title: 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.
abstract: OBJECTIVE
  We compared the symptoms of hypoglycaemia induced by insulin detemir (NN304) (B29Lys(epsilon-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-(2)H(2)]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
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00760448.
authors.affiliation: Department of Medicine, Nevill Hall Hospital, Abergavenny, Monmouthshire, UK.
authors.forename: F
authors.initials: F
authors.lastname: Smeeton
authors.forename: F
authors.initials: F
authors.lastname: Shojaee Moradie
authors.forename: R H
authors.initials: RH
authors.lastname: Jones
authors.forename: L
authors.initials: L
authors.lastname: Westergaard
authors.forename: H
authors.initials: H
authors.lastname: Haahr
authors.forename: A M
authors.initials: AM
authors.lastname: Umpleby
authors.forename: D L
authors.initials: DL
authors.lastname: Russell-Jones
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000097:blood*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069057:Insulin Detemir; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000627:therapeutic use*; D049528:Insulin, Long-Acting; D008099:Liver / Q000378:metabolism*; D018579:Patient Selection; D011930:Reaction Time
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069057:Insulin Detemir; D007336:Insulin, Isophane; D013006:Growth Hormone; D005947:Glucose; D004837:Epinephrine
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