换用阿立哌唑对精神分裂症患者代谢的影响

目的:探讨换用阿立哌唑治疗后精神分裂症患者各项代谢指标的改善情况。方法:选择43例换用阿立哌唑治疗的精神分裂症患者,分别在换药前和换药12周对患者的血糖、血脂和体质量等代谢指标进行检测。结果:换用阿立哌唑12周,患者的体质量(t=3.38,P<0.01)和体质量指数(t=3.07,P<0.01)显著改善,空腹血糖(t=2.96,P<0.01)、2h血糖(t=2.58,P<0.01)、糖化血红蛋白(t=3.50,P<0.01)、空腹胰岛素(t=19.71,P<0.01)、和稳态模型评估的胰岛素抵抗系数(t=2.70,P<0.05)均较治疗前显著降低,总胆固醇(t=2.78,P<0.01)、三酰甘油(t=4.38,P<0.01)和低密度脂蛋白(t=2.81,P<0.01)亦有显著降低,代谢综合征的患病率(χ2=19.07,P<0.01)显著降低。结论:换用阿立哌唑治疗对精神分裂症患者的代谢有显著改善作用。     

The prevalence of metabolic syndrome in Korean patients with schizophrenia receiving a monotherapy with aripiprazole, olanzapine or risperidone

Second-generation antipsychotics (SGAs) increase the risk of metabolic syndrome (MetS). Although ethnicity also contributes to MetS risk, the majority of the studies on the relationship of SGAs to this syndrome come from Western countries, whereas few reports have come from Asian countries, especially regarding patients taking a single SGA. We reviewed the electronic medical records of patients with schizophrenia who received aripiprazole, olanzapine or risperidone monotherapies for at least three months. We evaluated the prevalence of MetS in our sample as well as the indirect standardized prevalence ratio (ISPR) using data from the 4th Korean National Health and Nutrition Examination Survey (KNHNES, 2007). The prevalence of MetS in our sample (n = 145) was 31.7%, and the ISPR was 2.09. Male patients had a higher prevalence of MetS than female patients (odds ratio [OR] = 4.18, 95% CI = 1.93-9.03). The ISPR of male patients was 2.67 and statistically significant, whereas the ISPR of female patients was not significant. In our sample, the frequency of abnormal MetS subcomponents occurred in descending order: increased waist circumference, increased triglyceride levels, decreased HDL-cholesterol levels, elevated blood pressure and elevated fasting blood glucose levels. Patients who received aripiprazole were significantly less likely to have MetS. However, a logistic regression showed that age and sex, but not the type of antipsychotic, its dose or the use of antidepressants, were significantly related to the presence of MetS. There were no statistically significant differences among SGAs in terms of MetS subcomponent abnormalities of after adjusting for age and sex. In conclusion, only male Korean patients with schizophrenia who received a monotherapy of aripiprazole, olanzapine or risperidone for more than three months were more likely to have MetS than the general population.     

Oral glucose tolerance tests in treated patients with schizophrenia.: Data to support an adaptation of the proposed guidelines for monitoring of patients on second generation antipsychotics?

OBJECTIVE: A recent consensus conference has proposed guidelines for the monitoring for diabetes in patients with schizophrenia and also identifies the need of long-term prospective studies. METHOD: A large scale prospective study on metabolic risks of antipsychotic medication is currently ongoing. At baseline, patients get a full laboratory screening, ECG and an oral glucose tolerance test (OGTT). Baseline data on 100 non-diabetic patients at study inclusion and stable on medication for at least 6 months are presented. RESULTS: Glucose abnormalities are found in 22% of patients at baseline. A monitoring protocol based only on fasting glucose would not have detected 63.6% of these patients with classifiable glucose abnormalities in our sample. Fasting insulin and measures for insulin resistance have a high predictive value for abnormalities late in the OGTT. CONCLUSION: Already at baseline, metabolic problems are frequently present in patients with schizophrenia treated with antipsychotics. Adding assessment of fasting insulin in a monitoring protocol improves detection of glucose abnormalities late in an OGTT.     

