Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy.
Cardiovasc Diabetol. 2013 Jul 5;12:98. doi: 10.1186/1475-2840-12-98.
Previous reports have clearly indicated a significant relationship between hemoglobin (Hb) A1c change from one visit to the next and microvascular complications, especially nephropathy (albuminuria and albuminuric chronic kidney disease, CKD). In contrast, data on macrovascular disease are less clear. This study was aimed at examining the association of HbA1c variability with cardiovascular disease (CVD) in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study.
Serial (3-5) HbA1c values obtained during the 2-year period preceding recruitment, including that obtained at the enrolment, were available from 8,290 subjects from 9 centers (out of 15,773 patients from 19 centers). Average HbA1c and HbA1c variability were calculated as the intra-individual mean (HbA1c-MEAN) and standard deviation (HbA1c-SD), respectively, of 4.52 ± 0.76 values. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events. Diabetic retinopathy (DR) was assessed by dilated fundoscopy. CKD was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate, as calculated from serum creatinine.
HbA1c-MEAN, but not HbA1c-SD, was significantly higher (P<0.0001) in subjects with history of any CVD (n. 2,133, 25.7%) than in those without CVD (n. 6,157, 74.3%). Median and interquartile range were 7.78 (7.04-8.56) and 7.49 (6.81-8.31), respectively, for HbA1c-MEAN, and 0.47 (0.29-0.75) and 0.46 (0.28-0.73), respectively, for HbA1c-SD. Logistic regression analyses showed that HbA1c-MEAN, but not HbA1c-SD (and independent of it), was a significant correlate of any CVD. Similar findings were observed in subjects with versus those without any coronary or cerebrovascular event or myocardial infarction. Conversely, none of these measures were associated with stroke, whereas both correlated with any lower limb vascular event and HbA1c-SD alone with ulceration/gangrene. All these associations were independent of known CVD risk factors and microvascular complications (DR and CKD).
In patients with type 2 diabetes, HbA1c variability has not a major impact on macrovascular complications, at variance with average HbA1c, an opposite finding as compared with microvascular disease, and particularly nephropathy.
ClinicalTrials.Gov NCT00715481.
先前的报告清楚地表明，血红蛋白（Hb）A1c 从一次就诊到下一次就诊的变化与微血管并发症，尤其是肾病（蛋白尿和白蛋白尿性慢性肾脏病，CKD）之间存在显著关系。相比之下，关于大血管疾病的数据则不太清楚。本研究旨在检查 HbA1c 变异性与来自肾脏不足和心血管事件（RIACE）意大利多中心研究的 2 型糖尿病大队列中心血管疾病（CVD）之间的关联。
在招募前的 2 年期间，可获得 9 个中心的 8290 名受试者的（3-5）次 HbA1c 值，包括招募时获得的 HbA1c 值。平均 HbA1c 和 HbA1c 变异性分别计算为个体内平均值（HbA1c-MEAN）和标准偏差（HbA1c-SD），分别为 4.52±0.76 个值。通过记录先前记录的主要急性事件，从病史中评估现患 CVD、总血管床和各血管床的 CVD。通过散瞳眼底检查评估糖尿病视网膜病变（DR）。根据蛋白尿（通过免疫比浊法或免疫散射比浊法测量）和估计肾小球滤过率（根据血清肌酐计算）定义 CKD。
HbA1c-MEAN （P<0.0001）在有任何 CVD 病史（n=2133，25.7%）的受试者中显著高于无 CVD 病史（n=6157，74.3%）的受试者。中位数和四分位距分别为 7.78（7.04-8.56）和 7.49（6.81-8.31），分别为 HbA1c-MEAN，0.47（0.29-0.75）和 0.46（0.28-0.73），分别为 HbA1c-SD。Logistic 回归分析表明，HbA1c-MEAN 是任何 CVD 的显著相关因素，但不是 HbA1c-SD（并且独立于它）。在有或没有任何冠状动脉或脑血管事件或心肌梗死的受试者中均观察到类似的发现。相反，这些措施均与中风无关，而所有这些措施均与任何下肢血管事件相关，HbA1c-SD 与溃疡/坏疽相关。所有这些关联均独立于已知的 CVD 危险因素和微血管并发症（DR 和 CKD）。
在 2 型糖尿病患者中，HbA1c 变异性对大血管并发症的影响不大，与平均 HbA1c 相反，与微血管疾病，特别是肾病的情况相反。
ClinicalTrials.gov NCT00715481。
