Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 De Soto St, Pittsburgh, PA, 15261, USA.
Diabetes and Lipid Research Clinic, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 3512 Fifth Avenue, Pittsburgh, PA, 15213, USA.
Acta Diabetol. 2020 Mar;57(3):271-278. doi: 10.1007/s00592-019-01422-6. Epub 2019 Sep 16.
The haptoglobin (Hp) 2-2 genotype has been shown to increase the risk of coronary artery disease, kidney dysfunction and mortality from cardiovascular and renal causes in type 1 diabetes (T1D). Similar associations, however, have not been observed in those without diabetes. As cardiac autonomic neuropathy (CAN) is a cardiovascular disease risk factor, we assessed the presence of an association between the Hp 2-2 genotype and CAN.
The study included 216 individuals with childhood-onset T1D and 200 individuals with normal glucose tolerance (NGT) of similar age and gender distribution to their counterparts with T1D. CAN was assessed using an electrocardiogram as an abnormal, age-specific, heart rate response to deep breathing. Multivariable logistic regression models were used to assess the association between the Hp 2-2 genotype and CAN.
Compared with NGT, participants with T1D had a similar proportion of Hp 2-2 carriers (41.5% vs. 32.0%, p = 0.05) but a greater CAN prevalence (28.2% vs. 5.0%, p < 0.0001). In multivariable logistic regression models, those carrying the Hp 2-2 genotype had significantly higher odds of CAN compared with Hp 1-1 or Hp 2-1 carriers (OR = 2.27, p = 0.01). The presence of T1D (OR = 4.20, p = 0.0003), hypertension (OR = 2.08, p = 0.03), eGFR (OR = 0.98, p = 0.01) and WBC count (OR = 1.21, p = 0.02) were also associated with CAN. There was no T1D by Hp interaction (p = 0.92), although in stratified analyses, the Hp-CAN association was significant only in T1D.
The Hp 2-2 genotype was independently associated with greater odds of CAN in T1D though no definitive conclusions could be made in NGT.
已有研究表明，在 1 型糖尿病（T1D）患者中，触珠蛋白（Hp）2-2 基因型可增加患冠状动脉疾病、肾功能障碍以及心血管和肾脏疾病导致的死亡率的风险。然而，在无糖尿病的人群中，并未观察到类似的关联。由于心脏自主神经病变（CAN）是心血管疾病的一个危险因素，我们评估了 Hp 2-2 基因型与 CAN 之间是否存在关联。
该研究纳入了 216 名儿童起病的 T1D 患者和 200 名血糖正常（NGT）的个体，这些 NGT 个体与 T1D 患者的年龄和性别分布相似。采用心电图评估 CAN，即通过年龄特异性的深呼吸测试评估异常的心率反应。采用多变量逻辑回归模型评估 Hp 2-2 基因型与 CAN 之间的关联。
与 NGT 相比，T1D 患者中 Hp 2-2 携带者的比例相似（41.5% vs. 32.0%，p=0.05），但 CAN 的患病率更高（28.2% vs. 5.0%，p<0.0001）。在多变量逻辑回归模型中，与 Hp 1-1 或 Hp 2-1 携带者相比，携带 Hp 2-2 基因型的个体发生 CAN 的几率显著更高（OR=2.27，p=0.01）。T1D（OR=4.20，p=0.0003）、高血压（OR=2.08，p=0.03）、估算肾小球滤过率（eGFR）（OR=0.98，p=0.01）和白细胞计数（OR=1.21，p=0.02）的存在也与 CAN 相关。未观察到 T1D 与 Hp 之间存在交互作用（p=0.92），但在分层分析中，仅在 T1D 中 Hp 与 CAN 之间存在关联。
尽管在 NGT 中无法得出明确的结论，但 Hp 2-2 基因型与 T1D 患者发生 CAN 的几率增加独立相关。
