Identification of Subjects with Insulin Resistance and β-Cell Dysfunction Using Alternative Definitions of the Metabolic Syndrome

Abstract

Recently, the metabolic syndrome (MetS) has attracted much attention as a risk cluster for cardiovascular disease. Although it is believed that individuals with the MetS have insulin resistance (IR), there are few data using direct measures of IR such as glucose clamps or frequently sampled intravenous glucose tolerance tests (FSIGTTs). We examined associations of MetS with FSIGTT-derived measures of insulin sensitivity and secretion among nondiabetic subjects in the Insulin Resistance Atherosclerosis Study. Two sets of MetS criteria were evaluated: those from the 1999 World Health Organization (WHO) and the 2001 National Cholesterol Education Program (NCEP). Both WHO and NCEP MetS definitions were significantly associated with risk of being in the lowest quartile of directly measured insulin sensitivity (P < 0.0001 for all subjects as well as within ethnic subgroups). However, the associations with WHO-MetS were stronger for all subjects combined (WHO: odds ratio [OR] ‫؍‬ 10.2; 95% CI 7.5-13.9; NCEP: OR ‫؍‬ 4.6; 3.4 -6.2) and in separate analyses of nonHispanic whites, blacks, and Hispanics. WHO and NCEP MetS definitions were also significantly associated with risk of being in the lowest quartile of insulin sensitivity-adjusted acute insulin response (AIR) and disposition index (DI; all P < 0.01), although the associations were generally weaker than those for insulin sensitivity and there was no difference between the two definitions in all subjects combined (low AIR, WHO: OR ‫؍‬ 1.7, 1.2-2.4; NCEP: OR ‫؍‬ 1.7, 1.2-2.5). There were, however, a number of ethnic differences, including a stronger association of NCEP-MetS with low AIR among blacks. WHO-MetS was significantly more sensitive than NCEPMetS in detecting low insulin sensitivity (65.4 vs. 45.6%, respectively; P < 0.0001), with no significant differences in specificity between the definitions (84.4 vs.84.6%; P ‫؍‬ 0.91), although WHO-MetS had a larger area under the receiver operating characteristic curve (75% vs. 65%; P < 0.0001). In conclusion, although both the WHO and NCEP MetS criteria identify nondiabetic individuals with low insulin sensitivity, the associations were notably stronger using the WHO definition. The definitions are generally less useful for identifying those with low AIR or DI, although NCEP-MetS seems to differentiate black subjects with insulin secretion defects.

Measures of Insulin Resistance Add Incremental Value to the Clinical Diagnosis of Metabolic Syndrome in Association With Coronary Atherosclerosis

“…1 Estimates of the prevalence of the WHO criteria were slightly lower ( Table 2). Consistent with previous reports of a lack of sensitivity of NCEP-defined MetSyn for insulin resistance, 8,12,15 15.1% (19.2% of men and 10.7% of women) of subjects classified as non-MetSyn by NCEP criteria (ie, expected not to be insulin resistant) had WHOdefined insulin resistance (HOMA values in the upper quartile). In fact, of subjects with HOMA values in the upper quartile, 45% were classified as not having MetSyn by the NCEP definition.…”

“…3,4,16 Insulin resistance is thought to be the most prominent pathophysiological process underlying MetSyn. 2,14,15 The WHO definition of MetSyn 11 requires the presence of insulin resistance plus 2 other of central obesity, hypertension, or dyslipidemia, whereas the NCEP definition does not require a laboratory measure of insulin. 10 Despite this, the NCEP criteria, based on features typically correlated with insulin resistance, should identify insulin-resistant subjects.…”

“…5,8,12,13 Furthermore, the association of MetSyn with incident diabetes and CVD has varied substantially when the two definitions have been applied in a single study. 5,[7][8][9] Additional definitions of MetSyn have been proposed, 14,15 underscoring the need for unified criteria for use in clinical practice.…”

Nonalcoholic Fatty Liver Disease and Risk of Future Cardiovascular Events Among Type 2 Diabetic Patients

“…Unfortunately, we did not directly measure insulin resistance in our population. Recent evidence has raised concern that the current ATP III definition of the metabolic syndrome has low sensitivity for identifying insulin resistance in subjects (18). Conversely, several studies have consistently documented that insulin resistance predicts incident CVD events (19,20) and plays a pivotal role in the development of poor clinical outcomes in NAFLD patients (1,2,13).…”

National Cholesterol Education Program Versus World Health Organization Metabolic Syndrome in Relation to All-Cause and Cardiovascular Mortality in the San Antonio Heart Study

“…However, in a recent publication of the Insulin Resistance Atherosclerosis Study population, only between 5.5% and 6.2% of participants without diabetes had evidence of microalbuminuria. 17 Furthermore, in our study, because most participants with diabetes already had WHO-MetS (78.2%) and an additional 4.3% of participants even with microalbuminuria would not have been classified as having WHOMetS, only 17.5% of participants with diabetes could have been affected by the inclusion of information on microalbuminuria. Hence, the effect of inclusion or exclusion of microalbuminuria in defining the MetS in individuals with normoglycemia, in individuals with IFG and/or impaired glucose tolerance, and in individuals with diabetes appears minimal.…”