Effects of 3 months of 10-h per-day time-restricted eating and 3 months of follow-up on bodyweight and cardiometabolic health in Danish individuals at high risk of type 2 diabetes: the RESET single-centre, parallel, superiority, open-label, randomised controlled trial.

BACKGROUND: Time-restricted eating (TRE) has been suggested to be a simple, feasible, and effective dietary strategy for individuals with overweight or obesity. We aimed to investigate the effects of 3 months of 10-h per-day TRE and 3 months of follow-up on bodyweight and cardiometabolic risk factors in individuals at high risk of type 2 diabetes. METHODS: This was a single-centre, parallel, superiority, open-label randomised controlled clinical trial conducted at Steno Diabetes Center Copenhagen (Denmark). The inclusion criteria were age 30-70 years with either overweight (ie, BMI ≥25 kg/m2) and concomitant prediabetes (ie, glycated haemoglobin [HbA1c] 39-47 mmol/mol) or obesity (ie, BMI ≥30 kg/m2) with or without prediabetes and a habitual self-reported eating window (eating and drinking [except for water]) of 12 h per day or more every day and of 14 h per day or more at least 1 day per week. Individuals were randomly assigned 1:1 to 3 months of habitual living (hereafter referred to as the control group) or TRE, which was a self-selected 10-h per-day eating window placed between 0600 h and 2000 h. Randomisation was done in blocks varying in size and was open for participants and research staff, but outcome assessors were masked during statistical analyses. The randomisation list was generated by an external statistician. The primary outcome was change in bodyweight, assessed after 3 months (12 weeks) of the intervention and after 3 months (13 weeks) of follow-up. Adverse events were reported and registered at study visits or if participants contacted study staff to report events between visits. This trial is registered on ClinicalTrials.gov (NCT03854656). FINDINGS: Between March 12, 2019, and March 2, 2022, 100 participants (66 [66%] were female and 34 [34%] were male; median age 59 years [IQR 52-65]) were enrolled and randomly assigned (50 to each group). Of those 100, 46 (92%) in the TRE group and 46 (92%) in the control group completed the intervention period. After 3 months of the intervention, there was no difference in bodyweight between the TRE group and the control group (-0·8 kg, 95% CI -1·7 to 0·2; p=0·099). Being in the TRE group was not associated with a lower bodyweight compared with the control group after subsequent 3-month follow-up (-0·2 kg, -1·6 to 1·2). In the per-protocol analysis, participants who completed the intervention in the TRE group lost 1·0 kg (-1·9 to -0·0; p=0·040) bodyweight compared with the control group after 3 months of intervention, which was not maintained after the 3-month follow-up period (-0·4 kg, -1·8 to 1·0). During the trial and follow-up period, one participant in the TRE group reported a severe adverse event: development of a subcutaneous nodule and pain when the arm was in use. This side-effect was evaluated to be related to the trial procedures. INTERPRETATION: 3 months of 10-h per-day TRE did not lead to clinically relevant effects on bodyweight in middle-aged to older individuals at high risk of type 2 diabetes. FUNDING: Novo Nordisk Foundation, Aalborg University, Helsefonden, and Innovation Fund Denmark.

