Diabetes NewsJanuary 2011
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Age at Onset and the Risk of Proliferative Retinopathy in Type 1 Diabetes
Diabetes Care • June 2010
Proliferative retinopathy is a severe microvascular complication in patients with type 1 diabetes. After 20 years of diabetes, almost all patients with type 1 diabetes and 58% of patients with type 2 diabetes show signs of retinopathy. When retinopathy worsens, severe visual loss eventually threatens 5-10% of the patients. The most severe form of retinopathy is proliferative retinopathy, and most of the patients with this complication will become blind after 5-10 years without treatment. The prevalence of retinopathy varies between 13 and 50% after 15-25 years of diabetes in patients who need insulin.
Several risk factors for diabetic retinopathy have already been identified. The prevalence of any retinopathy is strongly related to duration of diabetes and glycemic control. Poor glycemic control increases both the incidence and progression of retinopathy. Male gender and high blood pressure further increase the risk of retinopathy. Genetic factors are likely to play a major role. It is of note that age of onset of diabetes may modify the metabolic phenotype of the patients and thus predispose certain patients to diabetic retinopathy. In particular, diabetes onset at age <5 years may have a protective effect on the development of retinopathy. Thus it can be hypothesized that because of the incidence of diabetes is on the rise and the increase has been the greatest in children aged 0-4 years, there may possibly be a decrease in the risk of overall retinopathy. The studies have thus far not focused upon the onset of type 1 diabetes in adulthood, and therefore the number of patients with late-onset diabetes has been rather small and not large enough to study the effect of late age at onset on the risk of proliferative retinopathy. Furthermore, it is not yet known whether young age at onset is a protective factor in the long term or whether it only delays the onset of proliferative retinopathy. Therefore, the aim of this study was to elucidate how the age of onset of type 1 diabetes influences the long-term risk of proliferative retinopathy in patients with type 1 diabetes.
Objective - Age at onset of type 1 diabetes influences the risk of microvascular complications. However, the long term risk of proliferative retinopathy within the wide spectrum of age of onset of type 1 diabetes is less well known.
Research Design and Methods - A sample of 1,117 consecutively recruited patients were drawn from the FinnDiane Study population. Type 1 diabetes was defined as age at onset <40 years, insulin treatment initiated within one year, and C-peptide <0.3 nmol/l. Retinopathy status was graded based upon ophthalmic records and/or fundus photographs. The risk of proliferative retinopathy was studied in age-at-onset groups 0-4, 5-14 and 15-40.
The present study is a retrospective cohort study, undertaken as a part of the ongoing FinneDiane Study (Finnish Diabetic Nephropathy Study), which has since 1997 collected comprehensive data from patients with type 1 diabetes at 92 centers throughout Finland, including primary care as well as secondary and tertiary care hospitals with the aim at identifying genetic and environmental risk factors for diabetic complications.
Fundus photographs and/or records of fundus examinations performed by an eye specialist were obtained for 1,117 consecutively recruited patients. These patients were required to have onset of diabetes at age of <40 years, C-peptide < 0.3 nmol/l and insulin treatment initiated within one year of diagnosis. The Early Treatment of Diabetic Retinopathy Study (ETDRS) grading scale was used, for which 10 represents no retinopathy, >61 represents proliferative retinopathy and 81-85 represents advanced retinopathy. The eye with the more severe retinopathy was used to represent the overall retinopathy severity for a patient. In this study laser treatment alone was not taken as evidence of proliferative retinopathy because severe nonproliferative retinopathy is also an indication for scatter photocoagulation.
Results - The mean durations to proliferative retinopathy were 24.3 years in the 0-4 years group, 20.1 years in the 5-14 years group and 21.6 years in the 15-40 years group. Ina Cox regression model with A1c, blood pressure, sex and BMI as covarites, the highest risk of proliferative retinopathy was observed in the 5-14 years group. Diabetes onset 0-4 versus 5-14 years made no difference in the long-term risk of proliferative retinopathy. When spilt into two groups, age onset <15 years was associated with a higher long-term risk than at onset > 15 years.
Conclusions - Age at onset significantly modifies the long-term risk of prolifertive retinopathy. The highest risk is in age-at-onset group 5-14 years, whereas the lowest risk is in age-at-onset group 15-40 years.
The study shows that the patients with the youngest age at onset (0-4 years) have the longest mean duration of type 1 diabetes without proliferative retinopathy (24.3%). This finding is in line with earlier findings regarding diabetic retinopathy and nephropathy. However, the long-term risk of all proliferative retinopathy is no different between age-at-onset groups 0-4 and 5-14 years despite the initial advantage for those with earlier onset of diabetes. Ultimately, the survival curves for those two groups cross each other when the duration of diabetes approaches 30 years. The survival curve for those patients with age at onset of type 1 diabetes at 15-40 years appears to be consistently better than that for patients with younger age of onset.
Good self care of diabetes correlates with good metabolic control. It can be hypothesized that it may be easier to learn good self-care skills at a very young age compared with the prepubertal period. Learning good self-care skills may take longer in prepubertal children compared with young children, which would explain the delayed onset of proliferative retinopathy in the youngest patients. In addition to behavioral factors, hormonal changes in puberty may contribute to worse metabolic control. Furthermore, the initial advantage for the younger patients may be due to more stringent management of type 1 diabetes, because this has shown to reduce the decline in insulin production.
Diabetes onset at puberty has been linked to a less aggressive form of type 1 diabetes, and it has been observed that B-cells are better preserved when type 1 diabetes begins in adulthood. Researchers observed a longer time without proliferative retinopathy was well as a lower risk of retinopathy for age-at-onset group 15-40 years. This finding could be explained by preservation of the B-cells as these patients also had the highest C-peptide concentrations. The Diabetes Control and Complications Trial (DCCT) indicated that patients with any residual C-peptide secretion, but especially those with the highest stimulated concentrations, had reduced incidence of retinopathy and nephropathy. The role of C-peptide has been somewhat controversial, because it has not been linked to proliferative retinopathy in other studies. The association of age of onset with the risk of diabetic retinopathy may not be limited to type 1 diabetes. It has recently been noted that a higher age at onset of diabetes reduces the risk of retinopathy in type 2 diabetic patients as well.
In summary, the study shows a longer time free of proliferative retinopathy in the youngest patients. It appears that this initial advantage gradually wears off in the long term. In contrast, those patients with age at onset of type 1 diabetes between 15 and 40 years may have a consistently better prognosis that any patient group with age of onset <15 years.
Reprinted with permission from the American Diabetes Association