doi: 10.1161/CIRCULATIONAHA.108.789495
(Circulation. 2008;118:e157.)
© 2008 American Heart Association, Inc.
Correspondence |
Response to Letter Regarding Article, "Use of Alternative Thresholds Defining Insulin Resistance to Predict Incident Type 2 Diabetes Mellitus and Cardiovascular Disease"
The Cardiovascular Research Group, University of Manchester, Manchester, UK
Emory University School of Medicine, Atlanta, Ga
Department of Biostatistics, Boston University School of Public Health, Boston, Mass
The National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Mass
Department of Mathematics and Statistics/Consulting Unit, Boston University, Boston, Mass
General Medicine Division, Department of Medicine, Massachusetts General Hospital, Boston, Mass
Bell and O’Keefe question the clinical utility of the triglyceride:high-density lipoprotein (TG:HDL) cholesterol ratio compared with fasting insulin–based surrogate makers for diabetes or cardiovascular disease prediction that were used in our study.1 This issue was addressed in a recent study by several of our Framingham colleagues.2 They found that the performance of the TG:HDL ratio was modest for predicting insulin resistance, and that in regression models, the homeostasis model assessment of insulin resistance was superior to the TG:HDL ratio for prediction of coronary heart disease events. The area under the receiver operating characteristic curve for TG:HDL predicting an elevated homeostasis model assessment of insulin resistance was 0.745. In a prospective analysis, elevated homeostasis model assessment of insulin resistance was strongly associated with coronary heart disease events even after adjusting for lipid variables, including the TG:HDL cholesterol ratio. These additional observations from Framingham suggest that the TG:HDL cholesterol ratio is an imperfect surrogate for insulin resistance and its associated coronary heart disease risk.
No study has specifically assessed the diabetes risk associated with lipid ratios. We have shown in Framingham offspring cohort that surrogate measures of insulin resistance were strongly and significantly related to 7-year incident diabetes mellitus in multivariable models that included triglyceride and HDL cholesterol levels,3 suggesting that lipid variables (or their ratios) do not adequately capture the diabetes risk associated with insulin resistance.
We conclude that the simplest approach to identifying insulin resistance for clinical or research use is to measure it with a close proxy–using fasting insulin or the homeostasis model assessment of insulin resistance–rather than with a more distant proxy such as lipid ratios.
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Sources of Funding
Supported by the National Heart, Lung and Blood Institute’s Framingham Heart Study (Contract No. N01-HC-25195), an American Diabetes Association Career Development Award (Dr Meigs), and a grant from GlaxoSmithKline. Dr Meigs was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant K24 DK080140. The funding agencies had no influence over the decision to publish the findings.
Disclosures
Dr Rutter has received research grants from GlaxoSmithKline, and has served on Advisory boards for GlaxoSmithKline. Dr Meigs has received research grants from GlaxoSmithKline, Wyeth, and Sanofi-aventis, and has served on safety boards for GlaxoSmithKline and Eli Lilly. Dr Wilson is supported by research grants from GlaxoSmithKline, Sanofi-Aventis, and Wyeth. Drs Sullivan, Fox, and D’Agostino have no disclosures.
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 Top References |
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1. Rutter MK, Wilson PWF, Sullivan LM, Fox CS, D'Agostino RB Sr, Meigs JB. Use of alternative thresholds defining insulin resistance to predict incident type 2 diabetes mellitus and cardiovascular disease. Circulation. 2008; 117: 1003–1009.
2. Kannel WB, Vasan RS, Keyes MJ, Sullivan LM, Robins SJ. Usefulness of the triglyceride-high-density lipoprotein versus the cholesterol-high-density lipoprotein ratio for predicting insulin resistance and cardiometabolic risk (from the Framingham Offspring Cohort). Am J Cardiol. 2008; 101: 497–501.[CrossRef][Medline] [Order article via Infotrieve]
3. Wilson PW, Meigs JB, Sullivan L, Fox CS, Nathan DM, D'Agostino RB Sr. Prediction of incident diabetes mellitus in middle-aged adults: the Framingham Offspring Study. Arch Intern Med. 2007; 167: 1068–1074.
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