Fromentin · Diabetes 2013 · Single-arm metabolic tracer study · n=8

Dietary proteins contribute little to glucose production, even under optimal gluconeogenic conditions in healthy humans.

Cited 49 times in the scientific literature.

Level 4 - case-series / case-control

Single-arm metabolic tracer study without a control group

PubMed 23274906 · doi:10.2337/db12-1208 · record verified 2026-08-28

What was done

Eight healthy volunteers underwent an overnight fast and received an intravenous infusion of [6,6-²H₂]-glucose. Two hours later, they ingested four eggs containing 23 g of intrinsically, uniformly [¹⁵N]-[¹³C]-labeled protein. Gas exchange, expired CO₂, blood, and urine were collected over an 8-hour postprandial period to measure amino acid deamination, oxidation, endogenous glucose production (EGP), and the specific contribution of dietary amino acids to EGP.

What was found

Cumulative dietary amino acid deamination over 8 hours was 18.1 ± 3.5%, with 17.5% oxidized. Total EGP over the 8 hours was 50.4 ± 7.7 g, of which only 3.9 ± 0.7 g originated directly from dietary amino acids. EGP remained stable for 6 hours before declining alongside blood glucose levels.

Why it matters

Direct conversion of dietary protein to blood glucose is minimal (~8% of total production) even under optimal gluconeogenic conditions (overnight fast and a carbohydrate-free protein meal), showing that endogenous substrates drive glucose homeostasis.

Limits

The sample size was very small (n = 8). There was no comparator group (such as prolonged fasting or a carbohydrate control). Findings apply to healthy subjects habituated to medium-protein diets and may not generalize to diabetic populations or higher protein intakes.

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