Long-term assessment of the NHS hybrid closed-loop real-world study on glycaemic outcomes, time-in-range, and quality of life in children and young people with type 1 diabetes.

Hybrid closed-loop (HCL) systems seamlessly interface continuous glucose monitoring (CGM) with insulin pumps, employing specialised algorithms and user-initiated automated insulin delivery. This study aimed to assess the efficacy of HCLs at 12 months post-initiation on glycated haemoglobin (HbA1c), time-in-range (TIR), hypoglycaemia frequency, and quality of life measures among children and young people (CYP) with type 1 diabetes mellitus (T1DM) and their caregivers in a real-world setting. Conducted between August 1, 2021, and December 10, 2022, the prospective recruitment took place in eight paediatric diabetes centres across England under the National Health Service England's (NHSE) HCL pilot real-world study. A cohort of 251 CYP (58% males, mean age 12.3 years) with T1DM participated (89% white, 3% Asian, 4% black, 3% mixed ethnicity, and 1% other). The study utilised three HCL systems: (1) Tandem Control-IQ AP system, which uses the Tandem t:slim X2 insulin pump (Tandem Diabetes Care, San Diego, CA, USA) with the Dexcom G6® CGM (Dexcom, San Diego, CA, USA) sensor; (2) Medtronic MiniMed™ 780G with the Guardian 4 sensor (Medtronic, Northridge, CA, USA); and (3) the CamAPS FX (CamDiab, Cambridge, UK) with the Ypsomed insulin pump (Ypsomed Ltd, Escrick, UK) and Dexcom G6® CGM.All systems were fully funded by the NHS. Results demonstrated significant improvements in HbA1c (average reduction at 12 months 7 mmol/mol; P < 0.001), time-in-range (TIR) (average increase 13.4%; P < 0.001), hypoglycaemia frequency (50% reduction), hypoglycaemia fear, and quality of sleep (P < 0.001) among CYP over a 12-month period of HCL usage. Additionally, parents and carers experienced improvements in hypoglycaemia fear and quality of sleep after 6 and 12 months of use. In addition to the improvements in glycaemic management, these findings underscore the positive impact of HCL systems on both the well-being of CYP with T1DM and the individuals caring for them.

Effects of high-intensity interval training and its different protocols on lipid profile and glycaemic control in type 2 diabetes: A meta-analysis.

This meta-analysis of randomised clinical trials aimed to compare the effects of high-intensity interval training (HIIT) and its different protocols versus moderate-intensity continuous training (MICT) and/or control on total cholesterol, HDL, LDL, triglycerides, HbA1c levels, and fasting glucose in individuals with type 2 diabetes mellitus (T2DM). The search strategy was performed in PubMed/MEDLINE, Cochrane CENTRAL, EMBASE, Web of Science, Sport DISCUS, and PEDro, until January 2023. A total of 31 studies (1092 individuals) were included. When compared to control, HIIT decreased total cholesterol by -0.31 mmol/L (95% CI -0.49; -0.12), LDL by -0.31 mmol/L (95% CI -0.49; -0.12), triglycerides by -0.27 mmol/L (95% CI -0.33; -0.2), HbA1c by -0.75% (95% CI -0.97; -0.53), fasting glucose by -1.15 mmol/L (95% CI -1.44; -0.86), and increased HDL by 0.24 mmol/L (95% CI 0.06; 0.42). No difference was found in the comparison between HIIT versus MICT for any of the outcomes analysed, however subgroup analysis showed that a moderate-interval (>30s to < 2 min) and moderate-term (>4 to < 12 weeks) HIIT protocol reduced total cholesterol, when compared to MICT. HIIT is able to improve lipid profile and glycaemic control in T2DM individuals, and specific protocols can be recommended for improving total cholesterol levels.

Diabetes Technology in People with Type 2 Diabetes: Novel Indications.

PURPOSE OF REVIEW: Diabetes technology has been continuously evolving. Current versions of continuous glucose monitors (CGM) use minimally invasive designs, monitor glucose values with high accuracy, and can be used to guide insulin dosing. Extensive evidence supports the use of diabetes technology for monitoring and insulin administration in people with type 1 diabetes. However, there is emerging evidence for people with type 2 diabetes. In this review, we present the different technological devices used to monitor glucose and deliver insulin and the evidence supporting their use in people with type 2 diabetes. RECENT FINDINGS: The use of CGMs in people with type 2 diabetes treated with insulin or non-insulin therapies has been associated with improvements in glycemic control and time spent in hypoglycemia. Smart insulin pens and smart connected devices are options to track compliance and guide insulin delivery in people who do not require insulin pump therapy. Mechanical patch pumps can be used to reduce the burden of multiple daily insulin injections. Automated insulin delivery algorithms improve glycemic control without an increase in hypoglycemia. The use of technology in the management of type 2 diabetes generates glycemic data previously inaccessible, reduces barriers for insulin initiation, improves glycemic control, tracks adherence to therapy, and improves user satisfaction.

