustment, those with DM had higher risks of all-cause death (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 1.28-1.66), CV death (HR: 1.53 95% CI: 1.27-1.86), major bleeding (HR: 1.23, 95% CI: 1.01-1.48), MI (HR: 1.50, 95% CI: 1.17-1.94) and MACE (HR: 1.42, 95% CI: 1.23-1.63). Compared to individuals with DM receiving oral hypoglycaemic agents, those receiving insulin alone were associated with increased risks of all-cause death (HR: 2.16, 95% CI: 1.61-2.91), CV death (HR: 2.24, 95% CI: 1.45-3.47), major bleeding (HR: 1.89, 95% CI: 1. 21-2.95), MI (HR: 2.24, 95% CI: 1.31-3.82) and MACE (HR: 2.11, 95% CI: 1.54-2.88). CONCLUSIONS: DM was independently associated with higher risks of all-cause death, CV death, MI, major bleeding and MACE in AF individuals. Individuals receiving insulin alone were associated with higher risks of all-cause death, CV death, MI, major bleeding and MACE.

Treatment responses to basal insulin glargine 300 U/ml and glargine 100 U/ml in newly defined subphenotypes of type 2 diabetes: A post hoc analysis of the EDITION 3 randomized clinical trial.

INTRODUCTION: To compare responses to basal insulin glargine 300 U/ml (IGlar-300) and 100 U/ml (IGlar-100) in newly defined subphenotypes of type 2 diabetes. METHODS: Insulin-naive participants (n = 858) from the EDITION 3 trial were assigned to subphenotypes 'Mild Age-Related Diabetes (MARD)', 'Mild Obesity Diabetes (MOD)', 'Severe Insulin Resistant Diabetes (SIRD)' and 'Severe Insulin Deficient Diabetes (SIDD)'. Key variables were analysed at baseline and 26 weeks. RESULTS: Participants were comprised of MOD 56.1% (n = 481), SIDD 22.1% (n = 190), MARD 18.2% (n = 156) and SIRD 3.0% (n = 26). After 26 weeks a similar decrease in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) of 16-19 mmol/mol and 1.4-1.7 mmol/L, respectively, occurred in MARD and MOD with both insulins. SIDD had the most elevated HbA1c and FPG (80-83 mmol/mol/11.1-11.4 mmol/L) and reduction in both HbA1c and FPG was greater with IGlar-100 than with IGlar-300 (-18 vs. -15 mmol/mol and -1.6 vs. -1.3 mmol/L, respectively; each p = .03). In SIDD, despite receiving the highest basal insulin doses, HbA1c decline (57-60 mmol/mol/7.3-7.6%) was suboptimal at week 26. In MOD and SIDD lower incidences with IGlar-300 were found for level 1 nocturnal hypoglycaemia [odds ratio (OR) 0.59, 95% confidence intervals (CI) 0.36-0.97; OR 0.49, 95% CI 0.24-0.99]. In addition, fewer level 2 hypoglycaemia episodes occurred at any time with IGlar-300 in SIDD (OR 0.31, 95% CI 0.13-0.77). CONCLUSION: Both insulins produce comparable outcomes in type 2 diabetes subphenotypes, but in SIDD, add-on treatment to basal insulin is required to achieve glycaemic targets.

The relationship between glycated haemoglobin and blood glucose-lowering treatment trajectories in type 2 diabetes: The Fremantle Diabetes Study Phase II.

