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DSX-467; No. of Pages 9 Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2015) xxx–xxx

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Diabetes & Metabolic Syndrome: Clinical Research & Reviews journal homepage: www.elsevier.com/locate/dsx

Original Article

Levels of triglycerides, cholesterol, LDL, HDL and glucose in patients with schizophrenia, unipolar depression and bipolar disorder Adam Wysokin´ski a,*, Dominik Strzelecki b, Iwona Kłoszewska a a b

Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Lodz, Poland Department of Affective and Psychotic Disorders, Medical University of Lodz, Lodz, Poland

A R T I C L E I N F O

A B S T R A C T

Keywords: Lipid profile Glucose Schizophrenia Depression Bipolar disorder

Aims: The aim of this study is to investigate differences in triglycerides (TGA), cholesterol (TC), HDL, LDL and glucose (FPG) levels in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Results: Results for 2305 Caucasian patients were included in the study (1377 women, 59.7%; mean age 45.6). Mean TGA level was: schizophrenia: 139.9  90.6 mg/dL, unipolar depression: 125.4  70.8 mg/dL, bipolar disorder: 141.1  81.9 mg/dL, bipolar depression: 147.7  82.8 mg/dL mg/dL, bipolar mania: 120.2  76.1 mg/dL, inter-group differences were significant (p < 0.001). Mean TC level was: schizophrenia: 188.5  40.4 mg/dL, unipolar depression: 198.8  50.7 mg/dL, bipolar disorder: 194.4  48.3 mg/dL, bipolar depression: 198.9  48.8 mg/dL, bipolar mania: 180.1  43.8 mg/dL, inter-group differences were significant (p < 0.001). Mean HDL level was: schizophrenia: 45.3  13.9 mg/dL, unipolar depression: 48.1  14.8 mg/dL, bipolar disorder: 45.4  15.3 mg/dL, bipolar depression: 45.1  15.4 mg/dL, bipolar mania: 46.4  15.1 mg/dL, inter-group differences were significant (p < 0.001). Mean LDL level was: schizophrenia: 115.4  34.7 mg/dL, unipolar depression: 125.7  44.1 mg/dL, bipolar disorder: 120.9  42.1 mg/dL, bipolar depression: 124.5  43.1 mg/dL, bipolar mania: 109.3  36.9 mg/dL, inter-group differences were significant (p < 0.001). Mean FPG level was: schizophrenia: 95.9  24.9 mg/dL, unipolar depression: 94.8  22.9 mg/dL, bipolar disorder: 97.2  24.4 mg/dL, bipolar depression: 98.3  25.3 mg/dL, bipolar mania: 93.9  21.1 mg/dL, inter-group differences were not significant (p = 0.08). Odds ratios for glucose and lipids abnormalities, correlations with age, sex distribution in diagnostic groups for normal ranges of glucose and lipids, differences in glucose and lipids levels between the age groups were also calculated. Conclusions: Our results confirm that there is a high prevalence of lipid and glucose abnormalities in patients with schizophrenia and mood disorders (both unipolar and bipolar). However, we have demonstrated that these diagnostic groups differ in terms of types and frequency of these metabolic dysfunctions. Women and patients aged 40+ are at particularly high risk. ß 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

1. Introduction Schizophrenia, bipolar disorder and unipolar depression are among the most severe psychiatric disorders. They are associated with high prevalence, chronic course, significant mental and somatic comorbidities and very high personal and societal costs (lost productivity and increased medical expenses). Also, many

* Corresponding author at: Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Czechosłowacka 8/10, 92-216 Ło´dz´, Poland. Tel.: +48 42 675 73 72; fax: +48 42 675 77 29. E-mail address: [email protected] (A. Wysokin´ski).

patients respond poorly to medications and have frequent and disrupting relapses. Finally, patients with these disorders have increased mortality resulting from, among others, increased risk of cardiovascular events (e.g. myocardial infarction, sudden cardiac death and stroke) [1]. These events are closely related to metabolic abnormalities (raised lipids and glucose blood levels, central (abdominal) obesity, diabetes, hypertension). Metabolic syndrome (MetS) is a cluster of disorders comprising of abdominal obesity, hypercholesterolemia, hypertriglyceridemia, hypertension and raised blood glucose levels. The presence of MetS increases the risk of death due to cardiovascular diseases. Comparing to general population, the prevalence of MetS is increased in patients taking psychotropic agents [2]. This applies not only to antipsychotics, but also to mood stabilizers [3] and antidepressants [4].

