Dose-response associations between serum creatinine and type 2 diabetes mellitus risk: A Chinese cohort study and meta-analysis of cohort studies

Background This study aims to investigate the association between serum creatinine and risk of type 2 diabetes mellitus (T2DM) based on a cohort analysis and meta-analysis of cohort studies. Methods We enrolled 41 439 participants aged >= 18 years without T2DM at baseline, who had >= 2 health examinations based on an ongoing prospective cohort in Beijing. Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs. For the meta-analysis, cohort studies reporting risk estimates for the serum creatinine-T2DM association were included. A random-effects model was used to calculate summary relative risks (RRs) and restricted cubic splines to model the dose-response association. Results During a mean follow-up of 3.54 years, 1867 developed T2DM. Low serum creatinine was associated with increased risk of T2DM; adjusted HRs (95% CIs) across sex-specific quartiles were 1.45 (1.24, 1.71), 1.19 (1.02, 1.39), 1.07 (0.92, 1.24), and 1.00 (reference). The association was significant for both sexes and individuals with overweight or obesity. In the meta-analysis of six cohort studies (including the current study) involving 115 767 participants and 5370 T2DM events, the pooled RR was 1.61 (95% CI 1.35, 1.92), comparing the lowest with the highest category of serum creatinine. We found a linear association between serum creatinine and T2DM risk (P-nonlinearity = .082) and an increased risk of T2DM with each 0.1-mg/dL decrease in serum creatinine (RR = 1.07; 95% CI 1.04, 1.09). Conclusions The cohort study and meta-analysis provide further evidence supporting the negative association between serum creatinine and T2DM risk in a linear dose-response pattern. Highlights Low serum creatinine level was associated with increased risk of type 2 diabetes mellitus (T2DM) among people who were overweight and obese. A linear association was found between serum creatinine and T2DM risk.