Prevalence and Management of Diabetes in Korean Adults : Korea National Health and Nutrition Examination Surveys 1998–2005

Choi, Yong Jun,Kim, Hyeon Chang,Kim, Hee Man,Park, Seok Won,Kim, Jongoh,Kim, Dae Jung American Diabetes Association 2009 Diabetes Care Vol.32 No.11

<P><B>OBJECTIVE</B></P><P>This research investigated recent changes in the prevalence and management status of diabetes among Korean adults.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>The Korea National Health and Nutrition Examination Survey (KNHANES), a nationwide survey examining the general health and nutrition status of the Korean people, was conducted in 1998, 2001, and 2005. Using the first (1998; <I>n</I> = 5,645), second (2001; <I>n</I> = 4,154), and third (2005; <I>n</I> = 4,628) KNHANES datasets, in the present study, we estimated the prevalence of diabetes among Korean adults (aged ≥30 years), the proportions of known cases of diabetes, and the proportions of well-controlled cases of diabetes, as defined by either the American Diabetes Association (A1C <7%) or the International Diabetes Federation guidelines (A1C <6.5%).</P><P><B>RESULTS</B></P><P>In 2005, the prevalence of diabetes was estimated to be 9.1% (∼2.58 million people: 10.2% of men and 7.9% of women), including 6.2% with known diabetes and 2.9% with newly diagnosed diabetes. The prevalence of impaired fasting glucose was 17.4% (∼4.94 million people). The proportion of known cases of diabetes drastically increased from 23.2% in 1998 to 41.2% in 2001 and 68.0% in 2005 (<I>P</I> < 0.0001). Among known diabetic patients in 2005, 43.5 and 22.9% had A1C levels <7.0 and <6.5%, respectively.</P><P><B>CONCLUSIONS</B></P><P>The overall prevalence of diabetes in Korea has not changed significantly between 1998 and 2005. Physician diagnosis and treatment rates of diabetes have significantly improved during this period, but glycemic control was still poorer than that in other developed countries.</P>

Prevalence and Determinant Factors of Sarcopenia in Patients With Type 2 Diabetes : The Korean Sarcopenic Obesity Study (KSOS)

Kim, Tae Nyun,Park, Man Sik,Yang, Sae Jeong,Yoo, Hye Jin,Kang, Hyun Joo,Song, Wook,Seo, Ji A.,Kim, Sin Gon,Kim, Nan Hee,Baik, Sei Hyun,Choi, Dong Seop,Choi, Kyung Mook American Diabetes Association 2010 Diabetes care Vol.33 No.7

<P><B>OBJECTIVE</B></P><P>We examined prevalence of sarcopenia in Korean patients with type 2 diabetes and compared body compositional parameters between subjects with and without type 2 diabetes.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>The Korean Sarcopenic Obesity Study (KSOS) included 810 subjects (414 patients with diabetes and 396 control subjects) who were examined using dual-energy X-ray absorptiometry. Prevalence of sarcopenia was defined using the skeletal muscle index (SMI).</P><P><B>RESULTS</B></P><P>Prevalence in patients with diabetes and in the control group was 15.7 and 6.9%, respectively. In both men and women, SMI values were significantly decreased in patients with diabetes compared with subjects without diabetes. Furthermore, multiple logistic regression analysis showed that type 2 diabetes was independently associated with sarcopenia.</P><P><B>CONCLUSIONS</B></P><P>Type 2 diabetes was associated with increased risk of sarcopenia. These characteristics may contribute to physical disability and metabolic disorders in older adults with diabetes.</P>

Novel Leptin Receptor Mutation in NOD/LtJ Mice Suppresses Type 1 Diabetes Progression: II. Immunologic Analysis

Lee, C.-H.,Chen, Y.-G.,Chen, J.,Reifsnyder, P. C.,Serreze, D. V.,Clare-Salzler, M.,Rodriguez, M.,Wasserfall, C.,Atkinson, M. A.,Leiter, E. H. American Diabetes Association 2006 Diabetes Vol.55 No.1

