title: Evaluation of various biomarkers as potential mediators of the association between coffee consumption and incident type 2 diabetes in the EPIC-Potsdam Study.
abstract: BACKGROUND
  The inverse association between coffee consumption and the risk of type 2 diabetes (T2D) is well established; however, little is known about potential mediators of this association.
  
  
  OBJECTIVE
  We aimed to investigate the association between coffee consumption and diabetes-related biomarkers and their potential role as mediators of the association between coffee consumption and T2D.
  
  
  METHODS
  We analyzed a case-cohort study (subcohort: n = 1610; verified incident T2D cases: n = 417) nested within the European Prospective Investigation into Cancer and Nutrition-Potsdam study involving 27,548 middle-aged participants. Habitual coffee consumption was assessed with a validated, semiquantitative food-frequency questionnaire. We evaluated the association between coffee consumption and several T2D-related biomarkers, such as liver markers (reflected by γ-glutamyltransferase, fetuin-A, and sex hormone-binding globulin), markers of dyslipidemia (high-density lipoprotein cholesterol and triglycerides), inflammation [C-reactive protein (CRP)], an adipokine (adiponectin), and metabolites, stratified by sex.
  
  
  RESULTS
  Coffee consumption was inversely associated with diacyl-phosphatidylcholine C32:1 in both sexes and with phenylalanine in men, as well as positively associated with acyl-alkyl-phosphatidylcholines C34:3, C40:6, and C42:5 in women. Furthermore, coffee consumption was inversely associated with fetuin-A (P-trend = 0.06) and CRP in women and γ-glutamyltransferase and triglycerides in men. Coffee consumption tended to be inversely associated with T2D risk in both sexes, reaching significance only in men [HR (95% CI): women: ≥4 compared with >0 to <2 cups coffee/d: 0.78 (0.46, 1.33); men: ≥5 compared with >0 to <2 cups coffee/d: 0.40 (0.19, 0.81)]. The association between coffee consumption and T2D risk in men was slightly reduced after adjustment for phenylalanine or lipid markers.
  
