The Effect of Intravenous Lactate Administration on Brain Lactate Concentrations and pH During Euglycemia and Hypoglycemia in Patients With Type 1 Diabetes With and Without Impaired Awareness of Hypoglycemia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- the effect of intravenous lactate administration, compared to placebo, on brain lactate concentrations during euglycemia and hypoglycemia in patients with T1DM and normal awareness of hypoglycemia
研究概览
简要总结
Patients with type 1 diabetes (T1DM) who are unable to perceive symptoms of hypoglycemia, referred to as impaired awareness of hypoglycemia (IAH), are at very high risk of severe hypoglycemia. IAH affects approximately 25% of patients with T1DM. Brain lactate may be involved in the development of IAH. A recent study indicated increased brain lactate utilization during hypoglycemia in T1DM patients with IAH, which did not occur in patients with normal awareness of hypoglycemia (NAH). Conversely, administration of lactate to patients with NAH has been shown to attenuate counterregulatory hormone responses to and symptomatic awareness of hypoglycemia, thus causing a situation that resembles IAH. It has, however, not been demonstrated whether the excess of lactate is actually taken up or metabolized by the brain, and if so whether this occurs under euglycemic or hypoglycemic conditions or both.
This project consists of two related studies. The objective of part 1 is to investigate the effect of elevated plasma lactate levels that are sufficient to impair awareness of hypoglycemia on brain lactate concentrations during euglycemia and hypoglycemia in T1DM patients with NAH. The objective of part 2 is to compare the effect of exogenous lactate on brain lactate concentrations between T1DM patients with NAH and T1DM patients with IAH.
Furthermore, this study aims to determine the effect of acute hypoglycemia on the inflammatory function and composition of peripheral blood mononuclear cells.
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 or >=3
- •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, known liver disease, anxiety disorders or a history of panic attacks.
- •Microvascular complications of T1DM: Proliferative retinopathy, Symptomatic diabetic neuropathy (including autonomic neuropathy), Nephropathy; clinical/overt albuminuria or an estimated glomerular filtration rate <60ml/min/1.73m2
- •MR(I) 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: SodiumChloride (Drug)
结局指标
主要结局
the effect of intravenous lactate administration, compared to placebo, on brain lactate concentrations during euglycemia and hypoglycemia in patients with T1DM and normal awareness of hypoglycemia
时间窗: during stable euglycemia (40 min) and hypoglycemia (45 min)
the effect of exogenous lactate on brain lactate concentrations during euglycemia and hypoglycemia between T1DM patients with normal awareness of hypoglycemia and T1DM patients with impaired awareness of hypoglycemia
时间窗: during stable euglycemia (40 min) and hypoglycemia (45 min)
次要结局
- The changes in and symptoms to hypoglycemia in response to lactate infusion, compared to placebo, in patients with normal awareness of hypoglycemia(during stable euglycemia (40 min) and hypoglycemia (45 min))
- The changes in brain pH in response to intravenous lactate administration, compared to placebo(during stable euglycemia (40 min) and hypoglycemia (45 min))
- Changes in immune cell composition capacity in response to hypoglycemia compared to euglycemia and in response to lactate infusion compared to placebo(during stable euglycemia (40 min) and hypoglycemia (45 min))
- The changes in counterregulatory hormone and to hypoglycemia in response to lactate infusion, compared to placebo, in patients with normal awareness of hypoglycemia(during stable euglycemia (40 min) and hypoglycemia (45 min))
- Changes in immune cell cytokine production capacity in response to hypoglycemia compared to euglycemia and in response to lactate infusion compared to placebo(during stable euglycemia (40 min) and hypoglycemia (45 min))