Diabetes In Koreans Research Articles

1-Hour Post-Load Glucose: Early Screening for High Risk of Type 2 Diabetes in Koreans with Normal Fasting Glucose.

With rising the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes, the importance of 1-hour post-load plasma glucose (1-h PG) for early hyperglycemia screening is emphasized. This study investigates the utility of 1-h PG in predicting T2DM in adults with normal fasting plasma glucose (FPG) levels. 7,504 participants were categorized into three groups: normal glucose tolerance (NGT) with 1-h PG < 155 mg/dL, NGT with 1-h PG ≥ 155 mg/dL, and impaired glucose tolerance (IGT). Insulin sensitivity and secretion indices were compared between groups at baseline, and T2DM incidence was analyzed using Cox proportional hazards models. The predictive abilities of 1-h PG and 2-hour post-load plasma glucose (2-h PG) were assessed with receiver operating characteristic analysis. At baseline, the composite insulin sensitivity index in the NGT & 1-h PG ≥ 155 mg/dL group was similarly reduced as in the IGT group (P = .076). Over a mean follow-up of 7.4 years, T2DM developed in 960 patients (12.8%). The highest risk was in the IGT group (hazard ratio [HR] 5.47), followed by the NGT & 1-h PG ≥ 155 mg/dL group (HR 2.74), compared to the NGT & 1-h PG < 155 mg/dL group. The 1-h PG level had a higher area under the curve (0.772) than other glycemic parameters, including 2-h PG. Even with normal FPG, a 1-h PG ≥ 155 mg/dL indicates lower insulin sensitivity similar to IGT and increased T2DM risk, making it a more effective early screening tool than 2-h PG.

Insulin Resistance and Impaired Insulin Secretion Predict Incident Diabetes: A Statistical Matching Application to the Two Korean Nationwide, Population-Representative Cohorts.

To evaluate whether insulin resistance and impaired insulin secretion are useful predictors of incident diabetes in Koreans using nationwide population-representative data to enhance data privacy. This study analyzed the data of individuals without diabetes aged >40 years from the Korea National Health and Nutrition Examination Survey (KNHANES) 2007-2010 and 2015 and the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Owing to privacy concerns, these databases cannot be linked using direct identifiers. Therefore, we generated 10 synthetic datasets, followed by statistical matching with the NHIS-HEALS. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were used as indicators of insulin resistance and insulin secretory function, respectively, and diabetes onset was captured in NHIS-HEALS. A median of 4,580 (range, 4,463 to 4,761) adults were included in the analyses after statistical matching of 10 synthetic KNHANES and NHIS-HEALS datasets. During a mean follow-up duration of 5.8 years, a median of 4.7% (range, 4.3% to 5.0%) of the participants developed diabetes. Compared to the reference low-HOMA-IR/high-HOMA-β group, the high-HOMA-IR/low- HOMA-β group had the highest risk of diabetes, followed by high-HOMA-IR/high-HOMA-β group and low-HOMA-IR/low- HOMA-β group (median adjusted hazard ratio [ranges]: 3.36 [1.86 to 6.05], 1.81 [1.01 to 3.22], and 1.68 [0.93 to 3.04], respectively). Insulin resistance and impaired insulin secretion are robust predictors of diabetes in the Korean population. A retrospective cohort constructed by combining cross-sectional synthetic and longitudinal claims-based cohort data through statistical matching may be a reliable resource for studying the natural history of diabetes.

Association between restrictive pulmonary disease and type 2 diabetes in Koreans: A cross-sectional study.

