Department of Chemical Pathology, University of Ibadan, Ibadan, Nigeria.
Department of Chemical Pathology, University of Ibadan, Ibadan, Nigeria.
J Natl Med Assoc. 2018 Oct;110(5):504-511. doi: 10.1016/j.jnma.2018.01.003. Epub 2018 Feb 1.
Insulin resistance and metabolic alteration continue to be essential features of major mental health disorders (MMHD) with poorly understood and multifaceted mechanisms. This study was carried out to provide information on insulin resistance, beta-cell function, metabolic clearance rate of glucose and their possible interplay with duration of antipsychotic use in patients with major mental health disorders.
Plasma levels of glucose and insulin were determined in 124 patients with MMHD after an overnight fast and at 30 and 120 min of standard Oral Glucose Tolerance Test. Thereafter, indices of insulin resistance, beta-cell function and estimated metabolic clearance rate of glucose (eMCR) were calculated appropriately. Statistical analysis was done using ANOVA, Kruskal Wallis, independent Student's t-test and Mann-Whitney U. P-values less than 0.05 were considered as statistically significant.
Metabolic factors (fasting and postprandial glucose and insulin), indices of insulin sensitivity and β-cell function were not significantly different when patients with schizophrenia, bipolar and depression were compared with one another. Postprandial insulin level at 30 min (30 min PPI), estimated First and Second Phases of Insulin Release (eFPIR, eSPIR) were significantly lower in patients on atypical antipsychotic drugs [18.15 (3.57-40.35) μIU/ml), 617.63 (320.06-911.31) pmol/l, 180.30 (114.82-249.39) pmol/l] compared with patients on typical antipsychotic drugs [27.48 (13.33-47.68) μIU/ml, 767.69 (530.58-1198.35) pmol/l, 209.89 (154.01-310.97) pmol/l]. Furthermore, the mean waist circumference and body mass index were significantly higher in patients who have been on anti-psychotic drug for more than 10 years compared with patients with less than 5 years history of anti-psychotic use. eMCR of glucose progressively declined with increasing duration of antipsychotic use and it was significantly lower in patients who have been on antipsychotic drugs for more than 10 years [8.09 (5.90-9.44) ml.kg.min] compared with patients who have been on the drugs for less than 5 years [9.03 (7.47-10.04) ml.kg.min].
Patients on atypical antipsychotics seem to have insulin secretion phases consistent with β-cell dysfunction. Also, chronicity of antipsychotic treatment predisposes patients with major mental health disorders to central adiposity and low metabolic clearance rate of glucose, a forerunner of glucose intolerance.
胰岛素抵抗和代谢改变仍然是主要精神健康障碍（MMHD）的重要特征，其机制复杂且尚未完全阐明。本研究旨在提供有关胰岛素抵抗、β细胞功能、葡萄糖代谢清除率及其与抗精神病药物使用时间之间可能相互作用的信息，这些信息在患有主要精神健康障碍的患者中。
124 名 MMHD 患者在隔夜禁食后和口服葡萄糖耐量试验 30 分钟和 120 分钟时测定血糖和胰岛素水平。然后，适当计算胰岛素抵抗、β细胞功能和估计的葡萄糖代谢清除率（eMCR）的指数。使用方差分析、克鲁斯卡尔-沃利斯检验、独立学生 t 检验和曼-惠特尼 U 检验进行统计分析。P 值小于 0.05 被认为具有统计学意义。
当比较精神分裂症、双相情感障碍和抑郁症患者时，代谢因素（空腹和餐后血糖和胰岛素）、胰岛素敏感性和β细胞功能指数没有显著差异。使用非典型抗精神病药物的患者餐后 30 分钟胰岛素水平（30 分钟 PPI）、估计的第一和第二相胰岛素释放（eFPIR、eSPIR）显著降低[18.15（3.57-40.35）μIU/ml），617.63（320.06-911.31）pmol/l，180.30（114.82-249.39）pmol/l]与使用典型抗精神病药物的患者[27.48（13.33-47.68）μIU/ml，767.69（530.58-1198.35）pmol/l，209.89（154.01-310.97）pmol/l]。此外，与使用抗精神病药物少于 5 年的患者相比，使用抗精神病药物超过 10 年的患者的平均腰围和体重指数明显更高。随着抗精神病药物使用时间的延长，葡萄糖的 eMCR 逐渐下降，使用抗精神病药物超过 10 年的患者[8.09（5.90-9.44）ml.kg.min]明显低于使用抗精神病药物少于 5 年的患者[9.03（7.47-10.04）ml.kg.min]。
使用非典型抗精神病药物的患者似乎存在与β细胞功能障碍一致的胰岛素分泌阶段。此外，抗精神病药物治疗的慢性会使主要精神健康障碍患者易患中心性肥胖和低葡萄糖代谢清除率，这是葡萄糖耐量不良的先兆。
