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Background: To evaluate the effects of teneligliptin on glycosylated hemoglobin (HbA1c) levels, continuous glucose monitoring (CGM)-derived time in range, and glycemic variability in elderly type 2 diabetes mellitus patients.Methods: This randomized, double-blinded, placebo-controlled study was conducted in eight centers in Korea (clinical trial registration number: NCT03508323). Sixty-five participants aged ≥65 years, who were treatment-naïve or had been treated with stable doses of metformin, were randomized at a 1:1 ratio to receive 20 mg of teneligliptin (n=35) or placebo (n=30) for 12 weeks. The main endpoints were the changes in HbA1c levels from baseline to week 12, CGM metrics-derived time in range, and glycemic variability.Results: After 12 weeks, a significant reduction (by 0.84%) in HbA1c levels was observed in the teneligliptin group compared to that in the placebo group (by 0.08%), with a between-group least squares mean difference of –0.76% (95% confidence interval [CI], –1.08 to –0.44). The coefficient of variation, standard deviation, and mean amplitude of glycemic excursion significantly decreased in participants treated with teneligliptin as compared to those in the placebo group. Teneligliptin treatment significantly decreased the time spent above 180 or 250 mg/dL, respectively, without increasing the time spent below 70 mg/dL. The mean percentage of time for which glucose levels remained in the 70 to 180 mg/dL time in range (TIR70–180) at week 12 was 82.0%±16.0% in the teneligliptin group, and placebo-adjusted change in TIR70–180 from baseline was 13.3% (95% CI, 6.0 to 20.6).Conclusion: Teneligliptin effectively reduced HbA1c levels, time spent above the target range, and glycemic variability, without increasing hypoglycemia in our study population.

Background Type 2 diabetes and cardiovascular disease (CVD) are the most important sequelae of obesity and the leading cause of death. We evaluated the association between body mass index (BMI) and the risk of incident type 2 diabetes, CVD, and all-cause mortality in a prospective study of a Korean population. Methods The shapes of the associations were modeled by restricted cubic splines regression analysis. After categorizing all subjects (n=8,900) into octiles based on their BMI levels, we estimated the hazard ratio (HR) for the association of categorized BMI levels with the risk of incident CVD and type 2 diabetes using a Cox's proportional hazard analysis. Results The mean age of participants was 52 years and 48% were men. Of the subjects at baseline, 39.0% of men and 45.6% of women were classified as obese (BMI ≥25 kg/m2). Over a mean follow-up of 8.1 years, CVD events occurred in 509 participants; 436 died; and 1,258 subjects developed type 2 diabetes. The increased risk of incident diabetes began to be significant at BMI 23 to 24 kg/m2 in both sexes (HR, 1.8). For CVD events, the risk began to increase significantly at BMI 26 to 28 kg/m2 (HR, 1.6). We found a reverse J-shaped relationship between BMI and all-cause mortality, with an increased risk among individuals with BMI values in lower range (BMI l21 kg/m2). Conclusion These results suggest that the BMI cut-off points for observed risk were varied depending on the diseases and that the BMI classification of obesity need to be revised to reflect differential risk of obesity-related diseases.

Background: The current American Thyroid Association risk-stratification system for papillary thyroid carcinoma (PTC) incorporates the number and size of positive lymph nodes (LNs) but places less ...

