Explore the vast range of titles available.

Objective: Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years. Design: A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers. Subjects: A total of 564 adults ( n =90–98 per group; body mass index 30–40 kg m −2 ) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n =90–95), placebo ( n =98) or open-label orlistat (120 mg × 3, n =95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007–April 2009 and is registered with Clinicaltrials.gov , number NCT00480909. Results: From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7–8.0) more weight than those on placebo and 3.8 kg (1.6–6.0) more than those on orlistat ( P ⩽0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n =184) lost 3.0 kg (1.3–4.7) more weight than those on orlistat ( n =95; P <0.001). Completers on liraglutide 2.4/3.0 mg ( n =92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids. Conclusion: Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors.

Aims/hypothesis Although the Diabetes Prevention Program (DPP) established lifestyle changes (diet, exercise and weight loss) as the ‘gold standard’ preventive therapy for diabetes, the relative contribution of exercise alone to the overall utility of the combined diet and exercise effect of DPP is unknown; furthermore, the optimal intensity of exercise for preventing progression to diabetes remains very controversial. To establish clinical efficacy, we undertook a study (2009 to 2013) to determine: how much of the effect on measures of glucose homeostasis of a 6 month programme modelled after the first 6 months of the DPP is due to exercise alone; whether moderate- or vigorous-intensity exercise is better for improving glucose homeostasis; and to what extent amount of exercise is a contributor to improving glucose control. The primary outcome was improvement in fasting plasma glucose, with improvement in plasma glucose AUC response to an OGTT as the major secondary outcome. Methods The trial was a parallel clinical trial. Sedentary, non-smokers who were 45–75 year old adults ( n  = 237) with elevated fasting glucose (5.28–6.94 mmol/l) but without cardiovascular disease, uncontrolled hypertension, or diabetes, from the Durham area, were studied at Duke University. They were randomised into one of four 6 month interventions: (1) low amount (42 kJ kg body weight −1 week −1 [KKW])/moderate intensity: equivalent of expending 42 KKW (e.g. walking ∼16 km [8.6 miles] per week) with moderate-intensity (50% V . O 2 reserve ) exercise; (2) high amount (67 KKW)/moderate intensity: equivalent of expending 67 KKW (∼22.3 km [13.8 miles] per week) with moderate-intensity exercise; (3) high amount (67 KKW)/vigorous intensity: equivalent to group 2, but with vigorous-intensity exercise (75% V . O 2 reserve ); and (4) diet + 42 KKW moderate intensity: same as group 1 but with diet and weight loss (7%) to mimic the first 6 months of the DPP. Computer-generated randomisation lists were provided by our statistician (G. P. Samsa). The randomisation list was maintained by L. H. Willis and C. A. Slentz with no knowledge of or input into the scheduling, whereas all scheduling was done by L. A. Bateman, with no knowledge of the randomisation list. Subjects were automatically assigned to the next group listed on the randomisation sheet (with no ability to manipulate the list order) on the day that they came in for the OGTT, by L. H. Willis. All plasma analysis was done blinded by the individuals doing the measurements (i.e. lipids, glucose, insulin). Subjects and research staff (other than individuals analysing the blood) were not blinded to the group assignments. Results Number randomised, completers and number analysed with complete OGTT data for each group were: low-amount/moderate-intensity (61, 43, 35); high-amount/moderate-intensity (61, 44, 40); high-amount/vigorous-intensity (61, 43, 38); diet/exercise (54, 45, 37), respectively. Only the diet and exercise group experienced a decrease in fasting glucose ( p  < 0.001). The means and 95% CIs for changes in fasting glucose (mmol/l) for each group were: high-amount/moderate-intensity −0.07 (−0.20, 0.06); high-amount/vigorous 0.06 (−0.07, 0.19); low-amount/moderate 0.05 (−0.05, 0.15); and diet/exercise −0.32 (−0.46, −0.18). The effects sizes for each group (in the same order) were: 0.17, 0.15, 0.18 and 0.71, respecively. For glucose tolerance (glucose AUC of OGTT), similar improvements were observed for the diet and exercise (8.2% improvement, effect size 0.73) and the 67 KKW moderate-intensity exercise (6.4% improvement, effect size 0.60) groups; moderate-intensity exercise was significantly more effective than the same amount of vigorous-intensity exercise ( p  < 0.0207). The equivalent amount of vigorous-intensity exercise alone did not significantly improve glucose tolerance (1.2% improvement, effect size 0.21). Changes in insulin AUC, fasting plasma glucose and insulin did not differ among the exercise groups and were numerically inferior to the diet and exercise group. Conclusions/interpretation In the present clinical efficacy trial we found that a high amount of moderate-intensity exercise alone was very effective at improving oral glucose tolerance despite a relatively modest 2 kg change in body fat mass. These data, combined with numerous published observations of the strong independent relation between postprandial glucose concentrations and prediction of future diabetes, suggest that walking ∼18.2 km (22.3 km prescribed with 81.6% adherence in the 67 KKW moderate-intensity group) per week may be nearly as effective as a more intensive multicomponent approach involving diet, exercise and weight loss for preventing the progression to diabetes in prediabetic individuals. These findings have important implications for the choice of clinical intervention to prevent progression to type 2 diabetes for those at high risk. Trial registration : ClinicalTrials.gov NCT00962962 Funding : The study was funded by National Institutes for Health National Institute of Diabetes and Digestive and Kidney Diseases (NIH-NDDK) (R01DK081559)

