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In a multicenter, randomized, crossover trial involving children 1 to 7 years of age with type 1 diabetes, a closed-loop system was compared with sensor-augmented pump therapy in random order. The closed-loop system improved glycemic control in very young children with type 1 diabetes, without increasing the time spent in a hypoglycemic state.

In this randomized, controlled trial involving critically ill patients not receiving early parenteral nutrition, tight glucose control did not affect the length of time that ICU care was needed or mortality.

Orforglipron is a small-molecule, nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist in clinical development for type 2 diabetes and weight management. Additional data on the efficacy and safety of orforglipron are needed. In this phase 3, double-blind, placebo-controlled trial, we randomly assigned participants in a 1:1:1:1 ratio to receive orforglipron at one of three doses (3 mg, 12 mg, or 36 mg) or placebo once daily for 40 weeks. Participants had type 2 diabetes treated only with diet and exercise, a glycated hemoglobin level of at least 7.0% but no more than 9.5%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 23.0. The primary end point was the change from baseline to week 40 in the glycated hemoglobin level. A key secondary end point was the percent change in body weight from baseline to week 40. A total of 559 participants underwent randomization. The mean glycated hemoglobin level at baseline was 8.0%. At week 40, the estimated mean change from baseline in the glycated hemoglobin level was -1.24 percentage points with the 3-mg dose, -1.47 percentage points with the 12-mg dose, -1.48 percentage points with the 36-mg dose, and -0.41 percentage points with placebo. All three doses of orforglipron were superior to placebo with respect to the primary end point; the estimated mean difference from placebo was -0.83 percentage points (95% confidence interval [CI], -1.10 to -0.56) with the 3-mg dose, -1.06 percentage points (95% CI, -1.33 to -0.79) with the 12-mg dose, and -1.07 percentage points (95% CI, -1.33 to -0.81) with the 36-mg dose (P<0.001 for all comparisons). The mean glycated hemoglobin level at week 40 was 6.5 to 6.7% with orforglipron. The percent change in body weight from baseline to week 40 was -4.5% with the 3-mg dose, -5.8% with the 12-mg dose, -7.6% with the 36-mg dose, and -1.7% with placebo. The most common adverse events were mild-to-moderate gastrointestinal events, most of which occurred during dose escalation. No episodes of severe hypoglycemia were reported. Permanent discontinuation of orforglipron or placebo due to adverse events occurred in 4.4 to 7.8% of participants receiving orforglipron and 1.4% of participants receiving placebo. In adults with early type 2 diabetes, orforglipron significantly reduced the glycated hemoglobin level over a period of 40 weeks. (Supported by Eli Lilly; ACHIEVE-1 ClinicalTrials.gov number, NCT05971940.).

