Impaired insulin signaling in unaffected siblings and patients with first-episode psychosis.
Impaired insulin signaling in unaffected siblings and patients with first-episode psychosis.
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DOI：
10.1038/s41380-018-0045-1
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发表时间：
2019-10
影响因子：
11
通讯作者：
Öngür D
中科院分区：
文献类型：
--
作者：
Chouinard VA;Henderson DC;Dalla Man C;Valeri L;Gray BE;Ryan KP;Cypess AM;Cobelli C;Cohen BM;Öngür D
精神障碍患者患2型糖尿病的风险很高，越来越多的证据表明，患者在大量服用抗精神病药物之前就表现出糖代谢异常。在目前的研究中，我们使用基于生理的模型和综合评估组合，通过量化首发精神病(FEP)患者和未受影响的同胞与健康人的胰岛素敏感性来检验胰岛素的作用。对22例正常同胞、18例FEP患者和15例健康对照进行2小时口服葡萄糖耐量试验(OGTT)，测定7个样本的血糖和血清胰岛素浓度。用口服最小模型法测定胰岛素敏感性。同时检测血脂、瘦素、游离脂肪酸和炎症标志物水平。进行人体测量、营养和活动度评估；采用全身双能X射线吸收测量仪测定总体身体成分和脂肪分布。胰岛素敏感性在不同组之间有显著差异(F=6.01，P=0.004)，患者和兄弟姐妹的胰岛素敏感性低于对照组(分别为P=0.006和P=0.002)。体重指数、内脏脂肪组织面积(Cm2)、血脂、瘦素、游离脂肪酸、炎症标志物和活动分级在组间无显著差异。与兄弟姐妹和对照组相比，患者的营养摄入量有显著差异，总卡路里/公斤体重较低。总体而言，这些发现表明，家族性糖代谢异常或主要胰岛素信号通路异常与精神病的风险有关，与疾病表现和治疗效果无关。未来的研究应该检查精神障碍中胰岛素信号异常的潜在生物学机制。
Patients with psychotic disorders are at high risk for type 2 diabetes mellitus, and there is increasing evidence that patients display glucose metabolism abnormalities before significant antipsychotic medication exposure. In the present study, we examined insulin action by quantifying insulin sensitivity in first episode psychosis (FEP) patients and unaffected siblings, compared to healthy individuals, using a physiological-based model and comprehensive assessment battery. Twenty-two unaffected siblings, 18 FEP patients and 15 healthy unrelated controls were evaluated using a 2-hour oral glucose tolerance test (OGTT), with 7 samples of plasma glucose and serum insulin concentration measurements. Insulin sensitivity was quantified using the oral minimal model method. Lipid, leptin, free fatty acids and inflammatory marker levels were also measured. Anthropometric, nutrient and activity assessments were conducted; total body composition and fat distribution were determined using whole-body dual energy x-ray absorptiometry. Insulin sensitivity significantly differed among groups (F=6.01, P=0.004), with patients and siblings showing lower insulin sensitivity, compared to controls (P=0.006, and P=0.002, respectively). Body mass index, visceral adipose tissue area (cm2), lipids, leptin, free fatty acids, inflammatory markers and activity ratings were not significantly different among groups. There was a significant difference in nutrient intake with lower total kilocalories/kilogram body weight in patients, compared to siblings and controls. Overall, the findings suggest that familial abnormal glucose metabolism or a primary insulin signaling pathway abnormality is related to risk for psychosis, independent of disease expression and treatment effects. Future studies should examine underlying biological mechanisms of insulin signaling abnormalities in psychotic disorders.
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