The Effectiveness of Digital Health Lifestyle Interventions on People With Prediabetes: Protocol for a Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: There has been an increasing interest in the use of digital health lifestyle interventions for people with prediabetes, as these interventions may offer a scalable approach to preventing type 2 diabetes. Previous systematic reviews on digital health lifestyle interventions for people with prediabetes had limitations, such as a narrow focus on certain types of interventions, a lack of statistical pooling, and no broader subgroup analysis of intervention characteristics. The identified limitations observed in previous systematic reviews substantiate the necessity of conducting a comprehensive review to address these gaps within the field. This will enable a comprehensive understanding of the effectiveness of digital health lifestyle interventions for people with prediabetes. OBJECTIVE: The objective of this systematic review, meta-analysis, and meta-regression is to systematically investigate the effectiveness of digital health lifestyle interventions on prediabetes-related outcomes in comparison with any comparator without a digital component among adults with prediabetes. METHODS: This systematic review will include randomized controlled trials that investigate the effectiveness of digital health lifestyle interventions on adults (aged 18 years or older) with prediabetes and compare the digital interventions with nondigital interventions. The primary outcome will be change in body weight (kg). Secondary outcomes include, among others, change in glycemic status, markers of cardiometabolic health, feasibility outcomes, and incidence of type 2 diabetes. Embase, PubMed, CINAHL, and CENTRAL (Cochrane Central Register of Controlled Trials) will be systematically searched. The data items to be extracted include study characteristics, participant characteristics, intervention characteristics, and relevant outcomes. To estimate the overall effect size, a meta-analysis will be conducted using the mean difference. Additionally, if feasible, meta-regression on study, intervention, and participant characteristics will be performed. The Cochrane risk of bias tool will be applied to assess study quality, and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of evidence. RESULTS: The results are projected to yield an overall estimate of the effectiveness of digital health lifestyle interventions on adults with prediabetes and elucidate the characteristics that contribute to their effectiveness. CONCLUSIONS: The insights gained from this study may help clarify the potential of digital health lifestyle interventions for people with prediabetes and guide the decision-making regarding future intervention components. TRIAL REGISTRATION: PROSPERO CRD42023426919; http://tinyurl.com/d3enrw9j. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50340.

Associations Between Physical Activity and Gastrointestinal Transit Times in People with Normal Weight, Overweight, and Obesity.

BACKGROUND: Rapid gastric emptying is associated with obesity and overeating, whereas delayed gastric emptying is associated with anorexia. Acute effects of exercise on gastric emptying have been investigated extensively, but the influence of habitual physical activity on gastric emptying and transit time in other regions of the gastrointestinal tract is poorly understood. OBJECTIVE: The objective was to investigate associations between objectively measured habitual physical activity and gastrointestinal transit times in adults with varying degrees of adiposity. METHODS: 50 adults (58% women) were included in this cross-sectional study. Physical activity was measured by an accelerometer placed on the lower back for 7 d. Gastric emptying time, small bowel transit time, colonic transit time, and whole gut transit time were simultaneously evaluated by a wireless motility capsule, which was ingested together with a standardized mixed meal. Linear regression models were applied to assess the associations of total activity counts and time spent at different intensities-sedentary activity (0-100 counts/min), low light activity (101-759 counts/min), high light activity (760-1951 counts/min); moderate and vigorous activity (≥1952 counts/min)) with gastrointestinal transit times. RESULTS: Median [Q1; Q3] age was 56.5 [46.6-65.5] y, and body mass index (BMI) was 32.1 [28.5-35.1] kg/m2. For every additional hour spent performing high light intensity physical activity, colonic transit time was 25.5 % [95% CI: 3.10, 42.7] more rapid (P = 0.028), and whole gut transit time was 16.2 % [95% CI: 1.84, 28.4] more rapid (P = 0.028) when adjusted for sex, age, and body fat. No other associations were observed. CONCLUSIONS: More time spent on physical activity at high light intensity was associated with more rapid colonic and whole gut transit time, independent of age, sex, and body fat, whereas other intensities of physical activity and gastrointestinal transit times were not associated. TRIAL REGISTRATION: Clinicaltrials.gov IDs (NCT03894670, NCT03854656).

The effect of metformin treatment on volumes of free-living physical activity and sedentary behaviour: A post-hoc analysis of the PRE-D trial.

Perceived physical exertion is increased when exercise is performed on metformin treatment, but the clinical relevance of this is unknown. In this post hoc analysis of a randomized, controlled trial, we investigated whether metformin treatment was associated with lower levels of free-living physical activity. Ninety individuals with overweight/obesity (BMI>25 m2/kg) and HbA1c-defined prediabetes (39-47 mmol/mol) were randomized to treatment with dapagliflozin (SGLT2-inhibitor; 10 mg once daily, n=30), metformin (850 mg twice daily, n=30) or no treatment (control, n=30) for 13 weeks in a parallel-group, open-label trial. Before (baseline), during (6 weeks) and immediately after (13 weeks) cessation of treatment, a 6-day assessment of physical activity and sedentary behaviour was performed using accelerometer-based physical activity monitors. Intention-to-treat analyses revealed no within-group changes or differences in change between the groups for any measures of physical activity or sedentary behaviour at neither 6 nor 13 weeks. Short-term metformin treatment does not reduce free-living physical activity level in individuals with overweight/obesity and HbA1c-defined prediabetes.

