Insulin, proinsulin, proinsulin:insulin ratio, and the risk of developing type 2 diabetes mellitus in women.
OBJECTIVE
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 (< or =4.0 pmol/L, 4.01 to 6.99 pmol/L, > or =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 (> or =7.0 pmol/L vs. < or =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 A(1c) level < or =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.


CONCLUSIONS
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.
Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA. apradhan@rics.bwh.harvard.edu
Aruna D
AD
Pradhan
JoAnn E
JE
Manson
James B
JB
Meigs
Nader
N
Rifai
Julie E
JE
Buring
Simin
S
Liu
Paul M
PM
Ridker
D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D005215:Fasting / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology; D007515:Islets of Langerhans / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011384:Proinsulin / Q000097:blood*; D012044:Regression Analysis; D012307:Risk Factors
D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D011384:Proinsulin