Background/Objectives: Despite advances in public health and medical treatment, the number of patients with type 2 diabetes is increasing and it remains among the top 10 causes of death and a leading cause of disability in the United States. Early interventions with innovative approaches are essential to improving dietary intake and blood glucose control, potentially preventing or delaying type 2 diabetes and related complications. This study examined the effects of integrating real-time feedback from continuous glucose monitoring (CGM) into individualized nutrition therapy (INT) on diet and sleep quality in individuals with prediabetes and overweight or obesity. Methods: Thirty participants were randomized to either the treatment (n = 15) or the control group (n = 15). Both groups received individualized nutrition recommendations tailored to energy needs for weight maintenance and blood glucose control. The treatment group had real-time access to CGM data, while the control group remained blinded. Dietary intake and sleep quality were assessed using ASA24 recall and analyzed via general linear model repeated measures. Results: Incorporating CGM feedback into nutrition therapy significantly increased whole-grain (p = 0.02) and plant-based protein intake (p = 0.02) in the treatment group, with trends toward increased fruit intake (p = 0.07) and a reduced percentage of calories from carbohydrates (p = 0.08). Sleep efficiency also improved significantly by 5% (p = 0.02) following the intervention. Conclusions: These findings support the effectiveness of CGM-enhanced nutrition therapy in improving diet and sleep quality in individuals with prediabetes and overweight or obesity. Further research is needed to assess the sustainability and long-term impact of this approach.

Aims/hypothesisWe aimed to investigate the short-term efficacy and safety of three glucose-lowering interventions in overweight or obese individuals with prediabetes defined by HbA1c.MethodsThe PRE-D Trial was a randomised, controlled, parallel, multi-arm, open-label, non-blinded trial performed at Steno Diabetes Center Copenhagen, Gentofte, Denmark. One hundred and twenty participants with BMI ≥25 kg/m2, 30–70 years of age, and prediabetes (HbA1c 39–47 mmol/mol [5.7–6.4%]) were randomised 1:1:1:1 to dapagliflozin (10 mg once daily), metformin (1700 mg daily), interval-based exercise (5 days/week, 30 min/session) or control (habitual lifestyle). Participants were examined at baseline and at 6, 13 and 26 weeks after randomisation. The primary outcome was the 13 week change in glycaemic variability (calculated as mean amplitude of glycaemic excursions [MAGE]) determined using a continuous glucose monitoring system (pre-specified minimal clinically important difference in MAGE ∼30%).ResultsOne hundred and twelve participants attended the examination at 13 weeks and 111 attended the follow-up visit at 26 weeks. Compared with the control group, there was a small decrease in MAGE in the dapagliflozin group (17.1% [95% CI 0.7, 30.8], p = 0.042) and a small, non-significant, reduction in the exercise group (15.3% [95% CI −1.2, 29.1], p = 0.067), whereas MAGE was unchanged in the metformin group (0.1% [95% CI −16.1, 19.4], p = 0.991)). Compared with the metformin group, MAGE was 17.2% (95% CI 0.8, 30.9; p = 0.041) lower in the dapagliflozin group and 15.4% (95% CI −1.1, 29.1; p = 0.065) lower in the exercise group after 13 weeks, with no difference between exercise and dapagliflozin (2.2% [95% CI −14.8, 22.5], p = 0.815). One serious adverse event occurred in the control group (lung cancer).Conclusions/interpretationTreatment with dapagliflozin and interval-based exercise lead to similar but small improvements in glycaemic variability compared with control and metformin therapy. The clinical importance of these findings in prediabetes is uncertain.Trial registrationClinicalTrials.gov NCT02695810FundingThe study was funded by the Novo Nordisk Foundation, AstraZeneca AB, the Danish Innovation Foundation, the University of Copenhagen and Ascensia Diabetes Care Denmark ApS

