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Prevalence of diabetes, obesity, and metabolic syndrome in subjects with and without schizophrenia (CURES-104)
Subashini R, Deepa M, Padmavati R1, Thara R1, Mohan V
Epidemiology and Background: There are some reports that diabetes and metabolic syndrome (MS) are more prevalent among Diabetology, Madras Diabetes Research schizophrenia patients. However, there are very few studies in India which have estimated the prevalence of diabetes and MS in schizophrenia patients. Aims: The aim of this study was to determine the prevalence Dr. Mohan's Diabetes of diabetes, obesity, and MS in subjects with and without schizophrenia. Settings and Design: This case Specialities Centre, WHO control study comprised of "cases" i.e. subjects with schizophrenia recruited from a schizophrenia centre at Collaborating Centre Chennai and "controls" i.e. healthy age‑ and gender‑matched subjects without psychiatric illness selected for Noncommunicable from an ongoing epidemiological study in Chennai in a 1:4 ratio of cases: Controls. Materials and Methods: Diseases Prevention and Fasting plasma glucose and serum lipids were estimated for all subjects. Anthropometric measures including Control, IDF Centre for height, weight, and waist circumference were assessed. Diabetes and impaired fasting glucose (IFG) were Education, 1Schizophrenia defined using American Diabetes Association criteria. Statistical analysis: One‑way ANOVA or student's Research Foundation "t" test was used to compare continuous variables and Chi‑square test to compare proportion between two [SCARF], Chennai, Tamil Nadu, India groups. Results: The study group comprised of 655 subjects, 131 with schizophrenia and a control group of 524 subjects without schizophrenia. The prevalence of the diabetes, IFG, abdominal obesity and MS were Address for correspondence: significantly higher among subjects with schizophrenia compared to those without schizophrenia–diabetes (15.3% vs. 7.3%, P=0.003), IFG (31.3% vs. 8.6%, P<0.001), abdominal obesity (59.2% vs. 44.7%, P<0.001), and MS (34.4% vs. 24%, P=0.014). Conclusion: In subjects with schizophrenia, the prevalence of diabetes, IFG, abdominal obesity, and MS is significantly higher than in those without schizophrenia.
Review completed : 15‑05‑11Accepted KEY WORDS: Impaired fasting glucose, metabolic syndrome, obesity, schizophrenia, south India, type 2 diabetes susceptibility to diabetes[2] and premature cardiovascular disease.[3] T he prevalence of type 2 diabetes is rising globally and
according to the International Diabetes Federation Earlier studies have shown that schizophrenia subjects have (IDF), in 2010, India had 50.8 million people with diabetes higher rates of impaired glucose tolerance and diabetes than the and this number is set to increase to 87 million by the general population.[4,5] Some global studies have reported on the year 2030 (Diabetes Atlas, 2009).[1] Earlier studies have prevalence of MS in subjects with schizophrenia.[6,7] However, reported that Asian Indians have certain unique clinical and there is only one study on the prevalence of MS among subjects biochemical characteristics that are collectively referred to with schizophrenia in the Indian population and a figure of 37.8% as the "Asian Indian Phenotype" which confers an increased was quoted in that study.[8] The prevalence of MS in schizophrenia subjects is reported to be two to four times higher than in the Access this article online
general population.[9] Estimates of the prevalence of MS and Quick Response Code:
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diabetes among schizophrenia subjects could provide vital data for planning appropriate care services. Moreover, a recent study reports that subjects with schizophrenia have limited access to general health care and less opportunity for cardiovascular risk screening. [10] Hence, the present study was undertaken with the PubMed ID:
objective of estimating the prevalence of diabetes, impaired fasting glucose, obesity, and MS among subjects with schizophrenia.
Journal of Postgraduate Medicine October 2011 Vol 57 Issue 4 Subashini, et al.: Prevalence of diabetes and metabolic syndrome among subjects with schizophrenia Materials and Methods in a relaxed position with both feet together on a flat surface. Waist circumference was measured as the smallest horizontal In this case control study, the cases are subjects with schizophrenia girth between the costal margins and the iliac crests. Two (aged ≥20 years) diagnosed as having schizophrenia as per ICD measurements were made and the mean of the two was taken 10 diagnosis and recruited from a schizophrenia care center in as the waist circumference.
