Abstract
BackgroundHigh serum levels of the pro-inflammatory adipokine resistin have been associated with decreased renal function in the general population. The goal of this study was to investigate whether such association is also present among diabetic subjects, who are at increased risk of renal function loss.MethodsThe cross-sectional association between serum resistin levels and estimated glomerular filtration rate (eGFR) was investigated in 1,560 type 2 diabetic (T2D) patients of European ancestry comprised in two different cohorts: 762 patients from San Giovanni Rotondo (SGR; Italy) and 798 patients from Boston (US).ResultsSerum resistin was inversely associated with eGFR in SGR [β (SE) for one SD of resistin increment = -1.01 (0.70) ml/min/1.73m2, p = 0.019] and in Boston [β (SE) = -5.31 (0.74) ml/min/1.73m2, p < 0.001] samples, as well as in the two studies combined [β (SE) = -3.42 (0.52) ml/min/1.73m2, p < 0.001]. The association was unaffected by adjustment for smoking habits, BMI, waist circumference, diabetes duration, HbA1c, insulin treatment, hypertension and lipid-lowering therapy: β (SE) for one SD of resistin increment = -1.07 (0.70), p = 0.02; -5.50 (0.88), p < 0.001; and -2.81 (0.55) ml/min/1.73m2, p < .001, in SGR, Boston and the two studies combined, respectively. The association was significantly stronger in men than in women (p for resistin-by-gender interaction = 0.003). For each resistin SD increment, the odds of having eGFR < 0 ml/min/1.73m2 increased by 22% (OR = 1.22; 95% CI 1.02–1.44; p = 0.025) in SGR sample, 69% (OR = 1.69; 95% CI 1.38–2.07; p < 0.001) in Boston sample, and 47% (OR = 1.47; 95% CI 1.29–1.68; p < 0.001) in the two studies considered together. Similar associations were observed in the adjusted model: OR 95% CI for each SD resistin increment being 1.23 (1.03–1.46), p = 0.021; 1.52 (1.20–1.92), p < 0.001; 1.33 (1.16–1.53), p < 0.001, in SGR, Boston and the two studies combined, respectively.ConclusionsThis is the first report of an association between high serum resistin and low eGFR in patients with T2D of European ancestry.
Highlights
Chronic kidney disease (CKD), defined as reduced glomerular filtration rate (GFR), is a leading cause of premature death in patients with type 2 diabetes (T2D) [1,2,3]
Serum resistin was inversely associated with estimated glomerular filtration rate (eGFR) in San Giovanni Rotondo (SGR) [β (SE) for one standard deviation (SD) of resistin increment = -1.01 (0.70) ml/min/1.73m2, p = 0.019] and in Boston [β (SE) = -5.31 (0.74) ml/min/1.73m2, p < 0.001] samples, as well as in the two studies combined [β (SE) = -3.42 (0.52) ml/min/1.73m2, p < 0.001]
For each resistin SD increment, the odds of having eGFR < 0 ml/min/1.73m2 increased by 22% (OR = 1.22; 95% confidence interval (95% CI) 1.02–1.44; p = 0.025) in SGR sample, 69% (OR = 1.69; 95% CI 1.38–2.07; p < 0.001) in PLOS ONE | DOI:10.1371/journal.pone
Summary
Chronic kidney disease (CKD), defined as reduced glomerular filtration rate (GFR), is a leading cause of premature death in patients with type 2 diabetes (T2D) [1,2,3]. Cytokines secreted by adipose tissue (collectively known as adipokines) have been linked to both insulin resistance and low-grade inflammation [8]. Several cross-sectional studies have reported an inverse relationship between serum resistin levels and kidney function [14,15,16,17]. Such association has been described in the general populations [16] and in selected clinical settings [14,15,17] but not in T2D, for which only scant data, derived from post-hoc, subgroup analyses, are available [15]. The goal of this study was to investigate whether such association is present among diabetic subjects, who are at increased risk of renal function loss
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