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Meta-Analysis
. 2017 Mar 1;74(3):261-269.
doi: 10.1001/jamapsychiatry.2016.3803.

Impaired Glucose Homeostasis in First-Episode Schizophrenia: A Systematic Review and Meta-analysis

Toby Pillinger  1 , Katherine Beck  1 , Cristian Gobjila  1 , Jacek G Donocik  1 , Sameer Jauhar  1 , Oliver D Howes  2
Affiliations
Meta-Analysis

Impaired Glucose Homeostasis in First-Episode Schizophrenia: A Systematic Review and Meta-analysis

Toby Pillinger et al. JAMA Psychiatry. .

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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Conflict of interest statement

Declaration of Interest

Professor Howes has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organised by Astra-Zeneca, Autifony, BMS, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Otsuka, Servier, Sunovion, Rand and Roche. Neither Professor Howes nor his family have been employed by or have holdings/a financial stake in any biomedical company.

Figures

Figure 1
Figure 1
Search process. OGTT: Oral Glucose Tolerance Test; HOMA-IR: Homeostatic Model Assessment (Insulin Resistance); HbA1c: glycated haemoglobin.
Figure 2
Figure 2
Forest plots showing fasting glucose concentrations in patients with first episode schizophrenia and controls (figure 2.1: significant elevation in patients, ES: 0.20 p = 0.028); and glucose concentrations post-OGTT in patients with first episode schizophrenia and controls (figure 2.2: significant elevation in patients, ES: 0.61 p = 0.007).
Figure 3
Figure 3
Forest plots showing fasting insulin concentrations in patients with first episode schizophrenia and controls (figure 3.1: significant elevation in patients, ES: 0.41 p = 0.011); and insulin resistance (HOMA-IR) in patients with first episode schizophrenia and controls (figure 3.2: significant elevation in patients, ES: 0.35 p = 0.001).
See this image and copyright information in PMC

Comment in

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