Blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in patients with symptoms suggesting reactive hypoglycemia

We evaluated the impact of postprandial glycemia on blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in non-diabetic patients with symptoms suggesting reactive hypoglycemia. Eleven patients with clinical symptoms suggesting reactive hypoglycemia received an oral glucose solution (75 g) Blood was collected at 0 (baseline), 30, 60, 120 and 180 min after glucose ingestion and the plasma concentrations of interferon-α (IFN-α), interferon-γ (IFN-γ), interleukin-1 receptor antagonist (IL-1RA), interleukin 2 (IL-2), interleukin-2 receptor (IL-2R), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin-12 (IL-12), interleukin 13 (IL-13), interleukin 15 (IL-15), interleukin 17 (IL-17), IFN-γ inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein-1α (MIP-1α), interleukin-1β (IL-1β), colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), basic fibroblast growth factor (FGF-basic), eotaxin, tumor necrosis factor α (TNFα), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), macrophage inflammatory protein-1α (MIP-1α), and 1β (MIP-1β) were evaluated. Overall, glycemic levels increased, reached its maximum at 30 min (phase 1), returned to baseline levels at 120 min (phase 2), followed by a mild hypoglycemia at 180 min (phase 3). During phase 1, cytokine blood levels were maintained. However, we observed a synchronous fall (P<0.05) in the concentrations of pro-inflammatory (IL-15, IL-17, MCP-1) and anti-inflammatory cytokines (FGF-basic, IL-13, IL-1RA) during phase 2. Furthermore, a simultaneous rise (P<0.05) of pro-inflammatory (IL-2, IL-5, IL-17) and anti-inflammatory cytokines (IL-4, IL-1RA, IL-2R, IL-13, FGF-basic) occurred during phase 3. Thus, mild acute hypoglycemia but not a physiological increase of glycemia was associated with increased blood levels of anti-inflammatory and pro-inflammatory cytokines.

本研究针对存在疑似反应性低血糖（reactive hypoglycemia）症状的非糖尿病患者，于口服葡萄糖耐量试验（oral glucose tolerance test）期间，探究餐后血糖对血液促炎细胞因子（pro-inflammatory cytokines）与抗炎细胞因子（anti-inflammatory cytokines）水平的影响。本研究纳入11例存在疑似反应性低血糖临床症状的受试者，给予其口服75g葡萄糖溶液。分别于葡萄糖摄入后0min（基线）、30min、60min、120min及180min采集血液样本，对血浆中干扰素-α（IFN-α）、干扰素-γ（IFN-γ）、白细胞介素-1受体拮抗剂（IL-1RA）、白细胞介素-2（IL-2）、白细胞介素-2受体（IL-2R）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、白细胞介素-12（IL-12）、白细胞介素-13（IL-13）、白细胞介素-15（IL-15）、白细胞介素-17（IL-17）、干扰素-γ诱导蛋白10（IP-10）、单核细胞趋化蛋白1（MCP1）、干扰素-γ诱导单核因子（MIG）、巨噬细胞炎症蛋白-1α（MIP-1α）、白细胞介素-1β（IL-1β）、粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、碱性成纤维细胞生长因子（FGF-basic）、嗜酸性粒细胞趋化因子（eotaxin）、肿瘤坏死因子-α（TNFα）、表皮生长因子（EGF）、肝细胞生长因子（HGF）、血管内皮生长因子（VEGF）、巨噬细胞炎症蛋白-1α（MIP-1α）及巨噬细胞炎症蛋白-1β（MIP-1β）的浓度进行检测。整体而言，受试者血糖水平先升高，于30min达到峰值（阶段1），随后于120min回落至基线水平（阶段2），最终在180min出现轻度低血糖反应（阶段3）。阶段1期间，血液细胞因子水平保持稳定。而在阶段2，我们观察到促炎细胞因子（IL-15、IL-17、MCP-1）与抗炎细胞因子（FGF-basic、IL-13、IL-1RA）的浓度同步下降（P<0.05）。此外，在阶段3，促炎细胞因子（IL-2、IL-5、IL-17）与抗炎细胞因子（IL-4、IL-1RA、IL-2R、IL-13、FGF-basic）的浓度同时升高（P<0.05）。由此可见，血液中抗炎与促炎细胞因子水平升高与轻度急性低血糖相关，而非生理性血糖升高。