Research report
Increased prevalence of type 2 diabetes mellitus among psychiatric inpatients with bipolar I affective and schizoaffective disorders independent of psychotropic drug use

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Abstract

Background: There are numerous reports of abnormal glucose metabolism, including increased rates of type 2 diabetes mellitus, in psychiatric patients. It remains unclear, however, whether there is an intrinsic relationship between abnormal glucose metabolism and particular psychiatric disorders, because the relationship is complicated by treatment with psychotropic medications that promote weight gain and hyperglycemia. This study aimed to clarify this relationship. Methods: The medical records of 243 inpatients, aged 50–74 years, with diagnoses of major depression, bipolar I disorder, schizoaffective disorder, schizophrenia, and dementia were reviewed. Psychiatric and type 2 diabetes mellitus diagnoses, medications, body mass index (BMI), age, gender, and race were recorded. Diabetes rates were compared to age, race, and gender-matched rates in the US general population. Results: Rates of type 2 diabetes mellitus were: schizoaffective (50%)>bipolar I (26%)>major depression (18%)=dementia (18%)>schizophrenia (13%) (p<0.006). Diabetic patients had a higher mean BMI (p=0.01), but not a significantly higher use of psychotropic medications previously reported to be associated with new-onset type 2 diabetes (e.g., phenothiazines, clozapine, olanzapine). Logistic regression revealed that psychiatric diagnosis and BMI were the only significant and independent predictors of diabetes diagnosis. Compared to national norms, diabetes rates were significantly elevated only in bipolar I affective and schizoaffective patients. Limitations: This study was a retrospective chart review of older, hospitalized patients. Conclusions: This is the first published study to show an increased prevalence of type 2 diabetes mellitus among psychiatric patients with particular psychiatric illnesses independent of the effects of age, race, gender, medication, and body mass. This finding, which requires replication in a larger scale, prospective study, suggests an intrinsic relationship between abnormal glucose metabolism and bipolar I affective and schizoaffective disorders.

Introduction

Evidence of abnormal glucose metabolism in psychiatric patients has been accumulating since the early 20th century (Kooy, 1919). The evidence consists of numerous reports of increased rates of impaired glucose tolerance, insulin resistance, and frank diabetes mellitus among psychiatric patients (Braceland et al., 1945, Waitzkin, 1966, Mueller et al., 1969, Keskiner et al., 1973, Brambilla et al., 1976, Winokur et al., 1988). Major studies of diabetes prevalence are reviewed below.

Eaton et al. (1996), following up on individuals who had been diagnosed with major depression in 1981 as part of the Epidemiological Catchment Area Program survey, found that major depression was associated with a 2.23 relative risk of diabetes onset over the 13 years since diagnosis. In a study of spouses and first-degree relatives of probands in the NIMH Collaborative Depression Study, Moldin et al. (1993) found that individuals diagnosed and treated for major depression had a 1.87 relative odds of also having a diagnosis of diabetes. Conversely, studies of the prevalence of depression in diabetics report rates of major depression two to three times that of nondiabetics (Gavard et al., 1993, Anderson et al., 2001).

Regarding manic-depressive illness, there have been two chart review studies reporting an increased prevalence of diabetes in hospitalized manic-depressives. Lilliker (1980) found a threefold higher rate of diabetes in 203 manic-depressive inpatients compared to other psychiatric inpatients and to the general US population. Cassidy et al. (1999) compared the rate of diabetes in 345 hospitalized manic-depressives to the expected general US population rate weighted for age, race and gender and found a similarly increased rate.

There have been three large-scale chart review studies reporting increased rates of diabetes in schizophrenia. Tabata et al. (1987) found an increased rate of diabetes among 420 Japanese schizophrenics compared to 312 controls. Mukherjee et al. (1996) found an increased prevalence of diabetes among 95 Italian schizophrenic inpatients compared to the general population. More recently, using large databases that included Medicare and Medicaid claims data, Dixon et al. (2000) reported an increased rate of diabetes among schizophrenic individuals compared to the general US population.

Although not a study of diabetes prevalence, a study by Newcomer et al. (1999) is worth noting, because it compared schizophrenic and bipolar patients to controls on a glucose tolerance test and matched subjects for age and body mass. This study found that schizophrenic patients had significantly higher plasma glucose levels than both bipolar patients and controls 75 min after a 50 g oral dextrose load; however, schizophrenic and bipolar patients were equally insulin resistant with significantly elevated insulin levels compared to controls. As this was a small study with only 10 subjects in each group, it was unable to control for the effect of psychotropic medication.

Despite this considerable investigation, it remains unclear whether there is an intrinsic pathophysiologic relationship between abnormal glucose metabolism and particular psychiatric illnesses, because studies published so far have typically been limited to a single diagnostic group and/or have not controlled for a number of factors, which can confound the relationship. In addition to factors that are typically controlled in diabetes prevalence studies, such as age, race, and gender, diabetes prevalence in psychiatric patients can be affected by treatment with psychotropic medications, many of which can cause weight gain and several of which have been associated with new-onset diabetes. Psychotropic medications of a newer (e.g., clozapine and olanzapine) and an older (e.g., phenothiazines) vintage have been reported to be associated with new-onset diabetes (Thonnard-Neumann, 1968, Wirshing et al., 1998, Goldstein et al., 1999). By including psychiatric patients with a range of diagnoses and by controlling for the effects of age, race, gender, body mass, and the use of potentially hyperglycemic psychotropic medications, this study aimed to determine whether there is an intrinsic pathophysiologic relationship between abnormal glucose metabolism and particular psychiatric disorders. Making this determination may help in understanding the etiologic significance of comorbid diabetes in psychiatric illness (Tsuang et al., 1983). Moreover, it could provide helpful information for the practicing psychiatrist who treats patients who already have or are particularly vulnerable to comorbid diabetes.

Section snippets

Methods

This was a retrospective, chart-review study. We examined the medical records of all consecutive admissions to our older adult acute inpatient unit at the University of Maryland Medical Center (UMMC) from January 1993 to July 1999. Referral sources included: UMMC Emergency Department, 62%; private practice psychiatrists, 10%; Psychiatry Consultation-Liaison Service, 9%; non-psychiatrist outpatient physicians; and others, 19%. Five hundred and four patients from the initial group of 1011

Results

As shown in Table 1, rates of type 2 diabetes among the five diagnostic groups were significantly different as follows: schizoaffective (50%)>bipolar I (26%)>major depression (18%)=dementia (18%)>schizophrenia (13%) (χ2=14.5, df=4, p=0.006). Use of potentially hyperglycemic psychotropic medication also differed significantly, with highest use among schizophrenic and schizoaffective patients (χ2=41.4, df=4, p<0.00001), as did mean age, with the depressed group significantly older than

Discussion

Our data suggest that particular psychiatric diagnoses are associated with abnormal glucose metabolism, as evidenced by type 2 diabetes mellitus comorbidity, independent of the effects of body mass and of psychotropic medications—phenothiazines, olanzapine, and clozapine—that have been associated with new-onset diabetes. Type 2 diabetes prevalence was highest among bipolar I affective and schizoaffective disorder patients at 26 and 50%, respectively, significantly above the rates expected from

Acknowledgements

This study was funded in part by a University of Maryland, Department of Psychiatry, Faculty Research Initiative Program award and a NARSAD Young Investigator award to W.T.R. Thanks to Dr. Mitchel A. Kling for his advice on the manuscript.

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