Some people with diabetes type 1 spend fifty or more years with the condition and have no complications at all, while others develop proliferative diabetic retinopathy, nephropathy (kidney damage), neuropathy (nerve damage) or cardiovascular disease. Researchers from the Joslin Diabetes Center wrote in the journal Diabetes Care that some diabetes type 1 patients possess certain factors, not yet identified fully, that considerably lower their risk of developing complications, and sometimes prevent them from ever occurring.

The researchers believe that some patients with diabetes type 1 have a protective mechanism that lets them live their lives free of the complications generally associated with diabetes. The mechanisms are not the same for microvascular and macrovascular complications.

Microvascular, in simple terms refers to the tiny blood vessels, while macrovascular refers to the larger ones. Examples of microvascular complications include nerve, eye or kidney damage, while heart disease is an example of a macrovascular complication.

Lead researcher, Professor George King, said:

“If we can identify what constitutes this protective mechanism, we have the potential to induce such protections in others living with diabetes. That’s huge.”

They assessed the long-term health of 351 American citizens they termed the Medalist cohort and found that some of them had lived complication-free with diabetes type 1 for over 50 years.

Below is a percentage of diabetes 1 patients who lived free of typical complications for over 50 years:

  • Proliferative diabetic retinopathy (PDR) – 42.6%.
    96% of those who did not develop PDR had no retinopathy progression in the first 17 years of their diabetes and no worsening of symptoms. The researchers believe they carry some kind of specific protection.
  • Kidney damage (nephropathy) – 86.9%
  • Nerve damage (neuropathy) – 39.4%
  • Cardiovascular disease – 51.5%

They were also surprised to find that glycemic control was not linked to this protective mechanism.

King said:

“That doesn’t mean of course that glycemic control doesn’t help to prevent complications. Numerous other studies have shown that it unquestionably does. In this case, it means only that there is a separate, protective mechanism in play that is not related to glycemic control that also helps to protect against diabetes-related problems. We are still working on identifying just what that is.”

The authors add that most of the people they studied had developed diabetes type 1 well before strict glycemic control was ever possible, or used in standard medical care. These individuals lived complication-free a good number of decades without strict glycemic control.

An individual with high plasma carboxyethyl-lysine and pentosidine, or advanced glycation end products (AGEs) was much more likely to experience complications – 7.2 times more likely – compared to those with low levels.

After long exposure to high glucose levels, levels of AGEs go up. AGEs have long been linked to complications related to diabetes.

The researchers found, though, that individuals with other types of AGE molecules had significantly lower risks of complications, suggesting that not all AGEs are harmful, some are in fact protective.

Dr. Aaron Vinik, Eastern Virginia Medical School Diabetes Research Center, wrote:

“The accumulation of AGEs may be one of the important factors in metabolic memory,” a phenomenon in which an initial period of good glycemic, lipid and blood pressure control results in a prolonged period of health benefits that last beyond the period of control.

We are sure some kind of protective mechanism is at play. We do not know whether metabolic memory is an important factor. Glycemic control was not seen as important until 1993, a long-time after the start of the study.

Among those with the most severe complications, levels of the circulating soluble receptor for AGEs – sRAGE – are low, while they are high among those who live the longest.

Vinik added:

“If this is the missing link, it is huge for the possible emergence of a new biomarker and the potential for therapy that might increase circulating sRAGE or sRAGE itself.”

“Protection From Retinopathy and Other Complications in Patients With Type 1 Diabetes of Extreme Duration – The Joslin 50-Year Medalist Study”
Jennifer K. Sun, MD, MPH, Hillary A. Keenan, PHD, Jerry D. Cavallerano, OD, PHD, Bela F. Asztalos, PHD, Ernst J. Schaefer, MD, David R. Sell, PHD, Christopher M. Strauch, BSC, Vincent M. Monnier, MD, Alessandro Doria, MD, PHD, MPH, Lloyd Paul Aiello, MD, PHD and George L. King, MD
Diabetes Care. March 29, 2011 vol. 34 no. 4 968-974
doi: 10.2337/dc10-1675

Written by Christian Nordqvist