Insufficient adaptation of hypoglycaemic threshold for cognitive impairment in tightly controlled type 1 diabetes

It is well known that hypoglycaemic thresholds for hormones and symptoms occur at lower plasma glucose levels in patients with strict glycaemic control. However, whether the threshold for cognitive impairment also shifts is still an unresolved question. We studied 19 type 1 diabetic patients, including 8 with hypoglycaemia unawareness, aged 37.0 +/- 7.4 y.r., with diabetes duration 15.2 +/- 10.7 yr, and HbA1c 7.6 +/- 1.1%. Hypoglycaemic thresholds for hormones, symptoms, awareness and cognitive function using the 4-choice reaction time test (4RT), were measured every 30 min during a 150 min stepped 4.4 to 2.2 mM hypoglycaemic hyperinsulinemic clamp. We found that 4RT- accuracy deteriorated earlier than 4RT-time (3.2 and 2.7 mM, respectively, p<0.01), and that both correlated poorly with HbA1C before and after adjustment for age and diabetes duration (r=0.11, and 0.18, respectively). On the opposite, adrenaline, autonomic and neuroglycopenic symptoms, and awareness significantly correlated with HbA1c values (r=0.56, 0.70, 0.61, and 0.63, after adjustment, respectively). Furthermore, after allocating the patients into two subgroups according to HbA1c values (<8% n=12, and >=8% n=7), we found that, as opposed to other thresholds, accuracy and 4RT-time were minimally and not significantly influenced by glycaemic control, therefore exhibiting the smaller glucose thresholds shifts (- 0.2 and - 0.5 mM for accuracy and time, respectively, vs. 0.6 -0.8 for other thresholds).

1) the hypoglycaemic thresholds for cognitive dysfunction shift with strict glycaemic control, but not significantly and less than other thresholds, 2) as opposed to other reports, accuracy deteriorates earlier than speed during the 4RT test, and 3) these "maladapted" reactions may contribute to the higher risk for severe hypoglycaemia in subjects with tight glycaemic control.