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。     

氯氮平和经典抗精神病药的长期治疗对患者体重、糖代谢及血脂的影响

目的 探讨长期应用氯氮平和经典类抗精神病药(APS)对精神分裂症患者体重、血糖和血脂等代谢指标的影响及其可能的相关因素.方法 共调查使用APS≥5年的精神分裂症患者271例,分别测量其身高和体重,检测空腹和餐后2h血糖、空腹血清游离脂肪酸、血清胰岛素和瘦素水平.按药物使用情况将患者分为氯氮平组、经典APS单一治疗组(经典组)或联合用药组进行比较.结果 [1]联合用药组体质量指数、空腹血糖、血甘油三酯和血游离脂肪酸水平均显著高于经典组(P＜0.05);血胰岛素和胰岛素抵抗指数也均显著高于经典组和氯氮平组(P＜0.05).[2]氯氮平组和联合用药组糖耐量降低和2型糖尿病发生率均明显高于经典组(P＜0.05).[3]患者体质量指数与其空腹血糖、血清瘦素、血甘油三酯、胆固醇水平以及与胰岛素抵抗指数均呈正相关(P均小于0.05);患者血清瘦素水平与其血胰岛素水平也呈正相关(P=0.008).[4]多元逐步线型回归分析表明,进入影响空腹血糖水平方程的因素分别为胰岛素抵抗指数、血胰岛素、胆固醇和体质量指数(P＜0.05).结论 单用氯氮平及其与经典抗精神病药联用,均易导致患者肥胖,且易导致患者血糖、血脂、血游离脂肪酸水平升高,并与胰岛素抵抗和糖耐量降低发生相关,可能增加2型糖尿病的发生.     

长期服用抗精神病药对脂肪酸与血糖的影响

目的 :研究慢性精神分裂症患者长期服用抗精神病药物与空腹游离脂肪酸及空腹血糖的关系。　方法 :2 18例病程 >5年的慢性精神分裂症患者接受糖尿病流行病学调查 ,测定空腹血糖、餐后2h血糖及空腹游离脂肪酸。　结果 :糖尿病组空腹游离脂肪酸水平显著高于血糖正常组 ;相关分析显示 2 18例患者空腹游离脂肪酸与空腹血糖呈显著正相关 ;糖尿病组、血糖调节异常组 2项指标间无显著相关性 ;血糖正常组空腹游离脂肪酸与空腹血糖呈显著正相关。　结论 :长期服用抗精神病药可导致部分患者游离脂肪酸及血糖处于平衡失调状态     

胰岛素抵抗对2型糖尿病患者周围神经病变的影响

目的探讨及分析胰岛素抵抗对2型糖尿病患者周围神经病变的影响。方法选取2型糖尿病患者161例为研究对象,按照是否合并周围神经病变将患者分为糖尿病周围神经病变组(DPN组,n=102)和非糖尿病周围神经病变组(NDPN组,n=59);比较2组一般资料、餐后胰岛素敏感性(Matsuda指数)、空腹胰岛素抵抗(HOMA-IR)、空腹及糖耐量实验(OGTT)后各时间点的血糖、胰岛素素及C-肽水平之间的差异。结果 DPN组年龄、糖尿病病程、HbA1c、LDL-C水平均高于NDPN组,差异有统计学意义(P0.05),Matsuda指数、HOMA-IR、空腹血糖及胰岛素水平[OGTT(0 min)]均高于NDPN组(P0.05),OGTT(120min)胰岛素水平显著低于NDPN组(P0.05);Logistic回归分析提示:年龄、空腹血糖(FBG)、胰岛素(FIRI)水平、HOMA-IR、Matsuda指数与患者周围神经病变的发生呈正相关(P0.05),而OGTT(120min)胰岛素水平与其呈负相关(P0.05)。结论 2型糖尿病患者空腹胰岛素抵抗与周围神经病变的发生密切相关,而患者餐后胰岛素抵抗则可能对周围神经病变的发生起到抑制作用。     

