Immunological characteristics of diabetes in schizophrenia

Abstract

Abbreviations IA2: insulinoma antigen 2 . LADA: latent autoimmune diabetes of adults To the EditorIn 1899, Henry Maudsley, the first psychiatrist to link diabetes to psychiatric illness, wrote that "diabetes is a disease which often shows itself in families in which insanity prevails" [1]. With this observation, Maudsley suggested that patients with schizophrenia are genetically predisposed to diabetes. The introduction of chlorpromazine (in 1953) and, more recently, the atypical antipsychotics was followed by an increase in the number of cases of new-onset diabetes and the worsening of glycaemic control in cases of existing diabetes in patients with schizophrenia [2]. These findings suggest an iatrogenic, rather than a genetic, origin of diabetes in schizophrenia, in the form of antipsychoticinduced weight gain. However, this debate has not, as yet, been settled.In general, diabetes associated with schizophrenia is classified as type 2 diabetes. However, there are two arguments against this classification. The first argument is the rapid onset of schizophrenia-associated diabetes: over 80% of patients who develop diabetes do so within 6 months of initiating antipsychotic therapy [2]. With such a rapid onset, weight gain is unlikely to be the main stimulus for the development of the diabetes. A prospective randomised trial comparing the classical antipsychotic haloperidol with the three atypicals clozapine, olanzapine and risperidone found no relationship between glucose change and weight gain at endpoint, thereby confirming the independence of these two measures [3]. The second argument is the dramatic clinical presentation of diabetes in schizophrenia. There is an enhanced risk of metabolic complications, such as ketosis, acidosis and ketoacidosis, which are associated with a mortality rate of 26.5% [4][5][6]. These features are suggestive of type 1 diabetes or latent autoimmune diabetes of adults (LADA) rather than type 2 diabetes.Type 1 diabetes and LADA are characterised by diabetes-related antibodies, i.e. antibodies against insulin, GAD and insulinoma antigen 2 (IA2), which are found in over 80% of type 1 diabetic subjects and in fewer than 5% of the general population [7,8]. The aim of this study was to determine the prevalence of the three diabetes-related antibodies in schizophrenic patients, thereby establishing whether autoimmune phenomena play a role in diabetes associated with schizophrenia.Patients (81 men [68.1%], 38 women [31.9%]; mean age 41.5 years [SD=10.9, range 19-65]) gave informed consent to participate in the study, which was approved by the Ethics Committee of the University of Utrecht. The psychiatric diagnosis was based on the shortened version of the

Hyperglycemia and Diabetes in Patients With Schizophrenia or Schizoaffective Disorders

“…The results reveal that the less severe form of glucose metabolism (hyperglycemia) was less prevalent (7%) compared with the 14.5% with the more severe form (diabetes). This result seems to confirm earlier findings that disturbance of glucose metabolism tends to be more severe in patients with schizophrenia than in the general population (27,28). The differences in prevalence of impaired fasting glucose (1.5%) and impaired glucose tolerance (5.5%) reflect the differences in sensitivity between fasting and 2-h measurements.…”

Diabetes mellitus and severe mental illness: mechanisms and clinical implications

“…17,18 No evidence exists for enhanced pancreatic autoimmunity in individuals with SMI and so the excess prevalence relates to an increased incidence of type 2 diabetes mellitus (T2DM). 19 Exactly when the increased risk of diabetes mellitus begins to manifest is controversial, with some studies showing subtle metabolic abnormalities before patients begin antipsychotic treatment. 20 However, the majority of studies suggest that metabolic abnormalities accu mulate rapidly after the initiation of treatment.…”

Autoantibodies against voltage‐gated potassium channel and glutamic acid decarboxylase in psychosis: A systematic review, meta‐analysis, and case series

“…The literature search revealed nine studies satisfying eligibility criteria. Eight of these were case-control studies 20,29,30,[33][34][35][36][37] and one was an observational study (with general population rates of GAD65 positivity used for comparison in Cohen et al 38 ). All of the included studies assessed serum for GAD antibody positivity.…”

“…Yarlagadda et al 35 Yarlagadda et al 36 Padmos et al 33 Yarlagadda et al 20 Lennox et al 37 Cohen et al 38 Gaughran et al 34 Çoban et al 29 Dahm © 2017 The Authors Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology studies had small sample sizes, with contrasting methodologies used to measure and detect GAD antibodies. Three studies 29,35,36 used the enzymelinked immunosorbent assay method, with GAD levels calculated using absorbance values, rather than by antibody titers as in the 2011 Yarlagadda group study.…”