Aims/Introduction Several cross‐sectional studies have shown that delayed heart rate recovery (HRR) after exercise is associated with the development of metabolic syndrome (MetS). However, there has been a lack of comprehensively designed longitudinal studies. Therefore, our aim was to evaluate the longitudinal association of delayed HRR following a graded exercise treadmill test (GTX) with incident MetS. Materials and Methods This was a retrospective longitudinal cohort study of participants without MetS, diabetes, or cardiovascular diseases. The HRR was calculated as the peak heart rate minus the resting heart rate after a 1 min rest (HRR1), a 2 min rest (HRR2), and a 3 min rest (HRR3). Multivariate Cox proportional hazards analysis was performed to investigate the association between HRR and development of MetS. Results There were 676 (31.2%) incident cases of MetS identified during the follow‐up period (9,683 person‐years). The only statistically significant relationship was between HRR3 and the development of MetS. The hazard ratios (HRs) (95% confidence interval [CI]) of incident MetS comparing the first and second tertiles to the third tertile of HRR3 were 1.492 (1.146–1.943) and 1.277 (1.004–1.624) with P = 0.003 after adjustment for multiple risk factors. As a continuous variable, the HR (95% CI) of incident MetS associated with each one‐beat decrease in HRR3 was 1.015 (1.005–1.026) with P = 0.004 after full adjustments. An HRR3 value ≤45 beats per minute (bpm) was associated with a higher risk of incident MetS compared with values >45 bpm, with an HR (95% CI) of 1.304 (1.061–1.602) and P = 0.001. Conclusions The slow phase of HRR, particularly HRR3, might be more sensitive at predicting the risk of MetS., Delayed HRR3 after exercise could predict incident MetS in a general population, even after adjusting for fasting plasma glucose, HOMA‐IR, and HbA1c. And a HRR3 value of 45 beats per minute (bpm) or below was associated with a significantly higher risk of incident MetS compared with values over 45 bpm.

BACKGROUND It has not been determined whether changes in serum uric acid (SUA) level are associated with incident metabolic syndrome (MetS). The aim of the current study was to investigate the relationship between changes in SUA level and development of MetS in a large number of subjects. METHODS In total, 13,057 subjects participating in a medical health check-up program without a diagnosis of MetS at baseline were enrolled. Cox proportional hazards models were used to test the independent association of percent changes in SUA level with development of MetS. RESULTS After adjustment for age, systolic blood pressure, body mass index, fat-free mass (%), estimated glomerular filtration rate, smoking status, fasting glucose, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and baseline SUA levels, the hazard ratios (HRs) (95% confidence intervals [CIs]) for incident MetS in the second, third, and fourth quartiles compared to the first quartile of percent change in SUA level were 1.055 (0.936 to 1.190), 0.927 (0.818 to 1.050), and 0.807 (0.707 to 0.922) in male (P for trend

Background Differentiated thyroid carcinoma (DTC) shows a very good prognosis, but older patients have a higher recurrence rate and those show poor prognosis than younger patients. The aim of this study was to determine the clinical outcomes of thyroid cancer patients who experienced recurrence in old age according to the treatment strategy used. Methods This retrospective observational cohort study was conducted at Asan Medical Center, Seoul, Korea. Among DTC patients with no evidence of disease after initial treatment, we enrolled 86 patients who experienced recurrence at an age >65 years from 1994 to 2012. Sixty-nine patients had local recurrence and 17 patients showed distant metastasis. Results The mean age of patients at recurrence was 72 years. Patients were followed up for a median of 4.1 years after recurrence. Sixty-three of the 69 patients with local recurrence received additional treatment, while the other six received conservative care. The cancer-specific mortality rate was 15.5% in the local recurrence group. Airway problems were the main cause of death in patients who did not receive further treatment for local recurrence. Among the 17 patients with distant metastasis, 10 underwent specific treatment for metastasis and seven received only supportive management. Seven of those 17 patients died, and the cancer-specific mortality rate was 35% in the distant metastasis group. Conclusion The overall cancer-specific mortality rate was 20% in DTC patients in whom recurrence was first detected at an age >65 years. Mortality due to uncontrolled local disease occurred frequently in patients who did not receive definitive management for recurrence.

