- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT02068638
Impact of Physical Activity on Blood Glucose Stability and Energy Stores in Individuals With Type 1 Diabetes (CARBEX1)
Exercise-related Fuel Metabolism and Glucose Stability in Individuals With Type 1 Diabetes Mellitus
Přehled studie
Postavení
Detailní popis
Background
Regular physical activity enhances insulin sensitivity in both healthy subjects and patients with diabetes mellitus. However, while the effects of physical activity on glucose control are undoubtedly beneficial in patients with type 2 diabetes, exercise can cause major disturbances in blood glucose levels in type 1 diabetic individuals. Hypoglycemia is a common complication in patients with T1DM engaging in endurance activities such as running and cycling. So far there are limited strategies suggested to improve exercise-related blood sugar self-management. Current recommendations focus on variation in timing and dosage of insulin administration and adjustments in carbohydrate intake. Since rapid adaptation of insulin dosage may be difficult, alternative strategies to improve exercise-related glucose stability are required. Increasing evidence suggests that intermittent high intensity exercise (IHE), by triggering a counterregulatory hormone response, may counter-balance the risk of exercise-associated hypoglycemia. However, previous studies investigating IHE in T1DM were limited by heterogeneous study populations, comparably short exercise protocols, and deficits in standardization procedures. In addition, a comprehensive assessment of the underlying fuel metabolism has not been performed so far. As a consequence, the results remain controversial and their interpretation as well as applicability are restricted.
A further alternative strategy to maintain stable glycemia during exercise 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 gluconeogenic precursors, thereby reducing consumption of endogenous glycogen stores.Moreover, conversion of fructose into glucose and lactate may provide constant and efficient fuel for working muscles. However, studies assessing the impact of fructose ingestion during exercise in patients with T1DM have not been performed so far.
Objective
The investigators aim to assess the impact of two novel non-pharmaceutical and easily feasible approaches on exercise-related blood glucose stability and its underlying exercise-related fuel metabolism in patients with T1DM.
Substudy A will assess the influence on exercise-related glycemia and fuel metabolism of an IHE protocol compared to an iso-energetic continuous exercise (CONT). It will be investigated whether individuals reach more stable blood glucose levels when engaging in IHE compared to CONT.
Substudy B will investigate whether fueling the patients with a mixed oral 1:1 glucose-fructose carbohydrate solution will maintain glucose values within a more stable range when compared to carbohydrate supplementation by glucose alone.
Methods
Blood glucose levels, counterregulatory hormones, metabolites such as lactate and free fatty acids as well as inflammatory biomarkers will be assessed by regular blood samplings. By means of oral and intravenously given stable isotopes (U-13 C glucose and 2H glucose) exercise-related glucose kinetics will be investigated. Exercise-induced glycogen consumption will be measured using magnetic resonance spectroscopy technology. Late glycemic excursions will be recorded by continuous glucose monitoring systems.
In order to validate 13C magnetic resonance spectroscopy (MRS) measurement of hepatic and myocellular glycogen content a pre-study involving 10 patients and an equal number of matched healthy controls will be performed (validation and reproducibility study).
Typ studie
Zápis (Aktuální)
Fáze
- Nelze použít
Kontakty a umístění
Studijní místa
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Bern, Švýcarsko, 3010
- Division of Endocrinology, Diabetes and Clinical Nutrition, Bern University Hospital
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Male
- Aged 18 to 35 years
- Diabetes mellitus duration for at least 5 years
- No change in insulin regimen for at least 3 months prior to the study
- Under acceptable to good metabolic control
- Normal insulin sensitivity
- Regular physical activity
- BMI in the range of 18-25 kg/m2
- Written informed consent
Exclusion Criteria
- Diabetes-related complications (macro and microvascular)
- Anemia (hemoglobin concentration <130g/l)
- Abnormal thyroid function
- Dyslipidemia
- Major depression, psychosis and other severe personality disorders, claustrophobia
- Active neoplasia
- Contraindications to exposure to a 3 T magnetic field
- Abnormal liver or renal function
- Smoking, drug abuse, or daily alcohol consumption >60g
- Participation in another study
- Medication other than insulin
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Podpůrná péče
- Přidělení: Randomizované
- Intervenční model: Crossover Assignment
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: IHE first, CONT second, CSII and MDI therapy
IHE: intermittent high intensity exercise: integration of 10 s maximal sprints every 10 minutes in a continuous low to moderate intensity exercise of 90 minutes CONT (occurring after a washout period of 2-8 weeks): continuous moderate intensity exercise of 90 minutes
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IHE: intermittent high intensity exercise: integration of 10 s maximal sprints every 10 minutes in a continuous low to moderate intensity exercise of 90 minutes.
