Matsumoto Sachiko, Takebayashi Kohzo, Aso Yoshimasa
Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital, Koshigaya 343-8555, Japan.
Metabolism. 2006 Dec;55(12):1645-52. doi: 10.1016/j.metabol.2006.07.025.
Angiotensin II can influence adipocytokine levels in adipose tissue, but the association between aldosterone, which mediates the effect of angiotensin II, and adipocytokines has yet to be fully elucidated. This study was designed to investigate the effect of spironolactone, a representative aldosterone blocker, on adipocytokines such as adiponectin, visfatin, plasminogen activator inhibitor (PAI)-1 and tumor necrosis factor alpha in patients with type 2 diabetic nephropathy: the study included 33 patients, 22 of whom were randomly assigned to the spironolactone (50 mg/d) group and 11 to the amlodipine (2.5 mg/d) group. Data were collected at baseline and after 3 months of treatment and compared with baseline data for 25 age-matched healthy subjects. A significant decrease in plasminogen activator inhibitor 1 in the spironolactone group was observed (22.6 +/- 13.4 to 19.2 +/- 11.3 ng/mL, P =.0323), but this did not occur in the amlodipine group. Adiponectin and visfatin levels did not change in the spironolactone and amlodipine groups, but significant increases in these adipocytokines were found in a subgroup of patients in the spironolactone group with glycated hemoglobin A(1c) (HbA(1c)) 8.0% or greater (11.8 +/- 6.4 to 13.3 +/- 7.4 microg/mL, P = .0344; and 1.39 +/- 0.92 to 2.26 +/- 0.76 ng/mL, P =.0397, respectively). The tumor necrosis factor alpha level at baseline exceeded the lower detection limit of the assay in only 6 patients in the spironolactone group, and no change occurred in these patients. Moreover, neither spironolactone nor amlodipine therapy caused a change in high-sensitivity C-reactive protein or soluble CD40 ligand, but a significant decrease in the level of brain natriuretic peptide was found in the spironolactone group only. Furthermore, significant increases of HbA(1c), creatinine, potassium, and aldosterone levels and plasma renin activity, and a decrease in urinary albumin excretion were also observed only in the spironolactone group. The number of patients with HbA(1c) 8.0% or greater increased after spironolactone treatment. A significant decrease in systolic but not in diastolic blood pressure was observed in both treatment groups. In conclusion, our data suggest that in patients with type 2 diabetes mellitus complicated by diabetic nephropathy, spironolactone can decrease plasminogen activator inhibitor 1 and brain natriuretic peptide levels in addition to urinary albumin excretion, and systolic blood pressure, and that in patients with poor glycemic control, spironolactone can increase the levels of adiponectin and visfatin. However, the significant elevation of HbA(1c) levels by spironolactone should be emphasized.
血管紧张素II可影响脂肪组织中的脂肪细胞因子水平，但介导血管紧张素II作用的醛固酮与脂肪细胞因子之间的关联尚未完全阐明。本研究旨在探讨代表性醛固酮阻滞剂螺内酯对2型糖尿病肾病患者脂联素、内脂素、纤溶酶原激活物抑制剂（PAI）-1和肿瘤坏死因子α等脂肪细胞因子的影响：该研究纳入33例患者，其中22例被随机分配至螺内酯（50mg/d）组，11例被分配至氨氯地平（2.5mg/d）组。在基线及治疗3个月后收集数据，并与25名年龄匹配的健康受试者的基线数据进行比较。观察到螺内酯组纤溶酶原激活物抑制剂1显著降低（从22.6±13.4降至19.2±11.3ng/mL，P = 0.0323），但氨氯地平组未出现这种情况。螺内酯组和氨氯地平组的脂联素和内脂素水平未发生变化，但在螺内酯组糖化血红蛋白A1c（HbA1c）≥8.0%的患者亚组中，这些脂肪细胞因子显著升高（分别从11.8±6.4升至13.3±7.4μg/mL，P = 0.0344；从1.39±0.92升至2.26±0.76ng/mL，P = 0.0397）。螺内酯组仅6例患者的基线肿瘤坏死因子α水平超过检测下限，这些患者未发生变化。此外，螺内酯和氨氯地平治疗均未导致高敏C反应蛋白或可溶性CD40配体发生变化，但仅在螺内酯组发现脑钠肽水平显著降低。此外，仅在螺内酯组还观察到HbA1c、肌酐、钾和醛固酮水平以及血浆肾素活性显著升高，尿白蛋白排泄减少。螺内酯治疗后HbA1c≥8.0%的患者数量增加。两个治疗组均观察到收缩压显著降低，但舒张压未降低。总之，我们的数据表明，在合并糖尿病肾病的2型糖尿病患者中，螺内酯除了可降低尿白蛋白排泄和收缩压外，还可降低纤溶酶原激活物抑制剂1和脑钠肽水平，并且在血糖控制不佳的患者中，螺内酯可升高脂联素和内脂素水平。然而，应强调螺内酯可使HbA1c水平显著升高。
