Metabolic Risk Factors Contribute to Diabetic Macular Edema Development

Credit: Victor Freitas/Unsplash

Modifiable systemic factors in patients with diabetes, including hemoglobin A1c (HbA1c) and blood pressure levels, contributed to an elevated risk of diabetic macular edema (DME) development, according to results of a recent retrospective cohort study.¹

Among a population of nearly 48,000 patients with diabetes, Black race, elevated systolic blood pressure (SBP), and systemic hyperglycemia were linked to a greater DME risk. Other modifiable systemic markers, including obesity and dyslipidemia, demonstrated no notable impact.

“This work emphasizes the importance of early guidance to patients with diabetes on blood pressure control by eye care providers in conjunction with primary care providers and need for further mechanistic studies to understand the effects of blood pressure on DME development,” wrote the investigative team, led by Anjali R. Shah, MD, department of ophthalmology and visual sciences, W.K. Kellogg Eye Center, University of Michigan.

Diabetic retinopathy (DR) development and progression have been linked to duration and glycemic control, centering the control of diabetes as foundational for disease management.² However, while endocrinologists often manage these comorbidities, not all ophthalmologists consider systemic DME markers in clinical decision-making.

Clinical heterogeneity in DME has been hypothesized to stem from variations in individual metabolic control, but large-scale studies have yet to report this association.³ Using the Sight Outcomes Research Collaborative (SOURCE) Ophthalmology Data Repository, Shah and colleagues searched for a link between measurable markers of metabolic dysfunction and new DME onset.¹

The retrospective study used data from 10 active SOURCE sites, each contributing 5 to 12 years of data. Using a validated algorithm, investigators identified patients with diabetes and no preexisting DME, with ≥1 documented measurement of blood pressure, fasting lipid profile, body mass index (BMI), and HbA1c. Those with preexisting DME or coexisting conditions that might contribute to macular edema were excluded from the study.

For the analysis, a Cox proportional hazards model assessed the relationship between demographic variables, diabetes type, smoking status, baseline DR status, SBP, lipids, BMI, HbA1c, and the new onset of DME. Each patient was followed from the index date until development of the outcome of interest, death, or the end of time in SOURCE.

A total of 47,509 eligible individuals with diabetes were recruited from the 10 SOURCE sites. Patients had a mean age of 53 years and were primarily female (58%) and White (48%). Across the follow-up period, 3633 (7.6%) patients developed DME.

Average time to DME development in ≥1 eye was 875 days (~2.4 years). The time to DME varied significantly by baseline DR, with the longest time in those with no DR (846 days), followed by non-proliferative DR (632 days) and PDR (563 days).

After performing multivariable Cox regression analysis, investigators found Black patients had a 40% increased risk of DME compared with White patients (hazard ratio [HR], 1.40; 95% CI, 1.30 – 1.51). However, there were no significant differences in DME risk between patients with type 1 versus type 2 diabetes.

There was additionally no statistically significant association identified between cigarette smoking (HR, 0.98; 95% CI, 0.92 – 1.05) or sex (HR, 1.06; 95% CI, 0.98–1.13) and the development of DME. Each additional 5 years of age was linked to a 2% increased DME risk (HR, 1.02; 95% CI, 1.01 – 1.04; P <.01).

Moreover, every 1 unit increase in HbA1c was linked to a 15% increased risk of DME (HR, 1.15; 95% CI, 1.13 – 1.17; P <.001), and each 10 mmHg increase in SBP increased the risk of DME by 6% (HR, 1.06; 95% CI, 1.02 – 1.09). Meanwhile, Shah and colleagues identified no association between DME risk and BMI (P = .25), dyslipidemia measured by TG (P = .11), or HDL-C (P = .96) levels.

“Although we did not see increases in BMI or measured markers of dyslipidemia associated with MetS correspond with new-onset DME in this study, these variables have been shown to contribute to other macrovascular and microvascular comorbidities of diabetes, and patients should be counseled on treatment based on available recommendations,” they wrote.

References

1. _{Haliyur R, Marwah S, Mittal S, Stein JD, Shah AR; SOURCE Consortium. Demographic and Metabolic Risk Factors Associated with Development of Diabetic Macular Edema among Persons with Diabetes Mellitus. Ophthalmol Sci. 2024;4(6):100557. Published 2024 May 23. doi:10.1016/j.xops.2024.100557}
2. _{Varma R, Bressler NM, Doan QV, et al. Prevalence of and risk factors for diabetic macular edema in the United States. JAMA Ophthalmol. 2014;132(11):1334-1340. doi:10.1001/jamaophthalmol.2014.2854}
3. _{Shah AR, Van Horn AN, Verchinina L, et al. Blood Pressure Is Associated with Receiving Intravitreal Anti-Vascular Endothelial Growth Factor Treatment in Patients with Diabetes. Ophthalmol Retina. 2019;3(5):410-416. doi:10.1016/j.oret.2019.01.019}