title: Patients with type 1 diabetes show signs of vascular dysfunction in response to multiple high-fat meals.
abstract: BACKGROUND
  A high-fat diet promotes postprandial systemic inflammation and metabolic endotoxemia. We investigated the effects of three consecutive high-fat meals on endotoxemia, inflammation, vascular function, and postprandial lipid metabolism in patients with type 1 diabetes.
  
  
  METHODS
  Non-diabetic controls (n = 34) and patients with type 1 diabetes (n = 37) were given three high-caloric, fat-containing meals during one day. Blood samples were drawn at fasting (8:00) and every two hours thereafter until 18:00. Applanation tonometry was used to assess changes in the augmentation index during the investigation day.
  
  
  RESULTS
  Three consecutive high-fat meals had only a modest effect on serum LPS-activity levels and inflammatory markers throughout the day in both groups. Of note, patients with type 1 diabetes were unable to decrease the augmentation index in response to the high-fat meals. The most profound effects of the consecutive fat loads were seen in chylomicron and HDL-metabolism. The triglyceride-rich lipoprotein remnant marker, apoB-48, was elevated in patients compared to controls both at fasting (p = 0.014) and postprandially (p = 0.035). The activities of the HDL-associated enzymes PLTP (p < 0.001), and CETP (p = 0.007) were higher and paraoxonase (PON-1) activity, an anti-oxidative enzyme bound to HDL, decreased in patients with type 1 diabetes (p = 0.027).
  
  
  CONCLUSIONS
  In response to high-fat meals, early signs of vascular dysfunction alongside accumulation of chylomicron remnants, higher augmentation index, and decreased PON-1 activity were observed in patients with type 1 diabetes. The high-fat meals had no significant impact on postprandial LPS-activity in non-diabetic subjects or patients with type 1 diabetes suggesting that metabolic endotoxemia may be more central in patients with chronic metabolic disturbances such as obesity, type 2 diabetes, or diabetic kidney disease.
authors: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum, Helsinki, Finland ; Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland ; Diabetes & Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Mariann I
authors: MI
authors: Lassenius
authors: Department of Integrative Biology and Physiology, University of California, Los Angeles, USA.
authors: Ville-Petteri
authors: VP
authors: Mäkinen
authors: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum, Helsinki, Finland ; Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland ; Diabetes & Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Christopher L
authors: CL
authors: Fogarty
authors: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum, Helsinki, Finland ; Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland ; Diabetes & Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Lina
authors: L
authors: Peräneva
authors: Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors: Matti
authors: M
authors: Jauhiainen
authors: Institute of Dentistry, University of Helsinki, Helsinki, Finland.
authors: Pirkko J
authors: PJ
authors: Pussinen
authors: Diabetes & Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland ; Heart and Lung Center, Cardiovascular Research Group, HUCH, Helsinki, Finland.
authors: Marja-Riitta
authors: MR
authors: Taskinen
authors: Department of Bacteriology, HUSLAB, Helsinki, Finland.
authors: Juha
authors: J
authors: Kirveskari
authors: Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.
authors: Outi
authors: O
authors: Vaarala
authors: Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland.
authors: Janne K
authors: JK
authors: Nieminen
authors: Department of Medical Microbiology and Immunology, University of Oulu, and Nordlab, Oulu, Finland.
authors: Sohvi
authors: S
authors: Hörkkö
authors: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.
authors: Antti J
authors: AJ
authors: Kangas
authors: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland ; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors: Pasi
authors: P
authors: Soininen
authors: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland ; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland ; Oulu University Hospital, Oulu, Finland ; Computational Medicine, School of Social and Community Medicine & Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors: Mika
authors: M
authors: Ala-Korpela
authors: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum, Helsinki, Finland ; Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland ; Diabetes & Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Daniel
authors: D
authors: Gordin
authors: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum, Helsinki, Finland ; Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland ; Diabetes & Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Aila J
authors: AJ
authors: Ahola
authors: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum, Helsinki, Finland ; Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland ; Diabetes & Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Carol
authors: C
authors: Forsblom
authors: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum, Helsinki, Finland ; Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland ; Diabetes & Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland ; Baker IDI Heart & Diabetes Institute, Melbourne, Australia.
authors: Per-Henrik
authors: PH
authors: Groop
authors: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum, Helsinki, Finland ; Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland ; Diabetes & Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Markku
authors: M
authors: Lehto
keywords: High-fat diet; Type 1 diabetes; Vascular dysfunction