Using a large and nationally representative sample, we found that the TG/HDL-C ratio was significantly associated with FSI among nondiabetic adults of three major racial/ethnic subpopulations in the United States: non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. We also detected racial/ethnic differences in predicting hyperinsulinemia, as both non-Hispanic whites and Mexican Americans had a larger optimal cutoff point of the TG/HDL-C ratio for the determination of hyperinsulinemia than did non-Hispanic blacks.
The association of insulin resistance with TG/HDL-C has been reported in overweight and obese whites [9
]. Because the clinical samples that were used in these studies consisted primarily of white participants, the generalizability of this association has not been established. A recent study found that triglyceride concentration and the TG/HDL-C ratio were not significantly associated with insulin resistance (as determined from the insulin sensitivity index) in 125 African American participants [15
]; this failure to find an association between the TG/HDL-C ratio and insulin resistance in blacks was perhaps attributable to the small sample and thus a limited power to detect associations. Our results, however, provide evidence that the TG/HDL-C ratio is associated with FSI in nondiabetic adults regardless of race/ethnicity.
Racial/ethnic differences in triglyceride concentrations, HDL-C values, and the FSI have been widely reported among adults and adolescents in previous studies [14
]. In the present study, non-Hispanic blacks had lower triglyceride concentrations than non-Hispanic whites or Mexican Americans among both men and women; for HDL-C concentrations among males the values were highest among non-Hispanic blacks, but among women no real difference was seen in this value between blacks and whites. In both sexes the TG/HDL-C ratio was lower in blacks than in whites or Mexican Americans. In addition, a significant association of the TG/HDL-C ratio with insulin resistance (as measured by HOMA) was stronger among non-Africans than Africans [14
], and increased triglyceride concentrations were associated with hepatic insulin resistance in white but not black adolescents [16
]. Lipoprotein lipase activity has been found to be higher in blacks than in whites, and this may lead to a lower triglyceride concentration in blacks [29
]. An elevated triglyceride concentration commonly causes low HDL-C values or regulates HDL-C remodeling [30
], and thus these two clinically useful measures may be, at least in part, causally linked. In light of racial/ethnic differences in triglyceride concentrations, HDL-C, and the TG/HDL-C ratio, different cutoff points may be needed to define dyslipidemia. In fact, use of a single cutoff value of ≥ 150 mg/dl (or 1.69 mmol/L) for triglycerides as criteria to classify people with dyslipidemia have led to underestimation of the prevalence of the metabolic syndrome in blacks as compared with whites, particularly in men [33
A TG/HDL-C ratio ≥ 3.5 has been proposed as a cutoff value to predict the presence of small-density LDL phenotype; McLaughlin and colleagues found that this cutoff had high sensitivity (79%) and specificity (85%) in the white population [10
]. These authors also found, however, that this cutoff value had only moderate ability to predict insulin resistance (sensitivity 47%, specificity 88%) or the metabolic syndrome (sensitivity 46%, specificity 92%) [10
]. We found, however, that the magnitude of the association of hyperinsulinemia with an elevated TG/HDL-C ratio was different when using the single cutoff point of 3.5, suggesting that a single cutoff point may not be applicable across diverse populations. In fact, our study showed, for the first time, that the optimal cutoff point of the TG/HDL-C ratio for prediction of hyperinsulinemia was 3.0 (in mg/dL unit) for non-Hispanic whites and Mexican Americans and 2.0 (in mg/dL unit) for non-Hispanic blacks, with reasonable sensitivity and specificity. Applying these race/ethnicity-specific cutoff points yielded similar magnitude of strength in the association across racial/ethnic subgroups.
It is of great interest that the association of the TG/HDL-C ratio with hyperinsulinemia was stronger among people with a BMI <25 kg/m2
than those with a BMI ≥ 30 kg/m2
. As shown in a previous study, about 16% people with normal weight (BMI < 25 kg/m2
) was identified to be insulin resistant [35
]; thus search for clinically simple and useful biomarkers to detect insulin resistance among people with normal weight is necessary. Although BMI, a less expensive and convenient measure, may serve as an indicator for insulin resistance among people with excessive weight, an elevation in the TG/HDL-C ratio could be a novel marker for hyperinsulinemia among people with normal weight in routine clinical practice.
Our study has several strengths that deserve attention. First, the generalizability of our results has been enhanced by the use of a nationally representative sample. Second, the large sample for each of the three racial/ethnic groups enables us to empirically test differences between the groups in the associations of the TG/HDL-C ratio with FSI. A limitation stems from the use of FSI as a surrogate measure of insulin resistance in our data, but previous studies have shown that fasting insulin is a valid and reliable surrogate measure of insulin resistance [13
]. Furthermore, although a direct measure would theoretically be preferable, the lack of standardized insulin assay [36
] greatly limits the clinical utility of that approach for identifying insulin-resistant persons. Without a standard insulin assay, no absolute value can be developed to predict the presence of insulin resistance across laboratories or clinical settings. Thus, if one wants to use fasting insulin to assess the state of insulin resistance, it is necessary to develop different cut-points for every assay. In contrast, triglyceride and HDL cholesterol concentrations are standardized and readily available measures in routine clinical practice. Consequently, it seems more clinically effective to use relatively simple metabolic markers such as the TG/HDL-C concentration ratio in the effort to identify apparently healthy people at increased risk of developing a variety of adverse clinical outcomes.
In conclusion, our findings have clinical and public health implications. In clinical settings, the TG/HDL-C ratio could be used as an indicator of insulin resistance across racial/ethnic subpopulations. In large health surveys, it could be used to monitor trends in cardiovascular health in diverse populations. Our results add further support to the notion that the TG/HDL-C ratio may be a clinically simple and useful indicator for insulin resistance among nondiabetic adults regardless of race/ethnicity. Even so, racial/ethnic-specific cutoff points of the TG/HDL-C ratio for the determination of insulin resistance or the risk of type 2 diabetes or cardiovascular diseases may be needed. Future research is warranted to assess the predictive power of the TG/HDL-C ratio for the metabolic syndrome, type 2 diabetes, or cardiovascular disease.