title: Incidence of diabetes mellitus and evolution of glucose parameters in growth hormone-deficient subjects during growth hormone replacement therapy: a long-term observational study.
abstract: OBJECTIVE
  Growth hormone (GH) deficiency is associated with insulin resistance and diabetes. The aim of the current study was to determine incidence of diabetes during GH replacement therapy (GHRT) and the effect of GHRT on fasting plasma glucose concentrations and HbA(1c) in adult patients with GH deficiency.
  
  
  METHODS
  A total of 5,143 GH-deficient patients (male 49.9%; mean age ± SD, 49 ± 13 years; BMI 29.1 ± 5.9 kg/m(2)) were analyzed. Mean observation period was 3.9 years (range 0.01-13). Total number of patient-years was 20,106. Observed number of cases (O) was compared with expected number of cases (E). Reference rates were from Sweden, three additional European regions, and one U.S. region.
  
  
  RESULTS
  Patients who developed diabetes (n = 523) were older; had higher BMI, waist circumference, triglyceride concentrations, and blood pressure; and had lower HDL-cholesterol concentrations (P < 0.0001) than those who did not develop diabetes. Diabetes incidence was 2.6 per 100 patient-years, equal in both sexes, and significantly increased compared with the Swedish reference (O/E = 6.02; P < 0.0001) as well as with the four other populations (O/E = 2.11-5.22). O/E increased with BMI and decreased with duration of GHRT (P < 0.0001). There was no significant association with GH dose (P = 0.74) or IGF-I SDS (P = 0.47). In subjects not developing diabetes, plasma glucose concentrations increased from 84.4 ± 0.9 mg/dL to 89.5 ± 0.8 mg/dL (0.70 mg/dL/year) and HbA(1c) increased from 4.74 ± 0.04% to 5.09 ± 0.13% (0.036%/year) after 6 years of GHRT.
  
  
  CONCLUSIONS
  Diabetes incidence appears to be increased in GH-deficient patients receiving GHRT and exhibiting an adverse risk profile at baseline. Therefore, glucose homeostasis parameters should be monitored carefully in these patients.
authors.affiliation: Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria. anton.luger@meduniwien.ac.at
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.forename: Anders F
authors.initials: AF
authors.lastname: Mattsson
authors.forename: Maria
authors.initials: M
authors.lastname: Koltowska-Häggström
authors.forename: Maria
authors.initials: M
authors.lastname: Thunander
authors.forename: Miklos
authors.initials: M
authors.lastname: Góth
authors.forename: Johan
authors.initials: J
authors.lastname: Verhelst
authors.forename: Roger
authors.initials: R
authors.lastname: Abs
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy*; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D019382:Human Growth Hormone; C517652:hemoglobin A1c protein, human
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