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Exercise-related Fuel Metabolism and Glucose Stability in Individuals with Type 1 Diabetes Mellitus

English title Exercise-related Fuel Metabolism and Glucose Stability in Individuals with Type 1 Diabetes Mellitus
Applicant Stettler Christoph
Number 149321
Funding scheme Project funding (Div. I-III)
Research institution Poliklinik für Endokrinologie, Diabetologie und Klinische Ernährung Inselspital
Institution of higher education University of Berne - BE
Main discipline Clinical Endocrinology
Start/End 01.03.2014 - 28.02.2017
Approved amount 379'243.00
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All Disciplines (2)

Discipline
Clinical Endocrinology
Pathophysiology

Keywords (5)

Type 1 Diabetes Mellitus; Exercise-related Fuel Metabolism; Intermittent High Intensity Exercise; Fructose Metabolism; Exercise Physiology

Lay Summary (German)

Lead
Sportliche Aktivität ist bei Typ 1 Diabetes (T1DM) mit einem erhöhten Risiko für Unterzuckerungen verbunden und kann die Blutzuckerschwankungen verstärken. Dies erhöht das Risiko für langfristige Komplikationen. Um Patienten mit T1DM trotzdem sportliche Aktivität zu ermöglichen, untersucht dieses Projekt alternative Strategien zur Stabilisierung des Blutzuckers während des Sports und untersucht dabei auch den Energiestoffwechsel während Sport bei T1DM im Detail mit modernesten Methoden.
Lay summary
Typ 1 Diabetes (T1DM) ist gekennzeichnet durch eine Zerstörung der Insulin-produzierenden Zellen in der Bauchspeicheldrüse. Zwar machen Patienten mit T1DM aktuell nur 5-10% der Diabetesfälle aus, dies sind aber 25'000 bis 30'000 Patienten alleine in der Schweiz. Zudem nimmt die Häufigkeit von T1DM zu. Patienten mit T1DM sind oft aktive Menschen, die gerne Sport betreiben. Anders als bei Typ 2 Diabetes, wo Bewegung klar zu einer Verbesserung der Erkrankung führt, ist die Situation beim T1DM wesentlich heikler: Sport kann bei T1DM zu verstärkten Blutzuckerschwankungen führen und dabei insbesondere das Risiko von Unterzuckerungen erhöhen. Deshalb stellen viele Patienten mit T1DM den Blutzucker im Zusammenhang mit sportlichen Aktivitäten zur Sicherheit etwas zu hoch ein. Dadurch ist ihre Stoffwechseleinstellung aber entsprechend schlechter, was das Risiko für mittel- und langfristige Komplikationen erhöht. Eine Möglichkeit, diese Problematik anzugehen, besteht in der Reduktion der Insulinmenge anlässlich von sportlicher Aktivität (gut umsetzbar mittels Insulinpumpe). Gerade bei sportlich aktiven Patienten ist der Einsatz einer Insulinpumpe aber zT schwierig (Gefahr der mechanischen Beschädigung von Pumpe/Katheter). Bei Patienten, die ein modernes Insulinschema mit langwirkendem Basis- und raschwirkendem Bolusinsulin vorziehen, sind rasche Anpassungen schwieriger. Das aktuelle Projekt untersucht zwei alternative Strategien zur Stabilisierung des Blutzuckers bei T1DM während des Sports und studiert dabei den Stoffwechsel während des Sportes im Detail mittels modernster Technik. Studie 1 wird den Einfluss von unterschiedlichen Trainingsintensitäten (kontinuierlich gegenüber Intervall) untersuchen. Dahinter steht die Überlegung, dass mit hoher Intensität Gegenspielerhormone von Insulin stimuliert werden können. Studie 2 untersucht, ob die Zusammensetzung von Kohlehydratdrinks (Glucose gegenüber einer Mischung von Glucose und Fructose) die Blutzuckerstabilität beeinflusst.
Direct link to Lay Summary Last update: 27.09.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Metabolic Effects of Glucose-Fructose Co-Ingestion Compared to Glucose Alone during Exercise in Type 1 Diabetes.
Bally Lia, Kempf Patrick, Zueger Thomas, Speck Christian, Pasi Nicola, Ciller Carlos, Feller Katrin, Loher Hannah, Rosset Robin, Wilhelm Matthias, Boesch Chris, Buehler Tania, Dokumaci Ayse S, Tappy Luc, Stettler Christoph (2017), Metabolic Effects of Glucose-Fructose Co-Ingestion Compared to Glucose Alone during Exercise in Type 1 Diabetes., in Nutrients, 9(2), 1-13.
Accuracy of continuous glucose monitoring during differing exercise conditions
Bally Lia, Zueger Thomas, Pasi Nicola, Carlos Ciller, Paganini Daniela, Stettler Christoph (2016), Accuracy of continuous glucose monitoring during differing exercise conditions, in Diabetes Research and Clinical Practice, 112, 1-5.
Metabolic and hormonal response to intermittent high-intensity and continuous moderate intensity exercise in individuals with type 1 diabetes: a randomised crossover study
Bally Lia, Zueger Thomas, Buehler Tania, Dokumaci Ayse S., Speck Christian, Pasi Nicola, Ciller Carlos, Paganini Daniela, Feller Katrin, Loher Hannah, Rosset Robin, Wilhelm Matthias, Tappy Luc, Boesch Chris, Stettler Christoph (2016), Metabolic and hormonal response to intermittent high-intensity and continuous moderate intensity exercise in individuals with type 1 diabetes: a randomised crossover study, in Diabetologia, 59(4), 776-784.
Methodological and physiological test-retest reliability of 13 C-MRS glycogen measurements in liver and in skeletal muscle of patients with type 1 diabetes and matched healthy controls Test-Retest Reliability of Liver and Muscle Glycogen Determination
Buehler Tania, Bally Lia, Dokumaci Ayse Sila, Stettler Christoph, Boesch Chris (2016), Methodological and physiological test-retest reliability of 13 C-MRS glycogen measurements in liver and in skeletal muscle of patients with type 1 diabetes and matched healthy controls Test-Retest Reliability of Liver and Muscle Glycogen Determination, in NMR in Biomedicine, 29(6), 796-805.
Hepatic and intramyocellular glycogen stores in adults with type 1 diabetes and healthy controls
Bally L., Buehler T., Dokumaci A.S., Boesch C., Stettler C. (2015), Hepatic and intramyocellular glycogen stores in adults with type 1 diabetes and healthy controls, in Diabetes Research and Clinical Practice, 109(1), e1-e3.

