Low serum creatinine is associated with type 2 diabetes in morbidly obese women and men: a cross-sectional study

Abstract

Background: Low skeletal muscle mass is associated with insulin resistance and metabolic syndrome. Serum creatinine may serve as a surrogate marker of muscle mass, and a possible relationship between low serum creatinine and type 2 diabetes has recently been demonstrated. We aimed to validate this finding in a population of Caucasian morbidly obese subjects.

Methods: Cross-sectional study of 1,017 consecutive morbidly obese patients with an estimated glomerular filtration rate >60 ml/min/1.73 m2. Logistic regression (univariate and multiple) was used to assess the association between serum creatinine and prevalent type 2 diabetes, including statistically testing for the possibility of non-linearity in the relationship by implementation of Generalized Additive Models (GAM) and piecewise linear regression. Possible confounding variables such as age, family history of diabetes, waist-to-hip ratio, hypertension, current smoking, serum magnesium, albuminuria and insulin resistance (log HOMA-IR) were adjusted for in three separate multiple logistic regression models.

Results: The unadjusted GAM analysis suggested a piecewise linear relationship between serum creatinine and diabetes. Each 1 mumol/l increase in serum creatinine was associated with 6% (95% CI; 3%-8%) and 7% (95% CI; 2%-13%) lower odds of diabetes below serum creatinine levels of 69 and 72 mumol/l in women and men, respectively. Above these breakpoints the serum creatinine concentrations did not reduce the odds further. Adjustments for non-modifiable and modifiable risk factors left the piecewise effect for both women and men largely unchanged. In the fully adjusted model, which includes serum magnesium, albuminuria and log HOMA-IR, the piecewise effect for men was statistically non-significant, but it remained present for women. Patients with creatinine levels below median had approximately 50% (women) and 75% (men) increased odds of diabetes.

Conclusions: Low serum creatinine is a predictor of type 2 diabetes in Caucasian morbidly obese patients, independent of age, gender, family history of diabetes, anthropometric measures, hypertension, and current smoking. Longitudinal studies of both obese and non-obese populations are needed to investigate whether serum creatinine may be causally linked with type 2 diabetes, and if so, precisely how they are linked.

Figure 1

Relationship between serum creatinine and type 2 diabetes. Left: Estimated functional relationship between serum creatinine and T2DM using Generalized Additive Models (GAM). Breakpoints and 95% CIs from a piecewise linear models at the bottom. Right: Corresponding odds ratios (approximately 0.90 below and 1.0 above the breakpoints). Given the large uncertainty in the location of the breakpoints the graph does not take the shape of the idealized step function a piecewise linear model assumes, but has a marked transition face.