Pre-Diabetes: How Aggressive to Be?

#1

I have pre-diabetes. HA1C about 5.9 – steady since 2017 when first measured. Fasting Glucose around 105, after light meals around 140-150. I am on 1000 mg of Metformin. Does not seem to have made much difference but suddenly is becoming a stomach distressor (even the extended release).

My particular concern is that insulin is low, like in the range between 1 and 5. Low C peptide, high amylase. I am concerned about the Beta Cells. I did get testing to rule out LADA. I think my underlying primary problem is inadequate insulin being made by the pancreas.

Other than may-be sleep, no levers to pull: low BMI, low BP, decent lipids, daily exercise, careful diet, supplements . . . . gymnema sylvestre,cinnamon, curcumin, etc, (but not rapamycin, yet)

Family history of AD, and I know that low BP, low BMI, low insulin, early menopause are correlated.

My PHP is not concerned. He thinks that these levels might just be “normal” for me. Have been waiting months to get in to see the endocrinologist who is the top diabetes clinician/researcher around here.
Asked PHP for Rybelsus, was denied.

So, options:

-Just keep taking the 1000 mg metformin, nothing more. I can tolerate that, with some distress, but, I think the fundamental problem is the low insulin production, not addressed by metformin
-Get some harmine (which has been shown to take the brakes of DYRK1A and permit Beta cells to replicate). Dosages of 30-50mg are known to be safe and somewhat effective.
-Get some Rybelsus – which would stimulate insulin and amplfiy the effects of the Harmine (as per research using a GLP agonist – Exanitide) But might be really tough to “stomach” given experience with Metformin
– Take Berberine ? (also tough to stomach)
–??

Would appreciate thoughts –

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#2

This RCT assessed the efficacy and safety of a live multistrain probiotic in managing T2D by estimation of β-cell function. Supplementation with live multiprobiotic was associated with significant improvement of β-cell function and fasting glycemia. Prebiotic metabolites exert potent protective activities in β-cells and enhanced glucose-stimulated insulin secretion

Short-chain fatty acids (SCFAs), in the main acetate, butyrate and propionate, are synthesized through bacterial fermentative processes of dietary carbohydrates by such strains as Bacteroidales S24-7 , Parabacteroides , Mucispirillum , and Coprococcus [47]. SCFAs are signaling and energy molecules in the bowel and peripheral organs. They regulate energy and glucose homeostasis [48, 49]. Butyrate improves insulin sensitivity and acetate modulates secretion of insulin from pancreatic β-cells [50]. Extensive studies have been carried out to understand the mechanisms responsible for initiating the functionalities of these SCFAs toward body tissues, which greatly involves the SCFA-specific receptors free fatty acid receptor 2 (FFAR2) and free fatty acid receptor 3 (FFAR3). SCFA signaling by FFA2 and FFA3 is known now to affect not only insulin secretion but also β-cell survival and proliferation and represents an exciting novel link between the gut microbiota and the β-cells [51, 52].

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#3

I think an OGTT with insulin would be helpful here to rule out insulin resistance, the most likely culprit.

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#4

I am in a similar situation as Deborah in terms of pre-diabetes. My HA1C hovers around 5.7 and my last fasting glucose is typically around 120 mg/dL. I have reasonable BP, a healthy diet, exercise regularly, have good muscle and low fat, though I have room for tweaking. Of major concern, my insulin just came back off the charts low (<0.4 uIU/mL); reference range 2.6-24.9 uIU/mL. I can almost not believe it and will get it re-tested.

The other part of my labs that is very troublesome is my LDL and ApoB. I don’t have a family history of high LDL or ApoB, yet my LDL is around 230 mg/dL (99th percentile) and my ApoB is 159 mg/DL (roughly the 99th percentile). I don’t know how I can be such an outlier to my family (suggesting that it is more than genetics?). If anyone has an idea for the root cause or a stategy, I would be terribly interested. Surprisingly, my CAC in 2021 was zero and I am 48 yo now.

Because I am at risk of tipping over into T2D, I am concerned about statins, and have developed myopathies with past attempts to stay on the medication. My genetic testing says that I have a 5-6 times chance of developing myopathies above average. I have an appointment with a cardiologist in a week to discuss all this. I am just starting the adventure of tackling some of the problems above (and others), and will explore other non-statin options to lower my LDL and ApoB aggressively. I want to get the basics under control before trying rapamycin, which I hope sounds reasonable. Again, any suggestions at will be appreciated.

Lastly, thanks to JuanDaw, for the great probiotic RTC article. I just ordered NOW’s Probiotic-10, to see if it can help lower my glucose. If successful, I will report back here.

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#5

Armadillo, yes it does sound as though our situations have a lot in common. And I too want to get the lipids and glucose under control before starting rapamycin.
Re cholesterol: APOB is now 70, using just 5 mg Ezitimibe plus Cholestoff. TRIGS are quite low and HDL is high. I think that the main thing to focus on going forward is inflammation, which, more and more seems to be the major catalyist for damaging atherosclerosis. Diet! Exercise! Sleep! and (almost) no alcohol.

I am going to start taking Bempedoic Acid maybe a couple of times week to see if I can get the cholesterol down just a bit more. Like you I do not want to take anything right now that might raise glucose – statins, Rapamycin, even Repatha (as lowering PCSK9 operates on the pancreas as well as the liver).
I drink goat kefir, a good source of probiotics. A bit wary if taking anything in capsule form at the moment but considering.

I cannot know for sure but I suspect that the combination of low insulin with high-ish glucose means not enough insulin is being produced by the Beta cells. Tests ruled out LADA autoimmune disfunction, but it could still be some form of Beta cell fatigue. So I have just ordered Harmine HCl and am considering getting some Rybelsus, a GLP1 agonist in pill form, to boost the effects of the Harmine.

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#6

I can relate as I tend towards the low end of normal for insulin. My last fasting insulin was 2.8 with a reference range of 2.6-24.9. My last fasting glucose was 91 and my hbA1c was at the highest end of normal at 5.6 so that concerns me a bit. These results were all from the end of May of this year. In the last year I’ve transitioned off eating carnivore to a minimally processed omnivore diet and now get roughly 150g of carbs per day. I’m going to wait and see before taking meds because my BG on finger sticks are usually good. I’m hoping my hbA1c is just taking a little time to catch up with the diet shift. Otherwise I’m happy with my other things like improved lipids, body composition, lower visceral fat, excellent blood pressure etc so the hbA1c just seems odd.

#7

Would you consider eating less carbs?

Also, do weight training to build more muscle. The more muscle you have, the more glucose storage capacity you have.

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#8

@Kandice, I agree with you and do lift weights as I’m trying to build muscle. I would consider reducing carbs though if necessary. This sure gets a bit tricky when you’re aiming for optimal!

#9

Also not at diabetes but was on the way. Besides Metformin I added an SGLT-2 inhibitor (Dapaglifozin) and Acarbose. Both with potential longevity effects so why not? Dapaglifozin has no apparent side-effects and the farty side effects of acarbose disappeared after some months

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