title: Comparison of the effects on glucose and lipid metabolism of equipotent doses of insulin detemir and NPH insulin with a 16-h euglycaemic clamp.
abstract: OBJECTIVE
  The association of insulin detemir with non-esterified fatty acid binding sites on albumin may limit its transfer from the circulation into the extravascular extracellular space in adipose tissue and muscle, due to the capillary endothelial cell barrier. In the liver, the open sinusoids may expose hepatocytes to insulin detemir, enabling it to have a greater effect in the liver than in peripheral tissues.
  
  
  METHODS
  We investigated the effects of equipotent doses of insulin detemir and NPH insulin on hepatic glucose rate of appearance (Ra), peripheral glucose rate of disposal (Rd) and glycerol Ra (a measure of lipolysis) using stable isotope techniques. We also investigated the effects of these insulins on NEFA concentrations in seven healthy volunteers during a 16-h euglycaemic clamp. A higher dose of insulin detemir was also studied.
  
  
  RESULTS
  There was no difference in the glucose infusion profile between insulin detemir and NPH. Insulin detemir had a greater effect on mean suppression of glucose Ra (mean difference 0.24 mg kg(-1) min(-1); CI 0.09-0.39; p<0.01), and minimum glucose Ra, with minimum low dose detemir -0.10+/-0.15 mg.kg(-1).min(-1) and minimum NPH 0.17+/-0.10 mg.kg(-1).min(-1) (p<0.02). However, it had a lesser effect on mean suppression of NEFA concentrations (mean difference -0.10 mmol/l; CI -0.03 to -0.17; ANOVA, p<0.02) than NPH. The effect of insulin detemir on glucose Rd and glycerol Ra was not different from NPH. Following high-dose detemir, total glucose infused and maximum glucose Rd were higher (p<0.02, p<0.03) and plasma NEFA concentrations lower (p<0.01) than with low-dose determir.
  
  
  CONCLUSIONS
  This study suggests that insulin detemir, when compared to NPH insulin, has a greater effect on the liver than on peripheral tissues and thus has the potential to restore the physiological insulin gradient.
authors.affiliation: Department of Diabetes and Endocrinology, Post Graduate Medical School, University of Surrey, Guildford, Surrey, UK.
authors.forename: S V M
authors.initials: SV
authors.lastname: Hordern
authors.forename: J E
authors.initials: JE
authors.lastname: Wright
authors.forename: A M
authors.initials: AM
authors.lastname: Umpleby
authors.forename: F
authors.initials: F
authors.lastname: Shojaee-Moradie
authors.forename: J
authors.initials: J
authors.lastname: Amiss
authors.forename: D L
authors.initials: DL
authors.lastname: Russell-Jones
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000069057:Insulin Detemir; D007336:Insulin, Isophane / Q000494:pharmacology*; D049528:Insulin, Long-Acting; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D049528:Insulin, Long-Acting; D000069057:Insulin Detemir; D007336:Insulin, Isophane; D005947:Glucose
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