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Open Access Research

Patients with type 1 diabetes show signs of vascular dysfunction in response to multiple high-fat meals

Mariann I Lassenius123, Ville-Petteri Mäkinen4, Christopher L Fogarty123, Lina Peräneva123, Matti Jauhiainen5, Pirkko J Pussinen6, Marja-Riitta Taskinen37, Juha Kirveskari8, Outi Vaarala9, Janne K Nieminen9, Sohvi Hörkkö10, Antti J Kangas11, Pasi Soininen1112, Mika Ala-Korpela11121314, Daniel Gordin123, Aila J Ahola123, Carol Forsblom123, Per-Henrik Groop11523*, Markku Lehto123* and on behalf of the FinnDiane Study Group

Author Affiliations

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

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Nutrition & Metabolism 2014, 11:28  doi:10.1186/1743-7075-11-28

Published: 13 June 2014

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.

Keywords:
High-fat diet; Vascular dysfunction; Type 1 diabetes