  
  CONCLUSIONS
  Coffee consumption was inversely associated with a diacyl-phosphatidylcholine and liver markers in both sexes and positively associated with certain acyl-alkyl-phosphatidylcholines in women. Furthermore, coffee consumption showed an inverse trend with CRP in women and with triglycerides and phenylalanine in men. However, these markers explained only to a small extent the inverse association between long-term coffee consumption and T2D risk.
authors: From the Departments of Molecular Epidemiology (SJ, JK, and MBS) and Epidemiology (A Floegel, HB, CW, and DD), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (CP and JA); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, Berlin, Germany (TP); the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University Hospital of the Eberhard Karls University, Tübingen, Germany (A Fritsche); Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany (A Fritsche); the Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (BI); and the German Center for Diabetes Research (DZD), Neuherberg, Germany (SJ, A Fritsche, JK, and MBS).
authors: Simone
authors: S
authors: Jacobs
authors: From the Departments of Molecular Epidemiology (SJ, JK, and MBS) and Epidemiology (A Floegel, HB, CW, and DD), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (CP and JA); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, Berlin, Germany (TP); the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University Hospital of the Eberhard Karls University, Tübingen, Germany (A Fritsche); Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany (A Fritsche); the Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (BI); and the German Center for Diabetes Research (DZD), Neuherberg, Germany (SJ, A Fritsche, JK, and MBS).
authors: Janine
authors: J
authors: Kröger
authors: From the Departments of Molecular Epidemiology (SJ, JK, and MBS) and Epidemiology (A Floegel, HB, CW, and DD), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (CP and JA); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, Berlin, Germany (TP); the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University Hospital of the Eberhard Karls University, Tübingen, Germany (A Fritsche); Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany (A Fritsche); the Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (BI); and the German Center for Diabetes Research (DZD), Neuherberg, Germany (SJ, A Fritsche, JK, and MBS).
authors: Anna
authors: A
authors: Floegel
authors: From the Departments of Molecular Epidemiology (SJ, JK, and MBS) and Epidemiology (A Floegel, HB, CW, and DD), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (CP and JA); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, Berlin, Germany (TP); the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University Hospital of the Eberhard Karls University, Tübingen, Germany (A Fritsche); Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany (A Fritsche); the Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (BI); and the German Center for Diabetes Research (DZD), Neuherberg, Germany (SJ, A Fritsche, JK, and MBS).
authors: Heiner
authors: H
authors: Boeing
authors: From the Departments of Molecular Epidemiology (SJ, JK, and MBS) and Epidemiology (A Floegel, HB, CW, and DD), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (CP and JA); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, Berlin, Germany (TP); the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University Hospital of the Eberhard Karls University, Tübingen, Germany (A Fritsche); Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany (A Fritsche); the Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (BI); and the German Center for Diabetes Research (DZD), Neuherberg, Germany (SJ, A Fritsche, JK, and MBS).
authors: Dagmar
authors: D
authors: Drogan
authors: From the Departments of Molecular Epidemiology (SJ, JK, and MBS) and Epidemiology (A Floegel, HB, CW, and DD), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (CP and JA); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, Berlin, Germany (TP); the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University Hospital of the Eberhard Karls University, Tübingen, Germany (A Fritsche); Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany (A Fritsche); the Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (BI); and the German Center for Diabetes Research (DZD), Neuherberg, Germany (SJ, A Fritsche, JK, and MBS).
authors: Tobias
authors: T
authors: Pischon
authors: From the Departments of Molecular Epidemiology (SJ, JK, and MBS) and Epidemiology (A Floegel, HB, CW, and DD), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (CP and JA); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, Berlin, Germany (TP); the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University Hospital of the Eberhard Karls University, Tübingen, Germany (A Fritsche); Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany (A Fritsche); the Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (BI); and the German Center for Diabetes Research (DZD), Neuherberg, Germany (SJ, A Fritsche, JK, and MBS).
authors: Andreas
authors: A
authors: Fritsche
authors: From the Departments of Molecular Epidemiology (SJ, JK, and MBS) and Epidemiology (A Floegel, HB, CW, and DD), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (CP and JA); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, Berlin, Germany (TP); the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University Hospital of the Eberhard Karls University, Tübingen, Germany (A Fritsche); Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany (A Fritsche); the Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (BI); and the German Center for Diabetes Research (DZD), Neuherberg, Germany (SJ, A Fritsche, JK, and MBS).
authors: Cornelia
authors: C
authors: Prehn
authors: From the Departments of Molecular Epidemiology (SJ, JK, and MBS) and Epidemiology (A Floegel, HB, CW, and DD), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (CP and JA); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, Berlin, Germany (TP); the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University Hospital of the Eberhard Karls University, Tübingen, Germany (A Fritsche); Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany (A Fritsche); the Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (BI); and the German Center for Diabetes Research (DZD), Neuherberg, Germany (SJ, A Fritsche, JK, and MBS).
authors: Jerzy
authors: J
authors: Adamski
authors: From the Departments of Molecular Epidemiology (SJ, JK, and MBS) and Epidemiology (A Floegel, HB, CW, and DD), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (CP and JA); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, Berlin, Germany (TP); the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University Hospital of the Eberhard Karls University, Tübingen, Germany (A Fritsche); Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany (A Fritsche); the Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (BI); and the German Center for Diabetes Research (DZD), Neuherberg, Germany (SJ, A Fritsche, JK, and MBS).
authors: Berend
authors: B
authors: Isermann
authors: From the Departments of Molecular Epidemiology (SJ, JK, and MBS) and Epidemiology (A Floegel, HB, CW, and DD), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (CP and JA); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, Berlin, Germany (TP); the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University Hospital of the Eberhard Karls University, Tübingen, Germany (A Fritsche); Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany (A Fritsche); the Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (BI); and the German Center for Diabetes Research (DZD), Neuherberg, Germany (SJ, A Fritsche, JK, and MBS).
authors: Cornelia
authors: C
authors: Weikert
authors: From the Departments of Molecular Epidemiology (SJ, JK, and MBS) and Epidemiology (A Floegel, HB, CW, and DD), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (CP and JA); Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine Berlin-Buch, Berlin, Germany (TP); the Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University Hospital of the Eberhard Karls University, Tübingen, Germany (A Fritsche); Institute for Diabetes Research and Metabolic Diseases of the Helmholz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany (A Fritsche); the Department for Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany (BI); and the German Center for Diabetes Research (DZD), Neuherberg, Germany (SJ, A Fritsche, JK, and MBS).
authors: Matthias B
authors: MB
authors: Schulze
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003069:Coffee / Q000009:adverse effects*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D005247:Feeding Behavior; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012306:Risk; D012737:Sex Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003069:Coffee