Association between glycaemic control and malnutrition in older adults with type 2 diabetes mellitus: a cross-sectional study.

Malnutrition is a major problem among older adults with type 2 diabetes mellitus (T2DM). Some studies suggest that well glycaemic control increases the risk of frailty due to reduced intake. Therefore, it could be hypothesised that adequate glycaemic controlled patients may be at risk of malnutrition. This study aimed to examine, in older adults with T2DM, the association between adequate glycaemic control and malnutrition as well as identify the risk factors for malnutrition. Data including general characteristics, health status, depression, functional abilities, cognition and nutrition status were analysed. Poor nutritional status is defined as participants assessed with the Mini Nutritional Assessment as being at risk of malnutrition or malnourished. Adequate glycaemic control refers to an HbA1c level that meets the target base in the American Diabetes Association 2022 guidelines with individualised criteria. There were 287 participants with a median (interquartile range) age of 64 (61-70) years, a prevalence of poor nutrition, 15 %, and adequate glycaemic control, 83·6 %. This study found no association between adequate glycaemic control and poor nutrition (P = 0·67). The factors associated with poor nutritional status were low monthly income (adjusted OR (AOR) 4·66, 95 % CI 1·28, 16·98 for income < £118 and AOR 7·80, 95 % CI 1·74, 34·89 for income £118-355), unemployment (AOR 4·23, 95 % CI 1·51, 11·85) and cognitive impairment (AOR 5·28, 95 % CI 1·56, 17·93). These findings support the notion that older adults with T2DM should be encouraged to maintain adequate glycaemic control without concern for malnutrition, especially those who have low income, unemployment or decreased cognitive functions.

Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis.

OBJECTIVE: To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible. RESULTS: 76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A1c and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A1c concentrations (mean difference -2.10% (95% confidence interval -2.47% to -1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (-3.12 mmol/L (-3.59 to -2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference -14.03 kg (95% confidence interval -17.05 to -11.00); high confidence of evidence), followed by tirzepatide (-8.47 kg (-9.68 to -7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (-0.16 mmol/L (-0.30 to -0.02)) and total cholesterol (-0.48 mmol/L (-0.84 to -0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration. CONCLUSIONS: GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A1c and fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022342845.

Effectiveness and cost-effectiveness of six GLP-1RAs for treatment of Chinese type 2 diabetes mellitus patients that inadequately controlled on metformin: a micro-simulation model.

Objective: To systematically estimate and compare the effectiveness and cost-effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) approved in China and to quantify the relationship between the burden of diabetic comorbidities and glycosylated hemoglobin (HbA1c) or body mass index (BMI). Methods: To estimate the costs (US dollars, USD) and quality-adjusted life years (QALY) for six GLP-1RAs (exenatide, loxenatide, lixisenatide, dulaglutide, semaglutide, and liraglutide) combined with metformin in the treatment of patients with type 2 diabetes mellitus (T2DM) which is inadequately controlled on metformin from the Chinese healthcare system perspective, a discrete event microsimulation cost-effectiveness model based on the Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model was developed. A cohort of 30,000 Chinese patients was established, and one-way sensitivity analysis and probabilistic sensitivity analysis (PSA) with 50,000 iterations were conducted considering parameter uncertainty. Scenario analysis was conducted considering the impacts of research time limits. A network meta-analysis was conducted to compare the effects of six GLP-1RAs on HbA1c, BMI, systolic blood pressure, and diastolic blood pressure. The incremental net monetary benefit (INMB) between therapies was used to evaluate the cost-effectiveness. China's per capita GDP in 2021 was used as the willingness-to-pay threshold. A generalized linear model was used to quantify the relationship between the burden of diabetic comorbidities and HbA1c or BMI. Results: During a lifetime, the cost for a patient ranged from USD 42,092 with loxenatide to USD 47,026 with liraglutide, while the QALY gained ranged from 12.50 with dulaglutide to 12.65 with loxenatide. Compared to exenatide, the INMB of each drug from highest to lowest were: loxenatide (USD 1,124), dulaglutide (USD -1,418), lixisenatide (USD -1,713), semaglutide (USD -4,298), and liraglutide (USD -4,672). Loxenatide was better than the other GLP-1RAs in the base-case analysis. Sensitivity and scenario analysis results were consistent with the base-case analysis. Overall, the price of GLP-1RAs most affected the results. Medications with effective control of HbA1c or BMI were associated with a significantly smaller disease burden (p < 0.05). Conclusion: Loxenatide combined with metformin was identified as the most economical choice, while the long-term health benefits of patients taking the six GLP-1RAs are approximate.

