EFFECTS OF PREVIOUS GLYCEMIC CONTROL ON THE ONSET AND MAGNITUDE OF COGNITIVE DYSFUNCTION DURING HYPOGLYCEMIA IN TYPE-1 (INSULIN-DEPENDENT) DIABETIC-PATIENTS

To determine whether the degree of previous glycaemic control may modify cognitive responses to hypoglycaemia, the glycaemic thresholds for, and magnitude of cognitive dysfunction as assessed by P300 event-related potentials as well as subjective and hormonal responses during hypoglycaemia were evaluated. Hypoglycaemia was induced by intravenous insulin infusion in 18 Type 1 (insulin-dependent) diabetic patients, 7 of whom were strictly controlled (HbA1c: 6.3+/-0.3%; mean +/- SEM: Group 1) and 11 of whom were poorly controlled (HbA1c: 9.1 +/- 0.4 %; Group 2). Within 60 min, mean blood glucose declined from 5.6 and 5.7 mmol/l (baseline) to a nadir of 1.6 and 1.8 mmol/l followed by an increase to 5.6 and 4.3 mmol/l after 120 min in Group 1 and 2, respectively. There was no significant difference between the groups in regard to P300 latency at baseline, but between 50 and 70 min a significant prolongation of this component was noted in Group 2 as compared with Group 1 at blood glucose levels between 1.6 and 2.3 mmol/l (p < 0.05). The glycaemic thresholds at which a significant increase of P300 latency over baseline was first noted were 1.6 +/- 0.2 mmol/l in Group 1 and 3.5 +/- 0.2 mmol/l in Group 2 (p < 0.05). The glucose thresholds at which this prolongation was no longer demonstrable were 1.9 +/- 0.1 mmol/l in Group 1 and 3.8 +/- 1.4 mmol/l in Group 2, respectively (p < 0.05). The glycaemic threshold at which the P300 amplitude was first significantly reduced was 2.2 mmol/l in Group 2, whereas no such reduction was observed in Group 1. The glycaemic thresholds for the perception of subjective symptoms were 1.7 +/- 0.2 mmol/l in Group 1 and 2.5 +/- 0.2 mmol/l in Group 2 (p < 0.05), and those for the first significant rise of the counter-regulatory hormones were 2.3 +/- 0.1 and 1.6 +/- 0.2 mmol/l in Group 1 as well as 2.8 +/- 0.1 mmol/l in Group 2 (p < 0.05). Thus, the glycaemic threshold for and magnitude of, cognitive dysfunction during hypoglycaemia are reduced in strictly-controlled as compared with poorly-controlled Type 1 diabetic patients. In the latter group, cognitive impairment may precede the onset of counter-regulatory hormone responses and symptom awareness. These findings support the concept of cerebral adaptation to previous low blood glucose levels.