An important one is how little we know about (all varieties) diabetes mellitus. We (research scientists) are constantly discovering new antibodies associated with T1, new metabolic mechanisms affecting different varieties of diabetes, etc.
“Type 1 (including LADA and other adult onset) diabetes mellitus” is still a medical description of symptoms and clinical signs (as are most diseases, but that’s a different discussion), and from a biological perspective almost certainly involves several (to many) different disease causes, progressions, and even outcomes. How do we know this? Because of all the different antibodies that have been discovered to date associated with T1, and because of the existence of “Type 1b” (also called “idiopathic T1”) diabetics, who test positive for no known antibodies and yet have all the clinical signs and symptoms of Type 1.
To a certain way of thinking, if someone doesn’t have DKA and is not positive for anti-GAD65, then they are not Type 1. This is, of course, ridiculous, and yet that is what my doctor told me five years ago. “You cannot be Type 1, you are too old and don’t have anti-GAD. Therefore, you are Type 2.” I fired that doctor, but it isn’t uncommon for GPs and PCPs to use this line of reasoning.
Type 1, Type 2, MODY, Type 3, etc. are all just labels for constellations of symptoms and test results (including antibody tests), and the underlying causation is not known. Some people with extraordinarily high serum anti-GAD65 (and 67) antibodies develop other autoimmune disorders (like mine, Stiff Person Syndrome) but never develop diabetes. So, high levels of anti-GAD do not cause Type 1 diabetes. Presence of testable antibodies are one of the tools used to diagnose Type 1 diabetes, but they are primarily used clinically to confirm diagnosis based on clinical signs or to differentiate “LADA” from “Type 2s” when oral meds don’t work the way a GP expected them to.
Sorry, don’t have time this morning for sources and further thoughts. I’ve written about these topics (from both a research scientist’s and diabetic’s perspective) before here, and I certainly have plenty of thoughts on the topic. Most of the thoughts come down to something very, very simple: we just don’t understand the diseases of diabetes mellitus very well, so for scientists and doctors, we can only do the best we can. Which sometimes (say, pre-1920s) wasn’t very well at all. And sometimes, today, it still isn’t very well at all.