二甲双胍对抗精神病药所致肥胖患者胰岛素抵抗及血清白介素-18水平的影响

目的:探讨二甲双胍对抗精神病药所致肥胖患者胰岛素抵抗及血清白介素-18(IL-18)水平的影响。方法:对44例抗精神病药所致肥胖患者(肥胖组)给予二甲双胍治疗12周,监测治疗前后的体质量、体质量指数(BMI)、胰岛素抵抗指数(HOMA-IR)及血清IL-18水平;以27例非肥胖患者(非肥胖组)和47名正常人(正常对照组)作为对照。结果:治疗前肥胖组HOMA-IR、血清IL-18水平高于非肥胖组(Z=-5.05,P0.001;Z=-2.78,P0.01)及正常对照组(Z=5.98,Z=6.68;P均0.001);非肥胖组血清IL-18水平高于正常对照组(Z=4.58,P0.001)。治疗后肥胖组体质量及BMI均有明显下降(Z=2.07,Z=2.13;P均0.05);HOMA-IR虽有明显下降(Z=2.74,P0.01)但仍高于非肥胖组及正常对照组(Z=-4.01,Z=4.73;P均0.001);IL-18水平显著下降(Z=5.48,P0.001)并低于非肥胖组(Z=3.42,P0.01),但仍高于正常对照组(Z=3.59,P0.01)。HOMA-IR与IL-18水平治疗前后均无相关(r=0.108,r=0.034;P均0.05);HOMA-IR变化值与IL-18水平变化值也无相关(r=0.122,P0.05)。结论:二甲双胍能改善抗精神病药所致肥胖患者的胰岛素抵抗,降低血清IL-18水平。     

抗精神病药物奥氮平对精神病患者糖脂代谢的影响分析

目的分析抗精神病药物奥氮平对精神病患者糖脂代谢的影响。方法选取2012-03—2014-02入住我院的精神病患者216例,分成2组,观察组给予抗精神病药奥氮平治疗,对照组给予利培酮治疗,比较2组患者体质量变化,于治疗前、后分别采集患者空腹血用以比较空腹血糖、高密度脂蛋白、胆固醇和甘油三酯的变化情况。结果治疗后,2组体质量增加显著(P0.05);观察组空腹血糖、高密度脂蛋白、胆固醇、甘油三酯和空腹胰岛素均明显升高(P0.05或P0.01),对照组空腹血糖变化不明显(P0.05),而体质量、高密度脂蛋白、胆固醇和甘油三酯相比于治疗前明显升高(P0.05)。结论服用利培酮对精神病患者代谢有影响,但对空腹血糖水平无影响,而奥氮平对患者体质量、空腹血糖、高密度脂蛋白、胆固醇、甘油三酯均存在很大影响。为降低发生并发症的概率,临床上使用时要综合评估,慎重考虑。     

社区缺陷型精神分裂症患者肥胖的发生率及相关因素

目的:探讨社区缺陷型精神分裂症患者肥胖的发生率及相关危险因素。方法:收集180例社区缺陷型精神分裂症患者(患者组)的社会人口学和临床资料;检测体质量指数(BMI)、空腹血糖、血脂水平;采用阳性和阴性症状量表(PANSS)评估患者精神症状;以BMI 28定义为肥胖,并据此将患者分为肥胖与非肥胖亚组;比较患者组与对照组(323名一般情况相匹配的健康对照者)的肥胖率;比较肥胖与非肥胖亚组间人口学及临床资料;分析缺陷型精神分裂症患者肥胖的危险因素。结果:患者组肥胖率(29. 4%,53例)明显高于对照组(9. 3%,30名)(χ~2=73. 24,P 0. 001);肥胖亚组非典型抗精神病药使用率(χ~2=4. 87,P=0. 027)、高血压患病率(χ~2=5. 26,P=0. 022)、空腹血糖(t=2. 55,P=0. 006)、三酰甘油水平(t=3. 22,P=0. 001)显著高于非肥胖亚组,PANSS阴性因子分(t=-1. 164,P=0. 047)明显低于非肥胖亚组。多因素Logistic回归分析结果显示,女性、使用非典型抗精神病药、空腹血糖、血脂是肥胖的影响因素(P 0. 05或P 0. 01)。结论:社区缺陷型精神分裂症患者肥胖率高,女性、使用非典型抗精神病药、空腹血糖及血脂水平高是其危险因素。     

