title: Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels.
abstract: OBJECTIVE
  Acromegaly is associated with an increased prevalence of glucose metabolism disorders. Clinically confirmed diabetes mellitus is observed in approximately one quarter of all patients with acromegaly and is known to have a worse prognosis in these patients.
  
  
  METHODS
  Of 514 acromegalic patients treated with pegvisomant and recorded in the German Cohort of ACROSTUDY, 147 had concomitant diabetes mellitus. We analysed these patients in an observational study and compared patients with and without concomitant diabetes.
  
  
  RESULTS
  Under treatment with pegvisomant, patients with diabetes mellitus rarely achieved normalisation (64% in the diabetic cohort vs 75% in the non-diabetic cohort, P=0.04) for IGF1. Diabetic patients normalised for IGF1 required higher pegvisomant doses (18.9 vs 15.5 mg pegvisomant/day, P<0.01). Furthermore, those diabetic patients requiring insulin therapy showed a tendency towards requiring even higher pegvisomant doses to normalise IGF1 values than diabetic patients receiving only oral treatment (22.8 vs 17.2 mg pegvisomant/day, P=0.11).
  
  
  CONCLUSIONS
  Hence, notable interdependences between the acromegaly, the glucose metabolism of predisposed patients and their treatment with pegvisomant were observed. Our data support recent findings suggesting that intra-portal insulin levels determine the GH receptor expression in the liver underlined by the fact that patients with concomitant diabetes mellitus, in particular those receiving insulin therapy, require higher pegvisomant doses to normalise IGF1. It is therefore important to analyse various therapy modalities to find out whether they influence the associated diabetes mellitus and/or whether the presence of diabetes mellitus influences the treatment results of an acromegaly therapy.
authors.affiliation: Practice for Endocrinology and DiabetesElisenstraße 12, 26122 Oldenburg, GermanyDepartment of NeurosurgeryUniversity of Erlangen-Nürnberg, Erlangen, GermanyDepartment of EndocrinologyUniversity of Duisburg-Essen, Essen, GermanyEndocrine CarePfizer Pharma GmbH, Berlin, GermanyDepartment of EndocrinologyMax-Planck Institute of Psychiatry, Munich, GermanyDepartment of Medicine for EndocrinologyDiabetes and Nutritional Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany droste@endokrin-ol.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Droste
authors.affiliation: Practice for Endocrinology and DiabetesElisenstraße 12, 26122 Oldenburg, GermanyDepartment of NeurosurgeryUniversity of Erlangen-Nürnberg, Erlangen, GermanyDepartment of EndocrinologyUniversity of Duisburg-Essen, Essen, GermanyEndocrine CarePfizer Pharma GmbH, Berlin, GermanyDepartment of EndocrinologyMax-Planck Institute of Psychiatry, Munich, GermanyDepartment of Medicine for EndocrinologyDiabetes and Nutritional Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Domberg
authors.affiliation: Practice for Endocrinology and DiabetesElisenstraße 12, 26122 Oldenburg, GermanyDepartment of NeurosurgeryUniversity of Erlangen-Nürnberg, Erlangen, GermanyDepartment of EndocrinologyUniversity of Duisburg-Essen, Essen, GermanyEndocrine CarePfizer Pharma GmbH, Berlin, GermanyDepartment of EndocrinologyMax-Planck Institute of Psychiatry, Munich, GermanyDepartment of Medicine for EndocrinologyDiabetes and Nutritional Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Buchfelder
authors.affiliation: Practice for Endocrinology and DiabetesElisenstraße 12, 26122 Oldenburg, GermanyDepartment of NeurosurgeryUniversity of Erlangen-Nürnberg, Erlangen, GermanyDepartment of EndocrinologyUniversity of Duisburg-Essen, Essen, GermanyEndocrine CarePfizer Pharma GmbH, Berlin, GermanyDepartment of EndocrinologyMax-Planck Institute of Psychiatry, Munich, GermanyDepartment of Medicine for EndocrinologyDiabetes and Nutritional Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Mann
authors.affiliation: Practice for Endocrinology and DiabetesElisenstraße 12, 26122 Oldenburg, GermanyDepartment of NeurosurgeryUniversity of Erlangen-Nürnberg, Erlangen, GermanyDepartment of EndocrinologyUniversity of Duisburg-Essen, Essen, GermanyEndocrine CarePfizer Pharma GmbH, Berlin, GermanyDepartment of EndocrinologyMax-Planck Institute of Psychiatry, Munich, GermanyDepartment of Medicine for EndocrinologyDiabetes and Nutritional Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schwanke
authors.affiliation: Practice for Endocrinology and DiabetesElisenstraße 12, 26122 Oldenburg, GermanyDepartment of NeurosurgeryUniversity of Erlangen-Nürnberg, Erlangen, GermanyDepartment of EndocrinologyUniversity of Duisburg-Essen, Essen, GermanyEndocrine CarePfizer Pharma GmbH, Berlin, GermanyDepartment of EndocrinologyMax-Planck Institute of Psychiatry, Munich, GermanyDepartment of Medicine for EndocrinologyDiabetes and Nutritional Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Stalla
authors.affiliation: Practice for Endocrinology and DiabetesElisenstraße 12, 26122 Oldenburg, GermanyDepartment of NeurosurgeryUniversity of Erlangen-Nürnberg, Erlangen, GermanyDepartment of EndocrinologyUniversity of Duisburg-Essen, Essen, GermanyEndocrine CarePfizer Pharma GmbH, Berlin, GermanyDepartment of EndocrinologyMax-Planck Institute of Psychiatry, Munich, GermanyDepartment of Medicine for EndocrinologyDiabetes and Nutritional Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Strasburger
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D012189:Retrospective Studies
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant