The Effect of Exercise-induced Hyperlacticacidemia on Counterregulatory Responses, Symptoms, Cognitive Function and Brain Lactate Accumulation During Hypoglycemia in (Hypoglycemic Unaware)Type I Diabetes Patients and Normal Controls
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Plasma level of adrenaline in response to hypoglycemia (Adrenaline, measured in arterial plasma)
研究概览
简要总结
Iatrogenic hypoglycemia is the most frequent acute complication of insulin therapy in people with type 1 diabetes (T1DM). Recurrent hypoglycemic events initiate a process of habituation, characterized by suppression of hypoglycemic symptoms, eventually leading to hypoglycemia unawareness, which creates a particularly high risk of severe hypoglycemia. Recent evidence suggest a pivotal role for (brain) lactate in the pathogenesis of hypoglycemia unawareness. Indeed, exogenous lactate administration may preserve brain function and attenuate counterregulatory responses to and symptomatic awareness of hypoglycemia. It is unknown whether endogenous elevation of plasma lactate produces the same effects and whether such effects differ between patients with T1DM with and without hypoglycemia unawareness and healthy controls.
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for healthy subjects
- •Age: 18-40 years
- •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.
- •Inclusion criteria T1DM patients with normal hypoglycemic awareness
- •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
- •Inclusion criteria T1DM patients with hypoglycemia unawareness
- •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
排除标准
- •Inability to provide informed consent
- •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
- •Additional exclusion criteria for all T1DM patients:
- •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
研究组 & 干预措施
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
干预措施: High intensity exercise (Behavioral)
Lay down comfortably
As a control conditions, subjects wil lay down comfortably and rest
干预措施: Lay down comfortably (Behavioral)
结局指标
主要结局
Plasma level of adrenaline in response to hypoglycemia (Adrenaline, measured in arterial plasma)
时间窗: during 60 m of hypoglycemia
次要结局
- Plasma lactate levels (Lactate levels measured in arterial plasma)(During 60 min hypoglycemia)
- Glucose infusion rate (Amount of glucose 20% necessary to maintain plasma glucose at steady state values)(During 60 min hypoglycemia)
- Plasma levels of inflammatory markers (levels of cytokines)(During 60 min hypoglycemia)
- Brain perfusion measured with ASL-MRI(During 60 min hypoglycemia)
- Plasma levels of other counter-regulatory hormones (Levels of counter-regulatory hormones measured in arterial plasma)(During 60 min hypoglycemia)
- Cognitive functioning, as measured by cognitive tests(During 60 min hypoglycemia)
- Brain lactate accumulation measured with 1H-MRS(During 60 min of hypoglycemia)