Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Caress Sapporo Hokko Memorial Clinic, Sapporo, Japan.
Front Endocrinol (Lausanne). 2020 Sep 23;11:575557. doi: 10.3389/fendo.2020.575557. eCollection 2020.
Among fatty acid-binding proteins (FABPs), secreted forms of FABP4 and FABP5, which are expressed in adipocytes and macrophages, act as bioactive molecules. We investigated concentrations of FABP4 and FABP5 in patients with type 2 diabetes mellitus. As a sub-analysis study of the Randomized Evaluation of Anagliptin vs. Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial, 256 patients (male/female: 146/110, age: 68 ± 10 years) with type 2 diabetes mellitus and dyslipidemia who were receiving statin therapy were recruited. Patients who had been treated with a thiazolidinedione were excluded. Several drugs which may modulate FABP4 levels including statins, dipeptidyl peptidase-4 inhibitors and angiotensin II receptor blockers had been administered in 100, 81, and 51% of the recruited patients, respectively. The level of FABP4, but not that of FABP5, was significantly higher in females than in males. Multivariable linear regression analysis demonstrated that waist circumference (β = 0.21), estimated glomerular filtration rate (β = -0.31), triglycerides (β = 0.16), and FABP5 (β = 0.39) were independent predictors of FABP4 level after adjusting age and sex. On the other hand, FABP5 level was independently associated with levels of FABP4 (β = 0.57) and high-density lipoprotein (HDL) cholesterol (β = -0.12). Concentrations of FABP4 and FABP5 are independent predictors of each other in patients with type 2 diabetes mellitus. There are distinct independent associations of FABP4 with renal dysfunction, adiposity and hypertriglyceridemia and there is a distinct independent association of FABP5 with a low HDL cholesterol level in type 2 diabetic patients with dyslipidemia at high risks for cardiovascular disease who are receiving statin therapy.
在脂肪酸结合蛋白（FABP）中，脂肪细胞和巨噬细胞表达的分泌型 FABP4 和 FABP5 是生物活性分子。我们研究了 2 型糖尿病患者的 FABP4 和 FABP5 浓度。该研究为随机评估阿格列汀与西格列汀对糖尿病患者低密度脂蛋白胆固醇影响的试验（REASON）的亚分析研究，共纳入 256 例（男/女：146/110，年龄：68 ± 10 岁）接受他汀类药物治疗的 2 型糖尿病伴血脂异常患者，排除曾接受噻唑烷二酮类药物治疗的患者。分别有 100%、81%和 51%的入组患者正在使用可能调节 FABP4 水平的药物，包括他汀类药物、二肽基肽酶-4 抑制剂和血管紧张素 II 受体阻滞剂。女性的 FABP4 水平明显高于男性，而 FABP5 水平则无性别差异。多变量线性回归分析表明，校正年龄和性别后，腰围（β=0.21）、估算肾小球滤过率（β=-0.31）、三酰甘油（β=0.16）和 FABP5（β=0.39）是 FABP4 水平的独立预测因素。另一方面，FABP5 水平与 FABP4（β=0.57）和高密度脂蛋白（HDL）胆固醇（β=-0.12）水平独立相关。在 2 型糖尿病患者中，FABP4 和 FABP5 浓度是彼此的独立预测因素。FABP4 与肾功能障碍、肥胖和高三酰甘油血症有明显的独立关联，而 FABP5 与他汀类药物治疗的心血管疾病高危血脂异常 2 型糖尿病患者的低 HDL 胆固醇水平有明显的独立关联。
