Ethnic differences in the ability of triglyceride levels to identify insulin resistance
Introduction
The Metabolic Syndrome was designed to identify individuals at high risk for the development of heart disease and diabetes [1]. However a universal consensus on the definition of the Metabolic Syndrome does not yet exist. Different but overlapping definitions of the Metabolic Syndrome have been provided by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), the World Health Organization (WHO) and the International Diabetes Federation [2], [3], [4]. The NCEP-ATP III definition of the Metabolic Syndrome is the one most often used in the United States. According to the NCEP-ATP guidelines a diagnosis of the Metabolic Syndrome requires that three of five factors be present: hypertriglyceridemia, low high density lipoprotein-cholesterol (HDL-C), central obesity, hypertension and fasting hyperglycemia (Table 1). Despite its widespread use, the effectiveness of the Metabolic Syndrome in predicting the development of disease has been debated [5], [6].
One specific concern is that the Metabolic Syndrome may underestimate the number of non-Hispanic blacks at high risk for the development of diabetes and cardiovascular disease. The foundation for this concern is that even though the prevalence of obesity, hypertension, heart disease and diabetes is higher in non-Hispanic blacks than non-Hispanic whites, non-Hispanic blacks have a lower prevalence of the Metabolic Syndrome [7]. This counter-intuitive finding suggests that the Metabolic Syndrome is under-diagnosed in non-Hispanic blacks. The consequence of under-diagnosis of the Metabolic Syndrome in non-Hispanic blacks is the lost opportunity for early intervention.
Even though there is not universal consensus on the role of insulin resistance, central to most formulations of the Metabolic Syndrome is the concept that insulin resistance is a major etiologic factor [8]. Hypertriglyceridemia is not absolutely required for diagnosis of the Metabolic Syndrome. Nevertheless due to the strong relationship between insulin resistance and hypertriglyceridemia, hypertriglyceridemia is considered one of the most important Metabolic Syndrome criterions [8], [9]. Consequently, all of the Metabolic Syndrome definitions include hypertriglyceridemia as a criterion [2], [3], [4]. However, insulin resistant non-Hispanic blacks often have normal TG levels [10]. Therefore the use of TG as a diagnostic criterion of the Metabolic Syndrome may be a major reason for the under-diagnosis of the Metabolic Syndrome in non-Hispanic blacks [11].
The value of diagnosing Metabolic Syndrome lies in the potential for early diagnosis or even prevention of diabetes and cardiovascular disease. Evidence has emerged, however, which questions the ability of the Metabolic Syndrome to identify high risk individuals [5], [6], leading investigators to propose alternative syndromes. These syndromes include: the Enlarged Waist Elevated Triglyceride Syndrome, the Overweight-Lipid Syndrome and the Hypertriglyceridemic Waist Syndrome [12], [13], [14] (Table 1). Less well known than the Metabolic Syndrome, these newly proposed syndromes apply to specific groups. The first syndrome applies to postmenopausal women, the second to overweight individuals (BMI ≥ 25 kg/m2) and the third to men. A potential problem with these syndromes is that they were defined in non-Hispanic whites and never validated in other populations. Consequently it is unknown if they are applicable to non-Hispanic blacks.
Each of these syndromes has an absolute requirement of hypertriglyceridemia as a criterion. However, the TG level which constitutes hypertriglyceridemia is syndrome specific. For diagnosis of the Enlarged Waist Elevated Triglyceride Syndrome, TG must be ≥128 mg/dL. For the Overweight-Lipid Syndrome, TG must be ≥130 mg/dL (or the TG/HDL-C ratio must be ≥3). For diagnosis of the Hypertriglyceridemic Waist Syndrome, TG must be ≥176 mg/dL. Because these syndromes require hypertriglyceridemia (or increased TG/HDL ratio) and insulin resistant non-Hispanic blacks often have normal TG levels [10], [15], it is important to determine if these syndromes are able to identify high risk insulin resistant non-Hispanic blacks.
