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J. K. Sun, H. A. Keenan, J. D. Cavallerano, A. Doria, G. S. Eisenbarth, L. P. Aiello, G. L. King; Unique Risk Factor Profile for Retinopathy Progression in Patients With 50 Years or More of Type 1 Diabetes Mellitus. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1164.
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© ARVO (1962-2015); The Authors (2016-present)
To identify risk profile differences in patients with 50 or more years of type 1 diabetes (Medalists) with and without advanced diabetic retinopathy (DR).
ETDRS-protocol VA testing and fundus photography, evaluation for neuropathy, genotyping for HLA risk alleles, and measurement of HbA1c, lipids, islet cell antibodies, c-peptide, and urinary albumin were performed. Photos were graded by two masked readers and discrepancies adjudicated by a third. Longitudinal data on DR and HbA1c were also collected for subjects followed at Joslin Diabetes Center.
In 266 Medalists with mean DM duration 56 yrs (range: 50-80), there was a bimodal pattern of DR severity in the more advanced eye: 42% no-mild nonproliferative DR (NPDR), 7% moderate-severe NPDR, and 49% proliferative DR (PDR). Unreadable photos OU occurred in 2%. DR severity was not related to recent HbA1c or c-peptide status. More severe DR was independently related to the presence of neuropathy (p < 0.001), nephropathy (p = 0.044), and younger age at DM diagnosis (p = 0.004). DR severity was not associated with DM duration, hypertension, lipid levels, autoantibodies, or HLA risk alleles. Longitudinal data was available for 35 subjects with 58 yrs (51-69) mean duration of DM and 24 yrs (1-46) mean duration of follow-up. A bimodal DR profile was also evident in this group: 43% no-mild NPDR, 6% moderate-severe NPDR, and 51% PDR. Mean time to PDR development was 36 years (median: 32, range: 18-63). HbA1c levels over the last 7 years (N=27) were not related to progression to PDR. Medalists with nephropathy had 6 times higher risk of PDR than patients without (HR 5.9; 95% CL: 1.2, 15.3; p = 0.003). There was no relationship between time to development of PDR and age at diagnosis, c-peptide, neuropathy, lipids, BMI, HLA risk alleles, or autoantibodies.
Data from Medalists who do not develop advanced DR suggest that this unique subset have a risk factor profile different from those with advanced DR and different from risks classically associated with shorter duration disease. Longitudinal data reveal that progression to PDR and nephropathy are associated, but surprisingly, such progression does not appear related to recent glycemic control or residual islet cell function. Thus, it is possible that factors exist that independently or collectively provide long-term protection against development of DR and nephropathy in some patients with DM.
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