The 20-year UK Prospective Diabetes Study showed major clinical benefits for people with newly diagnosed type 2 diabetes randomly allocated to intensive glycaemic control with sulfonylurea or insulin therapy or metformin therapy, compared with conventional glycaemic control. 10-year post-trial follow-up identified enduring and emerging glycaemic and metformin legacy treatment effects. We aimed to determine whether these effects would wane by extending follow-up for another 14 years. 5102 patients enrolled between 1977 and 1991, of whom 4209 (82·5%) participants were originally randomly allocated to receive either intensive glycaemic control (sulfonylurea or insulin, or if overweight, metformin) or conventional glycaemic control (primarily diet). At the end of the 20-year interventional trial, 3277 surviving participants entered a 10-year post-trial monitoring period, which ran until Sept 30, 2007. Eligible participants for this study were all surviving participants at the end of the 10-year post-trial monitoring period. An extended follow-up of these participants was done by linking them to their routinely collected National Health Service (NHS) data for another 14 years. Clinical outcomes were derived from records of deaths, hospital admissions, outpatient visits, and accident and emergency unit attendances. We examined seven prespecified aggregate clinical outcomes (ie, any diabetes-related endpoint, diabetes-related death, death from any cause, myocardial infarction, stroke, peripheral vascular disease, and microvascular disease) by the randomised glycaemic control strategy on an intention-to-treat basis using Kaplan–Meier time-to-event and log-rank analyses. This study is registered with the ISRCTN registry, number ISRCTN75451837. Between Oct 1, 2007, and Sept 30, 2021, 1489 (97·6%) of 1525 participants could be linked to routinely collected NHS administrative data. Their mean age at baseline was 50·2 years (SD 8·0), and 41·3% were female. The mean age of those still alive as of Sept 30, 2021, was 79·9 years (SD 8·0). Individual follow-up from baseline ranged from 0 to 42 years, median 17·5 years (IQR 12·3–26·8). Overall follow-up increased by 21%, from 66 972 to 80 724 person-years. For up to 24 years after trial end, the glycaemic and metformin legacy effects showed no sign of waning. Early intensive glycaemic control with sulfonylurea or insulin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 10% (95% CI 2–17; p=0·015) for death from any cause, 17% (6–26; p=0·002) for myocardial infarction, and 26% (14–36; p<0·0001) for microvascular disease. Corresponding absolute risk reductions were 2·7%, 3·3%, and 3·5%, respectively. Early intensive glycaemic control with metformin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 20% (95% CI 5–32; p=0·010) for death from any cause and 31% (12–46; p=0·003) for myocardial infarction. Corresponding absolute risk reductions were 4·9% and 6·2%, respectively. No significant risk reductions during or after the trial for stroke or peripheral vascular disease were observed for both intensive glycaemic control groups, and no significant risk reduction for microvascular disease was observed for metformin therapy. Early intensive glycaemic control with sulfonylurea or insulin, or with metformin, compared with conventional glycaemic control, appears to confer a near-lifelong reduced risk of death and myocardial infarction. Achieving near normoglycaemia immediately following diagnosis might be essential to minimise the lifetime risk of diabetes-related complications to the greatest extent possible. University of Oxford Nuffield Department of Population Health Pump Priming.

Background: Alow carbohydrate diet (LCD) is more beneficial for the glycometabolism in type 2 diabetes (T2DM) and may be effective in reducing depression. Almond, which is a common nut, has been shown to effectively improve hyperglycemia and depression symptoms. This study aimed to determine the effect of an almond-based LCD (a-LCD) on depression and glycometabolism, as well as gut microbiota and fasting glucagon-like peptide 1 (GLP-1) in patients with T2DM. Methods: This was a randomized controlled trial which compared an a-LCD with a low-fat diet (LFD). Forty-five participants with T2DM at a diabetes club and the Endocrine Division of the First and Second Affiliated Hospital of Soochow University between December 2018 to December 2019 completed each dietary intervention for 3 months, including 22 in the a-LCD group and 23 in the LFD group. The indicators for depression and biochemical indicators including glycosylated hemoglobin (HbA1c), gut microbiota, and GLP-1 concentration were assessed at the baseline and third month and compared between the two groups. Results: A-LCD significantly improved depression and HbA1c (p < 0.01). Meanwhile, a-LCD significantly increased the short chain fatty acid (SCFAs)-producing bacteria Roseburia, Ruminococcus and Eubacterium. The GLP-1 concentration in the a-LCD group was higher than that in the LFD group (p < 0.05). Conclusions: A-LCD could exert a beneficial effect on depression and glycometabolism in patients with T2DM. We speculate that the role of a-LCD in improving depression in patients with T2DM may be associated with it stimulating the growth of SCFAs-producing bacteria, increasing SCFAs production and GPR43 activation, and further maintaining GLP-1 secretion. In future studies, the SCFAs and GPR43 activation should be further examined.