2型糖尿病并发脑梗死危险因素临床分析

目的探讨2型糖尿病并发脑梗死的危险因素。方法随机选取120例患者,分为2型糖尿病并发脑梗死者组(A组)和单纯2型糖尿病组(B组),每组60例。对所入选患者测量空腹血糖(FBG)、空腹胰岛素(FBI)、血流变、甘油三酯(TG)、血胆固醇(TCHO)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL),测量身高、体质量、血压,计算腹围指数(IBM)和胰岛素敏感指数(ISI),对所得结果进行分析。结果 2型糖尿病并发脑梗死患者其空腹血糖、甘油三酯、胆固醇、低密度脂蛋白、腹围指数、血压均高于单纯2型糖尿病者,而高密度脂蛋白、胰岛素敏感指数低于后者。结论高血压、高血糖、肥胖、高黏血症、高血脂、胰岛素抵抗是2型糖尿病并发脑梗死的危险因素。     

Relationship between SSRIs and Metabolic Syndrome Abnormalities in Patients with Generalized Anxiety Disorder: A Prospective Study

Objective

SSRIs are some of the most widely prescribed medications in the world. In addition to their effectiveness, SSRIs were reported to be associated with the side effects of weight gain, sexual dysfunction, drug interactions, extrapyramidal symptoms and discontinuation symptoms. However, the effects of SSRIs on metabolic parameters are poorly understood.

Methods

This study aims to describe the effects of SSRIs on the metabolic parameters of drug-naive first episode patients with generalized anxiety disorder. Ninety-seven female patients aged 20-41 years without any metabolic or psychiatric comorbidity were included in the study. Fluoxetine, sertraline, paroxetine, citalopram and escitalopram were randomly given to the patients. Metabolic parameters, including BMI, waist circumference and the levels of fasting glucose, total cholesterol, triglyceride, HDL, LDL and blood pressure, were measured before and after 16 weeks of treatment.

Results

In the paroxetine group, there was a significant increase in the parameters of weight, BMI, waist circumference, fasting glucose, total cholesterol, LDL and triglyceride after 16 weeks of treatment. There were significant increases in the levels of triglyceride in the citalopram and escitalopram groups. In the sertraline group, the total cholesterol level increased after treatment. In the fluoxetine group, there were significant reductions in the parameters of weight, total cholesterol and triglyceride.

Conclusion

To our knowledge, this study is the first to prospectively describe metabolic syndrome abnormalities in patients with first episode generalized anxiety disorder. Although the effectiveness of the different SSRIs is similar, clinicians should be more careful when prescribing SSRIs to patients who have cardiac risk factors. Larger and lengthier controlled clinical trials are needed to explore the associations between SSRI use and metabolic syndrome.     

Metabolic effects of adjunctive aripiprazole in clozapine‐treated patients with schizophrenia

Fan X, Borba CPC, Copeland P, Hayden D, Freudenreich O, Goff DC, Henderson DC. Metabolic effects of adjunctive aripiprazole in clozapine‐treated patients with schizophrenia. Objective: This study examined the effects of adjunctive aripiprazole therapy on metabolism in clozapine‐treated patients with schizophrenia. Method: In an 8‐week randomized, double‐blind, placebo‐controlled study, subjects received either aripiprazole (15 mg/day) or placebo. At baseline and week 8, metabolic parameters were assessed by the frequently sampled intravenous glucose tolerance test, nuclear magnetic resonance spectroscopy and whole‐body dual‐energy X‐ray absorptiometry (DXA). Results: Thirty subjects completed the study (16 in the aripiprazole group and 14 in the placebo group). Glucose effectiveness measured by the frequently sampled intravenous glucose tolerance test improved significantly in the aripiprazole group (0.003 ± 0.006 vs. ?0.005 ± 0.007/min, P = 0.010). The aripiprazole group showed significant reductions in both plasma low‐density lipoprotein (LDL) levels (?15.1 ± 19.8 vs. 4.4 ± 22.5 mg/dl, P = 0.019) and LDL particle numbers (?376 ± 632 vs. ?36 ± 301 nm , P = 0.035). Further, there was a significant reduction in the lean mass (?1125 ± 1620 vs. 607 ± 1578 g, P = 0.011) measured by whole‐body DXA scan in the aripiprazole group. All values were expressed as mean ± standard deviation, aripiprazole vs. placebo. Conclusion: Adjunctive therapy with aripiprazole may have some metabolic benefits in clozapine‐treated patients with schizophrenia.     

