Type 2 diabetes(T2D) is caused by a complex interplay between genetic and environmental factors and likely comprises heterogeneous disorders with common phenotype of chronic hyperglycemia. Current understanding of pathogenesis and natural history of T2D are mostly based on studies of European populations that insulin resistance precedes impaired beta cell function and T2D develops only when insulin secretion fails to compensate insulin resistance.
However, it has long been recognized that clinical and metabolic characteristics of T2D in Korean and east Asian are quite different from those in European. Korean patients with T2D have less degree of both obesity and insulin resistance and lower beta cell function compared to European. To elucidate natural history of T2D in Korean, we investigated the longitudinal change in beta cell function and insulin sensitivity in the development of T2D in Korean. 10 year trajectory of beta cell function and insulin sensitivity in the development of diabetes revealed that subjects with normal glucose tolerance(NGT) who progressed to diabetes had lower insulin secretory function and lower insulin sensitivity index compared to those who remained NGT. This observation suggest that metabolic phenotypes associated with the development of T2D in Korean are quite different from those in European.
Genome-wide association studies(GWAS) and whole exome sequencing analysis in Korean T2D showed substantial overlap of common variants with European populations. However, number of variants showed different frequencies and effect size from those in European populations and many of them are related to beta cell function. Particularly an east Asian specific nonsynonymous variant in PAX4 (rs2233580, R192H) was associated with T2D in genome-wide significance (OR = 1.81, P = 6.36×10-9). This variant was associated with lower age at diagnosis and decreased C-peptide level in T2D cases. Weighted genotype risk score(using 36 variants) was significantly associated with lower age at diagnosis, lower body mass index and decreased C-peptide level.
In summary, genotypes and metabolic phenotypes of T2DM in Korean are different from European populations. Further studies are required to translate these differences in prevention and management of T2D in Korean.
- 1991-1993, Graduate School, Seoul National University ; major in Internal Medicine: Ph.D.
- 1986-1988, Graduate School, Seoul National University ; major in Internal Medicine: M.S.
- 1980-1984, Seoul National University College of Medicine: M.D.
- 1978-1980, Premedical Course, Seoul National University College of Natural Science
- 1999.09-2006.03, Associate Professor, Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine
- 1995.02-1997.01, Postdoctoral fellow, Endocrinology and metabolism, University of California, San Diego
- 1995-1999.08, Assistant Professor, Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine
- 1992-1995, Instructor, Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine
- 2017, Order of Science and Technology Merit, Hyeosin Medal
- 2016, Wunsch Medical Award
- 2012, Hamchun DongA Award
- 2009, Commendation from Ministet of Health and Welfare
- 2009, Sulwon Award, Korean Diabetes Association
- 2008, Namgok Award, Korean Endocrine Society
- 2007 Best research award, Seoul National University