Validating a dimensionless number for glucose homeostasis in humans.
Validating a dimensionless number for glucose homeostasis in humans.
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DOI：
10.1007/s10439-009-9733-y
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发表时间：
2009-09
影响因子：
3.8
通讯作者：
Klinke, David J., II
中科院分区：
文献类型：
--
作者：
Klinke, David J., II
关键词：
了解2型糖尿病的挑战是患者表型的多样性。跨物种和个体之间的数据转换是理解这种多因素疾病的遗传位点的障碍。基于量纲分析的动态缩放是工程中用于在不同系统之间转换数据的常用技术。本研究的目的是使用量纲分析来了解代表疾病进展不同阶段的患者组中胰岛素产生能力与胰岛素依赖性葡萄糖代谢的相对变化。使用涉及胰岛素产生和葡萄糖代谢对胰岛素的敏感性的变量推导出无量纲数。由此产生的动态缩放关系进行了验证，对患者的数据，获得超过2000个人的表型范围从正常到严重的2型糖尿病。在第三次全国健康和营养评估调查中确定了个人。根据临床症状的严重程度，患者群体聚集在不同的地区。患者组间的横断面比较显示，2型糖尿病从正常到临床发作的进展表现出胰岛素产生与胰岛素依赖性葡萄糖代谢的比率的非线性变化：正常人平衡，糖尿病前期个体表现出增加，临床2型糖尿病个体表现出该比率的降低。这个无量纲数提供了一种从第一原理区分患者组的方法。通过与其他无量纲数类比，该数可用于监测负责葡萄糖稳态的基本生理变量。此外，与临床人群相似的动态轨迹可以为选择糖尿病相关动物模型提供标准。
Understanding type 2 diabetes is challenged by the diversity of patient phenotypes. Translating data across species and among individuals is a barrier for understanding the genetic loci that underpin this multifactorial disease. Dynamic scaling, based upon dimensional analysis, is a common technique in engineering used to translate data among different systems. The objective of this study was to gain insight using dimensional analysis into the relative changes in insulin production capacity versus insulin-dependent glucose metabolism in patient groups that represent distinct stages of disease progression. A dimensionless number was derived using variables involved in the production of insulin and in the sensitivity of glucose metabolism to insulin. The resulting dynamic scaling relationship was validated against patient data obtained for over 2000 individuals that range in phenotype from normal to severe type 2 diabetes. Individuals were identified in the third National Health and Nutrition Evaluation Survey. Patient groups clustered in different regions based upon the severity of clinical symptoms. The cross-sectional comparison among patient groups shows that progression from normal to clinical onset of type 2 diabetes exhibits a non-linear change in the ratio of insulin production to insulin-dependent glucose metabolism: normals are balanced, pre-diabetic individuals exhibit an increase, and individuals with clinical type 2 diabetes exhibit a decrease in this ratio. This dimensionless number provides a method for discriminating between patient groups from first principles. By analogy with other dimensionless numbers, this number may be used to monitor basic physiological variables responsible for glucose homeostasis. In addition, a similar dynamic trajectory to the clinical populations could provide a criterion for selecting relevant animal models for diabetes.
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