Effect of novel dietary ketone ester on heart function in type 2 diabetes

PROJECT PROPOSAL
within the 2018 Marie Skłodowska-Curie Action of European Union Framework programme Horizon 2020

Project Proposal

KE2Dia.eu

Ketone Ester for type 2 Diabetes


Obesity along with type 2 diabetes mellitus is becoming more frequent in the past 20 years. Chronic disturbances in glucose and lipid levels in plasma increase cardiac morbidity and mortality. Diabetic heart diseases are characterized by metabolic, functional and structural alterations, lead to excess risk of cardiovascular incidents. The ketone bodies are produced normally in the liver from mobilized free fatty acids (FFA) in response to changes in glucose and insulin levels, during fasting.

Circulating ketone bodies are a high energy fuel, that could supply a heart, yet ketosis is often inappropriately feared because high ketone levels are involved in the adverse effects of uncontrolled type 1 diabetes. This misapprehension has overshadowed the therapeutic potential of ketosis resulting from a ketogenic diet, which has been used for over 70 years to treat diabetes. However, the ketogenic diet leads to the increased level of free fatty acids. A better alternative could be an edible ester form of d-beta-hydroxybutyrate [(R)-3-hydroxybutyl (R)-3-hydroxybutyrate] called ∆G, that has been developed in the hope that the ingestion of ∆G drinks would create a novel physiological ketosis for diabetes without elevating FFA. Novel ∆G can be consumed in conjunction with a normal diet, thereby offering the same benefits as the ketogenic diet. 

Recent experiments on rats showed that ∆G improves heart energy supply and lipid profile. Thus, the aim of this project is to evaluate if and why the novel ketone ester improves the function, morphology and energetics of the diabetic heart (1) in obese mice and (2) in obese mice after myocardial infarction (3) considering differences related to the gender by introducing both-male & female mice.

The result will contribute to the better understanding of type 2 diabetes pathology and diabetic heart diseases in gender context. Due to the more frequent obesity along with type 2 diabetes in the past 20 years, the results will bring the benefits to the society through better prophylaxis and treatment of motioned civilization diseases.

The proposal was awarded Marie Skłodowska-Curie Actions Seal of Excellence in 2016.

Project Proposal Status:

WHY IS IT IMPORTANT?
ABOUT THE HOST
UNIVERSITY OF OXFORD
WHAT ABOUT INNOVATION?
SUPERVISOR

Kieran Clarke

Professor of Physiological Biochemistry

Kieran Clarke, the Professor of Physiological Biochemistry and British Heart Foundation Principal Scientist in the Department of Physiology, Anatomy and Genetics at the University of Oxford. Prior to her current appointment, she was a Group Leader for the National Research Council of Canada (in Biomedical Nuclear Magnetic Resonance Spectroscopy) and an Adjunct Professor in the Department of Physiology at Ottawa University in Canada. Prof. Clarke has gained her Ph.D. in Biochemistry from the University of Queensland in Australia. She conducted her postdoctoral research at Harvard University Medical School Nuclear Magnetic Resonance Laboratory. Prof. Clarke has over 20 years of experience in cardiac function and energy metabolism using cardiovascular MRI and spectroscopy Cardiac Metabolism Research Group

THE FUTURE FELLOW

Dorian Nowacki

Ph.D. in Medical Sciences, M.Sc., Eng.

Currently, as the co-founder and CEO of  Health Inn Med sp. o. o. [ltd.] he is involved in Dietetics and Innovative Medical Nutrition.

Dr. Nowacki received Ph.D. degree with high honours from the Faculty of Medicine of the Wroclaw Medical University. The subject of the Doctoral research was the effect of new generation phospholipid fraction on blood pressure and endothelial function in hypertensive rats. The research work was a part of one of the largest Wroclaw R&D project OVOCURA: ‘Innovative technologies of biospecimen production based on new generation of eggs.’

After graduation, he was hired as Assistant Professor at the Faculty of Biotechnology of the University of Wroclaw and at the Department of Human Nutrition of the Wroclaw University of Environmental and Life Sciences, where he conducted the research related to the role of functional food and bio-specimens in prevention of civilization dieses.

The research of his Master’s thesis regarded the effect of culture in simulated microgravity on embryoid bodies and mouse embryonic gonads development. The researches for the Master thesis were carried out in Italy at the Faculty of Medicine of the University of Rome Tor Vergata.

The implementation potential of his previous research allows to be a laureate of the Top 500 Innovators Programme led by Polish Ministry of Science and Higher Education. Within the programme he took a professional internship at the University of Cambridge and The University of Oxford. He also gained international experience during internships at the Laboratory of Behavioral Neuroscience of National Council of Research (Consiglio Nazionale delle Ricerche) in Rome in Italy and at the Sackler Medical Faculty of the University of Tel Aviv in Israel.

He is the author and co-author of international medical articles as well as a co-author of patents regarding the use of innovative phospholipids in the prevention of cardiovascular diseases.

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Why is it important?

Diabetes

International Diabetes Federation estimates that in Europe in 2015 about 59.8 million people had diabetes, moreover one of two adults is undiagnosed. Prognoses for 2040 shows about 71.1 million people in Europe will be suffering due to diabetes, the world’s estimate number of people with diabetes will reach about 642 million. Social expenditures estimate 673 billion dollars is disbursed for diabetes per year. The incidence of obesity and, concomitantly, type 2 diabetes mellitus has been rapidly increasing over the last 20 years, such that it is now reaching epidemic proportions.

Gender and Diabetes

Pathology and pathogenesis of diabetes obviously depends on the gender. Women are less exposed to the implications related to obesity, this could be due to the differences in regional fat accumulation and insulin sensitivity. Whereas, males are less likely to pass on type 2 diabetes to the next generation. The stress and body weight status account for risk factors of type 2 diabetes are also related to the gender. Work stress is a more relevant risk factor in women, especially for obese women. Moreover, in non-obese men, work stress is related to lower risk of type 2 diabetes. In women with heart failure, diabetes is a higher risk factor for mortality in comparison to men. Gender should not be ignored in the context of future diabetic research. Understanding the role of gender in diabetes might be crucial in future treatment and prevention. This reason is why in this research proposal it is going to involve both-sex testing.

Benefits for the EU citizens

The results of the following project will bring the benefits to the EU citizens through better prophylaxis and treatment of diabetes. Thus, it will also decrease the social expenses including health expenditure related to the obesity and type 2 diabetes complications.

What about Innovation and Novelty?

Ketone Ester is the innovation in itself

THE HOST

University of Oxford

Department of Physiology, Anatomy and Genetics

Department of Physiology, Anatomy and Genetics is a pre-clinical department of Division of Medical Sciences of the University of Oxford. University of Oxford is one of the world’s leading Universities in research and education, and reached the 1st place by subject of Anatomy and Physiology in the QS World University Rankings for 2017 and 2018. The University of Oxford was awarded by logo HR Excellence in Research. Department of Physiology, Anatomy and Genetics has received ECU’s Silver Athena Swan award.

QS World University Rankings by Subject 2018QS World University Rankings by Subject 2017

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