The Effect of Intravenous Lactate on Brain Lactate Concentrations During Hypoglycemia

Radboud University Medical Center

Status

Completed

Conditions

Type 1 Diabetes Mellitus With Hypoglycemia

Treatments

Drug: Sodium Lactate

Drug: SodiumChloride

Study type

Interventional

Funder types

Other

Identifiers

NCT03286816

Lac_iv

Details and patient eligibility

About

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.

Enrollment

19 patients

Sex

All

Ages

18 to 50 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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)