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

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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). 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)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume285
Issue number6 48-6
StatePublished - Dec 2003
Externally publishedYes

Fingerprint

Age of Onset
Insulin
Phenotype
Insulin Resistance
Medical problems
Waist-Hip Ratio
Type 2 Diabetes Mellitus
Glucose
Glucose Tolerance Test
Homeostasis
Glucose Clamp Technique
Abdominal Obesity
Clamping devices

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Familiality of metabolic abnormalities is dependent on age at onset and phenotype of the type 2 diabetic proband. / Tripathy, Devjit; Lindholm, E.; Isomaa, B.; Saloranta, C.; Tuomi, T.; Groop, L.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 285, No. 6 48-6, 12.2003.

Research output: Contribution to journalArticle

Tripathy, Devjit ; Lindholm, E. ; Isomaa, B. ; Saloranta, C. ; Tuomi, T. ; Groop, L. / Familiality of metabolic abnormalities is dependent on age at onset and phenotype of the type 2 diabetic proband. In: American Journal of Physiology - Endocrinology and Metabolism. 2003 ; Vol. 285, No. 6 48-6.
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