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Serum resistin is causally related to mortality risk in patients with type 2 diabetes: preliminary evidences from genetic data.

ABSTRACT: Resistin has been firmly associated with all-cause mortality. We investigated, whether, in patients with type 2 diabetes (T2D), this association is sustained by a cause-effect relationship. A genotype risk score (GRS), created by summing the number of resistin increasing alleles of two genome-wide association studies (GWAS)-derived single nucleotide polymorphisms (SNPs), serum resistin measurements and all-cause death records were obtained in 1,479 (403 events/12,454 person-years), patients with T2D from three cohorts, Gargano Heart Study-prospective design (n?=?350), Gargano Mortality Study (n?=?698) and Foggia Mortality Study (n?=?431), from Italy. GRS was strongly associated with serum resistin in a non-linear fashion (overall p?=?3.5?*?10-7) with effect size modest for GRS?=?1 and 2 and much higher for GRS >3, with respect to GRS?=?0. A significant non-linear association was observed also between GRS and all-cause mortality (overall p?=?3.3?*?10-2), with a low effect size for GRS?=?1 and 2, and nearly doubled for GRS???3, with respect to GRS?=?0. Based on the above-reported associations, each genetic equivalent SD increase in log-resistin levels showed a causal hazard ratio of all-cause mortality equal to 2.17 (95%CI: 1.22-3.87), thus providing evidence for a causal role of resistin in shaping the risk of mortality in diabetic patients.

SUBMITTER: Fontana A

PROVIDER: S-EPMC5427821 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Serum resistin is causally related to mortality risk in patients with type 2 diabetes: preliminary evidences from genetic data.

Fontana Andrea A Ortega Moreno Lorena L Lamacchia Olga O De Bonis Concetta C Salvemini Lucia L De Cosmo Salvatore S Cignarelli Mauro M Copetti Massimiliano M Trischitta Vincenzo V Menzaghi Claudia C

Scientific reports 20170303 1

Resistin has been firmly associated with all-cause mortality. We investigated, whether, in patients with type 2 diabetes (T2D), this association is sustained by a cause-effect relationship. A genotype risk score (GRS), created by summing the number of resistin increasing alleles of two genome-wide association studies (GWAS)-derived single nucleotide polymorphisms (SNPs), serum resistin measurements and all-cause death records were obtained in 1,479 (403 events/12,454 person-years), patients with ...[more]

PMID: 28246403

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Project description: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 [? (SE) for one SD of resistin increment = -1.01 (0.70) ml/min/1.73 m(2), p = 0.019] and in Boston [? (SE) = -5.31 (0.74) ml/min/1.73 m(2), p < 0.001] samples, as well as in the two studies combined [? (SE) = -3.42 (0.52) ml/min/1.73 m(2), 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: ? (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/1.73 m(2), 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/1.7 3m(2) 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.

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Serum resistin is causally related to mortality risk in patients with type 2 diabetes: preliminary evidences from genetic data.

Publications

Serum resistin is causally related to mortality risk in patients with type 2 diabetes: preliminary evidences from genetic data.

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