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Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT
Published on: January 7, 2018
Beneficial Effects of Carbohydrate Restriction in Type 2 Diabetes Can Be Traced to Changes in Hepatic Metabolism
Barbara A Gower1, Marian L Yurchishin1, Amy M Goss1
1Department of Nutrition Sciences, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
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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