| The prevalence of type 2 diabetes mellitus(T2DM) was 8.3%, representing an estimated 382 million adults worldwide. In addition, the estimate is projected to rise to more than 552 million by 2030. With rapid economic growth and lifestyle changes, the prevalence of T2 DM have reached an alert level in the Chinese population. The most recent national survey in 2010 reported that 113.9 million Chinese adults are living with T2 DM, accounting for approximately one-third of T2 DM worldwide. In addition to a huge financial burden to the patients, diabetes has become a major risk factor for death worldwide.Dietary intervention for controlling T2 DM continues to attract health professionals, policy makers, and the general public.It has been demonstrated that increasing n-3 polyunsaturated fatty acid(PUFA) consumption has beneficial effects on multiple risk factors associated with diabetes such as lipid profile, blood pressure and inflammation. However, recent systematic review found that the results of human clinical trials investigating the effect of n-3 PUFA on glucose control were inconsistent. After carefully reading these articles, we found that these studies did not consider the n-6/n-3 PUFA ratio. In addition, the dietary carbohydrate percentages of the subjects in these studies might be too high.Therefore, we hypothesized that the combination of low carbohydrate and high n-3 PUFA with low n-6/n-3 PUFA ratio might be beneficial to glucose control in T2 DM. To test the hypothesis, we conducted the clinical randomized controlled trial. The T2 DM participants were randomly assigned into four groups and followed the high carbohydrate/low n-3 PUFA diet(HCD-3), high carbohydrate/high n-3 PUFA diet(HCD+3), low carbohydrate/low n-3 PUFA diet(LCD-3) or low carbohydrate/high n-3 PUFA diet(LCD+3) for 12 weeks. The biochemical biomarkers relative to glucose control and insulin sensitivity of the T2 DM subjects were tested and the data of measurements werecarefully analysized. In addition, recent evidence suggests patients with T2 DM exhibited a moderate intestinal dysbiosis. The intestinal dysbiosis may increase metabolic endotoxemia because of an impaired gut barrier. Subsequently, blood microbes may attain metabolically active organs inducing and sustaining the systemic inflammation and insulin resistance. Diet is an important driver of changes in the gut microbiota. It has been suggested that dietary intervention can effectively improve composition and function of gut microbiota and increasing n-3 PUFA consumption can inhibit postprandial endotoxin transport and preserve intestinal barrier integrity by decreasing inflammatory cytokines. Therefore, we investigated the effect of LCD+3 on gut microbiota and evaluated the association between change of gut microbioata and glucose control.In addition to how to make a dietary change, the public may also be confused by what beverage should be chosen in their daily life. One study cannot solve all the problems, the above part cannot provide information on beverage choosing because all of the subjects received the same individualized dietary suggestions on beverage choosing. In addition, we did not have enough time and funds to conduct more randomized controlled trials. However, meta-analysis may be an economical and efficient approach. In addition, meta-analysis can provide stronger statistical power to evaluate the treatment effect than a single randomized controlled trial. Therefore, we conducted studies on the effects of some popular beverages such as fruit juice, green tea and resveratrol, which is the main phytochemical of wine, on glucose control and insulin sensitivity. The main methods of statistical analyses contained meta-analysis of continuous data, meta-regression analysis, sensitivity analysis, publication bias analysis and analysis of hetegeneity etc. The included studies were randomized controlled trials. We also performed subgroup analyses according the clinical characteristics of the included studies.Results:1. Effects of LCD+3 dietary intervention on glycemic control and gut microbiota inpatients with T2DMAt week 8, greater reduction in Hb A1 c was only observed in the LCD+3 group in comparison with the HCD-3 group(P = 0.02). At week 12, Hb A1 c reductions were-0.51%(95% CI,-0.64 to-0.37%) in the LCD+3 group, which was greater than those in the HCD+3(P = 0.01) and LCD-3 diet group(P = 0.03). The LCD+3 group had showed greater changes in fasting glucose at 4 weeks(P = 0.007 vs HCD-3 group). Compared with the HCD-3group, greater fasting glucose decreases were observed in all of the other three diet groups at 12 weeks. The reductions of fasting glucose(-1.32 mmol/L; 95% CI,-1.72 to-0.93 mmol/L) in the LCD+3 group were greater when comparing with the HCD+3(P = 0.03) and LCD-3 groups(P = 0.04).At 12 week, all of the dietary interventions did not significantly changed beta diversity of gut microbiota as suggested by the Uni Frac PCo A, clustering analysis and RDA. In addition, similar results were found in permutational multivariate analysis of variance(P = 0.58). LCD+3 diet intervention significantly decreased the relative abundance of genus