Can original post (which is obvs. 4o) be replaced with this o3 text below? 4o hallucinates and goes sycophantic, but o3 is better than most people for first pass.
Short answer:
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Yes—for gauging how much insulin your pancreas is making, C-peptide is usually the better test than measuring insulin directly.
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Rapamycin can lower C-peptide (i.e., reduce endogenous insulin secretion) in some contexts—especially with chronic/systemic exposure—though effects vary by dose and schedule.
Why C-peptide is preferred (most of the time)
- It’s released 1:1 with insulin but lasts longer in blood (≈20–30 min vs. 3–5 min for insulin) and isn’t cleared by the liver, so levels are stabler and better reflect total beta-cell output. (PMC, NCBI)
- It’s the standard readout of endogenous insulin in many diabetes studies/clinics (e.g., mixed-meal–stimulated C-peptide). (Diabetes Journals)
- Exception/caveat: kidney function matters—C-peptide is cleared by the kidneys, so reduced GFR can artifactually raise it. Always interpret alongside glucose at the time of draw and renal status. (Lippincott Journals)
What about rapamycin?
- Human data show beta-cell function (C-peptide) can fall during rapamycin-based regimens. In a T1D trial, C-peptide AUC dropped markedly during rapamycin + low-dose IL-2. (PMC)
- Case/physiology studies with everolimus (a rapalog) suggest impaired insulin secretion without clear peripheral insulin-resistance changes—again implying a C-peptide decrease. (J-STAGE)
- Separate work shows chronic/high, continuous rapamycin can produce insulin resistance and glucose intolerance (which complicates interpretation), whereas intermittent dosing blunts these metabolic downsides. (PMC)
Practical takeaways
- If you’re assessing your own insulin production (e.g., on or off exogenous insulin), ask for fasting C-peptide with a simultaneous glucose, or a stimulated C-peptide (mixed-meal) for sensitivity. Note kidney function on the lab report. (PMC)
- If starting or changing rapamycin, track fasting glucose/A1c and consider repeating C-peptide after a few weeks to see your personal metabolic response (ideally keeping your dosing schedule consistent between tests). (PMC)
If you want, I can sketch a simple testing plan (timing, fasting vs. mixed-meal, how to interpret ranges) tailored to your regimen.
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My C-peptide was measured at 227 pmol/L (reference range 270–1290) after approximately 15 hours of fasting, with the blood sample taken at 13:30. My fasting glucose was 4.8 mmol/L, and my HbA1c is 36 mmol/mol.
For context, I have been taking oral rapamycin off-label at a relatively high dose of about 3 mg Rapacan with GF, but only once every 11 days (based on Sirolimus blood test results) for the last year. And a bit on and off, did not use it the weeks before the blood test if I remember correctly (I can go back and check).
In addition, my recent labs showed a slightly elevated conjugated (direct) bilirubin of 7 µmol/L and a low vitamin A level at 1.1 µmol/L (reference 1.3–3.5). I wonder what this could indicate (rapamycin usage) and how to proceed. Thanks!
we often discuss fasting glucose, HbA1c, and sometimes fasting insulin.
But rarely C‑peptid — even though it is a stable and mechanistically informative marker of endogenous insulin production.
C‑peptid is released in a 1:1 ratio with insulin when proinsulin is cleaved inside the β‑cell. Because it bypasses first‑pass hepatic clearance, it provides a cleaner, more reliable signal of pancreatic output. Clinically, low C‑peptid reflects impaired insulin production (autoimmune diabetes, late β‑cell exhaustion), while elevated levels often indicate insulin resistance and compensatory hyperinsulinemia. These relationships are well‑established in endocrinology.
But rapamycin changes the interpretation — my C-peptid was on the lower side and fasting glucos a bit higher than I want it to be. Since high insulin can drive aging, I am ok with a C-peptid on the lower side. .
can low insulin cause high fasting glucose in rapamycin users? Yes.
Mechanistically, this can happens when, Rapamycin suppresses β‑cell insulin secretion (lower C‑peptid). The dose is high or too frequent. And if dose is to high it also inhibit mTORC2 and that reduces insulin sensitivity. This combination can produce higher fasting glucose even in otherwise healthy individuals.
C‑peptid reflects endogenous insulin production, it shows whether your pancreas is:
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Working harder: Elevated C‑peptid → compensating for reduced insulin sensitivity (e.g., rapamycin’s transient mTORC2 effect)
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Idling: Low C‑peptid → low insulin demand from SGLT2 inhibitors, berberine, fasting, or endurance training
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Struggling: Low C‑peptid + high glucose → impaired β‑cell function
What is the forum’s experience of rapamycin and c-peptid in relation to fasting glucos?