<P>Recently, we identified in normally type 1 diabetes-prone NOD/LtJ mice a spontaneous new leptin receptor (LEPR) mutation (designated Lepr(db-5J)) producing juvenile obesity, hyperglycemia, hyperinsulinemia, and hyperleptinemia. This early type 2 diabetes syndrome suppressed intra-islet insulitis and permitted spontaneous diabetes remission. No significant differences in plasma corticosterone, splenic CD4(+) or CD8(+) T-cell percentages, or functions of CD3(+) T-cells in vitro distinguished NOD wild-type from mutant mice. Yet splenocytes from hyperglycemic mutant donors failed to transfer type 1 diabetes into NOD.Rag1(-/-) recipients over a 13-week period, whereas wild-type donor cells did so. This correlated with significantly reduced (P < 0.01) frequencies of insulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD8(+) T-effector clonotypes in mutant mice. Intra-islet insulitis was also significantly suppressed in lethally irradiated NOD-Lepr(db-5J)/Lt recipients reconstituted with wild-type bone marrow (P < 0.001). In contrast, type 1 diabetes eventually developed when mutant marrow was transplanted into irradiated wild-type recipients. Mitogen-induced T-cell blastogenesis was significantly suppressed when splenic T-cells from both NOD/Lt and NOD-Lepr(db-5J)/Lt donors were incubated with irradiated mutant peritoneal exudate cells (P < 0.005). In conclusion, metabolic disturbances elicited by a type 2 diabetes syndrome (insulin and/or leptin resistance, but not hypercorticism) appear to suppress type 1 diabetes development in NOD-Lepr(db-5J)/Lt by inhibiting activation of T-effector cells.</P>

Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control

Pollack, Samuela,Igo Jr., Robert P.,Jensen, Richard A.,Christiansen, Mark,Li, Xiaohui,Cheng, Ching-Yu,Ng, Maggie C.Y.,Smith, Albert V.,Rossin, Elizabeth J.,Segrè,, Ayellet V.,Davoudi, Samaneh,Ta American Diabetes Association 2019 Diabetes Vol.68 No.2

<P>To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (<I>n</I> = 3,246) and seven African American cohorts (<I>n</I> = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a <I>P</I> value <1 × 10<SUP>−5</SUP> were investigated in replication cohorts that included 18,545 European, 16,453 Asian, and 2,710 Hispanic subjects. After correction for multiple testing, the C allele of rs142293996 in an intron of nuclear VCP-like (<I>NVL</I>) was associated with DR in European discovery cohorts (<I>P</I> = 2.1 × 10<SUP>−9</SUP>), but did not reach genome-wide significance after meta-analysis with replication cohorts. We applied the Disease Association Protein-Protein Link Evaluator (DAPPLE) to our discovery results to test for evidence of risk being spread across underlying molecular pathways. One protein–protein interaction network built from genes in regions associated with proliferative DR was found to have significant connectivity (<I>P</I> = 0.0009) and corroborated with gene set enrichment analyses. These findings suggest that genetic variation in <I>NVL,</I> as well as variation within a protein–protein interaction network that includes genes implicated in inflammation, may influence risk for DR.</P>

A Genome-Wide Association Study of Gestational Diabetes Mellitus in Korean Women

Kwak, Soo Heon,Kim, Sung-Hoon,Cho, Young Min,Go, Min Jin,Cho, Yoon Shin,Choi, Sung Hee,Moon, Min Kyong,Jung, Hye Seung,Shin, Hyoung Doo,Kang, Hyun Min,Cho, Nam H.,Lee, In Kyu,Kim, Seong Yeon,Han, Bok- American Diabetes Association 2012 Diabetes Vol.61 No.2

