Timing Is Everything: Age of Onset Influences Long-term Retinopathy Risk in Type 2 Diabetes, Independent of Traditional Risk Factors

Jencia Wong, MD; Lynda Molyneaux, RN; Maria Constantino; Stephen M. Twigg, MD, PHD; Dennis K. Yue, MD, PHD


Diabetes Care. 2008;31(10):1985-1990. 

In This Article


Increase in the Prevalence and Severity of Retinopathy in Those with a Younger Age of Diabetes Onset

The demographic profile of those with a long duration (group A) and those with a moderate duration (group B) of diabetes, stratified by age of diagnosis, is shown in Table 1 . For group A, there was an approximate threefold excess of retinopathy in those with early-onset disease (<45 years), including a notable excess in vision-threatening retinopathy. For group B, the older-onset group again had the lowest prevalence of retinopathy, whereas the <45- and the 45- to 55-year onset groups were not statistically different from one another (X 2 = 0.3; P = 0.6). Glycemic exposure was slightly less favorable in the early-onset groups, but the differences in A1C were small, at 0.2% for group A and 0.8% for group B. There was no difference in the prevalence of the metabolic syndrome between the groups. For group A, the younger patients are receiving more antihypertensive treatment, but blood pressure remains similar between the age-of-onset groups.

Increase in the Prevalence of Retinopathy in Those with Younger Age of Onset: Adjustment for Glycemic Exposure

Two approaches were used to address the extent to which excess of retinopathy in early-onset groups was due to slightly poorer glycemic control. First, retinopathy risk was stratified by average A1C. Table 2 and Figure 1 show the prevalence and ORs of retinopathy for each age of onset at each level of glycemic exposure for the duration cohorts. The impact of the younger age of diagnosis is greatest in those with the worst long-term glycemic control (mean A1C >9%), with at least a two- to threefold increase in the OR of retinopathy for those diagnosed before 45 years of age compared with those of similar disease duration and glycemic exposure but diagnosed at >55 years of age. However, this trend of differing retinopathy prevalence according to age of onset is also seen at lower levels of glycemic exposure, even into the target range of A1C <7% ( Table 2 ). The oldest-onset group invariably had the lowest risk of retinopathy. Second, regression analysis shows that each 1% rise in A1C is associated with a 13.9% increase in retinopathy for the main cohort of interest (group A). The small difference in A1C between the subgroups can only account for 12% of the observed difference in the prevalence of retinopathy between the youngest- and the oldest-onset group.

Group A (duration of type 2 diabetes 20-30 years): OR for retinopathy grouped by age of diagnosis and mean A1C. Reference group is age of diagnosis >55 years and A1C <7%.

Age of Diagnosis Is an Independent Predictor of Long-term Retinopathy

Table 3 shows the results of logistic regression analysis for both duration cohorts. There is a significant effect of age of diagnosis, irrespective of whether it was considered as a categorical variable (model 1 OR of retinopathy: 1.9, 1.1, and 1 for age of onset <45, 45-55, and >55 years, respectively, for group A with diabetes duration 20-30 years) or a continuous variable (model 2 OR of retinopathy: 0.88 [95% CI 0.83-0.94] for Group A). These findings were independent of A1C, hypertension, and other risk factors.


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