Investigating the Impact of Polyunsaturated Fatty Acids in Patients with Type 1 Diabetes mellitus – a Pilot Study
Background: Strong evidence indicates that fatty acid composition might modulate inflammation and autoimmunity. Since type 1 diabetes mellitus (T1DM) is an autoimmune disease due to a chronic inflammatory destruction of insulin-secreting pancreatic β cells by autoantibodies, we hypothesize that there is a difference in ectopic lipid composition, especially of polyunsaturated fatty acids (PUFA), in patients with T1DM compared to controls. Preliminary data of our study group demonstrate differences in ectopic lipid content in T1DM, with an almost 70% lower hepatic fat content compared to matched controls. However, not only the total amount of tissue triglycerides, but also the quality, e.g. the saturation/unsaturation profile of fatty acid chains, might be of important interest. So far, lipid composition and the amount of PUFA has not been determined in patients with T1DM in vivo.
Hypothesis: Based on our preliminary data and evidence from the literature we hypothesize:
• that patients with T1DM are characterized by a disease specific pattern of fatty acids in adipose tissue
• that alterations in lipid composition and the amount of PUFA between intra-individual fat depots is linked to autoimmunity.
• that the pattern of ectopic lipid deposition and composition is affected by metabolic control.
Methods: We intent to perform high resolution 1H magnetic resonance (MR) spectroscopy and imaging measurements at 3 and 7 Tesla to assess ectopic lipid composition in liver, skeletal muscle, heart and pancreas, as well as in visceral and subcutaneous fat mass in patients with recently diagnosed T1DM. MR measurements will be repeated after 3 months to distinguish between the effects of metabolic control and autoimmunity. They will be compared to T1DM patients with a long disease duration and to healthy controls matched for anthropometric characteristics.
Significance: This study will advance our knowledge on the relation between lipid composition and autoimmunity in patients with T1DM. We expect to provide novel mechanistic insights into the role of altered ectopic lipid composition and lipid storage. This might help to further advance our knowledge on the importance of PUFAs and potentially helps to optimize future prevention- and treatment strategies in T1DM.
Methods and Skills:
Clinical studies; magnetic resonance spectroscopy (MRS)
Smajis S, Gajdošík M, Pfleger L, Traussnigg S, Kienbacher C, Halilbasic E, Ranzenberger-Haider T, Stangl A, Beiglböck H, Wolf P, Lamp T, Hofer A, Gastaldelli A, Barbierri C, Luger A, Trattnig S, Kautzky-Willer A, Krššák M, Trauner M, Krebs M. Metabolic effects of a prolonged, very-high-dose dietary fructose challenge in healthy subjects. Am J Clin Nutr 2019 Dec 4 [Epub ahead of print]
Wolf P, Beiglböck H, Fellinger P, Pfleger L, Aschauer S, Gessl A, Marculescu R, Trattnig S, Kautzky-Willer A, Luger A, Winhofer Y, Krššák M, Krebs M. Plasma renin levels are associated with cardiac function in primary adrenal insufficiency. Endocrine 65: 399-407, 2019
Wolf P, Mayr J, Beiglböck H, Fellinger P, Winhofer Y, Poglitsch M, Gessl A, Kautzky-Willer A, Luger A, Krebs M. Identifying a disease-specific renin-angiotensin-aldosterone system fingerprint in patients with primary adrenal insufficiency. Eur J Endocrinol 181: 39-44, 2019
Wolf P, Fellinger P, Pfleger L, Smajis S, Beiglböck H, Gajdošík M, Anderwald CH, Trattnig S, Luger A, Winhofer Y, Krššák M, Krebs M. Reduced hepatocellular lipid accumulation and energy metabolism in patients with long standing type 1 diabetes mellitus. Sci Rep 9: 2576, 2019