AIMS: To examine the relationships between glycaemia and treatment complexity over 6 years in well-characterized community-based people with type 2 diabetes. MATERIALS AND METHODS: Fremantle Diabetes Study Phase II participants who had type 2 diabetes with glycated haemoglobin (HbA1c) and blood glucose-lowering therapy (BGLT) data over 6 years were included. Group-based multi-trajectory modelling identified combined HbA1c/BGLT trajectory subgroups for diabetes durations of ≤1.0 year (Group 1; n = 160), >1.0 to 10.0 years (Group 2; n = 382;) and >10.0 years (Group 3; n = 357). Multinomial regression was used to identify baseline associates of subgroup membership. RESULTS: The optimum numbers of trajectory subgroups were three in Group 1 (low, medium, high) and four in Groups 2 and 3 (low, low/high medium, high). Each low trajectory subgroup maintained a mean HbA1c concentration of <53 mmol/mol (<7.0%) on lifestyle measures, or monotherapy (Group 3). All five medium subgroups had stable HbA1c trajectories at <58 mmol/mol (<7.5%) but required increasing oral BGLT, or insulin (Group 3, high medium). The Group 1 high subgroup showed a falling then increasing HbA1c with steady progression to insulin. The high subgroups in Groups 2 and 3 showed stable HbA1c profiles at means of approximately 64 mmol/mol (8.0%) and 86 mmol/L (10.0%), respectively, on insulin. Non-Anglo Celt ethnicity, central obesity and hypertriglyceridaemia were strongly associated with Group 1 high subgroup membership. Younger age at diagnosis and central obesity were independent associates of the most adverse HbA1c trajectories in Groups 2 and 3. CONCLUSIONS: These data demonstrate diabetes duration-dependent heterogeneity in glycaemic and treatment profiles and related clinical and laboratory variables, which have implications for management.

Glycated haemoglobin, HOMA2-B, C-peptide to glucose ratio and type 2 diabetes clusters as predictors for therapy failure in individuals with type 2 diabetes without insulin therapy: A registry analysis.

AIM: Some people with type 2 diabetes mellitus (T2D) and declining ß-cell function do require insulin over time. Various laboratory parameters, indices of glucose metabolism or phenotypes of T2D (clusters) have been suggested, which might predict future therapy failure (TF), indicating the need for insulin therapy initiation. This analysis evaluated glycated haemoglobin (HbA1c), homeostatic model assessment (HOMA)2-B, C-peptide to glucose ratio (CGR) and diabetes clusters as predictive parameters for the occurrence of glycaemic TF in individuals diagnosed with T2D without previous insulin therapy. MATERIALS AND METHODS: In total, 159 individuals with T2D [41% female, median age 50 (IQR: 53-69) years, diabetes duration 9 (5-15) years], without insulin therapy were prospectively evaluated for the occurrence of a composite primary endpoint, including HbA1c increasing or remaining >8.0% (64 mmol/mol) 3 months after baseline on non-insulin glucose-lowering agents, insulin initiation or hospital admissions because of acute hyperglycaemic events. Diabetes clusters were formed according to previously described characteristics. Only severe autoimmune diabetes clusters were excluded because of a small amount of glutamate decarboxylase antibody-positive participants. The other clusters were distributed as mild age-related diabetes 33%; severe insulin-deficient diabetes 31%; mild obesity-related diabetes 20%; and severe insulin-resistant diabetes 15%. RESULTS: During a median observation of 57 months, higher tertiles of HbA1c at baseline, HOMA2-B, as well as a lower CGR were significantly predictive for the occurrence of the primary endpoint. The probability of meeting the primary endpoint was the highest for mild obesity-related diabetes [hazard ratio 3.28 (95% confidence interval 1.75-6.2)], followed by severe insulin-deficient diabetes [hazard ratio 2.03 (95% confidence interval 1.1-3.7)], mild age-related diabetes and the lowest for severe insulin-resistant diabetes. The best performance to predict TF with an area under the curve (AUC) of 0.77 was HbA1c at baseline, followed by HOMA2-B (AUC 0.69) and CGR (AUC 0.64). CONCLUSION: HbA1c, indices of insulin secretion capacity (HOMA2-B and CGR) and T2D clusters might be applicable tools to guide practitioners in the decision of whether insulin is required in people already diagnosed with T2D. These findings need to be validated in prospective studies.

The MiniMed 780G automated insulin delivery system adapts to substantial changes in daily routine: Lessons from real world users during Ramadan.