LEAP2 is associated with cardiometabolic markers but is unchanged by antidiabetic treatment in people with prediabetes.

To examine whether fasting plasma liver-expressed antimicrobial peptide 2 (FP-LEAP2) is associated with markers of cardiometabolic disease susceptibility in a cohort with prediabetes and overweight/obesity and whether antidiabetic interventions affect FP-LEAP2 levels. The analysis included 115 individuals with prediabetes [hemoglobin A1c (HbA1c) 39-47 mmol/mol, 5.7%-6.4%] and overweight/obesity [body mass index (BMI) ≥ 25 kg/m2] from a randomized controlled trial. Changes in FP-LEAP2 levels were assessed in relation to treatment with dapagliflozin (10 mg once daily), metformin (1,700 mg daily), or interval-based exercise (5 days/wk, 30 min/session) compared with control (habitual lifestyle) after 6 and 13 wk of treatment. FP-LEAP2 levels were positively associated with [standardized beta coefficient (95% CI)]: BMI 0.22 (0.03:0.41), P = 0.027; body weight 0.27 (0.06:0.48), P = 0.013; fat mass 0.2 (0.00:0.4), P = 0.048; lean mass 0.47 (0.13:0.8), P = 0.008; HbA1c 0.35 (0.17:0.53), P < 0.001; fasting plasma glucose (FPG) 0.32 (0.12:0.51), P = 0.001; fasting serum insulin 0.28 (0.09:0.47), P = 0.005; total cholesterol 0.19 (0.01:0.38), P = 0.043; triglycerides 0.31 (0.13:0.5), P < 0.001; and transaminases and fatty liver index (standardized beta coefficients 0.23-0.32), all P < 0.020. FP-LEAP2 levels were inversely associated with insulin sensitivity [-0.22 (-0.41: -0.03), P = 0.022] and kidney function [estimated glomerular filtration rate (eGFR) -0.34 (-0.56: -0.12), P = 0.003]. FP-LEAP2 levels were not associated with fat distribution or body fat percentage, fasting glucagon, postload glucose, ß-cell function, or low-density lipoprotein. The interventions were not associated with changes in FP-LEAP2. FP-LEAP2 is associated with body mass, impaired insulin sensitivity, liver-specific enzymes, and kidney function. The findings highlight the importance of studying LEAP2 in obesity, type 2 diabetes, and nonalcoholic fatty liver disease. FP-LEAP2 was not affected by metformin, dapaglifloxin, or exercise in this population.NEW & NOTEWORTHY LEAP2, primarily secreted by the liver, increases with greater body mass, insulin resistance, and liver-specific enzymes in individuals with prediabetes and overweight or obesity. Fasting glucose, body mass, and alanine aminotransferase independently predict LEAP2 levels. LEAP2 is inversely linked to impaired kidney function. Elevated LEAP2 levels might indicate an increased metabolic risk, warranting further investigation into its potential involvement in glucose and body weight control.

Designing a Co-created Intervention to Promote Motivation and Maintenance of Time-Restricted Eating in Individuals With Overweight and Type 2 Diabetes.

OBJECTIVE: To design an appealing time-restricted eating (TRE) intervention by exploring behavioral and social mechanisms to improve TRE adoption and maintenance among people with type 2 diabetes (T2D) and overweight. Time-restricted eating is an intermittent fasting regimen suggested to improve glycemic control and body weight. METHODS: Intervention development combined coherence theory and empirical data (workshops and semistructured interviews with the target group, their relatives, and health care professionals [HCPs]). Abductive analysis was applied. RESULTS: The analysis suggested designing the TRE intervention in 2 phases: a short period with strict TRE, followed by a longer period focusing on adapting TRE to individual needs with support from HCPs, relatives, and peers. To reinforce TRE motivation and maintenance, HCPs should adopt a whole-person approach that focuses on participants' previous experiences. CONCLUSIONS AND IMPLICATIONS: Important intervention elements to promote TRE adoption and maintenance are suggested to include a 2-phase design and support from professionals, family, and peers.

