Genetic influence on the associations between IGF-I and glucose metabolism in a cohort of elderly twins

Rikke Beck Jensen, Ajay Thankamony, Klaus K Holst, Joseph A M J L Janssen, Anders Juul, David Dunger, Pernille Poulsen, Thomas Scheike


OBJECTIVE: IGF-I may be a marker of later metabolic and cardiovascular disease. The interactions between IGF-I and glucose metabolism are multifactorial, and there is potential confounding from several secondary effects. In this study, we examined the interaction between IGF-I and glucose metabolism in a large cohort of clinically well-characterized elderly twins.

DESIGN: A total of 303 twin pairs of the same gender (606 twins) were included in the study; 125 monozygotic and 178 dizygotic twin pairs.

METHODS: A clinical examination including a standard oral glucose tolerance test (OGTT) and anthropometric measurements was performed.

RESULTS: The heritability estimates were high for IGF-I and IGFBP-3 (h2: 0.65 (95% CI: 0.55-0.74) and 0.71 (0.48-0.94), respectively) and for insulin secretion (h2 = 0.56, P < 0.0001), whereas the heritability estimates for insulin sensitivity were low (h2 = 0.14, P = 0.11). In a multiple regression analysis (adjusting for age, gender and twin status), there was a negative association between IGF-I and insulin sensitivity (B: -0.13, SE 0.03, P < 0.0001) and IGF-I and disposition index (B: -0.05, SE 0.02, P < 0.001) in the entire cohort of 606 twins. The associations between IGF-I and both DI and HOMA-S did not differ between the DZ and MZ twins. Forty-five twin pairs were discordant for T2D, but the discordant twins had similar concentrations of IGF-I or IGFBP-3.

CONCLUSIONS: There was a high heritability for IGF-I and IGFBP-3, but a low heritability for insulin secretion and insulin sensitivity in a group of elderly twins. In addition, we found a strong negative relationship between IGF-I and insulin sensitivity, which did not seem to be strongly genetically determined.

TidsskriftEuropean Journal of Endocrinology
Udgave nummer2
Sider (fra-til)155-163
Antal sider9
StatusUdgivet - feb. 2018


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