Department of Internal Medicine, Section Pharmacology, Vascular Medicine, Cardiovascular Research School COEUR, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
Department of Internal Medicine, Section Pharmacology, Vascular Medicine, Cardiovascular Research School COEUR, Erasmus MC, University Medical Center Rotterdam, the Netherlands.
J Diabetes Complications. 2021 Oct;35(10):107993. doi: 10.1016/j.jdiacomp.2021.107993. Epub 2021 Jul 15.
Dyslipidemia precedes type 2 diabetes (T2D) and worsens with increasing glucose intolerance. First degree relatives of T2D patients have an increased risk to develop dyslipidemia and glucose intolerance. The aim of the present study was to assess the relation between the development of dyslipidemia and glucose intolerance in first-degree relatives of T2D patients.
Fasting lipoprotein profiles were determined by density gradient ultracentrifugation in T2D patients and their first-degree relatives (42 Caucasians and 33 South Asians), and in 29 normoglycemic controls from non-T2D families. Glucose tolerance, insulin sensitivity index (ISI) and insulin disposition index (DI) were assessed by an extended, frequently sampled oral glucose tolerance test (OGTT), and fractional insulin synthesis rate (FSR) was measured by C-leucine enrichment in urinary C-peptide during the OGTT.
Of the first-degree relatives, 40, 16 and 19 had NGT, prediabetes and T2D, respectively. NGT family members had lower plasma HDL-cholesterol (HDLC) (1.34 ± 0.07 vs 1.58 ± 0.06 mmol/L; p = 0.015), HDL-C (0.41 ± 0.05 vs 0.57 ± 0.05 mmol/L; p = 0.021) and HDL-C (0.62 ± 0.03 vs 0.72 ± 0.02 mmol/L; p = 0.043) than controls. HDL-C levels tended to decrease with increasing glucose intolerance state. In South Asians, buoyant LDL-C levels decreased with increasing glucose intolerance state (p = 0.006). In South Asian families, HDL-C correlated with both ISI and DI (β 0.42; p = 0.04 and β 0.53; p = 0.01, respectively), whereas HDL-C and HDL-C levels correlated with DI (β 0.64; p = 0.002 and β 0.57; p = 0.005, respectively). HDL-C and plasma triglyceride correlated with FSR (β 0.48; p = 0.033 and β -0.50; p = 0.029, respectively).
Low HDL-C and HDL-C levels are present in NGT first-degree relatives of T2D patients, and HDL-C tend to decrease further with increasing glucose intolerance. In South Asian families HDL-C and HDL-C levels linked predominantly to deteriorating beta cell function.
血脂异常先于 2 型糖尿病（T2D）发生，并随着葡萄糖耐量的逐渐恶化而加重。T2D 患者的一级亲属发生血脂异常和葡萄糖耐量受损的风险增加。本研究旨在评估 T2D 患者一级亲属中血脂异常和葡萄糖耐量受损的发展之间的关系。
在 T2D 患者及其一级亲属（42 名高加索人和 33 名南亚人）和 29 名非 T2D 家族的正常血糖对照者中，通过密度梯度超速离心法测定空腹脂蛋白谱。通过扩展的、频繁采样的口服葡萄糖耐量试验（OGTT）评估葡萄糖耐量、胰岛素敏感指数（ISI）和胰岛素分泌指数（DI），并通过 OGTT 期间尿 C 肽中 C-亮氨酸的富集测量胰岛素合成率（FSR）。
一级亲属中，分别有 40、16 和 19 人具有 NGT、前驱糖尿病和 T2D。NGT 家族成员的血浆高密度脂蛋白胆固醇（HDLC）（1.34±0.07 与 1.58±0.06mmol/L；p=0.015）、HDL-C（0.41±0.05 与 0.57±0.05mmol/L；p=0.021）和 HDL-C（0.62±0.03 与 0.72±0.02mmol/L；p=0.043）均较低。HDL-C 水平随葡萄糖耐量状态的增加而降低。在南亚人群中，漂浮 LDL-C 水平随葡萄糖耐量状态的增加而降低（p=0.006）。在南亚家庭中，HDL-C 与 ISI 和 DI 均相关（β0.42；p=0.04 和 β0.53；p=0.01，分别），而 HDL-C 和 HDL-C 水平与 DI 相关（β0.64；p=0.002 和 β0.57；p=0.005，分别）。HDL-C 和血浆甘油三酯与 FSR 相关（β0.48；p=0.033 和 β-0.50；p=0.029，分别）。
T2D 患者的一级亲属中存在低 HDL-C 和 HDL-C 水平，且随着葡萄糖耐量的逐渐恶化，HDL-C 水平进一步降低。在南亚家庭中，HDL-C 和 HDL-C 水平主要与胰岛β细胞功能恶化有关。
