Some Type 1 Diabetics Seem Shielded Against Complications
TUESDAY March 29, 2011 -- While complications from type 1 diabetes are common, they aren't inevitable. New research suggests that some people with the disease apparently have an inherent protection against serious complications, such as eye, kidney and heart disease.
In a group of people who'd had type 1 diabetes for more than 50 years, nearly 43 percent remained free of serious eye disease, while about 87 percent never developed kidney disease, nearly 40 percent were free of nerve damage and more than 50 percent were free of cardiovascular disease, according to the study.
"We have identified a group of people who can clearly live well with diabetes for a long time," said the study's senior author, Dr. George King, chief scientific officer at the Joslin Diabetes Center in Boston. "Now, we're in the process of finding out why. In the meantime, if you have type 1 diabetes, try to control your disease. The reason that most of them eluded the problem of complications is that they manage their disease pretty well," said King.
But, this study found that even in this group of people who -- on average -- maintained good blood sugar control, some developed complications, while others appeared to have some sort of protection against them.
Results of the study are published in the April issue of Diabetes Care.
Almost 26 million Americans have diabetes, according to the U.S. Centers for Disease Control and Prevention (CDC). About 5 percent of those have type 1 diabetes, the CDC estimates. Type 1 diabetes is an autoimmune disease in which the body's immune system mistakenly attacks the insulin-producing cells in the pancreas. Insulin is a hormone that's necessary for the body and brain to be able to use the sugars found in carbohydrates as fuel. People with type 1 diabetes must take replacement insulin, through injections or an insulin pump, all of their lives.
Without insulin, or without enough insulin, the body can't use blood sugar for fuel, and the sugar builds up in the bloodstream. Long-term high blood sugar levels can cause a number of serious problems, including diabetic retinopathy in the eyes, kidney damage and possibly failure, nerve problems and heart disease.
Previous research has shown that good control of blood sugar levels can help prevent these complications. But, it's difficult to keep blood sugar levels low without going too low (hypoglycemia), a potentially dangerous condition itself.
For the current study, the researchers assessed complications in a group of 351 people with long-standing type 1 diabetes. These people were part of a group known as the diabetes "medalists." They've lived for more than 50 years with type 1 diabetes, and were initially diagnosed at a time when good blood sugar control wasn't really possible because blood glucose meters and other technologies that help people live with diabetes today just weren't available then.
The average A1C level in this group was 7.7 percent. A1C is a measure of blood sugar control over several months. People without diabetes have levels under 6 percent.
Overall, King said, about 35 percent of the medalists didn't develop any serious problems related to their diabetes. "There's something in those 35 percent that protects them from diabetic eye, kidney, nerve and heart disease," said King.
And exactly what that protective mechanism might be isn't yet known. It's hard to create a control group for comparison to the unusual group of diabetes survivors, the study noted. In addition, the protective mechanism may be different for microvascular complications (such as kidney and eye disease) and macrovascular complications (such as heart disease), according to background material accompanying the study.
One potential reason is suggested by a certain combination of substances called advanced glycation end products (AGEs), which the study found were 7.2 times more common in people with complications. AGEs develop in the body after long-term exposure to high blood sugar levels.
This particular combination of AGEs (high plasma carboxyethyl-lysine and pentosidine) was linked to complications, but other AGE molecules appeared to have a protective effect -- an exciting finding the researchers said may lead to new biomarkers for protection against complications.
And there may be other ways to keep the problematic AGEs under control.
The author of an accompanying editorial, Dr. Aaron Vinik, noted that a receptor for AGE called sRAGE is lacking in people with complications. "When you have diabetes early on, you have about a 50 percent reduction in sRAGE. People who develop serious complications have an 85 percent reduction in sRAGE. So, the best predictor of longevity and freedom from complications may be a good sRAGE mechanism," explained Vinik, who is the director of the Eastern Virginia Medical School Strelitz Diabetes Center in Norfolk, Va.
Vinick also pointed out that many of the drugs that are commonly prescribed today to help people with diabetes live longer and better lives -- such as ACE inhibitors to control their blood pressure and statins to control their cholesterol levels -- raise sRAGE levels.
Both King and Vinik said that once researchers figure out exactly which substances are at play in those who are protected from diabetes complications, the findings could lead to ways to screen for those most at risk of complications, and potentially to a treatment that could help prevent complications.
King said that while the researchers figure out how to better protect people with diabetes from complications, good blood sugar control remains the cornerstone of diabetes management. He added that the medalists as a group tended to be very proactive and involved in their diabetes care.
"In general, the medalists control their disease rather than letting the disease affect their life patterns. This is a group of patients that manages things rather than let things manage them," said King.
Learn more about type 1 diabetes and how to manage it from the U.S. National Library of Medicine.
Posted: March 2011
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