1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey.
2 Department of Neurology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey.
Cephalalgia. 2018 Oct;38(11):1773-1781. doi: 10.1177/0333102417748928. Epub 2017 Dec 20.
Background Chronic migraine has a well-documented association with increased insulin resistance and metabolic syndrome. The hypothalamus may play a role in the progression of insulin resistance in chronic migraine through the regulation of orexigenic peptides such as neuropeptide Y. Insulin resistance may lead to increased risk of future type 2 diabetes mellitus in patients with chronic migraine, which is more likely to occur if other pathogenetic defects of type 2 diabetes mellitus, such as impaired pancreatic β-cell functions and defects in intestinal glucagon-like peptide-1 secretion after meals. We studied the relationship of fasting neuropeptide Y with insulin resistance, β-cell function, and glucagon-like peptide-1 secretion in non-obese female chronic migraine patients. We also aimed to investigate glucose-stimulated insulin and glucagon-like peptide-1 secretions as early pathogenetic mechanisms responsible for the development of carbohydrate intolerance. Methods In this cross-sectional controlled study, 83 non-obese female migraine patients of reproductive age categorized as having episodic migraine or chronic migraine were included. The control group consisted of 36 healthy females. We studied glucose-stimulated insulin and glucagon-like peptide-1 secretion during a 75 g oral glucose tolerance test. We investigated the relationship of neuropeptide Y levels with insulin resistance and β-cell insulin secretion functions. Results Fasting glucose levels were significantly higher in migraine patients. Plasma glucose and insulin levels during the oral glucose tolerance test were otherwise similar in chronic migraine, episodic migraine and controls. Patients with chronic migraine were more insulin resistant than episodic migraine or controls ( p = 0.048). Glucagon-like peptide-1 levels both at fasting and two hours after glucose intake were similar in chronic migraine, episodic migraine, and controls. Neuropeptide Y levels were higher in migraineurs. In chronic migraine, neuropeptide Y was positively correlated with fasting glucagon-like peptide-1 levels (r = 0.57, p = 0.04), but there was no correlation with insulin resistance (r = 0.49, p = 0.09) or β-cell function (r = 0.50, p = 0.07). Discussion Non-obese premenopausal female patients with chronic migraine have higher insulin resistance, but normal β-cell function is to compensate for the increased insulin demand during fasting and after glucose intake. Increased fasting neuropeptide Y levels in migraine may be a factor leading to increased insulin resistance by specific alterations in energy intake and activation of the sympathoadrenal system.
背景 慢性偏头痛与胰岛素抵抗和代谢综合征的关系已有充分的文献记载。下丘脑可能通过调节神经肽 Y 等食欲肽在慢性偏头痛患者胰岛素抵抗的进展中发挥作用。胰岛素抵抗可能会导致慢性偏头痛患者未来发生 2 型糖尿病的风险增加，如果存在 2 型糖尿病的其他发病缺陷，如餐后胰腺β细胞功能受损和肠胰高血糖素样肽-1 分泌缺陷，这种风险就会增加。我们研究了非肥胖女性慢性偏头痛患者空腹神经肽 Y 与胰岛素抵抗、β细胞功能和胰高血糖素样肽-1 分泌之间的关系。我们还旨在研究葡萄糖刺激的胰岛素和胰高血糖素样肽-1 分泌作为导致碳水化合物不耐受的早期发病机制。
方法 在这项横断面对照研究中，纳入了 83 名年龄在生育期的非肥胖女性偏头痛患者，分为发作性偏头痛或慢性偏头痛。对照组由 36 名健康女性组成。我们在 75g 口服葡萄糖耐量试验期间研究了葡萄糖刺激的胰岛素和胰高血糖素样肽-1 分泌。我们研究了神经肽 Y 水平与胰岛素抵抗和β细胞胰岛素分泌功能之间的关系。
结果 偏头痛患者的空腹血糖水平明显升高。在口服葡萄糖耐量试验中，慢性偏头痛、发作性偏头痛和对照组的血糖和胰岛素水平相似。慢性偏头痛患者比发作性偏头痛或对照组患者的胰岛素抵抗更严重（p=0.048）。空腹和葡萄糖摄入后两小时，胰高血糖素样肽-1 水平在慢性偏头痛、发作性偏头痛和对照组中相似。偏头痛患者的神经肽 Y 水平较高。在慢性偏头痛中，神经肽 Y 与空腹胰高血糖素样肽-1 水平呈正相关（r=0.57，p=0.04），但与胰岛素抵抗（r=0.49，p=0.09）或β细胞功能（r=0.50，p=0.07）无关。
讨论 非肥胖绝经前女性慢性偏头痛患者的胰岛素抵抗更高，但正常的β细胞功能可以在空腹和葡萄糖摄入后增加胰岛素的需求。偏头痛患者空腹神经肽 Y 水平升高可能是通过特定的能量摄入改变和交感神经肾上腺系统激活导致胰岛素抵抗增加的一个因素。