急性脑梗死患者简易胰岛素抵抗指数水平的临床研究

目的观察急性脑梗死患者的甘油三酯血糖指数(简易胰岛素抵抗指数TyG)和稳态模型评估的胰岛素抵抗指数(HOMA-IR)特点,并分析两指数的相关性。方法采用放射免疫法测定46例急性脑梗死(ACI)及40例健康对照者的空腹血胰岛素、空腹血糖、TG水平,计算简易胰岛素抵抗指数(TyG)和稳态模型评估法胰岛素抵抗指数(HOMA-IR)。结果急性脑梗死组TyG和HOMA-IR均较对照组增高(P0.05);急性脑梗死组和对照组TyG和HOMA-IR具有良好的相关性(分别为r=0.34,P0.05;r=0.27,P0.05)。结论急性脑梗死患者存在胰岛素抵抗,TyG评价胰岛素抵抗是一种简单准确的方法。     

睡眠时长对抑郁症患者胰岛素抵抗水平的影响

目的研究抑郁症患者不同睡眠时长对其胰岛素抵抗水平的影响,为抑郁症患者糖尿病的病因学机制研究提供参考。方法于2012年10月-2015年12月在天津市精神卫生中心精神科门诊及住院患者中抽取86例重度抑郁症患者,均符合《精神障碍诊断与统计手册(第4版)》(DSM-IV)诊断标准。检测患者空腹血糖(FBG)、空腹血清甘油三酯(FTG)水平;采用FBG和FTG水平计算所得简易胰岛素抵抗指数(Ty G)评估受试者胰岛素抵抗水平;采用匹兹堡睡眠指数量表(PSQI)评估患者睡眠情况,根据评估结果计算患者近1个月的日均睡眠时长,按日均睡眠时间长短将患者分为极短时组(4h)、短时组(4~6h)、参照组(6~8h)和长时组(≥8h),比较四组胰岛素抵抗水平;采用多重线性回归分析胰岛素抵抗水平的影响因素。结果与参照组比较,极短时组与短时组FBG和FTG水平更高,但各组之间差异无统计学意义(P均0.05);极短时组与短时组的平均简易胰岛素抵抗指数高于参照组(P0.05);多重线性回归分析结果显示,胰岛素抵抗指数与年龄(β=0.005,P0.05)、BMI(β=0.012,P0.05)正向关联,与睡眠时长(β=-0.014,P0.05)负向关联。结论短时睡眠可能是抑郁症患者发生胰岛素抵抗进而诱发糖尿病的危险因素之一。     

胰岛素抵抗、血脂异常与急性脑梗死关系的初步研究

目的探讨胰岛素抵抗、血脂异常与急性脑梗死之间的关系.方法对45例急性脑梗死患者作空腹血糖(FPG)、血清胰岛素(FINS)及血脂测定,并与25例原发性高血压(EH)患者及25例健康体检者比较.采用李光伟提出的方法计算胰岛素敏感性指数(ISI)为空腹血清胰岛素与空腹血糖乘积的倒数,即1/(FINS×FPG),取其自然对数.结果急性脑梗死患者FINS明显高于两对照组(P＜0.01);胰岛素敏感性指数明显低于两健康对照组(P＜0.01);TG、CHOL、apoB明显高于健康对照组(P＜0.01),HDL明显低于对照组(P＜0.01).FPG、LDL及apoA1三组间无明显差异.结论急性脑梗死存在胰岛素抵抗,胰岛素抵抗和血脂异常可能在脑梗死的发生中起重要作用.胰岛素抵抗在脑梗死中的重要作用有待于进一步深入研究.     

Serum Free Fatty Acids and Glucose Metabolism, Insulin Resistance in Schizophrenia with Chronic Antipsychotics

BACKGROUND: Weight gain and type 2 diabetes mellitus (DM) are often linked to antipsychotics treatment. The aim of the study is to investigate serum free fatty acids (FFA) levels in schizophrenic patients who received long-term antipsychotics treatment, and to explore the associations between serum FFA and fasting blood glucose, and insulin resistance. METHODS: 308 inpatients with schizophrenia who met with the criteria of DSM-IV were recruited into this study, and were divided into four groups: control subjects, single obesity, impaired glucose tolerance (IGT) and type 2 DM according to different body mass index, fasting blood glucose level and 2-hour postprandial blood glucose. Serum FFA was measured with colorimetry. Serum insulin and leptin were measured with radioimmunoassay respectively. RESULTS: There was a significant elevation in serum FFA levels in schizophrenic patients who received long-term antipsychotics treatment, especially in single obesity, IGT, and DM groups. The elevated serum FFA was remarkably positive correlated with fasting blood glucose and insulin resistance. CONCLUSIONS: The study suggested the elevated serum FFA in schizophrenic patients with long-term antipsychotics treatment affected the blood glucose metabolism, may have played an important role in insulin resistance and type 2 DM, and was also an important trait of metabolic syndromes.     