Tight Blood-Glucose Control without Early Parenteral Nutrition in the ICU.

BACKGROUND: Randomized, controlled trials have shown both benefit and harm from tight blood-glucose control in patients in the intensive care unit (ICU). Variation in the use of early parenteral nutrition and in insulin-induced severe hypoglycemia might explain this inconsistency. METHODS: We randomly assigned patients, on ICU admission, to liberal glucose control (insulin initiated only when the blood-glucose level was >215 mg per deciliter [>11.9 mmol per liter]) or to tight glucose control (blood-glucose level targeted with the use of the LOGIC-Insulin algorithm at 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]); parenteral nutrition was withheld in both groups for 1 week. Protocol adherence was determined according to glucose metrics. The primary outcome was the length of time that ICU care was needed, calculated on the basis of time to discharge alive from the ICU, with death accounted for as a competing risk; 90-day mortality was the safety outcome. RESULTS: Of 9230 patients who underwent randomization, 4622 were assigned to liberal glucose control and 4608 to tight glucose control. The median morning blood-glucose level was 140 mg per deciliter (interquartile range, 122 to 161) with liberal glucose control and 107 mg per deciliter (interquartile range, 98 to 117) with tight glucose control. Severe hypoglycemia occurred in 31 patients (0.7%) in the liberal-control group and 47 patients (1.0%) in the tight-control group. The length of time that ICU care was needed was similar in the two groups (hazard ratio for earlier discharge alive with tight glucose control, 1.00; 95% confidence interval, 0.96 to 1.04; P = 0.94). Mortality at 90 days was also similar (10.1% with liberal glucose control and 10.5% with tight glucose control, P = 0.51). Analyses of eight prespecified secondary outcomes suggested that the incidence of new infections, the duration of respiratory and hemodynamic support, the time to discharge alive from the hospital, and mortality in the ICU and hospital were similar in the two groups, whereas severe acute kidney injury and cholestatic liver dysfunction appeared less prevalent with tight glucose control. CONCLUSIONS: In critically ill patients who were not receiving early parenteral nutrition, tight glucose control did not affect the length of time that ICU care was needed or mortality. (Funded by the Research Foundation-Flanders and others; TGC-Fast ClinicalTrials.gov number, NCT03665207.).

Mind- and Body-Based Interventions Improve Glycemic Control in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Aims/Hypothesis: Only 51% of patients with type 2 diabetes achieve the hemoglobin A1c (HbA1c) <7% target. Mind and body practices have been increasingly used to improve glycemic control among patients with type 2 diabetes, but studies show inconsistent efficacy. The authors conducted a systematic review and meta-analysis to assess the association between mind and body practices, and mean change in HbA1c and fasting blood glucose (FBG) in patients with type 2 diabetes. Methods: The authors conducted a literature search of Ovid MEDLINE, Embase, and ClinicalTrials.gov seeking through June 10, 2022, published articles on mind and body practices and type 2 diabetes. Two reviewers independently appraised full text of articles. Only intervention studies were included. Reviewers extracted data for meta-analysis. Restricted maximum likelihood random-effects modeling was used to calculate the mean differences and summary effect sizes. The authors assessed heterogeneity using Cochran's Q and I2 statistics. Funnel plots were generated for each outcome to gauge publication bias. Weighted linear models were used to conduct study-level meta-regression analyses of practice frequency. Results: The authors identified 587 articles with 28 meeting the inclusion criteria. A statistically significant and clinically relevant mean reduction in HbA1c of -0.84% (95% confidence interval [CI]: -1.10% to -0.58%; p < 0.0001) was estimated. Reduction was observed in all intervention subgroups: mindfulness-based stress reduction: -0.48% (95% CI: -0.72% to -0.23%; p = 0.03), qigong: -0.66% (95% CI: -1.18% to -0.14%; p = 0.01), and yoga: -1.00% (95% CI: -1.38% to -0.63%; p < 0.0001). Meta-regression revealed that for every additional day of yoga practice per week, the raw mean HbA1c differed by -0.22% (95% CI: -0.44% to -0.003%; p = 0.046) over the study period. FBG significantly improved following mind and body practices, with overall mean difference of -22.81 mg/dL (95% CI: -33.07 to -12.55 mg/dL; p < 0.0001). However, no significant association was found between the frequency of weekly yoga practice and change in FBG over the study period. Conclusions/Interpretation: Mind and body practices are strongly associated with improvement in glycemic control in patients with type 2 diabetes. The overall mean reduction in HbA1c and FBG was clinically significant, suggesting that mind and body practices may be an effective, complementary nonpharmacological intervention for type 2 diabetes. Additional analyses revealed that the mean decrease in HbA1c was greater in studies requiring larger number of yoga practice sessions each week.

