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糖谱揭示了葡萄糖失调的新模式。

Glucotypes reveal new patterns of glucose dysregulation.

机构信息

Stanford University, Stem Cell Biology and Regenerative Medicine, Stanford, California, United States of America.

Stanford University, Department of Genetics, Stanford, California, United States of America.

出版信息

PLoS Biol. 2018 Jul 24;16(7):e2005143. doi: 10.1371/journal.pbio.2005143. eCollection 2018 Jul.


DOI:10.1371/journal.pbio.2005143
PMID:30040822
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6057684/
Abstract

Diabetes is an increasing problem worldwide; almost 30 million people, nearly 10% of the population, in the United States are diagnosed with diabetes. Another 84 million are prediabetic, and without intervention, up to 70% of these individuals may progress to type 2 diabetes. Current methods for quantifying blood glucose dysregulation in diabetes and prediabetes are limited by reliance on single-time-point measurements or on average measures of overall glycemia and neglect glucose dynamics. We have used continuous glucose monitoring (CGM) to evaluate the frequency with which individuals demonstrate elevations in postprandial glucose, the types of patterns, and how patterns vary between individuals given an identical nutrient challenge. Measurement of insulin resistance and secretion highlights the fact that the physiology underlying dysglycemia is highly variable between individuals. We developed an analytical framework that can group individuals according to specific patterns of glycemic responses called "glucotypes" that reveal heterogeneity, or subphenotypes, within traditional diagnostic categories of glucose regulation. Importantly, we found that even individuals considered normoglycemic by standard measures exhibit high glucose variability using CGM, with glucose levels reaching prediabetic and diabetic ranges 15% and 2% of the time, respectively. We thus show that glucose dysregulation, as characterized by CGM, is more prevalent and heterogeneous than previously thought and can affect individuals considered normoglycemic by standard measures, and specific patterns of glycemic responses reflect variable underlying physiology. The interindividual variability in glycemic responses to standardized meals also highlights the personal nature of glucose regulation. Through extensive phenotyping, we developed a model for identifying potential mechanisms of personal glucose dysregulation and built a webtool for visualizing a user-uploaded CGM profile and classifying individualized glucose patterns into glucotypes.

摘要

糖尿病是一个全球性的日益严重的问题;在美国,几乎有 3000 万人,即近 10%的人口被诊断患有糖尿病。另有 8400 万人处于糖尿病前期,如果不进行干预,其中多达 70%的人可能会发展为 2 型糖尿病。目前用于量化糖尿病和糖尿病前期血糖失调的方法受到限制,因为这些方法依赖于单点测量或对整体血糖的平均测量,而忽略了血糖动态。我们使用连续血糖监测(CGM)来评估个体餐后血糖升高的频率、升高的类型以及在给予相同营养挑战时个体之间的模式如何变化。对胰岛素抵抗和分泌的测量突出了这样一个事实,即血糖失调的生理基础在个体之间存在高度的可变性。我们开发了一种分析框架,可以根据称为“血糖类型”的特定血糖反应模式对个体进行分组,这些模式揭示了传统葡萄糖调节诊断类别中的异质性或亚表型。重要的是,我们发现,即使使用 CGM,即使通过标准测量被认为是血糖正常的个体,也会表现出很高的血糖变异性,血糖水平分别有 15%和 2%的时间达到糖尿病前期和糖尿病的范围。因此,我们表明,CGM 所描述的血糖失调比以前认为的更为普遍和多样化,并且可能影响到被标准测量认为是血糖正常的个体,而特定的血糖反应模式反映了不同的潜在生理。标准化餐食引起的个体间血糖反应的可变性也突出了葡萄糖调节的个体性。通过广泛的表型分析,我们开发了一种识别个体葡萄糖失调潜在机制的模型,并构建了一个用于可视化用户上传的 CGM 图谱和将个体血糖模式分类为血糖类型的网络工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/73a3021a7f60/pbio.2005143.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/f3033954cf58/pbio.2005143.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/a0b863daf47f/pbio.2005143.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/dcd3016dce48/pbio.2005143.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/19dfb75d2912/pbio.2005143.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/73eb35fb4f21/pbio.2005143.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/73a3021a7f60/pbio.2005143.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/f3033954cf58/pbio.2005143.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/a0b863daf47f/pbio.2005143.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/dcd3016dce48/pbio.2005143.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/19dfb75d2912/pbio.2005143.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/73eb35fb4f21/pbio.2005143.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a824/6057684/73a3021a7f60/pbio.2005143.g006.jpg

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