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Long-Time Diabetics May Show Ways to Prevent Complications


Diabetes has a way of wreaking havoc on the body's eyes, cardiovascular system, kidneys and nerves over time, but a major study by Joslin Diabetes Center researchers has found that some long-time diabetics exhibit remarkably few complications —a discovery that points toward the presence of protective factors that guard against the disease's effects.

George King, M.D., Joslin's chief scientific officer and head of the Dianne Nunnally Hoppes laboratory, and colleagues conducted a cross-sectional, observational study of 351 participants in the Joslin 50-Year Medalist study. These participants are all people who have lived with type 1 diabetes for 50 years or more.

Retinopathy, nephropathy, neuropathy, and cardiovascular disease were assessed in relation to HbA1c, lipids, and advanced glycation end products (AGEs). Retrospective chart review provided longitudinal ophthalmic data for a subgroup.

Among these Medalists, 43% are free from advanced diabetic eye complications (proliferative diabetic retinopathy), 87% from kidney disease, 39% from nerve disease and 52% from cardiovascular disease.

The surprising numbers of Medalists without complications "are strong evidence that protective molecular, physiologic or genetic mechanisms, in these fortunate individuals, fight against the toxic effects of high blood sugars over many decades," says Jennifer Sun, M.D., first author on the paper published in Diabetes Care.

As a group, the Joslin Medalists are very careful about controlling their blood glucose levels. However, within a reasonable range of glucose control, the study found current and longitudinal (the past 15 years) glycemic control were unrelated to complications. This conclusion differs from results shown in every other major recent study of diabetes management.

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The researchers feel clues to this protection may be found in analyses of a family of proteins called advanced glycation end products (AGEs), which are increased by high blood sugar levels. In the study, subjects who exhibited two specific AGEs (high plasma carboxyethyl-lysine and pentosidine) were 7.2 times more likely to have any complication.

Additionally, the researchers found a group of Medalists, followed at Joslin's Beetham Eye Institute, whose diabetic eye complications stabilized after 17 years at a mild stage rather than continuing to worsen as expected. This finding again indicated that protective factors are present in this group.

The Joslin Medalist study has gathered data on more than 600 people and is running a broad series of investigations into what guards so many of them from complications.

Moreover, these diabetes veterans can provide other important lessons, as Dr. Sun points out.

"Insights from the Medalist Study are great motivators for patients who have just been diagnosed with diabetes or are early in the disease, particularly younger kids and adolescents," she says. "We can tell these patients that we encourage them to control their blood sugars and get their recommended diabetes care, because they can live many decades with excellent vision and the chance to avoid other severe complications."

Joslin Diabetes Center

Protection From Retinopathy and Other Complications in Patients With Type 1 Diabetes of Extreme Duration: The Joslin 50-Year Medalist Study; Sun JK, Keenan HA, Cavallerano JD, Asztalos BF, Schaefer EJ, Sell DR, Strauch CM, Moonier VM, Doria A, Aiello LP, King GL; Diabetes Care March 29, 2011 vol. 34 no. 4 968-974; doi: 10.2337/dc10-1675