title: Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not β-cell function in humans.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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).
authors.forename: Mario
authors.initials: M
authors.lastname: Kratz
authors.affiliation: 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).
authors.forename: Santica
authors.initials: S
authors.lastname: Marcovina
authors.affiliation: 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).
authors.forename: James E
authors.initials: JE
authors.lastname: Nelson
authors.affiliation: 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).
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.affiliation: 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).
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.affiliation: 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).
authors.forename: Holly S
authors.initials: HS
authors.lastname: Callahan
authors.affiliation: 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).
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Song
authors.affiliation: 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).
authors.forename: Chongzhi
authors.initials: C
authors.lastname: Di
authors.affiliation: 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).
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Utzschneider
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003611:Dairy Products; D004041:Dietary Fats / Q000378:metabolism / Q000627:therapeutic use*; D005227:Fatty Acids / Q000097:blood; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000178:diet therapy* / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D044242:Trans Fatty Acids / Q000009:adverse effects / Q000097:blood
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D007328:Insulin; D044242:Trans Fatty Acids; C008757:palmitoleic acid; C117025:pentadecanoic acid; C013102:margaric acid
references.citation: Am J Physiol Endocrinol Metab. 2003 Oct;285(4):E906-16
references.pmid: 12959938
references.citation: Cell Metab. 2005 Feb;1(2):107-19
references.pmid: 16054052
references.citation: Diabetes Care. 2011 Jan;34 Suppl 1:S62-9
references.pmid: 21193628
references.citation: Hepatology. 2005 Jun;41(6):1313-21
references.pmid: 15915461
references.citation: J Biol Chem. 1957 May;226(1):497-509
references.pmid: 13428781
references.citation: Eur J Nutr. 2013 Feb;52(1):1-24
references.pmid: 22810464
references.citation: Clin Chem. 1972 Jun;18(6):499-502
references.pmid: 4337382
references.citation: J Lipid Res. 1965 Apr;6:317-9
references.pmid: 14328439
references.citation: Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E243-51
references.pmid: 20959530
references.citation: Am J Clin Nutr. 2007 Oct;86(4):929-37
references.pmid: 17921367
references.citation: Am J Clin Nutr. 2013 Apr;97(4):854-61
references.pmid: 23407305
references.citation: Ann N Y Acad Sci. 2010 Mar;1190:42-9
references.pmid: 20388135
references.citation: Ann Intern Med. 2010 Dec 21;153(12):790-9
references.pmid: 21173413
references.citation: Cell. 2008 Sep 19;134(6):933-44
references.pmid: 18805087
references.citation: J Lipid Res. 1986 Jan;27(1):114-20
references.pmid: 3958609
references.citation: Invest Radiol. 1993 Apr;28(4):297-302
references.pmid: 8478169
references.citation: Prog Lipid Res. 2008 Sep;47(5):348-80
references.pmid: 18435934
references.citation: Am J Clin Nutr. 1998 Aug;68(2):291-5
references.pmid: 9701185
references.citation: Int J Epidemiol. 1989 Dec;18(4):858-67
references.pmid: 2621022