title: Impaired Glucose Homeostasis in First-Episode Schizophrenia: A Systematic Review and Meta-analysis.
abstract: OBJECTIVE
  Schizophrenia is associated with an increased risk of type 2 diabetes. However, it is not clear whether schizophrenia confers an inherent risk for glucose dysregulation in the absence of the effects of chronic illness and long-term treatment.
  
  
  OBJECTIVE
  To conduct a meta-analysis examining whether individuals with first-episode schizophrenia already exhibit alterations in glucose homeostasis compared with controls.
  
  
  METHODS
  The EMBASE, MEDLINE, and PsycINFO databases were systematically searched for studies examining measures of glucose homeostasis in antipsychotic-naive individuals with first-episode schizophrenia compared with individuals serving as controls.
  
  
  METHODS
  Case-control studies reporting on fasting plasma glucose levels, plasma glucose levels after an oral glucose tolerance test, fasting plasma insulin levels, insulin resistance, and hemoglobin A1c (HbA1c) levels in first-episode antipsychotic-naive individuals with first-episode schizophrenia compared with healthy individuals serving as controls. Two independent investigators selected the studies.
  
  
  METHODS
  Two independent investigators extracted study-level data for a random-effects meta-analysis. Standardized mean differences in fasting plasma glucose levels, plasma glucose levels after an oral glucose tolerance test, fasting plasma insulin levels, insulin resistance, and HbA1c levels were calculated. Sensitivity analyses examining the effect of body mass index, diet and exercise, race/ethnicity, and minimal (≤2 weeks) antipsychotic exposure were performed.
  
  
  RESULTS
  Of 3660 citations retrieved, 16 case-control studies comprising 15 samples met inclusion criteria. The overall sample included 731 patients and 614 controls. Fasting plasma glucose levels (Hedges g = 0.20; 95% CI, 0.02 to 0.38; P = .03), plasma glucose levels after an oral glucose tolerance test (Hedges g = 0.61; 95% CI, 0.16 to 1.05; P = .007), fasting plasma insulin levels (Hedges g = 0.41; 95% CI, 0.09 to 0.72; P = .01), and insulin resistance (homeostatic model assessment of insulin resistance) (Hedges g = 0.35; 95% CI, 0.14 to 0.55; P = .001) were all significantly elevated in patients compared with controls. However, HbA1c levels (Hedges g = -0.08; CI, -0.34 to 0.18; P = .55) were not altered in patients compared with controls.
  
  
  CONCLUSIONS
  These findings show that glucose homeostasis is altered from illness onset in schizophrenia, indicating that patients are at increased risk of diabetes as a result. This finding has implications for the monitoring and treatment choice for patients with schizophrenia.
authors.affiliation: Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England.
authors.forename: Toby
authors.initials: T
authors.lastname: Pillinger
authors.affiliation: Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England.
authors.forename: Katherine
authors.initials: K
authors.lastname: Beck
authors.affiliation: Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England.
authors.forename: Cristian
authors.initials: C
authors.lastname: Gobjila
authors.affiliation: Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England.
authors.forename: Jacek G
authors.initials: JG
authors.lastname: Donocik
authors.affiliation: Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England.
authors.forename: Sameer
authors.initials: S
authors.lastname: Jauhar
authors.affiliation: Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, England2MRC London Institute of Medical Sciences, Hammersmith Hospital, London, England3Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, England.
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D012306:Risk; D012559:Schizophrenia / Q000097:blood*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human