Predicting the HbA1c level following glucose-lowering interventions in individuals with HbA1c-defined prediabetes: a post-hoc analysis from the randomized controlled PRE-D trial.

PURPOSE: To investigate whether the prediction of post-treatment HbA1c levels can be improved by adding an additional biomarker of the glucose metabolism in addition to baseline HbA1c. METHODS: We performed an exploratory analysis based on data from 112 individuals with prediabetes (HbA1c 39-47 mmol) and overweight/obesity (BMI ≥ 25 kg/m2), who completed 13 weeks of glucose-lowering interventions (exercise, dapagliflozin, or metformin) or control (habitual living) in the PRE-D trial. Seven prediction models were tested; one basic model with baseline HbA1c as the sole glucometabolic marker and six models each containing one additional glucometabolic biomarker in addition to baseline HbA1c. The additional glucometabolic biomarkers included: 1) plasma fructosamine, 2) fasting plasma glucose, 3) fasting plasma glucose × fasting serum insulin, 4) mean glucose during a 6-day free-living period measured by a continuous glucose monitor 5) mean glucose during an oral glucose tolerance test, and 6) mean plasma glucose × mean serum insulin during the oral glucose tolerance test. The primary outcome was overall goodness of fit (R2) from the internal validation step in bootstrap-based analysis using general linear models. RESULTS: The prediction models explained 46-50% of the variation (R2) in post-treatment HbA1c with standard deviations of the estimates of ~2 mmol/mol. R2 was not statistically significantly different in the models containing an additional glucometabolic biomarker when compared to the basic model. CONCLUSION: Adding an additional biomarker of the glucose metabolism did not improve the prediction of post-treatment HbA1c in individuals with HbA1c-defined prediabetes.

Feasibility of time-restricted eating in individuals with overweight, obesity, prediabetes, or type 2 diabetes: A systematic scoping review.

OBJECTIVE: This systematic scoping review aimed to map and synthesize research on feasibility of time-restricted eating (TRE) in individuals with overweight, obesity, prediabetes, or type 2 diabetes, including recruitment rate, retention rate, safety, adherence, and participants' attitudes, experiences, and perspectives. METHODS: The authors searched MEDLINE, Embase, and Cumulative Index to Nursing and Allied Health Literature from inception to November 22, 2022, supplemented by backward and forward citation search. RESULTS: From 4219 identified records, 28 studies were included. In general, recruitment was easy and median retention rate was 95% among studies with <12 weeks duration and 89% among studies ≥12 weeks. Median (range) adherence to the target eating window for studies <12 and ≥12 weeks was 89% (75%-98%) and 81% (47%-93%), respectively. Variation in adherence among participants and studies was considerable, indicating that following TRE was difficult for some people and that intervention conditions influenced adherence. These findings were supported by qualitative data synthetized from seven studies, and determinants of adherence included calorie-free beverages outside the eating window, provision of support, and influence on the eating window. No serious adverse events were reported. CONCLUSIONS: TRE is implementable, acceptable, and safe in populations with overweight, obesity, prediabetes, or type 2 diabetes, but it should be accompanied by support and options for individual adjustments.

Type 2 Diabetes risk alleles in Peptidyl-glycine Alpha-amidating Monooxygenase influence GLP-1 levels and response to GLP-1 Receptor Agonists.

Patients with type 2 diabetes vary in their response to currently available therapeutic agents (including GLP-1 receptor agonists) leading to suboptimal glycemic control and increased risk of complications. We show that human carriers of hypomorphic T2D-risk alleles in the gene encoding peptidyl-glycine alpha-amidating monooxygenase (PAM), as well as Pam-knockout mice, display increased resistance to GLP-1 in vivo. Pam inactivation in mice leads to reduced gastric GLP-1R expression and faster gastric emptying: this persists during GLP-1R agonist treatment and is rescued when GLP-1R activity is antagonized, indicating resistance to GLP-1's gastric slowing properties. Meta-analysis of human data from studies examining GLP-1R agonist response (including RCTs) reveals a relative loss of 44% and 20% of glucose lowering (measured by glycated hemoglobin) in individuals with hypomorphic PAM alleles p.S539W and p.D536G treated with GLP-1R agonist. Genetic variation in PAM has effects on incretin signaling that alters response to medication used commonly for treatment of T2D.