Observaciones en el mundo real sobre la efectividad del sistema flash de monitorización de glucosa en la práctica clínica en Chile / Real-world observations of the effectiveness of the flash glucose monitoring in clinical practice in Chile

OBJETIVO: Evaluar el tiempo en rango de glucosa y su asociación con otras medidas del control glicémico establecidas por el consenso internacional del tiempo en rango en usuarios de vida real del sistema flash de monitorización de glucosa FreeStyle LibreTM en Chile. MÉTODOS: Se analizaron los datos provenientes de la base de datos Freestyle Libre™ entre diciembre de 2014 y enero de 2022. Las lecturas se dividieron en 10 grupos (deciles) del mismo tamaño (cada decil contenía aproximadamente 498 usuarios) en función del tiempo en rango. Para cada decil se calculó la media de determinaciones diarias, el promedio de glucosa, la HbA1c, la desviación estándar de glucosa, el coeficiente de variación de la glucosa, el tiempo en rango, el tiempo de glucosa (porcentaje) por encima de 250 mg/dL (TA250), el tiempo de glucosa (porcentaje) por encima de 180 mg/dL (TA180), el tiempo por debajo (porcentaje) de 70 mg/dL (TB70) y el tiempo por debajo (porcentaje) de 54 mg/dL (TB54). RESULTADOS: Desde diciembre de 2014 hasta enero de 2022 hubo 4984 lectores. El grupo con el mayor tiempo en rango mostró significativamente una menor glucosa promedio que el grupo con el tiempo en rango más bajo (decil 1: media 248,3 mg/dL, decil 10: media 113,2 mg/L, diferencia ­135,1 mg/dL, p<0.05). Asimismo, el mayor tiempo en rango se asoció con una menor desviación estándar (decil 1: media 93,7mg/dL, decil 10: media 26,7mg/L, diferencia: -67,0 mg/ dL, p<0,05), menor coeficiente de variación (decil 1: media 37,8%, decil 10: media 23,3%, diferencia: -14,5%, p<0,05), menor TA250 (decil 1: media 46,5%, decil 10: media 0,2%, diferencia: -46,3%, p<0.05), menor TA180 (decil 1: media 73,9%, decil 10: media 3,8%, diferencia: -70,1%, p<0.05), menor TB70 (decil 5: mediana 6,13%, decil 10: mediana 1,70%, diferencia: -4,43%, p<0.05) y menor TB54 (decil 5: mediana 1,79%, decil 10: mediana 0,12%, diferencia: -1,67%, p<0.05). El mayor tiempo en rango se asoció también significativamente con más determinaciones diarias (decil 1: media 11,4, decil 10: media 16,6, diferencia: 5,2, p<0,05). La frecuencia media de las determinaciones entre todos los lectores fue de 14,7 determinaciones diarias. CONCLUSIONES: En los pacientes con diabetes en Chile, el empleo del sistema flash de monitorización demuestra la asociación entre el mayor tiempo en rango, la reducción de la variabilidad de la glucosa y un menor riesgo de hiperglucemias e hipoglicemias y también con un mayor compromiso.

