Demographic and Metabolic Risk Factors Associated with Development of Diabetic Macular Edema among Persons with Diabetes Mellitus

Abstract

Purpose: Diabetic macular edema (DME), a leading cause of visual impairment, can occur regardless of diabetic retinopathy (DR) stage. Poor metabolic control is hypothesized to contribute to DME development, although large-scale studies have yet to identify such an association. This study aims to determine whether measurable markers of dysmetabolism are associated with DME development in persons with diabetes.

Design: Retrospective cohort study.

Participants: Using data from the Sight Outcomes Research Collaborative (SOURCE) repository, patients with diabetes mellitus and no preexisting DME were identified and followed over time to see what factors associated with DME development.

Methods: Cox proportional hazard modeling was used to assess the relationship between demographic variables, diabetes type, smoking history, baseline DR status, blood pressure (BP), lipid profile, body mass index (BMI), hemoglobin A1C (HbA1C), and new onset of DME.

Main outcome measures: Adjusted hazard ratio (HR) of developing DME with 95% confidence intervals (CIs).

Results: Of 47 509 eligible patients from 10 SOURCE sites (mean age 63 ± 12 years, 58% female sex, 48% White race), 3633 (7.6%) developed DME in the study period. The mean ± standard deviation time to DME was 875 ± 684 days (∼2.4 years) with those with baseline nonproliferative DR (HR 3.67, 95% CI: 3.41-3.95) and proliferative DR (HR 5.19, 95% CI: 4.61-5.85) more likely to develop DME. There was no difference in DME risk between type 1 and type 2 patients; however, Black race was associated with a 40% increase in DME risk (HR 1.40, 95% CI: 1.30-1.51). Every 1 unit increase in HbA1C had a 15% increased risk of DME (HR 1.15, 95% CI: 1.13-1.17), and each 10 mmHg increase in systolic BP was associated with a 6% increased DME risk (HR 1.06, 95% CI: 1.02-1.09). No association was identified between DME development and BMI, triglyceride levels, or high-density lipoprotein levels.

Conclusions: These findings suggest that in patients with diabetes modifiable risk factors such as elevated HbA1C and BP confer a higher risk of DME development; however, other modifiable systemic markers of dysmetabolism such as obesity and dyslipidemia did not. Further work is needed to identify the underlying contributions of race in DME.

Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Black race; Blood pressure; Diabetic macular edema; Diabetic retinopathy; Metabolic syndrome.

Figure 3

Use of Sight Outcomes Research Collaborative for cohort development to identify individuals who develop diabetic macular edema (DME). A record of diabetes mellitus (DM) diagnosis (Dx) by international classification code (ICD) or medications was used to identify adult patients (>18 years of age). A 2-year baseline period from first encounter (0) to index date (2Y) was employed to include those without DME and exclude those with preexisting macular edema of any type or known diagnosis of DME. Patients were then followed for the development of DME in the follow-up period. All included individuals had at least one record of blood pressure, high-density lipoprotein, and triglyceride levels, body mass index, and hemoglobin A1C captured at time point closest to index date.

Figure 4

Baseline metabolic variables at index date for those who develop diabetic macular edema (DME) compared those with diabetes mellitus (DM) who do not develop DME. Metabolic values (mean ± standard deviation) measured at record closest to the index date for each included individual comparing those with DM that do (dot pattern bars) and do not (gray bars) develop DME in the follow-up period. BMI = body mass index; BP = blood pressure; HbA1C = hemoglobin A1C; HDL = high-density lipoprotein; TG = triglyceride levels. In the figures, ∗ indicates P < 0.05, ∗∗ indicates P < 0.01, ∗∗∗ indicates P < 0.001.

Figure 5

Risk factors for developing diabetic macular edema (DME) in patients with diabetes mellitus (DM) identified by multivariable regression. Forest plots of adjusted hazard ratios from a multivariate Cox regression analysis of demographic and metabolic risk factors on a new diagnosis of DME with corresponding 95% confidence interval (CI). Reference group is female for gender, White for race, no diabetic retinopathy (DR) for baseline DR, no history of smoking for smoking status, and type 1 DM for diabetes type. For continuous variables, risk is associated with 1 corresponding unit except for age, which has increments of 5 years, and systolic blood pressure, which has increments of 10 mmHg. adj HR = adjusted hazard ratio; BMI = body mass index; BP = blood pressure; Dec = decreased; HbA1C = hemoglobin A1C; HDL = high-density lipoprotein; Inc = increased; NPDR = nonproliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy; TG = triglyceride levels.