Creatine in type 2 diabetes: A randomized, double-blind, placebo-controlled trial


Journal Title (Medline/Pubmed accepted abbreviation): Med. Sci. Sports Exerc.
Year: 2011
Volume: 43
Number: 5
Page numbers:770-778
doi (if applicable): 10.1016/j.metabol.2010.07.003

Summary of background and research design:

Background: Healthy diet and exercise are the first recommendations in the treatment of diabetes. Creatine has been proposed to aid in the treatment of diabetes by regulating blood glucose. GLUT-4, the transporter that brings glucose from the blood into the body cells, declines with the progression of diabetes, and there is some evidence that creatine may slow this decline.

Hypothesis:Creatine supplementation in combination with exercise training will lead to a greater improvement in glucose sensitivity than aerobic training alone in type 2 diabetic patients.

Subjects: Male (9) and female (16) obese, type 2 diabetic individuals (BMI ≥ 30 kg/m2) who were not involved in regular exercise programs participated in this study.

Experimental design: randomized, double-blind, placebo-controlled, parallel groups. There were 13 people in the creatine group and 12 people in the placebo group.

Protocol: All participants were involved in a moderate-intensity exercise routine involving aerobic and strength training for a little more than 1 hour per day, 3 days per week, for 12 wks. Before and after the 12 wks of training, participants were assessed for HbA1c concentrations and area under the curve for blood glucose, insulin, and C-peptide following a mixed meal (500 kcal, 60% carbohydrates, 20% fat, and 20% protein). Participants were also assessed for muscle strength, aerobic conditioning, body composition, and lipid profile. Finally, muscle biopsies were performed to assess muscle creatine stores and glucose transporter concentration/localization.

Notes:
  • Glycosylated hemoglobin or HbA1c- a metric of long-term blood glucose fluctuations - When blood glucose rises, some of the glucose molecules will become affixed to the hemoglobin in the blood.  If a person experiences many episodes of very high blood glucose, they will exhibit a higher percentage of glycosylated hemoglobin.  This is a routine measure for management of diabetes.
  • C-peptide-  a fragment of the insulin molecule that is cleaved off to release mature insulin.  C-peptide is a good measure of the amount of insulin secretion.

 Treatment: Creatine monohydrate (5 g/day) or a placebo (pure glucose), taken with lunch every day for the 12 wks.
 

Summary of research findings
  • Approximately half of the participants in each group were able to identify which treatment group they were in.  Since they had a 50% chance of guessing correctly, it is suggested that there were little, if any, noticeable effects of the creatine in their daily lives.
  • After the intervention, the creatine group had significantly higher phosphocreatine levels in their muscles compared to the placebo group (70 ± 18 mmol/kg for the creatine group and  46 ± 13 mmol/kg for the placebo group).
  • After intervention, HbA1c concentration was reduced significantly in the creatine group compared to the placebo group, implying better glucose control (p = 0.0001).
  • Fasting blood glucose was reduced in the creatine group as well as that area under the curve for glucose vs. time after a mixed meal.
  • Interestingly, there was no discernable difference in glucose response after the exercise intervention within the placebo group.
  • There were no significant differences in fasting insulin or C-peptide concentrations, nor were there differences in insulin or C-peptide vs. time responses to the mixed meal in either group.
  • All participants experienced increases in strength and muscle function from exercise training, with no significant differences between dietary treatment groups.
  • There were not any significant differences in blood lipoproteins when comparing before and after intervention for either group.
  • GLUT-4 quantity increased to a similar amount after training in both groups.  After training, the GLUT-4 content in the diabetic patients was not significantly different from non-diabetic patients.  However, after creatine supplementation, a greater proportion of GLUT-4 had translocated to the cell membrane compared with placebo.  This was reflected in the membrane-associated GLUT-4 and membrane-associated:total GLUT-4 ratio.

Interpretation of findings/Key practice applications

There has been previous research showing that creatine can help improve insulin sensitivity, especially when coupled with an exercise regimen, and this study further corroborates this previous research. The decline in hemoglobin A1c due to creatine supplementation was approximately 1 percentage point, which is comparable to or exceeds the effects of some pharmaceutical interventions. This study was also interesting because it also provided some mechanistic information (e.g., the GLUT-4 data) on how creatine might work.

Limitations

The participants did not achieve improved glycemic control with exercise alone, as the protocol was designed to do. This is likely because there was only about 64.4% ? 19.9% compliance for the creatine group and 73.3% ? 19.8% compliance for the placebo group in regard to attending the exercise classes. In addition, the sample size was small. However, if these findings can be repeated by other researchers, creatine supplementation may represent a valuable therapeutic option for type 2 diabetes.

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