Chennai. This is a non-governmental organization involved in the care and rehabilitation of persons with serious mental Hip circumference was taken as the greatest circumference at illnesses. All subjects were requested to be on at least 8 h the level of greater trochanters (the widest portion of the hip) overnight fast by the clinic nurse.
on both sides. Two measurements were made and the mean of the two was taken as the hip circumference.
To match for the cases, age- and sex-matched healthy controls (adults aged ≥20 years) (without psychiatric illness) were Blood pressure was recorded in the sitting position in recruited from the Chennai Urban Rural Epidemiology Study the right arm to the nearest 2 mmHg using the mercury (CURES), one of the largest epidemiological studies on sphygmomanometer (Diamond Deluxe BP apparatus, Pune, diabetes carried out in India. From a total of 155 Corporation India). Two readings were taken 5 min apart and the mean of wards in Chennai, 46 wards were randomly selected for the two was taken as blood pressure.
CURES. The detailed study design is described in previous American Diabetes Association guidelines[14] were used to Briefly, in Phase 1 of the urban component of CURES, 26,001 establish the diagnosis of diabetes (Fasting glucose levels individuals were recruited based on a systematic sampling ≥126 mg/dl).
technique. Phase 2 of CURES deals with studies of the prevalence of microvascular and macrovascular complications Impaired fasting glucose of diabetes among those identified with diabetes in Phase 1. Impaired fasting glucose (IFG) was diagnosed if fasting plasma In Phase 3 of CURES, every tenth subject recruited in glucose ≥100 mg/dl to 125 mg/dl based on ADA guidelines.[14] Phase 1 (n=2,600) was invited to the centre for detailed anthropometric measurements and biochemical tests. Of Metabolic syndrome these, 2350 participated in the study (response rate: 90.4%). MS was diagnosed using the IDF criteria:[15] Abdominal The control subjects, defined as those who had no history of obesity plus two or more of the following risk factors: Waist psychiatric illness, were randomly selected from Phase 3 of circumference ≥90 cm in men and ≥80 cm in women; CURES and were age and sex matched in the ratio, 1:4 (cases: Controls). The study was conducted between December 2004 fasting plasma glucose (FPG) ≥100 mg/dl; blood pressure and January 2005.
≥130/85 mm/Hg; serum triglycerides ≥150 mg/dl, serum HDL cholesterol <40 mg/dl in men and, <50 mg/dl in women.
A structured questionnaire was administered to the subjects to collect information on medical history and anthropometric Typical and atypical antipsychotic drugs measurements, which included height, weight, waist, and Typical antipsychotics (sometimes referred to as conventional hip circumferences were taken using standard techniques as antipsychotics or conventional neuroleptics) are a class of described in the definition section.[11] Blood samples were antipsychotic drugs first developed in the 1950s and used to collected between 7 and 8 am, after ensuring at least 8 h treat psychosis (in particular, schizophrenia), and are generally of overnight fasting, for estimating fasting plasma glucose being replaced by atypical antipsychotic drugs. First generation and lipids. The samples were immediately transferred to the antipsychotic (FGA) acts by blocking D2 receptors. This action central laboratory where they were analyzed. Plasma glucose in the mesolimbic receptors is responsible for the antipsychotic and serum lipids were estimated using a Hitachi 912 Auto efficacy of this group of drugs. However, these drugs also analyser (Mannheim, Germany) utilizing kits supplied by Roche block Dopamine receptors in mesocortical regions (causing Diagnostics GmbH (Mannheim, Germany).
worsening of negative and cognitive symptoms); nigrostriatal pathway (causing extrapyramidal side effects), and the Measurements and definitions
tuberoinfundiblar regions (causing prolactinemia). Examples Height was measured with a tape to the nearest 0.1 cm. Subjects of typical antipsychotics are haloperidol, trifluperazine, and were requested to stand upright without shoes with their back against the wall, heels together, and eyes directed forward. Weight was measured with a spring balance that was kept on Atypical antipsychotics (also known as second generation a firm horizontal surface. Subjects wore light clothing, stood antipsychotics) are a class of prescription medications upright without shoes and weight was recorded to the nearest used to treat psychiatric conditions. The atypicality of the 0.5 kg. Body mass index (BMI) was calculated as body weight second-generation antipsychotics (SGA) is attributed to the in kilogram divided by the height in meter (kg/m²).
coupling of D2 antagonism with Serotonin 2A antagonism. All atypical antipsychotics are FDA approved for use in the Waist circumference was measured using a non-stretchable treatment of schizophrenia. Examples of atypical antipsychotics fiber measuring tape. The subjects were asked to stand erect are clozapine, rispridone, and olanzapine.
