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Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

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Published on: November 16, 2011

Serum alanine aminotransferase levels decrease further with carbohydrate than fat restriction in insulin-resistant

Marno Celeste Ryan¹, Fahim Abbasi, Cindy Lamendola

¹Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, 300 Pasteur Dr., Stanford University, Stanford, CA 94305-5406, USA. mryan@cvmed.stanford.edu

|March 14, 2007

Summary

A lower-carbohydrate diet significantly reduced liver enzymes (ALT) more than a low-fat diet in obese, insulin-resistant individuals. This dietary approach may improve nonalcoholic fatty liver disease (NAFLD) markers by lowering insulin levels.

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Published on: October 23, 2018

Area of Science:

Metabolic Health
Hepatology
Nutritional Science

Background:

Nonalcoholic fatty liver disease (NAFLD) is a growing health concern, particularly in obese, insulin-resistant populations.
Weight loss interventions are known to reduce steatosis in NAFLD, but the role of dietary macronutrient composition remains unclear.
Serum alanine aminotransferase (ALT) is a key biomarker for liver injury in NAFLD.

Purpose of the Study:

To investigate the impact of two hypocaloric diets, differing in carbohydrate and fat content, on serum ALT concentrations.
To assess the effect of dietary macronutrient composition on liver enzyme levels in obese individuals with insulin resistance.
To determine if changes in insulin sensitivity and daylong insulin concentrations mediate the effects of diet on ALT levels.

Main Methods:

A post hoc analysis of 52 obese, insulin-resistant subjects with normal baseline ALT was conducted.
Participants were randomized to either a 60% carbohydrate/25% fat diet or a 40% carbohydrate/45% fat hypocaloric diet for 16 weeks.
Changes in ALT, weight, steady-state plasma glucose (SSPG), and daylong insulin concentrations were evaluated.

Main Results:

Both diets led to significant reductions in weight, SSPG, daylong insulin, and ALT.
The diet lower in carbohydrate (40% carbohydrate/45% fat) resulted in significantly greater reductions in SSPG, insulin, and ALT compared to the higher-carbohydrate diet.
ALT reductions correlated positively with improvements in insulin sensitivity and decreases in daylong insulin.

Conclusions:

A hypocaloric diet moderately lower in carbohydrate achieved greater reductions in serum ALT than a higher-carbohydrate/low-fat diet, even with equivalent weight loss.
The enhanced reduction in ALT may be attributed to a more pronounced decrease in daylong insulin concentrations.
Further research utilizing histological endpoints is warranted to confirm these findings in NAFLD patients.