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DIABETES MELLITUS IN HOSPITALIZED BIPOLAR PATIENTS

Habibolah Khazaie, Soraya Siabani, Mehrali Rahimi, Azita Chehri.

Abstract

Introduction

Diabetes mellitus (DM) has several important complications. Early diagnosis and identify risk factors can prevent complications. comorbidity of DM in major mood disorders has been reported by some studies. The aim of this study was to determine frequency of DM in BMD in Kermanshah.

Methods:

In this study,140 hospitalized (BMD)patients were evaluated for a comorbidity diabetes mellitus. Diagnosis of BMD was made according to a structured clinical interview based on DSM IV. If a subject had Fasting blood sugar (FBS) >126 for two time, was diagnosed as a diabetic. We compared the present or absence of DM with sex , duration of BMD , diagnostic subtype of bipolar and mean age ,by x2 & T-test (α=%5).

Results:

The frequency of diabetes mellitus among bipolar patients was (9.3%).There was significant relation between diabetes frequency with age and duration of (BMD) ,But between diabetes frequency with subtype there wasn’t significant relation .Only 1 patient, with DM, were known about their illness.

Conclusions:

The frequency of DM in hospitalized bipolar patients was higher than general population.The association between BMD and DM is clinically relevant and underscores the importance of screening for diabetes mellitus in the BMD, because earlier detection and control of DM is considered important for prevention of the medical comorbidity of it.

Key Words: Diabetes mellitus, Bipolar Affective Disorder

Introduction

Diabetes mellitus (DM) is one of the most common diseases that have a lot of important complications such as retinopathy, nephropathy, cardiovascular disease. So diagnosis and identification of risk factors of Diabetes mellitus and can helps us in control it and to prevent complications(1).

Abnormal glucose regulation in psychiatric populations has been suggested since the first half of this century (1-6). Sudden onset in diabetes is often associated with emotional stress, which disturbs the homeostatic balance in persons who are predisposed to the disorder. Psychological factors that seem significant are those provoking feelings of frustration, loneliness, and rejection (7, 8). Increased comorbidity of diabetes mellitus in persons with major mood disorders has also been suggested. Gordon and van der velde reported increased frequencies of abnormal results on glucose tolerance tests in manic patients compared with schizophrenic patients (9). Lilliker reported increased rates of
comorbidity diabetes mellitus in patients diagnosed with manic-depressive disorder (10).

Also Ryan &Collins reported that schizophrenia and bipolar disorder was diabetic risk factors (11). These reports were confounded by diagnostic systems that predated the separation of unipolar depression from manic depressive disorder. Cassidy et al. reported elevated frequency of diabetes mellitus in hospitalized manic depressive patients than in the general population (12). These researchers also reported that manic depressive patients with diabetes mellitus have a more severe course of illness as indicated by a greater number of psychiatric hospitalizations(12).Any finding about DM in bipolar disorders patients in Iran wasn’t founded. The purpose of this study was to evaluated whether patients diagnosed with bipolar disorder (manic or mixed) subtype , according to the DSM-IV criteria (in Kermanshah)have a higher prevalence of diabetics mellitus than the general population.

MATERIAL AND METHODS

In this descriptive study 140 patient, aged 20-74 years old, admitted to Farabi Hospital (psychiatric center),from May2002-Des2002, were selected through convenience sampling. Diagnosis of BMD was made according to a structured clinical interview based on DSM IV criteria (13) .Two psychiatrist, performed this part of the evaluation, each of them independently examined all the subjects. The diagnostic agreement between the 2 psychiatrists was high (0.97).

Patients were required to be euthymic at the time of the study and not using insulin or other glucose-lowering agents and not suffering from any physical illness that could affect fasting blood sugar. We excluded patients using olanzapine. These patients were evaluated for a comorbid diagnosis of diabetes mellitus. The National Diabetes Data Group and world Health Organization have issued based on the fasting plasma glucose > 7.Ommol / L (126mg / dl). Blood samples were collected from the fore arm vein in glass, red-topped vacuum tubes without any anticoagulant in the morning between 8.00 and 9.00 AM, after an overnight fasting of 12h and 30min of rest immediately prior to blood collection. If a subject had FBS>normal range FBS test was repeated the next day, diagnostic criteria for DM, was FBS>126 of 2 tests. In addition their demographic information and past history plus results of FBS test were written in check list. At last the frequency of diabetes mellitus in the study group was compared with the expected frequency from national norm .To this comparison we restricted our study group to the racial and socioeconomic composition and age range of the subjects in the study by Naseripoor. We compared the present or absence of DM with sex , race , diagnostic subtype of bipolar(mixed,mania) and mean age ,by x2 & T-test (α=5%).

The mean ages of the diabetic and nondiabetic patients within the study group were compared by means of -T tests. Comparing the present or absence of diabetic co morbidity with sex, age, and diagnostic subtype (manic or mixed) were computed by means of chi - square analyses.
All patients that have co morbid diagnosis of diabetes mellitus refer to endocrinologist for treatment

Results:

This group consisted of 86 men and 54 women. Their mean age was 40.2 years (SD = 12.6, range = 17-70)
The prevalence of diabetes mellitus in this patients was 9.3% (N = 13),9 men and 4 women. Twenty patients had not been diagnosed with diabetes mellitus before their current psychiatric hospitalization and only 1 patient had been diagnosed before hospitalization. Characteristics of the diabetic and nondiabetic patients are shown in table 1.

The results of chi - square analyses were not significant for diagnostic subtype (mixed versus manic), or sex, but the difference in the mean ages of the diabetic and nondiabetic groups was significant (p<0.001).