BACKGROUNDDiabetes is a progressive disease that increases glucose levels in the blood. While studies have shown that patients with pulmonary disease (both obstructive and restrictive pulmonary disease) have a higher prevalence of type 2 diabetes mellitus (T2DM), there have been more studies on restrictive patterns than chronic obstructive pulmonary disease.AIMTo assess whether restrictive and obstructive pulmonary diseases are associated with T2DM in Koreans.METHODSFor our analysis, we used data from the Korea National Health and Nutrition Examination Survey. A total of 2830 subjects were included in this study. Spirometry results were categorized into three patterns: Normal, restrictive pulmonary disease (RPD), and obstructive pulmonary disease (OPD).RESULTSThe factors used as diabetic indicators (i.e. homeostatic model assessment of insulin resistance, homeostatic model assessment of beta-cell function, glycated hemoglobin, and fasting insulin) were among the highest in RPD but not in OPD. Based on multivariate logistic regression analysis, subjects with RPD were found with an increased odds ratio [OR: 1.907, 95% confidence interval (CI): 1.110-3.277] for T2DM compared with subjects with normal pulmonary function, whereas in patients with OPD, the OR had not increased. Model 4, which adjusted for the variables that could affect diabetes and pulmonary disease, showed a significant increase in the T2DM OR to RPD (OR: 2.025, 95%CI: 1.264-3.244). On the other hand, no statistically significant difference was shown in OPD (OR: 0.982, 95%CI: 0.634-1.519).CONCLUSIONRPD, not OPD, is highly associated with T2DM regardless of the risk factors of various T2DMs that can be confounds.

Serum Transferrin Predicts New-Onset Type 2 Diabetes in Koreans: A 4-Year Retrospective Longitudinal Study.

BackgroundIt is well known that high serum ferritin, a marker of iron storage, predicts incident type 2 diabetes. Limited information is available on the association between transferrin, another marker of iron metabolism, and type 2 diabetes. Thus, we investigated the association between transferrin and incident type 2 diabetes.MethodsTotal 31,717 participants (mean age, 40.4±7.2 years) in a health screening program in 2005 were assessed via cross-sectional analysis. We included 30,699 subjects who underwent medical check-up in 2005 and 2009 and did not have type 2 diabetes at baseline in this retrospective longitudinal analysis.ResultsThe serum transferrin level was higher in the type 2 diabetes group than in the non-type 2 diabetes group (58.32±7.74 μmol/L vs. 56.17±7.96 μmol/L, P<0.001). Transferrin correlated with fasting serum glucose and glycosylated hemoglobin in the correlational analysis (r=0.062, P<0.001 and r=0.077, P<0.001, respectively) after full adjustment for covariates. Transferrin was more closely related to homeostasis model assessment of insulin resistance than to homeostasis model assessment of β cell function (r=0.042, P<0.001 and r=−0.019, P=0.004, respectively) after full adjustment. Transferrin predicted incident type 2 diabetes in non-type 2 diabetic subjects in a multivariate linear regression analysis; the odds ratio (95% confidence interval [CI]) of the 3rd tertile compared to that in the 1st tertile of transferrin for incident diabetes was 1.319 (95% CI, 1.082 to 1.607) after full adjustment (P=0.006).ConclusionTransferrin is positively associated with incident type 2 diabetes in Koreans.

The Association between Pulmonary Functions and Incident Diabetes: Longitudinal Analysis from the Ansung Cohort in Korea.

BackgroundWe sought to explore whether reduced pulmonary function is an independent risk factor for incident diabetes in Koreans.MethodsWe conducted a prospective cohort study of pulmonary function as a risk factor for incident diabetes using 10-year follow-up data from 3,864 middle-aged adults from the Ansung cohort study in Korea. The incidence of diabetes was assessed using both oral glucose tolerance tests and glycosylated hemoglobin levels.ResultsDuring 37,118 person-years of follow-up, 583 participants developed diabetes (incidence rate: 15.7 per 1,000 person-years). The mean follow-up period was 8.0±3.7 years. Forced vital capacity (FVC; % predicted) and forced expiratory volume in 1 second (FEV1; % predicted) were significantly correlated with incident diabetes in a graded manner after adjustment for sex, age, smoking, exercise, and metabolic parameters. The adjusted hazard ratio (HR) and confidence interval (CI) for diabetes were 1.408 (1.106 to 1.792) and 1.469 (1.137 to 1.897) in the first quartiles of FVC and FEV1, respectively, when compared with the highest quartile. Furthermore, the FVC of the lowest first and second quartiles showed a significantly higher 10-year panel homeostasis model assessment of insulin resistance index, with differences of 0.095 (95% CI, 0.010 to 0.018; P=0.028) and 0.127 (95% CI, 0.044 to 0.210; P=0.003), respectively, when compared to the highest quartiles.ConclusionFVC and FEV1 are independent risk factors for developing diabetes in Koreans. Pulmonary factors are possible risk factors for insulin resistance and diabetes.

