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January 28, 2007


Question from Winnipeg, Manitoba, Canada:

I would like to know: If I do not have any complications after 23 years of type 1 and moderately good control, is there a very good chance that I have genetic protection and will NEVER develop them to any appreciable extent? Is it true that damage from hyperglycemia does not accumulate or contribute to complications prior to puberty? What evidence supports/rejects this theory? Should I still think that I am not over the "hump"? I was diagnosed at age two and am now 25. Do people with multiple autoimmunities (I also have Celiac, Hashimoto's, and possibly Addison's, although all tests have been negative so far despite symptoms) tend to have a overall lower incidence of complications? What studies indicate/disprove this? How many people with autoimmune type 1 diabetes still make their own insulin? I suspect that I do from time to time (I am VERY insulin sensitive, labile, and have periods of intense unexplained lows in which I need to drink Coke constantly to maintain a normal blood sugar, until all of the basal insulin has cleared out of my system (I have to turn off the pump). I am also able to eat without needing any, or very little, insulin. Could this contribute to fewer complications due to a positive C-Peptide level, which has been linked to less nephropathy and neuropathy? As I am finding it more and more difficult to control my blood sugars without severe lows (A1c used to be around 7, is now 7.5), how long can I go running higher without developing complications? I feel much better running a little high at 10 mmol/L [180 mg/dl] to 11 mmol/l [198 mg/dl], than bouncing all over trying to maintain tight control. What trials are available to me if I am not newly diagnosed, but still make my own insulin? I would like to stop the autoimmunity (bone marrow transplant, immune modulation/blocking, etc.) and see if I can regenerate any remaining cells via current experimental drugs. How can I get convince my endocrinologist to test my C-Peptide and, if positive, to work with me?


Neuropathy is probably the hardest to prevent. There is evidence you can still develop neuropathy after years without it and it still relates to blood sugar control. The big win is in the area of kidney disease. If you do not have kidney involvement after 15 years of diabetes, it is less likely. It is also true that the clock on complications does not really begin until puberty begins. It is not understood why that is the case. Genetic protection has something to do with it, however, it is not known what that protection is. Retinopathy does occur over time and still requires annual evaluations. This information does not mean you can let your guard down and not worry. It also gives you some good news.

I do not think there is good information about that. Multiple endocrine deficiency syndromes suggest multiple targets, but I am not aware that there is a major impact on the course of diabetes.

Some of the work that has come out of the DCCT in the 1990s does show that some people retain their ability to make some insulin. If so, this also suggests that these patients do better with lower A1c levels. How to preserve beta cell function is not clear. The best way to tell if you retain the function of making insulin is to have a stimulation test with I.V. glucose or oral glucose or oral test meal and measure C-Peptide in response to the challenge. You may not need as much insulin if you have insulin antibodies that bind up a significant amount of insulin and then release it occasionally. It is just another explanation for what you describe.

Hypoglycemia is the most limiting factor in the treatment of type 1 diabetes. Running 10 mmol/L [180 mg/dl] to 11 mmol/? [198 mg/dl] is fairly high. It suggests that you are used to running high and when your sugars are lowered into the normal range, your body protests with signals that suggest you are too low because you have acquired a new set point for your blood sugars. This does not protect you from the end-organ complications of diabetes. In addition, too many lows puts you at risk for hypoglycemia unawareness. This means that your insulin therapy needs to be discussed with your physician. You have to have a plan for the gradual lowering of blood sugars without developing severe hypoglycemia, a difficult challenge.

I am not aware of any trials that are testing this particular questions in someone with diabetes for a long time. There are trials looking at this question in newly diagnosed patients with type 1 diabetes. There are web sites for diabetes-related research at the National Institute of diabetes & Digestive & Kidney Diseases and other research institutions. You may also want to contact the JDRF and ADA for a list of funded studies in which you could participate.