Haupt D W, Newcomer J W
Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA.
J Clin Psychiatry. 2001;62 Suppl 27:15-26; discussion 40-1.
Type 2 diabetes mellitus and impaired glucose tolerance are associated with antipsychotic treatment. Risk factors for type 2 diabetes and impaired glucose tolerance include abdominal adiposity, age, ethnic status, and certain neuropsychiatric conditions. While impaired glucose metabolism was first described in psychotic patients prior to the introduction of antipsychotic medications, treatment with antipsychotic medications is associated with impaired glucose metabolism, exacerbation of existing type 1 and 2 diabetes, new-onset type 2 diabetes mellitus, and diabetic ketoacidosis, a severe and potentially fatal metabolic complication. The strength of the association between antipsychotics and diabetes varies across individual medications, with the largest number of reports for chlorpromazine, clozapine, and olanzapine. Recent controlled studies suggest that antipsychotics can impair glucose regulation by decreasing insulin action, although effects on insulin secretion are not ruled out. Antipsychotic medications induce weight gain, and the potential for weight gain varies across individual agents with larger effects observed again for agents like chlorpromazine, clozapine, and olanzapine. Increased abdominal adiposity may explain some treatment-related changes in glucose metabolism. However, case reports and recent controlled studies suggest that clozapine and olanzapine treatment may also be associated with adverse effects on glucose metabolism independent of adiposity. Dyslipidemia is a feature of type 2 diabetes, and antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, with agents such as haloperidol, risperidone, and ziprasidone associated with reductions in plasma triglycerides. Diabetes mellitus is associated with increased morbidity and mortality due to both acute (e.g., diabetic ketoacidosis) and long-term (e.g., cardiovascular disease) complications. A progressive relationship between plasma glucose levels and cardiovascular risk (e.g., myocardial infarction, stroke) begins at glucose levels that are well below diabetic or "impaired" thresholds. Increased adiposity and dyslipidemia are additional, independent risk factors for cardiovascular morbidity and mortality. Patients with schizophrenia suffer increased mortality due to cardiovascular disease, with presumed contributions from a number of modifiable risk factors (e.g., smoking, sedentary lifestyle, poor diet, obesity, hyperglycemia, and dyslipidemia). Patients taking antipsychotic medications should undergo regular monitoring of weight and plasma glucose and lipid levels, so that clinicians can individualize treatment decisions and reduce iatrogenic contributions to morbidity and mortality.
2型糖尿病和糖耐量受损与抗精神病药物治疗相关。2型糖尿病和糖耐量受损的危险因素包括腹部肥胖、年龄、种族状况以及某些神经精神疾病。虽然在抗精神病药物应用之前就已在精神病患者中首次描述了糖代谢受损，但抗精神病药物治疗与糖代谢受损、现有1型和2型糖尿病的加重、新发2型糖尿病以及糖尿病酮症酸中毒（一种严重且可能致命的代谢并发症）相关。不同的抗精神病药物与糖尿病之间关联的强度有所不同，其中氯丙嗪、氯氮平和奥氮平的相关报告数量最多。近期的对照研究表明，抗精神病药物可通过降低胰岛素作用来损害血糖调节，不过对胰岛素分泌的影响也不能排除。抗精神病药物会导致体重增加，不同药物导致体重增加的可能性各异，氯丙嗪、氯氮平和奥氮平等药物的影响更为显著。腹部肥胖增加可能解释了一些与治疗相关的糖代谢变化。然而，病例报告和近期的对照研究表明，氯氮平和奥氮平治疗也可能与独立于肥胖的糖代谢不良反应相关。血脂异常是2型糖尿病的一个特征，氯氮平和奥氮平等抗精神病药物也与高甘油三酯血症相关，而氟哌啶醇、利培酮和齐拉西酮等药物则与血浆甘油三酯水平降低相关。糖尿病因急性并发症（如糖尿病酮症酸中毒）和长期并发症（如心血管疾病）而导致发病率和死亡率增加。血浆葡萄糖水平与心血管风险（如心肌梗死、中风）之间的渐进关系在远低于糖尿病或“糖耐量受损”阈值的葡萄糖水平时就已开始。肥胖增加和血脂异常是心血管发病和死亡的另外独立危险因素。精神分裂症患者因心血管疾病导致的死亡率增加，许多可改变的危险因素（如吸烟、久坐不动的生活方式、不良饮食、肥胖、高血糖和血脂异常）可能起了作用。服用抗精神病药物的患者应定期监测体重以及血浆葡萄糖和脂质水平，以便临床医生能够个体化制定治疗决策并减少医源性因素对发病率和死亡率的影响。