A simultaneous comparison by ethnicity of the prevalence of the Metabolic Syndrome using the NCEP-ATPIII definition and these three alternative syndromes has not been performed, nor has the strength of the association between TG and insulin resistance been compared by ethnicity. Using the National Health and Nutrition Examination Survey (NHANES) 1999–2002, our goals were to determine by ethnicity: (1) the prevalence of each of these syndromes and (2) the ability of fasting TG concentrations to identify insulin resistance at cut-off levels established by these syndromes, specifically 130, 150, and 176 mg/dL.
Section snippets
Methods
In 1999, the NHANES became a continuous annual survey conducted by the National Center for Health Statistics with data released every two years [16]. The survey includes a nationally representative sample of the U.S. civilian non-institutionalized population, based on a stratified, multistage probability sampling design with oversampling of non-Hispanic blacks and Mexican Americans. Survey participants are interviewed at home and subsequently receive a physical and laboratory examination in a
Results
Participant characteristics are shown in Table 2. We noted a significant age difference by ethnic group, with non-Hispanics whites being the oldest and Mexican Americans being the youngest. Mean BMI was highest in non-Hispanic blacks and lowest in non-Hispanic whites. Waist circumference did not vary by ethnicity. Compared with non-Hispanic whites, non-Hispanic blacks and Mexican Americans had higher HOMA levels while HOMA levels for non-Hispanic blacks and Mexican Americans were similar.
Discussion
Three of the four syndromes described in this investigation were designed to identify individuals at high risk for the development of diabetes or cardiovascular disease [12], [14], [21]. These three syndromes are: The Enlarged Waist Elevated TG Syndrome, the Metabolic Syndrome and the Hypertriglyceridemic Waist. The fourth syndrome, the Overweight-Lipid Syndrome, was designed to detect insulin resistance in overweight individuals [13]. All of the syndromes require the determination of TG
Acknowledgements
We thank Danita Byrd-Holt, BBA from Social & Scientific Systems, Inc. for her computer programming support and Keith Rust, PhD from Westat for his statistical guidance. In addition, we thank Drs. Barbara A. Frempong and Sabysashi Sen for their thoughtful critiques of the manuscript.
Funding sources: This research was supported by the intramural (AES) and extramural (CCC) research programs of NIDDK. Support for analyses was funded by NIDDK through contract #N01-DK-1-2478.
References (36)
- et al.
The metabolic syndrome—a new worldwide definition: IDF epidemiology task force consensus group
Lancet
(2005) - et al.
The Metabolic Syndrome
Lancet
(2005) - et al.
Lipid and Lipid Protein Dysregulation in Insulin Resistant States
Clin Clim Acta
(2006) - et al.
Normal triglyceride levels despite insulin resistance in African Americans: role of lipoprotein lipase
Metabolism
(2005) - et al.
Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart. Lung and Blood Institute Scientific Statement
Curr Opin Cardiol
(2006) Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
JAMA
(2001)- et al.
Definition, diagnosis and classification of diabetes Mellitus and Its complications. Part 1. Diagnosis and classification of diabetes mellitus. Provisional Report of a WHO Consultation
Diabet Med
(1998) - et al.
The metabolic syndrome: time for a critical appraisal: joint statement from the American diabetes association and the European association for the study of diabetes
Diab Care
(2005) - et al.
Does the metabolic syndrome improve identification of individuals at risk of Type 2 diabetes and/or cardiovascular disease?
Diab Care
(2004) - et al.
The metabolic syndrome, prevalence and associated risk factor findings in the US Population from the Third National Health and Nutrition Examination Survey, 1988–1994
Arch Intern Med
(2003)
The metabolic syndrome: all criteria are equal, but some criteria are more equal than others
Arch Intern Med
Enlarged waist combined with elevated triglycerides is a strong predictor of accelerated atherogenesis and related cardiovascular mortality in postmenopausal women
Circulation
Use of metabolic markers to identify overweight individuals who are insulin resistant
Ann Intern Med
Hypertriglyceridemic waist: a marker of the atherogenic metabolic triad (Hyperinsulinemia; Hyperapolipoprotein B; small dense LDL) in men?
Circulation
Fasting triglyceride and the triglyceride-hdl cholesterol ratio are not markers of insulin resistance in African Americans
Arch Intern Med
Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man
Diabetologia
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