Multiple metabolic abnormalities in normal glucose tolerant relatives of NIDDM families.

Abstract:

:Non-diabetic first degree relatives of non-insulin-dependent diabetic (NIDDM) families are at increased risk of developing diabetes mellitus, and have been studied to identify early metabolic abnormalities. Hormone concentrations measured by specific enzyme immunoassays were assessed in non-diabetic relatives of North European extraction, and control subjects with no family history of diabetes were matched for age, sex and ethnicity. A 75-g oral glucose tolerance test was conducted and those with newly diagnosed NIDDM were excluded. Basal insulin resistance was determined by homeostasis model assessment (HOMA), and hepatic insulin clearance by C-peptide:insulin molar ratio. Relatives (n = 150) were heavier (BMI: p < 0.0001) than the control subjects (n = 152), and had an increased prevalence of impaired glucose tolerance (15 vs 3%, p < 0.01). The relatives had increased fasting proinsulin levels and decreased C-peptide levels following the glucose load, while insulin levels were increased at all time points. To examine whether the differences in hormone levels were secondary to the differences in glucose tolerance and adiposity, we studied 100 normal glucose tolerant relatives and control subjects pair-matched for age, sex, waist-hip ratio and BMI. The differences in proinsulin levels were no longer apparent. However, the relatives remained more insulin resistant, and had decreased C-peptide levels and C-peptide:insulin ratios at all time points. In conclusion, we have identified several metabolic abnormalities in the normal glucose tolerant relatives, and propose that the decreased hepatic insulin clearance helps to maintain normoglycaemia in the face of combined insulin resistance and decreased insulin secretion.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Humphriss DB,Stewart MW,Berrish TS,Barriocanal LA,Trajano LR,Ashworth LA,Brown MD,Miller M,Avery PJ,Alberti KG,Walker M

doi

10.1007/s001250050805

subject

Has Abstract

pub_date

1997-10-01 00:00:00

pages

1185-90

issue

10

eissn

0012-186X

issn

1432-0428

journal_volume

40

pub_type

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