Plasma creatine concentrations are lower in men than in women, and men with higher plasma creatine are at greatly increased risk of developing type 2 diabetes (T2D), according to data from the PREVEND study.
A total of 4,735 participants (49 percent male) with a mean age of 52 years participated in the study. Mean fasting plasma creatine concentrations at baseline, measured using nuclear magnetic resonance spectroscopy, were 36.7 µmol/L; 30.4 µmol/L in males and 42.7 µmol/L in females (p<0.001).
Over 7.3 years of follow‐up, T2D occurred in 235 individuals (5.4 percent). T2D was defined as a fasting plasma glucose ≥7.0 mmol/L (126 mg/dl), a random sample plasma glucose ≥11.1 mmol/L (200 mg/dl), self‐report of a physician diagnosis, or the use of glucose‐lowering medications based on a central pharmacy registration.
Multivariable Cox proportional hazards analysis revealed higher plasma creatine concentrations to be associated with an increased T2D incidence. Each SD-change in creatine levels conferred a 27-percent risk increase (hazard ratio [HR], 1.27, 95 percent confidence interval [CI], 1.11–1.44; p<0.001).
The association was strongly modified by sex (p<0.001), such that higher plasma creatine contributed to an increased risk of incident T2D in males (HR, 1.40, 95 percent CI, 1.17–1.67; p<0.001) but not in females (HR, 1.10, 95 percent CI, 0.90–1.34; p=0.37).
Additional studies are needed to establish the underlying mechanisms for the sex‐based differences seen in the association between plasma creatine and T2D.