Journal of Postgraduate Medicine October 2011 Vol 57 Issue 4 Subashini, et al.: Prevalence of diabetes and metabolic syndrome among subjects with schizophrenia respectively among subjects with and without schizophrenia Statistical analysis was performed using SAS 9.2. One-way (P<0.001). The overall prevalence of diabetes was 15.3% ANOVA or student's "t" test was used to compare groups for among subjects with schizophrenia and 7.3% in those without continuous variables and Chi-square test was used to compare proportion between two groups. Values are expressed as mean±SD. P values of <0.05 were considered as the level of All schizophrenia subjects were receiving antipsychotic medications. This included 11.5% (n=15) who were on typical antipsychotics, 60% (n=78) on atypical antipsychotics and 28.5% (n=37) on both typical and Institutional ethical committee approval was obtained and atypical antipsychotics [Table 3]. The subjects on atypical written informed consent was also obtained from all study antipsychotics showed a higher frequency of diabetes, subjects prior to the study. Confidentiality of both subjects and impaired fasting glucose, abdominal obesity, and metabolic physician-related information was ensured.
syndrome, compared to those who were receiving only typical antipsychotics or a combination of typical and atypical antipsychotics. The differences however did not reach One hundred and thirty-four schizophrenia subjects were recruited. Of these, three physically ill patients were excluded Figure 1 shows that the prevalence of abdominal obesity was from the study as they were unable to participate. Thus, higher among subjects with schizophrenia compared to those 131 subjects with schizophrenia (male n=68, female n=63) without (59.2% (n=74) vs. 44.7% (n=234), P<0.001).
were finally included in this study. The controls comprised of 524 subjects (male n=272, female n=252) recruited from the The prevalence of metabolic syndrome in subjects with and CURES study.
without schizophrenia is shown in Figure 2. Among subjects with schizophrenia, the prevalence of MS was 34.4% (n=43), Table 1 reports on the clinical characteristics of the two groups. while among those without schizophrenia, it was 24.0% (n=126) The mean age of the study population was 44±12 years (range 20– 80 years) and 51.9% were males. The BMI was significantly higher in subjects with schizophrenia as compared to those without schizophrenia (23.6±4.8 kg/m² vs. 23.0±3.7 kg/m², P=0.042]. Subjects with schizophrenia also had higher waist Very few studies have been conducted so far on Indian subjects circumference (males: 87.0±12.3 cm vs. 83.1±10.8 cm, with schizophrenia in relation to the prevalence of diabetes and P=0.015 and females: 88.8±11.7 cm vs. 82.8±11.0 cm, MS. This study makes the following points: (i) the prevalence P<0.001), higher hip circumference (in females) (95.7±13.4 cm of diabetes and IFG, as well as abdominal obesity and MS are vs. 92.3±8.7 cm, P=0.018) and higher fasting plasma glucose significantly higher in subjects with schizophrenia compared (105±32 mg/dl vs. 92±31 mg/dl, P<0.001) compared to the to those without; (ii) subjects with schizophrenia treated with respective subjects without schizophrenia.
atypical medications had relatively higher rates of cardio-metabolic risk factors when compared to those on typical medications The prevalence of diabetes and impaired fasting glucose among although the differences did not reach statistical significance.
