Association of non-traditional lipid indices with diabetes and insulin resistance in US adults: mediating effects of HOMA-IR and evidence from a national cohort

Aug 7, 2025Clinical and experimental medicine

Non-traditional blood fat measures linked to diabetes and insulin resistance in US adults, with insulin resistance partly explaining this connection

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

15.0% of participants in the study had diabetes.

Four lipid indices, excluding CRI-II and EsdLDL-C, were linked with diabetes after adjustment.
The (AIP) and (RC) were associated with significantly increased diabetes risk, with odds ratios of 2.52 and 2.13, respectively, for the highest versus lowest quartiles.
All lipid indices showed dose-dependent associations with insulin resistance (IR), with AIP and RC displaying the strongest links, having odds ratios of 5.74 and 4.09, respectively.
AIP and RC demonstrated high diagnostic performance for diabetes (AUC: 0.824 and 0.822) compared to other lipid indices, but were less effective than fasting glucose and HbA1c.
AIP and RC also showed superior diagnostic capability for IR (AUC: 0.837 and 0.830) among lipid indices, comparable to traditional IR assessment methods.
Mediation analysis indicated that HOMA-IR accounted for a significant portion of the associations between AIP/RC and diabetes, particularly in older adults, males, and those with a higher BMI.

AI simplified

Dyslipidemia, diabetes mellitus, and insulin resistance (IR) are intricately linked. In recent years, a series of novel lipid indices have emerged. Investigating their correlation with diabetes and IR is critical for early intervention. This study analyzed 19,780 National Health and Nutrition Examination Survey (NHANES) participants (1999-2020), examining the (AIP), Castelli risk index I (CRI-I) and II (CRI-II), estimated small dense LDL cholesterol (EsdLDL-C), non-HDL cholesterol-to-HDL cholesterol ratio (NHHR), and (RC). Covariates were selected via Boruta and LASSO regression. Multivariate logistic regression, restricted cubic splines, ROC, subgroup, and mediation analyses were employed, validated by sensitivity analyses. The prevalence of diabetes was 15.0%. After adjustment, four indices (excluding CRI-II and EsdLDL-C) were associated with diabetes. For Q4 vs Q1, AIP and RC showed significantly elevated risk (OR: 2.52 [2.07-3.07] and 2.13 [1.75-2.58], respectively). Regarding IR, all indices exhibited dose-dependent associations, with AIP (OR: 5.74 [5.00-6.59]) and RC (4.09 [3.58-4.67]) showing the strongest links. For diabetes diagnosis, AIP (AUC: 0.824) and RC (0.822) outperformed other lipid indices (cutoffs: 0.31, 31.0) but were less effective than fasting glucose and HbA1c. For IR, AIP (AUC: 0.837) and RC (0.830) remained superior among lipid indices and showed no significant diagnostic disadvantage vs IR-related indicators. Subgroup analyses indicated stronger AIP/RC-diabetes/IR associations in females. Mediation analyses showed HOMA-IR mediated 43.1% and 50.3% of AIP/RC-diabetes associations, more pronounced in older adults (> 65 years), males and those with BMI ≥ 25 kg/m, while fatty acid intake did not affect these mediators. All six indices correlate with IR, but only AIP and RC strongly associate with diabetes, mediated by HOMA-IR. Females show enhanced AIP/RC-diabetes links, while older, male, and overweight groups exhibit greater HOMA-IR mediation. And AIP or RC's diagnostic performance for IR is not inferior to other IR assessment indices. Thus, AIP and RC are prioritized biomarkers for diabetes and IR monitoring. 2

Key numbers

2.52

Increase in Diabetes Risk ()

Odds ratio for diabetes in highest quartile of vs. lowest

2.13

Increase in Diabetes Risk ()

Odds ratio for diabetes in highest quartile of vs. lowest

5.74

Odds Ratio for Insulin Resistance ()

Odds ratio for insulin resistance associated with

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text (PDF) ↗View full text (HTML) ↗

Association of non-traditional lipid indices with diabetes and insulin resistance in US adults: mediating effects of HOMA-IR and evidence from a national cohort

Abstract

Key numbers

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief