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

TY - JOUR

T1 - Genetic influence on the associations between IGF-I and glucose metabolism in a cohort of elderly twins

AU - Jensen, Rikke Beck

AU - Thankamony, Ajay

AU - Holst, Klaus K.

AU - Janssen, Joseph A M J L

AU - Juul, Anders

AU - Dunger, David

AU - Poulsen, Pernille

AU - Scheike, Thomas

N1 - © 2018 European Society of Endocrinology.

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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.

KW - Aged

KW - Anthropometry

KW - Blood Glucose

KW - Cohort Studies

KW - Denmark

KW - Diabetes Mellitus, Type 2

KW - Diseases in Twins

KW - Female

KW - Glucose Tolerance Test

KW - Humans

KW - Insulin

KW - Insulin Resistance

KW - Insulin-Like Growth Factor Binding Protein 3

KW - Insulin-Like Growth Factor I

KW - Linear Models

KW - Male

KW - Middle Aged

KW - Twins, Dizygotic

KW - Twins, Monozygotic

KW - Journal Article

KW - Twin Study

U2 - 10.1530/eje-17-0754

DO - 10.1530/eje-17-0754

M3 - Journal article

C2 - 29208737

SN - 0804-4643

VL - 178

SP - 155

EP - 163

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 2

ER -