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Background and Aims: High levels of serum uric acid (SUA) are associated with increased mortality risk in the general population. Contrasting results are available in people with diabetes. The aim of our study was to investigate the association and its functional form between SUA and all cause-mortality in patients with type 2 diabetes mellitus (T2DM)., Methods: We studied three cohorts of patients with T2DM: Gargano Mortality Study, Foggia Mortality Study, Pisa Mortality Study. All-cause mortality rate was the end point of this study., Results: The most reliable relationship between SUA levels and all-cause mortality rate was quadratic, with such model being well approximated by SUA tertiles. Both tertiles 1 and 3 were at higher risk of mortality as compared to tertile 2: Hazard Ratio (HR) [95% Confidence Interval (CI)] = 1.34 (1.07-1.68) and 1.61 (1.29-1.99), respectively. In the pseudo-sample, created from the real pooled sample, the best relationship between SUA and all-cause mortality rate was quadratic. In a tree-based Recursive Partitioning and Regression Tree analysis two subgroups at increased risk of mortality were identified, namely those with SUA levels ≥7.28 mg/dl and with SUA levels <4.16 mg/dl as compared to patients with intermediate SUA levels (i.e. 4.16-7.28), thus providing further evidence on the J-shaped relationship between SUA levels and mortality rate., Conclusions: SUA was not linearly associated with all-cause mortality rate in patients with T2DM. For clinical and public health purposes such association is J-shaped., (Copyright © 2017. Published by Elsevier B.V.)

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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The paradoxical relationship between high adiponectin and increased mortality, described in several clinical subsets, has been reported only once in type 2 diabetes (T2D) and only in selected elderly patients. We investigated this relationship in unselected patients with T2D and, then, addressed its possible modulation by several demographic and clinical conditions, known to affect per se mortality rate., Methods: Patients from the Gargano Mortality Study (GMS; N = 897, follow-up = 10.5 ± 3.7 years; 290 events) and the Foggia Mortality Study (FMS; N = 529, follow-up = 7.1 ± 2.5 years; 143 events), were investigated., Results: For each SD adiponectin increase, HRs (95% CI) for all-cause mortality were 1.30 (1.19-1.43) in GMS, 1.43 (1.26-1.64) in FMS and 1.34 (1.24-1.45) in the combined studies. This association was independent of the possible confounding effect of demographics, adiposity measures, diabetes-related features, kidney function-related parameters and medications (p = 9.34 × 10(-9)). While no interaction was observed between adiponectin and sex, age, smoking habits, BMI, waist circumference, HbA1c, diabetes duration, micro-/macro-albuminuria and medications, a strong interaction was observed with GFR, with a significant adiponectin-mortality association observed in individuals with GFR ≥ but not those with GFR < 60 ml/min/1.73 m(2); p for adiponectin-by-GFR status interaction = 2.13 × 10(-6))., Conclusion: This is the first study reporting a paradoxical association of adiponectin with all-cause mortality in a large sample of unselected diabetic patients and indicating that such counterintuitive effect is observed only among patients with preserved kidney function. Further studies are needed to address if the strong interwoven effect of adiponectin and GFR turns to be useful in improving previously validated tools for predicting mortality in T2D., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)