Kato Kenichi, Osawa Haruhiko, Ochi Masaaki, Kusunoki Yukiko, Ebisui Osamu, Ohno Keizo, Ohashi Jun, Shimizu Ikki, Fujii Yasuhisa, Tanimoto Mitsune, Makino Hideichi
Ehime Prefectural Hospital, Ehime, Japan.
Clin Endocrinol (Oxf). 2008 Mar;68(3):442-9. doi: 10.1111/j.1365-2265.2007.03063.x. Epub 2007 Oct 29.
Adiponectin is secreted specifically from adipocytes, and improves insulin sensitivity. Of its isoforms, the high molecular weight (HMW) complex is thought to be the most active. The aim of this study was to determine the relationship between serum total or HMW adiponectin and diabetic microangiopathy.
DESIGN, PATIENTS AND MEASUREMENTS: We analysed 198 Japanese patients with type 2 diabetes mellitus (T2DM) whose fasting serum samples were available. Serum total adiponectin and HMW adiponectin were measured using an enzyme-linked immunosorbent assay (ELISA).
Serum total adiponectin was found to have increased in the advanced stages of diabetic retinopathy (mean +/- SE, none, 6.9 +/- 0.3; simple, 8.3 +/- 1.0; preproliferative, 8.4 +/- 0.8; proliferative, 12 +/- 1.1 mg/l; anovaP = 0.0004) and nephropathy (stage I, 7.0 +/- 0.3; II, 7.7 +/- 0.5; III, 9.5 +/- 0.9; IV, 16 +/- 4.5 mg/l, P < 0.0001). Similarly, serum HMW adiponectin had increased in the advanced stages of retinopathy (3.7 +/- 0.2, 4.6 +/- 0.5, 4.6 +/- 0.6 and 6.9 +/- 0.8 mg/l, respectively, P = 0.0005) and nephropathy (3.7 +/- 0.2, 4.3 +/- 0.4, 5.3 +/- 0.7 and 7.9 +/- 2.2 mg/l, respectively, P = 0.0007). Neither serum total nor HMW adiponectin was correlated with neuropathy. The HMW/total adiponectin ratio was not correlated with microangiopathy. Multiple regression analysis revealed that serum total and HMW adiponectin were independent factors for retinopathy stage (P = 0.0055 and P = 0.0027, respectively) and nephropathy stage (P = 0.0003 and P = 0.0018, respectively), when adjusted for age, gender, body mass index (BMI) and the duration of T2DM. This correlation remained significant when serum creatinine (or estimated glomerular filtration rate) and hypertension were added as independent variables. Treatment with thiazolidinediones (TZDs) did not affect these findings.
Serum total adiponectin and HMW adiponectin were found to be positively correlated with the severity of retinopathy and nephropathy but not with neuropathy in T2DM.
脂联素由脂肪细胞特异性分泌，可改善胰岛素敏感性。在其多种亚型中，高分子量（HMW）复合物被认为活性最强。本研究旨在确定血清总脂联素或HMW脂联素与糖尿病微血管病变之间的关系。
设计、患者与测量方法：我们分析了198例可获取空腹血清样本的日本2型糖尿病（T2DM）患者。采用酶联免疫吸附测定（ELISA）法测量血清总脂联素和HMW脂联素。
发现在糖尿病视网膜病变晚期血清总脂联素升高（均值±标准误，无病变，6.9±0.3；单纯性病变，8.3±1.0；增殖前期，8.4±0.8；增殖期，12±1.1mg/L；方差分析P = 0.0004）以及肾病（I期，7.0±0.3；II期，7.7±0.5；III期，9.5±0.9；IV期，16±4.5mg/L，P < 0.0001）。同样，血清HMW脂联素在视网膜病变晚期（分别为3.7±0.2、4.6±0.5、4.6±0.6和6.9±0.8mg/L，P = 0.0005）和肾病（分别为3.7±0.2、4.3±0.4、5.3±0.7和7.9±2.2mg/L，P = 0.0007）也升高。血清总脂联素和HMW脂联素均与神经病变无关。HMW/总脂联素比值与微血管病变无关。多元回归分析显示，在调整年龄、性别、体重指数（BMI）和T2DM病程后，血清总脂联素和HMW脂联素分别是视网膜病变分期（P = 0.0055和P = 0.0027）和肾病分期（P = 0.0003和P = 0.0018）的独立因素。当将血清肌酐（或估计肾小球滤过率）和高血压作为自变量加入时，这种相关性仍然显著。噻唑烷二酮类药物（TZDs）治疗不影响这些结果。
发现血清总脂联素和HMW脂联素与T2DM患者视网膜病变和肾病的严重程度呈正相关，但与神经病变无关。
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