I've lived with type 1 diabetes for 41 years and without complications. Probably the one thing I do have is Diabetic Mastopathy, but it's not a major complication that threatens the rest of my life. I have known other people who have lived by the diabetes book and still developed diabetes complications such as retinopathy, neuropathy, nephropathy.
Recently, an article caught my eye that mentioned new research, out of Joslin Diabetes Center, on why some people seem to be shielded from diabetes complications. In a study of 351 people living type 1 diabetes for 50 years, nearly 43% remained free of diabetes retinopathy, 87% never developed kidney disease, nearly 40% were free of nerve damage or neuropathy and 51% showed no cardiovascular disease.
What makes some people immune from the complications? Dr. George King, Chief Science Officer at Joslin Diabetes Center, basically says they don't know exactly why, but they are looking into why some of us seem to have endogenous protective factors. What is clear is that most of these people manage their diabetes pretty well and clearly better control is part of the recipe for success. Even more striking was the average A1c of the group: 7.7! Most of these people had diabetes well before blood glucose meters, advanced insulin and pump technology and even management for tight control, yet they have little resulting negative consequences.
What was assessed from the data so far is that in relation to HbA1c, lipids, and advanced glycation end products (AGEs), AGEs seem to be a culprit in developing complications. This information is not new, but what is new is the reported low levels of AGEs within this group.
The definition of AGEs is this: Advanced Glycation End Products are the result of a chain of chemical reactions after an initial glycation reaction. AGEs may be formed external to the body by heating (an examples would be cooked food), or they can be formed internally through metabolism and aging. Under certain pathogenic conditions, like oxidative stress due to high blood sugar, AGE formation can be increased beyond normal levels.
AGEs have been attributed to in the progression of age related diseases because they act as photosensitizers implicating AGEs responsibility for cateract development. AGEs has been implicated in Alzhiemer's disease, cardiovascular disease and stroke.
In diabetes, hyperglycemia results in higher cellular glucose levels and those cells are unable to reduce the glucose levels. In turn, this results in increased levels of coenzymes NADH and FADH, increasing the proton gradient beyond a particular threshold at which the coenyme Q, also known as complex III, prevents further increase by stopping the electron transport chain. This results in mitochrondial production of reactive oxygen species, activating PARP1 by damaging DNA. PARP1 activates another protein involved in glucose metabolism, leading to its activation and accumulation of byproducts called metabolites. These metabolites activate the production of high levels of AGEs. (Talk about a chain reaction! And, wiki rocks!)
