Endocrinol Metab.  2018 Mar;33(1):9-16. 10.3803/EnM.2018.33.1.9.

Pathophysiology of Type 2 Diabetes in Koreans

• Kwak SH
• Park KS

• KMID: 2407116
• DOI: http://doi.org/10.3803/EnM.2018.33.1.9

Abstract

The pathophysiology of type 2 diabetes is characterized by variable degrees of insulin resistance and impaired insulin secretion. Both genetic and environmental factors serve as etiologic factors. Recent genetic studies have identified at least 83 variants associated with diabetes. A significant number of these loci are thought to be involved in insulin secretion, either through β-cell development or β-cell dysfunction. Environmental factors have changed rapidly during the past half century, and the increased prevalence of obesity and diabetes can be attributed to these changes. Environmental factors may affect epigenetic changes and alter susceptibility to diabetes. A recent epidemiologic study revealed that Korean patients with type 2 diabetes already had impaired insulin secretion and insulin resistance 10 years before the onset of diabetes. Those who developed diabetes showed impaired β-cell compensation with an abrupt decrease in insulin secretion during the last 2 years before diabetes developed. The retrograde trajectory of the disposition index differed according to the baseline subgroups of insulin secretion and insulin sensitivity. We hope that obtaining a more detailed understanding of the perturbations in the major pathophysiologic process of diabetes on the individual level will eventually lead to the implementation of precision medicine and improved patient outcomes.

Keyword

Diabetes mellitus, type 2; Environment; Genetics; Insulin-secreting cells; Insulin resistance; Physiopathology

MeSH Terms

Compensation and Redress
Diabetes Mellitus, Type 2
Epidemiologic Studies
Epigenomics
Genetics
Hope
Humans
Insulin
Insulin Resistance
Insulin-Secreting Cells
Obesity
Precision Medicine
Prevalence
Insulin

Figure

• 

  Fig. 1 Classification of 83 genetic loci according to their suggested roles in the pathogenesis of type 2 diabetes. The loci were classified as being involved in insulin secretion if a variant was associated with measures of insulin secretion, such as the homeostasis model assessment of β-cell function, insulinogenic index, or the disposition index. Loci were further classified as being involved in β-cell development if the implicated gene played a role as a transcription factor in β-cell development. Genes that played a role in the insulin secretion cascade or β-cell apoptosis were classified as being involved in β-cell dysfunction. Loci were classified as being involved in insulin resistance if a variant was associated with measures of insulin resistance, such as the homeostasis model assessment of insulin resistance or the Matsuda index. Genes known to be associated with the body mass index were classified as being involved in obesity, and genes known to be involved in the insulin signaling pathway were classified as being involved in insulin action. Modified and updated from Kwak et al., with permission from Springer Nature [12].

• 

  Fig. 2 Retrograde trajectory of (A) insulin sensitivity and (B) the insulinogenic index. Diabetes onset or the end of follow-up was set as time zero and each follow-up was traced towards the back. Modified and updated from Ohn et al., with permission from Elsevier [33]. ISI, composite (Matsuda) insulin sensitivity index (unitless); IGI, 1-hour insulinogenic index.

• 

  Fig. 3 Subgroup analysis of the retrograde trajectory of the disposition index. (A) Participants with a high 1-hour insulinogenic index (IGI) and composite (Matsuda) insulin sensitivity index (ISI), (B) participants with a high IGI and a low ISI, (C) participants with a low IGI and a high ISI, (D) participants with a low IGI and a low ISI. Modified and updated from Ohn et al., with permission from Elsevier [33].

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