Explore the vast range of titles available.

Observational studies suggest an association between a low 25-hydroxyvitamin D level and the risk of type 2 diabetes; whether vitamin D supplements reduce the risk is unknown. In this trial in which high-risk persons received either vitamin D 3 (4000 IU per day) or placebo, such supplementation did not significantly decrease the risk of type 2 diabetes.

Healthy dietary patterns rich in legumes can improve metabolic health, although their additional benefits in conjunction with calorie restriction have not been well-established. We investigated effects of a calorie-restricted, legume-enriched, multicomponent intervention diet compared with a calorie-restricted control diet in 127 Chinese prediabetes participants, living in Singapore. The study was a 16-week, single-blind, parallel-design, randomized controlled trial (n = 63 intervention group (IG), n = 64 control group (CG); mean ± SD age 62.2 ± 6.3 years, BMI 23.8 ± 2.6 kg/m 2 ). Primary outcomes were markers of glycemia and all measurements were taken at 2 or 4-weekly intervals. At the end of 16 weeks, both groups had significantly lower BMI ( q ( Time )  = 1.92 ×10 -42 , β   = -0.02) compared with baseline, with minimal difference between groups. The IG had significantly greater reductions in LDL cholesterol ( q ( Treatment×Time )  = 0.01, β   = -0.16), total cholesterol ( q ( Treatment×Time )  = 0.02, β   = -0.3) and HbA1c ( q ( Treatment×Time )  = 0.04, β   = -0.004) compared with CG, alongside increases in fiber degrading species in IG, mediated through metabolites such as bile acids and amino acids. A legume-enriched, multicomponent intervention diet can improve metabolic health in a prediabetes population, in addition to benefits obtained from calorie restriction alone, partially mediated through changes in gut microbial composition and function. Trial registration: Clinical Trials NCT04745702. Prediabetics have an increased risk of type 2 diabetes. In this parallel-design, randomized controlled trial, the authors show improvements in metabolic health in a prediabetes population consuming a legume-rich diet, which are mediated through favorable changes in gut microbiome.

Aims/hypothesisThis randomised controlled trial was performed in India and the UK in people with prediabetes to study whether mobile phone short message service (SMS) text messages can be used to motivate and educate people to follow lifestyle modifications, to prevent type 2 diabetes.MethodsThe study was performed in people with prediabetes (n = 2062; control: n = 1031; intervention: n = 1031) defined by HbA1c ≥42 and ≤47 mmol/mol (≥6.0% and ≤6.4%). Participants were recruited from public and private sector organisations in India (men and women aged 35–55 years) and by the National Health Service (NHS) Health Checks programme in the UK (aged 40–74 years without pre-existing diabetes, cardiovascular disease or kidney disease). Allocation to the study groups was performed using a computer-generated sequence (1:1) in India and by stratified randomisation in permuted blocks in the UK. Investigators in both countries remained blinded throughout the study period. All participants received advice on a healthy lifestyle at baseline. The intervention group in addition received supportive text messages using mobile phone SMS messages 2–3 times per week. Participants were assessed at baseline and at 6, 12 and 24 months. The primary outcome was conversion to type 2 diabetes and secondary outcomes included anthropometry, biochemistry, dietary and physical activity changes, blood pressure and quality of life.ResultsAt the 2 year follow-up (n = 2062; control: n = 1031; intervention: n = 1031), in the intention-to-treat population the HR for development of type 2 diabetes calculated using a discrete-time proportional hazards model was 0.89 (95% CI 0.74, 1.07; p = 0.22). There were no significant differences in the secondary outcomes.Conclusions/interpretationThis trial in two countries with varied ethnic and cultural backgrounds showed no significant reduction in the progression to diabetes in 2 years by lifestyle modification using SMS messaging.Trial registrationThe primary study was registered on www.ClinicalTrials.gov (India, NCT01570946; UK, NCT01795833).FundingThe study was funded jointly by the Indian Council for Medical Research and the UK Medical Research Council.

