Abstract
BackgroundThe pathogenesis of cardiovascular (CV) mortality, whose rate is increased in type 2 diabetes, is poorly understood.While high serum adiponectin is associated with increased CV mortality in the general population, no data are available in type 2 diabetes.We here investigated whether this counterintuitive association was observable also in diabetic patients and whether it was sex-specific.MethodsThree prospective cohorts were analyzed: 1) Gargano Heart Study (GHS; 359 patients, 58 events/1,934 person-years; py); 2) Health Professional Follow-up Study (HPFS; 833 men, 146 events/10,024 py); 3) Nurses’ Health Study (NHS; 902 women, 144 events/15,074 py).ResultsIn GHS serum adiponectin predicted CV mortality in men (hazard ratio, HR, and 95% CI per standard deviation, SD, increment = 1.54, 1.19-2.01), but not women (HR = 0.98, 0.48-2.01).Circulating adiponectin predicted CV mortality in men from HPFS (HR = 1.44, 1.21-1.72), but not in women from NHS (HR = 1.08, 0.86-1.35), used as replication samples. In a pooled analysis, HRs were 1.47 (1.27-1.70) in 1,075 men and 1.07 (0.86-1.33) in 1,019 women (p for HRs heterogeneity across sexes = 0.018).ConclusionsThis is the first report showing that high circulating adiponectin predicts increased CV mortality in men, but not in women with type 2 diabetes. Further studies are necessary to unravel the mechanisms through which adiponectin influences CV mortality in a sex-specific manner.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-014-0130-y) contains supplementary material, which is available to authorized users.
Highlights
The pathogenesis of cardiovascular (CV) mortality, whose rate is increased in type 2 diabetes, is poorly understood
Adiponectin, a 244-amino acid protein secreted by adipocytes has insulin-sensitizing, anti-inflammatory, and
It has been recently reported that in humans there is a sex-specific effect of serum adiponectin in the development of type 2 diabetes [24] and in the progression of chronic kidney disease [25]; data in mice with genetically induced endothelial dysfunction in which adiponectin exerts its beneficial effect on heart function and remodeling in female but not male are compatible with a sexual dimorphism [26]
Summary
Three prospective cohorts were analyzed: 1) Gargano Heart Study (GHS; 359 patients, 58 events/1,934 person-years; py); 2) Health Professional Follow-up Study (HPFS; 833 men, 146 events/10,024 py); 3) Nurses’ Health Study (NHS; 902 women, 144 events/15,074 py). Study populations GHS-prospective design This study comprises 368 patients with type 2 diabetes (ADA 2003 criteria) and coronary artery disease who were consecutively recruited at the Endocrine Unit of IRCCS “Casa Sollievo della Sofferenza” in San Giovanni Rotondo (Gargano, Center East Coast of Italy) from 2001 to 2008, as recently described [29,30]. The time variable was defined as the time between the baseline examination and date of the event (CV mortality), or, for subjects who did not experience the event, the date of the last available clinical follow-up. The same analyses were carried out in males and females from the GHS-prospective design, separately
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