Patients with type 1 diabetes show signs of vascular dysfunction in response to multiple high-fat meals
1 Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum, Helsinki, Finland
2 Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland
3 Diabetes & Obesity Research Program, Research Program’s Unit, University of Helsinki, Helsinki, Finland
4 Department of Integrative Biology and Physiology, University of California, Los Angeles, USA
5 Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
6 Institute of Dentistry, University of Helsinki, Helsinki, Finland
7 Heart and Lung Center, Cardiovascular Research Group, HUCH, Helsinki, Finland
8 Department of Bacteriology, HUSLAB, Helsinki, Finland
9 Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland
10 Department of Medical Microbiology and Immunology, University of Oulu, and Nordlab, Oulu, Finland
11 Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland
12 NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
13 Oulu University Hospital, Oulu, Finland
14 Computational Medicine, School of Social and Community Medicine & Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK
15 Baker IDI Heart & Diabetes Institute, Melbourne, Australia
Nutrition & Metabolism 2014, 11:28 doi:10.1186/1743-7075-11-28Published: 13 June 2014
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.
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.
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).
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.