高密度脂蛋白胆固醇和载脂蛋白 A-I 可预测已确诊 2 型糖尿病患者的长期血糖进展。
HDL-C and HDL-C/ApoA-I predict long-term progression of glycemia in established type 2 diabetes.
机构信息
NHMRC Clinical Trials Centre, Sydney Medical School, University of Sydney, Sydney, Australia
NHMRC Clinical Trials Centre, Sydney Medical School, University of Sydney, Sydney, Australia.
出版信息
Diabetes Care. 2014 Aug;37(8):2351-8. doi: 10.2337/dc13-2738. Epub 2014 May 7.
OBJECTIVE
Low HDL cholesterol (HDL-C) and small HDL particle size may directly promote hyperglycemia. We evaluated associations of HDL-C, apolipoprotein A-I (apoA-I), and HDL-C/apoA-I with insulin secretion, insulin resistance, HbA1c, and long-term glycemic deterioration, reflected by initiation of pharmacologic glucose control.
RESEARCH DESIGN AND METHODS
The 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study followed 9,795 type 2 diabetic subjects. We calculated baseline associations of fasting HDL-C, apoA-I, and HDL-C/apoA-I with HbA1c and, in those not taking exogenous insulin (n = 8,271), with estimated β-cell function (homeostasis model assessment of β-cell function [HOMA-B]) and insulin resistance (HOMA-IR). Among the 2,608 subjects prescribed lifestyle only, Cox proportional hazards analysis evaluated associations of HDL-C, apoA-I, and HDL-C/apoA-I with subsequent initiation of oral hypoglycemic agents (OHAs) or insulin.
RESULTS
Adjusted for age and sex, baseline HDL-C, apoA-I, and HDL-C/apoA-I were inversely associated with HOMA-IR (r = -0.233, -0.134, and -0.230; all P < 0.001; n = 8,271) but not related to HbA1c (all P > 0.05; n = 9,795). ApoA-I was also inversely associated with HOMA-B (r = -0.063; P = 0.002; n = 8,271) adjusted for age, sex, and HOMA-IR. Prospectively, lower baseline HDL-C and HDL-C/apoA-I levels predicted greater uptake (per 1-SD lower: hazard ratio [HR] 1.13 [CI 1.07-1.19], P < 0.001; and HR 1.16 [CI 1.10-1.23], P < 0.001, respectively) and earlier uptake (median 12.9 and 24.0 months, respectively, for quartile 1 vs. quartile 4; both P < 0.01) of OHAs and insulin, with no difference in HbA1c thresholds for initiation (P = 0.87 and P = 0.81). Controlling for HOMA-IR and triglycerides lessened both associations, but HDL-C/apoA-I remained significant.
CONCLUSIONS
HDL-C, apoA-I, and HDL-C/apoA-I were associated with concurrent insulin resistance but not HbA1c. However, lower HDL-C and HDL-C/apoA-I predicted greater and earlier need for pharmacologic glucose control.
目的
低水平高密度脂蛋白胆固醇（HDL-C）和小粒径高密度脂蛋白颗粒可能直接促进高血糖。我们评估了 HDL-C、载脂蛋白 A-I（apoA-I）和 HDL-C/apoA-I 与胰岛素分泌、胰岛素抵抗、糖化血红蛋白（HbA1c）以及长期血糖恶化的关系，反映为启动药物控制血糖。
研究设计和方法
为期 5 年的非诺贝特干预和糖尿病事件降低（FIELD）研究纳入了 9795 例 2 型糖尿病患者。我们计算了空腹 HDL-C、apoA-I 和 HDL-C/apoA-I 与 HbA1c 的基线关联，并且在未服用外源性胰岛素的患者（n=8271）中，与胰岛素β细胞功能（稳态模型评估的β细胞功能[HOMA-B]）和胰岛素抵抗（HOMA-IR）的关系。在 2608 例仅接受生活方式治疗的患者中，Cox 比例风险分析评估了 HDL-C、apoA-I 和 HDL-C/apoA-I 与随后开始使用口服降糖药（OHA）或胰岛素的关系。
结果
校正年龄和性别后，基线 HDL-C、apoA-I 和 HDL-C/apoA-I 与 HOMA-IR 呈负相关（r=-0.233、-0.134 和-0.230；均 P<0.001；n=8271），但与 HbA1c 无关（均 P>0.05；n=9795）。apoA-I 也与 HOMA-B 呈负相关（r=-0.063；P=0.002；n=8271），校正年龄、性别和 HOMA-IR 后仍如此。前瞻性研究显示，较低的基线 HDL-C 和 HDL-C/apoA-I 水平预示着更大的药物治疗需求（每降低 1-SD：风险比[HR]1.13[95%CI 1.07-1.19]，P<0.001；和 HR 1.16[95%CI 1.10-1.23]，P<0.001）和更早的药物治疗需求（四分位数 1 与四分位数 4 相比，中位数分别为 12.9 和 24.0 个月；均 P<0.01），而启动药物治疗的 HbA1c 阈值没有差异（P=0.87 和 P=0.81）。校正 HOMA-IR 和甘油三酯后，这两种关联均有所减弱，但 HDL-C/apoA-I 仍有显著意义。
结论
HDL-C、apoA-I 和 HDL-C/apoA-I 与同时存在的胰岛素抵抗有关，但与 HbA1c 无关。然而，较低的 HDL-C 和 HDL-C/apoA-I 预示着更大和更早的药物控制血糖的需求。
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