Familiality of metabolic abnormalities is dependent on age at onset and phenotype of the type 2 diabetic proband

D. Tripathy, E. Lindholm, B. Isomaa, C. Saloranta, T. Tuomi, L. Groop

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17 Scopus citations


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). Relatives of diabetic patients with age at onset <44 yr had higher HOMA IR (P < 0.005) and lower DI (P < 0,005) than relatives of patients with age at onset >65 yr (highest quartile). We conclude that early age at onset of type 2 diabetes and abdominal obesity have a significant influence on the metabolic phenotype in the nondiabetic first-degree relative.

Original languageEnglish (US)
Pages (from-to)E1297-E1303
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number6 48-6
StatePublished - Dec 2003


  • Genetics of type 2 diabetes
  • Insulin secretion
  • Insulin sensitivity
  • Metabolic syndrome

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology
  • Endocrinology, Diabetes and Metabolism


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