Their mean age was 51 years (SD, 10.2). One of these subjects met the criteria for bipolar disorder, mixed subtype, and others for bipolar disorder, manic subtype. The mean age of the nondiabetic bipolar was 38 years (SD = 10.0). This group consisted of 77 men and 50 women. Twenty of them met the DSM-IV criteria for bipolar disorder, mixed and 107 for bipolar disorder, manic subtype.

The difference in the mean ages of the diabetic and nondiabetic groups was significant (t = 6.40, df = 138, P < 0.001). The age at the onset of diabetes mellitus could not be determined in this study.
The total number of psychiatric hospitalizations in the diabetic group (mean = 9.9, SD = 105) was significantly greater than that in the nondiabetic group. There was significant relation between diabetes frequency with duration (>10 years) of bipolar mood disorder (p=0.00).

Table 1: Characteristics of 140 patients with Bipolar Disorder
According to nondiabetic or diabetic status.

Variables		Diabetic		Non-Diabetic		Analysis
Variables		No.	%	No.	%	Chi squared =1.36 df=1 p>0.5
Sex	male	9		77
	female	4		50
	sum	13		127
Bipolar Subtype	mixed	1		20		Chi squared =0.36 df=1 p>0.05
	manic	12		107
	sum	13		127
Age (year)	mean +/- sd	51.2+/-12.4		38.6 +/- 9		t=6.40 p<0.001

Discussion:

The main purpose of this study was to determine frequency of diabetes mellitus in bipolar patients in Kermanshah. According to the results of the study, the overall frequency of diabetes mellitus in patients with bipolar disorder, manic or mixed subtype (9.3%) was significantly higher than in the general population that previously were studied. In the study by Naseripoor et al frequency of DM in Kermanshah was % 3.44 (15) .Also others studies supported his results, for example: 2.5% reported in a national research in Iran (16), &3.4% reported by Cassidy (12).In addition endocrinology’s textbook agree with 2.3% (1).

The results of this study support the 10.1% frequency which was reported by Cassidy (12) and is in agreement with the 10% frequency which was reported by liliker (11). Although, the demographics of the general population and our study group were alike, a direct comparison of our group with population norm may be limited by methodological differences and selection biases. Possible explanations for this comorbidity include:

A causal relationship in which the development of diabetes mellitus or mania increases the risk of the development of the other disorder.
A genetic relationship between the two diseases.
A functionally overlapping disturbance present in both diseases.
Psychotropic medication may further increase the risk of the development of diabetes, either directly or as a result of weight gain.

Each of these possibilities derives some support from our understanding of these diseases. There is a consensus that multiple genes are likely to be involved in the pathogenesis of manic – depression (16). The tyrosine hydroxylas – INS – insulin – like growth factor II gene cluster on the short arm of chromosome 11 has been implicated as a susceptibility low for diabetes mellitus (17, 18).

Although initial reports of the INS gene being a susceptibility locus for bipolar disorder (18) were subsequently discounted after a reanalysis of a larger sample (20), tyrosine hydroxyls markers have been shown to have some associations with bipolar disorder (21).
Increased glucocorticoids have been reported to induce diabetes mellitus (22) and hypercortisolemia has been reported during depressive episodes (23).

For this reason manic episodes might also predispose to the development of diabetes mellitus. Both diabetes mellitus and mania have associated disturbances of the hypothalamic – pituitary – adrenal axis, as reflected by high rates of nonsuppression of cortisol on the dexamethosone suppression test (24, 25). Moreover, the suprachiasmatic nucleolus of the hypothalamus has been implicated both in disturbances of the sleep – wake cycle noted during mania (25) and in the regulation of glucose metabolism (26).
Higher rates of lesions of small intraparenchymal cerebral vessels and focal infarction have been reported in diabetic patients (27).Although it is not known whether diabetes related vascular lesion chat occur in the brain can result in psychopathology,subcortical white matter lesion have also been observed in t2-weighted magnetic resonance imaging(M.R.I)scan in bipolar disorder(25). In the other hand Diabetes mellitus has been implicated as a risk factor for similar hyper intensities on T2 weighted (M.R.I) scans (28).
Leslie citrome and coworker in a review article reported the second generation antipsychotic agents are not free of burdensome side effects, however. Issues that have recently become a focus of much attention have been weight gain, risk for the development of diabetes mellitus, and/or the metabolic syndrome (29).Results of Leslie et al support this reason (5).

The association between bipolar disorder and diabetes mellitus is clinically relevant and underscores the importance of screening for diabetes mellitus in the bipolar population, particularly because earlier detection and control of diabetes mellitus is considered important for prevention of the medical comorbidity of diabetes mellitus and for prevention of cerebral micro vascular disease that may exacerbate the course of bipolar disorder.

Further controlled studies of the relationship of these two disorders are warranted.

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Authors:

Habibolah. Khazaie. MD1, Soraya. Siabani. MD, 2 Mehrali.Rahimi.MD 3, Azita.Chehri 4

1- Professor Assistant, Department of Psychiatry, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
2- General Physician, Department of Research, Kermanshah University of Medical Sciences, Kermanshah, Iran
3- Professor Assistant, Department of Endocrinology, Faculty of Medicine, Kermanshah University of
Medical Sciences, Kermanshah, Iran
4- Masster, Department of Psychometry.Azad University of Kermanshah, Kermanshah, Iran

Correspondance:
Habibolah Khazaie MD. Farabi Hospital, Dolat Abad st, Kermanshah , Iran