CONT (occurring after a washout period of 2-8 weeks): continuous moderate intensity exercise of 90 minutes
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Experimentální: CONT first, IHE second,CSII and MDI therapy
CONT: continuous moderate intensity exercise of 90 minutes.
IHE (occurring after a washout period of 2-8 weeks): intermittent high intensity exercise: integration of 10 s maximal sprints every 10 minutes in a continuous low to moderate intensity exercise of 90 minutes
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CONT: continuous moderate intensity exercise of 90 minutes.
IHE (occurring after a washout period of 2-8 weeks): intermittent high intensity exercise: integration of 10 s maximal sprints every 10 minutes in a continuous low to moderate intensity exercise of 90 minutes
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Experimentální: GLU first, GLUFRU second, CSII and MDI therapy
GLU: ingestion of a 6% carbohydrate solution (consisting of 100 g glucose dissolved in 1000 ml tap water) over a continuous moderate exercise of 90 minutes.
GLU FRU (occurring after a washout period of 2-8 weeks): ingestion of a 20% carbohydrate solution (consisting of 100 g glucose + 100 g fructose dissolved in 1000 ml tap water) over a continuous moderate exercise of 90 minutes.
CSII = continuous subcutaneous insulin infusion.
MDI=multiple daily injections.
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: ingestion of a 6% carbohydrate solution (consisting of 90 g glucose dissolved in 1500 ml tap water) over a continuous moderate exercise of 90 minutes.
GLU FRU (occurring after a washout period of 2-8 weeks): ingestion of a 12% carbohydrate solution (consisting of 90 g glucose + 90 g fructose dissolved in 1500 ml tap water) over a continuous moderate exercise of 90 minutes
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Experimentální: GLU-FRU first, GLU second, CSII therapy
GLU-FRU : ingestion of a 20% carbohydrate solution (consisting of 100 g glucose + 100 g fructose dissolved in 1000 ml tap water) over a continuous moderate exercise of 90 minutes.
GLU (occurring after a washout period of 2-8 weeks): ingestion of a 10% carbohydrate solution (consisting of 100 g glucose dissolved in 1000 ml tap water) over a continuous moderate exercise of 90 minutes.
CSII = continuous subcutaneous insulin infusion.
MDI=multiple daily injections.
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GLU-FRU : ingestion of a 12% carbohydrate solution (consisting of 90 g glucose + 90 g fructose dissolved in 1500 ml tap water) over a continuous moderate exercise of 90 minutes.
GLU (occurring after a washout period of 2-8 weeks): : ingestion of a 6% carbohydrate solution (consisting of 90 g glucose dissolved in 1500 ml tap water) over a continuous moderate exercise of 90 minutes.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Časové okno |
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Amount of exogenous glucose required to maintain glycemia within a range between 7-10mM
Časové okno: 30 minutes (last 30 minutes of 90 min exercise period)
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30 minutes (last 30 minutes of 90 min exercise period)
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Exercise - related glycogen consumption
Časové okno: 90 minutes
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90 minutes
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Glucose kinetics
Časové okno: 180 minutes
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Rate of glucose appearance and disappearance
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180 minutes
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Counterregulatory hormones, metabolites, and inflammatory response
Časové okno: 300 minutes
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300 minutes
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Spiroergometric parameters
Časové okno: 180 minutes
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CO2 and O2 production, RER
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180 minutes
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Pre- and post-exercise glycemic excursions
Časové okno: 72 h pre-exercise and 72 h post-exercise respectively
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72 h pre-exercise and 72 h post-exercise respectively
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Heart rate variability
Časové okno: 90 minutes
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90 minutes
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Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Christoph Stettler, Professor, MD, University of Bern
Publikace a užitečné odkazy
Obecné publikace
- Eckstein ML, Farinha JB, McCarthy O, West DJ, Yardley JE, Bally L, Zueger T, Stettler C, Boff W, Reischak-Oliveira A, Riddell MC, Zaharieva DP, Pieber TR, Muller A, Birnbaumer P, Aziz F, Brugnara L, Haahr H, Zijlstra E, Heise T, Sourij H, Roden M, Hofmann P, Bracken RM, Pesta D, Moser O. Differences in Physiological Responses to Cardiopulmonary Exercise Testing in Adults With and Without Type 1 Diabetes: A Pooled Analysis. Diabetes Care. 2021 Jan;44(1):240-247. doi: 10.2337/dc20-1496. Epub 2020 Nov 12.
