Genetic influence on the associations between IGF-I and glucose metabolism in a cohort of elderly twins
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Genetic influence on the associations between IGF-I and glucose metabolism in a cohort of elderly twins. / Jensen, Rikke Beck; Thankamony, Ajay; Holst, Klaus K.; Janssen, Joseph A M J L; Juul, Anders; Dunger, David; Poulsen, Pernille; Scheike, Thomas.
I: European Journal of Endocrinology, Bind 178, Nr. 2, 02.2018, s. 155-163.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
VL - 178
SP - 155
EP - 163
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 2
ER -
ID: 189156968