<P><B/></P><P>Knowledge regarding the genetic risk loci for gestational diabetes mellitus (GDM) is still limited. In this study, we performed a two-stage genome-wide association analysis in Korean women. In the stage 1 genome scan, 468 women with GDM and 1,242 nondiabetic control women were compared using 2.19 million genotyped or imputed markers. We selected 11 loci for further genotyping in stage 2 samples of 931 case and 783 control subjects. The joint effect of stage 1 plus stage 2 studies was analyzed by meta-analysis. We also investigated the effect of known type 2 diabetes variants in GDM. Two loci known to be associated with type 2 diabetes had a genome-wide significant association with GDM in the joint analysis. rs7754840, a variant in <I>CDKAL1</I>, had the strongest association with GDM (odds ratio 1.518; <I>P</I> = 6.65 × 10<SUP>−16</SUP>). A variant near <I>MTNR1B</I>, rs10830962, was also significantly associated with the risk of GDM (1.454; <I>P</I> = 2.49 × 10<SUP>−13</SUP>). We found that there is an excess of association between known type 2 diabetes variants and GDM above what is expected under the null hypothesis. In conclusion, we have confirmed that genetic variants in <I>CDKAL1</I> and near <I>MTNR1B</I> are strongly associated with GDM in Korean women. There seems to be a shared genetic basis between GDM and type 2 diabetes.</P>

Hypoglycemia at Admission in Patients With Acute Myocardial Infarction Predicts a Higher 30-Day Mortality in Patients With Poorly Controlled Type 2 Diabetes Than in Well-Controlled Patients

Lee, Sang Ah,Cho, Suk Ju,Jeong, Myung Ho,Kim, Young Jo,Kim, Chong Jin,Cho, Myeong Chan,Kim, Hyo-Soo,Ahn, Youngkeun,Koh, Gwanpyo,Lee, Jeong mi,Oh, Seok Kyu,Yun, Kyeong Ho,Kim, Ha Young,Cho, Chung Gu,Le American Diabetes Association 2014 Diabetes Care Vol.37 No.8

<P><B>OBJECTIVE</B></P><P>We aimed to evaluate the association between hypoglycemia at admission and 30-day mortality in patients with acute myocardial infarction (AMI) and to determine whether these associations differed according to diabetes-control status in AMI patients with diabetes.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>We analyzed the prognostic significance of hypoglycemia and hyperglycemia in 34,943 AMI patients with or without type 2 diabetes from two AMI registries: the Korea Acute Myocardial Infarction Registry (KAMIR) and the Korea Working Group on Myocardial Infarction (KorMI).</P><P><B>RESULTS</B></P><P>The patients were divided into five groups according to serum-glucose levels at admission: <3.9 mmol/L (<70 mg/dL); 3.9–7.72 mmol/L (70–139 mg/dL); 7.78–11.06 mmol/L (140–199 mg/dL); 11.11–14.39 mmol/L (200–259 mg/dL); and ≥14.44 mmol/L (≥260 mg/dL). The 30-day mortality rates in the lowest and highest glucose groups were higher than those in other groups; the lowest glucose group had the highest mortality for patients with type 2 diabetes, after adjusting for multiple factors. We also extracted and compared four subgroups from the patients with type 2 diabetes, based on hemoglobin A1c and serum-glucose levels at admission: group A, <6.5% (48 mmol/mol) and <3.9 mmol/L; group B, <6.5% (48 mmol/mol) and ≥11.11 mmol/L; group C, ≥8% (64 mmol/mol) and <3.9 mmol/L; and group D, ≥8% (64 mmol/mol) and ≥11.11 mmol/L. Group C had the highest 30-day mortality rate among the groups.</P><P><B>CONCLUSIONS</B></P><P>These data suggest that hypoglycemia at admission affects clinical outcomes differently in AMI patients with type 2 diabetes depending on the diabetes-control status.</P>

Essential role for signal transducer and activator of transcription-1 in pancreatic beta-cell death and autoimmune type 1 diabetes of nonobese diabetic mice.

