Pathophysiology of Type 2 Diabetes in Koreans

곽수헌,박경수 대한내분비학회 2018 Endocrinology and metabolism Vol.33 No.1

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 associatedwith diabetes. A significant number of these loci are thought to be involved in insulin secretion, either through β-cell developmentor β-cell dysfunction. Environmental factors have changed rapidly during the past half century, and the increased prevalence of obesityand diabetes can be attributed to these changes. Environmental factors may affect epigenetic changes and alter susceptibility todiabetes. A recent epidemiologic study revealed that Korean patients with type 2 diabetes already had impaired insulin secretion andinsulin resistance 10 years before the onset of diabetes. Those who developed diabetes showed impaired β-cell compensation with anabrupt decrease in insulin secretion during the last 2 years before diabetes developed. The retrograde trajectory of the disposition indexdiffered according to the baseline subgroups of insulin secretion and insulin sensitivity. We hope that obtaining a more detailedunderstanding of the perturbations in the major pathophysiologic process of diabetes on the individual level will eventually lead tothe implementation of precision medicine and improved patient outcomes.

Finding Genetic Risk Factors of Gestational Diabetes

곽수헌,박경수,장학철 한국유전체학회 2012 Genomics & informatics Vol.10 No.4

Gestational diabetes mellitus (GDM) is a complex metabolic disorder of pregnancy that is suspected to have a strong genetic predisposition. It is associated with poor perinatal outcome, and both GDM women and their offspring are at increased risk of future development of type 2 diabetes mellitus (T2DM). During the past several years, there has been progress in finding the genetic risk factors of GDM in relation to T2DM. Some of the genetic variants that were proven to be significantly associated with T2DM are also genetic risk factors of GDM. Recently, a genome-wide association study of GDM was performed and reported that genetic variants in CDKAL1 and MTNR1B were associated with GDM at a genome-wide significance level. Current investigations using next-generation sequencing will improve our insight into the pathophysiology of GDM. It would be important to know whether genetic information revealed from these studies could improve our prediction of GDM and the future development of T2DM. We hope further research on the genetics of GDM would ultimately lead us to personalized genomic medicine and improved patient care.

부신선종에 의한 쿠싱증후군 환자에서 발생한 대동맥박리 1예

곽수헌,이은정,조선욱,최형진,이은경,조영민,김성연 대한내분비학회 2006 Endocrinology and metabolism Vol.21 No.6

Herein is reported the case of a 43-year-old woman, who experienced an acute aortic dissection associated with underlying Cushing's syndrome. The patient had central obesity and a moon face of ten years duration, but had never sought medical consultation. On the day of her presentation, she experienced a severe chest pain radiating to her back. Computed tomography revealed a Stanford type B acute aortic dissection and a left adrenal mass. From her hormonal study results, clinical symptoms and signs, she was diagnosed with Cushing's syndrome, which was due to a left adrenal adenoma. After medical treatment to stabilize the aortic dissection, she underwent left adrenalectomy. The aortic lesion of the present patient suggests that hypercortisolemia arising from Cushing's syndrome might be related to the development of acute aortic dissection. (J Kor Endocrinol Soc 21:556~559, 2006) 본 증례는 부신선종에 의한 쿠싱증후군 환자에서 발생한 Stanford type B 대동맥박리의 국내 첫 예로써, 대동맥박리가 고코르티솔혈증과 관련하여 발생할 수 있음을 보여 주고 있기에 문헌고찰과 함께 보고하는 바이다

Genetic Studies on Diabetic Microvascular Complications: Focusing on Genome-Wide Association Studies

곽수헌,박경수 대한내분비학회 2015 Endocrinology and metabolism Vol.30 No.2

Diabetes is a common metabolic disorder with a worldwide prevalence of 8.3% and is the leading cause of visual loss, end-stage renal disease and amputation. Recently, genome-wide association studies (GWASs) have identified genetic risk factors for diabetic microvascular complications of retinopathy, nephropathy, and neuropathy. We summarized the recent findings of GWASs on diabetic microvascular complications and highlighted the challenges and our opinion on future directives. Five GWASs were conducted on diabetic retinopathy, nine on nephropathy, and one on neuropathic pain. The majority of recent GWASs were underpowered and heterogeneous in terms of study design, inclusion criteria and phenotype definition. Therefore, few reached the genome-wide significance threshold and the findings were inconsistent across the studies. Recent GWASs provided novel information on genetic risk factors and the possible pathophysiology of diabetic microvascular complications. However, further collaborative efforts to standardize phenotype definition and increase sample size are necessary for successful genetic studies on diabetic microvascular complications.

