Intermittent Fasting Improves Cardiometabolic Risk Factors and Alters Gut Microbiota in Metabolic Syndrome Patients.

CONTEXT: Intermittent fasting (IF) is an effective strategy to improve cardiometabolic health. OBJECTIVE: The objective of this work is to examine the effects of IF on cardiometabolic risk factors and the gut microbiota in patients with metabolic syndrome (MS). DESIGN AND SETTING: A randomized clinical trial was conducted at a community health service center. PATIENTS: Participants included adults with MS, age 30 to 50 years. INTERVENTION: Intervention consisted of 8 weeks of "2-day" modified IF. MAIN OUTCOME MEASURE: Cardiometabolic risk factors including body composition, oxidative stress, inflammatory cytokines, and endothelial function were assessed at baseline and at 8 weeks. The diversity, composition, and functional pathways of the gut microbiota, as well as circulating gut-derived metabolites, were measured. RESULTS: Thirty-nine patients with MS were included: 21 in the IF group and 18 in the control group. On fasting days, participants in the IF group reduced 69% of their calorie intake compared to nonfasting days. The 8-week IF significantly reduced fat mass, ameliorated oxidative stress, modulated inflammatory cytokines, and improved vasodilatory parameters. Furthermore, IF induced significant changes in gut microbiota communities, increased the production of short-chain fatty acids, and decreased the circulating levels of lipopolysaccharides. The gut microbiota alteration attributed to the IF was significantly associated with cardiovascular risk factors and resulted in distinct genetic shifts of carbohydrate metabolism in the gut community. CONCLUSION: IF induces a significant alteration of the gut microbial community and functional pathways in a manner closely associated with the mitigation of cardiometabolic risk factors. The study provides potential mechanistic insights into the prevention of adverse outcomes associated with MS.

Circulating Retinol-Binding Protein 4 Is Inversely Associated With Pancreatic ß-Cell Function Across the Spectrum of Glycemia.

OBJECTIVE: The aim of this study was to examine the association of circulating retinol-binding protein 4 (RBP4) levels with ß-cell function across the spectrum of glucose tolerance from normal to overt type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 291 subjects aged 35-60 years with normal glucose tolerance (NGT), newly diagnosed impaired fasting glucose or glucose tolerance (IFG/IGT), or type 2 diabetes were screened by a standard 2-h oral glucose tolerance test (OGTT) with the use of traditional measures to evaluate ß-cell function. From these participants, 74 subjects were recruited for an oral minimal model test, and ß-cell function was assessed with model-derived indices. Circulating RBP4 levels were measured by a commercially available ELISA kit. RESULTS: Circulating RBP4 levels were significantly and inversely correlated with ß-cell function indicated by the Stumvoll first-phase and second-phase insulin secretion indices, but not with HOMA of ß-cell function, calculated from the 2-h OGTT in 291 subjects across the spectrum of glycemia. The inverse association was also observed in subjects involved in the oral minimal model test with ß-cell function assessed by both direct measures and model-derived measures, after adjustment for potential confounders. Moreover, RBP4 emerged as an independent factor of the disposition index-total insulin secretion. CONCLUSIONS: Circulating RBP4 levels are inversely and independently correlated with ß-cell function across the spectrum of glycemia, providing another possible explanation of the linkage between RBP4 and the pathogenesis of type 2 diabetes.

Association of Serum Retinol-Binding Protein 4 Levels and the Risk of Incident Type 2 Diabetes in Subjects With Prediabetes.

OBJECTIVE: To explore the association of serum retinol-binding protein 4 (RBP4) levels and risk for the development of type 2 diabetes in individuals with prediabetes. RESEARCH DESIGN AND METHODS: A population-based prospective study was conducted among 1,011 Chinese participants with prediabetes (average age 55.6 ± 7.2 years). Incident type 2 diabetes was diagnosed according to the American Diabetes Association 2010 criteria. Serum RBP4 levels were measured using a commercially available ELISA. We analyzed the association of serum RBP4 levels with the risk of incident type 2 diabetes using the Cox proportional hazards model. RESULTS: During a median follow-up period of 3.1 years, 153 participants developed incident type 2 diabetes. A U-shaped association was observed between serum RBP4 levels and the risk of incident type 2 diabetes, with the lowest risk in the RBP4 range of 31-55 µg/mL. Multivariate Cox regression model analysis showed that serum RBP4 levels <31 µg/mL and RBP4 levels >55 µg/mL were associated with an increased risk of incident type 2 diabetes. The adjusted hazard ratios (95% CI) were 2.01 (1.31-3.09) and 1.97 (1.32-2.93), respectively, after adjusting for age, sex, BMI, waist circumference, γ-glutamyltransferase, HOMA of insulin resistance index, fasting plasma glucose, 2-h plasma glucose, and glycated hemoglobin (HbA1c) levels. CONCLUSIONS: A U-shaped relationship exists between serum RBP4 levels and the risk of incident type 2 diabetes in subjects with prediabetes.

Small dense LDL cholesterol is associated with metabolic syndrome traits independently of obesity and inflammation.

BACKGROUND: Small dense LDL cholesterol (sdLDL-c) has been established to be highly associated with metabolic disorder. However, the relationship between circulating sdLDL-c and the presence of metabolic syndrome (MetS) has not been fully established. METHODS: A total of 1065 Chinese males (45.07 ± 11.08 years old) without diabetes and general obesity was recruited into a population-based, cross-sectional study. The MetS was defined based on the updated National Cholesterol Education Program/ Adult Treatment Panel III criteria for Asian Americans. Serum sdLDL-c concentration was measured by a homogeneous assay method and its relationship with MetS and its traits was investigated. RESULTS: Serum sdLDL-c concentrations increased gradually with increasing numbers of MetS components (p < 0.001) and the proportion of patients with MetS increased gradually with increasing sdLDL-c levels (p for trend< 0.001). For the second, third, and fourth sdLDL-c quartiles versus the first, the OR (95% CI) for MetS were 4.47(2.41,8.28), 5.47(2.97,10.07) and 8.39(4.58,15.38) (p < 0.001 for trend) after multivariate adjustment. The stratified analysis conducted according to LDL-c levels showed that the OR between serum sdLDL-c levels and MetS was greater in those LDL-c levels lower than 3.3 mmol/L (OR = 22.97; 95% CI, 7.64-69.09) than in those LDL-c levels higher than 3.3 mmol/L (OR = 17.49; 95% CI, 4.43-68.98). Mediation analysis showed sdLDL-c mediated 38.6% of the association of waist circumference with triglycerides, while the association between sdLDL-c and MetS components did not mediate by hsCRP. CONCLUSIONS: This study found that high sdLDL-c concentrations were associated with the presence of MetS independently of central obesity and inflammation.