Polymorphisms of the <i>Reg</i> 1α Gene and Early Onset Type 2 Diabetes in the Korean Population

Koo, Bo Kyung,Cho, Young Min,Kimm, Kuchan,Lee, Jong-Young,Oh, Bermseok,Park, Byung Lae,Cheong, Hyun Sub,Shin, Hyoung Doo,Ko, Kyung Soo,Park, Sang Gyu,Lee, Hong Kyu,Park, Kyong Soo Korean Diabetes Association 2010 Korean diabetes journal Vol.34 No.4

<P><B>Background</B></P><P>The <I>Reg</I> gene has been reported to be expressed in regenerating islets and Reg1 protein to be up-regulated at an early stage of diabetes in mice. As human <I>Reg</I>1α is homologous with murine <I>Reg</I>1, we investigated whether common variants in <I>Reg</I>1α are associated with type 2 diabetes in the Korean population.</P><P><B>Methods</B></P><P>We sequenced the <I>Reg</I>1α gene to identify common polymorphisms using 24 Korean DNA samples. Of 11 polymorphisms found, five common ones (g.-385T>C [rs10165462], g.-36T>G [rs25689789], g.209G>T [rs2070707], g.1385C>G [novel], and g.2199G>A [novel]) were genotyped in 752 type 2 diabetic patients and 642 non-diabetic subjects.</P><P><B>Results</B></P><P>No polymorphism was associated with the risk of type 2 diabetes. However, g.-385C and g.2199A lowered the risk of early-onset type 2 diabetes, defined as a diagnosis in subjects whose age at diagnosis was 25 years or more but less than 40 years (odds ratio [OR], 0.721 [0.535 to 0.971] and 0.731 [0.546 to 0.977] for g.-385C and g.2199A, respectively) and g.1385G increased the risk of early-onset diabetes (OR, 1.398 [1.055 to 1.854]). Although adjusting for errors in multiple hypotheses-testing showed no statistically significant association between the three individual polymorphisms and early-onset diabetes, the haplotype <I>H1</I>, composed of g.-385C, g.1385C, and g.2199A, was associated with a reduced risk of early-onset diabetes (OR, 0.590 [0.396 to 0.877], <I>P</I> = 0.009).</P><P><B>Conclusion</B></P><P>Polymorphisms in the <I>Reg</I>1α were not found to be associated with overall susceptibility to type 2 diabetes, though some showed modest associations with early-onset type 2 diabetes in the Korean population.</P>

Prevalence of Chronic Complications in Korean Patients with Type 2 Diabetes Mellitus Based on the Korean National Diabetes Program

Rhee, Sang Youl,Chon, Suk,Kwon, Mi Kwang,Park, Ie Byung,Ahn, Kyu Jeung,Kim, In Ju,Kim, Sung-Hoon,Lee, Hyoung Woo,Koh, Kyung Soo,Kim, Doo Man,Baik, Sei Hyun,Lee, Kwan Woo,Nam, Moon Suk,Park, Yong Soo,W Korean Diabetes Association 2011 Diabetes and Metabolism Journal Vol.35 No.5

<P><B>Background</B></P><P>The Korean National Diabetes Program (KNDP) cohort study is performing an ongoing large-scale prospective multicenter investigation to discover the pathogenesis of type 2 diabetes in Korean patients. This study was performed to examine the prevalence of chronic complications in patients with type 2 diabetes among those registered in the KNDP cohort within the past 4 years.</P><P><B>Methods</B></P><P>This study was performed between June 2006 and September 2009 at 13 university hospitals and included 4,265 KNDP cohort participants. Among the participants, the crude prevalence of microvascular and macrovascular diseases of those checked for diabetes-related complications was determined, and the adjusted standard prevalence and standardization of the general population prevalence ratio (SPR) was estimated based on the 2005 Korean National Health and Nutrition Examination Survey (KNHANES) population demographics.</P><P><B>Results</B></P><P>Among the KNDP registrants, 43.2% had hypertension, 34.8% had dyslipidemia, 10.8% had macrovascular disease, and 16.7% had microvascular disease. The SPR of the KNDP registrants was significantly higher than that of the KNHANES subjects after adjusting for demographics in the KNHANES 2005 population. However, with the exception of cardiovascular disease in females, the standardized prevalence for the most complicated items in the survey was significantly higher than that in the KNHANES subjects.</P><P><B>Conclusion</B></P><P>The prevalence of macrovascular disease and peripheral vascular disease were significantly higher in Korean patients with type 2 diabetes than in the normal population. However, no significant difference was noted in the prevalence of cardiovascular disease in females.</P>