Genetics of type 2 diabetes and potential clinical implications

곽수헌,박경수 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.2

Type 2 diabetes (T2DM) is a common complexmetabolic disorder that has a strong genetic component. Recent advances in genome-wide association studies haverevolutionized our knowledge regarding the genetics ofT2DM. There are at least 64 common genetic variants thatare strongly associated with T2DM. However, the pathophysiologicroles of these variants are mostly unknown andrequire further functional characterization. The variantsidentified so far have a small effect size and their addedeffect explains less than 10 %of the T2DM heritability. Thecurrent ongoing whole exome and whole genome studies ofT2DM are focused on identifying functionally importantrare variants that have a stronger effect. Through theseefforts, we will have a better understanding of the geneticarchitecture ofT2DMand its pathophysiology. The potentialclinical applications of genetic studies of T2DMinclude riskprediction, identification of novel therapeutic targets,genetic prediction of efficacy and toxicity of anti-diabeticmedications, and eventually optimization of patient carethrough personalized genomic medicine. We hope furtherresearch in genetics of T2DM could aid patient care andimprove outcomes of T2DM patients.

Association of HLA Genotype and Fulminant Type 1 Diabetes in Koreans

곽수헌,김윤지,채제수,이현규,한범,김종일,정규성,조영민,박경수 한국유전체학회 2015 Genomics & informatics Vol.13 No.4

Fulminant type 1 diabetes (T1DM) is a distinct subtype of T1DM that is characterized by rapid onset hyperglycemia, ketoacidosis, absolute insulin deficiency, and near normal level of glycated hemoglobin at initial presentation. Although it has been reported that class II human leukocyte antigen (HLA) genotype is associated with fulminant T1DM, the genetic predisposition is not fully understood. In this study we investigated the HLA genotype and haplotype in 11 Korean cases of fulminant T1DM using imputation of whole exome sequencing data and compared its frequencies with 413 participants of Korean Reference Panel. HLA-DRB1*04:05–HLA-DQB1*04:01 haplotype was significantly associated with increased risk of fulminant T1DM in Fisher’s exact test (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.56 to 10.86, p = 0.009). Histidine residue at HLA-DRβ1 position 13 was marginally associated with increased risk of fulminant T1DM (OR, 2.45; 95% CI ,1.01 to 5.94; p = 0.054). Although we had limited statistical power, we provide evidence that HLA haplotype and amino acid change can be a genetic risk factor for fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings.

Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population (Diabetes Metab J 2014;38:375-87)

곽수헌 대한당뇨병학회 2014 Diabetes and Metabolism Journal Vol.38 No.6

Recent progress in genetic and epigenetic research on type 2 diabetes

곽수헌,박경수 생화학분자생물학회 2016 Experimental and molecular medicine Vol.48 No.-

Type 2 diabetes (T2DM) is a common complex metabolic disorder that has a strong genetic predisposition. During the past decade, progress in genetic association studies has enabled the identification of at least 75 independent genetic loci for T2DM, thus allowing a better understanding of the genetic architecture of T2DM. International collaborations and large-scale metaanalyses of genome-wide association studies have made these achievements possible. However, whether the identified common variants are causal is largely unknown. In addition, the detailed mechanism of how these genetic variants exert their effect on the pathogenesis of T2DM requires further investigation. Currently, there are ongoing large-scale sequencing studies to identify rare, functional variants for T2DM. Environmental factors also have a crucial role in the development of T2DM. These could modulate gene expression via epigenetic mechanisms, including DNA methylation, histone modification and microRNA regulation. There is evidence that epigenetic changes are important in the development of T2DM. Recent studies have identified several DNA methylation markers of T2DM from peripheral blood and pancreatic islets. In this review, we will briefly summarize the recent progress in the genetic and epigenetic research on T2DM and discuss how environmental factors, genetics and epigenetics can interact in the pathogenesis of T2DM.

임신성 당뇨병의 유전자

곽수헌,장학철,박경수 대한의사협회 2009 대한의사협회지 Vol.52 No.7

Gestational diabetes mellitus (GDM) is defined as abnormal glucose tolerance diagnosed for the first time during pregnancy. The pathogenesis of GDM is characterized by relatively reduced insulin secretion insufficient to meet the increased insulin demand, which is quite similar to that of type 2 diabetes mellitus. Thus GDM is considered to have a common genetic background as type 2 diabetes mellitus. However, only limited information is available for the genetic basis of GDM. In this review article, we will briefly discuss the definition, epidemiologic features, and pathophysiology of GDM. In addition, we will present the data of two recent genetic association studies regarding GDM. Most of the previously proven type 2 diabetes associated single nucleotide polymorphisms were also associated with the risk of GDM. Rapidly increasing knowledge in genetics of GDM will provide us with new insights into the pathophysiology, treatment, and prevention of GDM.

당뇨병 예방법

곽수헌 대한내과학회 2018 대한내과학회 추계학술대회 Vol.2018 No.2