Beneficial Effects of Carbohydrate Restriction in Type 2 Diabetes Can Be Traced to Changes in Hepatic Metabolism

Barbara A Gower, Marian L Yurchishin, Amy M Goss, John Knight, William T Garvey
The Journal of Clinical Endocrinology & Metabolism, Volume 111, Issue 1, January 2026, Pages e134–e141
https://doi.org/10.1210/clinem/dgaf324

Abstract

Context

Carbohydrate restriction benefits metabolic health in patients with type 2 diabetes (T2D), possibly through changes in hepatic metabolism.

Objective

To test the hypothesis that the ketogenic diet (KD) would decrease de novo lipogenesis (DNL) and liver fat, which would be associated with restored beta-cell function.

Methods

Participants were 57 adults with mild T2D. A hyperglycemic clamp was used to assess acute C-peptide response (ACP), and magnetic resonance imaging to assess hepatic fat fraction, at baseline and after 12 weeks of either a eucaloric KD (∼9% energy from carbohydrate, 65% energy from fat) or a eucaloric low-fat diet (LFD) (∼55% energy from carbohydrate, 20% energy from fat).

Results

The KD led to decreases in pyruvate (−23%, P < .001) and palmitoleic acid, a marker of DNL (−32%, P < .01). Participants on the KD had higher fasting glucagon (25%, P < .05) and lower liver fat (28%, P < .05) at week 12 than those on the LFD. In all combined, the change in liver fat was positively associated with the change in pyruvate (r = 0.45, P = .05), and inversely associated with changes in glucagon (r = −0.34, P < .05), the glucagon to C-peptide ratio (r = −0.44, P < .01), and ACP (r = −0.34, P < .05). The change in ACP was inversely associated with the change in pyruvate in the KD group (r = −0.5, P < .05), but not in the LFD group.

Conclusion

A shift in hepatic metabolism to favor fat oxidation over DNL may underlie the beneficial effects of carbohydrate restriction on hepatic steatosis and glucose-induced insulin secretion.

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