Mario Kratz1, Santica Marcovina1, James E Nelson1, Matthew M Yeh1, Kris V Kowdley1, Holly S Callahan1, Xiaoling Song1, Chongzhi Di1, Kristina M Utzschneider1. 1. From the Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Cancer Prevention Program (MK and XS) and Biostatistics Program (CD), Seattle, WA; the Division of Metabolism, Endocrinology & Nutrition, Department of Medicine, University of Washington, Seattle, WA (MK and KMU); the Departments of Epidemiology (MK) and Pathology (MMY), University of Washington, Seattle, WA; the University of Washington Northwest Lipid Research Laboratories, Seattle, WA (SM); Benaroya Research Institute, Virginia Mason Medical Center, Seattle, WA (JEN and KVK); the University of Washington Institute of Translational Health Sciences, Seattle, WA (HSC); and the VA Puget Sound Health Care System, Department of Medicine, Division of Endocrinology, Seattle, WA (KMU).
Abstract
BACKGROUND: Plasma phospholipid concentrations of trans-palmitoleic acid (trans-16:1n-7), a biomarker of dairy fat intake, are inversely associated with incident type 2 diabetes in 2 US cohorts. OBJECTIVE: The objective was to investigate whether the intake of trans-16:1n-7 in particular, or dairy fat in general, is associated with glucose tolerance and key factors determining glucose tolerance. DESIGN: A cross-sectional investigation was undertaken in 17 men and women with nonalcoholic fatty liver disease and 15 body mass index (BMI)- and age-matched controls. The concentrations of trans-16:1n-7 and 2 other biomarkers of dairy fat intake, 15:0 and 17:0, were measured in plasma phospholipids and free fatty acids (FFAs). Liver fat was estimated by computed tomography-derived liver-spleen ratio. Intravenous-glucose-tolerance tests and oral-glucose-tolerance test (OGTT) and hyperinsulinemic-euglycemic clamps were performed to assess β-cell function and hepatic and systemic insulin sensitivity. RESULTS: In multivariate analyses adjusted for age, sex, and BMI, phospholipid 17:0, phospholipid trans-16:1n-7, FFA 15:0, and FFA 17:0 were inversely associated with fasting plasma glucose, the area under the curve for glucose during an OGTT, and liver fat. Phospholipid trans-16:1n-7 was also positively associated with hepatic and systemic insulin sensitivity. None of the biomarkers were associated with β-cell function. The associations between dairy fat intake and glucose tolerance were attenuated by adjusting for insulin sensitivity or liver fat, but strengthened by adjusting for β-cell function. CONCLUSION: Although we cannot rule out reverse causation, these data support the hypothesis that dairy fat improves glucose tolerance, possibly through a mechanism involving improved hepatic and systemic insulin sensitivity and reduced liver fat.
BACKGROUND: Plasma phospholipid concentrations of trans-palmitoleic acid (trans-16:1n-7), a biomarker of dairy fat intake, are inversely associated with incident type 2 diabetes in 2 US cohorts. OBJECTIVE: The objective was to investigate whether the intake of trans-16:1n-7 in particular, or dairy fat in general, is associated with glucose tolerance and key factors determining glucose tolerance. DESIGN: A cross-sectional investigation was undertaken in 17 men and women with nonalcoholic fatty liver disease and 15 body mass index (BMI)- and age-matched controls. The concentrations of trans-16:1n-7 and 2 other biomarkers of dairy fat intake, 15:0 and 17:0, were measured in plasma phospholipids and free fatty acids (FFAs). Liver fat was estimated by computed tomography-derived liver-spleen ratio. Intravenous-glucose-tolerance tests and oral-glucose-tolerance test (OGTT) and hyperinsulinemic-euglycemic clamps were performed to assess β-cell function and hepatic and systemic insulin sensitivity. RESULTS: In multivariate analyses adjusted for age, sex, and BMI, phospholipid 17:0, phospholipid trans-16:1n-7, FFA 15:0, and FFA 17:0 were inversely associated with fasting plasma glucose, the area under the curve for glucose during an OGTT, and liver fat. Phospholipid trans-16:1n-7 was also positively associated with hepatic and systemic insulin sensitivity. None of the biomarkers were associated with β-cell function. The associations between dairy fat intake and glucose tolerance were attenuated by adjusting for insulin sensitivity or liver fat, but strengthened by adjusting for β-cell function. CONCLUSION: Although we cannot rule out reverse causation, these data support the hypothesis that dairy fat improves glucose tolerance, possibly through a mechanism involving improved hepatic and systemic insulin sensitivity and reduced liver fat.
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