HbA1c-Based Metabolic Stratification: A Retrospective Study of Clinical and Biological Differences Across Normoglycemic, Prediabetic, and Diabetic Subjects

TL;DR

This study shows that HbA1c levels can help identify early metabolic and complication risks in prediabetic individuals, suggesting HbA1c could be used for early diabetes prevention.

Contribution

The study demonstrates that prediabetic individuals show early signs of complications, supporting HbA1c as a tool for metabolic stratification and risk assessment.

Findings

Prediabetic individuals showed higher prevalence of peripheral neuropathy and retinopathy compared to normoglycemic subjects.

Diabetic patients had the highest complication burden, with increased odds of complications compared to normoglycemic individuals.

Abstract

Background: Glycated hemoglobin (HbA1c) is widely used for the diagnosis and monitoring of diabetes mellitus. However, its potential role as a marker of metabolic stratification and early complication risk beyond diagnostic thresholds remains insufficiently explored. Prediabetes is often considered a transitional state, although growing evidence suggests the presence of early metabolic and microvascular alterations. Methods: In this cross-sectional observational study, adult subjects were stratified into three groups based on HbA1c levels: normoglycemic (HbA1c < 5.7%), prediabetic (HbA1c 5.7–6.4%), and diabetic (HbA1c ≥ 6.5%). Demographic data, metabolic parameters, cardiometabolic comorbidities, and diabetes-related complications were analyzed. Group differences were assessed using appropriate statistical tests. Cumulative complication burden was evaluated, and risk estimation was performed using univariate logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 839 subjects were included in the analysis. HbA1c and fasting glucose levels increased progressively across groups (p < 0.001). Prediabetic individuals already exhibited a higher prevalence of peripheral neuropathy and retinopathy compared to normoglycemic subjects, while diabetic patients showed the highest overall complication burden. The cumulative number of complications increased significantly across HbA1c-based groups (p = 0.033). Risk estimation analyses revealed increased odds for presenting at least one complication and for peripheral neuropathy in diabetic subjects, with intermediate risk levels observed in the prediabetic group. Conclusions: HbA1c-based stratification captures meaningful differences in metabolic status, complication burden, and estimated risk across normoglycemic, prediabetic, and diabetic individuals. Prediabetes is associated with detectable microvascular involvement and higher complication risk. Given the cross-sectional design, these findings reflect associations rather than causal relationships. These findings highlight the potential clinical value of HbA1c for early risk assessment and targeted preventive strategies.

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