subjects with and without schizophrenia is presented in Table 2. The prevalence of impaired fasting glucose using ADA criteria Screening for cardio-metabolic risk factors among subjects with was 31.3% in subjects with schizophrenia and 8.6% in subjects schizophrenia poses several challenges. Earlier studies have without schizophrenia (P<0.001). Self-reported diabetes was observed that even when subjects with schizophrenia consent not significantly different between the groups. However, newly to participate in diabetes screening studies, many investigators diagnosed diabetes (fasting ≥126 mg/dl) was 9.9% and 3.8% struggle to successfully complete the oral glucose tolerance Table 1: Clinical characteristics of subjects with and without schizophrenia
Variables

Subjects with
Control subjects (without
Mean difference
(95% confidence interval)
Male n (%) Body mass index (kg/m²) 0.6 (0.16–1.40) Waist circumference (cm) 3.9 (0.94–6.90) 6.0 (2.91–9.08) Hip circumference (cm) −1.9 (−4.23–0.43) 3.4 (0.68–6.12) Fasting plasma glucose (mg/dl) 13 (7.01–18.90) Values are presented as mean±standard deviation; aStudent's t-test; *P<0.05 Journal of Postgraduate Medicine October 2011 Vol 57 Issue 4 Subashini, et al.: Prevalence of diabetes and metabolic syndrome among subjects with schizophrenia With schizophrenia Without schizophrenia With schizophrenia Without schizophrenia Figure 1: Prevalence of abdominal obesity among subjects with and
Figure 2: Prevalence of metabolic syndrome among subjects with and
without schizophrenia without schizophrenia Table 2: Prevalence of diabetes and impaired fasting glucose in subjects with and without schizophrenia
Prevalence

Subjects with
Control subjects (without
Difference in proportion
schizophrenia n (%)
schizophrenia n (%)
(95% confidence interval)
Impaired fasting glucose [FBS ≥100 mg/dl to 125 mg/dl – ADA criteria]Self-reported diabetes n (%) Newly diagnosed diabetes n (%) [FBS ≥126 mg/dl] Overall diabetes n (%) [Self‑reported + newly diagnosed diabetes]FBS: Fasting blood sugar; ADA: American Diabetes Association; aChi- square; *P<0.05 Table 3: Antipsychotic medication utilization and its
The prevalence of diabetes (15.3%) and impaired fasting glucose relation to risk factors among subjects with schizophrenia
(31.3%) was higher among subjects with schizophrenia Risk factors
Atypical
Typical and P valuea
compared to the control subjects (CURES) which suggests antipsychotic antipsychotic
atypical
that the prevalence of dysglycemia is much higher among medication
medication antipsychotic
medication
A study from Singapore[4] reported a diabetes prevalence of 30.9% Diabetes (n=19) while impaired glucose tolerance was reported in 16% among Impaired fasting subjects with schizophrenia. The Patient Outcomes Research glucose (n=41) Team (PORT) study[5] reported the diabetes prevalence of 14.9% among schizophrenia subjects. The prevalence of impaired obesity (n=73) fasting glucose (IFG) was reported to be 15% among Caucasian syndrome (n=42) drug–naïve subjects with schizophrenia.[20] Another study among middle-aged European subjects with schizophrenia, reported a prevalence rate of IFG of 8.5%.[21] In the present study, the testing[16] or even to obtain fasting blood glucose levels. This can prevalence of impaired fasting glucose (31.3%) among subjects lead to high study drop-out rates, or use of less reliable indicators with schizophrenia was much higher compared to the European of diabetes such as non-fasting blood glucose levels.[17] There studies. This may be a reflection of higher diabetes rates in India is one study in a drug-naïve population that has used OGTT in general, which is attributed to the "Asian Indian Phenotype," in 50 patients.[18] In the present study, we could not perform associated with increased waist circumference and body fat OGTT due to unwillingness of the subjects with schizophrenia; (particularly visceral fat) leading to greater insulin resistance.[22] hence, prevalence rates were estimated using the ADA fasting plasma glucose criteria.[14] Abdominal obesity, another component of the Asian Indian Phenotype and a component of MS, is a well-established risk According to the Chennai Urban Rural Epidemiology Study factor for a high prevalence of diabetes. The present study found (CURES), the prevalence of diabetes (in the age group of the that the prevalence of abdominal obesity was higher in subjects control group studied) in the general population of Chennai with schizophrenia compared to those without. Earlier studies was 7.3%, while that of impaired fasting glucose was 8.6%.[19] have shown that women with schizophrenia were more frequently Journal of Postgraduate Medicine October 2011 Vol 57 Issue 4 Subashini, et al.: Prevalence of diabetes and metabolic syndrome among subjects with schizophrenia obese than men.[23] In the present study also, the prevalence out and secondly, the duration of the psychiatric drugs, which of the abdominal obesity was higher among female subjects is one of the major causes of increasing obesity in subjects with (80%) with schizophrenia compared to males (40%). A Chinese schizophrenia, has not been taken into account in this study. study on schizophrenia[24] however, found no significant gender Finally, the cross-sectional nature of the study does not allow difference in the prevalence of obesity (39.6% in females and for cause-effect relationships to be established. However, one of 40% in males).