Combined effect of serum alanine aminotransferase and gamma-glutamyltransferase on incidence of diabetes mellitus: A longitudinal study.

High levels of serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are associated with increased diabetes risk. In the present study, we investigated the combined effects of ALT and GGT on the development of diabetes in a Korean population. A total of 9405 individuals (4020 women and 5385 men) without diabetes were enrolled in this study. From the baseline health screening to the follow-up examination, the development of diabetes, based on changes in ALT and GGT quartile levels, was analyzed. In addition, we analyzed the quartiles of ALT and GGT together to determine any synergistic effect from the fourth quartile of ALT and GGT on the development of diabetes. The development of diabetes gradually increased with an increase in the circulating levels of ALT and GGT. For the fourth quartile ALT and GGT, the hazard ratios of diabetes compared with the first quartile were 1.892 (95% confidence interval [CI]: 1.26–2.83, P = .002) and 3.526 (95% CI: 2.12–5.85, P < .001) after adjusting for confounders, respectively. Hazard ratios of diabetes after combining both fourth quartiles of ALT and GGT were 3.663 (95% CI: 2.42–5.52, P < .001), as compared with the first and second quartiles. Serum ALT and GGT levels are well associated with diabetes in Koreans after adjusting for confounders, and a combination of ALT and GGT levels can have a synergy in predicting the development of diabetes.

The Association Between Lung Function and Type 2 Diabetes in Koreans.

ObjectivesThis study was performed to test the association between lung function and type 2 diabetes mellitus (T2DM) in Korean patients.MethodsData from the 6th Korea National Health and Nutrition Examination Survey (2013 to 2015) was used in this study. There were 3,466 individuals aged between 40 and 80 years, with T2DM, who had a smoking and alcohol status listed, and blood analysis (including blood pressure), were included in this study. Lung function, measured by spirometer ventilatory dysfunction was categorized into 3 patterns: normal, restrictive ventilatory dysfunction, and obstructive ventilatory dysfunction (OVD).ResultsBased on multivariate logistic regression analysis, individuals with restrictive ventilatory dysfunction had an increased odds ratio (OR 1.615, 95% CI 1.137–2.294) for T2DM compared with individuals with normal ventilatory function, whereas OVD had no increase in the odds ratio (OR 1.169, 95 % CI 0.857–1.594). Model 1, which adjusted for age and gender, showed that the probability of having restrictive disorder was 1.559 times (95% CI 1.617–2.082) higher for prediabetes patients, and 2.320 times (95% CI 1.611–3.343) higher for T2DM patients, compared to normal individuals. For Model 4, which was fully adjusted for variables, the probability of having a restrictive disorder was 1.837 times higher for T2DM patients (95% CI 1.260–2.679).ConclusionRestrictive ventilatory dysfunction, but not OVD, was associated independently with T2DM.

Gender differences of visceral fat area for predicting incident type 2 diabetes in Koreans

AimsVisceral fat accumulation is known to be an independent risk factor for type 2 diabetes. We aimed to determine the optimal cutoff values of visceral fat area (VFA) for predicting incident type 2 diabetes in Koreans. MethodsOur study population consisted of 13,004 individuals initially free of type 2 diabetes the ages between 20 and 69 years, who underwent routine health examinations between January 2012 and December 2012 and returned for follow–up examinations between January 2016 and December 2016. VFA values were derived from bioelectrical impedance analysis (BIA) at baseline. ResultsDuring a median follow–up of 4.02 years, a total of 481 (4.6% for men and 2.3% for women) incident cases of type 2 diabetes were identified. According to the receiver operating characteristic (ROC) curve, the optimal VFA cutoff values for predicting incident type 2 diabetes were 118.8 cm2 in men and 82.6 cm2 in women, respectively. In a multivariable–adjusted model including obesity and glycemic status, the odds ratios (ORs) of VFA over 120 cm2 in men and 80 cm2 in women were 1.72 and 3.56, respectively. ConclusionsHigher VFA at baseline was an independent risk factor for developing type 2 diabetes and the optimal VFA cutoff values were markedly different between men and women. Therefore, sex–specific reference values for visceral fat obesity such that men with a VFA ≥120 cm2 and women with a VFA ≥80 cm2 should be considered to predict incident type 2 diabetes.

