Lean, HBA1C 6.1, no antibodies, low morning insulin/C-Peptide. Now what?

Hi everyone,

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 Latent autoimmune diabetes in adults - Wikipedia ). 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?

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Hi. In my opinion I’d push for low dose insulin (small dose of fast acting before meals). You could still be lada, even without the obvious antibodies. I am against any drugs that push the pancreas to work harder.

You could probably try metformin (Just to see if it makes any difference- - likely it would not).

I would recommend that you continue to work with your doctor to find out more about your abnormal glucose regulation. You might talk with your doctor about things like MODY. I would recommend that you be prudent and conservative before leaping to something like insulin. I agree with @JustLookin that something like metformin would be a good first drug to try that is both safe of often very effective.

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Could you explore further why metformin could be a good choice? We briefly discussed it with my dr, and we came to the conclusion that it wouldn’t be, for the following reasons:

Metformin has three actions: appetite suppression, decreased gluconeogenesis, and increased insulin sensitivity in peripheral tissues.

I don’t need increased insulin sensitivity as insulin resistance doesn’t seem to be an issue.

I am trying to maintain strength and muscle mass, and I don’t want to lose any weight, so appetite suppression is actually not something that I want to experience.

Gluconeogenesis might be the only thing that is helpful is it would also decrease the work that the beta cells are doing across 24 hours; one out of three, however, doesn’t seem like enough of a benefit.

Metformin seems to have a broad range of effects from what I’ve read. I would want to try it as it is a ‘safe’ first line drug. If it works, super! If it does nothing, it would further advance the theory that you could be mody or lada, even antibody negative.

I did try metformin first back in the day and could not see any impact on blood sugar. That cemented my decision to use insulin and not bother with oral meds.

Just because it has a “broad range of effects from what I’ve read” doesn’t mean it should be °1 choice for @YN1. Metformin is introduced to patients who develop signs of T2 as a first drug. But with YN knowing so much about his insulin production already, it doesn’t seem very helpful for him. I don’t know starlix, but it doesn’t seem like the stupidest idea. If insulin levels are low, they should be brought up, and increasing peripheral insulin sensitivity (one of the broad range of effects of metformin) would not really help there IMO.
If the pancreas is attacked though (LADA), I agree that insulin must be introduced as fast as possible.
What I would do here is continue the great lifestyle YN is already living, with starlix and monitor Cpep regularly to notice any further decrease in insulin production right away.
discovering other possibilities as MODY seems a good idea as well.
If you start experiencing symptoms of DKA (diabetic ketoacidosis) head to a doctor straight away. DKA is not to be joked with.

Abnormal blood sugars can be caused by lots of problems. There is one model that has eight defects in type 2 alone with each of the defects potentially having a different treatment. And beyond that you could have thyroid problems or MODY or something else. And you say your blood sugar readings from your meter are all in normal range. You don’t even know when (if ever) your blood sugar is going high. Your A1c may in fact not be right due to inaccuracies.

I’m just urging you to work with your doctor to find out what is wrong. You usually don’t get diagnosed with T1/LADA until you have antibodies and a low c-peptide. There isn’t some pre-T1. Your c-peptide test suggest you don’t have insulin deficiency at this time, so I wouldn’t just leap to insulin. Ask your doctor whether he thinks you would be helped by metformin. You have made medical conclusions that you don’t have insulin resistance or have an overactive liver, but something is going on. Ask their opinion and advice. Get your moneys worth.

Another idea: your A1c could also be elevated due to higher glycolyzation rates in your body. which would mean that your body just glycolyzates sugar faster than other people, and your blood sugar is actually perfectly fine. not very likely due to high t2 prevalence in your family (which would make a diabetes dx more logical) but is worth looking into.

I should’ve mentioned that TSH was tested as well, and it came out a 1.37 in the range of 0.4 - 4.5.

Thanks for the link regarding A1C inaccuracies. I am indeed of Mediterranean descent, and maybe I have a hemoglobin variant, and maybe the lab used a mechanism that is sensitive to the variant. Will inquire.


Regarding my BG readings from the meter: I’ve gotten 2 hr pc results at 140, which according to my endo is high; according to what I’ve read, the tight BG control is within the 80 - 120 range.

If your TSH is elevated, you have hypothyroidism.

No, TSH is fine: 0.4 < 1.37 < 4.5

Do you have any references for this? What kind of test could figure this out?

My bad!!! I misread your result. Sorry! :astonished:

The ADAG study had patients wear CGM devices and compared their blood sugars to their A1c. That is the basis for the most current relationship between A1c and average blood sugars. But if you look at the graph of the results from the ADAG study, patients were actually all over the map, some had much higher or lower A1cs than would be expected.

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yup, the only thing i could think of would be wearing a CGM for a week and look at your average glucose. seems a bit of a lot of effort though (also financially).

I reckon this boils down to your treatment targets and satisfaction with where you are now. Are you happy with hba1c of 6.1?

Given your family history and the described outcomes. Personally i would be wanting to manage this aggressively. More than likely you will need insulin sooner or later. An a1c in the low 5s ( close to normal) would likely be achievable with low dose insulin though obviously no longer without.

The next step and how aggressive you want to be is probably up to you.

Would love to get my A1C into the low 5s range. Aside from the health benefits which are super-important, life insurance rates are better when you demonstrate low A1C numbers even w. a D diagnosis, and I do have a family.

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If it’s LADA (late-onset Type 1 in adults), pre-D is not a given. My Type 1, developed at 43, started in May of 2009. There was no pre involved at all-with one caveat. I had a one-time, non-repeatable (at the time) A1C of 6.8% a year before my diagnosis (which I was not informed of at the time). But if it’s Type 1 (which it is), what can I do to stop it? Nothing.

If it is indeed Type 1 (or LADA, whatever), you could just be on an extended honeymoon. But I think the most important thing to do is not worry about what it is as much as what you need to do.

Whether Type 1 or Type 2, finding the right amount to eat and to exercise is important. Learning to count carbs. Testing your blood glucose to keep an eye on what’s going on. All of these things will help you now and prepare you for possible changes.

I was diagnosed as a diabetic, not Type 1 or Type 2. But after 18 months, using just basal insulin and oral meds was not working. Would it have been nice to know from the beginning that I was Type 1? Yes. But while it lasted, I could treat it with Lantus and metformin.

Don’t expect to know or understand everything. Learn to deal with what’s in front of you and learn to recognize when it’s not working. Then talk to your medical team to get your treatment adjusted. Your medical team will know that you have been vigilant in your attention to what’s going on and will have no problem advocating for you should your symptoms change.

Pre-Type 1 diabetes is a real thing! Now, YN1, that may not be your situation, but pre-Type 1 is real and is well documented in the Type 1 scientific literature. There is a time period in autoimmune diabetes when the autoimmune attack has begun, but the person has not yet crossed over into overt diabetes.


Thank you everyone for chiming in. I have some updates: without even checking for whether or not I have a deficiency, my endo recommended that start taking Vit. D supplements. When I asked him “do you think I am deficient?”, he said “I bet you are.”; I insisted on a test: it is 32 ng/ml for a normal range of 30 to 100; so, I am within range, but only two points above the cutoff. I am supposed to take 2000 iU daily for 3 months, and then retest everything again.
Opinions? I’ve seen some mention that Vitamin D helps, but it seems that the clinical studies that I’ve found, results were “meh”:
High-dose vitamin D supplementation in people with prediabetes and hypovitaminosis D - PubMed
Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial - PubMed