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

Tripathy, Devjit LU ; Lindholm, Eero LU ; Isomaa, B; Saloranta, C; Tuomi, T and Groop, Leif LU (2003) In American Journal of Physiology: Endocrinology and Metabolism 285(6). p.1297-1303
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 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... (More)
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 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Physiology: Endocrinology and Metabolism
volume
285
issue
6
pages
1297 - 1303
publisher
American Physiological Society
external identifiers
  • wos:000186474500018
  • pmid:12954593
  • scopus:0345327565
ISSN
1522-1555
DOI
language
English
LU publication?
yes
id
9feae619-7a12-452f-af36-64cf6170fbd7 (old id 117954)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12954593&dopt=Abstract
date added to LUP
2007-07-30 15:51:01
date last changed
2018-05-29 11:03:57
@article{9feae619-7a12-452f-af36-64cf6170fbd7,
  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 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 &lt; 44 years had higher HOMA IR (P &lt; 0.005) and lower DI (P &lt; 0.005) than relatives of patients with age at onset &gt;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},
  author       = {Tripathy, Devjit and Lindholm, Eero and Isomaa, B and Saloranta, C and Tuomi, T and Groop, Leif},
  issn         = {1522-1555},
  language     = {eng},
  number       = {6},
  pages        = {1297--1303},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Endocrinology and Metabolism},
  title        = {Familiality of metabolic abnormalities is dependent upon age at onset and phenotype of the type 2 diabetic proband.},
  url          = {http://dx.doi.org/},
  volume       = {285},
  year         = {2003},
}