Nonalcoholic fatty liver disease (NAFLD) has been associated with relative skeletal muscle mass in several cross-sectional studies. We explored the effects of relative skeletal muscle mass and changes in relative muscle mass over time on the development of incident NAFLD or the resolution of baseline NAFLD in a large, longitudinal, population-based 7-year cohort study. We included 12,624 subjects without baseline NAFLD and 2943 subjects with baseline NAFLD who underwent health check-up examinations. A total of 10,534 subjects without baseline NAFLD and 2631 subjects with baseline NAFLD were included in analysis of changes in relative skeletal muscle mass over a year. Subjects were defined as having NAFLD by the hepatic steatosis index, a previously validated NAFLD prediction model. Relative skeletal muscle mass was presented using the skeletal muscle mass index (SMI), a measure of body weight-adjusted appendicular skeletal muscle mass, which was estimated by bioelectrical impedance analysis. Of the 12,624 subjects without baseline NAFLD, 1864 (14.8%) developed NAFLD during the 7-year follow-up period. Using Cox proportional hazard analysis, compared with the lowest sex-specific SMI tertile at baseline, the highest tertile was inversely associated with incident NAFLD (adjusted hazard ratio [AHR] = 0.44, 95% confidence interval [CI] = 0.38-0.51) and positively associated with the resolution of baseline NAFLD (AHR = 2.09, 95% CI = 1.02-4.28). Furthermore, compared with the lowest tertile of change in SMI over a year, the highest tertile exhibited a significant beneficial association with incident NAFLD (AHR = 0.69, 95% CI = 0.59-0.82) and resolution of baseline NAFLD (AHR = 4.17, 95% CI = 1.90-6.17) even after adjustment for baseline SMI. Conclusion: Increases in relative skeletal muscle mass over time may lead to benefits either in the development of NAFLD or the resolution of existing NAFLD.

AIM To evaluate the efficacy and safety of a fixed-dose combination (FDC) of gemigliptin and rosuvastatin in patients with type 2 diabetes and dyslipidaemia. RESEARCH DESIGN AND METHODS A total of 33 hospitals in Korea participated in this randomized, double-blind trial of diabetic patients with dyslipidaemia. A total of 290 participants were randomly assigned at a 1:1:1 ratio to receive an FDC of gemigliptin (50 mg) and rosuvastatin (20 mg) (GEMI/ROSU FDC group), gemigliptin (50 mg) (GEMI group) or rosuvastatin (20 mg) (ROSU group). Rosuvastatin was up-titrated from 5 to 20 mg/d throughout the study period. Primary efficacy measures were changes in HbA1c and LDL-C from baseline to Week 24 between the GEMI/ROSU FDC and ROSU groups and between the GEMI/ROSU FDC and GEMI groups, respectively. Secondary efficacy measures were changes in HbA1c and LDL-C between the GEMI/ROSU FDC and GEMI groups and between the GEMI/ROSU FDC and ROSU groups, respectively. RESULTS After 24 weeks of treatment, a significant reduction in HbA1c from baseline was noted in the GEMI/ROSU FDC group (-0.81% of LS mean; P

Background Serum albumin and uric acid have been positively linked to metabolic syndrome (MetS). However, the association of MetS incidence with the combination of uric acid and albumin levels has not been investigated. We explored the association of albumin and uric acid with the risk of incident MetS in populations divided according to the levels of these two parameters. Methods In this retrospective longitudinal study, 11,613 non-MetS participants were enrolled among 24,185 individuals who had undergone at least four annual check-ups between 2006 and 2012. The risk of incident MetS was analyzed according to four groups categorized by the sex-specific medians of serum albumin and uric acid. Results During 55,407 person-years of follow-up, 2,439 cases of MetS developed. The risk of incident MetS increased as the uric acid category advanced in individuals with lower or higher serum albumin categories with hazard ratios (HRs) of 1.386 (95% confidence interval [CI], 1.236 to 1.554) or 1.314 (95% CI, 1.167 to 1.480). However, the incidence of MetS increased with higher albumin levels only in participants in the lower uric acid category with a HR of 1.143 (95% CI, 1.010 to 1.294). Conclusion Higher levels of albumin were associated with an increased risk of incident MetS only in individuals with lower uric acid whereas higher levels of uric acid were positively linked to risk of incident MetS regardless of albumin level.