AIM: To report on the effectiveness and safety of the MiniMed 780G automated insulin delivery system in real-world users during the month of Ramadan. MATERIALS AND METHODS: CareLink Personal data were extracted from MiniMed 780G system users from the Gulf region. Users were included if they had ≥10 days of sensor glucose data during the month of Ramadan 2022 as well as in the month before and after. For the main analysis, continuous glucose monitoring endpoints were aggregated per month and were reported by time of day (daytime: 05.31-18.00 h, and night-time). Additional analyses were performed to study the pace at which the algorithm adapts. RESULTS: Glycaemic control was well kept in the 449 included users (mean sensor glucose = 152.6 ± 18.7 mg/dl, glucose management indicator = 7.0 ± 0.4%, time in range = 70.7 ± 11.0%, time below 70 mg/dl = 2.3 ± 2.3%). Albeit some metrics differed from the month before (p < .0001 for all), absolute differences were very small and considered clinically irrelevant. During Ramadan, there was no increased risk of hypoglycaemia during daytime (time below 70 mg/dl = 2.3 ± 2.4%), time in range was highest during daytime (80.0 ± 10.7%, night: 60.4 ± 15.3%), while time above 180 mg/dl was highest during night-time (37.3 ± 16.3%, day: 17.7 ± 10.7%). The algorithm adapted immediately upon lifestyle change. CONCLUSION: The MiniMed 780G automated insulin delivery system is effective, safe and fast in adapting to the substantial changes that occur in the lifestyle of people with type 1 diabetes during Ramadan.

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.

ADO09, a co-formulation of pramlintide and insulin A21G, lowers body weight versus insulin lispro in type 1 diabetes.

AIM: To study safety, efficacy and weight loss with ADO09, a co-formulation of insulin A21G and pramlintide, in type 1 diabetes. MATERIALS AND METHODS: A randomized, two-arm ambulatory 16-week study compared ADO09 with insulin lispro in 80 participants with type 1 diabetes. We compared changes of weight, glycated haemoglobin, glycaemic patterns during continuous glucose monitoring, and insulin doses at baseline and at the end of treatment. RESULTS: A significant and continuing weight loss, the primary endpoint, was observed with ADO09 compared with lispro as prandial insulin. In the whole group, the weight loss with ADO09 relative to lispro was 2.1 kg. Glycaemic control was relatively good (7.7% mean glycated haemoglobin) in both groups and did not change during treatment. Prandial insulin doses were reduced by 21% in the ADO09 group, whereas basal insulin dosage was not modified. Gastrointestinal symptoms were more frequent with ADO09, but no clear difference in hypoglycaemia was observed. CONCLUSIONS: These results extend previous observations on the efficacy and safety of this insulin/pramlintide co-formulation. They show a beneficial effect on weight, using less mealtime insulin and without increased hypoglycaemia.

Differential associations of risk factors with severe and non-severe hypoglycaemia: the Hypoglycaemia Assessment Tool prospective observational study in people with insulin-treated type 1 diabetes and type 2 diabetes.

AIM: To assess the differential association of risk factors with severe and non-severe hypoglycaemia. MATERIALS AND METHODS: The Hypoglycaemia Assessment Tool study evaluated the risk of hypoglycaemia over a 4-week period in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) on insulin in 24 countries. Negative binomial regressions were applied to examine the associations of several risk factors with severe and non-severe hypoglycaemia. RESULTS: The median age was 41 years in 5949 patients with T1D and 62 years in 12 914 patients with T2D. The 4-week rates of non-severe hypoglycaemic were 5.57 and 1.40 episodes per person in T1D and T2D, respectively; the corresponding rates for severe hypoglycaemia were 0.94 and 0.30. The excess risk was 42% higher for severe than non-severe hypoglycaemia in females versus males with T2D; 27% higher in patients with T2D with versus without a continuous glucose monitoring (CGM); and 47% lower in patients with T1D with versus without an insulin pump. The excess risk also differed across geographical areas and was marginally lower for severe than non-severe hypoglycaemia for higher values of HbA1c in patients with T2D. Associations with severity of hypoglycaemia were not different for age, diabetes and insulin therapy duration, previous hypoglycaemic episodes and insulin regimen. CONCLUSIONS: The risk of severe versus non-severe hypoglycaemia differs in patients with T1D and T2D; sex, the use of a CGM and insulin pump, and geographical areas were differently associated with one type of hypoglycaemia than the other.