http://dx.doi.org/10.1016/j.dsx.2015.04.004 1871-4021/ß 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Wysokin´ski A, et al. Levels of triglycerides, cholesterol, LDL, HDL and glucose in patients with schizophrenia, unipolar depression and bipolar disorder. Diab Met Syndr: Clin Res Rev (2015), http://dx.doi.org/10.1016/ j.dsx.2015.04.004

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DSX-467; No. of Pages 9 A. Wysokin´ski et al. / Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2015) xxx–xxx

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Studies of general population demonstrated that the overall prevalence of MetS in European countries varies from 5.9% in men and 2.1% in women (France) [5] to 11.0% in men and 23.1% in women (Russia) [6]. Meta-analysis of 126 analyses in 77 publications (n = 25,692) revealed that the overall rate of MetS in schizophrenia and related disorders is 32.5% [7]. European study by De Hert et al. showed that prevalence of the MetS in patients with schizophrenia treated with antipsychotics is up to 36% [2]. Yumru et al. found that the prevalence of MetS in bipolar patients was 32% [8]. Central obesity is the core symptom of metabolic syndrome, leading to its other pathological components (hypertension, dyslipidemia, insulin resistance and diabetes). While dyslipidemia and increased fasting plasma glucose seem to be common in patients with schizophrenia and mood disorders, reports show that many patients do not get proper treatment for these abnormalities [9]. All these indicate that proper monitoring of blood levels of glucose and lipids in patients with schizophrenia and mood disorders if of the utmost importance. The majority of psychiatric studies on metabolic syndrome are focused on schizophrenia and antipsychotics, less is known for unipolar depression and bipolar disorder. Therefore, we have carried out this study in order to investigate differences in lipid and glucose levels in patients with schizophrenia, unipolar depression, bipolar depression and bipolar mania. 2. Methods This was a retrospective, cross-sectional, naturalistic study. Our psychiatry clinical hospital database was screened for fasting levels of triglycerides (TGA), total cholesterol (TC), HDL cholesterol (HDL), LDL cholesterol (LDL) and glucose (FPG) levels. Only the first entry for each patient from inpatient care units was used for analysis. Usually the first blood tests are done next day after admission to our units. Thus, we have assumed that most patients that we included in the study were in acute phase of their disorder. We focused on patients with schizophrenia (all subtypes), bipolar disorder and unipolar depression. Results for 2305 Caucasian patients of all ages were included in the study. Patients were grouped under diagnostic criteria as schizophrenia (F20 according to ICD-10, 295 according to DSM-IV), unipolar depression (F31 and F32 according to ICD-10, 296.2 and 296.3 according to DSM-IV), bipolar disorder (F30 and F31 according to ICD-10, 296.[0,4,6] according to DSM-IV), which included: bipolar depression (F31.3–F31.5 according to ICD-10, 296.6 according to DSM-IV) and bipolar mania (F30 and F31.0–F31.2 according to ICD-10, 296.0 and 296.4 according to DSM-IV). In our unit diagnosis is based on the ICD-10 criteria, DSM-IV codes were given as reference. Blood samples were drawn for all patients between 8 and 9 a.m. after 12 h overnight fast. Immediately after collecting blood samples TGA, TC, LDL, HDL and FPG levels were determined using automatic analyzer Dirui CS-400 (Dirui, China). raised fasting plasma glucose was defined as FPG level 100 mg/dL mg/dL based on IDF criteria [10]. Impaired fasting glucose (IFG) was defined as FPG level 110–125 mg/dL based on American Diabetes Association guidelines, new onset of type 2 diabetes (DM2) was defined as FPG level 125 mg/dL. TGA 150 mg/dL and/or TC 200 mg/dL and/or HDL level 60 years. Table 3 shows age distribution of TGA, TC, HDL, LDL and FPG levels in diagnostic groups. There were significant differences between diagnostic groups with regard to raised TGA category (X2 = 26.52, df = 3, p < 0.001). When patients with bipolar depression and bipolar mania were combined into one group (bipolar disorder) the difference was also significant (X2 = 15.42, df = 2, p < 0.001). Patients with raised TGA levels were significantly older (46.9  16.4 vs. 44.9  20.6, t = 2.07, p = 0.019). There were significant differences between diagnostic groups with regard to raised TC category (X2 = 23.24, df = 3, p < 0.001). When patients with bipolar depression and bipolar mania were combined into one group (bipolar disorder) the difference was also significant (X2 = 15.52, df = 2, p < 0.001). Patients with raised TC levels were significantly older (49.8  17.1 vs. 42.7  20.4, t = 8.27, p < 0.001). There were no significant differences between diagnostic groups with regard to low HDL category (p = 0.39). There were significant differences between diagnostic groups with regard to raised LDL category (X2 = 17.90, df = 3, p < 0.001). When patients with bipolar depression and bipolar mania were combined into one group (bipolar disorder) the difference was also significant (X2 = 14.41, df = 2, p = 0.001). Patients with raised LDL levels were significantly older (50.4  17.2 vs. 43.4  19.9, t = 7.68, p < 0.001). There were no significant differences between diagnostic groups with regard to high AILDL/HDL (p = 0.09), high AITC/HDL (p = 0.33), hyperlipidemia (p = 0.18), raised FPG (p = 0.40), IFG (p = 0.55) and diabetes (p = 0.05) categories.

Please cite this article in press as: Wysokin´ski A, et al. Levels of triglycerides, cholesterol, LDL, HDL and glucose in patients with schizophrenia, unipolar depression and bipolar disorder. Diab Met Syndr: Clin Res Rev (2015), http://dx.doi.org/10.1016/ j.dsx.2015.04.004

High TGA

High TC

Low HDL

High LDL

High AILDL/HDL

High AITC/HDL

Hyperlipidemia

Raised FPG

IFG

DM2

1.00 356 (32.8)

1.00 394 (36.3)

1.00 574 (52.8)

1.00 292 (26.8)

1.00 378 (34.8)

1.00 418 (38.5)

1.00 886 (81.6)

1.00 359 (29.7)

1.00 95 (7.9)

1.00 60 (5.0)

216 (37.9) 186 (32.6) 294 (51.6) 152 (26.6) 217 (38.1) 234 (41.0) 465 (81.6) 198 (30.7) 62 (9.6) 18 (2.8) 140 (27.1) 208 (40.3) 280 (54.3) 140 (27.1) 161 (31.2) 184 (35.7) 421 (81.6) 161 (28.6) 33 (5.9) 42 (7.5) 0.70 [0.57–0.86] 1.47 [1.21–1.78] 0.98 [0.81–1.18] 1.47 [1.20–1.81] 0.88 [0.72–1.08] 0.95 [0.78–1.16] 1.05 [0.82–1.34] 0.93 [0.76–1.14] 0.97 [0.69–1.36] 1.46 [1.00–2.14] 182 (25.5)

325 (45.6)

373 (52.3)

250 (35.1)

228 (31.9)

266 (37.3)

587 (82.3)

215 (28.3)

58 (7.6)

54 (7.1)

55 (32.5) 62 (36.7) 78 (46.1) 50 (29.8) 65 (38.5) 72 (42.6) 137 (81.1) 61 (33.5) 14 (7.7) 21 (11.5) 127 (23.3) 263 (48.3) 295 (54.2) 200 (36.8) 163 (30.0) 194 (35.7) 450 (82.7) 154 (26.6) 44 (7.6) 33 (5.7) 1.15 [0.89–1.50] 1.17 [0.90–1.51] 1.15 [0.90–1.48] 1.30 [0.99–1.70] 1.20 [0.93–1.56] 1.22 [0.95–1.57] 1.31 [0.92–1.85] 1.09 [0.84–1.42] 1.31 [0.87–1.98] 1.53 [0.94–2.47] 115 (36.0) 40 (41.2) 75 (33.8) 1.41 [1.07–1.89] 99 (40.9) 32 (47.8) 67 (38.3) 0.54 [0.31–0.95] 16 (20.8) 8 (26.7) 8 (17.0)

127 (39.9)

180 (56.4)

29 (30.2) 53 (54.6) 98 (44.1) 127 (57.2) 1.39 [1.05–1.85] 1.24 [0.94–1.65]

102 (32.3)

125 (39.2)

138 (43.3)

272 (85.3)

34 (10.1)

25 (7.4)

25 (26.0) 77 (35.0) 1.47 [1.09–1.97]

49 (50.5) 76 (34.2) 1.30 [0.97–1.72]

84 (35.0)

99 (40.9)

26 (38.8) 40 (59.7) 81 (46.3) 101 (57.7) 0.63 [0.37–1.06] 0.91 [0.57–1.45] 20 (26.3) 39 (50.6)

23 (34.3) 61 (35.3) 0.84 [0.49–1.46] 18 (23.7)

37 (55.2) 62 (35.4) 0.95 [0.59–1.56] 26 (33.8)

35 (52.2) 59 (88.1) 70 (40.0) 152 (86.9) 1.20 [0.75–1.91] 0.86 [0.48–1.52] 33 (42.9) 61 (79.2)

21 (30.0) 7 (10.0) 4 (5.7) 64 (34.8) 19 (10.3) 18 (9.8) 0.84 [0.51–1.38] 1.23 [0.58–2.63] 0.71 [0.22–2.31] 22 (26.2) 8 (9.5) 3 (3.6)

3 (10.3) 17 (36.2)

2 (6.9) 16 (34.0)

12 (40.0) 14 (29.8)

13 (43.3) 20 (42.5)

7 (21.9) 15 (28.8)

107 (44.2)

141 (58.3)

13 (43.3) 26 (55.3)

48 (49.5) 83 (85.6) 90 (40.5) 189 (85.1) 1.22 [0.92–1.62] 1.53 [1.02–2.31]

107 (31.7)

105 (43.4)

211 (87.2)

24 (80.0) 37 (78.7)

28 (27.4) 9 (8.8) 5 (4.9) 79 (33.5) 25 (10.6) 20 (8.5) 1.19 [0.89–1.58] 1.33 [0.84–2.11] 1.81 [1.09–3.01] 85 (33.5)

26 (10.2)

2 (6.2) 6 (11.5)

22 (8.7)

1 (3.1) 2 (3.8)

OR = odds ratios [95% CI] for raised TGA, raised TC, low HDL, raised LDL, high AILDL/HDL, high AITC/HDL, hyperlipidemia, IFG and diabetes with the schizophrenia group as reference. TGA, triglycerides; TC, total cholesterol; HDL, high density lipoproteins; LDL, low density lipoproteins; AI, atherogenic index; FPG, fasting plasma glucose; IFG, impaired fasting glucose; DM2, type 2 diabetes.

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Schizophrenia OR Schizophrenia n (%) Men n (%) Women n (%) Unipolar depression OR Unipolar depression n (%) Men n (%) Women n (%) Bipolar disorder OR Bipolar disorder n (%) Men n (%) Women n (%) Bipolar depression OR Bipolar depression n (%) Men n (%) Women n (%) Bipolar mania OR Bipolar mania n (%) Men n (%) Women n (%)

A. Wysokin´ski et al. / Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2015) xxx–xxx

Please cite this article in press as: Wysokin´ski A, et al. Levels of triglycerides, cholesterol, LDL, HDL and glucose in patients with schizophrenia, unipolar depression and bipolar disorder. Diab Met Syndr: Clin Res Rev (2015), http://dx.doi.org/10.1016/ j.dsx.2015.04.004

Table 2 Odds ratios and sex distribution in diagnostic groups for normal ranges of glucose and lipids.

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DSX-467; No. of Pages 9 A. Wysokin´ski et al. / Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2015) xxx–xxx

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Table 3 Mean levels of lipids and glucose in diagnostic groups. Total

py

Age category 60

139.8  90.6 152.6  101.5 125.7  74.4 z = 4.80, p = 60, while for bipolar disorder, bipolar depression and bipolar mania highest levels were observed in patients aged 40–60; lowest levels were found in patients aged

Levels of triglycerides, cholesterol, LDL, HDL and glucose in patients with schizophrenia, unipolar depression and bipolar disorder.

The aim of this study is to investigate differences in triglycerides (TGA), cholesterol (TC), HDL, LDL and glucose (FPG) levels in patients with acute...
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