SUBSTITUTION OF NIGHTTIME CONTINUOUS SUBCUTANEOUS INSULIN INFUSION THERAPY FOR BEDTIME NPH INSULIN IN A MULTIPLE INJECTION REGIMEN IMPROVESCOUNTERREGULATORY HORMONAL RESPONSES AND WARNING SYMPTOMS OF HYPOGLYCEMIA IN IDDM

In patients with insulin-dependent diabetes mellitus (IDDM) good glyca emic control confers an enhanced risk of hypoglycaemia. Nocturnal hypo glycaemia occurs frequently and contributes to the syndrome of hypogly caemia unawareness. In order to avoid nocturnal hypoglycaemia we subst ituted night-time continuous subcutaneous insulin infusion (CSII) ther apy in 14 patients with well-controlled IDDM using a multiple injectio n regimen for the more variable bedtime NPH insulin. During a stepwise hypoglycaemic clamp we studied the effect of this regimen on counterr egulatory hormonal responses, warning symptoms and cognitive function. In addition, we investigated the incidence of daytime hypoglycaemia a nd the acceptability of night-time CSII treatment. CSII was associated with a lower frequency of hypoglycaemia (mean +/- SEM): (16.1 +/- 3.1 vs 23.6 +/- 3.3) episodes during the last 6 weeks of treatment, p = 0 .03 (CSII vs NPH) with maintenance of good glycaemic control (HbA(1c) 7.2 +/- 0.2 vs 7.1 +/- 0.2%, p = 0.2). Hypoglycaemic thresholds for th e growth hormone response and for autonomic symptoms were lower for CS II treatment than for NPH treatment. Of 14 patients 6 decided to conti nue with the nocturnal CSII treatment. In conclusion, nocturnal CSII i mproves warning symptoms and counterregulatory hormonal responses to h ypoglycaemia and is an acceptable treatment strategy for patients suff ering from hypoglycaemia unawareness, as demonstrated in this acute fe asibility study.