Ngai Ying Fai, Sabatini Paul, Nguyen Duc, Davidson Jana, Chanoine Jean-Pierre, Devlin Angela M, Lynn Francis C, Panagiotopoulos Constadina
From the *Department of Pediatrics, Faculty of Medicine, University of British Columbia; †Child & Family Research Institute; Departments of ‡Surgery, and §Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
J Clin Psychopharmacol. 2014 Jun;34(3):359-64. doi: 10.1097/JCP.0000000000000118.
Second-generation antipsychotics (SGAs) are commonly prescribed to youth but are associated with metabolic effects including obesity and diabetes. The mechanisms underlying diabetes development are unclear. The purpose of this study was to compare glucose homeostasis, insulin sensitivity, insulin secretion, and overall β-cell function in risperidone-treated, quetiapine-treated, and SGA-naive youth with mental illness. We conducted a cross-sectional study in which youth aged 9 to 18 years underwent a 2-hour oral glucose tolerance test. Indices for insulin sensitivity (Matsuda index), insulin secretion (insulinogenic index), and β-cell function (insulin secretion-sensitivity index-2 [ISSI-2]) were calculated. A total of 18 SGA-naive, 20 risperidone-treated, and 16 quetiapine-treated youth participated. The 3 groups were similar in age, sex, ethnicity, body mass index standardized for age and sex, pubertal status, degree of psychiatric illness, psychiatric diagnoses, and other medications. The median treatment duration was 17 months (range, 3-91 months) for risperidone-treated youth and 10 months (range, 3-44 months) for quetiapine-treated youth. The quetiapine-treated group had lower insulinogenic index (P < 0.01) and lower ISSI-2 (P < 0.01) compared with that in the SGA-naive group. Only the body mass index standardized for age and sex was negatively associated with Matsuda index (β = -0.540, P < 0.001) in all youth. Quetiapine treatment was negatively associated with insulinogenic index (β = -0.426, P = 0.007) and ISSI-2 (β = -0.433, P = 0.008). Quetiapine reduced the insulin expression in isolated mouse islets suggesting a direct β-cell effect. Our results suggest that quetiapine treatment in youth is associated with impaired β-cell function, specifically lower insulin secretion. Prospective longitudinal studies are required to understand the progression of β-cell dysfunction after quetiapine initiation.
第二代抗精神病药物（SGA）常用于青少年，但与包括肥胖和糖尿病在内的代谢效应有关。糖尿病发展的潜在机制尚不清楚。本研究的目的是比较接受利培酮治疗、喹硫平治疗以及未使用过SGA的患有精神疾病的青少年的葡萄糖稳态、胰岛素敏感性、胰岛素分泌和整体β细胞功能。我们进行了一项横断面研究，9至18岁的青少年接受了2小时口服葡萄糖耐量试验。计算了胰岛素敏感性指标（松田指数）、胰岛素分泌指标（胰岛素生成指数）和β细胞功能指标（胰岛素分泌-敏感性指数-2 [ISSI-2]）。共有18名未使用过SGA的青少年、20名接受利培酮治疗的青少年和16名接受喹硫平治疗的青少年参与。三组在年龄、性别、种族、按年龄和性别标准化的体重指数、青春期状态、精神疾病程度、精神诊断和其他药物使用方面相似。接受利培酮治疗的青少年的中位治疗持续时间为17个月（范围3至91个月），接受喹硫平治疗的青少年为10个月（范围3至44个月）。与未使用过SGA的组相比，接受喹硫平治疗的组胰岛素生成指数较低（P < 0.01），ISSI-2较低（P < 0.01）。在所有青少年中，仅按年龄和性别标准化的体重指数与松田指数呈负相关（β = -0.540，P < 0.001）。喹硫平治疗与胰岛素生成指数呈负相关（β = -0.426，P = 0.007）和ISSI-2呈负相关（β = -0.433，P = 0.008）。喹硫平降低了分离的小鼠胰岛中的胰岛素表达，提示对β细胞有直接作用。我们的结果表明，青少年使用喹硫平治疗与β细胞功能受损有关，特别是胰岛素分泌降低。需要进行前瞻性纵向研究以了解开始使用喹硫平后β细胞功能障碍的进展情况。
