Abstract
Purpose
To assess the associations among baseline levels of fasting insulin and proinsulin,
proinsulin:insulin ratio, and the development of type 2 diabetes mellitus in apparently
healthy middle-aged women.
Methods
In a nested case-control study involving a nationwide cohort of 27,628 participants
from the Women’s Health Study, 126 women with diabetes diagnosed during a 4-year follow-up
period were compared with 225 age-matched controls. Fasting insulin level and proinsulin:insulin
ratio were assessed in quartiles, and proinsulin level was assessed in categories
(≤4.0 pmol/L, 4.01 to 6.99 pmol/L, ≥7.0 pmol/L). The risk of developing type 2 diabetes
was determined using conditional logistic regression analysis that adjusted for body
mass index and other diabetes risk factors.
Results
Baseline insulin and proinsulin levels and proinsulin:insulin ratios were significantly
higher among cases than among controls. Women with elevated insulin levels in the
highest as compared with the lowest quartile were more likely to develop diabetes
(odds ratio [OR] = 5.6; 95% confidence interval [CI]: 1.8 to 17.6), as were women
with elevated (≥7.0 pmol/L vs. ≤4.0 pmol/L) proinsulin levels (OR = 16.4; 95% CI:
5.8 to 46.8) and women with proinsulin:insulin ratios in the highest quartile (OR
= 9.6; 95% CI: 3.1 to 30.8). Similar results were observed among women with a baseline
hemoglobin A1c level ≤6.0%. In time-trend analyses, fasting insulin was a consistent predictor of
long-term risk. Proinsulin and proinsulin:insulin ratio, although predictive throughout
the study, were especially strong predictors of rapid progression to type 2 diabetes.
Conclusion
Elevated fasting insulin and proinsulin levels and proinsulin:insulin ratio are associated
with an increased risk of developing type 2 diabetes in apparently healthy middle-aged
women.
Keywords
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Article info
Publication history
Accepted:
December 5,
2002
Received in revised form:
November 20,
2002
Received:
April 3,
2002
Footnotes
☆Supported by grants from the National Heart, Lung, and Blood Institute (HL43851, HL58755, and HL63293) and the National Cancer Institute (CA47988), Bethesda, Maryland. Dr. Ridker is supported by a Distinguished Clinical Scientist Development Award from the Doris Duke Foundation, New York, New York.
Identification
Copyright
© 2003 Excerpta Medica Inc. Published by Elsevier Inc. All rights reserved.