Background/Objectives: prediabetes is a significant risk factor for the development of type 2 diabetes, cardiovascular diseases, chronic kidney disease, and other complications. Early diagnosis of prediabetes, coupled with education on lifestyle changes that support blood glucose management, are crucial for the prevention or delay of type 2 diabetes and related complications. This study aimed to evaluate the impact of incorporating real-time feedback from continuous glucose monitoring (CGM) into individualized nutrition therapy (INT) on blood glucose control in individuals with prediabetes who are overweight or obese. Methods: participants (mean age ± SD: 55 ± 6 years; BMI: 31.1 ± 4.1 kg/m²) were randomly assigned to either the treatment group (n = 15) or the control group (n = 15). Both groups received INT and CGM, but the control group was blinded to the CGM data until the end of this study. Participants were followed for 30 days and visited the lab every 10 days for CGM replacement, study measurements, and dietary consultations. Results: the treatment group showed a significant increase in the percentage of time spent in the target blood glucose range (p = 0.02) and a significant decrease in the mean blood glucose concentration (p < 0.05), glucose management indicator (p = 0.02), percent coefficient of variation for blood glucose (p = 0.01), and percent time spent in the high or very high blood glucose ranges (p = 0.04). These changes were not statistically significant for the control group. Conclusions: adding CGM feedback to INT resulted in better management of blood glucose levels in overweight or obese individuals with prediabetes.

The complex interactions between intestinal microbiota and metabolic disorders are well-documented, with implications for glucose metabolism, energy expenditure, and intestinal permeability. Prebiotics induce beneficial changes in gut microbiota composition in prediabetes, while postbiotics can enhance gut barrier function, complementing each other to improve glucose metabolism and insulin sensitivity. This study investigated the effects of a 12-week dietary fibre (DF) supplement on gut health, metabolic function, and diet. The supplement contained konjac glucomannan (KGM), galacto-oligosaccharides (GOSs), and exopolysaccharides (EPSs) from Bifidobacterium breve. In a randomised, double-blind, placebo-controlled, parallel-group clinical trial, 53 prediabetic volunteers were randomly assigned to either a daily DF supplement (YMETA) or a placebo (cellulose microcrystalline) for 12 weeks, followed by a 4-week follow-up. Measurements included gut microbiota composition, glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), plasma lipids, anthropometry, body composition, blood pressure, and dietary intake. The intervention group showed a significant increase in alpha diversity and butyrate-producing bacteria, with reductions in HbA1c and FPG levels below prediabetes thresholds. No significant changes were observed in the placebo group. This study suggests that manipulating the human gut microbiome through dietary interventions could be a promising therapeutic approach to managing prediabetes and preventing or delaying diabetes.

Obesity stands out as a primary risk factor for diabetes. Attaining healthy weight loss, especially reducing body fat, is important in managing prediabetes and preventing progression to full diabetes and its co-morbidities. This study examined the effects of personalized nutrition therapy (PNT) combined with continuous glucose monitoring (CGM) on body weight and composition in individuals with prediabetes. A total of 30 individuals with prediabetes who were overweight or obese were assigned randomly to either the treatment, observed CGM data plus PNT, or the control group which was blinded to their blood glucose results throughout the study. Both groups were provided with dietary recommendations for calorie intake and macronutrient distribution, coupled with personalized goal setting for glucose control and healthy eating, without any specific emphasis on weight reduction or changes in physical activity. Regular visits were scheduled every 10 days to perform measurements and replace CGMs. Data were analyzed using General Linear Model with repeated measures. Over the 30-day follow-up period, both groups experienced significant reductions in weight and fat mass. The treatment group exhibited two-fold greater reductions in both weight and fat mass, a significant decrease in carbohydrate intake, and a significant increase in time spent on physical activitycompared to the control group. In addition, compliance was notably higher in the treatment group. These findings indicate that overweight or obese individuals with prediabetes can achieve weight loss and improved body composition through personalized education for glucose control, without exclusively emphasizing weight loss as the primary objective. Additionally, the real-time feedback provided by CGM enhances these improvements.

Hypertriglyceridemia and diabetes mellitus type 2 are among the most important metabolic diseases globally. Diet plays a vital role in the development and progression of both clinical pictures. For the 10-week randomized, controlled, intervention study, 67 subjects with elevated plasma triglyceride (TG) concentrations (≥1.7 mmol/L) and 69 subjects with elevated fasting glucose concentrations (≥5.6 < 7.0 mmol/L) were recruited. The intervention groups received specially developed, individualized menu plans and regular counseling sessions to lower (A) TG or (B) fasting glucose and glycated hemoglobin A1c as well as other cardiovascular and diabetic risk factors. The hypertriglyceridemia intervention group was further supplemented with fish oil (3.5 g/d eicosapentaenoic acid + docosahexaenoic acid). The two control groups maintained a typical Western diet. Blood samples were taken every 2 weeks, and anthropometric data were collected. A follow-up examination was conducted after another 10 weeks. In both intervention groups, there were comparable significant reductions in blood lipids, glucose metabolism, and anthropometric parameters. These results were, with a few exceptions, significantly more pronounced in the intervention groups than in the corresponding control groups (comparison of percentage change from baseline). In particular, body weight was reduced by 7.4% (6.4 kg) and 7.5% (5.9 kg), low-density lipoprotein cholesterol concentrations by 19.8% (0.8 mmol/L) and 13.0% (0.5 mmol/L), TG concentrations by 18.2% (0.3 mmol/L) and 13.0% (0.2 mmol/L), and homeostatic model assessment for insulin resistance by 31.8% (1.1) and 26.4% (0.9) (p < 0.05) in the hypertriglyceridemia and prediabetes intervention groups, respectively. Some of these changes were maintained until follow-up. In patients with elevated TG or fasting glucose, implementing individualized menu plans in combination with regular counseling sessions over 10 weeks led to a significant improvement in cardiovascular and diabetic risk factors.