Aims/hypothesis We conducted the largest and longest clinical trial comparing a whole-food, plant-based intervention with standard medical care (SMC) in individuals with type 2 diabetes. Methods We randomised (parallel-arm; computerised 1:1 randomisation ratio) 169 adults aged 18–75 years with type 2 diabetes in the Marshall Islands to an intensive whole-food, plant-based intervention with moderate exercise (PB+Ex) or SMC for 24 weeks. The PB+Ex intervention included 12 weeks of meals, exercise sessions and group classes. Primary outcomes were glycaemic control (HbA 1c , glucose, insulin and HOMA-IR) and glucose-lowering medication use. Secondary outcomes included lipids, blood pressure, heart rate and C-reactive protein. Only lab analysts were blinded. Results Compared with SMC ( n =90 randomised; n =70 analysed), the PB+Ex ( n =79 randomised; n =66 analysed) intervention decreased HbA 1c by an additional 14 mmol/mol (1.3%) at week 12 (−22 vs −7 mmol/mol [−2.0% vs −0.7%]; p <0.0001) and 8 mmol/mol (0.7%) at week 24 (−16 vs −8 mmol/mol [−1.4% vs −0.7%]; p =0.01). Concomitantly, 63% of medicated PB+Ex participants reduced their glucose-lowering medications (vs 24%; p =0.006), and 23% of PB+Ex participants with a baseline HbA 1c <75 mmol/mol (<9%) achieved remission. Additionally, the PB+Ex intervention reduced weight (−2.7 kg; p <0.0001), C-reactive protein (−11 nmol/l; p =0.005) and cardiovascular medication use compared with SMC. At intermediate timepoints, it improved glucose, insulin, HOMA-IR, cholesterol, triglycerides and heart rate, but not at week 24. Conclusions/interpretation A whole-food, plant-based lifestyle intervention was more effective for improving glycaemic control than SMC. It also reduced the need for diabetes and cardiovascular medications and induced diabetes remission in some participants. Therefore, it is an effective, evidence-based lifestyle option for individuals with type 2 diabetes. Trial registration ClinicalTrials.gov NCT03862963 Funding This research was funded by the Department of the Army (W81XWH-05-1-0547). CJH received support through a National Institutes of Health Predoctoral T32 Obesity Fellowship (T32 HL105349). Graphical Abstract

Patients with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM) have a substantially increased risk for major cardiovascular events and mortality. Increasing physical activity and improving a healthy diet may effectively reduce cardiovascular risk factors; however, the effects are often transient. In a multicenter, 1:1 randomized controlled trial including 502 patients with combined CHD and T2DM (68 ± 8 years; 84% men), we assessed the effects of a home-based telemedicine-supported lifestyle intervention (exercise training, nutritional recommendations and health literacy training) with regular individualized feedback versus usual care. The study met its primary endpoint of reduced glycated hemoglobin after 6 months in favor of the lifestyle intervention group (mean between-group difference in the complete-case analysis ( n  = 197 and n  = 193), −0.13% (95% confidence interval, −0.25 to −0.01), P  = 0.04). When individualized feedback and health literacy training were discontinued after 6 months (while other telemedicine tools were maintained), no statistically significant between-group differences were observed at 12 months. At 12 months, 31 patients (6.2%) had a major adverse cardiovascular event (lifestyle intervention, n  = 20 (8.0%); usual care, n  = 11 (4.4%); P  = 0.15), with the main reason being hospitalization for angina or revascularization (lifestyle intervention, n  = 15; usual care, n  = 8). There were five deaths (lifestyle intervention, n  = 2; usual care, n  = 3), none of which were categorized as related to the intervention. However, three events that resulted in hospitalization were categorized as potentially related to the intervention (decompensation of heart failure, vertebral disc prolapse and inguinal hernia). In conclusion, a home-based lifestyle intervention with telemedicine support showed modest effects in patients with CHD and T2DM. ClinicalTrials.gov registration: NCT03835923 . A randomized controlled trial showed that a home-based, telemedicine-supported lifestyle intervention, which consisted of exercise training, nutrition recommendations and health literacy training, reported improved glycemic control after 6 months in patients with coronary heart disease and type 2 diabetes compared to usual care.

Abstract Context In a clinical study, tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1RA), provided superior glycemic control vs the GLP-1RA semaglutide. The physiologic mechanisms are incompletely understood. Objective This work aimed to evaluate treatment effects by model-based analyses of mixed-meal tolerance test (MMTT) data. Methods A 28-week double–blind, randomized, placebo-controlled trial of patients with type 2 diabetes treated with metformin was conducted at 2 clinical research centers in Germany. Interventions included tirzepatide 15 mg, semaglutide 1 mg, and placebo. Main outcome measures included glycemic control, model-derived β-cell function indices including insulin secretion rate (ISR) at 7.2–mmol/L glucose (ISR7.2), β-cell glucose sensitivity (β-CGS), insulin sensitivity, and estimated hepatic insulin-to-glucagon ratio. Results Tirzepatide significantly reduced fasting glucose and MMTT total glucose area under the curve (AUC) vs semaglutide (P < .01). Incremental glucose AUC did not differ significantly between treatments; therefore, greater total glucose AUC reduction with tirzepatide was mainly attributable to greater suppression of fasting glucose. A greater reduction in total ISR AUC was achieved with tirzepatide vs semaglutide (P < .01), in the context of greater improvement in insulin sensitivity with tirzepatide (P < .01). ISR7.2 was significantly increased with tirzepatide vs semaglutide (P < .05), showing improved β-CGS. MMTT-derived β-CGS was increased but not significantly different between treatments. Both treatments reduced fasting glucagon and total glucagon AUC, with glucagon AUC significantly reduced with tirzepatide vs semaglutide (P < .01). The estimated hepatic insulin-to-glucagon ratio did not change substantially with either treatment. Conclusion These results suggest that the greater glycemic control observed for tirzepatide manifests as improved fasting glucose and glucose excursion control, due to improvements in ISR, insulin sensitivity, and glucagon suppression.