Glucose and lipid disturbances after 1 year of antipsychotic treatment in a drug-naïve population

ObjectiveThis study examined the main metabolic side effects induced by antipsychotic treatment in a cohort of first episode drug-naïve subjects after the first year of treatment.MethodsA randomized, open-label, prospective clinical trial was conducted. Participants were 164 consecutive subjects included in a first episode program and never treated with antipsychotic medication. Patients were assigned to haloperidol, olanzapine or risperidone. The main outcome measures were changes at 1 year in fasting glucose parameters (glucose, insulin levels and insulin resistance index) and changes in fasting lipid parameters (total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol).Results144 of the total sample were evaluated at 1 year. There was a statistically significant increase in the mean values of insulin levels, insulin resistance index, total cholesterol, LDL-cholesterol and triglycerides. No pathological values in fasting glucose plasma levels were found at baseline and there were no changes after 1 year. Weight gain was positively correlated with changes in insulin levels, insulin resistance index and triglyceride levels. We did not detect statistically significant differences between treatments in any of the parameters evaluated.ConclusionsFasting glycaemia and insulin concentrations at baseline do not support the hypothesis that schizophrenia is associated with an underlying abnormality in glucose metabolism. The changes in insulin and lipid parameters at 1 year seem to be related to the magnitude of weight gain. There were no significant differences between haloperidol, olanzapine and risperidone concerning metabolic adverse effects after the first year of treatment.     

阿立哌唑治疗奥氮平所致精神分裂症患者体质量增加的随机双盲对照研究

目的:探讨阿立哌唑干预奥氮平所致体质量增加的有效性及安全性。方法:将服用单一奥氮平治疗所致体质量增加≥7%的入组对象72例随机分为A组(加服阿立哌唑10 mg组,36例)及B安慰剂组(36例),入组时、治疗4周及8周分别测定体质量、体质量指数(BMI)、空腹血糖(FG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)及高密度脂蛋白(HDL),并用阳性和阴性症状量表(PANSS)评定精神症状。结果:两组治疗前体质量、BMI、FG、TC、TG、LDL、HDL,差异无统计学意义(P0.05)。与治疗前比较,治疗8周,A组体质量、BMI、FG均明显下降(P0.05或P0.01),而HDL有明显增高(P0.05);B组体质量、BMI、FG均明显增高(P0.05或P0.01)。治疗4周体质量、BMI的变化值、治疗第8周体质量、BMI、FG、HDL的变化值,两组均差异有统计学意义(P0.05或P0.01)。结论:阿立哌唑能有效减轻奥氮平所致体质量增加和糖脂代谢紊乱。     

Changes in metabolic parameters following a switch to aripiprazole in Japanese patients with schizophrenia: One-year follow-up study

The purpose of the present study was to evaluate changes in metabolic parameters after switching to aripiprazole in Japanese population. In this 1-year observation study, following a switch to aripiprazole, 32 patients with schizophrenia were observed and assessment was done of bodyweight, total cholesterol, triglyceride, serum prolactin level, and corrected QT (QTc) interval. Significant reductions were observed in these parameters other than QTc interval. Given known detrimental metabolic and hormonal effects of some atypical antipsychotics, a switch to aripiprazole may warrant serious consideration also in Asian patients who suffer those side-effects.     

Serum lipids after stroke

To ascertain the appropriate time for detecting lipid abnormalities for prophylaxis, serial analyses of fasting serum lipoproteins were undertaken prospectively in men with cerebral infarction or transient ischemic attacks. Serum total cholesterol (T CHOL) and low density lipoprotein cholesterol (LDL CHOL) in cerebral infarction patients aged 50 to 69 were lowest on day 7, intermediate on day 1, and highest at 3 months, whereas very low density lipoprotein and high density lipoprotein cholesterol (HDL CHOL) changed little. The day 1 mean fasting serum HDL CHOL of cerebral infarct patients was significantly lower in subjects aged 50 to 59 than in those aged 60 to 69 (23 +/- 3 versus 42 +/- 5 mg/dl), and there was a corresponding higher ratio of T CHOL:HDL CHOL (12.7 +/- 4.5 versus 4.7 +/- 0.4, p less than 0.01). Mean HDL CHOL levels were low normal to low in patients aged 50 to 69 with transient ischemic attacks. Both serum cholesterol and triglyceride levels are initially decreased in patients aged 50 to 69 with cerebral infarction, whereas only cholesterol is decreased in patients 60 to 69 with transient ischemic attacks. Important lipoprotein abnormalities may be missed in the acute phase.     

