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ForumsPharmacology & MechanismsIncretin effect in healthy vs T2DM — looking for input

Incretin effect in healthy vs T2DM — looking for input

PedsEndoPhilly Tue, Jun 25, 2024 at 10:31 PM 13 replies 2,056 viewsPage 1 of 3
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PedsEndoPhilly
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Jun 25, 2024 at 10:31 PM#1

Collecting this in one place because it comes up every few weeks and the answer is always assembled from scratch. It is about glycaemic control, and it is deliberately narrow — everything I am not confident about is marked as such.

What is actually established

HbA1c reflects roughly three months of average glycaemia weighted toward the most recent weeks, which is why repeating it at six weeks tells you very little. The improvement on this class comes from two directions — direct glucose-dependent insulin secretion and glucagon suppression, plus the indirect effect of weight loss on insulin sensitivity — and the second continues after the first has plateaued.

The condition it depends on

The caveat that HbA1c is unreliable in anaemia, haemoglobinopathies and recent blood loss, all of which are commoner than people assume. If it disagrees with fasting glucose or a CGM, that is worth chasing.

The practical version

Because it is glucose-dependent, this class carries a low intrinsic hypoglycaemia risk on its own — the risk arrives when it is combined with insulin or a sulfonylurea, which usually need reducing.

What I am not sure about

What I am after is why A1C lags the way it does, and what to look at in the meantime if you want to know sooner. If the honest answer is that nobody knows, that is a useful answer and I would rather have it.

— PedsEndoPhilly · corrections welcome and will be edited into this post with credit
12 7sarah_TO, wendy_avl, jason_paloalto and 9 others
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Dr.SportsMedIN
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Jun 25, 2024 at 10:45 PM#2
PedsEndoPhilly said:
HbA1c reflects roughly three months of average glycaemia weighted toward the most recent weeks, which is why repeating it at six weeks tells you very…

Complete metabolic panel trending on glycaemic control — sharing because comprehensive data helps everyone:

TestBaselineMonth 3Month 6Month 12
Glucose (fasting)121999383
Insulin (fasting)271396
HOMA-IR5.53.22.11.5
Uric Acid7.97.16.05.2

The insulin resistance improvement (HOMA-IR) is what my endo focuses on most. Going from 5.5 to near 1.0 is a metabolic transformation.

Last edited: Jun 26, 2024 at 3:45 AM
11 6lisa_labSD, adam_van, Dr.SurgeonPGH and 8 others
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KevinCompounds
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Jun 25, 2024 at 10:59 PM#3
PedsEndoPhilly said:
HbA1c reflects roughly three months of average glycaemia weighted toward the most recent weeks, which is why repeating it at six weeks tells you very…

Glycemic variability as the key metric for glycaemic control success: my coefficient of variation (CV) on CGM dropped from 39% to 20%. Target is <36%, with <30% being ideal.

Why this matters more than average glucose: large glucose swings cause oxidative stress, endothelial damage, and promote advanced glycation end-products (AGEs). A flat glucose line at 95 mg/dL is metabolically healthier than oscillating between 60 and 160, even if the average is the same.

Last edited: Jun 26, 2024 at 12:59 AM
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julia.endo
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Jun 25, 2024 at 11:13 PM#4
KevinCompounds said:
Glycemic variability as the key metric for glycaemic control success: my coefficient of variation (CV) on CGM dropped from 39% to 20%.

Insulin sensitivity test (HOMA-IR) on glycaemic control — arguably the most important metabolic marker most people aren't tracking:

HOMA-IR = (fasting insulin × fasting glucose) ÷ 405

My numbers: Baseline HOMA-IR = 6.0 (insulin resistant) → Current = 1.0 (insulin sensitive)

Anything above 2.0 indicates insulin resistance. The goal is below 1.5. GLP-1 agonists address the root metabolic dysfunction, not just the symptoms. This is why they work so much better than calorie restriction alone.

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KarenAZ_mom
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Jun 26, 2024 at 12:26 AM#5
Dr.SportsMedIN said:
Complete metabolic panel trending on glycaemic control — sharing because comprehensive data helps everyone: Test Baseline Month 3 Month 6 Month 12…

Can confirm. Same sequence, different timescale. Posting only so the count is not one.

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