title: Substitution of night-time continuous subcutaneous insulin infusion therapy for bedtime NPH insulin in a multiple injection regimen improves counterregulatory hormonal responses and warning symptoms of hypoglycaemia in IDDM.
abstract: In patients with insulin-dependent diabetes mellitus (IDDM) good glycaemic control confers an enhanced risk of hypoglycaemia. Nocturnal hypoglycaemia occurs frequently and contributes to the syndrome of hypoglycaemia unawareness. In order to avoid nocturnal hypoglycaemia we substituted night-time continuous subcutaneous insulin infusion (CSII) therapy in 14 patients with well-controlled IDDM using a multiple injection regimen for the more variable bedtime NPH insulin. During a stepwise hypoglycaemic clamp we studied the effect of this regimen on counterregulatory hormonal responses, warning symptoms and cognitive function. In addition, we investigated the incidence of daytime hypoglycaemia and 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 (HbA1c 7.2+/-0.2 vs 7.1+/-0.2 %, p=0.2). Hypoglycaemic thresholds for the growth hormone response and for autonomic symptoms were lower for CSII treatment than for NPH treatment. Of 14 patients 6 decided to continue with the nocturnal CSII treatment. In conclusion, nocturnal CSII improves warning symptoms and counterregulatory hormonal responses to hypoglycaemia and is an acceptable treatment strategy for patients suffering from hypoglycaemia unawareness, as demonstrated in this acute feasibility study.
authors.affiliation: Research Institute for Endocrinology, Reproduction and Metabolism, Department of Endocrinology, Vrije Universiteit Hospital, Amsterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Kanc
authors.forename: M M
authors.initials: MM
authors.lastname: Janssen
authors.forename: E T
authors.initials: ET
authors.lastname: Keulen
authors.forename: M A
authors.initials: MA
authors.lastname: Jacobs
authors.forename: C
authors.initials: C
authors.lastname: Popp-Snijders
authors.forename: F J
authors.initials: FJ
authors.lastname: Snoek
authors.forename: R J
authors.initials: RJ
authors.lastname: Heine
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000627:therapeutic use; D015309:Glucose Clamp Technique; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000517:prevention & control; D007003:Hypoglycemia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007260:Infusion Pumps; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D007332:Insulin Infusion Systems; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D010342:Patient Acceptance of Health Care; D010465:Perception
chemical_list: D001786:Blood Glucose; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D007336:Insulin, Isophane; D005947:Glucose