Kim, Sunshin,Kim, Hun Sik,Chung, Kun Wook,Oh, Seung Hoon,Yun, Jong Won,Im, Sin-Hyeog,Lee, Moon-Kyu,Kim, Kwang-Won,Lee, Myung-Shik American Diabetes Association] 2007 Diabetes Vol.56 No.10

<P>OBJECTIVE: We have reported important roles for signal transducer and activator of transcription-1 (STAT1) in pancreatic beta-cell death by cytokines in vitro. However, in vivo evidence supporting the role for STAT1 in natural type 1 diabetes has not been reported. We studied whether STAT1 plays an important role in the development of natural type 1 diabetes. RESEARCH DESIGN AND METHODS: We produced nonobese diabetic (NOD)/STAT1(-/-) mice by backcrossing and studied the in vivo role of STAT1 in beta-cell death and type 1 diabetes. RESULTS: STAT1(-/-) islet cells were resistant to death by interferon (IFN)-gamma/tumor necrosis factor (TNF)-alpha or IFN-gamma/interleukin (IL)-1 beta combination. Cytochrome c translocation by IFN-gamma/TNF-alpha was abrogated in STAT1(-/-) islet cells. The induction of X-linked inhibitor of apoptosis protein by TNF-alpha was inhibited by IFN-gamma in STAT1(+/-) islet cells but not in STAT1(-/-) islet cells. Inducible nitric oxide (NO) synthase induction and NO production by IFN-gamma/IL-1 beta were impaired in STAT1(-/-) islet cells. Strikingly, diabetes and insulitis were completely abrogated in NOD/STAT1(-/-) mice. Development of diabetes after CD4(+) diabetogenic T-cell transfer was inhibited in those mice. STAT1(-/-) neonatal pancreata were not destroyed when grafted into diabetic NOD/BDC2.5 mice that developed CD4(+) T-cell-dependent islet cell death. In NOD/STAT1(-/-) mice, autoreactive T-cell priming was not impaired, but Th1 differentiation was impaired. A janus kinase (JAK) 2 inhibitor upstream of STAT1 attenuated islet cell death by IFN-gamma/TNF-alpha or IFN-gamma/IL-1 beta and delayed diabetes onset in NOD/BDC2.5-SCID mice. CONCLUSIONS: These data demonstrate a critical role for STAT1 in beta-cell death, T-cell immunoregulation, and type 1 diabetes in vivo and suggest potential therapeutic values of STAT1 or JAK inhibitors in the treatment/prevention of type 1 diabetes.</P>

Hemoglobin A _1c as a Diagnostic Tool for Diabetes Screening and New-Onset Diabetes Prediction : A 6-year community-based prospective study

Choi, Sung Hee,Kim, Tae Hyuk,Lim, Soo,Park, Kyong Soo,Jang, Hak C.,Cho, Nam H. American Diabetes Association 2011 Diabetes care Vol.34 No.4

<P><B>OBJECTIVE</B></P><P>Various cutoff levels of hemoglobin A<SUB>1c</SUB> (A1C) have been suggested to screen for diabetes, although more consensus about the best level, especially for different ethnicities, is required. We evaluated the usefulness of A1C levels when screening for undiagnosed diabetes and as a predictor of 6-year incident diabetes in a prospective, population-based cohort study.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>A total 10,038 participants were recruited from the Ansung-Ansan cohort study. All subjects underwent a 75-g oral glucose tolerance test at baseline and at each biennial follow-up. Excluding subjects with a previous history of diabetes (<I>n</I> = 572), the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of the A1C cutoff. The Cox proportional hazards model was used to predict diabetes at 6 years.</P><P><B>RESULTS</B></P><P>At baseline, 635 participants (6.8%) had previously undiagnosed diabetes. An A1C cutoff of 5.9% produced the highest sum of sensitivity (68%) and specificity (91%). At 6 years, 895 (10.2%) subjects had developed incident diabetes. An A1C cutoff of 5.6% had the highest sum of sensitivity (59%) and specificity (77%) for the identification of subsequent 6-year incident diabetes. After multivariate adjustment, men with baseline A1C ≥5.6% had a 2.4-fold increased risk and women had a 3.1-fold increased risk of new-onset diabetes.</P><P><B>CONCLUSIONS</B></P><P>A1C is an effective and convenient method for diabetes screening. An A1C cutoff of 5.9% may identify subjects with undiagnosed diabetes. Individuals with A1C ≥5.6% have an increased risk for future diabetes.</P>

