Insulin resistance with creatine supplementation in laboratory animals

Introduction and objective: Creatine supplementation has been used in order to improve muscular performance. This substance affects glucose metabolism and stimulates the in vitro as well as the in vivo insulin secretion. Nevertheless, long-term insulin hypersecretion may also induce insulin resistance. The present work analyzed the effects of creatine oral supplementation in order to evaluate the possibility of occurrence of resistance to in vivo insulin. Methods: Forty-eight Wistar rats (24 female/ 24 male) were divided in two groups of 24 (control and study) and subdivided in six groups of eight. They were fed with standard food during four weeks, having water ad libitum. Moreover, the study group received dietetic supplement of creatine (0.4 g creatine for 30 ml of water per rat/day). In the 7 th, 14 th, 21st and 28 th day of the experiment, 12 rats were anesthetized (sodium thiopental 0.15 mL/ 100 g) after six hour-fasting, being submitted to intravenous insulin tolerance test (0.5 mL of 30% regular human insulin and 70% saline solution). The blood samples were collected from the tail veins of the rats, in the basal, three, six, nine, 12 and 15 minutes after insulin administration times. The glucose measurement was performed through the glucose oxidase method. The study was previously approved by the Research Ethics Committee of CCMB- PUCSP. Results: The mean of the glucose decrease constant (K ITT ) was calculated through the formula 0.693/ T 1/2 . The study group, when compared with the control group, presented insulin resistance at day 21 (p < 0.0004) and day 28 (p < 0.0001). Conclusion: This study shows that extended creatine supplementation may lead to insulin resistance. Besides that, it should be carefully used in individuals with glucose metabolism disturbances.