International Journal of Epidemiology, Vol 28, 735-741, Copyright © 1999 by International Epidemiological Association
IJ Perry, SG Wannamethee, AG Shaper and KG Alberti
BACKGROUND: There is considerable evidence that insulin resistance with
compensatory hyperinsulinaemia is an early and modifiable defect in the
pathogenesis of non-insulin dependent diabetes (NIDDM). Current data,
however, are largely based on studies that have used insulin assays which
cross-react with proinsulin and other insulin precursors. Using a specific
assay, we have addressed the hypothesis that an elevation of serum true
insulin concentration, reflecting insulin resistance, is an early event in
the pathogenesis of NIDDM. METHODS: We have used a prospective cohort study
design in which a group of 5550 non-diabetic men aged 40-59 years, from 18
British towns, have been followed for incident cases of physician-diagnosed
NIDDM for an average of period of 14.8 years (range 13.5-15 years). We have
estimated the incidence of physician-diagnosed NIDDM by quintile of
non-fasting serum true insulin concentration at entry into the study.
RESULTS: There were 168 cases of clinically diagnosed NIDDM among the group
of 5550 men during follow- up. Mean serum insulin at entry (geometric mean
and 95% range, adjusted for time of sampling) was significantly higher in
men who subsequently developed NIDDM than in the rest of the cohort, 19.5
mU/l (4.3-88.2) versus 12.2 mU/l (2.7-54.0), P < 0.0001. There was a
highly significant linear trend of increasing risk of NIDDM by quintile of
serum insulin which was not attenuated substantially after adjustment for
age and body mass index (BMI) and additional lifestyle and biological
factors associated with serum insulin and risk of NIDDM. However, in men
with non-fasting serum glucose > or =6.1 mmol/l at baseline (80th
percentile, n = 1125, 82 cases), the risk of NIDDM, adjusted for age and
BMI, was higher in the first quintile of serum insulin than in all other
quintiles. CONCLUSION: These findings are consistent with the hypothesis
that the majority of cases of adult onset NIDDM in this population are
characterized by the early development of insulin resistance with
compensatory true hyperinsulinaemia.
ARTICLES
Serum true insulin concentration and the risk of clinical non-insulin dependent diabetes during long-term follow-up
Department of Primary Care and Population Sciences, The Royal Free Hospital School of Medicine, London, UK. i.perry@ucc.ie
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