Alcohol Intake Interacts with CDKAL1, HHEX, and OAS3 Genetic Variants, Associated with the Risk of Type 2 Diabetes by Lowering Insulin Secretion in Korean Adults.

Since alcohol intake increases the prevalence of type 2 diabetes (T2DM) in Koreans, we tested the hypothesis that the interactions of genetic variants involved in β-cell function and mass with alcohol intake increase the T2DM risk. The single nucleotide polymorphisms (SNPs) were selected by genome-wide association study for insulin secretion after adjusting for age, gender, area of residence, body mass index, and alcohol intake (p<1×10-4 ) in 8,842 middle-aged adults in the Ansan/Ansung cohort. Genetic risk scores (GRSs) were calculated by summing the risk alleles of 4 selected SNPs, CDKAL1 rs7754840 and rs9460546, HHEX rs5015480, and OAS3 rs2072134. The GRSs were categorized into 3 groups by tertiles, and the association between GRS and insulin secretion was measured using logistic regression after adjusting for confounding factors in the Ansan/Ansung cohort. The results were confirmed by the Rural cohort. HOMA-IR was higher and HOMA-B was much lower in the High-GRS than the Low-GRS in both cohorts. T2DM risk was higher by approximately 1.5-fold in the High-GRS than in the Low-GRS in both cohorts. In the High-GRS group, HOMA-B decreased by 0.89- and 0.62-fold in comparison with the Low-GRS in the Ansan/Ansung cohort and Rural cohort. The GRS interacted with alcohol intake to increase the risk of developing T2DM in the Ansan/Ansung cohort (p=0.036) and Rural cohort (p=0.071). The risk of T2DM increased in the High-GRS group with high alcohol intake and it was associated with decreased HOMA-B. High alcohol intake decreased HOMA-B regardless of GRS, and HOMA-B was lower in the descending order of Medium-GRS, Low-GRS, and High-GRS. However, HOMA-IR was not altered by alcohol intake, but was elevated in the High-GRS more than in the other groups. Subjects with a High-GRS had an elevated risk of T2DM even with moderate alcohol intakes due to lower HOMA-B. High alcohol intake appears to be a risk factor for all Asians regardless of alcohol intake.

A Nonsynonymous Variant in GLP-1R Is Associated with Decreased Risk of Type 2 Diabetes in Koreans

Type 2 diabetes (T2D) is a common complex disorder with strong genetic predisposition. Although different ethnic groups share most of the common variants of T2D, there might be nonsynonymous variants that are specific to an ethnic group. In this study, we used whole exome sequencing (N=917) and exome genotyping array (N=3,026) to identify nonsynonymous variants in Korean T2D cases and controls (stage 1) and validated the findings in an independent set of 15,095 T2D cases and controls (stage 2). Whole exome capture was prepared using Agilent SureSelect version 4+UTR and sequencing was performed by Illumina HiSeq 2000. Nonsynonymous variants were incorporated into customized Axiom Biobank Plus Genotyping array. Genotype imputation was performed with 1,000 Genomes Project phase 3 reference. In silico data look-up was done for stage 2 analyses. EPACTS software was used for association testing and METAL was used for meta-analysis of stage 1 and 2 results. We identified 728,838 variants using whole exome sequencing, which include 258,463 novel variants. A nonsynonymous variant in GLP-1R (rs3765467, R131Q) was associated with decreased risk of T2D in genome-wide significance (OR = 0.85, P = 3.01x10-8). This variant was associated with lower fasting glucose concentration (P = 0.00020) and lower HbA1c level (P = 0.0085) in nondiabetic controls. The minor allele frequency of this variant was 21.1% in Koreans but it was monomorphic in Europeans. We also validated the previous association between PAX4 nonsynonymous variant (rs2233580, R192H) and increased risk of T2D (OR = 1.52, P = 6.41x10-15). This variant was associated with lower age at diagnosis and decreased C-peptide level in T2D cases (P &amp;lt; 0.05). Gene-wise analysis revealed that SLC30A8 was most significantly associated with decreased risk of T2D (P = 0.00010) by Madsen and Browning method. In summary, we have identified East Asian specific nonsynonymous variants in GLP-1R and PAX4 to be associated with T2D in genome-wide significance. Disclosure S. Kwak: None. J. Chae: None. J. Yoon: None. S. Choi: None. S. Lim: None. M. Moon: None. Y. Cho: None. H. Jang: None. Y. Cho: None. H. Kang: None. J. Kim: None. K. Park: None.

