Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction The Maastricht Study
Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction The Maastricht Study
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DOI：
10.1161/circulationaha.116.023446
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发表时间：
2016-11-01
期刊：
影响因子：
37.8
通讯作者：
Stehouwer, Coen D. A.
中科院分区：
文献类型：
--
作者：
Sorensen, Ben M.;Houben, Alfons J. H. M.;Stehouwer, Coen D. A.
背景：2型糖尿病（T2 DM）与心血管疾病风险增加相关。这可以部分由大动脉功能障碍来解释，这种情况已经发生在糖尿病前期（“滴答作响的时钟假说”）。类似的现象是否也适用于微血管功能障碍尚不清楚。因此，我们检验了微血管功能障碍在糖尿病前期已经存在，并且在T2 DM中更严重的假设。为此，我们研究了前驱糖尿病、T2 DM和高血糖与微血管功能的关系，微血管功能测量为闪烁光诱导的视网膜小动脉扩张和热诱导的皮肤充血。在马斯特里赫特研究中，一项T2 DM富集人群队列研究（n=2213，51%男性，年龄[平均值+/-标准差] 59.7 +/- 8.2岁），我们测定了闪烁光诱导的视网膜小动脉%-扩张（动态血管分析仪），热诱导皮肤充血%（激光多普勒血流仪）和葡萄糖代谢状态（口服葡萄糖耐量试验;正常葡萄糖代谢[n=1269]、前驱糖尿病[n=335]或T2 DM [n=609]）。通过多变量回归分析对差异进行评估，调整了年龄、性别、体重指数、吸烟、体力活动、收缩压、血脂、视网膜病变、估计肾小球滤过率、（微量）白蛋白尿、调脂和降压药物的使用以及既往心血管疾病。正常葡萄糖代谢组的视网膜小动脉扩张%为（平均值±标准差）3.4 ± 2.8，前驱糖尿病组为3.0 ± 2.7，T2 DM组为2.3 ± 2.6。校正分析显示，与正常葡萄糖代谢相比，糖尿病前期（B=-0.20，95%置信区间-0.56至0.15）的小动脉扩张%较低，T2 DM（B=-0.61 [-0.97至0.25]）进一步恶化（趋势P =0.001）。正常葡萄糖代谢的皮肤充血%为（平均值+/-标准差）1235 +/- 810，前驱糖尿病为1109 +/- 748，T2 DM为937 +/- 683。校正分析显示，与正常葡萄糖代谢相比，糖尿病前期（B=-46 [-163至72]）的充血%较低，T2 DM（B=-184 [-297至71]）进一步恶化（趋势P =0.001）。此外，在完全校正的模型中，较高的糖化血红蛋白A1 c和空腹血糖与较低的视网膜小动脉扩张%和皮肤充血%相关（糖化血红蛋白A1 c，标准化B=-0.10 [-0.15 to -0.05]，P< 0.001，标准化B=-0.13 [-0.19 to -0.07]，P <0.001）。
BACKGROUND: Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes ("ticking clock hypothesis"). Whether a similar phenomenon also applies to microvascular dysfunction is not known. We therefore tested the hypothesis that microvascular dysfunction is already present in prediabetes and is more severe in T2DM. To do so, we investigated the associations of prediabetes, T2DM, and measures of hyperglycemia with microvascular function measured as flicker light-induced retinal arteriolar dilation and heat-induced skin hyperemia.METHODS: In the Maastricht Study, a T2DM-enriched population-based cohort study (n=2213, 51% men, aged [mean +/- standard deviation] 59.7 +/- 8.2 years), we determined flicker light-induced retinal arteriolar %-dilation (Dynamic Vessel Analyzer), heat-induced skin %-hyperemia (laser-Doppler flowmetry), and glucose metabolism status (oral glucose tolerance test; normal glucose metabolism [n=1269], prediabetes [n=335], or T2DM [n=609]). Differences were assessed with multivariable regression analyses adjusted for age, sex, body mass index, smoking, physical activity, systolic blood pressure, lipid profile, retinopathy, estimated glomerular filtration rate, (micro) albuminuria, the use of lipid-modifying and blood pressure-lowering medication, and prior cardiovascular disease.RESULTS: Retinal arteriolar %-dilation was (mean +/- standard deviation) 3.4 +/- 2.8 in normal glucose metabolism, 3.0 +/- 2.7 in prediabetes, and 2.3 +/- 2.6 in T2DM. Adjusted analyses showed a lower arteriolar %-dilation in prediabetes (B=-0.20, 95% confidence interval -0.56 to 0.15) with further deterioration in T2DM (B=-0.61 [-0.97 to -0.25]) versus normal glucose metabolism (P for trend=0.001). Skin %-hyperemia was (mean +/- standard deviation) 1235 +/- 810 in normal glucose metabolism, 1109 +/- 748 in prediabetes, and 937 +/- 683 in T2DM. Adjusted analyses showed a lower %-hyperemia in prediabetes (B=-46 [-163 to 72]) with further deterioration in T2DM (B=-184 [-297 to -71]) versus normal glucose metabolism (P for trend=0.001). In addition, higher glycohemoglobin A1c and fasting plasma glucose were associated with lower retinal arteriolar %-dilation and skin %-hyperemia in fully adjusted models (for glycohemoglobin A1c, standardized B=-0.10 [-0.15 to -0.05], P< 0.001 and standardized B=-0.13 [-0.19 to -0.07], P