Background: There have been several cross-sectional studies reporting that delayed heart rate recovery (HRR) after exercise is associated with the development of the metabolic syndrome (MetS). However, there have been few longitudinal studies. We evaluated the longitudinal association of delayed HRR following a graded exercise treadmill test (GTX) with the incident MetS including metabolic parameters as adjusting factors. Methods: A retrospective longitudinal cohort study of participants without MetS, diabetes or cardiovascular diseases has been designed. HRR was calculated as peak heart rate minus heart rate after a 1-minute rest (HRR 1), heart rate after a 2-minute rest (HRR 2), and heart rate after a 3-minute rest (HRR 3). To investigate the association between HRR and incident MetS, multivariate Cox proportional hazards analysis was performed. Results: During 9,683 person-years of follow-up between 2006 and 2012, there were 676 (31.2%) incident cases of the MetS. After adjustment for age, sex, smoking status, baseline heart rate, peak heart rate, peak oxygen uptake, hs-CRP, waist circumference, systolic blood pressure, TG, LDL-C, HDL-C, fasting plasma glucose, HOMA-IR, and HbA1c, the hazard ratios (HR) [95% confidence interval (CI)] of incident MetS comparing the first and second tertiles to the third tertile of HRR 3 were 1.492 (1.146-1.943) and 1.277 (1.004-1.624) (P for trend = 0.003). As a continuous variable, after full adjustments, the HR (95% CI) of incident MetS associated with each 1-second decrease in HRR3 was 1.015 (1.005 -1.026) (P = 0.004). Conclusion: Delayed HRR 3 after exercise could predict incident MetS, even after adjusting for metabolic parameters. However, HRR 1 and HRR 2 have not shown the statistic significance. Disclosure T. Yu: None. S. Jin: None. K. Hur: None. J. Bae: None. J. Jee: None. J. Kim: None. M. Lee: None.

The aim of this study was to evaluate the effect of gemigliptin, a potent and selective dipeptidyl peptidase-4 inhibitor versus dapagliflozin, a sodium glucose co-transporter-2 inhibitor on glycemic variability in patients with type 2 diabetes mellitus (T2DM). This randomized, parallel group, blinded end-point, multicenter, 12-week clinical trial was conducted in 71 patients with T2DM inadequately controlled with metformin alone or drug naïve patients. Subjects were randomized to receive gemigliptin 50mg (N=35) or dapagliflozin 10mg (N=36) daily for 12 weeks. Glycemic variability parameters such as mean amplitude of glycemic excursions (MAGE), standard deviation (SD) and coefficient of variation (CV) were evaluated during 6-day continuous glucose monitoring at baseline and after 12 weeks of treatment. The primary efficacy endpoint was change in MAGE after 12 weeks compared to baseline. Measures of glycemic control, oxidative stress and inflammation, as well as safety profiles were assessed. Adjusted mean change ± standard error in MAGE after 12 weeks were -27.2 ± 4.4 mg/dL (P In conclusion, gemigliptin significantly improved glycemic variability than dapagliflozin with similar glycemic efficacy and safety profiles in patients with T2DM inadequately controlled with metformin alone or drug naïve patients. ClinicalTrials.gov Identifier: NCT03202563. Disclosure Y. Hwang: None. J. Kim: None. S. Kwak: None. S. Kim: None. J. Won: None. J. Bae: None. H. Kim: None. S. Suh: None. E. Lee: None. S. Lee: Employee; Self; LG Chem. Funding LG Chem, Ltd.

Aims The aim of this study was to compare the effect of gemigliptin, a dipeptidyl peptidase-4 inhibitor, and dapagliflozin, a sodium glucose co-transporter-2 inhibitor, on glycaemic variability in type 2 diabetes patients. Materials and methods In this randomized, blinded end point, multicentre clinical trial, we enrolled 71 patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naive. The participants were randomized to receive gemigliptin 50 mg (n = 35) or dapagliflozin 10 mg (n = 36) daily for 12 weeks. Glycaemic variability was estimated by mean amplitude of glycaemic excursions (MAGE), standard deviation (SD) and coefficient of variation (CV) using a 6-day continuous glucose monitoring system. The primary efficacy endpoint was change in MAGE after 12 weeks compared to baseline. Results Intergroup differences in baseline characteristics were not significant. The adjusted mean change (± standard error) in MAGE after 12 weeks in the gemigliptin and dapagliflozin groups was -27.2 ± 4.4 mg/dL and -7.9 ± 4.9 mg/dL, respectively. Between-group comparisons showed a significantly larger reduction in MAGE in the gemigliptin group (-19.2 mg/dL; 95% CI, -31.3 to -7.2; P = .002). Measures of SD and CV also showed a significantly larger reduction in the gemigliptin group. Average glycaemic control, estimated by HbA1c, fasting glucose and safety profiles, was comparable between the two groups. Conclusions Compared to dapagliflozin, gemigliptin significantly improved glycaemic variability, with similar glucose-lowering efficacy and safety profiles in patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naive.

