The Effect of Lactate Administration on Cerebral Blood Flow During Hypoglycemia; Are the Suppressive Effects of Lactate on Counterregulatory Responses to Hypoglycemia Reflected in an Altered CBF Response?
试验速览
- 阶段
- 不适用
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Regional CBF in ml/100g/min measured with ASL-MRI
研究概览
简要总结
It is thought that altered brain lactate handling is involved in the development of impaired awareness of hypoglycemia (IAH), i.e. the inability to timely detect hypoglycemia in people with type 1 diabetes (T1DM). Infusion of lactate diminishes symptomatic and hormonal responses to hypoglycemia in patients with normal awareness of hypoglycemia (NAH), resembling the situation of patients with IAH. It is unknown whether this attenuating effect is due to brain lactate oxidation or the result of lactate-induced alterations of global and regional cerebral blood flow (CBF).
Normally, hypoglycemia causes a redistribution of CBF towards the thalamus, from where the sympathetic response to hypoglycemia is coordinated, but in IAH this effect is absent and global CBF is increased. We hypothesize that lactate infusion in patients with NAH will result in blunting of thalamic activation and/or enhanced global CBF. If so, these results may help delineating the pathogenesis of IAH which eventually creates new avenues to protect against the morbidity associated with hypoglycemia and IAH.
Study design: Single-blind placebo controlled, randomized cross-over intervention study Study population: T1DM patients with NAH (n=10) Intervention: On two separate occasions, patients with T1DM and NAH will undergo a hyperinsulinemic euglycemic-hypoglycemic glucose clamp with or without the infusion of exogenous lactate. ASL-MRI will be applied to measure global and regional changes in CBF.
Main study parameters/endpoints: The change in regional thalamic CBF in response to intravenous lactate infusion compared to placebo, during hypoglycemia
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diabetes duration ≥ 1 year
- •Age: 18-50 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
排除标准
- •Inability to provide informed consent
- •Use medication other than insulin, except for oral contraceptives or stable thyroxin supplementation therapy
- •Presence of any other medical condition that might interfere with the study protocol, such as brain injuries, epilepsy, a major cardiovascular disease event or cardiac failure, known liver disease, anxiety disorders or a history of panic attacks.
- •Microvascular complications of T1DM: Proliferative retinopathy, symptomatic diabetic neuropathy (including autonomic neuropathy) or Nephropathy; clinical/overt albuminuria or an estimated glomerular filtration rate <60ml/min/1.73m
- •MRI contraindications (pregnancy, severe claustrophobia, metal parts in body)
研究组 & 干预措施
Lactate infusion
Subjects will receive an intravenous lactate infusion to elevate plasma lactate levels
干预措施: Sodium Lactate (Drug)
NaCl infusion
As a control condition, subjects will receive intravenous NaCl infusion
干预措施: Sodium chloride (Drug)
结局指标
主要结局
Regional CBF in ml/100g/min measured with ASL-MRI
时间窗: during stable euglycemia (40 minutes) and hypoglycemia (45 minutes)
The change in regional thalamic CBF in response to intravenous lactate infusion compared to placebo, during hypoglycemia
次要结局
- Global CBF in ml/100g/min measured with ASL-MRI(during stable euglycemia (40 minutes) and hypoglycemia (45 minutes))
- Counterregulatory hormone responses to hypoglycemia(during stable euglycemia (40 minutes) and hypoglycemia (45 minutes))
- Symptom responses to hypoglycemia(during stable euglycemia (40 minutes) and hypoglycemia (45 minutes))
- Measurements of metabolites in cell lysates or supernatants of the cultured immune cells(during stable euglycemia (40 minutes) and hypoglycemia (45 minutes))