Abstract
BackgroundLow 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.MethodsCross-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.ResultsThe unadjusted GAM analysis suggested a piecewise linear relationship between serum creatinine and diabetes. Each 1 μmol/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 μmol/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.ConclusionsLow 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.
Highlights
Low skeletal muscle mass is associated with insulin resistance and metabolic syndrome
The log (HOMA-IR) is presented both because it has a stronger linear correlation with glucose clamp estimates of insulin sensitivity and because it is useful for the evaluation of insulin resistance in glucose intolerant individuals, those with mild to moderate diabetes, and those with other insulin-resistant conditions [20]
Clinical characteristics and risk factors according to gender and presence or absence of type 2 diabetes mellitus (T2DM) are shown in table 1 (Additional file 1)
Summary
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. Muscle mass has been shown to be inversely associated with insulin resistance [4] and the metabolic syndrome [5]. Kuk et al found that whole-body skeletal muscle mass was not associated with either glucose tolerance or insulin sensitivity in overweight and obese men and women [6]. Creatinine is the only metabolite of creatine which is mainly (98%) located in striated muscle [7], and 24-h urinary creatinine excretion is highly correlated with muscle mass estimates by dual-energy X-ray absorptiometry [8].
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