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Heritability of Insulin Secretion, Peripheral and Hepatic Insulin Action, and Intracellular Glucose Partitioning in Young and Old Danish Twins
Open accessAbstract
The etiology of type 2 diabetes is multifactorial, including genetic as well as pre- and postnatal factors that influence several different defects of glucose homeostasis, primarily in muscle, β-cells, and liver. In the present twin study, we report heritability estimates (h2) for measures of insulin secretion, insulin resistance, hepatic glucose production (HGP), and intracellular glucose partitioning using gold standard methods (euglycemic-hyperinsulinemic clamp technique, tritiated glucose infusion, indirect calorimetry, and intravenous glucose tolerance testing) among 110 younger (22–31 years of age) and 86 older (57–66 years of age) twins. To obtain a valid estimate of β-cell function, insulin secretion was adjusted for the individual degree of insulin action (disposition index). In both age-groups there was a major genetic component in the etiology of insulin secretion that was statistically significantly higher among older twins (young h2 = 0.75 [0.55–0.86] and old h2 = 0.84 [0.69–0.92], P < 0.05). The heritability estimates for peripheral insulin sensitivity (young h2 = 0.53 [0.28–0.71] and old h2 = 0.55 [0.20–0.76]) and nonoxidative glucose metabolism (young h2 = 0.50 [0.32–0.64] and old h2 = 0.48 [0.04–0.72]) were similar in younger and older twins, supporting the notion of both genetic and environmental etiological factors in the control of insulin action and nonoxidative glucose metabolism. The results suggested that HGP was predominantly controlled by nongenetic factors in both young and old twins. In conclusion, we provide further evidence for a role of genes in controlling insulin secretion, insulin action, and nonoxidative glucose metabolism. The relative contribution of genes versus environment on in vivo insulin secretion exhibited an age dependency with a slightly greater relative impact of genes among older as compared with younger twins.
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“Similarly, a genetic predisposition to defective insulin secretion when combined with insulin resistance can raise plasma glucose to abnormal levels.57”
From Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement (2005) · cites this paper as [57]
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Additional file 3 of Exploring Lead loci shared between schizophrenia and Cardiometabolic traits
He, Q., Bennett, A. N., Liu, J., Fan, B., Han, X. F., Cheng, L., Chen, Y., Yang, X., & Chan, K. H. K. (2022) · Figshare · doi:10.6084/m9.figshare.20652136
Additional file 4 of Exploring Lead loci shared between schizophrenia and Cardiometabolic traits
He, Q., Bennett, A. N., Liu, J., Fan, B., Han, X. F., Cheng, L., Chen, Y., Yang, X., & Chan, K. H. K. (2022) · Figshare · doi:10.6084/m9.figshare.20652139
Additional file 1 of Exploring Lead loci shared between schizophrenia and Cardiometabolic traits
He, Q., Bennett, A. N., Liu, J., Fan, B., Han, X. F., Cheng, L., Chen, Y., Yang, X., & Chan, K. H. K. (2022) · Figshare · doi:10.6084/m9.figshare.20652130
Additional file 2 of Exploring Lead loci shared between schizophrenia and Cardiometabolic traits
He, Q., Bennett, A. N., Liu, J., Fan, B., Han, X. F., Cheng, L., Chen, Y., Yang, X., & Chan, K. H. K. (2022) · Figshare · doi:10.6084/m9.figshare.20652133
Additional file 7 of Exploring Lead loci shared between schizophrenia and Cardiometabolic traits
He, Q., Bennett, A. N., Liu, J., Fan, B., Han, X. F., Cheng, L., Chen, Y., Yang, X., & Chan, K. H. K. (2022) · Figshare · doi:10.6084/m9.figshare.20652148
Additional file 5 of Exploring Lead loci shared between schizophrenia and Cardiometabolic traits
He, Q., Bennett, A. N., Liu, J., Fan, B., Han, X. F., Cheng, L., Chen, Y., Yang, X., & Chan, K. H. K. (2022) · Figshare · doi:10.6084/m9.figshare.20652142
Additional file 6 of Exploring Lead loci shared between schizophrenia and Cardiometabolic traits
He, Q., Bennett, A. N., Liu, J., Fan, B., Han, X., Cheng, L., Chen, Y., Yang, X., & Chan, K. H. K. (2022) · Figshare · doi:10.6084/m9.figshare.20652145
Rezki, A. (2019) · theses.fr (ABES) · doi:10.70675/392902d9z7810z4025zb9afz3081c32bac5d
Metadata
- Authors
- Poulsen, P., Levin, K., Petersen, I., Christensen, K., Beck-Nielsen, H., & Vaag, A.
- Affiliations
- Steno Diabetes Center, Gentofte, Denmark
- Odense University Hospital (DK)
- University of Southern Denmark (DK)
- Odense University Hospital, Odense, Denmark
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-01-01
- Volume
- 54
- Issue
- 1
- Pages
- 275-283
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2143531355
- Cited by
- 166
- References
- 35
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 1 · 2022: 9 · 2021: 6 · 2020: 4 · 2019: 10 · 2018: 6 · 2017: 7 · 2016: 7 · 2015: 6 · 2014: 10 · 2013: 9 · 2012: 5
- FWCI
- 13.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- heritability, insulin secretion, insulin resistance, hepatic glucose production, beta-cell function, disposition index, nonoxidative glucose metabolism, age differences, genetic versus environmental factors, twins
- MeSH terms
- Insulin Secretion, Adult, Aging, Blood Glucose, Denmark, Female, Glucose, Glycolysis, Humans, Insulin, Liver, Male, Middle Aged, Glucose Clamp Technique
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