Atherogenic lipid indices and diabetic retinopathy in type 2 diabetes: a systematic review and meta-analysis

TL;DR

This study finds that two lipid indices are higher in people with type 2 diabetes who have diabetic retinopathy, suggesting they might help identify those at higher risk.

Contribution

The study introduces and evaluates two novel atherogenic lipid indices as potential markers for diabetic retinopathy in type 2 diabetes.

Findings

Individuals with diabetic retinopathy had higher AIP values compared to those without.

The TG/HDL-C ratio was also elevated in diabetic retinopathy cases.

Both lipid indices increased progressively with the severity of retinopathy.

Abstract

This study conducts a quantitative synthesis of existing evidence to evaluate the association of two novel atherogenic lipid indices—the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) and the atherogenic index of plasma (AIP)—with the prevalence and severity of diabetic retinopathy (DR) in individuals with type 2 diabetes mellitus (T2DM).

We systematically searched Cochrane Library, PubMed, Web of Science, Embase, CBM, CNKI, Wanfang, and Weipu for observational studies published before July 30, 2025. Cross-sectional, cohort, and case–control studies reporting AIP or TG/HDL-C data in T2DM patients with or without DR were eligible. Given the anticipated clinical and methodological diversity across observational studies, we prespecified a random-effects meta-analysis as the primary model, estimating τ2 via restricted maximum likelihood and constructing confidence intervals using the Hartung–Knapp–Sidik–Jonkman adjustment. Between-study variance (τ2) and 95% prediction intervals (PIs) were reported under the random-effects framework when at least three studies contributed to a given contrast, and fixed-effect models were additionally fitted as sensitivity analyses alongside heterogeneity, sensitivity, and publication bias assessments.

A total of 10 studies (n = 5,071) were included. In the unadjusted pooled analysis, individuals with DR had higher AIP values than those without DR (mean difference [MD] = 0.078, 95% CI: 0.016–0.142; I2 = 91.6%). The triglyceride-to-HDL cholesterol (TG/HDL-C) ratio was also elevated in DR cases based on three studies (MD = 0.73, 95% CI: 0.11–1.38; I2 = 89.7%). Exploratory bias-adjusted analyses using the trim-and-fill method yielded similar but attenuated estimates (AIP = 0.10 [95% CI: 0.02–0.18]; TG/HDL-C = 1.32 [95% CI: 0.61–2.03]), supporting the robustness but remaining hypothesis-generating. Subgroup analyses suggested a progressive increase in both indices with DR severity, particularly between proliferative (PDR) and non-proliferative (NPDR) stages.

AIP and TG/HDL-C ratio were higher in patients with DR, suggesting potential roles as lipid-related markers for identifying individuals at greater risk of retinopathy. However, due to high heterogeneity, limited study numbers, and observational design, these results should be interpreted cautiously as exploratory until validated by large, well-adjusted prospective studies.

Most included studies were conducted in Chinese populations, which may restrict the generalizability of the results to other ethnic or regional groups. Variations in genetic background, lifestyle, metabolic profiles, and diabetic retinopathy screening practices could influence the observed associations between lipid indices and DR risk.

INPLASY.COM, Registration number: INPLASY2025100035.

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