OBJECTIVE: To evaluate glucose time in range and its association with other metrics of glucose control established by the International Consensus on TIR amongst real-life patients using the Flash Glucose Monitoring system FreeStyle LibreTM in Chile. METHODS: Data from the Freestyle Libre™ database between December 2014 and January 2022 were analyzed. Readers were divided into 10 groups (deciles) of the same size (each decile had approximately 498 users) according to time in range. For each decile of time in range, the mean of daily scans, average glucose, estimated HbA1c, glucose standard deviation, glucose coefficient of variation, time in range, glucose time (percentage) above 250 mg/dL (TA250), and glucose time (percentage) above 180 mg/dL (TA180), and the median of glucose time (percentage) below 70 mg/dL (TB70) and glucose time (percentage) below 54 mg/dL (TB54), were calculated. RESULTS: From December 2014 to January 2022, there were 4984 readers. The group with the highest TIR showed significantly lower average glucose than the group with the lowest TIR (decile 1: mean 248.3 mg/dL, decile 10: mean 113.2 mg/L, difference: ­135.1 mg/dL, p<0.05). In addition, more time in range was associated with a lower glucose standard deviation (decile 1: mean 93.7 mg/dL, decile 10: mean 26.7 mg/L, difference: -67.0 mg/dL, p<0.05), lower glucose coefficient of variation (decile 1: mean 37.8%, decile 10: mean 23.3%, difference: -14.5%, p<0.05), lower TA250 (decile 1: mean 46.5%, decile 10: mean 0.2%, difference: -46.3%, p<0.05),lower TA180 (decile 1: mean 73.9%, decile 10: mean 3.8%, difference: -70.1%, p<0.05), lower TB70 (decile 5: median 6.13%, decile 10: median 1.70%, difference: -4.43%, p<0.05) and lower TB54 (decile 5: median 1.79%, decile 10: median 0.12%, difference: -1.67%, p<0.05). Greater TIR was also associated with significantly more daily scans (decile 1: mean 11.4, decile 10: mean 16.6, difference: 5.2, p<0.05). Mean scan frequency amongst all readers was 14.7 daily scans. CONCLUSIONS: In patients with diabetes from Chile, the use of the flash glucose monitoring system demonstrates the association between greater TIR, reduced glucose variability, and reduced risk of hyperglycemia and hypoglycemia, and also its association with greater engagement.

Influence of Optimal Management of Hyperglycemia and Intensive Nursing on Blood Glucose Control Level and Complications in Patients with Postoperative Cerebral Hemorrhage.

Background: Cerebral hemorrhage, also known as hemorrhagic stroke, is a common clinical cerebrovascular disease, accounting for about 10%-30% of stroke, with high morbidity and mortality. Objective: To observe the effect of optimal management of hyperglycemia and intensive nursing on blood glucose control level and complications in patients with postoperative cerebral hemorrhage. Methods: One hundred and eight patients with postoperative cerebral hemorrhage comorbid with stress hyperglycemia admitted to our neurosurgery department from February 2019 to February 2022 were selected and divided into a general group of 54 cases and an optimized group of 54 cases by simple random method. The general group was managed with conventional care, while the optimized group developed optimized management of hyperglycemia for intensive care. The indexes related to blood glucose control, electrolytes, National Institutes of Health Stroke Scale (NIHSS) scores, Barthel Index (BI) scores, and time to achieve blood glucose standard, insulin pumping time, patient satisfaction, and prognosis were compared between the two groups. Results: Before intervention, there was no statistical significance in the comparison of blood glucose control-related indicators and electrolytes between the two groups (P > 0.05). After 7 d and 14 d of intervention, the fasting blood glucose and 2 h postprandial blood glucose in the two groups were lower than before, while K+ and Na+ were higher than before (P < 0.05). The blood glucose indexes at the same time point in the optimized group were found to be lower than those in the general group by statistical analysis, but electrolytes were not statistically significant when compared with the general group (P > 0.05). In the optimized group, the time to achieve blood glucose standard (6.59 ± 1.94) d and insulin pumping time (7.14 ± 1.89) d were shorter than those in the general group [(7.48 ± 2.12) d and (8.58 ± 2.14) d], insulin dosage (748.85 ± 63.61) U was less than that in the general group (923.54 ± 84.14) U, and the incidence of hypoglycemia (3.70%) was lower than that in the general group (16.67%), and the satisfaction rate (92.59%) was higher than that of the general group (77.78%), which was statistically significant (P < 0.05). Before intervention, there was no significant difference in NIHSS score and BI score between the two groups (P > 0.05). After 7 d and 14 d of intervention, the NIHSS scores of the two groups were lower than before, while the BI scores were higher than before, and the NIHSS scores of the optimized group at the same time point were all lower than those of the general group, and the BI scores were higher than those of the general group (P < 0.05). The incidence of pulmonary infection (11.11%) and rebleeding (7.41%) in the optimized group were lower than those in the general group (25.93% and 22.22%), while deep vein thrombosis, multiple organ dysfunction syndrome (MODS), and death within 28 d was not statistically significant when compared with the general group (P > 0.05). Conclusion: Optimal management of hyperglycemia and intensive nursing can effectively control the blood sugar level of patients after cerebral hemorrhage, reducing insulin dosage, and the occurrence of hypoglycemia, pulmonary infection, and rebleeding.

