The paradoxical association of adiponectin with mortality rate in patients with type 2 diabetes: Evidence of synergism with kidney function

Lorena Ortega Moreno, Olga Lamacchia, Lucia Salvemini, Concetta De Bonis, Salvatore De Cosmo, Mauro Cignarelli, Vincenzo Trischitta, Claudia Menzaghi

Research output: Contribution to journalArticlepeer-review


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 m2; 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.

Original languageEnglish
Pages (from-to)222-227
Number of pages6
Publication statusPublished - Feb 1 2016


  • Adipokines
  • Mortality
  • Renal dysfunction
  • Type 2 diabetes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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