Increased plasma branched short-chain fatty acids and improved glucose homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES)

Author:

Aslamy Arianne1,Wood Alexis C.2,Jensen Elizabeth T.3,Bertoni Alain G.3,Sheridan Patricia A.4,Wong Kari E.4,Ramesh Gautam5,Rotter Jerome I.6,Chen Yii-Der I.6,Goodarzi Mark O.1

Affiliation:

1. 1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA

2. 2USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA

3. 3Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA

4. 4Metabolon Inc., Morrisville, NC, USA

5. 5School of Medicine, University of California San Diego, La Jolla, CA, USA

6. 6Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA

Abstract

Short chain fatty acids (SCFA) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched short chain fatty acids (BSCFA), isobutyrate, isovalerate, and methylbutyrate, is largely unknown. In a cohort of 219 non-Hispanic Whites and 126 African Americans, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, lipid traits, and other SCFA. We observed a bimodal distribution of BSCFA, with 25 individuals having high levels (HBSCFA group) and 320 individuals having lower levels (L-BSCFA group). The prevalence of dysglycemia was lower in the H-BSCFA group compared to the L-BSCFA group (16% versus 49%, P=0.0014). This association remained significant after adjustment for age, sex, race, BMI, and levels of other SCFA. Consistent with the lower rate of dysglycemia, fasting and postprandial glucose were lower and disposition index was higher in the H-BSCFA group. Additional findings in H-BSCFA versus L-BSCFA included lower fasting and postprandial Cpeptide levels and lower insulin clearance without differences in insulin levels, insulin sensitivity, insulin secretion, or other variables examined, including diet and physical activity. As one of the first human studies associating higher BSCFA levels with lower odds of dysglycemia and improved glucose homeostasis, this study sets the stage for further investigation of BSCFA as a novel target for prevention or treatment of diabetes.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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