DR Risk Peaks at HbA1c of 9.4, Then Declines at Higher Levels

Chronic hyperglycemia causes ongoing oxidative stress and inflammation. When HbA1c exceeds 9.4%, these processes might plateau; thus, further increases in HbA1c won’t worsen them as much. This graph from the study shows the association between HbA1c and DR (red line). Blue bands represent the 95% confidence interval. Photo: Ling J, et al. BMC Ophthalmol. 2025;25:289. Click image to enlarge. It’s well known that diabetic retinopathy (DR) is a common enough complication of diabetes, and due to its potential severity, it is evaluated for regularly by eyecare providers. Although HbA1c level is known to be indicative as a critical biomarker for long-term glycemic control and is linked to risk of DR development, it has not thoroughly been explored in a nonlinear fashion with DR.Researchers recently published a paper in BMC Ophthalmology in which they conducted a cross-sectional investigation, including 2,001 total patients with type 2 diabetes who were evaluated in southern Taiwan; HbA1c levels were measured and the association between this and DR was analyzed.After analysis, a fully adjusted model displayed that HbA1c positively correlated with DR; however, this was demonstrated by an inverted, U-shaped association, in which DR risk reached a peak with HbA1c level, then started to decline. The inflection point of HbA1c level was found to be 9.4%--in the early phase of DR—and the inverted, U-shaped nonlinear relationship was also found to be true for age, sex and BMI.In a discussion about the findings, the authors explain that they found every 1% increase in HbA1c to be associated with a 7% increase in the odds of developing DR; this link was strengthened when adjusting for confounders of age and sex.They explore why this relationship may be present, offering one possibility having to do with metabolic memory. Long-term hyperglycemia may a metabolic memory sustaining DR risk even after glycemic control. At very high HbA1c levels, this memory is already established, so higher levels may add little to the risk. Another factor is that hyperglycemia-induced microvascular damage is partially irreversible, so extra HbA1c increases may cause limited additional harm.The investigators further elucidate how this curve may impact greater health initiatives and protocols. They highlight how this is important for aiding targeted intervention strategies, with early HbA1c screening and monitoring effectively being able to identify high-risk individuals, facilitate early intervention and reduce DR incidence. As the investigators say, “clinically, healthcare providers can optimize diabetes management using these results. Patients near the 9.4% HbA1c threshold need closer monitoring and timely intervention.”Along with this, they add that “our results back personalized treatment based on individual HbA1c levels. For patients above 9.4%, consider aggressive glycemic control with complication monitoring. For those below, balance glycemic control and hypoglycemia risk.”They are even hopeful that this main finding will extend into greater public health policy, hopeful that “the 9.4% HbA1c threshold can inform clinical guideline updates, DR screening and diabetes management recommendations, standardizing care and ensuring evidence-based interventions.”Click here for the journal source. Ling J, Xie ZL, Chen XJ, et al. Inverted U-shaped relationship between HbA1c and diabetic retinopathy in diabetic patients: a cross-sectional study. BMC Ophthalmol. 2025;25:289.