The product of fasting plasma glucose and triglycerides improves risk prediction of type 2 diabetes in middle-aged Koreans

BackgroundScreening for risk of type 2 diabetes mellitus (T2DM) is an important public health issue. Previous studies report that fasting plasma glucose (FPG) and triglyceride (TG)-related indices, such as lipid accumulation product (LAP) and the product of fasting glucose and triglyceride (TyG index), are associated with incident T2DM. We aimed to evaluate whether FPG or TG-related indices can improve the predictive ability of a diabetes risk model for middle-aged Koreans.Methods7708 Koreans aged 40–69 years without diabetes at baseline were eligible from the Korean Genome and Epidemiology Study. The overall cumulative incidence of T2DM was 21.1% (766 cases) in men and 19.6% (797 cases) in women. Therefore, the overall cumulative incidence of T2DM was 20.3% (1563 cases). Multiple logistic regression analysis was conducted to compare the odds ratios (ORs) for incident T2DM for each index. The area under the receiver operating characteristic curve (AROC), continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI) were calculated when each measure was added to the basic risk model for diabetes.ResultsAll the TG-related indices and FPG were more strongly associated with incident T2DM than WC in our study population. The adjusted ORs for the highest quartiles of WC, TG, FPG, LAP, and TyG index compared to the lowest, were 1.64 (95% CI, 1.13–2.38), 2.03 (1.59–2.61), 3.85 (2.99–4.97), 2.47 (1.82–3.34), and 2.79 (2.16–3.60) in men, and 1.17 (0.83–1.65), 2.42 (1.90–3.08), 2.15 (1.71–2.71), 2.44 (1.82–3.26), and 2.85 (2.22–3.66) in women, respectively. The addition of TG-related parameters or FPG, but not WC, to the basic risk model for T2DM (including age, body mass index, family history of diabetes, hypertension, current smoking, current drinking, and regular exercise) significantly increased cNRI, IDI, and AROC in both sexes.ConclusionsAdding either TyG index or FPG into the basic risk model for T2DM increases its prediction and reclassification ability. Compared to FPG, TyG index was a more robust T2DM predictor in the stratified sex and fasting glucose level. Therefore, TyG index should be considered as a screening tool for identification of people at high risk for T2DM in practice.

Serum metabolite profile associated with incident type 2 diabetes in Koreans: findings from the Korean Genome and Epidemiology Study

