title: Short-term effects of NPH insulin, insulin detemir, and insulin glargine on the GH-IGF1-IGFBP axis in patients with type 1 diabetes.
abstract: OBJECTIVE
  Insulin regulates the GH-IGF1 axis. Insulin analogs differ from human insulin in receptor affinity and possibly liver accessibility. Therefore, we compared the GH-IGF1 axis response with human NPH insulin, insulin detemir, and insulin glargine in patients with type 1 diabetes (T1D).
  
  
  METHODS
  A total of 17 patients (seven were women) with T1D (age of 42 (24-63) years (mean and range), BMI of 24.7 (19.5-28.3) kg/m(2), HbA1c of 7.2 (6.3-8.0) % (55 (45-64) mmol/mol), T1D duration of 26 (8-45) years) were studied using a randomized, three-period crossover design. Patients received s.c. injections of equal, individual doses of NPH, detemir, and glargine at 1800 h. Plasma glucose, serum total IGF1, bioactive IGF, IGF-binding protein (IGFBPs), and GH were measured hourly for 14 h post-injection.
  
  
  RESULTS
  When compared with the area under the curve (AUC) following NPH and glargine, detemir resulted in the lowest 6-14 h AUC (mean and range) of IGFBP1 (1518 (1280-1800)) vs 1621 (1367-1922) vs 1020 (860-1210) μg/l×h) and GH (17.1 (14.1-20.6) vs 15.4 (12.7-18.6) vs 10.2 (8.5-12.3) μg/l×h), but in the highest AUC of bioactive IGF (3.8 (3.5-4.2) vs 3.7 (3.4-4.0) vs 4.4 (4.1-4.8) μg/l×h) (all P<0.01). These differences were unrelated to plasma glucose. By contrast, profiles of total IGF1, IGFBP2, and IGFBP3 were comparable.
  
  
  CONCLUSIONS
  Independent of plasma glucose, a single dose of detemir caused larger suppression in serum IGFBP1 than NPH and glargine, whereas bioactive IGF was higher, thereby explaining the lower GH levels. Thus, detemir appears to be more liver specific than NPH insulin and glargine.
authors.affiliation: Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade, DK-8000 Aarhus C, DenmarkDepartment of Biomedicine - PharmacologyFaculty of Health, Aarhus University, DK-8000 Aarhus C, DenmarkSection of General PracticeDepartment of Public Health, Faculty of Health, Aarhus University, DK-8000 Aarhus C, Denmark Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade, DK-8000 Aarhus C, DenmarkDepartment of Biomedicine - PharmacologyFaculty of Health, Aarhus University, DK-8000 Aarhus C, DenmarkSection of General PracticeDepartment of Public Health, Faculty of Health, Aarhus University, DK-8000 Aarhus C, Denmark zhulin.ma@clin.au.dk.
authors.forename: Zhulin
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade, DK-8000 Aarhus C, DenmarkDepartment of Biomedicine - PharmacologyFaculty of Health, Aarhus University, DK-8000 Aarhus C, DenmarkSection of General PracticeDepartment of Public Health, Faculty of Health, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Jens Sandahl
authors.initials: JS
authors.lastname: Christiansen
authors.affiliation: Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade, DK-8000 Aarhus C, DenmarkDepartment of Biomedicine - PharmacologyFaculty of Health, Aarhus University, DK-8000 Aarhus C, DenmarkSection of General PracticeDepartment of Public Health, Faculty of Health, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Laursen
authors.affiliation: Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade, DK-8000 Aarhus C, DenmarkDepartment of Biomedicine - PharmacologyFaculty of Health, Aarhus University, DK-8000 Aarhus C, DenmarkSection of General PracticeDepartment of Public Health, Faculty of Health, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Torsten
authors.initials: T
authors.lastname: Lauritzen
authors.affiliation: Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade, DK-8000 Aarhus C, DenmarkDepartment of Biomedicine - PharmacologyFaculty of Health, Aarhus University, DK-8000 Aarhus C, DenmarkSection of General PracticeDepartment of Public Health, Faculty of Health, Aarhus University, DK-8000 Aarhus C, Denmark Medical Research LaboratoryDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade, DK-8000 Aarhus C, DenmarkDepartment of Biomedicine - PharmacologyFaculty of Health, Aarhus University, DK-8000 Aarhus C, DenmarkSection of General PracticeDepartment of Public Health, Faculty of Health, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D019382:Human Growth Hormone / Q000097:blood* / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000494:pharmacology*; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000494:pharmacology*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood / Q000187:drug effects; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000187:drug effects; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood* / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; C577903:IGFBP2 protein, human; C515497:IGFBP3 protein, human; D049528:Insulin, Long-Acting; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D000069036:Insulin Glargine; D000069057:Insulin Detemir; D007336:Insulin, Isophane; D007334:Insulin-Like Growth Factor I