Diabetes mellitus is a complex metabolic disorder characterised by persistent hyperglycaemia. The prevalence of diabetes is increased in people with schizophrenia.

To provide an update of current thinking in diabetes for practising psychiatrists.

Literature review.

Diabetes is a costly condition in individual, social and economic terms, and the global burden of diabetes is increasing in most populations. The insidious onset and asymptomatic nature of diabetes results in many people remaining undiagnosed and at great risk of developing life-threatening vascular complications. Lifestyle and pharmacological interventions can reduce incident diabetes and delay its progression.

Public health policies are urgently required to encourage people to follow a healthy lifestyle. Primary prevention strategies for diabetes should target individuals at especially high risk of developing type 2 diabetes, including those with severe mental illness.

Although recent research has focused on the possible role of antipsychotic medications in the development of diabetes mellitus, studies conducted in the pre-neurolepticera suggest that schizophrenia itself might predispose individuals to diabetes.

To test the hypothesis that diabetes mellitus is an integral part of schizophrenia.

Historical literature review.

Many people with severe mental illnesses, including dementia praecox, showed abnormal responses to insulin and diabetes-like glucose tolerance curves long before the advent of phenothiazines. Early studies with chlorpromazine suggested that a latent tendency towards diabetes in patients with schizophrenia could be unmasked by this treatment.

Diabetes and disturbed carbohydrate metabolism maybe an integral part of schizophrenia. Further research is required to explain how metabolic factors, medications and lifestyle factors might precipitate diabetes in patients with this mental disorder.

A number of studies have examined the prevalence of diabetes mellitus and impaired glucose tolerance in general populations and in those with schizophrenia and other forms of serious mental illness.

To establish whether it is possible to describe accurately comparative rates of diabetes mellitus and impaired glucose tolerance in populations of people with schizophrenia and those without mental illness.

Review of current literature.

Research published in the pre-neuroleptic era suggested that people with severe mental illness were at increased risk of developing glycaemic abnormalities. Recent studies appear to confirm that the prevalence of diabetes and impaired glucose tolerance may be higher in people with schizophrenia than in the general population, and suggest that patients with schizophrenia have impaired glucose tolerance even before they begin treatment.

Schizophrenia may be a significant and independent risk factor for both diabetes and impaired glucose tolerance. Current data preclude precise estimates of the prevalence of these conditions among people with schizophrenia.

The incidence of diabetes mellitus is higher in patients with schizophrenia than in the general population. Antipsychotic drugs have been implicated in the development of diabetes, but as non-medicated patients with schizophrenia have high rates of diabetes it is likely that factors other than medication are involved.

To examine the role of stress in the emergence of diabetes mellitus in patients with schizophrenia.

Selective literature review.

A model is developed suggesting that patients with schizophrenia show overactivation of both the hypothalamic–pituitary–adrenal and sympathoadrenal medullary axes, manifested by increased production of cortisol and adrenaline. Both of these hormones are known to be diabetogenic and are proposed as playing a part in the onset of diabetes mellitus in schizophrenia.

Stress has an important role in the onset of schizophrenia and may also play a part in relapse. Further research is needed to clarify the extent to which stress accounts for the genesis of diabetes in such patients.

Schizophrenia shortens life, e.g. through suicide and obesity-related diseases such as type 2 diabetes mellitus. It is assumed that medications play a major role, but most of the evidence for this comes from studies poorly controlled for variables such as lifestyle and medication status.

To determine whether schizophrenia is associated (independently of medication) with the development of certain metabolic disturbances and whether these might be explained by stress axis dysfunction.

Literature review.

Most studies did not control for confounding factors such as previous usage of medication, lifestyle, age and ethnicity. A few conducted in drug-naive patients with first-episode schizophrenia appear to indicate that these patients have higher than expected rates of visceral obesity and impaired fasting glucose concentrations, which may be related to a subtle disturbance of the hypothalamic–pituitary–adrenal axis.

Schizophrenia is independently associated with physical illnesses that have a metabolic signature. Therefore, patients need to have a thorough physical assessment at diagnosis and at regular intervals thereafter. Metabolic disturbances have been found in drug-naïve patients with first-episode illness and may be an inherent part of the illness.

