title: Glucometabolic hormones and cardiovascular risk markers in antipsychotic-treated patients.
abstract: OBJECTIVE
  Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear.
  
  
  METHODS
  Fifty nondiabetic (fasting plasma glucose ≤ 7.0 mmol/L), antipsychotic-treated male patients (ICD-10 diagnosis code F20, F21, F22, F25, F28, or F60; mean ± SD age = 33.0 ± 6.7 years; body mass index [BMI; kg/m²] = 26.0 ± 4.7; waist circumference = 95.9 ± 13.3 cm; glycated hemoglobin A1c [HbA1c] = 5.7% ± 0.3%) and 93 age- and waist circumference-matched healthy male controls (age = 33 ± 7.3 years; BMI = 26.1 ± 3.9; waist circumference = 94.6 ± 11.9 cm; HbA1c = 5.7% ± 0.3%) participated in this cross-sectional study. Blood was sampled in the fasting state and 90 minutes after ingestion of a standardized liquid meal (2,268 kJ). The primary outcomes were glucometabolic hormones and cardiovascular risk markers. Data were collected between March 2008 and February 2010.
  
  
  RESULTS
  Compared to healthy controls, patients were characterized by elevated fasting levels of proinsulin, C-peptide, and glucose-dependent insulinotropic polypeptide (GIP) (P < .05) and higher postprandial levels of insulin, proinsulin, C-peptide, and GIP (P ≤ .02). Also, patients exhibited elevated plasma levels of C-reactive protein and signs of dyslipidemia. Fasting plasma levels of insulin, glucagon, glucagon-like peptide-1 (GLP-1), ghrelin, leptin, adiponectin, tumor necrosis factor-α, plasminogen activator inhibitor-1, and interleukin-6 and postprandial levels of glucagon, GLP-1, ghrelin, leptin, and adiponectin did not differ between groups.
  
  
  CONCLUSIONS
  Presenting with an insulin resistant-like pattern, including beta cell hypersecretion and elevated GIP levels, nondiabetic antipsychotic-treated patients display emerging signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite-regulating hormones GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight into the pathophysiology associated with metabolic side effects of antipsychotic treatment and put emphasis on the importance of implementing metabolic screening into psychiatric practice.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT00627757.
authors.affiliation: Psychiatric Centre Glostrup, Copenhagen University Hospitals, Mental Health Services, Capital Region of Denmark.
authors.forename: Bjørn H
authors.initials: BH
authors.lastname: Ebdrup
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.forename: Anna
authors.initials: A
authors.lastname: Madsen
authors.forename: Henrik B
authors.initials: HB
authors.lastname: Mortensen
authors.forename: Birgitte
authors.initials: B
authors.lastname: Søgaard
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Pal B
authors.initials: PB
authors.lastname: Szecsi
authors.forename: Henrik
authors.initials: H
authors.lastname: Lublin
mesh_terms: D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000494:pharmacology; D002096:C-Peptide / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000503:physiopathology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005768:Gastrointestinal Hormones / Q000097:blood*; D054439:Ghrelin / Q000097:blood; D005934:Glucagon / Q000097:blood; D044882:Glucose Metabolism Disorders / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011384:Proinsulin / Q000097:blood; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D052242:Adiponectin; D014150:Antipsychotic Agents; D002096:C-Peptide; D005768:Gastrointestinal Hormones; D054439:Ghrelin; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; D005749:Gastric Inhibitory Polypeptide; D002097:C-Reactive Protein; D005934:Glucagon; D011384:Proinsulin