Long-term Effect of Lifestyle Interventions on the Cardiovascular and All-Cause Mortality of Subjects With Prediabetes and Type 2 Diabetes: A Systematic Review and Meta-analysis.

BACKGROUND: Lifestyle interventions improve the metabolic control of individuals with hyperglycemia. PURPOSE: We aimed to determine the effect of lifestyle interventions on cardiovascular and all-cause mortality in this population. DATA SOURCES: Searches were made through MEDLINE, Cochrane CENTRAL, Embase, and Web of Science (no date/language restriction, until 15 May 2022). STUDY SELECTION: We included randomized clinical trials (RCTs) of subjects with prediabetes and type 2 diabetes, comparing intensive lifestyle interventions with usual care, with a minimum of 2 years of active intervention. DATA EXTRACTION: Data from the 11 RCTs selected were extracted in duplicate. A frequentist and arm-based meta-analysis was performed with random-effects models to estimate relative risk (RR) for mortality, and heterogeneity was assessed through I2 metrics. A generalized linear mixed model (GLMM) was used to confirm the findings. DATA SYNTHESIS: Lifestyle interventions were not superior to usual care in reducing cardiovascular (RR 0.99; 95% CI 0.79-1.23) or all-cause (RR 0.93; 95% CI 0.85-1.03) mortality. Subgroup, sensitivity, and meta-regression analyses showed no influence of type of intervention, mean follow-up, age, glycemic status, geographical location, risk of bias, or weight change. All of these results were confirmed with the GLMM. Most studies had a low risk of bias according to the RoB 2.0 tool and the certainty of evidence was moderate for both outcomes. LIMITATIONS: Most studies had a low risk of bias according to the RoB 2.0 tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach resulted in moderate certainty of evidence for both outcomes. Differences in lifestyle programs and in usual care between the studies should be considered in the interpretation of our results. CONCLUSIONS: Intensive lifestyle interventions implemented so far did not show superiority to usual care in reducing cardiovascular or all-cause mortality for subjects with prediabetes and type 2 diabetes.

A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults.

PURPOSE: We sought to determine the effects of dietary fat on insulin sensitivity and whether changes in insulin sensitivity were explained by changes in abdominal fat distribution or very low-density lipoprotein (VLDL) fatty acid composition. METHODS: Overweight/obese adults with normal glucose tolerance consumed a control diet (35 % fat/12 % saturated fat/47 % carbohydrate) for 10 days, followed by a 4-week low-fat diet (LFD, n = 10: 20 % fat/8 % saturated fat/62 % carbohydrate) or high-fat diet (HFD, n = 10: 55 % fat/25 % saturated fat/27 % carbohydrate). All foods and their eucaloric energy content were provided. Insulin sensitivity was measured by labeled hyperinsulinemic-euglycemic clamps, abdominal fat distribution by MRI, and fasting VLDL fatty acids by gas chromatography. RESULTS: The rate of glucose disposal (Rd) during low- and high-dose insulin decreased on the HFD but remained unchanged on the LFD (Rd-low: LFD: 0.12 ± 0.11 vs. HFD: -0.37 ± 0.15 mmol/min, mean ± SE, p < 0.01; Rd-high: LFD: 0.11 ± 0.37 vs. HFD: -0.71 ± 0.26 mmol/min, p = 0.08). Hepatic insulin sensitivity did not change. Changes in subcutaneous fat were positively associated with changes in insulin sensitivity on the LFD (r = 0.78, p < 0.01) with a trend on the HFD (r = 0.60, p = 0.07), whereas there was no association with intra-abdominal fat. The LFD led to an increase in VLDL palmitic (16:0), stearic (18:0), and palmitoleic (16:1n7c) acids, while no changes were observed on the HFD. Changes in VLDL n-6 docosapentaenoic acid (22:5n6) were strongly associated with changes in insulin sensitivity on both diets (LFD: r = -0.77; p < 0.01; HFD: r = -0.71; p = 0.02). CONCLUSIONS: A diet very high in fat and saturated fat adversely affects insulin sensitivity and thereby might contribute to the development of type 2 diabetes. CLINICALTRIALS. GOV IDENTIFIER: NCT00930371.

The antioxidant N-Acetylcysteine does not improve glucose tolerance or ß-cell function in type 2 diabetes.