Metabolic changes in normal- and underweight children with obstructive sleep-disordered breathing

ObjectiveThis study evaluates the metabolic profile of normal- and underweight children with sleep-disordered breathing (SDB) due to adenotonsillar hypertrophy.MethodsA total of 39 children aged 3–15 years with SDB and 28 age- and gender-matched controls were included in the study. Body mass index z score, blood pressure, and fasting serum levels of triglycerides (TGs), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, very-low-density lipoprotein (VLDL), blood glucose, plasma insulin, and homeostatic model assessment (HOMA) were determined in both case patients and controls.ResultsWe observed significantly lower levels of fasting blood glucose (p = 0.015) and higher levels of HDL (p = 0.002), LDL (p = 0.002), and cholesterol (p = 0.001) in case patients than in controls. The mean values of fasting insulin and HOMA were higher in case patients (6.42 ± 6.47 and 1.40 ± 1.48) than in controls (5.31 ± 3.40 and 1.20 ± 0.84) respectively. No direct correlation between indices of severity of SDB and various metabolic and blood pressure parameters was found. When the effect of body weight was studied by subgrouping case patients according to normal weight and underweight, significant increases in the levels of fasting insulin (p = 0.039), HOMA (p = 0.017), and fasting blood glucose (p = 0.021) were observed. Also, a significant correlation was observed between the duration of illness and fasting insulin (p = 0.023), HOMA (p = 0.020), fasting glucose (p = 0.004), and diastolic blood pressure (p = 0.030).ConclusionThis study shows an independent effect of body weight and duration of illness on various metabolic and blood pressure parameters in normal- and underweight children with SDB     

Alzheimer disease and vascular dementia: relationships with fasting glucose and insulin levels

Cerebrovascular disease and Alzheimer disease are the leading causes of dementia in elderly subjects. In spite of it, relatively little is known about the pathogenesis and risk factors for dementia. We evaluated fasting plasma glucose and insulin, albumin, lipids, Lp(a) and uric acid levels in nondiabetic patients of both sexes affected by vascular dementia (VD) and senile dementia of the Alzheimer type (SDAT) as well as in a control group of age-matched nondemented subjects. Following a covariance analysis by gender, body mass index, albumin levels and prevalence of arterial hypertension, total and LDL cholesterol as well as HDL cholesterol levels were not significantly different among the three groups. Fasting glucose (p < 0.001 and p < 0.005, respectively) and insulin levels (p < 0.05 for both differences) were higher in patients with VD and SDAT than in control subjects. Our data show that nondiabetic patients with VD or SDAT have higher fasting glucose and insulin levels than healthy control subjects. These metabolic characteristics were not influenced by differences in gender, adiposity, nutritional status, lipids or presence of arterial hypertension.     

Insulin resistance accounts for metabolic syndrome‐related alterations in brain structure

Metabolic syndrome (MetS) is a major public health burden worldwide and associated with brain abnormalities. Although insulin resistance is considered a pivotal feature of MetS, its role in the pathogenesis of MetS‐related brain alterations in the general population is unclear. Therefore, in 973 participants (mean age 52.5 years) of the population‐based Rhineland Study, we assessed brain morphology in relation to MetS and insulin resistance, and evaluated to what extent the pattern of structural brain changes seen in MetS overlap with those associated with insulin resistance. Cortical reconstruction and volumetric segmentation were obtained from high‐resolution brain images at 3 Tesla using FreeSurfer. The relations between metabolic measures and brain structure were assessed through (generalized) linear models. Both MetS and insulin resistance were associated with smaller cortical gray matter volume and thickness, but not with white matter or subcortical gray matter volume. Age‐ and sex‐adjusted vertex‐based brain morphometry demonstrated that MetS and insulin resistance were related to cortical thinning in a similar spatial pattern. Importantly, no independent effect of MetS on cortical gray matter was observed beyond the effect of insulin resistance. Our findings suggest that addressing insulin resistance is critical in the prevention of MetS‐related brain changes in later life.     

