Protection from retinopathy and other complications in patients with type 1 diabetes of extreme duration: the joslin 50-year medalist study

Abstract

Objective: To assess complication prevalence and identify protective factors in patients with diabetes duration of ≥50 years. Characterization of a complication-free subgroup in this cohort would suggest that some individuals are protected from diabetes complications and allow identification of endogenous protective factors.

Research design and methods: Cross-sectional, observational study of 351 U.S. residents who have survived with type 1 diabetes for ≥50 years (Medalists). Retinopathy, nephropathy, neuropathy, and cardiovascular disease were assessed in relation to HbA(1c), lipids, and advanced glycation end products (AGEs). Retrospective chart review provided longitudinal ophthalmic data for a subgroup.

Results: A high proportion of Medalists remain free from proliferative diabetic retinopathy (PDR) (42.6%), nephropathy (86.9%), neuropathy (39.4%), or cardiovascular disease (51.5%). Current and longitudinal (the past 15 years) glycemic control were unrelated to complications. Subjects with high plasma carboxyethyl-lysine and pentosidine were 7.2-fold more likely to have any complication. Of Medalists without PDR, 96% with no retinopathy progression over the first 17 years of follow-up did not experience retinopathy worsening thereafter.

Conclusions: The Medalist population is likely enriched for protective factors against complications. These factors might prove useful to the general population with diabetes if they can be used to induce protection against long-term complications. Specific AGE combinations were strongly associated with complications, indicating a link between AGE formation or processing with development of diabetic vasculopathy.

Figure 1

A: Prevalence of micro- and macrovascular diabetes complications in the 50-year Medalist cohort. mod, moderate; microalb, microalbuminuria; NPDR, nonproliferative diabetic retinopathy. B: Bimodal distribution of diabetic retinopathy severity in the Medalist cohort. DR, diabetic retinopathy; HRC, high-risk characteristics; Mod, moderate; NPDR, nonproliferative diabetic retinopathy.

Figure 2

Worsening retinopathy in Medalists who do and do not progress to PDR. DR, diabetic retinopathy; sig, significant. (A high-quality color representation of this figure is available in the online issue.)

Figure 3

A: Relative odds of complications associated with high vs. low CEL and pentosidine levels. Cx, complication; Pent, pentosidine. B: Risk of PDR development by CEL and pentosidine levels. DM, diabetes; Pent, pentosidine. C: Progression to PDR in patients grouped by combined CEL and pentosidine and CML and fructose-lysine biomarker. Fru, fructose; Pent, pentosidine. (A high-quality color representation of this figure is available in the online issue.)

Figure 3

A: Relative odds of complications associated with high vs. low CEL and pentosidine levels. Cx, complication; Pent, pentosidine. B: Risk of PDR development by CEL and pentosidine levels. DM, diabetes; Pent, pentosidine. C: Progression to PDR in patients grouped by combined CEL and pentosidine and CML and fructose-lysine biomarker. Fru, fructose; Pent, pentosidine. (A high-quality color representation of this figure is available in the online issue.)