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

Abstract

Patients with Type I (insulin-dependent) diabetes mellitus receiving intensified insulin therapy and having strict metabolic control are exposed to the risk of recurrent episodes of hypoglycaemia [1]. Defective counterregulatory and symptomatic responses to hypoglycaemia are responsible for reduced awareness of hypoglycaemia [2] which can aggravate cerebral dysfunction by increasing the occurrence and severity Diabetologia (2000) 43: 733±741Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects Abstract 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 mUḱ g ±1´m in ±1 ) stepwise hypoglycaemic clamp (4.8 to 3.6, 3.0 and 2.8 mmo/l) with and without Na-lactate infusion (30 mmol´kg ±1´m in ±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

Synaptic Adaptation to Repeated Hypoglycemia Depends on the Utilization of Monocarboxylates in Guinea Pig Hippocampal Slices

“…In hypoglycemia unawareness, previous episodes of hypoglycemia cause delayed and diminished symptomatic and hormonal responses to subsequent hypoglycemia. Similar defects of neurohormonal responses to hypoglycemia are induced by intravenous infusion of lactate during hypoglycemia in nondiabetic individuals (35,36). These results suggest the possible involvement of lactate in hypoglycemic unawareness.…”

Increased Brain Monocarboxylic Acid Transport and Utilization in Type 1 Diabetes

“…Furthermore, exogenously supplied lactate and ␤-hydroxybutyrate have been associated with lower blood glucose concentrations before symptoms of hypoglycemia appear (28), and lactate infusions have been reported to improve cognitive function during hypoglycemia and to do so more effectively in diabetic patients (29).…”

Brain Lactate Concentration Falls in Response to Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia

“…Lactate is a valuable energy source for the brain during euglycemia (7)(8)(9) and may be critical to maintaining brain function during severe hypoglycemia (10). Administration of lactate during hypoglycemia impairs hypoglycemic symptoms, attenuates counterregulatory hormone responses, and preserves cognitive function, mirroring the changes seen in subjects with IAH (11,12). Finally, brain lactate transport capacity through monocarboxylic acid transporters was found to be increased during hypoglycemia in patients with IAH (13,14).…”