The combined effect of adiponectin and resistin on all-cause mortality in patients with type 2 diabetes: Evidence of synergism with abdominal adiposity

Background and aims: While elevated serum adiponectin and resistin levels have been singly associated with all-cause mortality in patients with type 2 diabetes (T2D), their combined effect has never been studied.We investigated such joint effect in patients with T2D and its possible modulation by several demographic and clinical conditions, known to affect per se mortality rate. Methods: Patients with T2D from the Gargano Mortality Study (GMS; N = 895, follow-up = 10.5 ± 3.7 years; 290 events) and the Foggia Mortality Study (FMS; N = 519, follow-up = 7.1 ± 2.5 years; 140 events) were examined. Results: As singly considered, adiponectin and resistin were independently associated with mortality rate in GMS and FMS (p <0.0001 for both). The two studies were then pooled, for investigating the nature of the joint effect of the two adipokines. In such sample, both adipokines were associated with death, independent of each other and of several additional covariates (p = 0.01-4.58 × 10^-12). Of note, no adiponectin-by-resistin interaction was observed (p = 0.40), thus pointing to an additive effect of the two adipokines. As compared to individuals with low levels of both adiponectin and resistin (i.e. below median values), those with high levels of both adipokines had an HR (95%CI) for death of 3.02 (2.26-4.03). Such increased risk was more pronounced in individuals with relatively low abdominal adiposity (p for HR heterogeneity below or above the median value of waist circumference = 0.03). Conclusions: Adiponectin and resistin show an additive independent effect on all-cause mortality in patients with T2D. Such effect is modified by abdominal adiposity.