Haupt Dan W, Fahnestock Peter A, Flavin Karen A, Schweiger Julie A, Stevens Angela, Hessler Martha J, Maeda Justin, Yingling Michael, Newcomer John W
Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA.
Neuropsychopharmacology. 2007 Dec;32(12):2561-9. doi: 10.1038/sj.npp.1301392. Epub 2007 Mar 21.
Cardiovascular disease is more common in schizophrenia patients than in the general population, with a hypothesized contribution from increases in adiposity produced by antipsychotic medications. We sought to test the relationship between adiposity and insulin resistance using frequently sampled intravenous glucose tolerance tests (FSIVGTTs) to quantify whole-body insulin sensitivity in chronically treated patients with schizophrenia or schizoaffective disorder and untreated healthy controls. FSIVGTTs, body mass index (BMI), and waist circumference were obtained in nondiabetic patients (n=63) receiving olanzapine, risperidone, ziprasidone, or first generation antipsychotics, as well as in healthy controls (n=14). Subject groups (including untreated healthy controls) were matched for BMI and all treated patient groups were additionally matched for age. Bergman's minimal model (MinMod) was used to calculate insulin sensitivity (S(I)), as well as secondary measures of interest. BMI and waist circumference significantly predicted insulin sensitivity measured as MinMod S(I) (F(1,62)=35.11, p<0.0001 and F(1,46)=24.48, p<0.0001, respectively). In addition, BMI and waist circumference significantly predicted the acute plasma insulin response to the glucose challenge (AIR(G)), consistent with a beta cell compensatory response to insulin resistance (MinMod AIR(G) F(1,65)=22.42, p<0.0001 and F(1,49)=11.72, p=0.0013, respectively). Adiposity levels occurring during antipsychotic treatment are strongly related to insulin resistance, confirming that antipsychotic-induced weight gain can contribute to increased cardiometabolic risk in this population.
心血管疾病在精神分裂症患者中比在普通人群中更常见，据推测这与抗精神病药物导致的肥胖增加有关。我们试图通过频繁采样静脉葡萄糖耐量试验（FSIVGTTs）来测试肥胖与胰岛素抵抗之间的关系，以量化长期接受治疗的精神分裂症或分裂情感性障碍患者以及未接受治疗的健康对照者的全身胰岛素敏感性。在接受奥氮平、利培酮、齐拉西酮或第一代抗精神病药物治疗的非糖尿病患者（n = 63）以及健康对照者（n = 14）中进行了FSIVGTTs、体重指数（BMI）和腰围测量。各受试者组（包括未接受治疗的健康对照者）按BMI进行匹配，所有接受治疗的患者组还按年龄进行匹配。使用伯格曼最小模型（MinMod）计算胰岛素敏感性（S(I)）以及其他感兴趣的次要指标。BMI和腰围显著预测了以MinMod S(I)衡量的胰岛素敏感性（分别为F(1,62)=35.11，p<0.0001和F(1,46)=24.48，p<0.0001）。此外，BMI和腰围显著预测了对葡萄糖挑战的急性血浆胰岛素反应（AIR(G)），这与β细胞对胰岛素抵抗的代偿反应一致（MinMod AIR(G)分别为F(1,65)=22.42，p<0.0001和F(1,49)=11.72，p = 0.0013）。抗精神病药物治疗期间出现的肥胖水平与胰岛素抵抗密切相关，证实抗精神病药物引起的体重增加会导致该人群心血管代谢风险增加。
