Blood Glucose / Cholesterol Whack-A-Mole: how to balance?

Statins and PCSK9i such as Repatha lower cholesterol but raise blood glucose. My experience bears this out, and I don’t know how to balance so would welcome inputs.

In May 2023 I started Repatha upon learning that my Lp(a) was 40. LDL-C was about 125 and HDL 117 so Chol/HDL ratio was good. APOB aout 93. But was concerned about the Lp(a) because of family history and genetics (9p21 risk allele, 1.9 x risk of coronary artery disease).

By June 2024, Repatha lowered LDL to 72, Lp(a) to 27 and even HDL to 92, with APOB of 76. Low Trigs (53) and CRP of 1.0.

But HA1C went from 5.6 to 5.9 and FBG also went up.

Concerned about the glucose, decided to go off Repatha. Added 500-800 Berberine to 500, sometimes 1000mg Metformin. Tried a bit of Rybelsus and lost weight and got kidney stones.

Insulin and C-peptide are low. I believe what I have is a glucokinase inactivating polymorphism which causes pre-diabetic levels of glucose that usually do not progress, nor cause problems, nor require treatment, and are not impacted by diet. I had a referral to an endocrinologist in March 2024 but by the time I was able to get in to see him, six months later, the blood glucose had gone down to low-moderate pre diabetic levels. He said: no treatment required.

October 2024 – Ha1C down to 5.5, but cholesterol levels are up to about where they were before starting Repatha.

I do recognize that neither the glucose or cholesterol levels are alarming. I am also concerned about the possible neuro cognitive adverse effects from PCSK9i (also statins). Given everything I know about my health and family history, I believe I will live long and get Alzheimers so my biggest concern is actually neither cardio nor diabetes. It is neurocognitive decline.

I was considering restarting the Rybelsus at a very low intermittent level, (primarily because research suggests it is neuroprotetcive) but am inclined not to do that. After getting the recent lipids retested, I am poised to restart Repatha, and monitor glucose carefully, may-be increase Berberine. Am already taking gymnema sylvestre and a couple of other supposed sugar-lowering supplements.

In my head I hear Tom Dayspring saying that if Lp(a) is elevated, you want to get LDL levels low “like a kid again.” Should I be following that advice? I don’t know LDL particle size but the low trigs and high HDL suggest that the LDL is likely mixed to the “large bouyant” end of the range. CAC score was 0.96 and I am thin, generally healthy.

How to optimize glucose versus cholesterol? Try a bit of an SGLT2? Is the glucose or cholesterol a greater concern? or is neither a concern at these levels? Should I just close the book on all of this?

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Not an answer but questions.

Is your Lp(a) value expressed in mg/dL or nmol/L?

How fit are you in terms of large muscle development?

What is your insulin level and how many reading do you have on it?

The Lp(a) is in mg/dl.

I am a small person with a BMI of about 18.5, but I am fairly fit for my age (75)
I do resistance training, Peloton, can easily swim (slowly) for an hour, walk five or more miles, curl 40 reps with an 8 pound weight, wall sit for 90+ seconds.

Insulin has ranged from less than 2 ulU/ml to 5 ulI/ml:
4/11/2024: less than 2 ulU/ml,
4/15,2024: 3 ulU/ml,
4/25/2024: 5 ulU/ml
6/12/2/24: 3 ulU/ml,
6/21/2024: 4ulU/ml,
9/30 2024 less than 2 ulU/ml.

I had very similar numbers to yours before starting Repatha. My LDL was 122, HDL 57, ApoB 120 HBA1C 5.7. What I have done is added Bempedoic Acid 180 mg, Ezetemibe 10 mg, SGLT2I (Jardiance 12.5 mg), Atorvastatin (5 mg) and Metformin 500 mg.

My new numbers are LDL 48, ApoB 48, HDL 51, and HBA1C 5.8. Jardiance didn’t help my HBA1C, but I believe it has strong neuro- and cardio-protective properties, is great for the kidneys, and counterbalances the Uric Acid increase from BA. Based on the plethora of research, I believe SGLT2Is are vital for longevity. However, the effects may not show up in your blood biomarkers.

I’m working on my HBA1C and hsCRP (1.59). It may be elevated because, during the immediate prior three months, I was on vacation and eating unhealthily at restaurants every day for every meal. The hsCRP is probably due to my poor sleep (teenage children).

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I think it is a balance of items, and the issue is understanding the little bit of bad a certain drug will do while doing much good, and anticipating this, and simultaneously medicating it. Ultimately getting all the numbers optimal is important.

As we all know Rapa will often make insulin sensitivity and HbA1C worse, along with potentially lipids. Anticipate it, and treat/optimize the triad of vascular disease risk. Yes, recognize diet and exercise are critical as is gut microbiome … but we can easily address BP, ApoB targeted to Lp(a) and whether vascular disease is present or not (e.g. image and see and if so, treat to an ApoB 20 points lower), and insulin sensitivity/HbA1C.

It’s not a complicated situation, and I have no problem optimizing these items. Even understanding a Statin will worsen insulin sensitivity, anticipate, preemptively treat.

The folks that panic based upon the fact that something is worsening on their profile occurs due to lack of expert opinion and guidance that predicts this and treats it before it occurs.

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This is not medical advice.
I’ve had somewhat similar issues, though a bit milder. Try Bempedoic acid 180 mg + Ezetimibe 5 mg. For me, there’s minimal effect on fasting blood glucose; Ezetimibe slightly raises fasting glucose (5 mg less than 10 mg), but it doesn’t affect post-meal glucose, for example. I would test this first to see if there’s any effect on blood glucose.

These, of course, won’t help with Lp(a) levels, but as far as I know, they don’t raise them either. I also have high Lp(a). If the Repatha dosage could somehow be reduced, it could be added as well, but that might be difficult since it’s pre-dosed.

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Thank you! Helps to know that others are also finding their way to a balance. Tried Bempedoic Acid – gave me bad leg cramps. Considering taking the Repatha once every 3 or 4 weeks rather than every 2. Half life is about 2 weeks. Reading all the information here, I understand that I can/should customize/tailor the types and amounts of meds and supplements. I seem to be on the sensitive/high responder side of things.

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It is unlikely that bempedoic acid would cause cramps, as it barely activates in muscle cells. Personally, I would try it again and add electrolytes during the first couple of weeks just to be safe. Sometimes the body takes time to adjust to a new medication.

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Discussed on the forum a couple of times how you can do sub-dosages of Repatha and other pen injectors - see posts by @DrFraser for example

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