November 16, 2009
Insulin, LADA and MODY
Question from Salt Lake City, Utah, USA:
I was diagnosed with type 2 diabetes a little over two years ago at age 43. It was a surprise, as I am lean, active, eat a healthy diet, and have no family history. I was tested for autoantibodies at that time (including GAD and IA2) and all were negative. Until recently, my A1c has been stable in the 5.5 to 5.8 range on 500 mg of metformin daily. A few months ago, my A1c went up to 6.9. My doctor had me double my metformin dose to 500 mg twice a day. I also increased the protein/carbohydrate proportion of my diet to lower my overall carbohydrate intake. The A1c dropped to 6.4, which is not bad, but it was deemed a rather sluggish response to the changes. The doctor, collaborating with a pharmD diabetes educator, is repeating autoantibody testing, suspecting this may actually be LADA, and that I should switch to insulin. Pending test results, I am switching to the timed release formulation of metformin. If autoantibodies come back positive, I assume they are right, but if tests are still negative, should I consider staying on metformin until my blood glucose is “unacceptable,” or add another medication? Instead, would insulin be a valid consideration at this point if GAD, etc. are negative? I’d really rather not, unless it’s clearly the best thing to do.
This is a common question. The more closely we look at newly diagnosed patients, the more often we see patients who do not follow the usual patterns for either type 1 or type 2 diabetes. The antibodies are helpful if they are positive. If they are negative, it is unlikely they will become positive. You can still have late-onset type 1 diabetes without positive antibodies. The anti-GAD antibody is the test I usually order because it stays up positive the longest. The other antibodies can be high and then go down quickly and stay down. The question always comes up as to whether a patient would be better off being treated with insulin if they have LADA, even though their blood sugars are relatively well controlled. I do not believe there is any clinical study to support that. If HbA1c values start to rise above 6.5%, I would be trying to increase the metformin with the goal of values below that. At some point, if blood sugars rise and you are at the point of eating cardboard for food, you have to say this doesn’t work and potentially consider insulin. My mindset on this topic is that LADA patients may be slower to develop their insulin dependence, but when it develops, it can happen fast. If the metformin adjustment works, that is good and no rush to insulin.