Abstract Context The precise glycemic impact and clinical relevance of postprandial exercise in type 1 diabetes (T1D) has not been clarified yet. Objective This work aimed to examine acute, subacute, and late effects of postprandial exercise on blood glucose (BG). Methods A randomized, controlled trial comprised 4 laboratory visits, with 24-hour follow-up at home. Participants included adults with T1D (n = 8), aged 44 ± 13 years, with body mass index of 24 ± 2.1. Intervention included 30 minutes of rest (CONTROL), walking (WALK), moderate-intensity (MOD), or intermittent high-intensity (IHE) exercise performed 60 minutes after a standardized meal. Main outcome measures included BG change during exercise/control (acute), and secondary outcomes included the subacute (≤2 h after) and late glycemic effects (≤24 h after). Results Exercise reduced postprandial glucose (PPG) excursion compared to CONTROL, with a consistent BG decline in all patients for all modalities (mean declines −45 ± 24, −71 ± 39, and −35 ± 21 mg/dL, during WALK, MOD, and IHE, respectively (P < .001). For this decline, clinical superiority was demonstrated separately for each exercise modality vs CONTROL. Noninferiority of WALK vs MOD was not demonstrated, noninferiority of WALK vs IHE was demonstrated, and equivalence of IHE vs MOD was not demonstrated. Hypoglycemia did not occur during exercise. BG increased in the hour after exercise (more than after CONTROL; P < .001). More than half of participants showed hyperglycemia after exercise necessitating insulin correction. There were more nocturnal hypoglycemic events after exercise vs CONTROL (P < .05). Conclusion Postprandial exercise of all modalities is effective, safe, and feasible if necessary precautions are taken (ie, prandial insulin reductions), as exercise lowered maximal PPG excursion and caused a consistent and clinically relevant BG decline during exercise while there was no hypoglycemia during or shortly after exercise. However, there seem to be 2 remaining challenges: subacute postexercise hyperglycemia and nocturnal hypoglycemia.

Purpose Postprandial glycaemic control is critical for diabetes prevention and management. Various dietary strategies have been explored to modulate postprandial glycaemia, with the inclusion of innovative fibres showing promising benefits in reducing daily glycaemic load and improving overall glycaemic control. Methods In this study, we conducted an 8-week, randomised, controlled, parallel-arm trial involving 78 healthy adults living in Singapore (average age: 39.9 ± 10.6 years; 48 men and 30 women), who were divided into two subgroups: the overweight group (OG) and the genetic risk group (GRG). Results Daily supplementation with 40 g of NUTRIOSE ® soluble fibre significantly improved 24 h glucose homeostasis under free-living conditions. Compared to the postprandial glycaemic response after breakfast and lunch, NUTRIOSE ® supplementation for 8 weeks resulted in a more substantial improvement in the glycaemic response after dinner. Furthermore, one day of NUTRIOSE ® supplementation led to improved glucose management in both participant subgroups, with more significant improvements observed in the OG group compared to the GRG. However, a reduction in appetite following NUTRIOSE ® supplementation was mostly observed in the GRG. Additionally, NUTRIOSE ® consumption led to a decrease in PBFtrunk% and an increase in FFMtrunk in female participants in the GRG. Conclusion Incorporating innovative fibres can serve as an effective dietary strategy to lower daily glycaemic load and enhance glycaemic control, offering significant public health benefits and encouraging the consumption of resistant dextrin. However, further investigation into the role of chrono-nutrition is warranted, as it plays a key role in understanding glucose homeostasis throughout the day.