Type 2 diabetes (T2D) is a risk factor for muscle loss and subsequent frailty. The reverse association, however, may also happen. This study examined whether serum creatinine level, an indicator of muscle mass, predicted diabetes development. In addition, a role for body mass index (BMI) as an effect modifier of creatinine levels was evaluated.

This cohort study included 9667 subjects without diabetes or hypertension and with normal creatinine levels at baseline. Multiple-adjusted hazard ratios (HRs) for associations between baseline creatinine and diabetes development were estimated using the Cox proportional-hazards model. Stratified analyses based on BMI were also performed.

During the follow-up period (mean: 5.6 years), 287 (5.5%) men and 115 (2.3%) women developed T2D. HR in men with serum creatinine≤0.7mg/dL compared with 0.9–1.2mg/dL was 1.40 (95% CI: 1.05–1.87) after adjusting for age, BMI, blood pressure and fasting plasma glucose at baseline, whereas the adjusted HR in women with creatinine≤0.5mg/dL compared with 0.7–1.1mg/dL was 1.69 (95% CI: 1.04–2.76). In a subgroup analysis stratified by BMI, interactions between BMI and baseline creatinine levels for T2D were statistically significant in women with the lowest creatinine levels (P=0.08 for interaction).

Low serum creatinine levels, a surrogate marker of muscle mass, predict T2D development in both genders, even after excluding the effect of diabetic and prediabetic glomerular hyperfiltration. BMI modified the association between creatinine and diabetes development in women.