Examinando por Autor "Fontana, Andrea"

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Evidence of a causal relationship between high serum adiponectin levels and increased cardiovascular mortality rate in patients with type 2 diabetes
(BioMed Central, 2016) Ortega Moreno, Lorena; Copetti, Massimiliano; Fontana, Andrea; De Bonis, Concetta; Salvemini, Lucia; Trischitta, Vincenzo; Menzaghi, Claudia
Background Despite its beneficial role on insulin resistance and atherosclerosis, adiponectin has been repeatedly reported as an independent positive predictor of cardiovascular mortality. Methods A Mendelian randomization approach was used, in order to evaluate whether such counterintuitive association recognizes a cause-effect relationship. To this purpose, single nucleotide polymorphism rs822354 in the ADIPOQ locus which has been previously associated with serum adiponectin at genome-wide level, was used as an instrument variable. Our investigation was carried out in the Gargano Heart Study-prospective design, comprising 356 patients with type 2 diabetes, in whom both total and high molecular weight (HMW) adiponectin were measured and cardiovascular mortality was recorded (mean follow-up = 5.4 ± 2.5 years; 58 events/1922 person-year). Results The A allele of rs822354 was associated with both total and HMW adiponectin [β (SE) = 0.10 (0.042), p = 0.014 and 0.17 (0.06), p = 0.003; respectively]. In a Poisson model comprising age, sex, smoking habits, BMI, HbA1c, total cholesterol, HDL-cholesterol, triglycerides, insulin therapy and hypertension, both rs822354 (IRR = 1.94, 95 % CI 1.23–3.07; p = 0.005), as well as the genetic equivalent of total adiponectin change (IRR = 1.07, 95 % CI 1.02–1.12; p = 0.003) were significantly associated with cardiovascular mortality. The observed genetic effect was significantly greater than that exerted by the genetic equivalent change of serum adiponectin (p for IRR heterogeneity = 0.012). In the above-mentioned adjusted model, very similar results were obtained when HMW, rather than total, adiponectin was used as the exposure variable of interest. Conclusions Our data suggest that the paradoxical association between high serum adiponectin levels and increased cardiovascular mortality rate is based on a cause-effect relationship, thus pointing to an unexpected deleterious role of adiponectin action/metabolism on atherosclerotic processes.
Serum resistin is causally related to mortality risk in patients with type 2 diabetes: preliminary evidences from genetic data
(2017) Ortega Moreno, Lorena; Fontana, Andrea; Lamacchia, Olga; De Bonis, Concetta; Salvemini, Lucia; De Cosmo, Salvatore; Cignarelli, Mauro; Copetti, Massimiliano; Trischitta, Vincenzo; Menzaghi, Claudia
Resistin has been firmly associated with all-cause mortality. We investigated, whether, in patients with type 2 diabetes (T2D), this association is sustained by a cause-effect relationship. A genotype risk score (GRS), created by summing the number of resistin increasing alleles of two genome-wide association studies (GWAS)-derived single nucleotide polymorphisms (SNPs), serum resistin measurements and allcause death records were obtained in 1,479 (403 events/12,454 person-years), patients with T2D from three cohorts, Gargano Heart Study-prospective design (n=350), Gargano Mortality Study (n=698) and Foggia Mortality Study (n=431), from Italy. GRS was strongly associated with serum resistin in a non-linear fashion (overall p=3.5*10−7) with effect size modest for GRS=1 and 2 and much higher for GRS >3, with respect to GRS=0. A significant non-linear association was observed also between GRS and all-cause mortality (overall p=3.3*10−2), with a low effect size for GRS=1 and 2, and nearly doubled for GRS≥3, with respect to GRS=0. Based on the above-reported associations, each genetic equivalent SD increase in log-resistin levels showed a causal hazard ratio of all-cause mortality equal to 2.17 (95%CI: 1.22–3.87), thus providing evidence for a causal role of resistin in shaping the risk of mortality in diabetic patients.
The combined effect of adiponectin and resistin on all-cause mortality in patients with type 2 diabetes: Evidence of synergism with abdominal adiposity
(2016) Ortega Moreno, Lorena; Lamacchia, Olga; Fontana, Andrea; Copetti, Massimiliano; Salvemini, Lucia; De Bonis, Concetta; Cignarelli, Mauro; Trischitta, Vincenzo; Menzaghi, Claudia
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.