The prediabetes conundrum: striking the balance between risk and resources.

The current definition of prediabetes is controversial and subject to continuous debate. Nonetheless, prediabetes is a risk factor for type 2 diabetes, is highly prevalent and is associated with diabetic complications and mortality. Thereby, it has the potential to become a huge strain on healthcare systems in the future, necessitating action from legislators and healthcare providers. But how do we best reduce its associated burden on health? As a compromise between differing opinions in the literature and among the authors of this article, we suggest stratifying individuals with prediabetes according to estimated risk and only offering individual-level preventive interventions to those at high risk. At the same time, we argue to identify those with prediabetes and already established diabetes-related complications and treat them as we would treat individuals with established type 2 diabetes.

Effects of acute exercise and exercise training on plasma GDF15 concentrations and associations with appetite and cardiometabolic health in individuals with overweight or obesity - A secondary analysis of a randomized controlled trial.

Growth Differentiation Factor 15 (GDF15) is seemingly involved in appetite control. Acute exercise increases GDF15 concentrations in lean humans, but acute and long-term effects of exercise on GDF15 in individuals with overweight/obesity are unknown. We investigated the effects of acute exercise and exercise training on GDF15 concentrations in individuals with overweight/obesity and associations with appetite and cardiometabolic markers. 90 physically inactive adults (20-45 years) with overweight/obesity were randomized to 6-months habitual lifestyle (CON, n=16), or isocaloric exercise of moderate (MOD, n=37) or vigorous intensity (VIG, n=37), 5 days/week. Testing was performed at baseline, 3, and 6 months. Plasma GDF15 concentrations, other metabolic markers, and subjective appetite were assessed fasted and in response to acute exercise before an ad libitum meal. Cardiorespiratory fitness, body composition, insulin sensitivity, and intraabdominal adipose tissue were measured. At baseline, GDF15 increased 18% (95%CI: 4; 34) immediately after acute exercise and 32% (16; 50) 60 min post-exercise. Fasting GDF15 increased 21% (0; 46) in VIG after 3 months (p=0.045), but this attenuated at 6 months (13% (-11; 43), p=0.316) and was unchanged in MOD (11% (-6; 32), p=0.224, across 3 and 6 months). Post-exercise GDF15 did not change in MOD or VIG. GDF15 was not associated with appetite or energy intake. Higher GDF15 was associated with lower cardiorespiratory fitness, central obesity, dyslipidemia, and poorer glycemic control. In conclusion, GDF15 increased in response to acute exercise but was unaffected by exercise training. Higher GDF15 concentrations were associated with a less favorable cardiometabolic profile but not with markers of appetite. This suggests that GDF15 increases in response to acute exercise independent of training state. Whether this has an impact on free-living energy intake and body weight management needs investigation.

Is time-restricted eating a robust eating regimen during periods of disruptions in daily life? A qualitative study of perspectives of people with overweight during COVID-19.

BACKGROUND: Time-restricted eating (TRE) has been suggested as a feasible dietary strategy in individuals with overweight. Disruptions in daily life e.g., severe illness can affect engagement in lifestyle interventions to obtain healthier body weight. This study examined if and how the engagement with TRE among people with overweight was affected by the Danish COVID-19 lockdowns as an example of disruptions in daily life. METHODS: Fifteen participants with overweight enrolled in a TRE intervention, i.e. restricting all eating and drinking except water to the same daily ten-hour window, were interviewed about their experiences and engagement with TRE during COVID-19 lockdowns. Interviews were semi-structured and conducted by phone or face-to-face with safe social distancing. Data analysis was grounded in a reflexive thematic analysis approach. RESULTS: Daily life rhythms were disrupted by lockdowns by preventing participants from performing ordinary daily activities such as going to work, socialising, eating out or exercising. For some, this challenged their TRE engagement, while most were able to undertake the TRE eating window but reported increased snacking and consumption of take-away food within their eating window. For all, exercise habits became unhealthier. The negative impact on TRE engagement primarily occurred during daytime, as social distancing made it easier to engage with TRE during evenings. CONCLUSIONS: This study showed that even people highly motivated to obtain healthier lifestyles practices struggled to maintain engagement with healthy behaviours, whereas sticking to the TRE window was manageable during COVID-19. TRE as a weight loss strategy was challenged which calls for more attention to supporting people in daily life to obtain healthier practices, also in case of periods of other disruptions such as divorce, serious illness etc.

