Universidade de Sao Paulo, Sao Paulo, Brazil.
Butantan Institute, Sao Paulo, Brazil.
Arthritis Care Res (Hoboken). 2018 Jan;70(1):114-124. doi: 10.1002/acr.23237. Epub 2017 Dec 6.
To assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT).
In this cross-sectional study, 33 adult females with mild/inactive SLE (SLE group) and 16 age- and body mass index-matched female healthy controls (CTRL group) underwent an MTT and were assessed for insulin sensitivity and beta cell function. Skeletal muscle protein expressions of total and membrane insulin-dependent glucose transporter 4 (GLUT-4) were also evaluated (SLE group: n = 10, CTRL group: n = 5); muscle biopsies were performed after MTT. Further measurements included inflammatory cytokines, adipocytokines, physical activity level, body composition, and food intake.
SLE and CTRL groups showed similar fasting glucose, glucose response, and skeletal muscle GLUT-4 translocation after MTT. However, the SLE group demonstrated higher fasting insulin levels (P = 0.01; effect size [ES] 1.2), homeostatic model assessment insulin resistance (IR) (P = 0.03; ES 1.1), insulin-to-glucose ratio response to MTT (P = 0.02; ES 1.2), fasting glucagon levels (P = 0.002; ES 2.7), glucagon response to MTT (P = 0.0001; ES 2.6), and a tendency toward lower Matsuda index of whole-body insulin sensitivity (P = 0.06; ES -0.5) when compared with the CTRL group. Fasting proinsulin-to-insulin ratio and proinsulin-to-insulin ratio response to MTT were similar between groups (P > 0.05), while the SLE group showed a higher insulinogenic index when compared with the CTRL group (P = 0.02; ES = 0.9).
We have identified that SLE patients had a bi-hormone metabolic abnormality characterized by increased IR and hyperglucagonemia despite normal glucose tolerance and preserved beta cell function and skeletal muscle GLUT-4 translocation. Strategies capable of ameliorating insulin sensitivity to reduce the risk of type 2 diabetes mellitus and cardiovascular disease in SLE may require more than targeting IR alone.
评估系统性红斑狼疮（SLE）患者对餐耐量试验（MTT）的胰岛素敏感性。
在这项横断面研究中，33 名轻度/不活跃的成年女性 SLE 患者（SLE 组）和 16 名年龄和体重指数匹配的健康女性对照（CTRL 组）接受了 MTT，并评估了胰岛素敏感性和胰岛β细胞功能。还评估了骨骼肌中总胰岛素依赖性葡萄糖转运蛋白 4（GLUT-4）和膜结合型 GLUT-4 的蛋白表达（SLE 组：n = 10，CTRL 组：n = 5）；MTT 后进行肌肉活检。进一步的测量包括炎症细胞因子、脂肪细胞因子、身体活动水平、身体成分和食物摄入量。
SLE 组和 CTRL 组的空腹血糖、MTT 后的血糖反应和骨骼肌 GLUT-4 转位均相似。然而，SLE 组的空腹胰岛素水平更高（P = 0.01；效应量 [ES] 1.2）、稳态模型评估胰岛素抵抗（IR）（P = 0.03；ES 1.1）、MTT 时胰岛素/葡萄糖比值反应更高（P = 0.02；ES 1.2）、空腹胰高血糖素水平更高（P = 0.002；ES 2.7）、MTT 时胰高血糖素反应更高（P = 0.0001；ES 2.6），并且整体胰岛素敏感性的 Matsuda 指数也有降低的趋势（P = 0.06；ES -0.5），与 CTRL 组相比。空腹胰岛素原/胰岛素比值和 MTT 时胰岛素原/胰岛素比值反应在两组之间相似（P > 0.05），而 SLE 组的胰岛素生成指数高于 CTRL 组（P = 0.02；ES = 0.9）。
我们发现尽管 SLE 患者的糖耐量正常且胰岛β细胞功能和骨骼肌 GLUT-4 转位正常，但仍存在双激素代谢异常，表现为 IR 增加和高胰高血糖素血症。为降低 SLE 患者发生 2 型糖尿病和心血管疾病的风险而改善胰岛素敏感性的策略可能需要的不仅仅是针对 IR。
