Reduced Glucose Tolerance and Skeletal Muscle GLUT4 and IRS1 Content in Cyclists Habituated to a Long-Term Low-Carbohydrate, High-Fat Diet

Feb 29, 2020International journal of sport nutrition and exercise metabolism

Lower Sugar Processing and Muscle Protein Levels in Cyclists Used to Long-Term Low-Carb, High-Fat Diets

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Abstract

The low-carbohydrate, high-fat (LCHF) diet was associated with reduced glucose tolerance in trained cyclists compared to those on a mixed diet.

Participants on the LCHF diet showed significantly higher plasma glucose concentrations during a 2-hour oral glucose tolerance test.
Serum insulin concentrations peaked later in the LCHF group, at 60 minutes, compared to 30 minutes in the mixed diet group.
Skeletal muscle GLUT4 and IRS1 protein content were lower in those following the LCHF diet.
No significant difference in whole-body insulin sensitivity was observed between the two diet groups.
Muscle enzyme activities indicative of energy pathways did not differ between the LCHF and mixed diet groups.

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Very little is known about how long-term (>6 months) adaptation to a low-carbohydrate, high-fat (LCHF) diet affects insulin signaling in healthy, well-trained individuals. This study compared glucose tolerance; skeletal muscle glucose transporter 4 (GLUT4) and insulin receptor substrate 1 (IRS1) content; and muscle enzyme activities representative of the main energy pathways (3-hydroxyacetyl-CoA dehydrogenase, creatine kinase, citrate synthase, lactate dehydrogenase, phosphofructokinase, phosphorylase) in trained cyclists who followed either a long-term LCHF or a mixed-macronutrient (Mixed) diet. On separate days, a 2-hr oral glucose tolerance test was conducted, and muscle samples were obtained from the vastus lateralis of fasted participants. The LCHF group had reduced glucose tolerance compared with the Mixed group, as plasma glucose concentrations were significantly higher throughout the oral glucose tolerance test and serum insulin concentrations peaked later (LCHF, 60 min; Mixed, 30 min). Whole-body insulin sensitivity was not statistically significantly different between groups (Matsuda index: LCHF, 8.7 ± 3.4 vs. Mixed, 12.9 ± 4.6; p = .08). GLUT4 (LCHF: 1.13 ± 0.24; Mixed: 1.44 ± 0.16; p = .026) and IRS1 (LCHF: 0.25 ± 0.13; Mixed: 0.46 ± 0.09; p = .016) protein content was lower in LCHF muscle, but enzyme activities were not different. We conclude that well-trained cyclists habituated to an LCHF diet had reduced glucose tolerance compared with matched controls on a mixed diet. Lower skeletal muscle GLUT4 and IRS1 contents may partially explain this finding. This could possibly reflect an adaptation to reduced habitual glucose availability rather than the development of a pathological insulin resistance.

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Reduced Glucose Tolerance and Skeletal Muscle GLUT4 and IRS1 Content in Cyclists Habituated to a Long-Term Low-Carbohydrate, High-Fat Diet

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