Much of the existing data regarding the relationship between antipsychotic medications and diabetes mellitus are non-prospective.

To review critically non-prospective studies examining antipsychotic medications as risk factors for diabetes mellitus.

Database and manual searches.

Anecdotal reports indicate that conventional and atypical antipsychotics can cause diabetes mellitus. However, retrospective studies cannot reliably quantify this association, as they do not adequately control for confounding risk factors for diabetes, or for variation in detection and diagnosis of this illness. Most studies report a higher rate of diabetes in patients who use antipsychotic medication than in non-users, and in patients taking atypical v. conventional antipsychotics. Studies assessing the relative risks of diabetes between individual atypical antipsychotics are contradictory.

Retrospective data are of limited value. Well-designed prospective studies, which account for potential confounders, are needed to investigate the true association between antipsychotic medications and diabetes.

Most evidence suggesting an association between schizophrenia, antipsychotic medications and diabetes has been based on retrospective studies not controlled for important confounders.

To compare diabetogenic risk between antipsychotic medications; and to describe the limitations of current prospective data-sets.

Systematic review of prospective clinical data.

No difference in the incidence of glycaemic abnormalities between placebo cohorts and antipsychotic medication cohorts was identified. No significant difference between any of the antipsychotic medications studied in terms of their association with glycaemic abnormalities was identified. Treatment-related weight gain did not appear to increase the risk of developing diabetes.

Diabetogenic potential ascribed to atypical antipsychotic drugs, resulting from retrospective studies, may be incorrect. Cohort sizes and incomplete sampling must preclude any definitive conclusions. Long-term, large, comparative prospective trials are needed, along with agreement upon glucose measurement of choice.

In this retrospective analysis, we assessed the short-term risk of treatment-emergent diabetes (TED) among patients with schizophrenia during clinical trials of antipsychotic medications.

From a non-diabetic cohort of patients with schizophrenia (n=5013), the relationship between baseline non-fasting glucose measurement, presence at baseline of risk factors for diabetes, weight gain and therapy assignment on the risk of treatment-emergent diabetes were assessed.

At the baseline assessment, about a third of patients identified with TED during treatment had non-fasting glucose levels over 7.8 mmol/l and two-thirds had multiple diabetes risk factors. Both baseline non-fasting glucose level and the presence of multiple pre-existing diabetes risk factors appeared to have a major impact on the risk of developing diabetes.

Overall, risk factors for diabetes in patients with schizophrenia overlap those in the general population. The results also suggest that many patients identified with TED might have had pre-existing glycaemic abnormalities or a high baseline burden of diabetes risk factors.

Diabetes is more common in people with schizophrenia than in the general population.

To explore the possible reasons for the association between diabetes and schizophrenia.

Diet and other lifestyle factors in patients with schizophrenia were reviewed as risk factors for diabetes.

People with schizophrenia show features of the metabolic syndrome at the onset of illness, before treatment. They also eat a poor diet, take little exercise and have high rates of smoking. Food intake may be increased further by antipsychotic medication. Nutritional factors appear to have a key role in the development of diabetes in patients with schizophrenia and may also affect the outcome and severity of schizophrenia. A common pathway through which diet might contribute to the development of both diabetes and schizophrenia is proposed.

Lifestyle factors may influence outcomes in both diabetes and schizophrenia. Lifestyle interventions are the key to improving the long-term health of people with schizophrenia.

Patients with schizophrenia have an increased risk of developing diabetes. However, no pragmatic pathway of care has ever been proposed in order to identify individuals at risk and manage that risk effectively.

To develop practical recommendations for the screening and management of diabetes in schizophrenia.

Staged review of evidence for the under recognition of diabetes in people with schizophrenia and of the applicability of current screening strategies to this population. Recommendations for pragmatic pathways of care were developed.

All patients with schizophrenia should be screened and managed as a high-risk group for the development of diabetes. Psychiatrists should be responsible for screening and diabetes risk management; primary care physicians and/or diabetologists should be responsible for managing diabetes. Choice of antipsychotics should be based on achieving good control of schizophrenia, which may improve compliance with diabetes risk reduction strategies.

Effective multi-disciplinary team working should reduce the burden of diabetes in schizophrenia.