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

Abstract and Introduction


Objective: To test the hypothesis that age of type 2 diabetes onset influences inherent susceptibility to diabetic retinopathy, independent of disease duration and degree of hyperglycemia.
Research Design and Methods: Retinopathy data from 624 patients with a type 2 diabetes duration of 20-30 years (group A) were analyzed by stratifying patients according to age of onset of diabetes and glycemic control. Retinopathy status was scored clinically as per a modified Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. To obviate possible bias due to a higher attrition from comorbidities in those with later-onset diabetes and retinopathy, 852 patients with type 2 diabetes of shorter duration (10-12 years, group B) were similarly studied.
Results: Prevalence and severity of retinopathy was significantly higher in the younger-onset, group A patients. When further stratified according to mean A1C, retinopathy risk remained increased in younger-onset patients. The greatest impact was seen in those with a mean A1C >9% (odds ratio [OR] for retinopathy 16.6, 7.5, and 2.7 for age of diagnosis <45, 45-55, and >55 years, respectively, P = 0.003). By logistic regression, earlier type 2 diabetes onset is associated with increased retinopathy risk, independent of traditional risk factors (OR of retinopathy 1.9, 1.1, and 1 for age of onset <45, 45-55, and >55 years, respectively). Similar results were found in group B patients.
Conclusions: These data suggest an increased inherent susceptibility to diabetic retinopathy with earlier-onset type 2 diabetes. This further supports the importance of delaying development of diabetes and also implies a need for more stringent metabolic targets for younger individuals.


Superimposed on the worldwide epidemic of diabetes that we are currently facing is the demographic trend to an ever younger age of diagnosis of type 2 diabetes.[1] In recent studies, type 2 diabetes constitutes up to 45% of incident pediatric diabetes, and 7-22% of adolescent diabetes presents with diabetes-specific complications at diagnosis.[2,3] To date, few studies have examined long-term outcomes as a function of age of diagnosis in type 2 diabetes, and even fewer have looked at the development of retinopathy specifically. There is some limited data suggesting that young-onset diabetes is associated with an increased risk for complications compared with later-onset diabetes[4] and that the development and progression of complications might be particularly rapid in early-onset disease.[2] What is hitherto unknown is whether the increased prevalence of complications associated with early-onset disease is simply a consequence of the longer duration of disease, a consequence of a more severe metabolic phenotype, or in fact something specific to the diabetic milieu in younger patients that makes tissues more inherently susceptible to hyperglycemic damage.

We therefore explore the hypothesis that in type 2 diabetes, susceptibility to retinopathy is dependent on age of diabetes onset. The isolated effect of age of diabetes onset on long-term retinopathy status was examined independent of duration of diabetes and glycemic control, the two most important risk factors for retinopathy.


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