氯氮平与利培酮对血清脂联素的影响

目的：研究氯氮平与利培酮对血清脂联素（Adi）等代谢的影响。方法：69例精神分裂症患者随机分为氯氮平组和利培酮组。治疗6周测定患者血清Adi，血脂，空腹血糖、胰岛素水平，计算胰岛素抵抗指数（IR），测量身高、体质量，计算体质量指数（BMI），并与36名正常对照者比较。结果：两患者组治疗后的血清Adi明显降低，氯氮平组血清Adi改变与BMI相关；利培酮组血清Adi改变与IR和利培酮剂量相关。结论：氯氮平与利培酮治疗精神分裂症患者可引起血清Adi降低，并与体质量增加、IR、血脂及利培酮剂量密切相关。     

Effects of risperidone and olanzapine on remnant-like lipoprotein particle cholesterol (RLP-C) in schizophrenic patients

Second generation antipsychotics are associated with the risk of metabolic disorders such as diabetes mellitus and hyperlipidemia. Remnant-like lipoprotein particles cholesterol (RLP-C) are a known risk factor for cardiovascular events. The present study was performed to determine possible differences in fasting blood RLP-C levels between schizophrenic patients treated with risperidone as compared to olanzapine. Patients on olanzapine had significantly higher RLP-C levels than those on risperidone (p < 0.01). In olanzapine-treated patients there was no abnormality in fasting blood glucose levels, but fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) were elevated. RLP-C levels were significantly correlated with plasma triglyceride concentrations in both the olanzapine- (p < 0.01) and risperidone-treated patients (p < 0.01). The regression line slope was greater for the olanzapine group, suggesting a greater influence of olanzapine on RLP-C. There was a significant correlation between RLP-C and HOMA-IR in the risperidone group (p < 0.01) but not in the olanzapine group (p = 0.80). These results suggest that blood glucose monitoring may not be sufficient to detect metabolic disorder and that measurement of RLP-C might be helpful for the screening for metabolic disorders associated with olanzapine therapy.     

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.     

A prospective study of glucose homeostasis in quetiapine-treated schizophrenic patients by using the intravenous glucose tolerance test

Increasing attention has been paid recently to the potential diabetogenic effect of second-generation antipsychotics (SGAs). The objective of this prospective study was to evaluate the effects of quetiapine treatment on pancreatic beta-cell function in SGA-naïve schizophrenic patients. Seventeen schizophrenic subjects completed an eight-week trial. The metabolic parameters were assessed at weeks 0, 2, 4, and 8. We measured glucose homeostasis with the intravenous glucose tolerance test. After the eight-week treatment, body weight and body mass index showed to be significantly increased compared to those at baseline. No significant changes were found in serum levels of fasting glucose, insulin, total cholesterol, and high-density lipoprotein. Insulin resistance and insulin secretion were significantly increased. Incidences of clinically significant weight gain and treatment-emergent metabolic syndrome were 11.8% and 11.8%, respectively. This study result confirms the association of quetiapine treatment and impairment of glucose homeostasis in schizophrenic patients.     

Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia

BACKGROUND: Hyperglycemia and type 2 diabetes mellitus are more common in schizophrenia than in the general population. Glucoregulatory abnormalities have also been associated with the use of antipsychotic medications themselves. While antipsychotics may increase adiposity, which can decrease insulin sensitivity, disease- and medication-related differences in glucose regulation might also occur independent of differences in adiposity. METHODS: Modified oral glucose tolerance tests were performed in schizophrenic patients (n = 48) receiving clozapine, olanzapine, risperidone, or typical antipsychotics, and untreated healthy control subjects (n = 31), excluding subjects with diabetes and matching groups for adiposity and age. Plasma was sampled at 0 (fasting), 15, 45, and 75 minutes after glucose load. RESULTS: Significant time x treatment group interactions were detected for plasma glucose (F(12,222) = 4.89, P<.001) and insulin (F(12,171) = 2.10, P =.02) levels, with significant effects of treatment group on plasma glucose level at all time points. Olanzapine-treated patients had significant (1.0-1.5 SDs) glucose elevations at all time points, in comparison with patients receiving typical antipsychotics as well as untreated healthy control subjects. Clozapine-treated patients had significant (1.0-1.5 SDs) glucose elevations at fasting and 75 minutes after load, again in comparison with patients receiving typical antipsychotics and untreated control subjects. Risperidone-treated patients had elevations in fasting and postload glucose levels, but only in comparison with untreated healthy control subjects. No differences in mean plasma glucose level were detected when comparing risperidone-treated vs typical antipsychotic-treated patients and when comparing typical antipsychotic-treated patients vs untreated control subjects. CONCLUSION: Antipsychotic treatment of nondiabetic patients with schizophrenia can be associated with adverse effects on glucose regulation, which can vary in severity independent of adiposity and potentially increase long-term cardiovascular risk.     

