Differential effects of insulin detemir and neutral protamine Hagedorn (NPH) insulin on hepatic glucose production and peripheral glucose uptake during hypoglycaemia in type 1 diabetes

• Published in: Diabetologia 2009-11, Vol.52 (11), p.2317-2323
• Main Authors: Smeeton, F, Shojaee Moradie, F, Jones, R. H, Westergaard, L, Haahr, H, Umpleby, A. M, Russell-Jones, D. L
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Blood Pressure - drug effects; Cross-Over Studies; Diabetes; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epinephrine - blood; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty acids; Glucose; Glucose - metabolism; Growth Hormone - blood; Heart Rate - drug effects; Human Physiology; Humans; Hypoglycemia; Hypoglycemia - blood; Hypoglycemic Agents - therapeutic use; Hypotheses; Infusions, Intravenous; Insulin; Insulin - administration & dosage; Insulin - analogs & derivatives; Insulin - therapeutic use; Insulin Detemir; Insulin, Isophane - administration & dosage; Insulin, Isophane - therapeutic use; Insulin, Long-Acting; Internal Medicine; Liver; Liver - metabolism; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Patient Selection; Plasma; Reaction Time
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-009-1487-4

Aims/hypothesis We compared the symptoms of hypoglycaemia induced by insulin detemir (NN304) (B29Lys(ε-tetradecanoyl),desB30 human insulin) and equally effective doses of neutral protamine Hagedorn (NPH) insulin in relation to possible differential effects on hepatic glucose production and peripheral glucose uptake. Methods After overnight intravenous infusion of soluble human insulin 18 participants with type 1 diabetes received subcutaneous injections of NPH insulin or insulin detemir (0.5 U/kg body weight) on separate occasions in random order. During the ensuing gradual development of hypoglycaemia cognitive function and levels of counter-regulatory hormones were measured and rates of endogenous glucose production and peripheral glucose uptake continuously evaluated using a primed constant infusion of [6,6-²H₂]glucose. The study was terminated when plasma glucose concentration had fallen to 2.4 mmol/l or had reached a minimum at a higher concentration. Results During the development of hypoglycaemia no difference between the two insulin preparations was observed in symptoms or hormonal responses. Significant differences were seen in rates of glucose flux. At and below plasma glucose concentrations of 3.5 mmol/l suppression of endogenous glucose production was greater with insulin detemir than with NPH insulin, whereas stimulation of peripheral glucose uptake was greater with NPH insulin than with insulin detemir. Conclusions/interpretation In participants with type 1 diabetes subcutaneously injected insulin detemir exhibits relative hepatoselectivity compared with NPH insulin, but symptoms of hypoglycaemia and hormonal counter-regulation are similar. Trial registration: ClinicalTrials.gov NCT00760448 Funding: Novo Nordisk A/S