Background The metabolic effects of combined metformin and aerobic exercise on skeletal muscle in prediabetes remain unclear. We evaluated individual and combined effects on skeletal muscle metabolism using multiparameter magnetic resonance imaging (MRI) and assessed prediabetes remission. Materials and methods In this 12-week randomized controlled trial, forty-two prediabetic adults aged 48.4 ± 13.1 years mean ± standard deviation) were randomized into control ( n  = 10), metformin ( n  = 10), exercise ( n  = 11), and combined therapy ( n  = 11) groups. Multiparameter MRI measured T2, apparent diffusion coefficient (ADC), fractional anisotropy (FA), intermuscular adipose tissue (IMAT), intramyocellular lipids, visceral adipose tissue (VAT), and muscle cross-sectional areas (MSCAs). Blood biomarkers were assessed by standard protocols. Analyses included ANOVA, Fisher's exact test, and correlation analysis. Results Normoglycemia occurred in 90% of the combined group, 80% of the exercise, 20% of the metformin, and 10% of the controls. Exercise alone significantly decreased IMAT%, T2, and ADC, and increased FA, whereas metformin alone had no significant effects. Combination therapy did not further improve blood biomarkers or change MRI parameters versus exercise, but uniquely reduced VAT and increased MSCAs. IMAT% reduction was borderline greater in subjects with high baseline IMAT after combination therapy ( p  = 0.051). MRI parameters, particularly IMAT%, T2, and FA, correlated with fasting glucose, incremental area under the curve of glucose and insulin, and hemoglobin A1c. Conclusion Aerobic exercise favorably altered skeletal muscle tissue characteristics and metabolic markers in prediabetes. Metformin did not attenuate these effects and may enhance IMAT reduction in subjects with high baseline IMAT. Relevance statement Multiparameter MRI provides a sensitive, noninvasive means to quantify skeletal muscle composition and function in prediabetes, enabling precise assessment of the metabolic effects of combined lifestyle and pharmacological interventions. Trial registration Chinese Clinical Trial Registry (ChiCTR2300072162), retrospectively registered on June 5, 2023. Key Points Aerobic exercise improves muscle composition and glucose metabolism in prediabetes. Metformin adds benefits for reducing muscle fat in high-fat individuals. Multiparameter MRI enables noninvasive monitoring of skeletal muscle metabolic changes. Graphical Abstract

Aims. Prediabetes has been proved as an important risk factor of both diabetes and cardiovascular disease (CVD). Previous studies have shown that both lifestyle intervention and pioglitazone may delay the development of diabetes in patients with prediabetes. However, no study has ever explored whether these interventions could revert prediabetes to normal glycemic status as the primary outcome. Interventions that may revert prediabetes back to normal glucose status would be of great clinical importance. Materials and Methods. We conducted a randomized, multicenter, 2×2 factorial designed study to examine whether intensive lifestyle intervention and/or pioglitazone could revert prediabetes to normal glucose tolerance. The participants were followed up for three years unless they reverted to normal glucose state or developed diabetes at the annual oral glucose tolerance test (OGTT). Reversion to normal glucose tolerance was confirmed on the basis of the results of OGTT. Results. In our study, 1945 eligible patients were ultimately randomized into four groups. In this three-year follow-up study, overall, 60.0%, 50.3%, 56.6% and 65.1% reverted back to normoglycemic state over 3 years of follow-up in the conventional lifestyle intervention plus placebo, intensive lifestyle intervention plus placebo, conventional lifestyle intervention plus pioglitazone, and intensive lifestyle intervention plus pioglitazone groups, respectively. Compared to the conventional lifestyle intervention plus placebo group, all the other three groups did not show any significant benefit in terms of reverting back to normoglycemic state. Conclusion. In our study, for patients with prediabetes, neither intensive lifestyle intervention nor pioglitazone had led to a higher reversion rate to normal glucose state. Trail registration.http://www.chictr.org.cn: ChiCTR-PRC-06000005.