Effects of a Lifestyle Intervention to Prevent Deterioration in Glycemic Status Among South Asian Women With Recent Gestational Diabetes: A Randomized Clinical Trial.

Importance: Women with recent gestational diabetes (GDM) have increased risk of developing type 2 diabetes. Objective: To investigate whether a resource-appropriate and context-appropriate lifestyle intervention could prevent glycemic deterioration among women with recent GDM in South Asia. Design, Setting, and Participants: This randomized, participant-unblinded controlled trial investigated a 12-month lifestyle intervention vs usual care at 19 urban hospitals in India, Sri Lanka, and Bangladesh. Participants included women with recent diagnosis of GDM who did not have type 2 diabetes at an oral glucose tolerance test (OGTT) 3 to 18 months postpartum. They were enrolled from November 2017 to January 2020, and follow-up ended in January 2021. Data were analyzed from April to July 2021. Interventions: A 12-month lifestyle intervention focused on diet and physical activity involving group and individual sessions, as well as remote engagement, adapted to local context and resources. This was compared with usual care. Main Outcomes and Measures: The primary outcome was worsening category of glycemia based on OGTT using American Diabetes Association criteria: (1) normal glucose tolerance to prediabetes (ie, impaired fasting glucose or impaired glucose tolerance) or type 2 diabetes or (2) prediabetes to type 2 diabetes. The primary analysis consisted of a survival analysis of time to change in glycemic status at or prior to the final patient visit, which occurred at varying times after 12 months for each patient. Secondary outcomes included new-onset type 2 diabetes and change in body weight. Results: A total of 1823 women (baseline mean [SD] age, 30.9 [4.9] years and mean [SD] body mass index, 26.6 [4.6]) underwent OGTT at a median (IQR) 6.5 (4.8-8.2) months postpartum. After excluding 160 women (8.8%) with type 2 diabetes, 2 women (0.1%) who met other exclusion criteria, and 49 women (2.7%) who did not consent or were uncontactable, 1612 women were randomized. Subsequently, 11 randomized participants were identified as ineligible and excluded from the primary analysis, leaving 1601 women randomized (800 women randomized to the intervention group and 801 women randomized to usual care). These included 600 women (37.5%) with prediabetes and 1001 women (62.5%) with normoglycemia. Among participants randomized to the intervention, 644 women (80.5%) received all program content, although COVID-19 lockdowns impacted the delivery model (ie, among 644 participants who engaged in all group sessions, 476 women [73.9%] received some or all content through individual engagement, and 315 women [48.9%] received some or all content remotely). After a median (IQR) 14.1 (11.4-20.1) months of follow-up, 1308 participants (81.2%) had primary outcome data. The intervention, compared with usual care, did not reduce worsening glycemic status (204 women [25.5%] vs 217 women [27.1%]; hazard ratio, 0.92; [95% CI, 0.76-1.12]; P = .42) or improve any secondary outcome. Conclusions and Relevance: This study found that a large proportion of women in South Asian urban settings developed dysglycemia soon after a GDM-affected pregnancy and that a lifestyle intervention, modified owing to the COVID-19 pandemic, did not prevent subsequent glycemic deterioration. These findings suggest that alternate or additional approaches are needed, especially among high-risk individuals. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2017/06/008744; Sri Lanka Clinical Trials Registry Identifier: SLCTR/2017/001; and ClinicalTrials.gov Identifier: NCT03305939.

Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial.