Perception of Clinicians and Diabetic Patients on the Importance of Postprandial Glucose Control and Diabetes Education Status: A Cross Sectional Survey

Choi, Ji Hun,Park, Cheol Young,Cha, Bong Soo,Kim, In Joo,Park, Tae Sun,Park, Joong Yeol,Park, Kyung Soo,Yoon, Kun Ho,Lee, In Kyu,Park, Sung Woo Korean Diabetes Association 2012 Diabetes and Metabolism Journal Vol.36 No.2

<P><B>Background</B></P><P>Recent studies have shown the importance of postprandial glucose (PPG) in the development of diabetes complications. This study was conducted in order to survey the perceptions of clinicians and diabetic patients with respect to PPG management and the current status of diabetes education.</P><P><B>Methods</B></P><P>This was a cross-sectional study involving face-to-face interviews and an open questionnaire survey conducted in Korea. A total of 300 patients and 130 clinicians completed questionnaires, which included current education status, self monitoring of blood glucose (SMBG), criteria of diagnosis and management, and perceptions relating to PPG management.</P><P><B>Results</B></P><P>While there was a significantly higher perceived need for diabetes education, the sufficiency of the current education was considered to be severely lacking. Fasting plasma glucose (FPG), PPG, and glycosylated hemoglobin (HbA1c) were all important considerations for clinicians when making a diagnosis of diabetes, although PPG was considered less important than FPG or HbA1c in the treatment of diabetes. Most clinicians and patients were aware of the importance of PPG, but actual education on the importance of PPG was not actively being delivered.</P><P><B>Conclusion</B></P><P>Our study showed that the current status of diabetes education is insufficient to meet the needs of the Korean population. A considerable gap was found to exist between awareness and what was actually taught in the current education program in regard to the importance of PPG. These results suggest that clinicians need to be more active in patient education, especially in regard to the importance of PPG.</P>

The Insulin Resistance but Not the Insulin Secretion Parameters Have Changed in the Korean Population during the Last Decade

Yang, Hae Kyung,Lee, Jin Hee,Choi, In-Young,Kwon, Hyuk Sang,Shin, Jeong Ah,Jeong, Seung Hee,Lee, Seung-Hwan,Cho, Jae Hyoung,Son, Ho Young,Yoon, Kun Ho Korean Diabetes Association 2015 Diabetes and Metabolism Journal Vol.39 No.2

<P><B>Background</B></P><P>This study aimed to compare the patterns of insulin secretion and resistance between Korean subjects in the 1990s and 2000s.</P><P><B>Methods</B></P><P>Insulin secretion and resistance indices were calculated from subjects who underwent 75-g oral glucose tolerance tests in the year 1997 to 1999 and 2007 to 2011 at the Seoul St. Mary's Hospital, Korea.</P><P><B>Results</B></P><P>A total of 578 subjects from the 1990s (mean age, 48.5 years) and 504 subjects from the 2000s (mean age, 50.2 years) were enrolled. Compared with the subjects from the 1990s, those from the 2000s exhibited increased insulin resistance (increased homeostatic model assessment for insulin resistance), and reduced insulin sensitivity (reduced Matsuda index and quantitative insulin sensitivity check index), regardless of their glucose tolerance status. However, insulinogenic index did not reveal significant differences between the 2 decades in subjects with or without diabetes. A distinct relationship was confirmed between Matsuda index and total area under the curve (insulin/glucose) in each glucose tolerance group. The mean product of the Matsuda index and the total area under the curve (insulin/glucose) as well as the oral disposition index, was lower in subjects with normal glucose tolerance from the 2000s than in those from the 1990s.</P><P><B>Conclusion</B></P><P>After rapid economic growth and changes in lifestyle patterns, insulin resistance has worsened across the glucose tolerance status; however, the insulin secretory function remained unchanged, which resulted in an increase in the susceptibility to the development of type 2 diabetes mellitus among Korean subjects without diabetes. We could not rule out the potential selection bias and therefore, further studies in general Korean population are needed.</P>

Development and Validation of a Semi-Quantitative Food Frequency Questionnaire to Assess Diets of Korean Type 2 Diabetic Patients

Hong, Seongbin,Choi, Yunjin,Lee, Hun-Jae,Kim, So Hun,Oe, Younju,Lee, Seung Youn,Nam, Moonsuk,Kim, Yong Seong Korean Diabetes Association 2010 Korean diabetes journal Vol.34 No.1