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.

Psychosocial outcomes with the Omnipod® 5 Automated Insulin Delivery System in caregivers of very young children with type 1 diabetes.

AIM: Automated insulin delivery (AID) systems have demonstrated improved glycaemic outcomes in people with type 1 diabetes (T1D), yet limited data exist on these systems in very young children and their impact on caregivers. We evaluated psychosocial outcomes following use of the tubeless Omnipod® 5 AID System in caregivers of very young children. MATERIALS AND METHODS: This 3-month single-arm, multicentre, pivotal clinical trial enrolled 80 children aged 2.0-5.9 years with T1D to use the Omnipod 5 AID System. Caregivers completed questionnaires assessing psychosocial outcomes-diabetes distress (Problem Areas in Diabetes), hypoglycaemia confidence (Hypoglycemia Confidence Scale), well-being (World Health Organization 5 Well-Being Index), sleep quality (Pittsburgh Sleep Quality Index), insulin delivery satisfaction (Insulin Delivery Satisfaction Survey) and system usability (System Usability Scale) at baseline with standard therapy and after 3 months of AID use. RESULTS: Following 3 months of Omnipod 5 use, caregivers experienced significant improvements across all measures, including diabetes-related psychosocial outcomes (Problem Areas in Diabetes; p < 0.0001, Hypoglycemia Confidence Scale; p < 0.01), well-being (World Health Organization 5 Well-Being Index; p < 0.0001) and perceived system usability (System Usability Scale; p < 0.0001). Significant improvements were seen in the Pittsburgh Sleep Quality Index total score and the overall sleep quality, sleep duration and efficiency subscales (all p < 0.05). Insulin Delivery Satisfaction Survey scores improved on all subscales (greater satisfaction, reduced burden and reduced inconvenience; all p < 0.0001). CONCLUSIONS: Caregivers face unique challenges when managing T1D in very young children. While glycaemic metrics have unquestioned importance, these results evaluating psychosocial outcomes reveal additional meaningful benefits and suggest that the Omnipod 5 AID System alleviates some of the burdens caregivers face with diabetes management.

Generating real-world evidence on diabetes technology using the CareLink Personal data management system.

AIM: To establish trust in real-world evidence (RWE) derived from CareLink Personal (CP), Medtronic's data management system for MiniMed system users, we show that this database and its analyses strictly adhere to the principles of RWE. METHODS: The methodology is applicable to all MiniMed iterations. We described every step from raw data to predefined outcomes. In addition, we showed CP's fitness-for-research by the below metrics (using last year's MiniMed 780G system data as a case study): representative population, relevant endpoints, appropriate granularity, high data completeness, high data representativity and consistency in results. RESULTS: The process from raw data to outcomes has been validated, and metrics/logics adhere to established definitions. Over 95% of users have a CP account; with 96% providing consent, this allows the use of >91% of the census population. There is no rationale for an over-representation of a specific phenotype among users not included. CP includes >50 endpoints, including 'International Consensus on Time in Range' based metrics. Data are recorded at 5-min intervals (maximum 288 per day), and on average there were 263 data points per person per day. Ninety-nine per cent of uploads were automated. For the last year, only 1 in 6 users had a data gap >1 day, and 1 in 50 had a gap >1 week. The time in range from in-silico studies was similar to that of real-world studies from different geographies and with ever growing populations. CONCLUSION: RWE from CP adheres to the principles of RWE and can serve as robust evidence on the performance and safety of MiniMed systems.

Diabetes mellitus and blood glucose variability increases the 30-day readmission rate after kidney transplantation.