Importance: The effects of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, as an addition to insulin glargine for treatment of type 2 diabetes have not been described. Objective: To assess the efficacy and safety of tirzepatide added to insulin glargine in patients with type 2 diabetes with inadequate glycemic control. Design, Setting, and Participants: Randomized phase 3 clinical trial conducted at 45 medical research centers and hospitals in 8 countries (enrollment from August 30, 2019, to March 20, 2020; follow-up completed January 13, 2021) in 475 adults with type 2 diabetes and inadequate glycemic control while treated with once-daily insulin glargine with or without metformin. Interventions: Patients were randomized in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of 5-mg (n = 116), 10-mg (n = 119), or 15-mg (n = 120) tirzepatide or volume-matched placebo (n = 120) over 40 weeks. Tirzepatide was initiated at 2.5 mg/week and escalated by 2.5 mg every 4 weeks until the assigned dose was achieved. Main Outcomes and Measures: The primary end point was mean change from baseline in glycated hemoglobin A1c (HbA1c) at week 40. The 5 key secondary end points included mean change in body weight and percentage of patients achieving prespecified HbA1c levels. Results: Among 475 randomized participants (211 [44%] women; mean [SD] age, 60.6 [9.9] years; mean [SD] HbA1c, 8.31% [0.85%]), 451 (94.9%) completed the trial. Treatment was prematurely discontinued by 10% of participants in the 5-mg tirzepatide group, 12% in the 10-mg tirzepatide group, 18% in the 15-mg tirzepatide group, and 3% in the placebo group. At week 40, mean HbA1c change from baseline was -2.40% with 10-mg tirzepatide and -2.34% with 15-mg tirzepatide vs -0.86% with placebo (10 mg: difference vs placebo, -1.53% [97.5% CI, -1.80% to -1.27%]; 15 mg: difference vs placebo, -1.47% [97.5% CI, -1.75% to -1.20%]; P < .001 for both). Mean HbA1c change from baseline was -2.11% with 5-mg tirzepatide (difference vs placebo, -1.24% [95% CI, -1.48% to -1.01%]; P < .001]). Mean body weight change from baseline was -5.4 kg with 5-mg tirzepatide, -7.5 kg with 10-mg tirzepatide, -8.8 kg with 15-mg tirzepatide and 1.6 kg with placebo (5 mg: difference, -7.1 kg [95% CI, -8.7 to -5.4]; 10 mg: difference, -9.1 kg [95% CI, -10.7 to -7.5]; 15 mg: difference, -10.5 kg [95% CI, -12.1 to -8.8]; P < .001 for all). Higher percentages of patients treated with tirzepatide vs those treated with placebo had HbA1c less than 7% (85%-90% vs 34%; P < .001 for all). The most common treatment-emergent adverse events in the tirzepatide groups vs placebo group were diarrhea (12%-21% vs 10%) and nausea (13%-18% vs 3%). Conclusions and Relevance: Among patients with type 2 diabetes and inadequate glycemic control despite treatment with insulin glargine, the addition of subcutaneous tirzepatide, compared with placebo, to titrated insulin glargine resulted in statistically significant improvements in glycemic control after 40 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT04039503.

Small molecule SWELL1 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes.

Type 2 diabetes is associated with insulin resistance, impaired pancreatic ß-cell insulin secretion, and nonalcoholic fatty liver disease. Tissue-specific SWELL1 ablation impairs insulin signaling in adipose, skeletal muscle, and endothelium, and impairs ß-cell insulin secretion and glycemic control. Here, we show that ICl,SWELL and SWELL1 protein are reduced in adipose and ß-cells in murine and human diabetes. Combining cryo-electron microscopy, molecular docking, medicinal chemistry, and functional studies, we define a structure activity relationship to rationally-design active derivatives of a SWELL1 channel inhibitor (DCPIB/SN-401), that bind the SWELL1 hexameric complex, restore SWELL1 protein, plasma membrane trafficking, signaling, glycemic control and islet insulin secretion via SWELL1-dependent mechanisms. In vivo, SN-401 restores glycemic control, reduces hepatic steatosis/injury, improves insulin-sensitivity and insulin secretion in murine diabetes. These findings demonstrate that SWELL1 channel modulators improve SWELL1-dependent systemic metabolism in Type 2 diabetes, representing a first-in-class therapeutic approach for diabetes and nonalcoholic fatty liver disease.

The Glycemic Control Potential of Some Amaranthaceae Plants, with Particular Reference to In Vivo Antidiabetic Potential of Agathophora alopecuroides.