Background An association between serum calcium level and risk of metabolic syndrome (MetS) has been suggested in cross-sectional studies. This study aimed to evaluate the association between baseline serum calcium level and risk of incident MetS in a longitudinal study. Methods We conducted a retrospective longitudinal study of 12,706 participants without MetS who participated in a health screening program, had normal range serum calcium level at baseline (mean age, 51 years), and were followed up for 4.3 years (18,925 person-years). The risk of developing MetS was analyzed according to the baseline serum calcium levels. Results A total of 3,448 incident cases (27.1%) of MetS developed during the follow-up period. The hazard ratio (HR) for incident MetS did not increase with increasing tertile of serum calcium level in an age- and sex-matched model (P for trend=0.915). The HRs (95% confidence interval [CI]) for incident MetS comparing the second and the third tertiles to the first tertile of baseline serum calcium level were 0.91 (95% CI, 0.84 to 0.99) and 0.85 (95% CI, 0.78 to 0.92) in a fully adjusted model, respectively (P for trend=0.001). A decreased risk of incident MetS in higher tertiles of serum calcium level was observed in subjects with central obesity and/or a metabolically unhealthy state at baseline. Conclusion There was no positive correlation between baseline serum calcium levels and incident risk of MetS in this longitudinal study. There was an association between higher serum calcium levels and decreased incident MetS in individuals with central obesity or two components of MetS at baseline.

Low serum albumin concentration is associated with a high risk of morbidity and mortality from cardiovascular diseases. However, high serum albumin level appears to be linked to metabolic syndrome (MetS). This study aimed to dissect the relative contributions of baseline and change in serum albumin concentration to the risk of incident metabolic syndrome.This was a 5-year (63,060 person-years) retrospective longitudinal study of 12,567 participants without metabolic syndrome, diabetes, or cardiovascular disease who were enrolled in a health screening program. The risk of developing MetS was analyzed according to baseline and change in serum albumin concentration.A total of 2582 incident cases of metabolic syndrome developed. The hazard ratio (HR) for incident MetS increased with increasing quartile of baseline serum albumin level compared with those in the lowest quartile, in a fully adjusted model (p for trend = 0.013). The HRs [95% confidence intervals (CIs)] of incident MetS comparing the second, third, and fourth quartiles to the first quartile of change in serum albumin level were 0.478 (0.421-0.544), 0.353 (0.307-0.405), and 0.262 (0.224-0.305) in the fully adjusted model, respectively (p for trend0.001). Percent change in serum albumin concentration inversely correlated with percent change in serum level of high-sensitivity C-reactive protein (r=-3.5444, p0.001).Although a higher baseline level of serum albumin was linked to increased risk of incident metabolic syndrome, increase in serum albumin concentration might be a protective factor against the risk of MetS.

Background and aims The objective of this study was to evaluate the ability of lipid variables to predict the development of chronic kidney disease (CKD). We investigated the longitudinal association between lipid profiles and incident CKD in a large apparently healthy cohort. Methods A retrospective longitudinal analysis of 10,288 subjects who had participated in comprehensive health check-ups at least four times over a 7-year period was conducted. The risk of incident CKD associated with lipid variables was analyzed using adjusted hazard ratio (HR) for CKD per 1 standard deviation (SD) increase in lipid level. The development of CKD was defined as estimated glomerular filtration rate 2 . Results Over a mean follow-up of 56.5 ± 14.3 months, 356 (3.5%) subjects developed CKD. The multivariate adjusted HRs for incident CKD per 1 SD increase in baseline lipid level were 1.29 (95% confidence interval [CI], 1.17–1.41) for triglycerides (TG), 0.77 (0.68–0.88) for high-density lipoprotein cholesterol (HDL-C), 1.22 (1.12–1.32) for the TG/HDL-C ratio, 0.82 (0.73–0.92) for the low-density lipoprotein cholesterol/apolipoprotein B (LDL-C/apoB) ratio, and 0.74 (0.66–0.83) for the HDL-C/apoA-1 ratio. No longitudinal association was found between incident CKD and baseline total cholesterol, LDL-C, non-HDL-C, the LDL-C/HDL-C ratio, apoB, apoA-I, or the apoB/apoA-I ratio. Conclusions The LDL-C/apoB and HDL-C/apoA-1 ratios as well as TG and HDL-C concentrations independently predicted an increased risk for developing CKD. Our findings suggest that particle size of HDLs and LDLs may contribute to the development of CKD.