Different influences of classical antipsychotics and clozapine on glucose-insulin homeostasis in patients with schizophrenia or related psychoses

BACKGROUND: The aim of this study was to investigate the influence of classical antipsychotics and the atypical antipsychotic agent clozapine on glucose-insulin homeostasis to explain possible mechanisms behind weight gain associated with antipsychotic treatment. METHOD: Twenty-eight patients on therapy with classical antipsychotics and 13 patients treated with clozapine (all meeting DSM-III-R criteria for schizophrenia or related psychoses) were studied. Fasting blood samples for glucose and insulin, as well as for 2 markers of the glucose-insulin homeostasis, i.e., the growth hormone (GH)-dependent insulin-like growth factor I (IGF-I) and the insulin-dependent insulin-like growth factor binding protein-1, were analyzed. Body mass index (BMI) was calculated and serum concentrations of the different antipsychotic drugs were measured. In addition, the relationship between the endocrine parameters and drug serum concentrations was examined. RESULTS: The insulin levels were positively correlated to the serum concentration of clozapine, whereas no correlations were found between insulin and the serum concentrations of perphenazine (N = 12) or zuclopenthixol (N = 9). Insulin elevation was seen in the patients receiving clozapine more frequently than in the patients receiving classical antipsychotics. In addition, the median level of IGF-I was significantly lower in the patients receiving clozapine than in the patients receiving classical antipsychotics. No significant difference in BMI was found between the 2 patient groups, and all patients but 1 were normoglycemic. CONCLUSION: The correlation between insulin and the clozapine concentration indicates a probable influence of clozapine on insulin secretion. The normal blood glucose levels in the clozapine group support the theory that clozapine induces concentration-dependent insulin resistance with secondary increased insulin secretion. In addition, lower median level of IGF-I in patients receiving clozapine compared with patients receiving classical antipsychotics points to a lower GH secretion in the clozapine group. This impaired GH secretion together with the clozapine-induced insulin resistance might be mechanisms behind weight gain during clozapine therapy.     

住院精神分裂症患者并发非酒精性脂肪肝的相关因素分析

目的 了解住院精神分裂症患者非酒精性脂肪肝的患病情况及相关因素.方法 对266例住院精神分裂症患者进行肝胆B超检查,心电图检查,并检测其空腹血糖、血脂、ALT、AST、GGT、AKP、LDH、UA等生化指标.结果 住院精神分裂症患者伴发非酒精性脂肪肝的比例为28.2％,远高于普通人群的患病率.BMI和TG值较大、EKG异常、患糖尿病、胆囊结石、是否服奥氨平与脂肪肝的患病与否等方面存在统计学意义.结论 住院精神分裂症患者伴发非酒精性脂肪肝的比例高,肥胖、高甘油三酯血症、EKG异常、糖尿病、胆囊结石、抗精神病药物是风险因素,值得临床关注.     

长期住院治疗的精神分裂症患者代谢综合征风险研究

目的调查长期服用抗精神病药的精神分裂症患者在糖脂代谢相关变量的情况及相关风险的评估,以便为进一步研究抗精神病药与代谢综合征发生的因果关系提供初步的调查线索。方法以上海市精神卫生中心住院诊断为精神分裂症且持续服用治疗剂量抗精神病药至少6个月以上而以往无代谢障碍的患者为调查对象,在6个病房中进行筛选,符合条件共170人,调查包括人口学资料(身高,体重,腰围,用药时间,糖尿病家族史)、最近一月的血脂水平(HDL,TG)、空腹血糖和血压等情况。结果精神分裂症患者中男性较女性更易罹患代谢综合征(P<0.01);精神分裂症患者中的吸烟者较不吸烟者更易罹患代谢综合征(P<0.05);而药物之间的比较并无显著性差异(P>0.05)。结论经典和非典型抗精神病药可能会引起代谢综合征或加重其发生的风险。