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

Aims/hypothesis. We have previously shown that lactate protects brain funct ion during insulin-induced hypoglycaemia. An adaptation process could, howe ver, not be excluded because the blood lactate increase preceded hypoglycae mia. Methods. We studied seven healthy volunteers and seven patients with Type I (insulin-dependent) diabetes mellitus with a hyperinsulinaemic (1.5 mU . k g(-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 mu mol . kg(-1) . min(-1)) give n after initiation of hypoglycaemic symptoms. Results. The glucose threshold for epinephrine response was similar (contro l 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, howe ver, 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 /- 0.3 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, neuroglycopeni c = 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 v s 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 thresho lds (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 l actate 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 a ssociated with an improvement in cognitive dysfunction (0.2 +/- 0.4 vs -38 +/- 0.2 Delta ms, p = 0.0001). Conclusion/interpretation. A blood lactate increase after the development o f hypoglycaemic symptoms reduces counterregulatory and symptomatic response s to insulin-induced hypoglycaemia and favours brain function rescue both i n normal and diabetic subjects. These findings confirm that lactate is an a lternative substrate to glucose for cerebral metabolism under hypoglycaemic conditions.