title: The paradoxical association of adiponectin with mortality rate in patients with type 2 diabetes: evidence of synergism with kidney function.
abstract: 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)).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Ortega Moreno
authors.affiliation: Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Lamacchia
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Salvemini
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: De Bonis
authors.affiliation: Division of Internal Medicine, IRCCS "Casa Sollievo Della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Cosmo
authors.affiliation: Unit of Endocrinology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Cignarelli
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy; Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. Electronic address: vincenzo.trischitta@uniroma1.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy. Electronic address: c.menzaghi@operapadrepio.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Menzaghi
mesh_terms: D052242:Adiponectin / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology* / Q000401:mortality; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007558:Italy / Q000453:epidemiology; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends
chemical_list: D052242:Adiponectin
keywords: Adipokines; Mortality; Renal dysfunction; Type 2 diabetes