<P><B>Background</B></P><P>Our aim was to assess the validity of a semi-quantitative food frequency questionnaire (FFQ) by comparison with the 3-day diet record (DR) in patients with type 2 diabetes.</P><P><B>Methods</B></P><P>Eighty five type 2 diabetic patients (aged 33 to 70 years) from the Korean National Diabetes Program (KNDP) completed 3-day DR and FFQ. The FFQ was designed to reflect the eating pattern of Korean type 2 diabetic patients, and was based on the 2003 Korean National Health and Nutrition Examination Survey. The FFQ consists of 85 food items and 12 food groups. The validity of FFQ was assessed by comparison with the 3-day DR.</P><P><B>Results</B></P><P>The mean age was 49 ± 10 years. Clinical characteristic including body weight, diabetic duration, and HbA1c were not different from the total cohort subjects (<I>n</I> = 1,478). There were no significant differences in the mean intake of protein, fat and calcium estimated by the FFQ and the 3-day DR. Energy and carbohydrate estimated by the FFQ were higher than those estimated by the 3-day DR. The correlation coefficient was highest for energy (<I>r</I> = 0.740; <I>P</I> < 0.00) and lowest for iron (<I>r</I> = 0.269; <I>P</I> < 0.05). The Kappa values for energy, carbohydrate, protein, fat and calcium were 0.54, 0.37, 0.36, 0.46, and 0.19, respectively.</P><P><B>Conclusion</B></P><P>The FFQ is a reasonable instrument for assessing the intake of most macronutrients in Korean type 2 diabetes, although careful consideration is required for the food groups and nutrients for which the FFQ had low validity.</P>

Identification of Two Cases of Ciliopathy-Associated Diabetes and Their Mutation Analysis Using Whole Exome Sequencing

Kim, Min Kyeong,Kwak, Soo Heon,Kang, Shinae,Jung, Hye Seung,Cho, Young Min,Kim, Seong Yeon,Park, Kyong Soo Korean Diabetes Association 2015 Diabetes and Metabolism Journal Vol.39 No.5

<P><B>Background</B></P><P>Alström syndrome and Bardet-Biedl syndrome are autosomal recessively inherited ciliopathies with common characteristics of obesity, diabetes, and blindness. Alström syndrome is caused by a mutation in the <I>ALMS1</I> gene, and Bardet-Biedl syndrome is caused by mutations in <I>BBS1-16</I> genes. Herein we report genetically confirmed cases of Alström syndrome and Bardet-Biedl syndrome in Korea using whole exome sequencing.</P><P><B>Methods</B></P><P>Exome capture was done using SureSelect Human All Exon Kit V4+UTRs (Agilent Technologies). HiSeq2000 system (Illumina) was used for massive parallel sequencing. Sanger sequencing was used for genotype confirmation and familial cosegregation analysis.</P><P><B>Results</B></P><P>A 21-year old Korean woman was clinically diagnosed with Alström syndrome. She had diabetes, blindness, obesity, severe insulin resistance, and hearing loss. Whole exome sequencing revealed a nonsense mutation in exon 10 of <I>ALMS1</I> (c.8776C>T, p.R2926X) and a seven base-pair deletion resulting in frameshift mutation in exon 8 (c.6410_6416del, p.2137_2139del). A 24-year-old Korean man had Bardet-Biedl syndrome with diabetes, blindness, obesity, and a history of polydactyly. Whole exome sequencing revealed a nonsynonymous mutation in exon 11 of the <I>BBS1</I> gene (c.1061A>G, p.E354G) and mutation at the normal splicing recognition site of exon 7 of the <I>BBS1</I> gene (c.519-1G>T).</P><P><B>Conclusion</B></P><P>We found novel compound heterozygous mutations of Alström syndrome and Bardet-Biedl syndrome using whole exome sequencing. The whole exome sequencing successfully identified novel genetic variants of ciliopathy-associated diabetes.</P>

Influence of the Duration of Diabetes on the Outcome of a Diabetes Self-Management Education Program

Ko, Seung-Hyun,Park, Sin-Ae,Cho, Jae-Hyoung,Ko, Sun-Hye,Shin, Kyung-Mi,Lee, Seung-Hwan,Song, Ki-Ho,Park, Yong-Moon,Ahn, Yu-Bae Korean Diabetes Association 2012 Diabetes and Metabolism Journal Vol.36 No.3