The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance.

Metformin is a blood-glucose-lowering medication with physiological effects that extend beyond its anti-diabetic indication. Recently, it was reported that metformin lowers body weight via induction of growth differentiation factor 15 (GDF15), which suppresses food intake by binding to the GDNF family receptor α-like (GFRAL) in the hindbrain. Here, we corroborate that metformin increases circulating GDF15 in mice and humans, but we fail to confirm previous reports that the GDF15-GFRAL pathway is necessary for the weight-lowering effects of metformin. Instead, our studies in wild-type, GDF15 knockout, and GFRAL knockout mice suggest that the GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance. The data presented here question whether metformin is a sufficiently strong stimulator of GDF15 to drive anorexia and weight loss and emphasize that additional work is needed to untangle the relationship among metformin, GDF15, and energy balance.

Does the Effect of a 3-Year Lifestyle Intervention on Body Weight and Cardiometabolic Health Differ by Prediabetes Metabolic Phenotype? A Post Hoc Analysis of the PREVIEW Study.

OBJECTIVE: To examine whether the effect of a 3-year lifestyle intervention on body weight and cardiometabolic risk factors differs by prediabetes metabolic phenotype. RESEARCH DESIGN AND METHODS: This post hoc analysis of the multicenter, randomized trial, PREVention of diabetes through lifestyle interventions and population studies In Europe and around the World (PREVIEW), included 1,510 participants with prediabetes (BMI ≥25 kg ⋅ m-2; defined using oral glucose tolerance tests). Of these, 58% had isolated impaired fasting glucose (iIFG), 6% had isolated impaired glucose tolerance (iIGT), and 36% had IFG+IGT; 73% had normal hemoglobin A1c (HbA1c; <39 mmol ⋅ mol-1) and 25% had intermediate HbA1c (39-47 mmol ⋅ mol-1). Participants underwent an 8-week diet-induced rapid weight loss, followed by a 148-week lifestyle-based weight maintenance intervention. Linear mixed models adjusted for intervention arm and other confounders were used. RESULTS: In the available-case and complete-case analyses, participants with IFG+IGT had greater sustained weight loss after lifestyle intervention (adjusted mean at 156 weeks -3.5% [95% CI, -4.7%, -2.3%]) than those with iIFG (mean -2.5% [-3.6%, -1.3%]) relative to baseline (P = 0.011). Participants with IFG+IGT and iIFG had similar cardiometabolic benefits from the lifestyle intervention. The differences in cardiometabolic benefits between those with iIGT and IFG+IGT were minor or inconsistent in different analyses. Participants with normal versus intermediate HbA1c had similar weight loss over 3 years and minor differences in cardiometabolic benefits during weight loss, whereas those with normal HbA1c had greater improvements in fasting glucose, 2-h glucose (adjusted between-group difference at 156 weeks -0.54 mmol ⋅ L-1 [95% CI -0.70, -0.39], P < 0.001), and triglycerides (difference -0.07 mmol ⋅ L-1 [-0.11, -0.03], P < 0.001) during the lifestyle intervention. CONCLUSIONS: Individuals with iIFG and IFG+IGT had similar improvements in cardiometabolic health from a lifestyle intervention. Those with normal HbA1c had greater improvements than those with intermediate HbA1c.

Effects of vegan diets on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials.