The identification of metabolic alterations in type 2 diabetes (T2D) is useful for elucidating the pathophysiology of the disease and in classifying high-risk individuals. In this study, we prospectively examined the associations between serum metabolites and T2D risk in a Korean community-based cohort (the Ansan–Ansung cohort). Data were obtained from 1,939 participants with available metabolic profiles and without diabetes, cardiovascular disease, or cancer at baseline. The acylcarnitine, amino acid, amine, and phospholipid levels in fasting serum samples were analyzed by targeted metabolomics. During the 8-year follow-up period, we identified 282 cases of incident T2D. Of all metabolites measured, 22 were significantly associated with T2D risk. Specifically, serum levels of alanine, arginine, isoleucine, proline, tyrosine, valine, hexose and five phosphatidylcholine diacyls were positively associated with T2D risk, whereas lyso-phosphatidylcholine acyl C17:0 and C18:2 and other glycerophospholipids were negatively associated with T2D risk. The associated metabolites were further correlated with T2D-relevant risk factors such as insulin resistance and triglyceride indices. In addition, a healthier diet (as measured by the modified recommended food score) was independently associated with T2D risk. Alterations of metabolites such as amino acids and choline-containing phospholipids appear to be associated with T2D risk in Korean adults.

Impact of weight changes on the incidence of diabetes mellitus: a Korean nationwide cohort study

Obesity is a well-known risk factor for type 2 diabetes, but few data exist on the association between weight changes and diabetes risk in non-obese subjects. This study aimed to investigate the effect of weight changes on the incidence of type 2 diabetes in Korea, using 51,405 non-diabetic subjects. Individuals who developed type 2 diabetes were more likely to be older and male, to have high body mass index (BMI), blood pressure, fasting blood glucose, and total cholesterol, to be current smokers and frequent drinkers, to be hypertensive and hyperlipidemic, and to have a family history of diabetes, compared to those without type 2 diabetes. Compared with the consistently non-obese group, there was a higher hazard ratio for incident diabetes (95% confidence interval) in subjects becoming obese [1.49 (1.26–1.77)] and remaining obese [2.56 (2.34–2.81)] after adjustment for confounding factors. Decreased BMI was significantly associated with lower risks for incident diabetes and the trends were more evident in the non-obese group. However, overall there was no significant association of increased BMI with incident diabetes. In conclusion, weight loss was significantly associated with lower risk for diabetes both in non-obese and obese Koreans, but particularly in the non-obese.

Calpain-10 and Adiponectin Gene Polymorphisms in Korean Type 2 Diabetes Patients.

BackgroundGenetic variations in calpain-10 and adiponectin gene are known to influence insulin secretion and resistance in type 2 diabetes mellitus. Recently, several single nucleotide polymorphisms (SNPs) in calpain-10 and adiponectin gene have been reported to be associated with type 2 diabetes and various metabolic derangements. We investigated the associations between specific calpain-10 and adiponectin gene polymorphisms and Korean type 2 diabetes patients.MethodsOverall, 249 type 2 diabetes patients and 131 non-diabetic control subjects were enrolled in this study. All the subjects were genotyped for SNP-43 and -63 of calpain-10 gene and G276T and T45G frequencies of the adiponectin gene. The clinical characteristics and measure of glucose metabolism were compared within these genotypes.ResultsAmong calpain-10 polymorphisms, SNP-63 T/T were more frequent in diabetes patients, and single SNP-63 increases the susceptibility to type 2 diabetes. However, SNP-43 in calpain-10 and T45G and intron G276T in adiponectin gene were not significantly associated with diabetes, insulin resistance, nor insulin secretion.ConclusionVariations in calpain-10, SNP-63 seems to increase the susceptibility to type 2 diabetes in Koreans while SNP-43 and adiponectin SNP-45, -276 are not associated with impaired glucose metabolism.

Pathophysiology of Type 2 Diabetes in Koreans.

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.

Metabolic markers associated with insulin resistance predict type 2 diabetes in Koreans with normal blood pressure or prehypertension.

