Printer-Friendly Format
	Email this to a friend
	Highlight Glossary

Diabetes Care

Low Insulin Sensitivity (S_i = 0) in Diabetic and Nondiabetic Subjects in the Insulin Resistance Atherosclerosis Study. Is it associated with components of the metabolic syndrome and nontraditional risk factors?
Haffner SM, MD¹, D’Agostino R, Jr., PhD², Festa A, MD¹, Bergman RN, PhD³, Mykkänen L, MD¹, Karter A, PhD⁴, Saad MF, MD⁵, Wagenknecht LE, DRPH²

¹ Department of Medicine, University of Texas Health Science Center, San Antonio, Texas
² Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
³ Department of Biophysics and Physiology, University of Southern California, Los Angeles, California
⁴ Kaiser Research Center, Northern California, Oakland, California
⁵ Department of Medicine, UCLA School of Medicine, Los Angeles, California

OBJECTIVE—To determine the meaning of S_i = 0 derived from the frequently sampled intravenous glucose tolerance test.

RESEARCH DESIGN AND METHODS—The issue of assessing insulin resistance in large studies is important because the most definitive method ("gold standard"), the hyperinsulinemic-euglycemic clamp, is expensive and invasive. The frequently sampled intravenous glucose tolerance test (FSIGTT) has been widely used, but in insulin-resistant subjects (especially diabetic subjects), it yields considerable numbers of subjects whose S_i is zero. The interpretation of an S_i equaling zero is unknown.

RESULTS—To address this issue, we examined 1,482 subjects from the Insulin Resistance Atherosclerosis Study (IRAS) using an insulin-modified FSIGTT and minimal model calculation of S_i. The proportion of insulin-resistant subjects (S_i < 1.61 x 10^-4 [min^-1 · µU^-1 · ml^-1] based on the median of the nondiabetic population) was 38.6% in subjects with normal glucose tolerance (NGT), 74% in subjects with impaired glucose tolerance (IGT), and 92% in subjects with type 2 diabetes. The proportion of subjects with S_i = 0 was 2.2% in subjects with NGT, 13.2% in subjects with IGT, and 35.7% in subjects with type 2 diabetes. In subjects with IGT, those with S_i = 0 had significantly lower HDL cholesterol levels and higher BMI, waist circumference, fibrinogen, plasminogen-activator inhibitor 1 (PAI-1), C-reactive protein (CRP), and 2-h insulin levels than insulin-resistant subjects with S_i > 0. In type 2 diabetes, subjects with S_i = 0 had significantly greater BMI and waist circumference and higher triglyceride, PAI-1, CRP, fibrinogen, and fasting and 2-h insulin levels than insulin-resistant subjects with S_i > 0. In addition, diabetic subjects with S_i = 0 had more metabolic disorders related to the insulin resistance syndrome than diabetic insulin-resistant subjects with S_i > 0.

CONCLUSIONS—We found very few subjects with S_i = 0 among subjects with NGT and few subjects with S_i = 0 among subjects with IGT. In contrast, S_i = 0 was common in subjects with diabetes. Subjects with S_i = 0 tended to have more features of the insulin resistance syndrome than other insulin-resistant subjects with S_i > 0, as would be expected of subjects with almost no insulin-mediated glucose disposal, thus suggesting that subjects with S_i = 0 are correctly classified as being very insulin resistant rather than having failed the minimal model program.

The full text of this article is available online. 

Additional Information

The Significance of Impaired Fasting Glucose Versus Impaired Glucose Tolerance: Importance of Insulin Secretion and Resistance Detection of Undiagnosed Diabetes and Other Hyperglycemia States: The Atherosclerosis Risk in Communities Study Performance of Recommended Screening Tests for Undiagnosed Diabetes and Dysglycemia HbA1c Measurement Improves the Detection of Type 2 Diabetes in High-Risk Individuals With Nondiagnostic Levels of Fasting Plasma Glucose Assessment of Insulin Sensitivity and Beta-cell Function from Measurements in the Fasting State and During an Oral Glucose Tolerance Test Insulin Secretion and Insulin Sensitivity in Relation to Glucose Tolerance: Lessons From the Botnia Study Insulin Sensitivity in Subjects With Type 2 Diabetes Relationship to Cardiovascular Risk Factors: The Insulin Resistance Atherosclerosis Study 59 Elevated PAI-1 Predicts Type 2 Diabetes in Subjects With NGT IRAS 258 Negative Association Between Insulin Sensitivity and Atherosclerosis IRAS Elevated C-Reactive Protein Is a Risk Factor for the Development of Type 2 Diabetes in Japanese Americans Inflammatory Cytokines Stimulated C-Reactive Protein Production by Human Coronary Artery Smooth Muscle Cells Identification of Subjects with Insulin Resistance and ß-Cell Dysfunction Using Alternative Definitions of the Metabolic Syndrome The Natural Course of {beta}-Cell Function in Nondiabetic and Diabetic Individuals: The Insulin Resistance Atherosclerosis Study