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Familiality of metabolic abnormalities is dependent on age at onset and phenotype of the type 2 diabetic proband
Abstract
To determine the impact of a family history of the common form of type 2 diabetes and the phenotype of the proband on anthropometric and metabolic variables in normoglycemic first-degree relatives, we studied 2,100 first-degree relatives of patients with the common form of type 2 diabetes (FH+) and 388 subjects without a family history of diabetes (FH-). All subjects participated in an oral glucose tolerance test to allow measurement of insulin secretion [30-min incremental insulin/glucose (I/G 30)] and insulin sensitivity [homeostasis model assessment (HOMA) of insulin resistance (IR)]. A subset participated in a euglycemic clamp (n = 75) and an intravenous glucose tolerance test (n = 300). To study the effect of a particular phenotype of the proband, insulin secretion and sensitivity were also compared between first-degree relatives of diabetic probands with high and low waist-to-hip ratio (WHR) and probands with early and late onset of diabetes. FH+ subjects were more insulin resistant, as seen from a higher HOMA-IR index (P = 0.006) and a lower rate of insulin-stimulated glucose uptake (P = 0.001) and had more features of the metabolic syndrome (P = 0.02, P = 0.0002) compared with FH- subjects. Insulin secretion adjusted for insulin resistance (disposition index, DI) was also lower in the FH+ vs. FH- subjects (P = 0.04). Relatives of diabetic probands with a high WHR had reduced insulin-mediated glucose uptake compared with relatives of probands with a low WHR (P = 0.04).…
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Lean NGT offspring of two parents with type 2 diabetes exhibit moderate to severe skeletal muscle insulin resistance.
“Multiple investigators unequivocally have demonstrated that lean NGT offspring of two parents with type 2 diabetes exhibit moderate to severe skeletal muscle insulin resistance ( 28 – 33 ).”
From Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes (2009) · cites this paper as [33]
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Metadata
- Authors
- Tripathy, D., Lindholm, E., Isomaa, B., Saloranta, C., Tuomi, T., & Groop, L.
- Affiliations
- Lund University (SE)
- University of Helsinki (FI)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2003-12
- Volume
- 285
- Issue
- 6
- Pages
- E1297-E1303
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2080081169
- Cited by
- 20
- References
- 40
- Citations by year
- 2024: 1 · 2018: 1 · 2017: 1 · 2015: 1 · 2013: 2 · 2012: 2
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- type 2 diabetes, familial risk, first-degree relatives, age of onset, waist-to-hip ratio, abdominal obesity, insulin resistance, insulin secretion, insulin sensitivity, disposition index, metabolic syndrome, glucose uptake
- MeSH terms
- Adolescent, Adult, Aged, Diabetes Mellitus, Diabetes Mellitus, Type 2, Female, Finland, Humans, Insulin Resistance, Male, Middle Aged, Obesity, Phenotype, Sweden, Comorbidity, Body Mass Index, Age of Onset, Genetic Predisposition to Disease, Metabolic Syndrome
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