Pancreaticoduodenectomy model demonstrates a fundamental role of dysfunctional β cells in predicting diabetes
Pancreaticoduodenectomy model demonstrates a fundamental role of dysfunctional β cells in predicting diabetes
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DOI：
10.1172/jci146788
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发表时间：
2021-06-15
影响因子：
15.9
通讯作者：
Giaccari, Andrea
中科院分区：
文献类型：
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作者：
Mezza, Teresa;Ferraro, Pietro Manuel;Giaccari, Andrea
背景资料。高血糖的出现是由于胰岛素抵抗、胰岛素分泌功能障碍和β细胞质量减少。关于这些因素在临床表现为β细胞功能障碍中的相对作用，长期以来一直存在争议。本研究的目的是验证其中一个因素，即胰岛β细胞质量的减少，对随后发生的高血糖的急性影响。方法：为了达到这一目的，非糖尿病患者在手术前后接受了口服葡萄糖耐量试验(OGTT)和高血糖钳夹(HC)检查，然后进行精氨酸刺激。根据术后OGTT，受试者根据糖耐量分为三组：正常糖耐量(NGT)、糖耐量受损(IGT后)或糖尿病(DM后)。结果：在基线时，三组的空腹血糖和胰岛素水平相似；然而，检查各种参数，我们发现第一时相胰岛素分泌减少、葡萄糖敏感性降低和心率敏感性是术后IGT和糖尿病最终发展的预测因素。结论。尽管基线时的功能质量、空腹血糖和胰岛素水平以及相同的质量减少50%，但只有第一时相胰岛素分泌减少和葡萄糖敏感性降低才能预测高血糖的出现。这些功能改变可能在2型糖尿病(T2 DM)的发病机制中起关键作用。
BACKGROUND. The appearance of hyperglycemia is due to insulin resistance, functional deficits in the secretion of insulin, and a reduction of beta cell mass. There is a long-standing debate as to the relative contribution of these factors to clinically manifesting beta cell dysfunction. The aim of this study was to verify the acute effect of one of these factors, the reduction of beta cell mass, on the subsequent development of hyperglycemia.METHODS. To pursue this aim, nondiabetic patients, scheduled for identical pancreaticoduodenectomy surgery, underwent oral glucose tolerance tests (OGTT) and hyperglycemic clamp (HC) procedures, followed by arginine stimulation before and after surgery. Based on postsurgery OGTT, subjects were divided into 3 groups depending on glucose tolerance: normal glucose tolerance (post-NGT), impaired glucose tolerance (post-IGT), or having diabetes mellitus (post-DM).RESULTS. At baseline, the 3 groups showed similar fasting glucose and insulin levels; however, examining the various parameters, we found that reduced first-phase insulin secretion, reduced glucose sensitivity, and rate sensitivity were predictors of eventual postsurgery development of IGT and diabetes. CONCLUSION. Despite comparable functional mass and fasting glucose and insulin levels at baseline and the very same 50% mass reduction, only reduced first-phase insulin secretion and glucose sensitivity predicted the appearance of hyperglycemia. These functional alterations could be pivotal to the pathogenesis of type 2 diabetes (T2DM).