Published Online
on February 4, 2008

A more recent version of this article appeared on February 26, 2008

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Submitted on July 13, 2007
Accepted on November 27, 2007

Use of Alternative Thresholds Defining Insulin Resistance to Predict Incident Type 2 Diabetes Mellitus and Cardiovascular Disease

Martin K. Rutter MD, Peter W.F. Wilson MD, Lisa M. Sullivan PhD, Caroline S. Fox MD, MPH, Ralph B. D'Agostino Sr PhD, and James B. Meigs MD, MPH^*

From The Cardiovascular Research Group, Division of Cardiovascular and Endocrine Sciences, University of Manchester, and The Manchester Diabetes Centre, Manchester Royal Infirmary, Manchester, United Kingdom (M.K.R.); Emory University School of Medicine (P.W.F.W.), Atlanta, Ga; Department of Biostatistics (L.M.S.), Department of Mathematics and Statistics/Consulting Unit (R.B.D.), Boston University, Boston, Mass; the National Heart, Lung, and Blood Institute's Framingham (Mass) Heart Study (C.S.F.), Harvard Medical School and the Department of Endocrinology and Metabolism, Brigham and Women's Hospital, Boston, Mass (C.S.F); and Harvard Medical School and the General Medicine Division, Department of Medicine, Massachusetts General Hospital, Boston, Mass (J.B.M.).

^* To whom correspondence should be addressed. E-mail: jmeigs{at}partners.org.

Background—The performance characteristics of surrogate insulin resistance (IR) measures, commonly defined as the top 25% of the measure's distribution, used to predict incident type 2 diabetes mellitus (DM) and cardiovascular disease (CVD) have not been critically assessed in community samples.

Methods and Results—Baseline IR was assessed among 2720 Framingham Offspring Study subjects by use of fasting insulin, the homeostasis model assessment of IR (HOMA-IR), and the reciprocal of the Gutt insulin sensitivity index, with 7- to 11-year follow-up for incident DM (130 cases) or CVD (235). Area under the receiver operating characteristic curve, sensitivity, specificity, and positive likelihood ratio were estimated at 12 diagnostic thresholds (quantiles) of IR measures. Positive likelihood ratios for DM or CVD increased in relation to IR quantiles; risk gradients were greater for DM than for CVD, with no 9th to 10th quantile (76th centile) threshold effects. IR had better discrimination for incident DM than for CVD (HOMA-IR area under the receiver operating characteristic curve: DM 0.80 versus CVD 0.63). The HOMA-IR 76th centile threshold was associated with these test-performance values: sensitivity (DM 68%, CVD 40%), specificity (DM 77%, CVD 76%), and positive likelihood ratio (DM 3.0, CVD 1.7). The HOMA-IR threshold that yielded >90% sensitivity was the 6th quantile for DM prediction and the 3rd quantile for CVD. Compared with the 76th centile threshold, these alternative thresholds yielded lower specificity (DM 43%, CVD 17%) and positive likelihood ratios (DM 1.6, CVD 1.1).

Conclusions—Surrogate IR measures have modest performance at the 76th centile, with no threshold effects. Different centile thresholds might be selected to optimize sensitivity versus specificity for DM versus CVD prediction if surrogate IR measures are used for risk prediction.

Key words: insulin resistance • cardiovascular diseases • diabetes mellitus • risk factors • prospective studies • prognosis

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Clinical Summaries
Circulation 2008 117: 987-989. [Extract] [Full Text]

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				D. S.H. Bell and J. H. O'Keefe Letter by Bell and O'Keefe Regarding Article, "Use of Alternative Thresholds Defining Insulin Resistance to Predict Incident Type 2 Diabetes Mellitus and Cardiovascular Disease" Circulation, September 9, 2008; 118(11): e156 - e156. [Full Text] [PDF]

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