caa a22 4500 475771176 CHVBK 20180406123617.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1007/s001250051371 doi (NATIONALLICENCE)springer-10.1007/s001250051371 Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects [Elektronische Daten] [A. Maran, C. Crepaldi, S. Trupiani, T. Lucca, E. Jori, I. A. Macdonald, A. Tiengo, A. Avogaro, S. Del Prato] Aims/hypothesis. 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 mmo/l) with and without Na-lactate infusion (30 μmol · 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 (Δ 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 Δ ms, p = 0.0001).¶Conclusion/interpretation. 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. [Diabetologia (2000) 43: 733-741] Springer-Verlag Berlin Heidelberg, 2000 Keywords Hypoglycaemia, lactate, cognitive function, reaction time nationallicence Maran A. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut Crepaldi C. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut Trupiani S. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut Lucca T. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut Jori E. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut Macdonald I. A. School of Biomedical Sciences, University of Nottingham, UK, GB aut Tiengo A. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut Avogaro A. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut Del Prato S. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut https://doi.org/10.1007/s001250051371 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051371 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Maran A. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut NATIONALLICENCE 700 1- Crepaldi C. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut NATIONALLICENCE 700 1- Trupiani S. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut NATIONALLICENCE 700 1- Lucca T. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut NATIONALLICENCE 700 1- Jori E. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut NATIONALLICENCE 700 1- Macdonald I. A. School of Biomedical Sciences, University of Nottingham, UK, GB aut NATIONALLICENCE 700 1- Tiengo A. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut NATIONALLICENCE 700 1- Avogaro A. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut NATIONALLICENCE 700 1- Del Prato S. Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padua, Italy, IT aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer