My first post here, so please forgive if I am breaking some etiquette here. My immediate question is: what should I try next?
Here’s some background information:
35 y.o. male, physically active, Height: 5’ 9.5", Weight: 143, BMI: 20.5
HbA1C: 6.1, has jumped around between 5.7 and 6.1 for the last 3 years. Official diagnosis is preD, obviously, but I agree with some posters here that the distinction between preD and frankD seems quite arbitrary.
Morning BG: almost always between 80 and 100.
2 hr pc bg: between 130 and 140 unless very precise about my meal.
Everything in my comprehensive metabolic and lipid panel was in the normal range, except for fasting insulin:
Insulin is 1.6, low, where the normal range is 2.0 - 19.6 uIU/mL. As an aside, C-Peptide came out as 0.91 for a normal range of 0.80 - 3.85 ng/mL, so within range, but on the very low side.
Significant history of diabetes in the family. At 40, grandma was diagnosed with full-blown insulin-dependent D, which means that she’s been preD for many years before, so similar to where I am now. She had many brothers; many of them ended up blind and without legs; everyone was by and large lean, and most diabetes diagnoses rolled in around 40, so even though I am at 6.1 right now, scary things are around the corner if I am not proactive.
Now, I’ve been reading around, and thin + around 40 + low morning insulin starts looking like LADA for a lot of posters here, so I requested the AB panels from my endo. He’s cooperative, so I got them. I got three tests: GAD65, “ISLET CELL ANTIBODY” and “INSULIN AUTOANTIBODY”. They all came out negative.
As another aside: I am writing them out instead of using the abbreviations because I am confused about the many abbreviations - they look a lot like each other. For example, I would’ve thought that “ISLET CELL ANTIBODY” is “ICA”, but for some reason the lab (Quest) encoded it as “IA-2”, which I thought stood for “insulinoma-associated (IA-2) autoantibodies” (from https://en.wikipedia.org/wiki/Latent_autoimmune_diabetes_of_adults#Autoantibody_panel ). Anyway, I am trying to figure out the precise details of the antibody encodings with my endo.
I bought the 23andMe test back when they were offering the Health Risks service, and for many D genes, I have the genotype that is associated with higher incidence. The three with the highest contribution seem to be: TCF7L2 Genotype CT, CDKAL1 Genotype GG, HHEX Genotype CC. These are associated with “impaired baseline insulin secretion”, “impaired first-phase insulin secretion”, and “decreased beta cell glucose sensitivity and 30-minute insulin response” (just copying this text from 23andMe)
Anecdotally: when I was a child I was always very thin, and have always had problems putting on muscle mass and keeping it. I now wonder whether this is because my insulin response was always under-performing.
With all that background information:
My endo suggested that besides the standard lifestyle modifications, he would suggest that I start taking the smallest nateglinide (Starlix) dose when I eat, to make the pancreas work harder during meals.
On the one hand, seems like reasonable advice: there’s lab and historical evidence that my beta cells are lazy overnight (low morning insuling/C-peptide, chronic thinness), which is evidence that they wouldn’t spike to necessary levels during meals, as evidenced by my 130-140 2 hr pc tests, so let’s force them to work harder during meals.
On the other hand, though I don’t have an antibodies for LADA, I am concerned about that, for example, we didn’t do the ZNT8 test, and also, it seems possible that in early stages these antibodies don’t get detected. I am aware that those with LADA who take medications that force beta cells to work harder progress towards insulin-dependency faster. In the paper that I am reading this has only been verified for sulfonylureas, which stimulates basal insulin only, but, though I haven’t been able to find a paper that discusses this, it seems reasonable to think that this would be the same for other mechanisms that stimulate beta cells as well. In this case, it seems that going straight to insulin seems to preserve beta cell mass.
So… Starlix? Fast-acting insulin only? Is that even possible? Something else? Are there any recent papers are there that discuss diabetes in lean individuals that test negative for antibodies?