Introduction

Early identification and accurate diagnosis of type-2 diabetes mellitus (T2DM) have a critical role in effective management of the disease. Recent research is suggestive on the potential role of total cholesterol (TC), high-density lipoprotein (HDL), and glucose (CHG) index as a promising biomarker for the prognosis of T2DM. The CHG index indicates disorders in both glucose and lipid metabolism, thus focusing on a holistic assessment of metabolic health. Nevertheless, the predictive performance and generalizability of the CHG index has been limited to Iranian cohorts till date and the same has not been ascertained in the United States (US), where ethnic heterogeneity and lifestyle factors may impact the diagnostic utility of CHG index.

Aim

To ascertain the association between the CHG index and prevalence of T2DM in adults in the US.

Patient Profile

• The study population comprised of participants from the National Health and Nutrition Examination Survey (NHANES) 2009–2018 cycles (age ≥20 years, N=11,390).
• Of the entire study population, 2710 subjects (23.79%) had T2DM and 8680 (76.21%) were without T2DM.
• Based on the World Health Organization (WHO) guidelines the body mass index (BMI) of the study subjects was categorized into three groups as follows: <25 kg/m² (normal weight), 25–29.9 kg/m² (overweight), and ≥30 kg/m² (obese).

Methods

Study Design

• A cross-sectional study based on NHANES.
• NHANES is a nationally representative cross-sectional survey conducted by the Centers for Disease Control and Prevention in the US.

Evaluations

• The CHG index was calculated by integrating TC, HDL, and fasting blood glucose (FBG) in the following formula:
  • ln [TC (mg/dL) X FBG (mg/dL)/ (2 X HDL) (mg/dL)].
• The association between the CHG index and the prevalence of T2DM was evaluated using weighted logistic regression [Model 1: not adjusted for any confounding variables; Model 2: adjusted for age, sex, educational level, marital status, and poverty-to-income ratio (PIR); Model 3: additionally adjusted for alcohol consumption, smoking status, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GCT), triglyceride (TG), fasting insulin, hypertension, and BMI].
• The potential nonlinear associations between CHG index and T2DM prevalence were analyzed using restricted cubic spline analysis.
• The diagnostic performance of the CHG index was evaluated based on the receiver operating characteristic (ROC) curves.
• The results were compared with those of the triglyceride-glucose (TyG) index.

Results

• Prevalence of T2DM was higher in men vs. women, moreover; subjects with T2DM had significantly higher levels of PIR, ALT, AST, GGT, ALP, TG, fasting insulin, and CHG index. A higher proportion of subjects with T2DM were smokers, obese, and married and had hypertension.
• As per the analysis in Model 1, a higher CHG index was associated with significantly higher prevalence of T2DM [odds ratio (OR): 6.90, 95% confidence interval (CI): 5.57–8.54, p<0.001] (Table 1).
• The association between higher CHG and T2DM prevalence remained strong and statistically significant in Model 2 (OR: 6.89, 95% CI: 5.46–8.69, p<0.001) (Table 1).
• The association between CHG and T2DM prevalence did not weaken in Model 3 (OR: 4.30, 95% CI: 3.21–5.77, p<0.001) (Table 1).

Table 1: Weighted logistic regression between the CHG index and T2DM prevalence

• The restricted cubic spline analysis demonstrated a nonlinear association with an increased risk of T2DM in patients with a CHG index of >5.24. The association remained consistent across all subgroups.
• As per the ROC analysis, the CHG index had good predictive value [area under the curve (AUC): 0.721; with an optimal cutoff value of 5.47; sensitivity: 0.53; specificity: 0.80), comparable to that of the TyG index (AUC: 0.730; with optimal cutoff value of 8.84; sensitivity: 0.62; specificity=0.73).

Conclusions

• This cross-sectional analysis of NHANES suggested that CHG index may be associated with prevalence of T2DM and could thus serve as a simple, accessible biomarker for early T2DM risk identification.
• Further prospective studies are warranted to validate the clinical utility of CHG index as a biomarker for the prognosis of T2DM.

J Int Med Res. 2025 Sep;53(9):3000605251375557. Doi: 10.1177/03000605251375557.