No abstract available.
Diabetes Mellitus, Type 2* ; Genome-Wide Association Study*

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.
Amputation ; Diabetic Retinopathy ; Genetics ; Genome-Wide Association Study* ; Kidney Failure, Chronic ; Neuralgia ; Phenotype ; Prevalence ; Risk Factors ; Sample Size

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 meta-analyses 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.
Cooperative Behavior ; DNA Methylation ; Epigenomics* ; Gene Expression ; Genetic Association Studies ; Genetic Loci ; Genetic Predisposition to Disease ; Genetics ; Genome-Wide Association Study ; Histones ; Islets of Langerhans ; MicroRNAs

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 with single nucleotide polymorphisms were also associated with the risk of GDM. Rapidly increasing knowledge in genetics of GDM will generate new insights into the pathophysiology, treatment, and prevention of GDM.
Diabetes Mellitus, Type 2 ; Diabetes, Gestational ; Female ; Genetic Association Studies ; Glucose ; Insulin ; Insulin Resistance ; Polymorphism, Single Nucleotide ; Pregnancy

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 with single nucleotide polymorphisms were also associated with the risk of GDM. Rapidly increasing knowledge in genetics of GDM will generate new insights into the pathophysiology, treatment, and prevention of GDM.
Diabetes Mellitus, Type 2 ; Diabetes, Gestational ; Female ; Genetic Association Studies ; Glucose ; Insulin ; Insulin Resistance ; Polymorphism, Single Nucleotide ; Pregnancy

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

Monogenic diabetes, including maturity-onset diabetes of the young, neonatal diabetes, and other rare forms of diabetes, results from a single gene mutation. It has been estimated to represent around 1% to 6% of all diabetes. With the advances in genome sequencing technology, it is possible to diagnose more monogenic diabetes cases than ever before. In Korea, 11 studies have identified several monogenic diabetes cases, using Sanger sequencing and whole exome sequencing since 2001. The recent largest study, using targeted exome panel sequencing, found a molecular diagnosis rate of 21.1% for monogenic diabetes in clinically suspected patients. Mutations in glucokinase (GCK), hepatocyte nuclear factor 1α (HNF1A), and HNF4A were most commonly found. Genetic diagnosis of monogenic diabetes is important as it determines the therapeutic approach required for patients and helps to identify affected family members. However, there are still many challenges, which include a lack of simple clinical criterion for selecting patients for genetic testing, difficulties in interpreting the genetic test results, and high costs for genetic testing. In this review, we will discuss the latest updates on monogenic diabetes in Korea, and suggest an algorithm to screen patients for genetic testing. The genetic tests and non-genetic markers for accurate diagnosis of monogenic diabetes will be also reviewed.

OBJECTIVES: Epidemiological and clinical studies have suggested that low cholesterol levels or clinical trals to reduce cholesterol concentrations may be associated with suicide, violent behavior or depression. The aim of the present study was to determined i) whether suicidal psychiatric patients is characterized by decreased serum cholesterol concentration ; ii) whether significant difference of cholesterol levels might be present according to the psychiatric diagnosis, and iii) whether significant association between suicide severity and cholesterol levels might be present. METHOD: The subjects were 102 psychiatric patients who were admitted to emergency ward following an attempted suicide during the period from January 1994 to July 1997 and 102 age, and sex matched psychiatric controls who were consecutively admitted to a psychiatric ward during the same period, and 102 age, sex matched healthy normal controls. The suicide attempters were divided into 5 grades according to the suicide severity. Serum cholesterol concentrations were measured by a enzymatic method. RESULTS: The serum cholesterol level in suicidal attempters were found to be significantly lower compared with both psychiatric and normal controls. This significant relationship between suicidal attempt and low cholesterol level was observed only in depressive patients, but not in schizophrenics or personality disorder patients. Low cholesterol was significantly associated with the severity of the suicide. CONCLUSIONS: These results support the previous finding that low cholesterol level might be associated with an increased risk of suicide. The fact that the significant relationship was observed only in depressive disorder, but not in schizophrenia or personality disorder raises the possibility that the association between low serum cholesterol and suicidal behavior may have relevance to biological mechanisms in depression. It is hypothesized that low cholesterol levels would be associated with depression by modifying the serotonin, the production of interleukin 2 and melatonin metabolism.
Cholesterol* ; Depression ; Depressive Disorder ; Emergencies* ; Emergency Service, Hospital* ; Humans ; Interleukin-2 ; Melatonin ; Mental Disorders ; Metabolism ; Personality Disorders ; Schizophrenia ; Serotonin ; Suicide* ; Suicide, Attempted

Precision medicine, which optimizes diagnosis and treatment of diseases according to individualized characteristics, is becoming a reality in the field of diabetes, especially for monogenic diabetes. Maturityonset diabetes of the young (MODY) is a type of monogenic diabetes characterized by early onset, relative non-obesity, non-insulin dependence, and autosomal dominant inheritance. With the trend toward precision medicine and improvement in genetic testing, there have been advances in the classification, diagnosis, and treatment of MODY. MODY accounts for about 1% of diabetes in Korea, with GCK (glucokinase)-MODY, HNF1α (hepatocyte nuclear factor-1 alpha)-MODY, and HNF4α (hepatocyte nuclear factor-4 alpha)-MODY being most common. In the diagnosis of MODY, applying guidelines for interpretation of variant pathogenicity is important. For the treatment of MODY, individualized treatment strategies according to the causative gene of MODY should be applied when available. Still, the majority of MODY is misdiagnosed and more genetic testing is required in Korea. We review updates regarding the classification, diagnosis, and treatment of MODY.