The Effects Of Leucine Supplementation On Type 2 Diabetes Mellitus

ObjectiveWe performed a meta-analysis of randomized controlled trials(RCT) to investigate the effect of whey protein, which is a rich source of leucine, on the diabetes related indicators(body weight, body compositions and blood lipids) in overweight/obese subjects. Then, the effects of leucine on blood glucose control and lipid metabolism were observed using animal model with type 2 diabetes mellitus(T2DM) and in the patients with T2 DM.Methods1. Meta-analysis: Relative RCTs through September 2013 were collected. Meta-analysis was applied to estimate the combined standardized mean difference(SMD) and 95% confidence interval(95% CI) according to the recommendation of Cochrane Collaboration.2. Animal experiment: Sixty male ICR mice were randomly divided into 5 groups. Among which, 4 groups used 100 mg/kg body weight of streptozocin(STZ) to induce models of T2 DM. Mice in model groups were free to access food and drink 0%, 0.5%, 1% and 1.5% of leucine solution, respectively, for 8 weeks. During experiment, the body weight was recorded every week, and the intakes of food and water were recorded every other week. At the end of the experiment, fasting blood glucose, serum insulin, total cholesterol(TC), triglyceride(TG), high-density lipoprotein-cholesterol(HDL-C), and low-density lipoprotein-cholesterol(LDL-C) were measured and the pancreas pathological changes were observed.3. Human trial: Thirty-four T2 DM patients without insulin therapy were randomly divided into leucine intervention group and control group. All participants maintained their therapy and life style, and the participants in the intervention group supplemented 3g of leucine per day. The study lasted 6 months. 3 days’ 24-h dietary recall was used to evaluate nutrient intake. Body composition was measured using body composition analyzer, and fasting blood glucose and lipid profiles were determined before and after the study.Results1. Twelve RCTs were included in this meta-analysis. Compared with the control group, the combined SMD(95% CI) of body weight, lean body tissue, and body fat mass were-1.30kg(-3.53~0.93), 1.35kg(0.20~2.51), and-1.24kg(-2.02~-0.47) respectively; serum LDL-C, HDL-C, TC and TG were-0.02mmol/L(-0.14~0.11), 0.01mmol/L(-0.05~0.06), 0.02mmol/L(-0.22~0.27) and-0.14mmol/L(-0.27~-0.02), respectively, in subjects supplemented with whey protein. Subgroup analysis found that combining studies with men, intervention doses more than 52 g, sports training and maintain of energy intake significantly increased lean body tissue and reduced body fat mass. Serum TG levels significantly reduced when intervention dose was less than 33.3g, or exercise training was not performed.2. The mice after STZ injection showed typical symptom of T2 DM. Mice in Leu H drank less water than that in only STZ injection group. There were no differences of lipid profiles among 4 groups. Fasting glucose significantly increased after STZ injection; however, no differences of serum insulin among groups were observed. STZ injection increased homeostasis model assessment insulin resistance(HOMA-IR) without significant different from control groups. On the other hand, isletβcell function index-HOMA-β significantly decreased after STZ injection and restored when leucine was fed. The mice in Leu H group even had higher HOMA-β than normal mice and was significantly higher than the only STZ injection group(p<0.05); Pancreatic pathology HE staining and immunohistochemical analysis showed that leucine could protect pancreas islet and maintain the number and the function of β cells.3. Thirty participants(15 in the intervention group and 15 in the control group) completed the study. Participants consumed about 5g of leucine per day from diet. There were no significant differences in body weight, fat mass, muscle mass between the control and intervention groups. In addition, the plasma levels of fasting blood glucose, glycosylated hemoglobin and blood lipids were similar between two groups. Little change of these parameters was observed before and after the study.Conclusions1. Supplemental whey protein increases lean body mass, decrease the body fat mass and blood triglycerides levels in overweight/obese subjects.2. Leucine can protect the number and the function of islet beta cells in model mice of T2 DM.3. Leucine supplementation for 6 months has no effects on body compositions, blood glucose and blood lipids in overweight/obese adult with T2 DM.