Division of Endocrinology & Nutrition, St-Luc University Clinics and Institute for Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium.
Division of Cardiology, St-Luc University Clinics and Cardiovascular Research Center, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium.
J Diabetes. 2019 Apr;11(4):301-308. doi: 10.1111/1753-0407.12840. Epub 2018 Sep 23.
This study investigated the isolated and crossed effects of familial histories (FH) of early onset coronary heart disease (EOCHD) and type 2 diabetes mellitus (T2DM) on diabetic offspring.
The cardiometabolic phenotype of 1098 T2DM patients was analyzed according to an FH of T2DM and/or EOCHD, including body composition, fasting insulinemia, insulin sensitivity, β-cell function (BCF), lipids, lipoprotein(a), high-density lipoprotein (HDL) number and functionality, and micro- and macrovascular complications.
Mean age and T2DM duration were 69 and 18 years, respectively; 64% of patients were male, 50% (n = 550) had an FH of T2DM (DM[+]), and 13% (n = 145) had an FH of EOCHD (EOCHD[+]). Four subgroups were generated by crossing FHs: DM[-]EOCHD[-] (44%; n = 487); DM[+]EOCHD[-] (42%; n = 466); DM[-]EOCHD[+] (6%; n = 61); and DM[+]EOCHD[+] (8%; n = 84). Microangiopathies were highest among DM[+] patients, whose BCF was deteriorating the fastest. More numerous/dysfunctional HDLs characterized EOCHD[+] patients. The greatest frequency of cardiovascular disease (CVD; 69%) was observed in DM[-]EOCHD[+] patients, whose lipoprotein(a) and insulinemia were also highest (81 nmol/L and 140 pmol/L, respectively). The lowest frequency of CVD (30%) was observed in DM[+]EOCHD[-] patients.
Familial histories of DM and EOCHD predispose to increased microvascular and macrovascular risk, respectively, with hyperinsulinemia, lipoprotein(a), and dysfunctional HDLs standing out as mediators of the inherited macrovascular risk. Yet, crossing these FHs did not randomly redistribute vascular risk, because patients with parental T2DM had fewer macrovascular diseases regardless of familial EOCHD. The odds of being left-handed were unexpectedly greater in patients with crossed parental histories.
本研究调查了早发性冠心病（EOCHD）和 2 型糖尿病（T2DM）家族史对糖尿病患者的单独和交互影响。
根据 T2DM 和/或 EOCHD 的家族史，分析了 1098 例 T2DM 患者的心脏代谢表型，包括身体成分、空腹胰岛素血症、胰岛素敏感性、β细胞功能（BCF）、血脂、脂蛋白（a）、高密度脂蛋白（HDL）数量和功能以及微血管和大血管并发症。
平均年龄和 T2DM 病程分别为 69 岁和 18 年；64%的患者为男性，50%（n=550）有 T2DM 的家族史（DM[+]），13%（n=145）有 EOCHD 的家族史（EOCHD[+]）。通过交叉 FH 生成了四个亚组：DM[-]EOCHD[-]（44%；n=487）；DM[+]EOCHD[-]（42%；n=466）；DM[-]EOCHD[+]（6%；n=61）和 DM[+]EOCHD[+]（8%；n=84）。DM[+]患者微血管并发症最高，BCF 恶化最快。更多数量/功能异常的 HDL 特征是 EOCHD[+]患者。DM[-]EOCHD[+]患者心血管疾病（CVD；69%）的发生率最高，其脂蛋白（a）和胰岛素血症也最高（81 nmol/L 和 140 pmol/L）。DM[+]EOCHD[-]患者 CVD 的发生率最低（30%）。
DM 和 EOCHD 的家族史分别使微血管和大血管风险增加，高胰岛素血症、脂蛋白（a）和功能异常的 HDL 是遗传大血管风险的主要介质。然而，这些 FH 的交叉并没有随机重新分配血管风险，因为无论是否存在家族性 EOCHD，有父母 2 型糖尿病的患者患大血管疾病的几率都较低。令人意外的是，具有交叉父母病史的患者中惯用左手的比例更高。