BackgroundQuestions remain as to the association between essential hypertension and increased incidence of type 2 diabetes (T2DM). The premise of this analysis is that insulin resistance/compensatory hyperinsulinemia is a major predictor of T2DM, and the greater the prevalence of insulin resistance within any population, normotensive or hypertensive, the more likely T2DM will develop. The hypothesis to be tested is that surrogate estimates of insulin resistance will predict incident T2DM to a significant degree in persons with normal blood pressure or prehypertension.MethodsAnalysis of data from a population-based survey of 10, 038 inhabitants of rural and urban areas of Korea, ≥40 years-old, initiated in 2001, with measures of demographic and metabolic characteristics at baseline and 8-years later. Participants were classified as having normal blood pressure or prehypertension, and three simple manifestations of insulin resistance related to the pathophysiology of T2DM used to predict incident T2DM: (1) glycemia (plasma glucose concentration 2-hour after 75 g oral glucose challenge = 2-hour PG); (2) hyperinsulinemia (plasma insulin concentration 2-hour after 75 g oral glucose challenge = 2-hour PI); and (3) dyslipidemia (ratio of fasting plasma triglyceride/high/density lipoprotein cholesterol concentration = TG/HDL-C ratio).ResultsFully adjusted hazard ratios (HR, 95 % CI) for incident T2DM were highest (P < 0.001) in the quartile of individuals with the highest 2-hour PG concentrations, ranging from 5.84 (3.37–10.1) in women with prehypertension to 12.2 (7.12–21.00) in men with normal blood pressure. T2DM also developed to a significantly greater degree in subjects within the highest quartile of TG/HDL-C ratios, with HRs varying from 2.91 (1.63–2.58) in women with prehypertension (P < 0.001) to 1.77 (1.12–2.81, P < 0.05) in men with prehypertension. The least predictive index of insulin resistance was the 2-hour PI concentration. Subjects with normal blood pressure in the highest quartile of 2-hour PI concentrations were significantly associated with incident T2DM, with HRs of 1.5 (1.02–2.20, P = 0.25) and 2.02 (1.35–3.02, P < 0.001), in men and women, respectively. Finally, incidence of T2DM in the highest quartile was somewhat greater in patients with prehypertension, irrespective of predictor.ConclusionsMetabolic variables associated with insulin resistance (glycemia, insulinemia, and dyslipidemia) predict the development of T2DM in patients with either normal blood pressure or prehypertension.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0368-7) contains supplementary material, which is available to authorized users.

Comparison of the Usefulness of the Updated Homeostasis Model Assessment (HOMA2) with the Original HOMA1 in the Prediction of Type 2 Diabetes Mellitus in Koreans.

BackgroundThe original homeostasis model assessment (HOMA1) and the updated HOMA model (HOMA2) have been used to evaluate insulin resistance (IR) and β-cell function, but little is known about the usefulness of HOMA2 for the prediction of diabetes in Koreans. The aim of this study was to demonstrate the usefulness of HOMA2 as a predictor of type 2 diabetes mellitus in Koreans without diabetes.MethodsThe study population consisted of 104,694 Koreans enrolled at a health checkup program and followed up from 2001 to 2012. Participants were divided into a normal glucose tolerance (NGT) group and a pre-diabetes group according to fasting glucose and glycosylated hemoglobin levels. Anthropometric and laboratory data were measured at the baseline checkup, and HOMA values were calculated at the baseline and follow-up checkups. The hazard ratios (HRs) of the HOMA1 and HOMA2 values and the prevalence of diabetes at follow-up were evaluated using a multivariable Cox proportional hazards model and Kaplan-Meier analysis.ResultsAfter adjusting for several diabetes risk factors, all of the HOMA values except 1/HOMA1-β and 1/HOMA2-β in the NGT group were significant predictors of the progression to diabetes. In the NGT group, there was no significant difference in HOMA1-IR (HR, 1.09; 95% confidence interval [CI], 1.04 to 1.14) and HOMA2-IR (HR, 1.11; 95% CI, 1.04 to 1.19). However, in the pre-diabetes group, 1/HOMA2-β was a more powerful marker (HR, 1.29; 95% CI, 1.26 to 1.31) than HOMA1-IR (HR, 1.23; 95% CI, 1.19 to 1.28) or 1/HOMA1-β (HR, 1.14; 95% CI, 1.12 to 1.16). In the non-diabetic group (NGT+pre-diabetes), 1/HOMA2-β was also a stronger predictor of diabetes (HR, 1.27; 95% CI, 1.25 to 1.29) than HOMA1-IR (HR, 1.14; 95% CI, 1.12 to 1.15) or 1/HOMA1-β (HR, 1.13; 95% CI, 1.11 to 1.14).ConclusionHOMA2 is more predictive than HOMA1 for the progression to diabetes in pre-diabetes or non-diabetic Koreans.