INTRODUCTION: Inpatient hyperglycemia is an established independent risk factor among several patient cohorts for hospital readmission. This has not been studied after kidney transplantation. Nearly one-third of patients who have undergone a kidney transplant reportedly experience 30-day readmission. METHODS: Data on first-time solitary kidney transplantations were retrieved between September 2015 and December 2018. Information was linked to the electronic health records to determine diagnosis of diabetes mellitus and extract glucometric and insulin therapy data. Univariate logistic regression analysis and the XGBoost algorithm were used to predict 30-day readmission. We report the average performance of the models on the testing set on bootstrapped partitions of the data to ensure statistical significance. RESULTS: The cohort included 1036 patients who received kidney transplantation; 224 (22%) experienced 30-day readmission. The machine learning algorithm was able to predict 30-day readmission with an average area under the receiver operator curve (AUC) of 78% with (76.1%, 79.9%) 95% confidence interval (CI). We observed statistically significant differences in the presence of pretransplant diabetes, inpatient-hyperglycemia, inpatient-hypoglycemia, minimum and maximum glucose values among those with higher 30-day readmission rates. The XGBoost model identified the index admission length of stay, presence of hyper- and hypoglycemia, the recipient and donor body mass index (BMI) values, presence of delayed graft function, and African American race as the most predictive risk factors of 30-day readmission. Additionally, significant variations in the therapeutic management of blood glucose by providers were observed. CONCLUSIONS: Suboptimal glucose metrics during hospitalization after kidney transplantation are associated with an increased risk for 30-day hospital readmission. Optimizing hospital blood glucose management, a modifiable factor, after kidney transplantation may reduce the risk of 30-day readmission.

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.

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.

Gene expression of protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), solute carrier family 2 member 1 (SLC2A1) and mechanistic target of rapamycin (MTOR) in metformin-treated type 2 diabetes patients with COVID-19: impact on inflammation markers.

The COVID-19 pandemic has resulted in a global health crisis that has severely impacted patients with type 2 diabetes (T2D). T2D patients have a higher risk of experiencing severe COVID-19 symptoms, hospitalization, and mortality compared to patients without diabetes. The dysregulated immune response in T2D patients can exacerbate the severity of COVID-19 symptoms. Insulin therapy, a common treatment for T2D patients, has been linked to increased mortality in COVID-19 patients with T2D. However, metformin, an anti-diabetic medication, has been shown to have anti-inflammatory properties that may mitigate the cytokine storm observed in severe COVID-19 cases. In this study, we investigated how the PRKAA1, SLC2A1, and MTOR genes contribute to inflammation markers in COVID-19 patients with T2D, who were receiving either insulin or metformin therapy. Our findings revealed that metformin treatment was associated with reduced expression of genes involved in Th1/Th17 cell differentiation. These results suggest that metformin could be a potential treatment option for T2D patients with COVID-19 due to its anti-inflammatory properties, which may improve patient outcomes.

[Effect of Intensive Insulin Therapy on Prognosis in Patients With Acute Myocardial Infarction].

Objective To evaluate the clinical efficacy and safety of intensive insulin therapy in the patients with acute myocardial infarction and provide guidance for improving the prognosis. Methods The articles involving the randomized controlled trials(RCT)focusing on the effects of intensive versus conventional insulin therapy on the clinical outcomes of the patients with acute myocardial infarction were retrieved from Cochrane,Embase,PubMed,CNKI,Wanfang Data,VIP,and CBM with the time interval from inception to October 2022.The data of each RCT were extracted and used for meta-analysis in RevMan5.4. Results A total of 8 articles were included in this study,involving 726 patients(372 in the intensive insulin group and 354 in the normal insulin group).The meta-analysis results showed that the intensive insulin group had lower incidence of major cardiovascular adverse events (RR=0.53, 95%CI=0.44-0.64, P<0.001), lower all-cause mortality (RR=0.51, 95%CI=0.33-0.78, P=0.002),lower high-sensitivity C-reactive protein level on day 7(WMD=-2.00,95%CI=-2.17- -1.83,P<0.001),higher left ventricular ejection fraction on day 30 (WMD=3.94, 95%CI=2.45-5.43,P<0.001), and higher incidence of hypoglycemia events (RR=2.96, 95%CI=1.12-7.83,P=0.030) than the normal insulin group.There was no significant difference between the two groups in terms of no-reflow event after percutaneous coronary intervention(RR=0.39,95%CI=0.14-1.13,P=0.080). Conclusion Intensive insulin therapy might be associated with more clinical benefits in the patients with acute myocardial infarction,while the conclusion remains to be confirmed by more studies.