To explore the effects of different time-restricted eating (TRE) windows on body weight, blood pressure, fasting plasma glucose, and lipid profile. We conducted a pooled analysis of individual participant data from five TRE trials lasting 3-6 months and timestamped food/drink ingestion recorded with the myCircadianClock app. Participants in the control arms followed habitual ad libitum diets or received brief nutritional counseling and/or written guidance on healthy eating guidelines. Regression models assessed the associations between TRE and cardiometabolic outcomes according to allocated (8 h, 10 h, 12 h, or control) and actual eating windows (measured during follow-up), and changes in habitual eating duration. We included 124 adults (67% women; mean age 47.1 ± SD 13.2 years; baseline eating duration 15 h 02 ± 1 h 24) who were assigned to TRE (n = 95) or control intervention (n = 29). Those allocated to 8 h-TRE experienced greater weight loss than those on 12 h-TRE (difference: 1.66 Kg loss, 95%CI 0.22–3.10, p = 0.02) and controls (difference: 2.25 Kg loss, 95%CI 0.84–3.66, p = 0.002), with a trend towards greater weight loss versus 10 h-TRE (mean difference: 1.02 Kg; 95% CI: −0.16 to 2.21; p = 0.09). These associations generally persisted after adjustment for age, sex, and baseline BMI. Greater weight loss was associated with shorter eating windows (0.27 Kg, 95%CI 0.05–0.49, per 1h-reduction, p = 0.02) and greater reductions in habitual eating windows after accounting for baseline eating window duration (0.26 Kg, 95%CI 0.03–0.49, per 1h-reduction, p = 0.03). These associations were attenuated after adjustments for major confounders, potentially due to the limited sample size. In this pooled analysis of individual data from five TRE trials, shorter eating windows and greater reductions in habitual eating windows were associated with modestly greater weight loss in unadjusted analyses, although some associations were attenuated after adjustments. Larger, longer-term TRE trials across a wider range of eating windows are needed to confirm these findings.
Skeletal muscle atrophy is a major complication associated with diabetes and hyperglycemia and contributes to poor prognosis and reduced quality of life. Vitamin C, an antioxidant, has shown beneficial effects against diabetic complications in rodents and other mammals. However, whether vitamin C can mitigate hyperglycemia-associated muscle atrophy and the underlying mechanisms remain unclear. The Drosophila larval body wall muscle provides a useful system for studying interventions that modulate muscle homeostasis. Hyperglycemic conditions were induced by feeding wild-type Canton-S Drosophila larvae a High Sugar Diet (HSD; 1 M sucrose) while control larvae received 0.15 M sucrose. Body wall muscles from wandering third-instar larvae were used for analysis. The effects of vitamin C were further evaluated in differentiating C2C12 myoblasts and streptozotocin (STZ)-induced hyperglycemic mice subjected to skeletal muscle injury. HSD-fed larvae exhibited growth inhibition, hyperglycemia, impaired insulin response, and increased triglyceride levels. Ventral longitudinal VL3 and VL4 myofibers were reduced in size and showed decreased expression of Myocyte Enhancer Factor 2 (MEF2) and Myosin Heavy Chain (MHC), along with increased expression of Drosophila Atrogin-1 homolog, CG11658, and Forkhead Box O (FOXO) target genes, consistent with a muscle atrophy-like phenotype. Vitamin C Supplementation partially rescued growth defects, improved food intake, and reduced several hyperglycemia-associated phenotypes. Transcriptomic analysis of larval muscles revealed enrichment of genes involved in metabolism, muscle development, and differentiation. Vitamin C reduced oxidative stress and restored the expression of the epigenetic regulator Ten-eleven-translocation (Tet). Furthermore, vitamin C enhanced myogenic differentiation under high sugar conditions and improved skeletal muscle regeneration in hyperglycemic mice. Vitamin C mitigates muscle atrophy-like phenotypes in hyperglycemic larvae, promotes myogenic differentiation under high-sugar conditions, and enhances skeletal muscle regeneration in hyperglycemic mice. These findings support further investigation of vitamin C as a potential adjuvant to mitigate hyperglycemia-associated skeletal muscle complications.
