Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects

• Published in: Diabetologia Vol. 43; no. 6; pp. 733 - 741
• Main Authors: MARAN, A, CREPALDI, C, TRUPIANI, S, LUCCA, T, JORI, E, MACDONALD, I. A, TIENGO, A, AVOGARO, A, DEL PRATO, S
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.06.2000; Springer Nature B.V
• Subjects: Acclimatization; Adult; Biological and medical sciences; Blood Glucose - metabolism; Brain - drug effects; Brain - physiology; Brain - physiopathology; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epinephrine - blood; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glucose Clamp Technique; Human Growth Hormone - blood; Humans; Hydrocortisone - blood; Hyperinsulinism; Hypoglycemia - physiopathology; Infusions, Intravenous; Inulin - administration & dosage; Inulin - pharmacology; Lactates - blood; Male; Medical sciences; Norepinephrine - blood; Reference Values; Sodium Lactate - administration & dosage; Sodium Lactate - pharmacology; Endocrinopathy; Human; Immunopathology; Lactates; Insulin dependent diabetes; Autoimmune disease; Cognition; Hypoglycemia; Metabolism; Protection
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s001250051371

We have previously shown that lactate protects brain function during insulin-induced hypoglycaemia. An adaptation process could, however, not be excluded because the blood lactate increase preceded hypoglycaemia. We studied seven healthy volunteers and seven patients with Type I (insulin-dependent) diabetes mellitus with a hyperinsulinaemic (1.5 mU.kg-1.min-1) stepwise hypoglycaemic clamp (4.8 to 3.6, 3.0 and 2.8 mmol/l) with and without Na-lactate infusion (30 mumol.kg-1.min-1) given after initiation of hypoglycaemic symptoms. The glucose threshold for epinephrine response was similar (control subjects 3.2 +/- 0.1 vs 3.2 +/- 0.1, diabetic patients = 3.5 +/- 0.1 vs 3.5 +/- 0.1 mmol/l) in both studies. The magnitude of the response was, however, blunted by lactate infusion (AUC; control subjects 65 +/- 28 vs 314 +/- 55 nmol/l/180 min, zenith = 2.6 +/- 0.5 vs 4.8 +/- 0.7 nmol/l, p < 0.05; diabetic patients = 102 +/- 14 vs 205 +/- 40 nmol/l/180 min, zenith = 1.4 +/- 0.4 vs 3.2 +/- 0.3 nmol/l, p < 0.01). The glucose threshold for symptoms was also similar (C = autonomic 3.0 +/- 0.1 vs 3.0 +/- 0.1, neuroglycopenic = 2.8 +/- 0.1 vs 2.9 +/- 0.1 mmol/l, D = autonomic 3.2 +/- 0.1 vs 3.2 +/- 0.1, neuroglycopenic 3.1 +/- 0.1 vs 3.2 +/- 0.1 mmol/l) but peak responses were significantly attenuated by lactate (score at 160 min C = 2.6 +/- 1 vs 8.8 +/- 1, and 0.4 +/- 0.4 vs 4.8 +/- 1, respectively; p = 0.02-0.01, D = 1.3 +/- 0.5 vs 6.3 +/- 1.7, and 2.3 +/- 0.6 vs 5.7 +/- 1.1 p = 0.07-0.02). Cognitive function deteriorated in both studies at similar glucose thresholds (C = 3.1 +/- 0.1 vs 3.0 +/- 0.1, D = 3.2 +/- 0.1 vs 3.3 +/- 0.2 mmol/l). Although in normal subjects a much smaller impairment was observed with lactate infusion (delta four-choice reaction time at 160 min = 22 +/- 12 vs 77 +/- 31 ms; p = 0.02), in Type I diabetic patients lactate infusion was associated with an improvement in cognitive dysfunction (0.2 +/- 0.4 vs -38 +/- 0.2 delta ms, p = 0.0001). A blood lactate increase after the development of hypoglycaemic symptoms reduces counterregulatory and symptomatic responses to insulin-induced hypoglycaemia and favours brain function rescue both in normal and diabetic subjects. These findings confirm that lactate is an alternative substrate to glucose for cerebral metabolism under hypoglycaemic conditions.