The relationship between metabolic syndrome,BDNF, and vitamin D in patients with schizophrenia

The objective of this study is to investigate the relationship between anthropometric (BMI and waist circumference), metabolic (glucose, insulin, insulin resistance, HbA1c, and lipid profile), psychopathologic (Positive and Negative Syndrome Scale, PANSS) parameters with vitamin D and serum brainderived neurotrophic factor (BDNF) levels in patients with schizophrenia. The study population consisted of 54 healthy control subjects, and 64 volunteer patients, monitored in the psychiatry outpatient clinics of Antalya Education and Research Hospital. Serum glucose, HDL, LDL, triglyceride, total cholesterol levels (spectrophotometric method), HbA1c (HPLC method), insulin, and vitamin 25(OH)D (chemiluminescence method), with HOMA-IR (numerical calculation), and serum BDNF levels (sandwich ELISA, enzymelinked immunosorbent assay) were quantitatively evaluated using respective analytical methods indicated in parentheses. Twenty-seven (42.18%) of 64 schizophrenia patients were diagnosed with MetS. In schizophrenia patients diagnosed with metabolic syndrome (MetS), PANSS-negative and -positive symptom scores were significantly higher, while serum BDNF levels were significantly lower. In patients with schizophrenia, significantly negative correlations were detected between PANSS-negative and -positive symptom scores, and BDNF (p < 0.001 and p < 0.001, respectively), and also between PANSS-negative symptom score and vitamin D (p = 0.022). Lower serum BDNF levels may be related to increases in the possible development of MetS and psychotic symptoms. Decrease in vitamin D levels in schizophrenia patients may be associated with an increase in PANSS-negative symptom scores. In schizophrenia patients with MetS, psychotic symptoms may be more severe.     

氯氮平对超敏C反应蛋白及糖脂代谢的影响

目的：探讨氯氮平对精神分裂症患者超敏C反应蛋白（hs-CRP）以及糖、脂代谢的影响。方法：对30例服用氯氮平治疗的精神分裂症患者（患者组）作hs-CRP、空腹血糖、三酰甘油、胆固醇、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、载脂蛋白A1（ApoA1）、载脂蛋白B（ApoB）检测，于治疗前、治疗第4、8、12周各检测1次。并与30名健康者（对照组）进行比较。结果：治疗前患者组和对照组糖脂各值差异无显著性。在治疗第4、8、12周的hs-CRP，第12周的空腹血糖、三酰甘油、胆固醇、LDL、ApoB比治疗前明显升高；治疗第12周的HDL、ApoA1比治疗前明显下降；hs-CRP与空腹血糖、三酰甘油、胆固醇以及氯氮平剂量呈正相关。结论：氯氮平对hs-CRP、糖脂代谢均会产生影响，氯氮平导致代谢综合征可能与hs-CRP有关。     

The factor structure of the metabolic syndrome in obese individuals with binge eating disorder

Objective

Metabolic syndrome (MetS) is strongly linked with cardiovascular disease and type-II diabetes, but there has been debate over which metabolic measures constitute MetS. Obese individuals with binge eating disorder (BED) are one of the high risk populations for developing MetS due to their excess weight and maladaptive eating patterns, yet, the clustering patterns of metabolic measures have not been examined in this patient group.

Methods

347 adults (71.8% women) were recruited for treatment studies for obese individuals with BED. We used the VARCLUS procedure in the Statistical Analysis System (SAS) to investigate the clustering pattern of metabolic risk measures.

Results

The analysis yielded four factors: obesity (body-mass-index [BMI] and waist circumference), lipids (HDL and triglycerides), blood pressure (systolic and diastolic blood pressure), and glucose regulation (fasting serum glucose and Hb1Ac). The four factors accounted for 84% of the total variances, and variances explained by each factor were not substantially different. There was no inter-correlation between the four factors. Subgroup analyses by sex and by race (Caucasian vs. African American) yielded the same four-factor structure.

