Diabetes mellitus is a complex metabolic disorder, caused by defects in insulin action and/or insulin production and is defined as afasting hyperglycaemia of >126 mg/dl, with normoglycaemia being ≥70 and ≤ 110 mg/dl. There are two main types of diabetes. Type 1 diabetes (around 10% of cases) is an autoimmune disease, usually of early onset, in which pancreatic islet beta cells that secrete insulin are destroyed. Type 2 diabetes (around 85% of cases) is characterised principally by insulin resistance and impaired insulin secretion. Heredity and obesity are major risk factors for Type 2 diabetes. Diabetes is associated with potentially life-threatening microvascular and macrovascular complications caused by elevated serum glucose levels. Treatment of diabetes aims at restoring glycaemic control. In Type 1 diabetes, this can be achieved by injecting insulin. Oral hypoglycaemic medications that stimulate insulin secretion and/or modify glucose metabolism can be used as a first-line treatment in Type 2 diabetes mellitus. However, insulin is usually necessary in later phases of the disease. Lifestyle changes, such as diet and exercise, are also important. Glycaemic control can be measured by fasting blood glucose levels and also by glycosylated haemoglobin levels. The latter measure gives an indication of glycaemic control over a period of three months, and a reduction in glycosylated haemoglobin is the most appropriate treatment goal in the management of diabetes.

The relatively high comorbidity of type 2 diabetes and schizophrenia may suggest a shared biological susceptibility to these twoconditions. Family studies have demonstrated an increased risk of diabetes in unaffected relatives of patients with schizophrenia, consistent with a heritable susceptibility trait. Linkage analyses have identified several loci that are associated with schizophrenia and some of these, notably those on chromosomes 2p22.1-p13.2 and 6g21-824.1 have also been observed in linkage studies in type 2 diabetes. In addition, the dopamine D5 receptor on chromosome 5 and the tyrosine hydroxylase gene on chromosome 11 have both been suggested as candidate genes in schizophrenia and may also be implicated in susceptibility to poor glycaemic control. In addition, an increased rate of type II diabetes has been observed in some patients treated with antipsychotics. Potential neurochemical substrates of this effect include the histamine H1 receptor, the 5-HT2C serotonin receptor or the β3 adrenoreceptor. However, the search for a genetic basis to the association between diabetes and schizophrenia is still in its infancy, and much further work needs to be performed, including the systematic screening of all confirmed susceptibility loci and quantitative trait locus mapping of glycaemic control.

To establish the impact of antipsychotic medication on the incidence of diabetes, we have analysed data from the prospective French Cohort study of mortality in schizophrenia. This generated a large database of 3470 patients with schizophrenia initially enrolled in 1993 for which data collection on comorbidity has been collected systematically every three years since. The primary objective of the study was to evaluate the mortality rate in the study cohort. From this database, the prevalence and incidence of diabetes can be studied. In 1993, nine patients in 10 were prescribed conventional antipsychotics and the remainder amisulpride and clozapine. Since the introduction of risperidone and olanzapine, atypical antipsychotics are now used in one-third of patients. Multiple antipsychotic medications are used in many patients, with the exception of those receiving clozapine. At inclusion, 2.2% of patients in the study cohort had a diagnosis of diabetes. Morbidity rates were higher in females than in males (3.4% and 1.6%, respectively) and it was only in females that the standard morbidity ratio with respect to the general population was significantly elevated (2.2; 95% confidence intervals: 1.6 and 2.9). The prevalence of diabetes in the study cohort rose over the course of the study. Multivariate regression analysis was performed in order to identify potential determinants of diabetes. For pre-existing diabetes, four factors were identified: age at first hospitalisation, age, obesity and duration of schizophrenia. The same factors with the exception of length of illness were identified for the incident cases. There was no evidence for an interaction between the class and type of antipsychotic medication and risk of treatment emergent diabetes. However, the use of multiple antipsychotic treatments makes the individualisation of specific risks associated with any other antipsychotic drug impossible.

The association of diabetes mellitus and mental illness, in particular, schizophrenia, has been remarked upon for over a century. Recentepidemiological studies have shown the age- and sex-matched prevalence of diabetes in patients with schizophrenia to be 1.5–2 times those in the general population. This difference is particularly noticeable in younger patients. The explanation for this finding probably resides in both environmental and biological factors. Patients with schizophrenia tend to be sedentary and have a poor diet, which are both known risk factors for diabetes. However, familial studies have indicated a heritable component to the risk of diabetes in patients with schizophrenia. A number of biological mechanisms have been proposed to explain this, including neuroendocrine changes and neurodevelopmental anomalies, but none are entirely satisfactory. In addition, it has been suggested that treatment with antipsychotic medication may potentially increase the risk of diabetes and account for some of the increased prevalence seen in patients with schizophrenia. It has been suggested that different antipsychotic drugs may differ in their ability to facilitate the emergence of poor glycaemic control in patients with schizophrenia. However, the situation is far from clear and more work is required to accurately assess the potential risk associated with different antipsychotic drugs.

Recently, attention has focused on a potential link between schizophrenia and diabetes, with speculation that this potential associationis stronger in patients who are prescribed atypical antipsychotics. Pharmacoepidemiological studies can help to evaluate this potential association. Source data on the incidence of diabetes in patients treated with antipsychotics is available in the FDA MedWatch database, prescription claims databases and other patient registries. These data indicate that antipsychotic drugs may increase the risk of developing diabetes and that there may be an interaction with age. However, current data are insufficient to accurately assess potential differences in the risk of diabetes between users of individual antipsychotic medications. In addition, antipsychotic treatment-emergent diabetes has several distinct features, notably relating to age of onset, gender ratio, rate of deterioration of glycaemic control, and independence from initial treatment emergent weight gain. Nonetheless, guidelines for the control of risk factors for diabetes developed for the general population appear to be applicable to patients with schizophrenia.

An interactive workshop was held to discuss the risk of diabetes in patients with schizophrenia, to evaluate the available data concerninghow such patients should be managed in terms of minimising the risk of diabetes and of optimising their care where diabetes to develop. The subjects discussed covered monitoring of risk factors, education about lifestyle and the risk of diabetes, patient care and treatment options, and interfaces between psychiatry and diabetology. The workshop noted that all patients with a diagnosis of schizophrenia had an elevated risk of developing diabetes and that this needed to be reflected in the follow-up of the patients in order to reduce the chances of the emergence of disease. The risk of diabetes is complicated by the presence of other risk factors and the intensity of the diabetes prevention programme needs to reflect adequately the overall risk. The most important prevention methods relate to lifestyle changes that patients with schizophrenia may be spontaneously unlikely to adopt and therefore necessitate the implementation of specific education measures aimed at patients and their families. The workshop proposed follow-up intensities, monitoring procedures and prevention programmes stratified according to the risk of developing diabetes. It was not considered that there was sufficient data available to orientate treatment choices between individual antipsychotic drugs according to the potential risk of developing diabetes.