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November 26, 2000

Honeymoon, Insulin

Question from New York, New York, USA:

I'm a 43 year old male, diagnosed five months ago with a blood glucose of 439 mg/dl [24.4 mmol/L] and an A1c of 9.2%. My father also developed type�1 in his mid-40s and has been taking insulin for 24 years. I was on Glucophage [metformin] for three weeks, then stopped it for control with diet and exercise. This summer, I had normal blood sugar levels in morning, low-normal insulin production at one hour post prandial, an A1c of 6.2%, and a C-peptide of 2.6. I was negative for islet cell antibodies. In early fall, I was positive for islet-cell antibodies and 57.6 on anti-GAD test. My doctor has recommended insulin in order to prolong pancreatic function. As there's so much ambiguity about why and how insulin at this stage may accomplish prolongation of function, he's not certain of what dose I should be on. I am now taking 5 units of Ultralente in evening. My fasting blood glucose readings have been in the normal to high normal range, and, although it's hard to say for sure, they be creeping up. Control after meals remains largely the same as during summer. What about this idea of prolonging function with insulin? Any published or clinical evidence to consider? What insulin program do you recommend? Larger dosage Ultralente? Should I also be taking fast-acting insulin to control post-prandial peaking? (My lifestyle is highly irregular and fast-paced. Mealtimes, exercise and physical challenges will not be predictable.) Should I do an intravenous glucose test to quantify remaining pancreatic function? As I understand it, even if I had a value to assign to remaining function, it wouldn't necessarily help predict what's going to happen to remaining function. Is there any implication it might have for treatment? Are there any other strategies currently available or soon-to-be available for arresting the autoimmune attack on the pancreas? I assume I don't have a long time to do something to protect the function I've got left.

Answer:

As you must already know, the onset of autoimmune diabetes is most common in childhood and in the teen years. but it has been reported as late as the sixth decade. In older age groups it has come to be known as Late-onset Autoimmune Diabetes of Adulthood (LADA), but in what way this might have a distinct immunological mechanism from type�1A (autoimmune) is not yet understood. I think that both you and your father have this condition. In your case, it is certainly reasonable to try to find out if insulin dependence can be or should be deferred.

Very little work has been done on this, but the analogy with type 1A can be used as a guide to the possibilities. In children, there is a national trial (DPT-1 ) of subcutaneous and oral insulin, and it is not yet known whether it is going to be effective despite the optimism in preliminary studies.You might ask your doctor whether antibody studies were done. If only one of these was positive, besides the older, less reliable immunofluorescent method, it might be worth just marking time. If all three were positive, it would be worth exploring what might be done despite your erratic lifestyle. At any rate, your doctor was quite right to suggest it. As another preliminary test an intravenous glucose tolerance test with one- and three-minute insulin levels would give you an idea as to what insulin reserves remained.

The next possibility would be nicotinamide in a dose of 25 mg/kilogram of body weight/day. I am sorry that I can’t find the reference that suggested its value in LADA, although there is an old and somewhat relevant one by Picq in Diabetalogia 32:316,1989. Inhaled insulin is another possibility, but I know of no trial in your age group.

Finally a commercial firm called Peptor is starting a trial specifically in subjects with LADA of a vaccine called DiaPep277. You might consider contacting them to see if you could participate.

DOB