title: The combined effect of adiponectin and resistin on all-cause mortality in patients with type 2 diabetes: Evidence of synergism with abdominal adiposity.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  Adiponectin and resistin show an additive independent effect on all-cause mortality in patients with T2D. Such effect is modified by abdominal adiposity.
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: Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.affiliation: Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
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: 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*; D050154:Adiposity; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009026:Mortality; D056128:Obesity, Abdominal / Q000150:complications* / Q000378:metabolism; D052243:Resistin / Q000097:blood*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055105:Waist Circumference
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D001786:Blood Glucose; C499624:RETN protein, human; D052243:Resistin
keywords: Additive effect; Adiponectin; Mortality risk; Resistin; Waist circumference