In parallel with an increased focus on climate changes and carbon footprint, the interest in plant-based diets and its potential health effects have increased over the past decade. The objective of this systematic review and meta-analysis was to examine the effect of vegan diets (≥12 weeks) on cardiometabolic risk factors in people with overweight or type 2 diabetes. We identified 11 trials (796 participants). In comparison with control diets, vegan diets reduced body weight (-4.1 kg, 95% confidence interval (CI) -5.9 to -2.4, p < 0.001), body mass index (BMI) (-1.38 kg/m2 , 95% CI -1.96 to -0.80, p < 0.001), glycated hemoglobin (HbA1c ) (-0.18% points, 95% CI -0.29 to -0.07, p = 0.002), total cholesterol (-0.30 mmol/L, 95% CI -0.52 to -0.08, p = 0.007), and low-density lipoprotein cholesterol (-0.24 mmol/L, 95% CI -0.40 to -0.07, p = 0.005). We identified no effect on blood pressure, high-density lipoprotein cholesterol, and triglycerides. We found that adhering to vegan diets for at least 12 weeks may be effective in individuals with overweight or type 2 diabetes to induce a meaningful decrease in body weight and improve glycemia. Some of this effect may be contributed to differences in the macronutrient composition and energy intake in the vegan versus control diets. Therefore, more research is needed regarding vegan diets and cardiometabolic health.

Is Time-Restricted Eating Safe in the Treatment of Type 2 Diabetes?-A Review of Intervention Studies.

Time-restricted eating (TRE) has been shown to improve body weight and glucose metabolism in people at high risk of type 2 diabetes. However, the safety of TRE in the treatment of type 2 diabetes is unclear. We investigated the safety of TRE interventions in people with type 2 diabetes by identifying published and ongoing studies. Moreover, we identified the commonly used antidiabetic drugs and discussed the safety of TRE in people with type 2 diabetes considering the use of these drugs. In addition, we addressed the research needed before TRE can be recommended in the treatment of type 2 diabetes. A literature search was conducted to identify published (MEDLINE PubMed) and ongoing studies (ClinicalTrials.gov) on TRE in people with type 2 diabetes. To assess the usage of antidiabetic drugs and to discuss pharmacodynamics and pharmacokinetics in a TRE context, the most used antidiabetic drugs were identified and analysed. Statistics regarding sale of pharmaceuticals were obtained from MEDSTAT.DK which are based on data from the national Register of Medicinal Product Statistics, and from published studies on medication use in different countries. Four published studies investigating TRE in people with type 2 diabetes were identified as well as 14 ongoing studies. The completed studies suggested that TRE is safe among people with type 2 diabetes. Common antidiabetic drugs between 2010 and 2019 were metformin, insulin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sulfonylureas, and sodium-glucose cotransporter-2 inhibitors. Existing studies suggest that TRE is not associated with major safety issues in people with type 2 diabetes as long as medication is monitored and adjusted. However, because of low generalisability of the few studies available, more studies are needed to make concrete recommendations regarding efficacy and safety of TRE in people with type 2 diabetes.

The Use and Effectiveness of Selected Alternative Markers for Insulin Sensitivity and Secretion Compared with Gold Standard Markers in Dietary Intervention Studies in Individuals without Diabetes: Results of a Systematic Review.

BACKGROUND: The gold-standard techniques for measuring insulin sensitivity and secretion are well established. However, they may be perceived as invasive and expensive for use in dietary intervention studies. Thus, surrogate markers have been proposed as alternative markers for insulin sensitivity and secretion. This systematic review aimed to identify markers of insulin sensitivity and secretion in response to dietary intervention and assess their suitability as surrogates for the gold-standard methodology. METHODS: Three databases, PubMed, Scopus, and Cochrane were searched, intervention studies and randomised controlled trials reporting data on dietary intake, a gold standard of analysis of insulin sensitivity (either euglycaemic-hyperinsulinaemic clamp or intravenous glucose tolerance test and secretion (acute insulin response to glucose), as well as surrogate markers for insulin sensitivity (either fasting insulin, area under the curve oral glucose tolerance tests and HOMA-IR) and insulin secretion (disposition index), were selected. RESULTS: We identified thirty-five studies that were eligible for inclusion. We found insufficient evidence to predict insulin sensitivity and secretion with surrogate markers when compared to gold standards in nutritional intervention studies. CONCLUSIONS: Future research is needed to investigate if surrogate measures of insulin sensitivity and secretion can be repeatable and reproducible in the same way as gold standards.

Age- and sex-specific effects of a long-term lifestyle intervention on body weight and cardiometabolic health markers in adults with prediabetes: results from the diabetes prevention study PREVIEW.

