Objective

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.

Research design and methods

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 ¹³C-leucine enrichment in urinary C-peptide during the OGTT.

Results

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), HDL₂-C (0.41 ± 0.05 vs 0.57 ± 0.05 mmol/L; p = 0.021) and HDL₃-C (0.62 ± 0.03 vs 0.72 ± 0.02 mmol/L; p = 0.043) than controls. HDL₂-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 HDL₂-C and HDL₃-C levels correlated with DI (β 0.64; p = 0.002 and β 0.57; p = 0.005, respectively). HDL₂-C and plasma triglyceride correlated with FSR (β 0.48; p = 0.033 and β −0.50; p = 0.029, respectively).

Conclusions

Low HDL₂-C and HDL₃-C levels are present in NGT first-degree relatives of T2D patients, and HDL₂-C tend to decrease further with increasing glucose intolerance. In South Asian families HDL₂-C and HDL₃-C levels linked predominantly to deteriorating beta cell function.

中文翻译：

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HDL与有2型糖尿病风险的南亚家庭的胰岛素抵抗和β细胞功能障碍有关

客观的

血脂异常先于 2 型糖尿病 (T2D)，并随着葡萄糖耐受不良的增加而恶化。T2D 患者的一级亲属发生血脂异常和葡萄糖耐受不良的风险增加。本研究的目的是评估 T2D 患者的一级亲属发生血脂异常与葡萄糖耐受不良之间的关系。

研究设计与方法

通过密度梯度超速离心法测定 T2D 患者及其一级亲属（42 名白种人和 33 名南亚人）以及来自非 T2D 家庭的 29 名血糖正常对照者的空腹脂蛋白谱。葡萄糖耐量、胰岛素敏感性指数 (ISI) 和胰岛素处置指数 (DI) 通过扩展的、频繁采样的口服葡萄糖耐量试验 (OGTT) 进行评估，而胰岛素合成率 (FSR) 则通过尿液中¹³ C-亮氨酸的富集来测量OGTT 期间的 C 肽。

结果

在一级亲属中，分别有 40、16 和 19 人患有 NGT、前驱糖尿病和 T2D。NGT 家族成员的血浆 HDL-胆固醇 (HDL C) (1.34 ± 0.07 vs 1.58 ± 0.06 mmol/L; p  = 0.015)、HDL ₂ -C (0.41 ± 0.05 vs 0.57 ± 0.05 mmol/L; p  = 0.021)和 HDL ₃ -C (0.62 ± 0.03 vs 0.72 ± 0.02 mmol/L; p  = 0.043) 比对照。HDL ₂ -C 水平倾向于随着葡萄糖不耐受状态的增加而降低。在南亚人中，活跃的 LDL-C 水平随着葡萄糖不耐受状态的增加而降低 ( p  = 0.006)。在南亚家庭中，HDL-C 与 ISI 和 DI 相关（β 0.42；p  = 0.04 和 β 0.53；p = 0.01），而 HDL ₂ -C 和 HDL ₃ -C 水平与 DI 相关（分别为β 0.64；p  = 0.002 和 β 0.57；p  = 0.005）。HDL ₂ -C 和血浆甘油三酯与 FSR 相关（分别为 β 0.48；p  = 0.033 和 β -0.50；p  = 0.029）。

结论

T2D 患者的 NGT 一级亲属中存在低 HDL ₂ -C 和 HDL _{3 -C 水平，并且 HDL 2} -C 会随着葡萄糖耐受性的增加而进一步降低。在南亚家庭中，HDL ₂ -C 和 HDL ₃ -C 水平主要与恶化的 β 细胞功能相关。