Fasting Glucose and All-Cause Mortality by Age in Diabetes: A Prospective Cohort Study

Yi, Sang-Wook,Park, Sangkyu,Lee, Yong-ho,Balkau, Beverley,Yi, Jee-Jeon American Diabetes Association 2018 Diabetes care Vol.41 No.3

<P><B>OBJECTIVE</B></P><P>To examine associations between fasting glucose and mortality and to identify the levels associated with lowest mortality by age in diabetes.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>A total of 359,645 Korean adults with known prevalent diabetes participated in health screening during 2001–2004 and were followed up until 2013.</P><P><B>RESULTS</B></P><P>U-curve associations were found. Fasting glucose levels associated with the lowest mortality were ∼90–130 mg/dL, except for in those aged 18–44 years (∼80–95 mg/dL). Multivariable-adjusted hazard ratios of fasting glucose <65, 65–74, 75–84, 140–169, 170–199, and ≥200 mg/dL were 1.46, 1.12, 1.09, 1.12, 1.31, and 1.78, respectively, compared with 85–99 mg/dL.</P><P><B>CONCLUSIONS</B></P><P>Optimal fasting glucose range for survival is higher in adults with than without known prevalent diabetes, except, perhaps, younger adults. Tight glucose control may lessen premature death in younger adults with diabetes. Hypoglycemia (<65 mg/dL) was associated with higher mortality than was fasting glucose 170–199 mg/dL, while fasting glucose 65–84 mg/dL had risks comparable with those at levels 140–169 mg/dL in diabetes.</P>

Common Presence of Non-Transferrin-Bound Iron Among Patients With Type 2 Diabetes

Lee, D.-H.,Liu, D. Y.,Jacobs, D. R.,Shin, H.-R.,Song, K.,Lee, I.-K.,Kim, B.,Hider, R. C. American Diabetes Association 2006 Diabetes care Vol.29 No.5

<P>OBJECTIVE: Recently, we reported increased cardiovascular disease mortality among supplemental vitamin C users with type 2 diabetes in a prospective cohort study. Because vitamin C may cause oxidative stress in the presence of redox active iron, we hypothesized that non-transferrin-bound iron (NTBI), a form of iron susceptible to redox activity, may be present in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We measured serum NTBI levels using high-performance liquid chromatography in 48 patients with known diabetes (at least 5 years duration since diagnosis), 49 patients with newly diagnosed diabetes, and 47 healthy control subjects (frequency matched on age and sex). RESULTS: NTBI was commonly present in diabetes: 59% in newly diagnosed diabetes and 92% in advanced diabetes. Mean NTBI values varied significantly between the three groups, with the highest values being observed in patients with known diabetes and the lowest in the control subjects (0.62 +/- 0.43 vs. 0.24 +/- 0.29 vs. 0.04 +/- 0.13 micromol/l Fe). Serum total iron or percent transferrin saturation were very similar among the three groups, yet NTBI was strongly associated with serum total iron (r = 0.74, P < 0.01) and percent transferrin saturation (r = 0.70, P < 0.01) among the patients with known diabetes. CONCLUSIONS: Consistent with our hypothesis, these data demonstrate the common existence of NTBI in type 2 diabetic patients with a strong gradient with severity. Prospective cohort studies are required to clarify the clinical relevance of increased NTBI levels.</P>