Background Recent studies have shown an association between thyroid hormone levels and metabolic syndrome (MetS) among euthyroid individuals; however, there have been some inconsistencies between studies. Here, we evaluated the relationship between thyroid hormone levels and MetS in euthyroid middle-aged subjects in a large cohort. Methods A retrospective analysis of 13,496 euthyroid middle-aged subjects who participated in comprehensive health examinations was performed. Subjects were grouped according to thyroid stimulating hormone, total triiodothyronine (T3), total thyroxine (T4), and T3-to-T4 ratio quartile categories. We estimated the odds ratios (ORs) for MetS according to thyroid hormone quartiles using logistic regression models, adjusted for potential confounders. Results Of the study patients, 12% (n=1,664) had MetS. A higher T3 level and T3-to-T4 ratio were associated with unfavourable metabolic profiles, such as higher body mass index, systolic and diastolic blood pressure, triglycerides, fasting glucose and glycated hemoglobin, and lower high density lipoprotein cholesterol levels. The proportion of participants with MetS increased across the T3 quartile categories (P for trend

Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

Some observational studies have suggested that serum uric acid (SUA) levels are one of the determinants of the metabolic syndrome (MetS). However, previous studies reported combined results for men and women after adjusting for sex and few studies take body composition into consideration. Therefore, we performed this sex-specific longitudinal study to investigate how baseline SUA levels influence incident MetS, including body composition as an adjusting factor in a large number of subjects.A total of 14,442 participants (8715 men and 5727 women) participating in a medical health check-up program without diagnosed MetS at baseline were enrolled. Separate analyses were performed for men and women including body composition as a confounding factor. Cox proportional hazards models were used to quantify independent associations between SUA levels and incident MetS.During 63,940person-years of follow-up, there were 4215 (2974 men, 1241 women) incident cases of MetS between 2006 and 2012. After adjustments for age, systolic BP, diastolic BP, BMI, eGFR, smoking status, TG, LDL-C, HDL-C, fasting glucose, and proportion of fat-free mass (100-fat mass, %), the hazard ratios (HR) [95% confidence interval (CI)] for incident MetS comparing the second, the third, and the fourth quartiles to the first quartile of SUA levels were 0.862 (0.770-0.965), 1.102 (0.991-1.225), and 1.246 (1.121-1.385) in men (p for trend0.001), and 1.045 (0.862-1.266), 1.251 (1.050-1.490), and 1.321 (1.109-1.574) in women (p for trend0.001), respectively. As a continuous variable, in fully-adjusted models, the HRs (95% CI) for incident MetS associated with each increase of 1mg/dl of SUA levels were 1.094 (1.060-1.130) in men (p0.001) and 1.148 (1.072-1.228) in women (p0.001), respectively.We demonstrated that SUA levels are strong and independent predictors of MetS. This relationship remained significant after full adjustments for multiple associated confounders including body composition in both men and women.

In iodine-sufficient areas, autoimmune hypothyroidism has been regarded as the major subtype of hypothyroidism. Non-immune-related hypothyroidism has received little attention because it is considered to be rare. The aim of this study was to evaluate the prevalence of non-immune-related hypothyroidism in Korea and to identify its associating factors. A total of 6434 participants in the Korea National Health and Nutrition Examination Survey VI (2013–2015) without known thyroid disease who were examined for thyroid stimulating hormone, free thyroxine, TPO Ab, and urine iodine concentration (UIC) were enrolled. The weighted proportions, demographic variables, and severity of immune-related and non-immune-related hypothyroidism were compared. To assess the effect of iodine on hypothyroidism in TPO Ab positive or negative populations, the weighted prevalence of hypothyroidism was assessed in each population according to UIC or estimated iodine intake subgroups. The prevalence of undetected hypothyroidism in Korea was 3.8% (n = 233). Of these 233 cases, 171 (71.8%) were non-immune-related. In the TPO Ab negative population, the prevalence of hypothyroidism was increased significantly in the subgroup with UIC between 250 and 749 µg/L (HR 2.12 [1.17, 3.83]) and ≥ 750 µg/L (HR 3.42 [1.93, 6.04]) or the subgroups with estimated iodine intake ≥ 750 µg/day (HR 2.81 [1.64, 4.80]). This nationwide study demonstrated that most cases of hypothyroidism in iodine-sufficient areas are non-immune-related and are associated with excess iodine above a certain level. More attention to this unrecognized but widespread potential health risk is needed.

