Comparison of Novel Biomarkers of Insulin Resistance With Homeostasis Model Assessment of Insulin Resistance, Its Correlation to Metabolic Syndrome in South Indian Population and Proposition of Population Specific Cutoffs for These Indices

Abstract

Background The clustering of risk factors of cardiovascular disease (CVD) in individuals has been defined as Metabolic Syndrome (MetS). The major forerunner of all the components of MetS is Insulin Resistance (IR) which is measured by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and requires the measurement of fasting plasma insulin levels. We attempted to study the performance of lipid-based biochemical markers of IR for the diagnosis of MetS and postulate a population-specific cutoff for these indices in the South Indian population. In this study, we analyzed three lipid-based indices, Triglyceride Glucose index (TyG index), triglyceride: high-Density Lipoprotein (TG:HDL) ratio, and lipid accumulation product (LAP). Methods This was a cross-sectional study and included apparently healthy individuals presenting to our hospital for routine Master Health Checkup assessment and apparently healthy population residing in Kallindhiri, a village near Madurai. Based on the anthropometric measurements and blood investigations, Body Mass Index (BMI), Waist hip ratio, Waist height ratio, HOMA-IR, TyG index, TG:HDL ratio, and LAP were calculated. The diagnostic efficacy of these indices was compared against the presence of MetS based on the NCEP ATP III criteria. The receiver operating characteristic (ROC) Curve was performed to discriminate decision levels (cutoffs) of serum markers in early diagnosis of metabolic syndrome. The results were considered significant with a p-value less than 0.05. Results We included a total of 192 patients in our study, consisting of 36% (n=70) males and 63% (n=122) females. All the baseline characteristics except height, weight, and HDL cholesterol were comparable between the male and female groups. The values of HOMA-IR, TyG index, TG:HDL ratio, and LAP showed an increasing trend with the BMI. The mean values of HOMA-IR, TyG index, TG:HDL ratio and LAP was significantly higher in patients with MetS than in patients without MetS. Based on the ROC curve plotted for the data, a population-specific cutoff for these indices was computed. Our proposed cutoff for the South Indian population for HOMA-IR is 1.23, for TyG index is 4.65, for TG:HDL ratio is 3.44 in males and 2.6 in females and for LAP is 43.81 Conclusion The cutoffs for the novel indices of insulin resistance which have been previously studied in Caucasian populations cannot be applied to Indian populations due to distinct ethnic characteristics. The diagnostic accuracy of these novel lipid-based biomarkers of Insulin Resistance is better than the biochemical gold standard of HOMA-IR based on the ROC curve. We propose the usage of these population-specific cutoffs in routine clinical practice for early diagnosis of metabolic syndrome.

Keywords: homa-ir; insulin resistance; lipid accumulation product; metabolic syndrome; tg: hdl ratio; tyg index.

Figure 1. Trend of markers of insulin resistance across various categories of BMI

BMI- body mass index; HOMA-IR- Homeostasis model assessment of insulin resistance; TyG index: triglyceride glucose index; TG:HDL ratio: Triglyceride: high density lipoprotein ratio; LAP: lipid accumulation product The x-axis depicts the body mass index (BMI) of the population, which has been subdivided into (i) underweight- BMI: <18.5 kg/m²; (ii) normal- BMI: 18.5-22.9 kg/m²; (iii) overweight- BMI: 23-24.9 kg/m² and (iv) obese- BMI: > 25 kg/m²

Figure 2. Receiver operating characteristics curve for HOMA-IR and novel lipid-based indices

ROC- receiver operating characteristics; HOMA-IR- homeostasis model assessment of insulin resistance, TyG index- triglyceride glucose index; TG:HDL ratio- triglyceride: high density lipoprotein ratio; LAP- lipid accumulation product