AIMS/HYPOTHESIS: Lifestyle interventions are the first-line treatment option for body weight and cardiometabolic health management. However, whether age groups or women and men respond differently to lifestyle interventions is under debate. We aimed to examine age- and sex-specific effects of a low-energy diet (LED) followed by a long-term lifestyle intervention on body weight, body composition and cardiometabolic health markers in adults with prediabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). METHODS: This observational study used longitudinal data from 2223 overweight participants with prediabetes in the multicentre diabetes prevention study PREVIEW. The participants underwent a LED-induced rapid weight loss (WL) period followed by a 3 year lifestyle-based weight maintenance (WM) intervention. Changes in outcomes of interest in prespecified age (younger: 25-45 years; middle-aged: 46-54 years; older: 55-70 years) or sex (women and men) groups were compared. RESULTS: In total, 783 younger, 319 middle-aged and 1121 older adults and 1503 women and 720 men were included in the analysis. In the available case and complete case analyses, multivariable-adjusted linear mixed models showed that younger and older adults had similar weight loss after the LED, whereas older adults had greater sustained weight loss after the WM intervention (adjusted difference for older vs younger adults -1.25% [95% CI -1.92, -0.58], p<0.001). After the WM intervention, older adults lost more fat-free mass and bone mass and had smaller improvements in 2 h plasma glucose (adjusted difference for older vs younger adults 0.65 mmol/l [95% CI 0.50, 0.80], p<0.001) and systolic blood pressure (adjusted difference for older vs younger adults 2.57 mmHg [95% CI 1.37, 3.77], p<0.001) than younger adults. Older adults had smaller decreases in fasting and 2 h glucose, HbA1c and systolic blood pressure after the WM intervention than middle-aged adults. In the complete case analysis, the above-mentioned differences between middle-aged and older adults disappeared, but the direction of the effect size did not change. After the WL period, compared with men, women had less weight loss (adjusted difference for women vs men 1.78% [95% CI 1.12, 2.43], p<0.001) with greater fat-free mass and bone mass loss and smaller improvements in HbA1c, LDL-cholesterol and diastolic blood pressure. After the WM intervention, women had greater fat-free mass and bone mass loss and smaller improvements in HbA1c and LDL-cholesterol, while they had greater improvements in fasting glucose, triacylglycerol (adjusted difference for women vs men -0.08 mmol/l [-0.11, -0.04], p<0.001) and HDL-cholesterol. CONCLUSIONS/INTERPRETATION: Older adults benefited less from a lifestyle intervention in relation to body composition and cardiometabolic health markers than younger adults, despite greater sustained weight loss. Women benefited less from a LED followed by a lifestyle intervention in relation to body weight and body composition than men. Future interventions targeting older adults or women should take prevention of fat-free mass and bone mass loss into consideration. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01777893.

Role of Weekday Variation on Glucose, Insulin, and Triglyceride: A Cross-Sectional Analysis From the Maastricht Study.

CONTEXT: The timing of sleep, physical activity, and dietary intake show variation over the week, with different timings in the weekend compared to the weekdays, which may potentially lead to impaired glucose and lipid regulation on Mondays compared to other weekdays. OBJECTIVE: The aim of the study was to investigate differences in glucose metabolism and fasting triglyceride concentrations on Mondays compared to the rest of the week. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study is based on data from the Maastricht Study, including 6067 participants without known diabetes and 1568 previously diagnosed with type 2 diabetes. MAIN OUTCOME MEASURES: Confounder-adjusted linear regression analysis was applied to study the associations of day of the week of examination with glucose and insulin responses to an oral glucose tolerance test and fasting triglyceride concentrations. RESULTS: In fully confounder-adjusted models, mean (95% CI) concentrations of fasting glucose, insulin, and triglycerides were slightly higher on Mondays compared with the other weekdays [glucose: 1% (0-2); insulin: 9% (1-18); triglycerides: 5% (2-8)]. Interaction analyses revealed that the association of weekday with insulin was only pronounced in men [18% (3-35)], but not in women [1% (-8-10)], whereas the associations with glucose and triglycerides were only apparent for individuals with known type 2 diabetes [glucose: 4% (0-7); triglycerides: 14% (6-23)] compared to the background population [glucose: 0% (0-1); triglycerides: 3% (0-6)]. DISCUSSION: Being examined on a Monday was associated with higher fasting insulin concentrations among men but not women.