In the present study, we examined whether lipid profiles (i.e., TG, HDL-C, LDL-C, TG/HDL-C ratio, LDL-C/HDL-C ratio and non-HDL-C) were associated with insulin resistance in Japanese adults, categorized by body mass index. Most fundamental is the fact that not all overweight or obese persons are insulin resistant. In non-obese subjects, 6.0% of them were insulin resistant, and the best marker of insulin resistance was LDL-C/HDL-C ratio, but HDL-C, TG/HDL-C ratio and non-HDL-C also discriminated insulin resistance. In overweight subjects, the areas of TG and TG/HDL-C ratio were greater than those of the other parameters. The optimal cut-off point to identifying insulin resistance for these markers yielded the following values: TG/HDL-C ratio of ≥1.50 and LDL-C/HDL-C ratio of ≥2.14 in non-obese subjects, and ≥2.20 and ≥2.25, respectively in overweight. The positive likelihood ratio was greatest for LDL-C/HDL-C ratio in non-obese subjects. Lipid ratio of LDL-C/HDL-C might be used as an integrated and simple lipid measure to evaluate insulin resistance in non-obese subjects.
Resistance to insulin-mediated glucose disposal is distributed continuously through the general population , and we have no criterion with which to identify a participant as being insulin resistance or insulin sensitive. However, we classified a participant as insulin resistant if he or she was in HOMA-IR > 2.5 . Previous studies have shown that HOMAIR-based insulin resistance scores strongly correlate with glucose clamp-assessed insulin resistance [13, 15]. However, the validation was carried out in only a few subjects, and HOMA-IR is less accurate and precise than the glucose clamp in measuring insulin resistance, but this limitation is mitigated when the number of subjects examined is large, as in our study .
Hypertriglyceridemia and low HDL-C almost never occurred as isolated disorders, and were nearly always associated with insulin resistance because insulin affects very low-density lipoprotein and HDL-C metabolism . In previous studies, several lipid ratios have been proposed as simple and useful clinical indicators of insulin resistance. The TG/HDL-C, the T-C/HDL-C, and the LDL-C/HDL-C ratio have shown similar potential for insulin resistance, though the reports are not entirely consistent. In 50 white Americans, both TG and TG/HDL-C ratio were acceptable markers for insulin resistance, with area under the ROC curve of 0.763 and 0.770, respectively, but poor predictors in 99 African Americans, with the values at 0.625 and 0.639, respectively . It was demonstrated that the relationship between TG and TG/HDL-C with insulin resistance differs by ethnicity. In 3,014 patients (mean age 54 years; 55% women), TG/HDL-C ratio and T-C/HDL-C ratio were related to insulin resistance assessed by the top quartile of the HOMA-IR, and the area under the ROC curves for predicting insulin resistance with TG/HDL-C ratio and T-C/HDL-C ratio were 0.745 and 0.707, respectively . LDL-C/HDL-C ratio  as well as TG/HDL-C ratio  have advantages for standardization and identification of patients with an atherogenic lipoprotein profile as a surrogate maker of insulin resistance. Also in our study, both LDL-C/HDL-C and TG/HDL-C ratio were useful makers of insulin resistance, especially in all subjects or non-obese subjects. However, these makers were weaker in overweight subjects. Kimm et al.  demonstrated that the lipid ratios of TC/HDL-C, LDL-C/HDL-C and TG/HDL-C, as well as TG and HDL-C, were consistently associated with metabolic syndrome and insulin resistance in participants without metabolic syndrome, though these relations were weaker in participants with metabolic syndrome. Lipid ratios that include information on at least two measures might have a more integrated explanation than single lipid measures such as TG or HDL-C .
Some limitations of this study must be considered. First, the response rate was as low as 35% that is usually the casein other conventional community studies in Japan. However, the relatively large sample size enabled the assessment of an extensive array of insulin resistances in relation to lipid profiles. Second, the cross-sectional study design is limited in its ability to eliminate causal relationships between lipid profiles and HOMA-IR. Third, our definition of HOMA-IR is based on a single assessment of FBS and IRI, which may introduce misclassification bias. Therefore the demographics and referral source may limit generalizability.
In conclusion, the present study demonstrated that special lipid profiles are associated with insulin resistance according to BMI in a general population. The ability to identify who is non-obese or overweight and who are insulin resistant could help health care professionals in bringing about lifestyle interventions. In that context, use of the cutoff-points of LDL-C/HDL-C ratio or TG/HDL-C ratio described in this report is simple and useful. The present data documented that insulin resistance was present even in subjects with BMI within the normal range. Further prospective population-based studies are needed to investigate the changes in lipid metabolism by lifestyle interventions.