Association of Serum Apolipoprotein B with the Increased Risk of Diabetes in Korean Men.

This study aimed to investigate the association of Apolipoprotein B (ApoB) with the risk of diabetes in Koreans. Korean men (n = 790, 40-79 years) who had been never diagnosed for diabetes before participating were enrolled. Subjects were categorized into normal fasting glucose (NFG, n = 519), impaired fasting glucose (IFG, n = 188) and newly-onset diabetes (n = 83) according to fasting glucose levels. Age was not significantly different among the subgroups. Mean values of BMI, waist circumference, Blood pressure(BP), triglyceride, non-HDL cholesterol were significantly higher in IFG or newly-onset diabetic subjects compared to NFG subjects. The levels of glucose, insulin, free fatty acid, insulin resistance and ApoB were highest in diabetic patients and lowest in NFG subjects. According to ApoB level, subjects were divided into two groups (high-ApoB group: ≥ 87.0 mg/dL vs. low-ApoB group: < 87.0 mg/dL). The risk of diabetes was higher in the high-ApoB group than the low-ApoB group [OR0: 2.392, (95% CI: 1.470-3.893), P0 < 0.001]. This association was maintained after adjusted for age and BMI [OR1: 2.228, (95% CI: 1.362-3.646), P1 = 0.001] and further adjustment for blood pressure, triglyceride, HDL-cholesterol, LDL-cholesterol, non-HDL-cholesterol, ApoA1 and adiponectin [OR2: 1.984, (95% CI: 1.001-4.064), P2 = 0.049]. The association was much greater in subjects with metabolic syndrome (MetS) [OR1: 2.805 (95% CI: 1.137-5.737), P1 = 0.005] than in those without [OR1: 1.917 (95% CI: 0.989-3.718), P1 = 0.054]. After 3-month, further investigation was randomly performed in subjects with NFG or IFG who agreed to reinvestigation. Multiple stepwise regression analysis revealed that net change of ApoB levels was a main contributor to the net change of glucose levels (standardized b-coefficient: 0.315, p = 0.002). In conclusion, ApoB levels are closely associated with the increased risk of diabetes in Korean men.

Association of HLA Genotype and Fulminant Type 1 Diabetes in Koreans.

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 levels 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 the Korean Reference Panel. The 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). A 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 of fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings.

Association between changes in body composition and risk of developing Type 2 diabetes in Koreans.

To examine the effects of longitudinal changes in fat mass or lean body mass on risk of Type 2 diabetes in Korean adults. Participants included 18 687 Korean adults (aged 20-79years) who underwent routine medical check-ups in 2007-2008 and again in 2011-2012 with a mean (range) of 4.3 (3.0-5.7) years interval. Total fat, fat-free, and soft fat-free masses were determined using bioelectrical impedance. A total of 692 subjects (3.7%) developed Type 2 diabetes during follow-up. Those who developed diabetes had a greater increase in percent body fat (2.9±3.0 vs 2.6±3.2 percentage points, P=0.043), as well as greater decreases in percent fat-free mass (-3.0±3.3 vs -2.7±3.3 percentage points, P=0.008) and percent soft fat-free mass (-2.8±3.1 vs -2.4±3.1 percentage points, P=0.003) compared with those who did not develop diabetes. In multiple logistic regression analysis, an increase in total fat mass of > 10% was associated with an increased odds ratio for diabetes (1.29, 1.05-1.60), and a decreased total fat mass was associated with lower odds ratio (0.75, 0.58-0.96). A loss of total fat-free mass of > 5% (odds ratio 1.08, 0.90-1.30) or an increase in total fat-free mass (odds ratio 0.96, 0.71-1.28) was not significantly associated with the risk of diabetes after adjustments for baseline waist circumference and glucose levels. These results show that changes in total body fat mass, but not lean body mass, are associated with development of Type 2 diabetes, independently of baseline measures of general or central obesity.