Abstract Rationale Although obstructive sleep apnea (OSA) is associated with impaired glucose tolerance and diabetes, it remains unclear whether OSA treatment with continuous positive airway pressure (CPAP) has metabolic benefits. Objectives To determine the effect of 8-hour nightly CPAP treatment on glucose metabolism in individuals with prediabetes and OSA. Methods In a randomized controlled parallel group study, 39 participants were randomly assigned to receive either 8-hour nightly CPAP (n = 26) or oral placebo (n = 13). Sleep was polysomnographically recorded in the laboratory on each night. CPAP adherence was ensured by continuous supervision. Participants continued their daily routine activities outside the laboratory. Glucose metabolism was assessed at baseline and after 2 weeks of assigned treatment using both the oral and intravenous glucose tolerance tests. The primary outcome was the overall glucose response as quantified by the area under the curve for glucose during 2-hour oral glucose tolerance testing. Secondary outcomes included fasting and 2-hour glucose and insulin, the area under the curves for insulin and insulin secretion, norepinephrine, insulin sensitivity, acute insulin response to glucose, and 24-hour blood pressure. Measurements and Main Results The overall glucose response was reduced (treatment difference: −1,276.9 [mg/dl] · min [95% confidence interval, −2,392.4 to −161.5]; P = 0.03) and insulin sensitivity was improved (treatment difference: 0.77 [mU/L]−1 · min−1 [95% confidence interval, 0.03–1.52]; P = 0.04) with CPAP as compared with placebo. Additionally, norepinephrine levels and 24-hour blood pressure were reduced with CPAP as compared with placebo. Conclusions In patients with prediabetes, 8-hour nightly CPAP treatment for 2 weeks improves glucose metabolism compared with placebo. Thus, CPAP treatment may be beneficial for metabolic risk reduction. Clinical trial registered with www.clinicaltrials.gov (NCT 01156116)

OBJECTIVE: Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program (DPP). We examined its long-term safety and tolerability along with weight loss, and change in waist circumference during the DPP and its long-term follow-up. RESEARCH DESIGN AND METHODS: The randomized double-blind clinical trial of metformin or placebo followed by a 7–8-year open-label extension and analysis of adverse events, tolerability, and the effect of adherence on change in weight and waist circumference. RESULTS: No significant safety issues were identified. Gastrointestinal symptoms were more common in metformin than placebo participants and declined over time. During the DPP, average hemoglobin and hematocrit levels were slightly lower in the metformin group than in the placebo group. Decreases in hemoglobin and hematocrit in the metformin group occurred during the first year following randomization, with no further changes observed over time. During the DPP, metformin participants had reduced body weight and waist circumference compared with placebo (weight by 2.06 ± 5.65% vs. 0.02 ± 5.52%, P < 0.001, and waist circumference by 2.13 ± 7.06 cm vs. 0.79 ± 6.54 cm, P < 0.001 in metformin vs. placebo, respectively). The magnitude of weight loss during the 2-year double-blind period was directly related to adherence (P < 0.001). Throughout the unblinded follow-up, weight loss remained significantly greater in the metformin group than in the placebo group (2.0 vs. 0.2%, P < 0.001), and this was related to the degree of continuing metformin adherence (P < 0.001). CONCLUSIONS: Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for at least 10 years of treatment.

Gut microbiota contributes to prediabetes progression, however, whether microbiota features can guide targeted prevention and treatment for diabetes requires validation through large-scale clinical trials. Here, in a randomized, open-label trial, we randomly assigned 802 prediabetic subjects to a usual care control group (patient education and dietary recommendations, n = 393) or a dietary fiber intervention group (n = 409) for 6 months. The primary outcome was the percentage change in whole-blood HbA1c, and secondary outcomes were the changes in other glucose, insulin, lipid, liver and kidney function, and anthropometric parameters. There were no statistically significant differences in the primary and secondary outcomes between groups. In post-hoc analysis, we reclassified subjects into four clusters using a multivariate clustering model based on age, BMI, HbA1c, HOMA2-IR and HOMA2-B. These clusters differed in metabolic status, risks of diabetes and its complications, gut microbiome and serum metabolites. Notably, dietary fiber improved glycemic control in Clusters 3 and 4, but not in Clusters 1 and 2, consistent with observed gut microbiota alleviations. By using a LightGBM machine learning model, we calculated a microbiome-based clinical decision score to predict personalized fiber intervention responses and identified individuals who can get glycemic benefits. In conclusion, our study suggests that the gut microbiota response influences the effectiveness of dietary fiber intervention and provides a clinically applicable model to guide microbiome-targeted personalized medicine for prediabetes. Clinical Trial Registry: ChiCTR1900027663. Here, in a large-scale clinical trial, the authors associate gut microbiota composition and metabolic status with effectiveness of dietary fiber intervention in prediabetes, and provide a clinically applicable model to guide microbiome-targeted personalized medicine.

We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (-0.6%, 95% CI, -1.1% to -0.03%, p = 0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications. This clinical trial was registered with ClinicalTrials.gov, number NCT01713764.