- Iscoe KE, Riddell MC. Continuous moderate-intensity exercise with or without intermittent high-intensity work: effects on acute and late glycaemia in athletes with Type 1 diabetes mellitus. Diabet Med. 2011 Jul;28(7):824-32. doi: 10.1111/j.1464-5491.2011.03274.x.
- Guelfi KJ, Ratnam N, Smythe GA, Jones TW, Fournier PA. Effect of intermittent high-intensity compared with continuous moderate exercise on glucose production and utilization in individuals with type 1 diabetes. Am J Physiol Endocrinol Metab. 2007 Mar;292(3):E865-70. doi: 10.1152/ajpendo.00533.2006.
- Stettler C, Jenni S, Allemann S, Steiner R, Hoppeler H, Trepp R, Christ ER, Zwahlen M, Diem P. Exercise capacity in subjects with type 1 diabetes mellitus in eu- and hyperglycaemia. Diabetes Metab Res Rev. 2006 Jul-Aug;22(4):300-6. doi: 10.1002/dmrr.608.
- Jenni S, Oetliker C, Allemann S, Ith M, Tappy L, Wuerth S, Egger A, Boesch C, Schneiter P, Diem P, Christ E, Stettler C. Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus--a prospective single-blinded randomised crossover trial. Diabetologia. 2008 Aug;51(8):1457-65. doi: 10.1007/s00125-008-1045-5. Epub 2008 May 30.
- Bussau VA, Ferreira LD, Jones TW, Fournier PA. The 10-s maximal sprint: a novel approach to counter an exercise-mediated fall in glycemia in individuals with type 1 diabetes. Diabetes Care. 2006 Mar;29(3):601-6. doi: 10.2337/diacare.29.03.06.dc05-1764.
- Bussau VA, Ferreira LD, Jones TW, Fournier PA. A 10-s sprint performed prior to moderate-intensity exercise prevents early post-exercise fall in glycaemia in individuals with type 1 diabetes. Diabetologia. 2007 Sep;50(9):1815-1818. doi: 10.1007/s00125-007-0727-8. Epub 2007 Jun 22.
- Guelfi KJ, Jones TW, Fournier PA. The decline in blood glucose levels is less with intermittent high-intensity compared with moderate exercise in individuals with type 1 diabetes. Diabetes Care. 2005 Jun;28(6):1289-94. doi: 10.2337/diacare.28.6.1289.
- Lecoultre V, Benoit R, Carrel G, Schutz Y, Millet GP, Tappy L, Schneiter P. Fructose and glucose co-ingestion during prolonged exercise increases lactate and glucose fluxes and oxidation compared with an equimolar intake of glucose. Am J Clin Nutr. 2010 Nov;92(5):1071-9. doi: 10.3945/ajcn.2010.29566. Epub 2010 Sep 8.
- Bally L, Zueger T, Buehler T, Dokumaci AS, Speck C, Pasi N, Ciller C, Paganini D, Feller K, Loher H, Rosset R, Wilhelm M, Tappy L, Boesch C, Stettler C. Metabolic and hormonal response to intermittent high-intensity and continuous moderate intensity exercise in individuals with type 1 diabetes: a randomised crossover study. Diabetologia. 2016 Apr;59(4):776-84. doi: 10.1007/s00125-015-3854-7. Epub 2016 Jan 6.
- Bally L, Zueger T, Pasi N, Carlos C, Paganini D, Stettler C. Accuracy of continuous glucose monitoring during differing exercise conditions. Diabetes Res Clin Pract. 2016 Feb;112:1-5. doi: 10.1016/j.diabres.2015.11.012. Epub 2015 Dec 19.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 001/14
- 320030_149321/1 (Jiný identifikátor: Swiss National Science Foundation (SNF))
- 191/10 (Jiný identifikátor: Ethics Committee (approval of measurements for healthy controls))
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