Schizophrenia and Diabetes: Shared Roots?

Megan Brooks

October 26, 2016

There is a link between first-episode psychosis and insulin resistance/impaired glucose tolerance, according to the first meta-analytic review on the topic.

Investigators found that biochemical markers of both prediabetic states were more common in antipsychotic-naive patients with first-episode psychosis than in healthy peers.

"Our results suggest that there might be an intrinsic link between abnormal glycemic control and psychosis, beneath the effects of diet, medication, and reduced access to healthcare that are all known causes for those with schizophrenia to suffer from diabetes," first author Benjamin Ian Perry, MBBS, of Coventry and Warwickshire Partnership NHS Trust, United Kingdom, told Medscape Medical News.

"People with schizophrenia are known to die younger than the general population, with a greater burden of physical comorbidity. If schizophrenia patients are intrinsically susceptible to abnormal glycemic indices, in addition to the known environmental risk factors they may be exposed to, we as clinicians must show increased vigilance to the physical health of our patients," Dr Perry said.

The study was published online October 5 in the Lancet Psychiatry.

Shared Pathways

"Schizophrenia might share intrinsic inflammatory disease pathways with type 2 diabetes," the investigators note. Patients with schizophrenia are up to 30% more likely to have diabetes than the general population. Patients with first-episode psychosis, who are generally younger and have fewer comorbidities and less exposure to antipsychotic medications, are a good group to study for a possible disease link, they add.

To determine whether intrinsic disease links could cause the disorders to develop in unison, Dr Perry's team assessed whether first-episode psychosis, which could be described as "developing schizophrenia," is associated with prediabetic markers, or "developing diabetes."

The researchers identified 12 case-control studies with 1137 participants that included biochemical assessment of prediabetic states in patients with first-episode psychosis and matched control participants.

All 12 studies measured fasting plasma glucose levels. The pooled data analysis found no significant difference in fasting plasma glucose levels between patients with first-episode psychosis and control patients (mean difference, 0.03 mmol/L; 95% confidence interval [CI], -0.04 to 0.09; P = .43).

Nine studies included homeostatic model assessment. The pooled data from eight of the studies showed that insulin resistance was higher in patients with first-episode psychosis than in control patients (mean difference, 0.30 units; 95% CI, 0.18 - 0.42; P < .0001).

Seven studies measured impaired glucose tolerance using the oral glucose tolerance test. The pooled data suggested increased impaired glucose tolerance in patients with first-episode psychosis (mean difference, 1.31 mmol/L; 95% CI, 0.37 - 2.25; P < .0001).

Owing to a high level of heterogeneity in this analysis, which was caused by one outlier, the researchers used a random-effects model. Seven studies compared the number of case patients who met criteria for impaired glucose tolerance with the number of control patients who met those criteria. Pooled data showed that the number of patients with first-episode psychosis who met criteria for impaired glucose tolerance was greater than the number of control patients who did so (odds ratio, 5.44; 95% CI, 2.63 - 11.27; P < .0001).

Differences in adiposity between the case patients and the control patients did not explain these findings, the authors note.

"Our findings," they conclude, "support the hypothesis that schizophrenia and diabetes share intrinsic disease links, which might be inflammatory in nature. If patients are at an increased risk of developing glycemic regulation abnormalities even before the administration of antipsychotics, heightened vigilance and stricter control of the metabolic indices of patients with schizophrenia is essential to help reduce the physical health burden associated with the disease."

Need for Metabolic Assessment Reinforced

In an accompanying commentary, Mehrul Hasnain, MBBS, of Eastern Health, Waterford Hospital, St John's, Newfoundland, Canada, notes that the findings "further signify the recommendation to do baseline metabolic assessment of all patients requiring treatment with an antipsychotic drug.

"The idea of studying markers of preclinical glucose dysregulation in first-episode psychosis is not new, but quality scientific literature on this topic is scarce," he writes, noting that Dr Perry and colleagues found only 12 of 1015 identified articles that were suitable for inclusion.

The findings of this meta-analysis, Dr Hasnain says, "strengthen the notion of the unique vulnerability of this patient population and show a need for further well-designed research on this topic.

"We need to start entertaining the idea that there is more to the metabolic vulnerability of patients with schizophrenia (and possibly bipolar disorder) than can be attributed to unhealthy lifestyle and drug adverse effects," Dr Hasnain concludes.

The study had no funding. The authors have disclosed no relevant financial relationships.

Lancet Psychiatry. Published online October 5, 2016. Abstract, Commentary

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