Pathophysiology of Type 2 Diabetes in Koreans

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.

Epigenetic Markers and Microbiota/Metabolite-Induced Epigenetic Modifications in the Pathogenesis of Obesity, Metabolic Syndrome, Type 2 Diabetes, and Non-alcoholic Fatty Liver Disease

“…However, these genetic variants explain only ~ 20% of T2D heritability, in part possibly due to the inclusion of participants of mostly European descent in these studies. Future research on ethnic-specific variants, copy number variants such as small deletions or insertions, and rare functional variants of strong effects may increase our understanding of T2D heritability using large-scale biobanks in diverse populations [ 6 , 50 , 51 ].…”

“…Insulin resistance (IR) is believed to be a common factor that is strongly correlated to most components of the metabolic syndrome [ 5 ]. It is a state in which the target tissues like skeletal muscle, adipose tissue, and the liver respond inadequately to insulin [ 6 ].…”

The cut-off values of surrogate measures for insulin resistance in the Korean population according to the Korean Genome and Epidemiology Study (KOGES)

“…Variable degrees of insulin resistance and impaired insulin secretion are major pathophysiological characteristics of type 2 diabetes mellitus (DM) [ 1 ]. Insulin resistance is characterized by a reduced physiological response of target tissues to normal levels of insulin and results in decreased glucose utilization in muscle and fat, as well as increased gluconeogenesis in the liver [ 2 – 4 ].…”

Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults

“…Hypertrophy of the diabetic heart is the consequence of myocardial triglyceride deposition [ 29 ]. In addition, hyperinsulinemia and insulin resistance, the well-known pathophysiologic cause of type 2 diabetes mellitus, is also thought to directly promote myocardial hypertrophy [ 30 31 ]. Deposition of advanced glycation end products constitutes a driving factor for microvascular damage in diabetes and is associated with cardiomyocyte stiffness and myocardial collagen deposition [ 32 33 ].…”