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

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

In: American Journal of Physiology: Endocrinology and Metabolism, Vol. 285, No. 6, 2003, p. E1297-E1303.

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T1 - Familiality of metabolic abnormalities is dependent upon age at onset and phenotype of the type 2 diabetic proband.

AU - Tripathy, Devjit

AU - Lindholm, Eero

AU - Isomaa, B

AU - Saloranta, C

AU - Tuomi, T

AU - Groop, Leif

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Endocrinology (013241500), Diabetes and Endocrinology (013241530), Pediatrics/Urology/Gynecology/Endocrinology (013240400)

PY - 2003

Y1 - 2003

N2 - 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 2100 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 (30min incremental insulin /glucose, I/G 30), and insulin sensitivity (HOMA insulin resistance). 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 higher HOMA-IR index (P=0.007) and 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 years had higher HOMA IR (P < 0.005) and lower DI (P < 0.005) than relatives of patients with age at onset >65 yrs (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 non-diabetic firstdegree relative

AB - 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 2100 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 (30min incremental insulin /glucose, I/G 30), and insulin sensitivity (HOMA insulin resistance). 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 higher HOMA-IR index (P=0.007) and 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 years had higher HOMA IR (P < 0.005) and lower DI (P < 0.005) than relatives of patients with age at onset >65 yrs (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 non-diabetic firstdegree relative

U2 - 10.1152/ajpendo.00113.2003

DO - 10.1152/ajpendo.00113.2003

M3 - Article

VL - 285

SP - E1297-E1303

JO - American Journal of Physiology - Endocrinology and Metabolism

T2 - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 1522-1555

IS - 6

ER -