The relationship between circulating adiponectin, ADIPOQ variants and incident cardiovascular disease in type 2 diabetes: The Fremantle Diabetes Study.

AIMS

To investigate the relationship between serum adiponectin, ADIPOQ variants and haplotypes, and cardiovascular disease (CVD) in type 2 diabetes (T2D).

METHODS

Baseline data including serum total adiponectin and 21 ADIPOQ polymorphisms were available for 1076 participants (mean age 64.0 years, 49.4% males) in a community-based cohort followed for an average of 12 years.

RESULTS

During 8843 patient-years of follow-up for coronary heart disease (CHD), 13,494 patient-years for ischaemic stroke (IS) and 12,028 patient-years for heart failure (HF), 40.4%, 11.8% and 31.9% of patients experienced a first episode of CHD, IS or HF, respectively. In Cox regression after adjustment for the most parsimonious models, log(serum adiponectin) and the ADIPOQ variant rs12495941 were inversely associated with incident CHD (hazard ratio [95% confidence interval] 0.79 [0.65-0.98] and 0.64 [0.44-0.94], respectively), while rs1648707 was positively associated with incident IS (2.05 [1.37-3.06]; all P ≤ 0.028). In males, rs9860747 and rs17366568 predicted CHD (0.22 [0.05-0.92] and 1.50 [1.01-2.20]; P ≤ 0.042), while rs1648707 and rs1063537 predicted IS (2.36 [1.32-4.23] and 2.09 [1.17-3.72]; P ≤ 0.012). In females, rs10937273 predicted CHD via an interaction with serum adiponectin (0.43 [0.21-0.91]; P = 0.027), while rs864265 predicted IS (0.43 [0.21-0.88], P = 0.021). The associations between ADIPOQ variants and outcomes were supported by haplotype block analysis. Neither serum adiponectin nor ADIPOQ variants predicted HF.

CONCLUSIONS

Serum total adiponectin and gender-specific ADIPOQ variants predict CHD and IS, but not HF, independently of other risk factors in community-based patients with T2D. In contrast to some previous studies, there was no relationship between a high serum total adiponectin and CVD.