Our objective was to quantify and predict diabetes risk reduction during the Diabetes Prevention Program Outcomes Study (DPPOS) in participants who returned to normal glucose regulation at least once during the Diabetes Prevention Program (DPP) compared with those who consistently met criteria for prediabetes. DPPOS is an ongoing observational study of participants from the DPP randomised trial. For this analysis, diabetes cumulative incidence in DPPOS was calculated for participants with normal glucose regulation or prediabetes status during DPP with and without stratification by previous randomised treatment group. Cox proportional hazards modelling and generalised linear mixed models were used to quantify the effect of previous (DPP) glycaemic status on risk of later (DPPOS) diabetes and normal glucose regulation status, respectively, per SD in change. Included in this analysis were 1990 participants of DPPOS who had been randomly assigned to treatment groups during DPP (736 intensive lifestyle intervention, 647 metformin, 607 placebo). These studies are registered at ClinicalTrials.gov, NCT00004992 (DPP) and NCT00038727 (DPPOS). Diabetes risk during DPPOS was 56% lower for participants who had returned to normal glucose regulation versus those who consistently had prediabetes (hazard ratio [HR] 0·44, 95% CI 0·37–0·55, p<0·0001) and was unaffected by previous group assignment (interaction test for normal glucose regulation and lifestyle intervention, p=0·1722; normal glucose regulation and metformin, p=0·3304). Many, but not all, of the variables that increased diabetes risk were inversely associated with the chance of a participant reaching normal glucose regulation status in DPPOS. Specifically, previous achievement of normal glucose regulation (odds ratio [OR] 3·18, 95% CI 2·71–3·72, p<0·0001), increased β-cell function (OR 1·28; 95% CI 1·18–1·39, p<0·0001), and insulin sensitivity (OR 1·16, 95% CI 1·08–1·25, p<0·0001) were associated with normal glucose regulation in DPPOS, whereas the opposite was true for prediction of diabetes, with increased β-cell function (HR 0·80, 95% CI 0·71–0·89, p<0·0001) and insulin sensitivity (HR 0·83, 95% CI 0·74–0·94, p=0·0001) having a protective effect. Among participants who did not return to normal glucose regulation in DPP, those assigned to the intensive lifestyle intervention had a higher diabetes risk (HR 1·31, 95% CI 1·03–1·68, p=0·0304) and lower chance of normal glucose regulation (OR 0·59, 95% CI 0·42–0·82, p=0·0014) than did the placebo group in DPPOS. We conclude that prediabetes is a high-risk state for diabetes, especially in patients who remain with prediabetes despite intensive lifestyle intervention. Reversion to normal glucose regulation, even if transient, is associated with a significantly reduced risk of future diabetes independent of previous treatment group. US National Institutes of Health.

Prebiotic fibre represents a promising and efficacious treatment to manage pre-diabetes, acting via complementary pathways involving the gut microbiome and viscosity-related properties. In this study, we evaluated the effect of using a diverse prebiotic fibre supplement on glycaemic, lipid and inflammatory biomarkers in patients with pre-diabetes. Sixty-six patients diagnosed with pre-diabetes (yet not receiving glucose-lowering medications) were randomised into treatment (thirty-three) and placebo (thirty-three) interventions. Participants in the treatment arm consumed 20 g/d of a diverse prebiotic fibre supplement, and participants in the placebo arm consumed 2 g/d of cellulose for 24 weeks. A total of fifty-one and forty-eight participants completed the week 16 and week 24 visits, respectively. The intervention was well tolerated, with a high average adherence rate across groups. Our results extend upon previous work, showing a significant change in glycated haemoglobin (HbA1c) in the treatment group but only in participants with lower baseline HbA1c levels (< 6 % HbA1c) (P = 0·05; treatment –0·17 ± 0·27 v. placebo 0·07 ± 0·29, mean ± sd). Within the whole cohort, we showed significant improvements in insulin sensitivity (P = 0·03; treatment 1·62 ± 5·79 v. placebo –0·77 ± 2·11) and C-reactive protein (P FWE = 0·03; treatment –2·02 ± 6·42 v. placebo 0·94 ± 2·28) in the treatment group compared with the placebo. Together, our results support the use of a diverse prebiotic fibre supplement for physiologically relevant biomarkers in pre-diabetes.

Obesity is important for the development of type-2 diabetes as a result of obesity-induced insulin resistance accompanied by impaired compensation of insulin secretion from pancreatic beta cells. Here, based on a randomized pilot clinical trial, we report that intranasal oxytocin administration over an 8-week period led to effective reduction of obesity and reversal of related prediabetic changes in patients. Using mouse models, we further systematically evaluated whether oxytocin and its analogs yield therapeutic effects against prediabetic or diabetic disorders regardless of obesity. Our results showed that oxytocin and two analogs including [Ser4, Ile8]-oxytocin or [Asu1,6]-oxytocin worked in mice to reverse insulin resistance and glucose intolerance prior to reduction of obesity. In parallel, using streptozotocin-induced diabetic mouse model, we found that treatment with oxytocin or its analogs reduced the magnitude of glucose intolerance through improving insulin secretion. The anti-diabetic effects of oxytocin and its analogs in these animal models can be produced similarly whether central or peripheral administration was used. In conclusion, oxytocin and its analogs have multi-level effects in improving weight control, insulin sensitivity and insulin secretion, and bear potentials for being developed as therapeutic peptides for obesity and diabetes.