NORMENT & K.G. Jebsen Center for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.
NORMENT & K.G. Jebsen Center for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.
Psychoneuroendocrinology. 2019 May;103:87-95. doi: 10.1016/j.psyneuen.2019.01.001. Epub 2019 Jan 6.
The prevalence of obesity, metabolic syndrome and type 2 diabetes mellitus is increased among patients with severe mental disorders, and particularly use of second generation antipsychotic drugs is associated with metabolic side effects. Antipsychotics have been found to alter levels of adipokines which regulate insulin sensitivity, but their role in antipsychotic-associated insulin resistance is not established, and it is unclear whether adipokines affect insulin resistance independently of body mass index (BMI).
We included 1050 patients with severe mental disorders and 112 healthy controls aged 18-65 years from the Oslo area, Norway. Clinical variables, BMI and use of medication were assessed, fasting blood samples were obtained for calculation of the leptin/adiponectin ratio (L/A ratio) and estimate of insulin resistance using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Case-control analyses were followed by mediation analyses to evaluate the possible direct effect of antipsychotics on HOMA-IR and indirect effect mediated via the L/A ratio. This was performed both with and without adjustment for BMI, in the total sample and in an antipsychotic monotherapy subsample (N = 387).
BMI, L/A ratio and HOMA-IR were significantly higher in patients than controls (p < 0.001-p = 0.01). There was a significant direct effect from use of antipsychotics in general on HOMA-IR both without (b = 0.03, p = 0.007) and with adjustment for BMI (b = 0.03, p = 0.013), as well as a significant mediating effect via L/A ratio both without (b = 0.03, p < 0.001) and with adjustment for BMI (b = 0.01, p = 0.041). Use of olanzapine (b = 0.03, p < 0.001) or aripiprazole (b = 0.04, p < 0.001) in monotherapy showed significant effects on HOMA-IR mediated via L/A ratio.
The study suggests that use of antipsychotics may alter adipokine levels, and that increased L/A ratio may play a role in the development of insulin resistance associated with use of antipsychotics also independently of BMI.
肥胖症、代谢综合征和 2 型糖尿病在严重精神障碍患者中的发病率较高，尤其是第二代抗精神病药物的使用与代谢副作用有关。已经发现抗精神病药会改变调节胰岛素敏感性的脂联素水平，但它们在抗精神病药相关胰岛素抵抗中的作用尚未确定，也不清楚脂联素是否独立于体重指数（BMI）影响胰岛素抵抗。
我们纳入了来自挪威奥斯陆地区的 1050 名患有严重精神障碍的患者和 112 名健康对照者，年龄在 18-65 岁之间。评估了临床变量、BMI 和药物使用情况，采集空腹血样以计算瘦素/脂联素比值（L/A 比值）并使用稳态模型评估胰岛素抵抗（HOMA-IR）进行胰岛素抵抗估计。病例对照分析后进行中介分析，以评估抗精神病药对 HOMA-IR 的直接影响和通过 L/A 比值的间接影响。这是在总样本和抗精神病药单药治疗亚组（N=387）中分别在调整和不调整 BMI 的情况下进行的。
患者的 BMI、L/A 比值和 HOMA-IR 明显高于对照组（p<0.001-p=0.01）。一般来说，使用抗精神病药对 HOMA-IR 有显著的直接影响，既不调整（b=0.03，p=0.007）也调整（b=0.03，p=0.013）BMI，以及通过 L/A 比值的显著中介作用，既不调整（b=0.03，p<0.001）也调整（b=0.01，p=0.041）BMI。奥氮平（b=0.03，p<0.001）或阿立哌唑（b=0.04，p<0.001）单药治疗对 HOMA-IR 的影响通过 L/A 比值介导。
研究表明，使用抗精神病药可能会改变脂联素水平，而 L/A 比值的增加可能在抗精神病药相关胰岛素抵抗的发展中发挥作用，并且独立于 BMI。
