Satoh Ken, Nagasawa Kan, Takebe Noriko, Kinno Hirofumi, Shozushima Masaharu, Onodera Ken, Oda Tomoyasu, Hasegawa Yutaka, Satoh Jo, Ishigaki Yasushi
Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Yahaba, Japan.
Department of Diabetes, Tohoku Medical and Pharmaceutical University, Wakabayashi Hospital, Sendai, Japan.
Diabetes Metab Syndr Obes. 2023 Jan 23;16:201-212. doi: 10.2147/DMSO.S387744. eCollection 2023.
AIMS/INTRODUCTION: Adiponectin is generally regarded as a beneficial molecule, protecting against insulin resistance and atherosclerosis, and its serum levels are low in individuals with obesity as well as in those with type 2 diabetes (T2DM). However, several clinical studies have shown associations between high adiponectin values and major health concerns. These conflicting findings are termed the "adiponectin paradox". Similarly, these paradoxical adiponectin elevations were observed in patients with diabetic microvascular complications. This cross-sectional study aimed to identify differences in factors, including adiponectin, related to diabetic vascular complications between non-obese and obese patients.
Study patients with T2DM were non-obese (n=197) or obese (n=197), matched by a propensity score model adjusted with age and gender. Independent factors for each of the microvascular complications were determined using multivariate logistic regression analyses.
The prevalence of nephropathy was high in obese T2DM patients. In addition to long diabetes duration, elevated adiponectin was a common characteristic of patients with microvascular complications. Logistic regression analyses for microvascular complications revealed adiponectin to be highly related to retinopathy (odds ratio [OR], 1.138; 95%confidence intervals [CI], 1.004-1.289, p<0.001), nephropathy (OR, 1.192; CI, 1.077-1.319, p<0.001) and neuropathy (OR, 1.217; CI, 1.071-1.384, p<0.001), in non-obese patients. In contrast, the association between adiponectin values and complications was modest in obese patients.
Adiponectin regulation in response to vascular damage differed between non-obese and obese patients, suggesting that adiponectin regulation is compromised by fat accumulation. Assuming that paradoxical elevation of adiponectin in vascular damage is a compensatory response, we speculate that responsive upregulation might be insufficient in obese patients. These newly-recognized differences in adiponectin values might lead to novel insights into adiponectin regulation and our understanding of the adiponectin paradox.
目的/引言：脂联素通常被视为一种有益分子，可预防胰岛素抵抗和动脉粥样硬化，肥胖个体以及2型糖尿病（T2DM）患者的血清脂联素水平较低。然而，多项临床研究表明脂联素值升高与主要健康问题之间存在关联。这些相互矛盾的发现被称为“脂联素悖论”。同样，在糖尿病微血管并发症患者中也观察到了这些矛盾的脂联素升高现象。这项横断面研究旨在确定非肥胖和肥胖患者中与糖尿病血管并发症相关的因素（包括脂联素）的差异。
研究对象为T2DM患者，分为非肥胖组（n = 197）和肥胖组（n = 197），通过年龄和性别调整的倾向评分模型进行匹配。使用多因素逻辑回归分析确定每种微血管并发症的独立因素。
肥胖T2DM患者的肾病患病率较高。除糖尿病病程长外，脂联素升高是微血管并发症患者的一个共同特征。微血管并发症的逻辑回归分析显示，脂联素与非肥胖患者的视网膜病变（优势比[OR]，1.138；95%置信区间[CI]，1.004 - 1.289，p < 0.001）、肾病（OR，1.192；CI，1.077 - 1.319，p < 0.001）和神经病变（OR，1.217；CI，1.071 - 1.384，p < 0.001）高度相关。相比之下，肥胖患者中脂联素值与并发症之间的关联较弱。
非肥胖和肥胖患者对血管损伤的脂联素调节存在差异，这表明脂联素调节受到脂肪堆积的影响。假设血管损伤中脂联素的矛盾升高是一种代偿反应，我们推测肥胖患者的反应性上调可能不足。这些新认识到的脂联素值差异可能会为脂联素调节以及我们对脂联素悖论的理解带来新的见解。
