P5362Metabolomic signature of incident type 2 diabetes: evidence from NMR in over 18,000 individuals

Diabetes / Cardiovascular cell biology 1133 creased with increasing age from 94.0% (35-44 years) to 60.2% (65-74 years), whereas the prevalence of hyperinsulinaemia (2.2% to 5.2%), prediabetes (2.3% to 16.6%) and T2D (1.4% to 18.0%) increased from the first to the last age decade.In multiple Poisson regression analysis, hyperinsulinaemia and prediabetes were independently associated with age (PR 1.24 [95%confidence interval] 1.15/1.34,and PR 1.77 [1.68/1.86]),obesity (PR 6.81 [5.69/8.14]and PR 2.07 [1.87/2.28]),active smoking (PR 1.47 [1.21/1.78]and PR 1.86 [1.66/2.08]),dyslipidaemia (PR 1.58 [1.35/1.86]and PR 1.55 [1.40/1.71])and arterial hypertension (PR 2.18 [1.77/2.68]and PR 1.31 [1.17/1.47];for all: p<0.0001).After adjustment for age and sex, hyperinsulinaemia (PR 1.20 [1.13/1.28])and prediabetes (PR=1.12[1.08/1.16])independently indicated an increased risk for AOD (p<0.0001).For clinically-manifest CVD, all entities of the diabetic continuum (hyperinsulinaemia: PR 1.26 [1.05/1.51],p=0.013; prediabetes: PR 1.25 [1.11/1.41],p<0.001;T2D: PR 1.44 [1.29/1.61],p<0.0001) were independent risk factors in addition to established CVRF.Both T2D (hazard ratio (HR) 4.29 [3.52/5.23])and its precursors (hyperinsulinaemia: HR 2.22 [1.55/3.18];prediabetes: HR 2.07 [1.61/2.68])inherited a higher risk of all-cause mortality compared to euglycaemia in the population (p<0.0001).Conclusions: The relation of hyperinsulinaemia and prediabetes with clinical and subclinical CVD highlights the relevance of T2D precursors in the pathophysiology of CVD and emphasizes the need for new concepts in primary prevention of CVD.