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Original Investigation
Meta-analysis
January 11, 2017

Impaired Glucose Homeostasis in First-Episode SchizophreniaA Systematic Review and Meta-analysis

Author Affiliations
  • 1Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, England
  • 2MRC London Institute of Medical Sciences, Hammersmith Hospital, London, England
  • 3Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, England
JAMA Psychiatry. Published online January 11, 2017. doi:10.1001/jamapsychiatry.2016.3803
Key Points

Question  Do individuals with first-episode schizophrenia already demonstrate evidence of glucose dysregulation?

Findings  In this meta-analysis of 14 case-control studies comprising 1345 participants, individuals with first-episode schizophrenia had elevated fasting plasma glucose levels, elevated plasma glucose levels after an oral glucose tolerance test, and elevated fasting plasma insulin levels, as well as greater insulin resistance compared with healthy individuals serving as controls.

Meanings  Glucose homeostasis is altered from illness onset in schizophrenia, indicating that patients are at increased risk for type 2 diabetes as a result; this finding has implications for the monitoring and treatment of patients with schizophrenia.

Abstract

Importance  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.

Data Sources  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.

Study Selection  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.

Data Extraction  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.

Data Synthesis  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 and Relevance  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.

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