the strengths of this study is that the controls were taken from an epidemiological study.
The term MS refers to a cluster of metabolic risk factors including central obesity, glucose intolerance, hyperinsulinemia, In conclusion, we report that prevalence of diabetes, impaired low HDL cholesterol, high triglycerides, and hypertension.[25] fasting glucose, obesity, and metabolic syndrome are higher Several studies have reported on the prevalence of MS in the in subjects with schizophrenia compared to those without general population. In CURES, we reported that the prevalence schizophrenia. This underscores the need to screen schizophrenia of MS using IDF criteria, was 25.8%.[26] An earlier Indian study[8] subjects for diabetes and MS. Early detection of these disorders revealed that subjects with schizophrenia had a 37.7% prevalence would enable us to take therapeutic measures, and thus delay the of MS using IDF criteria.[8] A study in Finland showed a fourfold complications of diabetes. The first step in prevention of diabetes risk of MS among young subjects with schizophrenia compared is to identify and screen these high risk groups. This can be done to the general population.[7] The Clinical Antipsychotic Trails using a simple screening tool like the Indian Diabetes Risk Score of Intervention Effectiveness (CATIE) study in USA, reported (IDRS)[40] which could be used in subjects with schizophrenia to 42.7% prevalence of MS using ATP III criteria.[27] Another study identify those who are likely to have diabetes or MS.[41] in a US population also reported a 38.6% prevalence of MS[28] while a study from Brazil showed a prevalence of MS of 29% using the same criteria.[29] The present study also confirms a higher prevalence of MS among subjects with schizophrenia We are grateful to the Chennai Willington Corporate Foundation, (34.4%), using IDF criteria. However, differences in the criteria Chennai for the financial support provided for the Chennai Urban used to define MS could contribute to the differences in Rural Epidemiology Study (CURES). We thank the epidemiology team prevalence rates of MS within studies.
members for conducting the CURES field studies. We thank Dr. M. Sarada Menon, Founder Advisor, Schizophrenia Research Foundation A number of recent studies have confirmed that the use of (SCARF), Chennai for her initiative to undertake this study. We thank any anti-psychotic drugs was associated with an increase in the subjects with schizophrenia for their kind cooperation to participate newly diagnosed diabetes.[30,31] Antipsychotic medication in in the study. This is the 104th publication of CURES (CURES - 104).
schizophrenia is known to induce weight gain and this is thought to be responsible for the excess weight among individuals with schizophrenia.[32] While weight gain may be a mechanism for the development of diabetes, a direct effect of these drugs on insulin International Diabetes Federation Diabetes Atlas. Unwin N, Whiting D, action in muscle may also be an important contributor to diabetes.
Gan D, Jacqmain O, Ghyoot G, editors. IDF Diabetes Atlas. 4th ed. Belgium: International Diabetes Federation; 2009. p. 11-3.
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How to cite this article: Subashini R, Deepa M, Padmavati R, Thara R, Mohan V.
26. Deepa M, Farooq S, Datta M, Deepa R, Mohan V. Prevalence of Prevalence of diabetes, obesity, and metabolic syndrome in subjects with metabolic syndrome using WHO, ATPIII and IDF definitions in Asian and without schizophrenia (CURES-104). J Postgrad Med 2011;57:272-7.
Indians; the Chennai urban rural epidemiology study (CURES-34). Diabetes Metab Res Rev 2007;23:12-34.
Source of Support: Nil, Conflict of Interest: None declared.
Journal of Postgraduate Medicine October 2011 Vol 57 Issue 4

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