Endocrine Abstracts (2004) 8 P40

Evolution of insulin resistance in adolescent and young men

FJ Charchar1, M Tomaszewski1, E Zukowska-Szczechowska2, W Grzeszczak2 & AF Dominiczak1

1BHF Glasgow Cardiovascular Research Center, University of Glasgow, UK; 2Dept of Internal Medicine, Diabetology and Nephrology, Silesian School of Medicine, Zabrze, Poland.

Transient insulin resistance (IR) is a recognized facet of metabolic phenotype in pubertal boys. However, it remains unknown how the Y chromosome and adolescence as a transition from pubertal period to adulthood affects markers of insulin resistance, particularly in relation to body mass index, blood pressure and androgens.We analyzed associations among indicators of insulin resistance, total adiposity, androgen profile and the Y chromosome in a sample of 1745 males divided into 1492 adolescents (aged 18.1±0.9 years) and 253 young adult men (aged 24.4±7.0 years). BMI was used as a marker of total adiposity. We measured free testosterone, BP, insulin resistance by homeostasis model assessment (HOMA-IR) and genotyped for a SNP on the Y chromosome. HOMA-IR (adjusted for BMI and testosterone) decreased gradually across four age categories of adolescence (2.2±1.7 vs. 2.0±1.4 vs.1.9±1.4 vs. 1.8±1.5 in men aged 16, 17, 18 and 19 years, respectively, p<0.0001). This reduction in IR was accompanied by progressive increase in BMI. There was no difference in levels of testosterone or BP among these age groups.In contrast, analysis of changes of HOMA-IR from late adolescence to young maturity increased with age (1.8±1.5 vs. 1.9±1.3 vs. 2.2±1.8, in men aged 19, 20 and 21 or older, respectively, p=0.004). Adjustment for BMI (but not testosterone) completely abolished the differences in HOMA-IR (p=0.501) and including testosterone as another covariant in the regression model had no significant effect on differences in HOMA-IR (p=0.566). Following IR, blood pressures increased with age among young adult men aged 19 and over (<0.0001). There was association between the Y chromosome and insulin resistance in the cohort. In conclusion IR undergoes substantial fluctuations throughout phases of development in healthy men. Future studies are warranted to elucidate mechanistic explanation and clinical relevance of this phenomenon.

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