Conclusion

The factor structure of MetS in obese individuals with BED is not different from those found in normative population studies. This factor structure may be applicable to the diverse population.     

首发精神分裂症患者代谢异常分析及奥氮平对其影响

目的 探讨首发精神分裂症患者代谢异常的情况及非典型抗精神病药物奥氮平对此可能的影响.方法 选取中山大学附属第三医院心理科自2010年2月至2011年2月收治的30例首发精神分裂症患者(病例组,予以奥氮平单药治疗4周)及40例健康者(对照组),分别在治疗前(基线)、后测定身高、体质量、腰围、臀围、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、载脂蛋白AI(aPOAI)、载脂蛋白B100(aPOB100)、脂蛋白a(LPa)、空腹血糖(FBS)、空腹胰岛素(INS)及C肽,计算胰岛素抵抗指数(Ⅱ)、腰臀比(WHR)和体重指数(BMI),并将病例组与对照组、病例组治疗前后各项代谢指标进行比较分析.结果 病例组HDL、aPOAI明显低于对照组,腰臀比、IR、INS、C肽明显高于对照组,差异均有统计学意义(P＜0.05).病例组治疗后BMI、腰围、腰臀比、胰岛素、IR、TC、TG、LDL、aPOB 100较治疗前均有明显增高,差异均有统计学意义(P＜0.05).结论 精神分裂症患者本身可能存在某些代谢异常的易感素质,其高代谢异常发生率可能是其易感素质与抗精神病药物共同作用的结果.     

Prevalence of diabetes and the metabolic syndrome in a sample of patients with bipolar disorder

OBJECTIVES: The presence of metabolic abnormalities is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of the metabolic abnormalities in disorders other than schizophrenia in which antipsychotic medication is part of routine treatment. METHODS: Sixty consecutive patients with bipolar disorder (BD) at our university psychiatric hospital and affiliate services were entered in an extensive prospective metabolic study including an oral glucose tolerance test. The prevalence of the metabolic syndrome was assessed based on the National Cholesterol Education Program Adult Treatment Protocol (ATP-III) criteria, the adapted ATP-III criteria using a fasting glucose threshold of 100 mg/dL, and the recently proposed criteria from the International Diabetes Federation (IDF). RESULTS: The analysis of 60 patients showed a prevalence of the metabolic syndrome of 16.7% (ATP-III), 18.3% (adapted ATP-III) and 30.0% (IDF), respectively. A total of 6.7% of the patients met criteria for diabetes and 23.3% for pre-diabetic abnormalities. CONCLUSIONS: The metabolic syndrome and glucose abnormalities are highly prevalent among patients with BD. They represent an important risk for cardiovascular and metabolic disorders. Assessment of the presence and monitoring of metabolic abnormalities and its associated risks should be part of the clinical management of patients with BD.     

Relation with HOMA-IR and thyroid hormones in obese Turkish women with metabolic syndrome

The aim of this study was to investigate the relationship between insulin resistance and thyroid function in obese pre- and postmenopausal women with or without metabolic syndrome (MetS). 141 obese women were divided into two groups, HOMA-IR<2.7 and HOMA-IR>2.7, to evaluate relation with HOMA-IR and fatness, hormone and blood parameters. They were then divided into four groups as pre- and postmenopausal with or without MetS. Various fatness, hormone and blood parameters were examined. Statistically significant difference was found in weight, body mass index (BMI), waist circumference, fat%, fasting insulin, TSH, FT3, FT4, FSH, Anti-microsomal antibody (ANTIM) and triglycerides levels in HOMA-IR<2.7 and HOMA-IR>2.7 obese Turkish women. This study showed that age, weight, BMI, waist circumference, fat%, fasting insulin, FT3, ANTIM, FSH, LH, total cholesterol, triglycerides, HDL, HOMA-IR, systolic and diastolic blood pressure levels were related in preand post menopausal status in obese women with or without MetS. Obesity may influence the levels of thyroid hormones and increases the risk of MetS in women. Postmenopausal status with MetS is associated with an increased TSH, FT3 and FT4 levels and HOMA-IR in obese women. Strong relation was observed with MetS and TSH and FT3 levels.