Time Course and Mechanisms of Circulating Progenitor Cell Reduction in the Natural History of Type 2 Diabetes
Time Course and Mechanisms of Circulating Progenitor Cell Reduction in the Natural History of Type 2 Diabetes
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DOI：
10.2337/dc09-1999
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发表时间：
2010-05-01
期刊：
影响因子：
16.2
通讯作者：
Avogaro, Angelo
中科院分区：
文献类型：
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作者：
Fadini, Gian Paolo;Boscaro, Elisa;Avogaro, Angelo
目的：骨髓来源的循环祖细胞减少被认为是2型糖尿病心血管疾病的一种新机制。本研究旨在描述2型糖尿病自然病程中祖细胞减少的程度和潜在机制，研究设计和方法-我们确定了425个个体，根据碳水化合物代谢状态分为7类（正常葡萄糖耐量[NGT]，空腹血糖受损，葡萄糖耐量受损[IGT]，和新诊断的2型糖尿病）和糖尿病持续时间（0-9、10-19和>= 20年）。这些类别被认为是2型糖尿病发展和进展的自然史的理想描述。我们通过流式细胞术测量CD 34+和CD 34 +KDR+祖细胞。我们还评估了祖细胞在20个耦合骨髓和外周血样本，并检查祖细胞凋亡在34 subjects.RESULTS -在NGT相比，CD 34+细胞显着减少IGT，并在新诊断的2型糖尿病的第一个最低点和第二个最低点后20年的糖尿病。对可能的混杂因素进行统计学调整证实，CD 34+细胞计数在诊断时大幅降低，在随后的0-19年期间部分恢复，并且在>= 20年后再次下降。在CD 34 +KDR+细胞中检测到类似但不太一致的趋势。外周血CD 34+细胞与骨髓CD 34+细胞直接相关，与CD 34+细胞凋亡呈负相关。结论-循环祖细胞减少标志着2型糖尿病的临床发病。这两个缺陷的动员和增加细胞凋亡可能占这种现象。虽然在随后的几年中出现了部分恢复，但骨髓储备似乎在长期内耗尽。
OBJECTIVE - Reduction of bone marrow derived circulating progenitor cells has been proposed as a novel mechanism of cardiovascular disease in type 2 diabetes. The present study was designed to describe the extent and potential mechanisms of progenitor cell reduction during the natural history of type 2 diabetes.RESEARCH DESIGN AND METHODS - We identified 425 individuals, divided into seven categories according to carbohydrate metabolism status (normal glucose tolerance [NGT], impaired fasting glucose, impaired glucose tolerance [IGT], and newly diagnosed type 2 diabetes) and diabetes duration (0-9, 10-19, and >= 20 years). These categories were examined as ideally describing the natural history of type 2 diabetes development and progression. We measured CD34+ and CD34+KDR+ progenitor cells by flow cytometry. We also evaluated progenitor cells in 20 coupled bone marrow and peripheral blood samples and examined progenitor cell apoptosis in 34 subjects.RESULTS - In comparison to NGT, CD34+ cells were significantly reduced in IGT and had a first nadir in newly diagnosed type 2 diabetes and a second nadir after 20 years of diabetes. Statistical adjustment for possible confounders confirmed that CD34+ cell counts are deeply reduced at time of diagnosis, that they partially recover during the subsequent 0-19 years, and that they dip again after >= 20 years. A similar, but less consistent, trend was detected for CD34+KDR+ cells. Peripheral blood CD34+ cells were directly correlated with bone marrow CD34+ cells and inversely correlated with CD34+ cell apoptosis.CONCLUSIONS - Circulating progenitor cell reduction marks the clinical onset of type 2 diabetes. Both defective mobilization and increased apoptosis may account for this phenomenon. While a partial recovery occurs during subsequent years, bone marrow reserve seems exhausted in the long term.