title: Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and type I diabetic subjects.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Padua, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Maran
authors.forename: C
authors.initials: C
authors.lastname: Crepaldi
authors.forename: S
authors.initials: S
authors.lastname: Trupiani
authors.forename: T
authors.initials: T
authors.lastname: Lucca
authors.forename: E
authors.initials: E
authors.lastname: Jori
authors.forename: I A
authors.initials: IA
authors.lastname: Macdonald
authors.forename: A
authors.initials: A
authors.lastname: Tiengo
authors.forename: A
authors.initials: A
authors.lastname: Avogaro
authors.forename: S
authors.initials: S
authors.lastname: Del Prato
mesh_terms: D000064:Acclimatization; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006946:Hyperinsulinism; D007003:Hypoglycemia / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007444:Inulin / Q000008:administration & dosage / Q000494:pharmacology; D007773:Lactates / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000097:blood; D012016:Reference Values; D019354:Sodium Lactate / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007773:Lactates; D019382:Human Growth Hormone; D007444:Inulin; D019354:Sodium Lactate; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine