Glucose and lipid metabolism of long-term risperidone monotherapy in patients with schizophrenia

Risperidone has a relatively low risk of causing obesity and diabetes mellitus and is a first-line treatment for schizophrenia. The aim of the present study was to investigate glucose and lipid metabolism, and feeding-control parameters in schizophrenia patients treated with long-term risperidone monotherapy. Fifteen patients with paranoid-type schizophrenia who had been treated with risperidone and had Global Assessment of Function (GAF) scores >70 were selected and compared with healthy volunteers (n = 25). Single assessments of psychotic symptoms, side-effects, Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) score, bodyweight, body fat percentage and blood sampling were performed. Fasting blood glucose, insulin, hemoglobin A1c, homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol, triglyceride, high density lipoprotein (HDL)-, low density lipoprotein-cholesterol, adiponectin, prolactin and feeding-control parameters (ghrelin and leptin) were analyzed. The body fat percentage (P = 0.0018), body mass index (BMI) (P = 0.0150), fasting blood glucose (P = 0.0358), triglyceride (P = 0.0377), leptin (P = 0.0243), total ghrelin (P = 0.0067), active ghrelin (P = 0.0241) and prolactin (P < 0.0001) levels of patients treated with risperidone were significantly higher than those of healthy volunteers, while the HDL-cholesterol level (P = 0.0222) was significantly lower. Although the patients had very mild psychiatric symptoms and maintained functionally high levels, the glucose and lipid parameters were significantly impaired compared to healthy volunteers. A high level of plasma ghrelin might increase appetite, leading to exacerbation of metabolic impairment.     

Increased cardiovascular risk markers in obesity are associated with body adiposity: role of leptin

Epidemiological studies have shown that obesity is associated with increased blood concentrations of proinflammatory factors and markers of endothelial dysfunction such as fibrinogen, C-reactive protein (CRP), and von Willebrand factor (vWF). We analyzed the association of these markers with percentage of body fat (BF), and the influence of leptin in a cross-sectional study of 1,089 subjects (366 men) aged 44 (34-53) [median (interquartile range)] years, who were classified as obese or nonobese according to BF estimated by whole-body air displacement plethysmography. Obesity was defined as BF >or= 25% in men and >or= 35% in women. Compared with non-obese subjects (mean +/- SD), obese patients had higher concentrations of fibrinogen (312 +/- 78 vs. 342 +/- 81 mg/dl, P < 0.001), CRP (0.41 +/- 0.75 vs. 0.75 +/- 1.04 mg/l, P = 0.014), vWF (107 +/- 29 vs. 123 +/- 55%, P < 0.001), and leptin (10.4 +/- 6.5 vs. 37.5 +/- 26.1 ng/ml, P < 0.0001). A positive correlation was observed between BF and fibrinogen (r = 0.266; P < 0.0001), logCRP (r = 0.409; P < 0.0001), and vWF (r = 206; P < 0.0001). Leptin was correlated with fibrinogen (r = 0.219, P < 0.0001), logCRP (r = 0., P < 0.0001), and vWF (r = 0.124, P = 0.002), but the statistical significance was lost after including BF in adjusted-correlation and multivariate analysis, suggesting that they are not regulated by leptin per se. In conclusion, the obesity-associated increase in the circulating concentrations of fibrinogen, CRP, and vWF is highly associated to BF and apparently not determined by leptin.     

Inverse relationship between plasminogen activator inhibitor-I activity and adiponectin in overweight and obese women. Interrelationship with visceral adipose tissue, insulin resistance, HDL-chol and inflammation

Adipose tissue is an active endocrine organ secreting different adipokines such as plasminogen activator inhibitor-1 (PAI-1) and adiponectin, among many others. In this study, we investigated the association between PAI-1 activity and serum adiponectin levels in a group of 444 overweight and obese women and assessed the interrelationship with visceral adipose tissue (VAT; CT-scan L4-L5), insulin resistance (HOMA-IR), HDL cholesterol (HDL-chol) and inflammation (hs-CRP). PAI-1 was inversely related to adiponectin (r = -0.25, p < 0.001; adjusted for age and BMI). After adjustment for age, VAT, HOMA-IR and hs-CRP, the relationship remained significant (r = -0.15; p = 0.001), but disappeared after additional adjustment for HDL-chol (r = -0.09; p = 0.067). Subjects were divided in two groups according to the median levels of adiponectin or PAI-1 levels. PAI-1 activity (19.1 +/- 11.4 vs. 15.8 +/- 8.6 AU/ml; p = 0.003) and adiponectin levels (9.8 +/- 4.6 vs. 8.4 +/- 4.0 microg/ml; p < 0.001) were significantly higher in the low adiponectin/PAI-1 groups. The difference in PAI-1 remained significant after adjustment for age and BMI (p = 0.001), became borderline significant after adjustment for age and VAT (p = 0.052), and disappeared after adjustment for age and HOMA-IR (p = 0.116) or age and HDL-chol (p = 0.443). The difference in adiponectin levels remained significant after adjustment for age, VAT, HOMA-IR and hs-CRP (p = 0.006), but disappeared after additional adjustment for HDL-chol (p = 0.089). Further analyses suggest a contribution of HOMA-IR and/or HDL-chol in the relationship between PAI-1 and adiponectin. HDL-chol was found to be the only factor independently determining both factors. In conclusion, in overweight and obese women, PAI-1 activity was inversely related to serum adiponectin, independent of visceral adipose tissue.     

药源性肥胖患者血清瘦素和脂联素水平检测

目的:探讨抗精神病药药源性肥胖患者血清瘦素和脂联素的水平及相关性.方法:选择21例药源性肥胖的住院患者(A组),20例首发精神分裂症患者(B组),20名健康体检人员作为对照组(C组),采用放射免疫法检测各组血清瘦素和脂联素水平,并分析各组血清瘦素及脂联素与体质量指数(BMI)相关性.结果:A组血清瘦素水平(13.3±8...     

血清瘦素与抗精神病药源性肥胖及糖尿病的相关性研究

目的　调查和探讨长期使用抗精神病药患者血瘦素水平及其与服用抗精神病药后体重 增加、肥胖及糖尿病之间的关系。方法　对符合入组标准的308例长期服用抗精神病药的精神分裂症 患者分为对照组、肥胖组、糖耐量减低组及糖尿病组,比较血清瘦素水平、胰岛素抵抗指数、血清甘油三 酯及总胆固醇水平。结果　(1)肥胖组、糖耐量减低组及糖尿病组患者的血清瘦素水平、胰岛素抵抗指 数、血清甘油三酯及总胆固醇水平均显著高于对照组(P<0.05)。(2)长期应用抗精神病药患者血瘦 素水平与体重指数、简易胰岛素抵抗指数、空腹血糖、血甘油三酯及胆固醇均呈极显著正相关(P<0.01 ～0.0001),而与餐后2h血糖水平及用药时间无相关性。结论　长期应用抗精神病药患者血瘦素水 平在肥胖、糖耐量降低及糖尿病患者中显著升高,且与体重指数、简易胰岛素抵抗指数、空腹血糖水平等 均呈显著正相关,提示高血清瘦素水平是长期应用抗精神病药所致的代谢紊乱综合征的重要指征之一。     

Plasma adiponectin elevation in elderly individuals with subsyndromal depression

Adiponectin, one of the adipokines, has believed to play a role in developing of depression, but the relationship between plasma adiponectin and depressive disorder is still unclear. To investigate the association between plasma adiponectin and depressive disorders, we measured plasma adiponectin concentrations in 785 randomly sampled elderly Koreans including 41 patients with major depressive disorder (MDD), 46 with minor depressive disorder (MnDD), and 61 with subsyndromal depression (SSD). Plasma adiponectin levels were different among the diagnostic groups (df=3, F=4.928, P=0.002). The plasma adiponectin level in the SSD patients was higher than in the non-depressed controls (NC) (12.48 ± 8.38 μg/ml versus 9.27 ± 6.21 μg/ml, P=0.001, Tukey's post hoc comparison). However, plasma adiponectin levels in the MnDD and MDD patients were comparable with those found in the NC (P>0.1, Tukey's post hoc comparison). The elevation of plasma adiponectin in the SSD patients remained significant in men (P=0.002, Tukey's post hoc comparison) but not in women. In the subjects without MDD and MnDD, plasma adiponectin level was positively correlated with the Hamilton Depression Rating Scale score (r=0.156, P<0.001) and the Geriatric Depression Scale (r=0.117, P=0.002). When men and women were analyzed separately, these significant correlations were confined to men. Circulating adiponectin concentration may play a role in compensation on process for depressive mood.     

Sex-specific, independent associations of insulin resistance with erythrocyte sedimentation rate in apparently healthy subjects

Insulin resistance and erythrocyte sedimentation rate (ESR, a non-specific marker of inflammation) are known risk factors for cardiovascular disease. Although obesity is associated with increased ESR, it is unclear whether insulin resistance is associated with ESR in humans. The relationship between insulin resistance and ESR was studied in a cross-sectional, health-area based study of 140 (89 men and 51 women) apparently healthy Caucasians subjects. ESR, additional inflammatory markers [soluble tumor necrosis alpha receptors 1 and 2 (sTNFR1 and sTNFR2); C-reactive protein (CRP)], and insulin sensitivity (SI, frequently sampled intravenous glucose tolerance test with minimal model analysis) were assessed in all subjects. An interaction with sex was documented in the relationship between ESR and both insulin resistance and obesity (p < 0.05), as log ESR correlated with log SI in men (r=-0.29, p=0.009), but not in women (r=-0.14, p=0.33), and correlated with body mass index (BMI) in women (r=0.49, p=<0.0001), but not in men (r=0.15, p=0.16). On multivariate analyses, these associations proved to be independent of known covariates, such as age, hematocrit, smoking and additional inflammatory markers in both men and women. In a replication study, variables independently associated with ESR were also insulin resistance (homeostasis model assessment) in men and obesity markers (either BMI or fat mass) in women. In conclusion, ESR is independently associated with either insulin resistance or obesity in a sex-specific manner. These findings contribute to explain the known relationship of this inflammatory marker with cardiovascular disease.     

Reduced plasma leptin concentrations in bulimia nervosa

Leptin is a protein produced by the ob-ob gene which inhibits food intake. Plasma levels have previously been reported to be altered in obesity and anorexia nervosa (AN) but not bulimia nervosa (BN). We measured fasting plasma leptin levels by radioimmunoassay in 53 subjects carefully studied at NIMH, including 37 women meeting DSM-III-R criteria for BN [10 with concurrent AN (body mass index (BMI)=14.1+/-1.4), 27 without AN (BMI=20.4+/-1.6)] and 16 normal control women (NCs) (BMI=21.1+/-2.0). Patients were medication-free and abstinent from bingeing and purging for three to four weeks prior to study. Plasma leptin levels were significantly correlated to BMI (r=0.41, P<0.002), weight (kg, r=0.43, P<0.001), and percent average body weight (%ABW, r=0.45, P<0.001) in the total group. Plasma leptin levels were lower in the BN subjects (3.4+/-2.5 ng/ml) compared to the NCs (6.1+/-2.6 ng/ml, P<0.001, ANCOVA) even after controlling for BMI and weight. There was no significant difference between BN subjects with AN (n=10, 2.6+/-2.6 ng/ml) and those without AN (n=27, 3.8+/-2.4 ng/ml), despite lower BMI in BN with AN. Furthermore, leptin levels were decreased in BN without AN compared with healthy controls, even though BMI was comparable in these two subgroups. Plasma leptin concentrations were negatively correlated with baseline plasma cortisol levels (n=49, r=-0.49, P<0.001) and positively correlated with prolactin responses following L-tryptophan (n=49, r=0.37, P<0.009) and m-chlorophenylpiperazine (n=52, r=0.24, P<0.09). This is the first known report of decreased plasma leptin levels in BN. The decrement in leptin concentration is not related to BMI, body weight, or the presence or absence of BN. HPA axis activation as well as serotonin dysregulation may be related to decreased leptin levels, which may in turn contribute to disinhibited eating in BN. Although current leptin levels were not correlated with self-reported previous binge frequency, the role of leptin in the pathophysiology of BN deserves further study.     

Plasma nitric oxide and leptin values in patients with olanzapine-induced weight gain

We previously investigated leptin levels in antipsychotic-induced weight gain and found that atypical antipsychotic, especially clozapine and olanzapine-induced weight gain is related to increased levels of leptin. It has been suggested that nitric oxide (NO) is a potential regulator of leptin-induced lipolysis. To explore the pathophysiology of weight gain during atypical antipsychotic treatment, we planned to investigate olanzapine's influence on leptin and NO levels and weight gain. The study comprised 21 patients with schizophrenia who were enrolled in olanzapine monotherapy, and 21 healthy controls. The fasting plasma NO and leptin levels were measured in both patients and controls at baseline. The patients were also evaluated at sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, serum leptin and NO levels. At baseline, the mean leptin level in the olanzapine group was not different compared to that in controls after BMI or age adjustment. A significant increase in leptin levels by means of olanzapine use was seen (P<0.01). Higher plasma NO levels were observed in patients with schizophrenia compared with the control group at baseline (P<0.01). At the evaluation of week 6, a significant decrease in the mean plasma NO level was found in the olanzapine group (P<0.05). The changes in total PANSS scores were correlated with change in leptin levels (r=0.58, P<0.05), and with the change in weight (r=0.54, P<0.05). In addition, there was a severe significant negative correlation between the changes in leptin levels and NO levels (r=0.73, P<0.01). The results confirmed that leptin and NO might be associated with olanzapine-induced weight gain.     

Increased levels of adipokines in bipolar disorder

Bipolar disorder (BD) is associated with considerable higher chronic medical comorbidities, overweight and obesity. Adipokines are adipocyte-derived secretory factors which have functions in immune response and seem to be associated with both BD and overweight. The aim of this study was to evaluate the plasma levels of adipokines (adiponectin, resistin and leptin) and TNF-α and its receptors (sTNFR1 and sTNFR2) in BD overweight patients in comparison with overweight controls. Thirty euthymic BD type-I patients and thirty controls matched by age, gender and body-mass index (BMI) were assessed by Mini-International Neuropsychiatric Interview, Young Mania and Hamilton Depression rating scales (YMRS and HDRS, respectively). Plasma levels of adiponectin, resistin, leptin, TNF-α and its soluble receptors were measured by ELISA. BD patients presented increased plasma levels of adiponectin (p < 0.001), leptin (p < 0.001) and sTNFR1 (p = 0.01). Plasma levels of adipokines were not correlated neither with clinical parameters nor TNF-α, sTNFR1 and sTNFR2 plasma levels. This study provides further support to the hypothesis of the immune/inflammatory imbalance in BD.     

奥氮平与阿立哌唑对精神分裂症患者体质量、血浆神经肽Y及瘦素影响的比较

目的:比较奥氮平和阿立哌唑对精神分裂症患者体质量、血浆神经肽Y及瘦素水平的影响。方法:60例精神分裂症患者随机分为奥氮平组和阿立哌唑组各30例分别治疗8周。在治疗前、治疗后4周和8周测定两组体质量、血浆神经肽Y和瘦素水平并进行治疗前后比较。结果:奥氮平组在治疗4周和8周时体质量(F=287.207,F=506.777)、血浆神经肽Y水平(F=725.697,F=5152.624)明显高于治疗前(P均=0.000);瘦素水平治疗4周时与治疗前差异无统计学意义(F=3.908,P=0.058),治疗8周时高于治疗前(F=1589.726,P=0.000)。阿立哌唑组治疗4周和8周时体质量(F=2.810,F=1.819)、血浆神经肽Y(F=0.232,F=0.376)及瘦素水平(F=0.975,F=1.295)与治疗前比较差异无统计学意义(均P0.05)。奥氮平组治疗4周和8周时体质量的变化与神经肽Y的变化明显正相关(r=0.632,r=0.576;均P0.001),与瘦素的变化无相关(r=0.254,r=0.085;P均0.05)。逐步回归分析显示,奥氮平组神经肽Y变化进入以体质量变化为因变量的回归方程,治疗4周和8周时,神经肽Y变化可以解释体质量变化变异的40.0%和33.1%。结论:与阿立哌唑相比,奥氮平能显著增加精神分裂症患者体质量;血浆神经肽Y水平的变化可能是体质量增加的原因之一。     

Leptin concentrations are increased in subjects treated with clozapine or conventional antipsychotics.

BACKGROUND: Overweight is a considerable clinical problem in patients treated with antipsychotic agents. Recent results suggest that insulin resistance with increased insulin levels is also associated with treatment with the atypical antipsychotic agent clozapine. Leptin is important for the control of body weight and has been proposed to be a link between obesity and the insulin resistance syndrome. This study examined if clozapine-treated subjects and subjects treated with conventional antipsychotics had increased leptin levels compared with the general population and whether there was a gender difference in this respect. METHOD: Clozapine-treated patients (N = 41), patients treated with conventional antipsychotic drugs (N = 62), and healthy subjects from the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) project (N = 189) were investigated with a cross-sectional study design. Weight, body mass index (BMI), and plasma leptin concentrations were measured, and all study subjects were investigated for the presence of diabetes mellitus. Drug treatment, health status, and smoking habits were registered. RESULTS: After adjustment for gender, BMI, smoking habits, age, and diabetes, hyperleptinemia was independently (p < .001) associated with clozapine treatment and with treatment with conventional antipsychotics (p < .005) within a multiple regression analysis. In separate multiple regression analyses, leptin levels were significantly associated with clozapine treatment in men (p = .002) and women (p =.023) and with conventional antipsychotic treatment in men (p = .027) but not in women. CONCLUSION: Treatment with clozapine as well as with conventional antipsychotics is associated with increased levels of circulating leptin. Hyperleptinemia can be an important link in the development of overweight and the insulin resistance syndrome in subjects receiving antipsychotic drugs, especially atypical agents like clozapine.     

Association of plasma retinol-binding protein-4, adiponectin, and high molecular weight adiponectin with metabolic adversities in patients with schizophrenia

Objective

Metabolic adversities are prevalent in patients with schizophrenia. Retinol-binding protein 4 (RBP4) and high molecular weight (HMW) adiponectin have been recently found to be associated with metabolic features in non-psychiatric population. The study aimed to evaluate the associations between metabolic features and RBP4, total adiponectin, and HMW adiponectin in patients with schizophrenia.

Methods

We recruited 109 patients with schizophrenia treated with clozapine or haloperidol and evaluated their body mass index (BMI), waist circumference, blood pressure, and fasting triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose, insulin, RBP4, total adiponectin, and HMW adiponectin levels.

Results

We found that patients with metabolic syndrome (MS) had higher RBP4 level, and lower total adiponectin and HMW adiponectin levels than those without MS. There were no significant differences in metabolic features and adipocytokine levels between patients treated with clozapine and haloperidol. Most of the metabolic indexes were significantly correlated with the levels of adipocytokines. After adjusting the effects of age, gender, and BMI, marginal significant correlations existed between TG and RBP4 levels; HDL-C and total adiponectin and HMW adiponectin; insulin and HOMA-IR and HMW adiponectin. Receiver operating curve analysis showed that all of the three adipocytokines could differentiate patients with MS from those without MS. Meanwhile, total adiponectin and HMW adiponectin, but not RBP4, had the differentiating power for insulin resistance.

Conclusion

Higher RBP4 and lower total adiponectin and HMW adiponectin levels were observed in schizophrenic patients with MS. Only HMW adiponectin is marginally correlated with insulin sensitivity. The finding that metabolic profiles, but not the antipsychotic types, are associated with adipocytokine levels should be confirmed in longitudinal studies.     

Exposure to early life trauma is associated with adult obesity

Exposure to traumatic events during childhood is associated with an elevated risk of adult obesity. It has been hypothesized that the psychological sequelae from childhood trauma account for this risk, though no study has examined whether an increased risk of obesity is found in persons without psychological disorders. We examined exposure to early life stressors and body mass index (BMI) in 696 adults without significant medical or psychiatric history. Bivariate correlation showed that the total number of early life stressors (r=0.08), age (r=0.19), and sex (r=0.16) were significantly related to adult BMI. Given the relationship between sex and BMI, we examined the contribution of early life stressors to adult obesity separately for men and women. In men, hierarchical regression showed that exposure to early life stressors predicted adult obesity. Specifically, history of being bullied/rejected (Obese 31%, Normal weight, 9%) and emotional abuse (Obese, 17%; Normal weight, 2%) predicted adult obesity after controlling for the effects of age. In women, no relationship between early life stressors and adult obesity was found. These findings suggest that multiple processes mediate the relationship between early life stress and adult obesity and that their relative contributions may differ between men and women.     

Plasma leptin, neuropeptide Y, ghrelin, and adiponectin levels and carotid artery intima media thickness in epileptic children treated with valproate

Background

Weight gain is a common side effect of valproate (VPA) treatment, although the mechanism is not clear. Abnormal weight gain and obesity are associated with dyslipidemia, hypertension, and atherosclerosis. Measurement of the common carotid artery intima media thickness (CAIMT) gives a picture of early arterial wall alterations and, currently, is considered a noninvasive marker of premature atherosclerosis. The aim of the present study was to evaluate plasma insulin, leptin, neuropeptide Y (NPY), ghrelin, and adiponectin levels in children with epilepsy treated with VPA and to evaluate these parameters for early atherosclerosis.

Material and methods

Twenty prepubertal children with idiopathic epilepsy treated with VPA were enrolled in this study. Body mass index (BMI) and fasting insulin glucose ratio (FIGR) were calculated, and the plasma insulin, leptin, NPY, ghrelin, and adiponectin levels; the lipid profiles; and CAIMT were measured for all subjects before the treatment and after a follow-up period of 6 and 12?months.

Results

When pretreatment values were compared with those at the end of 6 and 12?months, the mean BMI values, plasma insulin, leptin, NPY levels, and FIGR were increased, whereas the plasma ghrelin and adiponectin levels, lipid profiles, and CAIMT did not change significantly at the end of 6 and 12?months.

Conclusion

These results suggest that weight gain during VPA treatment may be related to increases in insulin, leptin, and NPY levels. Additionally, in this study, no increase in the risk for early atherosclerosis was determined by CAIMT in children with epilepsy treated with VPA.     

Cytokine and adipokine alterations in patients with schizophrenia treated with clozapine

Metabolic syndrome is associated with both schizophrenia and antipsychotic medication, especially clozapine, with alterations in inflammatory cytokines and adipokines. However, the data in this field is heterogeneous and the sample sizes of the patients are limited. In this study we assessed the serum levels of cytokines/adipokines IL-6, IL-1Ra, hs-CRP and adiponectin, and components of metabolic syndrome in 190 patients with treatment resistant schizophrenia treated with clozapine. Substantial metabolic comorbidity was found in this patient group; overweight/obesity, smoking, hypertriglyceridemia, low HDL-cholesterol, high HOMA-IR, low adiponectin levels, elevated hs-CRP levels and elevated IL-1Ra levels. Elevated IL-1Ra levels are associated with insulin resistance, obesity and hypertriglyceridemia. Low adiponectin levels were associated with hypertriglyceridemia, low HDL cholesterol and high glucose, and in male patients also with obesity and high IL-1Ra levels. After controlling for confounding factors age and smoking, levels of IL-1Ra and hs-CRP associated with obesity, and the levels of IL-6 associated with obesity in female patients. We conclude that there are partly gender dependent cytokine and adipokine alterations in patients with schizophrenia on clozapine treatment associated with metabolic comorbidity. The genetic background of these cytokine alterations needs to be further investigated.     

Metformin for prevention of weight gain and insulin resistance with olanzapine: a double-blind placebo-controlled trial.

OBJECTIVE: To assess whether metformin prevents body weight gain (BWG) and metabolic dysfunction in patients with schizophrenia who are treated with olanzapine. METHOD: Forty patients taking olanzapine (10 mg daily) were randomly allocated to a metformin (n = 20; 850 to 1700 mg daily) or placebo (n = 20) group in a 14-week double-blind study. Waist circumference (WC), BWG, body mass index (BMI) fasting glucose, insulin, and lipids were evaluated at baseline and at Weeks 7 and 14 of treatment. RESULTS: At Week 14, BWG (kg) was similar in the metformin group (5.5 kg) and the placebo group (6.3 kg), P = 0.4. There were no differences between the changes in BMI, WC, glucose, insulin, insulin resistance index (HOMA-IR), and plasma lipid levels observed in the treatment group and the placebo group; however, glucose levels decreased significantly after metformin administration (P = 0.02). The HOMA-IR decreased significantly in both groups, but 3 subjects from the placebo group developed fasting glucose levels greater than 5 mmol/L. After taking metformin, triglyceride levels increased, but the cholesterol profile improved significantly. CONCLUSIONS: Metformin did not prevent olanzapine-induced BWG. While some lipid parameters worsened during placebo, the HOMA-IR improved in both the placebo and the metformin groups. Carbohydrate metabolism impairment was not systematically observed during short-term olanzapine administration.     

The distribution of body mass index among individuals with and without schizophrenia

OBJECTIVE: The objective of this study was to estimate and compare the distributions of body mass index (BMI: kg/m2) among individuals with and without schizophrenia, and, thereby, place the weight gain-inducing effects of antipsychotic drugs into context. METHOD: Data sources were (1) the mental health supplement of the 1989 National Health Interview Survey (NHIS; N = 80,130 nonschizophrenic and 150 self-reported schizophrenic individuals), (2) baseline BMI data from a drug trial of the anti-psychotic ziprasidone supplied by Pfizer Inc (420 noninstitutionalized individuals with chronic psychotic disorders [DSM-IV schizophrenia or schizoaffective disorder]) and (3) data from the National Health and Nutrition Examination Survey III (NHANES III; N = 17,689 nonschizophrenic individuals) to act as a control group for the ziprasidone trial data. RESULTS: After age-adjusting BMI in each data set, the NHIS data revealed that men with schizophrenia have mean BMIs similar to those of men without schizophrenia (26.14 vs. 25.63, respectively). In contrast, women with schizophrenia in the NHIS data set had a significantly (p<.001) higher mean BMI than did women without schizophrenia (27.36 vs. 24.50, respectively). Moreover, each decile was higher for women with schizophrenia than for women without schizophrenia. Analysis of the ziprasidone and NHANES III data sets revealed that, on average, men with schizophrenia have mean BMIs comparable to those of men without schizophrenia (26.79 vs. 26.52, respectively). In these 2 data sets, women with schizophrenia also had a mean BMI similar to those of women without schizophrenia (27.29 vs. 27.39, respectively). CONCLUSION: Although there may be a small subpopulation of schizophrenic individuals who are underweight, individuals with schizophrenia were, on the whole, as obese as or more obese than individuals without schizophrenia, suggesting that weight gain induced by antipsychotic agents is an important concern for many individuals.     

Effect of clozapine on serum leptin,insulin levels,and body weight and composition in patients with schizophrenia

OBJECTIVE: Weight gain frequently occurs during treatment with clozapine. However, the pathophysiology of clozapine-induced weight gain remains unclear. The aim of this study was to investigate the influence of clozapine on hormones leptin and insulin in relation to body weight and composition measures to determine their contribution to clozapine-induced weight gain. METHOD: Data are reported on 19 patients with schizophrenia (11 women and 8 men) who completed 10 weeks of treatment with clozapine. Insulin levels, weight measurements, body mass index (BMI), and body composition measurements were evaluated at baseline and at the end of treatment. Leptin levels were assessed at baseline and after 4 and 10 weeks of treatment. Analysis of variance with repeated measures was used to evaluate changes in weight, body composition measures, leptin, and insulin. The Pearson correlations were used to assess the relationships between changes in hormone levels and weight along with body composition measurements. The correlations of change in Positive and Negative Syndrome Scale (PANSS) score with changes in hormone levels, weight gain and body composition measures were evaluated with Pearson correlations. RESULTS: Leptin and insulin levels did not show any significant alterations across time. The use of clozapine was associated with significant increases in BMI (F=19.8, P<.001), lean muscle mass (F=8.2, P=.01), and fat mass (F=15.4, P=.001), while total body fluid percentage (F=4.1, P=.05) significantly decreased. Improvement in PANSS scores was not correlated to change in leptin, insulin, weight, BMI, or body composition measurements. The change in leptin levels was correlated to change in body fat mass. CONCLUSION: The role of leptin in weight gain induced by clozapine might be a regulatory mechanism rather than being etiologic.     

Prevalence of metabolic syndrome among inpatients with schizophrenia

OBJECTIVE: Cardiovascular disease is one of the most prevalent factors responsible for excess mortality in schizophrenia. Metabolic syndrome (MetS) is associated with the development of coronary heart disease and diabetes mellitus. The aim in this cross-sectional study was to assess the prevalence of MetS in schizophrenic Turkish inpatients. METHOD: The study was conducted from January 2006 to June 2006, and included 231 patients with schizophrenia. All participants were enrolled from inpatients attending the Samsun Mental Health Hospital psychiatry clinic. All subjects were aged between 18 and 65 and met the DSM IV criteria for schizophrenia. MetS was taken as central obesity (defined as waist circumference: men > or = 94 cm, women > or = 80 cm) and meeting > or = 2 of the following abnormalities described by the International Diabetes Federation (IDF): a serum triglyceride level > 150 mg/dL, high-density lipoprotein (HDL) cholesterol < 40 mg/dL in men and < 50 mg/dL in women, blood pressure > or = 130/85 mm Hg, and a fasting serum glucose level > or = 100 mg/d/L. RESULTS: The study group consisted of 174 male and 57 female patients. Mean age was 38.5 +/- 10.5 and mean duration of illness was 15.76 +/- 9.95 years. The overall prevalence of MetS diagnosed according to the IDF criteria was 32.0% (n = 74) and was higher in females (61.4%) than in males (22.4%; p = 0.0001). In logistic regression analysis the last step of the regression model was gender (B = 1.70, p = 0.0001, OR = 5.50, 95% CI = 2.90-10.45). CONCLUSION: This study shows that the prevalence of MetS in Turkish patients with schizophrenia is similar to that of the general population, but lower than in other reports regarding the schizophrenia population.