Natural products continue to provide inspiring moieties for the treatment of various diseases. In this regard, investigation of wild plants, which have not been previously explored, is a promising strategy for reaching medicinally useful drugs. The present study aims to investigate the antidiabetic potential of nine Amaranthaceae plants: Agathophora alopecuroides, Anabasis lachnantha, Atriplex leucoclada, Cornulaca aucheri, Halothamnus bottae, Halothamnus iraqensis, Salicornia persia, Salsola arabica, and Salsola villosa, growing in the Qassim area, the Kingdom of Saudi Arabia. The antidiabetic activity of the hydroalcoholic extracts was assessed using in vitro testing of α-glucosidase and α-amylase inhibitory effects. Among the nine tested extracts, A. alopecuroides extract (AAE) displayed potent inhibitory activity against α-glucosidase enzyme with IC50 117.9 µg/mL noting better activity than Acarbose (IC50 191.4 µg/mL). Furthermore, AAE displayed the highest α- amylase inhibitory activity among the nine tested extracts, with IC50 90.9 µg/mL. Based upon in vitro testing results, the antidiabetic activity of the two doses (100 and 200 mg/kg) of AAE was studied in normoglycemic and streptozotocin (STZ)-induced diabetic mice. The effects of the extract on body weight, food and water intakes, random blood glucose level (RBGL), fasting blood glucose level (FBGL), insulin, total cholesterol, and triglycerides levels were investigated. Results indicated that oral administration of the two doses of AAE showed a significant dose-dependent increase (p < 0.05) in the body weight and serum insulin level, as well as a significant decrease in food and water intake, RBGL, FBGL, total cholesterol, and triglyceride levels, in STZ-induced diabetic mice, compared with the diabetic control group. Meanwhile, no significant differences of both extract doses were observed in normoglycemic mice when compared with normal control animals. This study revealed a promising antidiabetic activity of the wild plant A. alopecuroides.

The Cost-Effectiveness of Supplemental Carnosine in Type 2 Diabetes.

In this paper, we assess the cost-effectiveness of 1 g daily of carnosine (an over the counter supplement) in addition to standard care for the management of type 2 diabetes and compare it to standard care alone. Dynamic multistate life table models were constructed in order to estimate both clinical outcomes and costs of Australians aged 18 years and above with and without type 2 diabetes over a ten-year period, 2020 to 2029. The dynamic nature of the model allowed for population change over time (migration and deaths) and accounted for the development of new cases of diabetes. The three health states were 'Alive without type 2 diabetes', 'Alive with type 2 diabetes' and 'Dead'. Transition probabilities, costs, and utilities were obtained from published sources. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. Over the ten-year period, the addition of carnosine to standard care treatment resulted in ICERs (discounted) of AUD 34,836 per YoLS and AUD 43,270 per QALY gained. Assuming the commonly accepted willingness to pay threshold of AUD 50,000 per QALY gained, supplemental dietary carnosine may be a cost-effective treatment option for people with type 2 diabetes in Australia.

Effect of COVID 19 pneumonia on hyperglycemia: Is it different from non COVID pneumonia?

BACKGROUND AND AIMS: Glycemic control in critical illness has been linked to outcomes. We sought to investigate if COVID pneumonia was causing disrupted glycemic control compared to historically similar diseases. METHODS: At Intermountain Healthcare, a 23-hospital healthcare system in the intermountain west, we performed a multicenter, retrospective cohort observational study. We compared 13,268 hospitalized patients with COVID pneumonia to 6673 patients with non -COVID-pneumonia. RESULTS: Patients with COVID-19 were younger had fewer comorbidities, had lower mortality and greater length of hospital stay. Our regression models demonstrated that daily insulin dose, indexed for weight, was associated with COVID-19, age, diabetic status, HgbA1c, admission SOFA, ICU length of stay and receipt of corticosteroids. There was significant interaction between a diagnosis of diabetes and having COVID-19. Time in range for our IV insulin protocol was not correlated with having COVID after adjustment. It was correlated with ICU length of stay, diabetic control (HgbA1C) and prior history of diabetes. Among patients with subcutaneous (SQ) insulin only percent of glucose checks in range was correlated with diabetic status, having Covid-19, HgbA1c, total steroids given and Elixhauser comorbidity score even when controlled for other factors. CONCLUSIONS: Hospitalized patients with COVID-19 pneumonia who receive insulin for glycemic control require both more SQ and IV insulin than the non-COVID-19 pneumonia counterparts. Patients with COVID-19 who received SQ insulin only had a lower percent of glucose checks in range.