title: Effect of subcutaneous insulin detemir on glucose flux and lipolysis during hyperglycaemia in people with type 1 diabetes.
abstract: OBJECTIVE
  To investigate, using a novel non-steady-state protocol, the differential effects of subcutaneous (s.c.) detemir and NPH insulin on glucose flux and lipid metabolism after insulin withdrawal.
  
  
  METHODS
  After a period of insulin withdrawal resulting in whole-blood glucose concentration of 7 mmol/l, 11 participants (five men, mean age 41.0 years, mean body mass index 25 kg/m(2)) with type 1 diabetes (mean glycated haemoglobin concentration 57 mmol/mol, mean diabetes duration 14 years) received 0.5 units per kg body weight s.c. insulin detemir or NPH insulin in random order. Stable isotopes of glucose and glycerol were infused intravenously throughout the study protocol.
  
  
  RESULTS
  Glucose concentration decreased after insulin treatment as a result of suppression of endogenous glucose production, which occurred to a similar extent with both detemir and NPH insulin. The rate of glucose disappearance (Rd) was not increased significantly with either type of insulin. When the effect of detemir and NPH insulin on glucose flux at glucose concentrations between 9 and 6 mmol/l was examined, glucose rate of appearance (Ra) was similar with the two insulins; however, glucose Rd was greater with NPH insulin than with detemir at glucose concentrations of 8.0, 8.5, 7.0 and 6.0 mmol/l (p < 0.05) The percentage change in glycerol Ra, a measure of lipolysis, was greater in the NPH group than in the detemir group (p = 0.04).
  
  
  CONCLUSIONS
  The results of the study are consistent with the hypothesis that detemir has a lesser effect on the periphery, as evidenced by a lesser effect on peripheral glucose uptake at specific glucose concentrations.
authors.affiliation: Centre for Endocrinology, Diabetes and Research, Royal Surrey County Hospital, Guildford, UK; Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey Leggett Building, Daphne Jackson Rd, Manor Park, Guildford GU2 7WG, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Herring
authors.forename: F
authors.initials: F
authors.lastname: Shojaee-Moradie
authors.forename: A M
authors.initials: AM
authors.lastname: Umpleby
authors.forename: R
authors.initials: R
authors.lastname: Jones
authors.forename: N
authors.initials: N
authors.lastname: Jackson
authors.forename: D L
authors.initials: DL
authors.lastname: Russell-Jones
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000096:biosynthesis / Q000187:drug effects*; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D006442:Glycated Hemoglobin; D005990:Glycerol / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D000069057:Insulin Detemir / Q000008:administration & dosage / Q000494:pharmacology*; D007336:Insulin, Isophane / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D005990:Glycerol; D007004:Hypoglycemic Agents; D000069057:Insulin Detemir; D007336:Insulin, Isophane; C517652:hemoglobin A1c protein, human
keywords: insulin analogues; insulin therapy; liver; type 1 diabetes