Prevotella and increased the relative abundance of genus Roseburiaand Faecalibacterium at 12 weeks. The relative abundance of the Faecalibacterium were increased in the LCD-3 group whereas genus Prevotella were decreased. HCD+3 intervention showed a significant increasing effect on the relative abundance of genus Roseburia. Results of spearman’s correlation analysis indicated that the effects of LCD+3 on glucose control were associated with gut microbiota change. We found that changes of Prevotella were positively associated with changes of Hb A1 c and fasting glucose level in LCD+3 and LCD-3 group. In addition, changes of Roseburia were negtively associated with changes of Hb A1 c and fasting glucose level in both LCD+3 and HCD+3 group.2. Effect of fruit juice on glucose control and insulin sensitivityTwelve trials comprising a total of 412 subjects were included in the current meta-analysis. The numbers of thesestudies that reported the data on fasting glucose, fasting insulin, Hb A1 c and HOMA-IR were 12, 5, 3 and 3, respectively. Fruitjuice consumption did not show a significant effect on fasting glucose and insulin concentrations. The net change was0.79 mg/d L(95% CI: 21.44, 3.02 mg/d L; P = 0.49) for fasting glucose concentrations and 20.74 m IU/ml(95% CI: 22.62,1.14 m IU/ml; P = 0.44) for fasting insulin concentrations in the fixed-effects model. Subgroup analyses further suggested thatthe effect of fruit juice on fasting glucose concentrations was not influenced by population region, baseline glucoseconcentration, duration, type of fruit juice, glycemic index of fruit juice, fruit juice nutrient constitution, total polyphenolsdose and Jadad score.3. Effect of resveratrol on glucose control and insulin sensitivityEleven studies comprising a total of 388 subjects wereincluded in this meta-analysis. Resveratrol consumption significantlyreduced fasting glucose, insulin, glycated hemoglobin, and insulin resistance(measured by using the homeostatic model assessment) levelsin participants with diabetes. No significant effect of resveratrol onglycemic measures of nondiabetic participants was found in the meta-analysis.Subgroup and sensitivity analyses indicated that the pooledeffects of resveratrol on fasting glucose and insulin concentrations innondiabetic participants were not affected by body mass index, studydesign, resveratrol dose, study duration, or Jadad score.4. Effect of green tea on glucose control, insulin sentivity and blood pressureSeventeen trials comprising a total of 1133 subjects were included in the current meta-analysis. Green tea consumption significantly reduced the fasting glucose and hemoglobin A1c(Hb A1c) concentrations by-0.09 mmol/L(95% CI:-0.15,-0.03 mmol/L; P< 0.01) and-0.30 %(95% CI:-0.37,-0.22 %; P< 0.01), respectively. Further stratified analyses from high Jadad score studies revealed that green tea significantly reduced the fasting insulin concentrations(-1.16 μIU/ml; 95%CI:-1.91,-0.40 μIU/ml;P = 0.03).Thirteen trials comprising a total of 1,367 subjects were included in the meta-analysis investigating the effects of green tea on blood pressure. The overall outcome of the meta-analysis suggested that green tea consumption significantly decrease systolic blood pressure(SBP) level by-1.98 mm Hg(95% CI:-2.94,-1.01 mm Hg; P< 0.001). Compared with the control group, green tea also showed a significant lowering effect on diastolic blood pressure(DBP) in treatment group(-1.92 mm Hg; 95% CI:-3.17,-0.68 mm Hg;P = 0.002). Subgroup analyses further suggested that the positive effect of green tea polyphenols on BP was only showed in studies using a low-dose green tea polyphenol, with the long-term intervention duration or ruling out the confounding effects of caffeine.Conclusion:1. The LCD+3intervention provides a faster and greater beneficial effect on improving Hb A1 c and fasting glucose levels than HCD+3 diet and LCD-3 diet, indicating the potential necessity of combining n-3 PUFA with low carbohydrate diet in T2 DM control.Meanwhile, we found that the favorable effect of LCD+3 intervention on glucose control might partly depend on its beneficial effect on gut microbiota of Prevotella and Roseburia in T2 DM patients.2. The meta-analysis on the effect of fruit juice on glucose control and insulin sensitivity showed that fruit juice may have no overall effect on fasting glucose and insulin concentrations. Additionally, the results were not influenced by population region, baseline glucose concentration, duration, type of fruit juice or glycemic index of fruit juice etc.3. Resveratrol significantly improves glucose control and insulin sensitivity in persons with diabetes but does not affect glycemic measures in nondiabetic persons.4. The meta-analysis on the effect of green tea on glucose control and insulin sensitivity suggested that green tea had favorable effects on decreasing fasting glucose and Hb A1 c concentrations, and subgroup analyses showed a significant reduction of fastinginsulinconcentrations in high Jadad score trials.In addition, green tea consumption also have a favorable effect on decrease of BP. |
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