The Role of Endogenous Lactate in Brain Preservation and Counterregulatory Defenses Against Hypoglycemia
NCT ID: NCT02308293
Last Updated: 2016-11-25
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
30 participants
INTERVENTIONAL
2015-01-31
2016-07-31
Brief Summary
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Objective: To investigate the effect of elevated levels of endogenous lactate on brain lactate accumulation and on counterregulatory responses to, symptomatic awareness of and cognitive function during hypoglycemia in patients with T1DM with and without hypoglycemia unawareness and normal controls.
Hypothesis: The investigators hypothesize first that endogenous lactate, when raised through high intensity exercise, preserves neuronal metabolism during subsequent hypoglycemia, which in turn will attenuate counterregulatory hormone responses, appearance of symptoms and deterioration of cognitive function. Second, the investigators posit that these effects will be augmented in patients with hypoglycemia unawareness compared to healthy subjects and T1DM patients with normal awareness as a consequence of greater transport capacity of lactate into the brain.
Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
CROSSOVER
BASIC_SCIENCE
NONE
Study Groups
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High intensity exercise
Subjects will preform a high intensity training exercise (3\* 30 seconds all out sprint on a cycle ergometer) to raise plasma lactate levels
High intensity exercise
3x30 seconds 'all out' sprints
Lay down comfortably
As a control conditions, subjects wil lay down comfortably and rest
Lay down comfortably
rest
Interventions
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High intensity exercise
3x30 seconds 'all out' sprints
Lay down comfortably
rest
Eligibility Criteria
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Inclusion Criteria
* Body-Mass Index: 18-30 kg/m2
* Blood pressure: \<160/90 mmHg
* Recreationally active: i.e. taking part in competitive sport or regular exercise training, of a non-professional nature, once or more a week.
* Diabetes duration ≥ 1 year
* Age: 18-40 years
* Body-Mass Index: 18-30 kg/m2
* HbA1c: 42-75 mmol/mol (6-9%)
* Outcome Clarke questionnaire: 0-1
* Blood pressure: \<160/90 mmHg
* Recreationally active: i.e. taking part in competitive sport or regular exercise training, of a non-professional nature, once or more a week
* Diabetes duration ≥ 1 year
* Age: 18-40 years
* Body-Mass Index: 18-30 kg/m2
* HbA1c: 42-75 mmol/mol (6-9%)
* Outcome Clarke questionnaire: =\>3
* Blood pressure: \<160/90 mmHg
* Recreationally active
Exclusion Criteria
* Presence of any medical condition that might interfere with the study protocol, such as brain injuries, epilepsy, a major cardiovascular disease event or anxiety disorders
* Use of any medication, except for oral contraceptives
* MR(I) contraindications (pregnancy, severe claustrophobia, metal parts in body)
* Orthopedic and/or neurological diseases that impair exercise
* Cardiopulmonary disease as stated in the 2001 American heart association and 2002 American college of cardiology/American heart association guidelines
* Use of any other medication than insulin, except for oral contraceptives or stable thyroxine supplementation therapy
* complications of T1DM, including proliferative retinopathy, neuropathy or nephropathy
18 Years
40 Years
ALL
Yes
Sponsors
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Dutch Diabetes Research Foundation
OTHER
European Foundation for the Study of Diabetes
OTHER
Radboud University Medical Center
OTHER
Responsible Party
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Principal Investigators
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Bastiaan de Galan, Dr.
Role: PRINCIPAL_INVESTIGATOR
Radboud University Medical Center
Locations
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Radboud umc
Nijmegen, , Netherlands
Countries
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References
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van de Ven KC, van der Graaf M, Tack CJ, Klomp DW, Heerschap A, de Galan BE. Optimized [1-(13)C]glucose infusion protocol for 13C magnetic resonance spectroscopy at 3T of human brain glucose metabolism under euglycemic and hypoglycemic conditions. J Neurosci Methods. 2010 Jan 30;186(1):68-71. doi: 10.1016/j.jneumeth.2009.10.025. Epub 2009 Nov 11.
van de Ven KC, de Galan BE, van der Graaf M, Shestov AA, Henry PG, Tack CJ, Heerschap A. Effect of acute hypoglycemia on human cerebral glucose metabolism measured by (1)(3)C magnetic resonance spectroscopy. Diabetes. 2011 May;60(5):1467-73. doi: 10.2337/db10-1592. Epub 2011 Apr 4.
van de Ven KC, van der Graaf M, Tack CJ, Heerschap A, de Galan BE. Steady-state brain glucose concentrations during hypoglycemia in healthy humans and patients with type 1 diabetes. Diabetes. 2012 Aug;61(8):1974-7. doi: 10.2337/db11-1778. Epub 2012 Jun 11.
De Feyter HM, Mason GF, Shulman GI, Rothman DL, Petersen KF. Increased brain lactate concentrations without increased lactate oxidation during hypoglycemia in type 1 diabetic individuals. Diabetes. 2013 Sep;62(9):3075-80. doi: 10.2337/db13-0313. Epub 2013 May 28.
Maddock RJ, Casazza GA, Buonocore MH, Tanase C. Vigorous exercise increases brain lactate and Glx (glutamate+glutamine): a dynamic 1H-MRS study. Neuroimage. 2011 Aug 15;57(4):1324-30. doi: 10.1016/j.neuroimage.2011.05.048. Epub 2011 May 27.
Wiegers EC, Rooijackers HM, van Asten JJA, Tack CJ, Heerschap A, de Galan BE, van der Graaf M. Elevated brain glutamate levels in type 1 diabetes: correlations with glycaemic control and age of disease onset but not with hypoglycaemia awareness status. Diabetologia. 2019 Jun;62(6):1065-1073. doi: 10.1007/s00125-019-4862-9. Epub 2019 Apr 19.
Wiegers EC, Rooijackers HM, Tack CJ, Groenewoud HJMM, Heerschap A, de Galan BE, van der Graaf M. Effect of Exercise-Induced Lactate Elevation on Brain Lactate Levels During Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia. Diabetes. 2017 Dec;66(12):3105-3110. doi: 10.2337/db17-0794. Epub 2017 Sep 21.
Rooijackers HM, Wiegers EC, van der Graaf M, Thijssen DH, Kessels RPC, Tack CJ, de Galan BE. A Single Bout of High-Intensity Interval Training Reduces Awareness of Subsequent Hypoglycemia in Patients With Type 1 Diabetes. Diabetes. 2017 Jul;66(7):1990-1998. doi: 10.2337/db16-1535. Epub 2017 Apr 18.
Other Identifiers
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End_lac_sympt
Identifier Type: -
Identifier Source: org_study_id