Collaboration

Group / person Country
Types of collaboration
Group of Prof. Chris Boesch, Unit for Magnetic Resonance Spectroscopy Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
University Institute of Clinical Chemistry, Bern University Hospital and University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
University of Cambridge UK Great Britain and Northern Ireland (Europe)
- Exchange of personnel
Group of Prof. Luc Tappy, University of Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Universitätsklinik für Endokrinologie/Diabetologie Graz Austria (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Annual Meeting of the Swiss Society of Endocrinology & Diabetes Talk given at a conference Metabolomic profiling during different exercise conditions in type 1 diabetes 16.11.2016 Bern, Switzerland Stettler Christoph; Bally Lia;
Jahrestagung der Schweiz Gesellschaft für Sportmedizin Talk given at a conference Exercise and Hormones 28.10.2016 Interlaken, Switzerland Stettler Christoph;
52nd European Association for the Study of Diabetes (EASD) Annual Meeting Poster Metabolic effects of combined fructose-glucose supplementation versus glucose alone in exercising individuals with type 1 diabetes 12.09.2016 Munich, Germany Tappy Luc; Zwygart-Brügger Karin; Kempf Patrick; Boesch Chris; Bally Lia; Wilhelm Matthias; Stettler Christoph;
Annual Meeting of the Swiss Society for Endocrinology and Diabetes Talk given at a conference Type 1 Diabetes and Physical Exercise - from the lab to real world - Plenary Lecture 13.11.2015 Bern, Switzerland Stettler Christoph;
Annual Meeting of the Swiss Society of Endocrinology & Diabetes Talk given at a conference Differences in metabolic response to co-ingestion of fructose and glucose vs. glucose alone during prolonged exercise in individuals with type 1 diabetes 12.11.2015 Bern, Switzerland Boesch Chris; Stettler Christoph; Zwygart-Brügger Karin; Bally Lia; Tappy Luc; Wilhelm Matthias;
51st European Association for the Study of Diabetes (EASD) Annual Meeting Poster Glucose metabolism under differing exercise conditions in type 1 diabetes 16.09.2015 Stockholm, Sweden Zwygart-Brügger Karin; Boesch Chris; Wilhelm Matthias; Stettler Christoph; Tappy Luc; Bally Lia;
8th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD) Talk given at a conference Accuracy of continuous glucose monitoring during resting and exercise conditions in individuals with type 1 diabetes 18.02.2015 Paris, France Bally Lia; Stettler Christoph;
Annual Meeting of the Swiss Society of Endocrinology & Diabetes Talk given at a conference Carbohydrate requirements during intermittent high intensity exercise compared to continuous moderate intensity exercise in individuals with type 1 diabetes 27.11.2014 Bern, Switzerland Zwygart-Brügger Karin; Stettler Christoph; Boesch Chris; Tappy Luc; Wilhelm Matthias; Bally Lia;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
MEDGES DGRB Talk 24.11.2016 Basel, Switzerland Stettler Christoph;
Nordwestschweizer Diabetessymposium Talk 25.08.2016 Basel, Switzerland Stettler Christoph;