Women with type 2 diabetes mellitus (T2DM) often require interventions that are culturally acceptable, practical, sustainable, and can be easily fit into their daily routine to manage their blood sugar levels. Although plant-based dietary patterns and time-restricted fasting have demonstrated metabolic benefits, limited evidence exists on their combined effects in Indian women with T2DM. This trial evaluated whether a lactovegetarian diet combined with 14-hour time-restricted eating improves glycemic and cardiometabolic outcomes compared with usual diabetes care. 96 women (25–60 years) with T2DM were enrolled in a 24-week, multicenter, randomized, open-label parallel-arm trial; 90 completed the study. The participants were divided into two groups: an intervention group following a structured lacto-vegetarian diet combined with 14-hour fasting, and control group receiving usual diabetes care. The diet contained 15–20% protein, 20–25% fat, and improved carbohydrate quality (50–55% from whole grains/high-fiber foods). Biochemical estimations and anthropometric measurements were taken at baseline and 24 weeks. The study employed an intention-to-treat analysis protocol, and the perceived benefits and safety of the intervention were reported. At 24 weeks, baseline-adjusted between-group comparisons showed significantly greater improvements in the intervention group compared with usual diabetes care. The intervention group had lower adjusted values for body weight, BMI, glycemic, and lipid profiles. The adjusted mean HbA1c was 6.53% in the intervention group compared with 7.65% in the control group, with an adjusted mean difference of −1.12% (95% CI: −1.35 to −0.89; p < 0.001). HOMA-IR was also significantly lower in the intervention group, with an adjusted mean difference of −1.84 (95% CI: −2.27 to −1.41; p < 0.001). Adverse events were mild and transient, while most participants reported improved energy, mood, weight loss, and overall health. A culturally adaptable lacto-vegetarian diet combined with a 14-hour time-restricted fasting regimen safely improves metabolic control and insulin sensitivity in women with Type 2 Diabetes, offering a practical, women-centric strategy that may be implementable within structured clinical nutrition services, although its staffing requirements, cost, and scalability require further evaluation. CTRI/2024/09/073262, Ethical Approval by Institutional Committee: SIU/IEC/781A
Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential in diabetic nephropathy (DN), yet the underlying mechanisms remain incompletely understood, limiting strategies to enhance their efficacy. This study aimed to elucidate whether MSCs exert renoprotective effects by modulating the gut microbiota and its metabolite short-chain fatty acids (SCFAs). DN was induced in rats via a high-fat diet (HFD) combined with streptozotocin (STZ) injection. MSCs were administered via tail vein infusion. Therapeutic efficacy was evaluated by renal function parameters, urine biochemistry, and renal histopathology. Neutrophil extracellular trap (NET) formation was assessed using immunofluorescence staining and ELISA. Alterations in gut microbial composition and SCFA profiles were analyzed through 16S rRNA gene sequencing and targeted metabolomics, respectively. The causal role of the gut microbiota was validated using fecal microbiota transplantation (FMT). Administration of MSCs, as well as FMT from MSC-treated donors, significantly ameliorated renal injury and suppressed NET formation in DN rats. Notably, pharmacological induction of NETs abolished the protective effects conferred by MSC-FMT. 16S rRNA sequencing revealed that MSC intervention enriched beneficial bacterial populations, particularly within the family Muribaculaceae. Targeted metabolomic analysis identified a significant elevation of butyrate among fecal SCFAs in MSC-treated rats. Furthermore, exogenous butyrate supplementation recapitulated the inhibitory effects on NET formation and attenuated DN progression. MSC therapy alleviates diabetic nephropathy via a gut-kidney axis mechanism, driven by the enrichment of butyrate-producing microbiota and the subsequent inhibition of neutrophil extracellular trap formation.
Type 2 diabetes mellitus (T2DM) is marked by hyperglycemia, oxidative stress, and systemic inflammation. Prebiotics, such as bitter almond gum (Amygdalus communis L. var. amara), have the potential to influence gut microbiota and metabolic parameters, suggesting their role as dietary interventions for enhancing glycemic control in the management of T2DM. This study evaluated the effects of bitter almond gum on glycemic indices, oxidative stress, and oxidant biomarkers in individuals with T2DM. This randomized, triple-blinded, placebo-controlled, clinical trial included 44 women with T2DM. They were assigned to either the intervention (n = 22) or control (n = 22) groups receiving 5 g per day of bitter almond gum or maltodextrin, respectively, for a duration of 8 weeks. Various outcomes, including glycemic indices, lipopolysaccharide (LPS) levels, oxidative stress markers, and antioxidant biomarkers, were measured at baseline and again after 8 weeks. Bitter almond gum supplementation significantly reduced insulin levels (−1.23 mg/dL; 95% CI, [–2.40, –0.03]), LPS ( − 6.32 mg/dL; 95% CI, [–9.51, –3.09]), pentosidine (−38.02 mg/dL; 95% CI, [–55.18, –20.71]), and oxidative stress index (OSI) (−5.59 mg/dL; 95% CI, [–10.81, –0.30]), and increased McAuley_index (0.20 mg/dL; 95% CI, [0.14, 0.32]), total antioxidant capacity (TAC) (0.18 mg/dL; 95% CI, [0.07, 0.26]), superoxide dismutase (SOD) (180.20 mg/dL; 95% CI, [65.27, 295.14]), and glutathione peroxidase (GSH-Px) (2.21 mg/dL; 95% CI, [0.78, 3.62]) compared with the placebo group (P < 0.05, ANCOVA adjusted for baseline and confounding factors). Bitter almond gum supplementation for 8 weeks led to improvements in glycemic control, a reduction in oxidative stress, and an enhancement of antioxidant defenses in women with T2DM. These findings indicate its potential as a complementary functional food for managing diabetes.
