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Serum Alanine Aminotransferase Levels Decrease Further With Carbohydrate Than Fat Restriction in Insulin-Resistant Adults

¹ Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford University, Stanford, California
² Division of Endocrinology, Stanford University School of Medicine, Stanford University, Stanford, California

Address correspondence and reprint requests to Marno C. Ryan, MD, Falk Cardiovascular Research Center, 300 Pasteur Dr., Stanford University, Stanford, CA 94305-5406. E-mail: mryan{at}cvmed.stanford.edu

OBJECTIVE—Although weight loss interventions have been shown to reduce steatosis in nonalcoholic fatty liver disease (NAFLD), the impact of dietary macronutrient composition is unknown. We assessed the effect on serum alanine aminotransferase (ALT) concentrations of two hypocaloric diets varying in amounts of carbohydrate and fat in obese insulin-resistant individuals, a population at high risk for NAFLD.

RESEARCH DESIGN AND METHODS—Post hoc analysis of ALT concentrations was performed in 52 obese subjects with normal baseline values and insulin resistance, as quantified by the steady-state plasma glucose (SSPG) test, who were randomized to hypocaloric diets containing either 60% carbohydrate/25% fat or 40% carbohydrate/45% fat (15% protein) for 16 weeks. The primary end point was change in ALT, which was evaluated according to diet, weight loss, SSPG, and daylong insulin concentrations.

RESULTS—Although both diets resulted in significant decreases in weight and SSPG, daylong insulin, and serum ALT concentrations, the 40% carbohydrate diet resulted in greater decreases in SSPG (P < 0.04), circulating insulin (P < 0.01), and ALT (9.5 ± 9.4 vs. 4.2 ± 8.3 units/l; P < 0.04) concentrations. ALT changes correlated with improvement in insulin sensitivity (P = 0.04) and daylong insulin (P < 0.01). Individuals with ALT concentrations above the proposed upper limits experienced significant declines in ALT, unlike those with lower ALT levels.

CONCLUSIONS—In a population at high risk for NAFLD, a hypocaloric diet moderately lower in carbohydrate decreased serum ALT concentrations to a greater degree than a higher-carbohydrate/low-fat diet, despite equal weight loss. This may result from a relatively greater decline in daylong insulin concentrations. Further research with histological end points is needed to further explore this finding.

Abbreviations: ALT, alanine aminotransferase • AUC, area under the curve • NAFLD, nonalcoholic fatty liver disease • SSPG, steady-state plasma glucose

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