Self-organised

Title Date Place
Type 1 diabetes and exercise 03.06.2016 Bern, Switzerland

Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Type 1 diabetes and exercise German-speaking Switzerland 2016

Awards

Title Year
Swiss Society of Endocrinology and Diabetes: Award for the best oral presentation of a clinical research project, annual SGEDM (Swiss Society of Endocrinology & Diabetes Meeting) 2014
Swiss Society of Endocrinology and Diabetes: Award for the best oral presentation of a clinical research project, annual SGEDM (Swiss Society of Endocrinology & Diabetes Meeting) 2014

Associated projects

Number Title Start Funding scheme
130331 Die Wirkung von fettreicher Diät und körperlicher Aktivität auf die Flexibilität und die Einlagerung von Lipiden in ektope Fett Depots (intramyocellulär, intrahepatocellulär, intramyokardiale Lipide) 01.03.2011 Project funding (Div. I-III)

Abstract

Background: While the beneficial effects of physical exercise are well accepted in type 2 diabetes (T2DM), the role of exercise is more complex in type 1 diabetes (T1DM). Although less frequent than T2DM, T1DM is responsible for 5 to 10 percent of diabetic patients, translating into an estimated number of 25,000 to 30,000 patients with T1DM in Switzerland, many of them being physically active. T1DM is characterized by an autoimmune destruction of the pancreatic beta-cells and treatment essentially consists of exogenous insulin application. For these individuals exercise is associated with an increased risk for hypoglycemia due to increased exercise-associated insulin sensitivity. Since rapid adaptation of insulin dosage may be difficult, alternative strategies to improve exercise-associated glucose stability are required. In addition, exercise-related fuel metabolism in individuals with T1DM is still poorly investigated, and a better understanding of these metabolic pathways may help to refine therapeutic recommendations for these patients. Increasing evidence suggests that intermittent high intensity exercise (IHE) by increasing counter-regulatory hormones (eg. glucagon, catecholamines, cortisol, etc) and by providing glucose from endogenous stores (intrahepatic and intramyocellular glycogen) may counter-balance the risk of exercise-associated hypoglycemia. However, previous studies assessing IHE in T1DM were limited by heterogeneous study populations, comparably short exercise protocols, and deficits in standardization procedures. In addition, a comprehensive assessment of fuel metabolism associated with IHE has not been performed so far. As a consequence results were controversial and interpretation as well as clinical applicability was restricted. An alternative strategy to maintain glucose stability during exercise in T1DM may be deduced from recent studies in non-diabetic individuals suggesting that the combined ingestion of fructose and glucose during exercise provides the liver with an increased amount of gluconeogenetic precursors, thereby reducing consumption of endogenous glycogen stores by competitively increased oxidation of lactate. However, studies assessing the impact of fructose ingestion during exercise in T1DM have not been performed so far.Specific Aims: Based on two approaches the present proposal aims at comprehensively assessing exercise-related fuel metabolism in T1DM and investigating novel strategies to stabilize exercise-associated glycemia:Study 1 will assess exercise-related fuel metabolism of two specific IHE protocols (characterized by different baseline intensities - sub-studies 1A and 1B) compared with iso-energetic continuous exercise (CONT). It will be investigated whether IHE increases glucose stability during and after exercise compared with CONT.Study 2 will assess the impact of a carbohydrate supplementation using a defined mixture of glucose and fructose (GLU-FRU) compared with an iso-energetic supplementation with glucose alone (GLU) on exercise-related fuel metabolism. It will be studied whether GLU-FRU contributes to stabilization of glucose levels during and after exercise when compared to an iso-energetic supplementation with GLU alone.Experimental Design: In a standardized setting including continuous glucose monitoring and pre-exercise glycogen loading we will combine kinetic studies using stable isotopes and quantification of intrahepatic and intramyocellular glycogen stores using magnetic resonance spectroscopy. Expected Value: Results will improve our understanding of exercise-associated fuel metabolism in T1DM and will provide clinically applicable strategies for patients with T1DM. Study 1 will clarify if IHE in standardized conditions improves exercise-related glucose stability by defining underlying mechanisms. Study 2 will provide evidence on the effect of a combined ingestion of fructose and glucose on exercise-associated glycemia in T1DM as opposed to glucose alone, thereby broadening our insights into the metabolic role of fructose.
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