<P><B>Background</B></P><P>Diabetes education and lifestyle modification are critical components in controlling blood glucose levels of people with type 2 diabetes. Until now, available data on the effectiveness of education with respect to the duration of diabetes are limited. We investigated whether adherence to lifestyle behavior modification prompted by diabetes education was influenced by the duration of diabetes.</P><P><B>Methods</B></P><P>Two hundred and twenty-five people with type 2 diabetes were recruited for an intensive, collaborative, group-based diabetes education program with annual reinforcement. We divided the patients into two groups based on the duration of their diabetes prior to the education program (≤1 year [≤1Y] vs. ≥3 years [≥3Y]). Dietary habits, physical activity, and the frequency of blood glucose self-monitoring were evaluated with a questionnaire prior to education and at the follow-up endpoint.</P><P><B>Results</B></P><P>The mean follow-up period was 32.2 months. The mean hemoglobin A1c (A1C) value was significantly lower in the ≤1Y group. Self-care behaviors, measured by scores for dietary habits (<I>P</I>=0.004) and physical activity (<I>P</I><0.001), were higher at the endpoint in the ≤1Y group than in the ≥3Y group. Logistic regression analysis revealed that a longer diabetes duration before education was significantly associated with mean A1C levels greater than or equal to 7.0% (53 mmol/mol).</P><P><B>Conclusion</B></P><P>Diabetes duration influenced the effectiveness of diabetes education on lifestyle behavior modification and glycemic control. More-intense, regular, and sustained reinforcement with encouragement may be required for individuals with longstanding type 2 diabetes.</P>

Glucolipotoxicity in Pancreatic β-Cells

Kim, Ji-Won,Yoon, Kun-Ho Korean Diabetes Association 2011 Diabetes and Metabolism Journal Vol.35 No.5

<P>The recent epidemic of type 2 diabetes in Asia differs from that reported in other regions of the world in several key areas: it has evolved over a much shorter time, in an earlier stage of life, and in people with lower body mass indices. These phenotypic characteristics of patients strongly suggest that insulin secretory defects may perform a more important function in the development and progression of diabetes. A genetic element clearly underlies β-cell dysfunction and insufficient β-cell mass; however, a number of modifiable factors are also linked to β-cell deterioration, most notably chronic hyperglycemia and elevated free fatty acid (FFA) levels. Neither glucose nor FFAs alone cause clinically meaningful β-cell toxicity, especially in patients with normal or impaired glucose tolerance. Thus the term 'glucolipotoxicity' is perhaps more appropriate in describing the phenomenon. Several mechanisms have been proposed to explain glucolipotoxicity-induced β-cell dysfunction and death, but its major factors appear to be depression of key transcription factor gene expression by altered intracellular energy metabolism and oxidative stress. Therefore, stabilization of metabolic changes induced by glucolipotoxicity in β-cells represents a new avenue for the treatment of type 2 diabetes mellitus.</P>

Role of Pyruvate Dehydrogenase Kinase 4 in Regulation of Blood Glucose Levels

Jeoung, Nam Ho,Harris, Robert A. Korean Diabetes Association 2010 Korean diabetes journal Vol.34 No.5

<P>In the well-fed state a relatively high activity of the pyruvate dehydrogenase complex (PDC) reduces blood glucose levels by directing the carbon of pyruvate into the citric acid cycle. In the fasted state a relatively low activity of the PDC helps maintain blood glucose levels by conserving pyruvate and other three carbon compounds for gluconeogenesis. The relative activities of the pyruvate dehydrogenase kinases (PDKs) and the opposing pyruvate dehydrogenase phosphatases determine the activity of PDC in the fed and fasted states. Up regulation of PDK4 is largely responsible for inactivation of PDC in the fasted state. PDK4 knockout mice have lower fasting blood glucose levels than wild type mice, proving that up regulation of PDK4 is important for normal glucose homeostasis. In type 2 diabetes, up regulation of PDK4 also inactivates PDC, which promotes gluconeogenesis and thereby contributes to the hyperglycemia characteristic of this disease. When fed a high fat diet, wild type mice develop fasting hyperglycemia but PDK4 knockout mice remain euglycemic, proving that up regulation of PDK4 contributes to hyperglycemia in diabetes. These finding suggest PDK4 inhibitors might prove useful in the treatment of type 2 diabetes.</P>

Cell Replacement and Regeneration Therapy for Diabetes

Korean Diabetes Association 2010 Korean diabetes journal Vol.34 No.2

<P>Reduction of beta cell function and a beta cell mass is observed in both type 1 and type 2 diabetes. Therefore, restoration of this deficiency might be a therapeutic option for treatment of diabetes. Islet transplantation has benefits, such as reduced incidence of hypoglycemia and achievement of insulin independence. However, the major drawback is an insufficient supply of islet donors. Transplantation of cells differentiated <I>in vitro</I> or <I>in vivo</I> regeneration of insulin-producing cells are possible approaches for beta cell/islet regenerative therapy. Embryonic and adult stem cells, pancreatic ductal progenitor cells, acinar cells, and other endocrine cells have been shown to differentiate into pancreatic beta cells. Formation of fully functional beta cells and the safety of these cells are critical issues for successful clinical application.</P>