UNLABELLED: Hyperglycemia induces oxidative stress and thereby may exacerbate ß-cell dysfunction in type 2 diabetes (T2DM). Notably, glutathione (GSH), synthesized from N-Acetylcysteine (NAC), neutralizes reactive oxygen species within cells and is low in individuals with diabetes. AIM: Determine if NAC supplementation improves ß-cell function and glucose tolerance by decreasing oxidative stress in T2DM. METHODS: Thirteen subjects (6M/7F) with T2DM (duration: 0-13 years, median: 2 years), treated with diet/exercise alone (n=7) or metformin (n=6), underwent a 2-h oral glucose tolerance test (OGTT) at baseline, after 2 weeks supplementation with 600 mg NAC orally twice daily, and again after 2 weeks supplementation with 1200 mg NAC twice daily. The following measurements were made: fasting glucose and fructosamine for glycemic control, incremental AUC glucose (0-120 min) for glucose tolerance, and Δ insulin/Δ glucose (0-30 min) for the early insulin response to glucose. Fasting erythrocyte GSH and GSSG (oxidized glutathione) levels, plasma thiobarbituric acid reactive substances (TBARS), and urine F2α isoprostanes were measured to assess oxidative status. RESULTS: Subjects were middle aged (mean ± SEM: 53.9 ± 3.2 years), obese (BMI 37.3 ± 2.8 kg/m(2)), and relatively well-controlled (HbA1c 6.7 ± 0.3%, 50 mmol/mol). Glycemic control, glucose tolerance, insulin release, and oxidative markers did not change with either dose of NAC. CONCLUSIONS: Based on the lack of any short-term benefit from NAC supplementation on markers of glucose metabolism, ß-cell response, and oxidative status, it is unlikely to be a valuable therapeutic approach for treatment of type 2 diabetes.

Effect of dietary lipids on circulating adiponectin: a systematic review with meta-analysis of randomised controlled trials.

Different dietary interventions have been identified as potential modifiers of adiponectin concentrations, and they may be influenced by lipid intake. We identified studies investigating the effect of dietary lipids (type/amount) on adiponectin concentrations in a systematic review with meta-analysis. A literature search was conducted until July 2013 using databases such as Medline, Embase and Scopus (MeSH terms: 'adiponectin', 'dietary lipid', 'randomized controlled trials (RCT)'). Inclusion criteria were RCT in adults analysing adiponectin concentrations with modification of dietary lipids. Among the 4930 studies retrieved, fifty-three fulfilled the inclusion criteria and were grouped as follows: (1) total dietary lipid intake; (2) dietary/supplementary n-3 PUFA; (3) conjugated linoleic acid (CLA) supplementation; (4) other dietary lipid interventions. Diets with a low fat content in comparison to diets with a high-fat content were not associated with positive changes in adiponectin concentrations (twelve studies; pooled estimate of the difference in means: -0·04 (95% CI -0·82, 0·74) µg/ml). A modest increase in adiponectin concentrations with n-3 PUFA supplementation was observed (thirteen studies; 0·27 (95% CI 0·07, 0·47) µg/ml). Publication bias was found by using Egger's test (P= 0·01) and funnel plot asymmetry. In contrast, CLA supplementation reduced the circulating concentrations of adiponectin compared with unsaturated fat supplementation (seven studies; -0·74 (95% CI -1·38, -0·10) µg/ml). However, important sources of heterogeneity were found as revealed by the meta-regression analyses of both n-3 PUFA and CLA supplementation. Results of new RCT would be necessary to confirm these findings.

Major components of metabolic syndrome and adiponectin levels: a cross-sectional study.

BACKGROUND: Adiponectin is a major regulator of glucose and lipid homeostasis by its insulin sensitizer properties. Since decreased insulin sensitivity is linked to metabolic syndrome (MS), decreased adiponectin levels may be related to its development. The purpose of the study was to investigate the relationship between adiponectin levels and MS. METHODS: Firstly, we cross-sectionally examined subjects with or without MS submitted to an oral glucose tolerance test at Hospital de Clínicas de Porto Alegre (n = 172). A replication analysis was performed in subjects (n = 422) undergoing cardiac angiography at Hospital São Paulo. Subchronic inflammation (US-CRP), coagulation marker (fibrinogen), insulin sensitivity and resistance (Matsuda ISI and HOMA-IR) were estimated. Plasma total and high molecular weight (HMW) adiponectin were measured. RESULTS: Total and HMW adiponectin levels were lower in MS subjects (P < 0.05). Total adiponectin levels were lower in the presence of high waist circumference, low HDL-cholesterol and elevated triglyceride criteria in both samples and by elevated blood pressure and glucose criteria in Porto Alegre. HMW adiponectin levels were lower in the presence of low HDL-cholesterol, elevated triglycerides, and glucose criteria. Total adiponectin levels were positively related with HDL-cholesterol and ISI Matsuda, negatively related with waist circumference, glucose, triglycerides, HOMA-IR, and US-CRP and not related with blood pressure. While adjusting for sex and age, increased adiponectin levels remained associated with a reduced prevalence ratio for MS in both cohorts (P = 0.001). CONCLUSIONS: Adiponectin levels decreased with increasing number of MS criteria, and it is in part determined by its relationship with HDL, triglycerides and abdominal adiposity.