Major Risk Factors of Diabetic Retinopathy and their Relative Importance: a Meta-analysis Pooling Data from Individual Subjects in 13 Studies

Abstract

Purpose: To determine the major risk factors for diabetic retinopathy (DR) and their relative importance in over 7000 adults with type 2 diabetes, using participant-level data pooled from 13 population-based studies.

Methods: A systematic literature review was conducted to identify population-based studies that used retinal photographs to ascertain DR and reported risk factors associated with DR for subjects with type 2 diabetes. Investigators of identified studies were contacted and asked to provide, from subjects with type 2 diabetes mellitus, individual participant data on the presence or absence of DR and known potential risk factors (age, gender, race, smoking, systolic blood pressure, hypertension medication, diabetes treatment, duration of diabetes, HbA1c, and total cholesterol). Data from all study subjects were pooled and a meta-analysis was conducted using Stata. Commonality analysis was performed in R to partition the regression effects of the major risk factors into unique and common effects using the pooled individual patient data. Unique effect identifies how much variance is unique to a given risk factor and common effect identifies the joint effects among risk factors.

Results: Thirteen studies were identified comprising 7397 subjects aged 40+ years with type 2 diabetes mellitus. The pooled prevalence of any DR was 24.1% (95% confidence interval [CI] 23.1%-25.1%. After controlling for known risk factors, age (per year, Odds ratio [OR] 1.23, 95% CI 1.04-1.45), systolic blood pressure (per 1 mmHg increase, OR 1.01, 95% CI 1.01-1.01), duration of diabetes (per year, OR 1.07, 95% CI 1.06-1.09), HbA1c (per %, OR 1.23, 95% CI 1.04-1.45) were associated with the presence of DR. Commonality analysis identified the most important risk factor for DR as duration of diabetes, explaining 4.9% and 4.8% of unique and common variances of DR, respectively. The unique and common contribution of HbA1c to DR was 3.37% and 1.52%, respectively. Forty-six percent of the total explained variation in DR was due to joint effect among the four major risk factors.

Conclusions: While diabetes duration, glycemic and blood pressure control are associated with prevalent DR in type 2 diabetes, each factor alone explain low amounts of the variability.

Keywords: 499 diabetic retinopathy • 464 clinical (human) or epidemiologic studies: risk factor assessment