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Creatine supplementation improves glucose tolerance in healthy subjects.The aim was to investigate whether creatine supplementation has a beneficial effect on glycemic control of type 2 diabetic patients undergoing exercise training.A 12-wk randomized, double-blind, placebo-controlled trial was performed. The patients were allocated to receive either creatine (CR) (5 g·d−1) or placebo (PL) and were enrolled in an exercise training program. The primary outcome was glycosylated hemoglobin (HbA1c). Secondary outcomes included the area under the curve of glucose, insulin, and C-peptide and insulin sensitivity indexes. Physical capacity, lipid profile, and GLUT-4 protein expression and translocation were also assessed.Twenty-five subjects were analyzed (CR: n = 13; PL: n = 12). HbA1c was significantly reduced in the creatine group when compared with the placebo group (CR: PRE = 7.4 ± 0.7, POST = 6.4 ± 0.4; PL: PRE = 7.5 ± 0.6, POST = 7.6 ± 0.7; P = 0.004; difference = −1.1%, 95% confidence interval = −1.9% to −0.4%). The delta area under the curve of glucose concentration was significantly lower in the CR group than in the PL group (CR = −7790 ± 4600, PL = 2008 ± 7614; P = 0.05). The CR group also presented decreased glycemia at times 0, 30, and 60 min during a meal tolerance test and increased GLUT-4 translocation. Insulin and C-peptide concentrations, surrogates of insulin sensitivity, physical capacity, lipid profile, and adverse effects were comparable between the groups.Creatine supplementation combined with an exercise program improves glycemic control in type 2 diabetic patients. The underlying mechanism seems to be related to an increase in GLUT-4 recruitment to the sarcolemma.