Heritability of Insulin Secretion, Peripheral and Hepatic Insulin Action, and Intracellular Glucose Partitioning in Young and Old Danish Twins

Poulsen, Pernille; Levin, Klaus; Petersen, Inge; Christensen, Kaare; Beck-Nielsen, Henning; Vaag, Allan

doi:10.2337/diabetes.54.1.275

Cited by 169Pancreatic function and diabetesGenetic Associations and EpidemiologyDiabetes, Cardiovascular Risks, and Lipoproteins

Heritability of Insulin Secretion, Peripheral and Hepatic Insulin Action, and Intracellular Glucose Partitioning in Young and Old Danish Twins

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Poulsen, Pernille, Levin, Klaus, Petersen, Inge, Christensen, Kaare, Beck-Nielsen, Henning, Vaag, Allan·2005·Diabetes

DOI 10.2337/diabetes.54.1.275

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Abstract

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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A genetic predisposition to defective insulin secretion combined with insulin resistance can raise plasma glucose to abnormal levels.
“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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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
ORCID: Petersen, Inge
Christensen, Kaare
Vaag, Allan
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2005-01-01
Volume: 54
Issue: 1
Pages: 275-283
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.54.1.275
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 › Surgery › 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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Heritability of Insulin Secretion, Peripheral and Hepatic Insulin Action, and Intracellular Glucose Partitioning in Young and Old Danish Twins

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