Background We evaluated the separate and combined effect of metabolic syndrome (MS) and diabetes on incident cardiovascular disease (CVD), CVD mortality and case fatality risk (CFR). Methods 8898 subjects were categorized into four groups on the basis of the presence of MS and diabetes (with MS, with diabetes, with both or without either). We compared the development of CVD events, mortality and CFR. Results Over a mean follow-up of 8.0 years, 690 subjects developed CVD. There were 434 deaths, of which 101 were from CVD. The presence of diabetes alone, MS alone, or both was associated with an increased risk for incident CVD and CVD mortality. Compared with the MS only group, the adjusted hazard ratio (HR) for CVD events and CVD mortality in the diabetes only group was 1.07 (95% confidence interval [CI] 0.77–1.48) and 2.02 (95% CI 0.99–1.72), respectively. Among individuals with diabetes, the presence of MS did not significantly increase CVD risk and CVD mortality. The adjusted odds ratio for CVD CFR, including adjustment for the presence of MS, in subjects with diabetes versus without diabetes was 2.11 (95% CI 1.34–3.31). Conclusions There was no difference in the risk of incident CVD between individuals with diabetes alone and MS alone, whereas CVD mortality was much higher in individuals with diabetes only. The presence of MS did not exhibit an additive effect on CVD risk and mortality in individuals with diabetes. Individuals with diabetes had a higher CVD case fatality regardless of the presence of MS.

In this study, a new concept of a 3D-printed scaffold was introduced for the accurate placement of an implant and the application of a recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded bone graft. This preliminary study was conducted using two adult beagles to evaluate the 3D-printed polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP)/bone decellularized extracellular matrix (bdECM) scaffold conjugated with rhBMP-2 for the simultaneous use as an implant surgical guide stent and bone graft material that promotes new bone growth. Teeth were extracted from the mandible of the beagle model and scanned by computed tomography (CT) to fabricate a customized scaffold that would fit the bone defect. After positioning the implant guide scaffold, the implant was placed and rhBMP-2 was injected into the scaffold of the experimental group. The two beagles were sacrificed after three months. The specimen block was obtained and scanned by micro-CT. Histological analysis showed that the control and experimental groups had similar new bone volume (NBV, %) but the experimental group with BMP exhibited a significantly higher bone-to-implant contact ratio (BIC, %). Within the limitations of this preliminary study, a 3D-printed scaffold conjugated with rhBMP-2 can be used simultaneously as an implant surgical guide and a bone graft in a large bone defect site. Further large-scale studies will be needed to confirm these results.

Background Skeletal muscle mass was negatively associated with metabolic syndrome prevalence in previous cross-sectional studies. The aim of this study was to investigate the impact of baseline skeletal muscle mass and changes in skeletal muscle mass over time on the development of metabolic syndrome in a large population-based 7-year cohort study. Methods A total of 14,830 and 11,639 individuals who underwent health examinations at the Health Promotion Center at Samsung Medical Center, Seoul, Korea were included in the analyses of baseline skeletal muscle mass and those changes from baseline over 1 year, respectively. Skeletal muscle mass was estimated by bioelectrical impedance analysis and was presented as a skeletal muscle mass index (SMI), a body weight-adjusted appendicular skeletal muscle mass value. Using Cox regression models, hazard ratio for developing metabolic syndrome associated with SMI values at baseline or changes of SMI over a year was analyzed. Results During 7 years of follow-up, 20.1% of subjects developed metabolic syndrome. Compared to the lowest sex-specific SMI tertile at baseline, the highest sex-specific SMI tertile showed a significant inverse association with metabolic syndrome risk (adjusted hazard ratio [AHR] = 0.61, 95% confidence interval [CI] 0.54–0.68). Furthermore, compared with SMI changes 1% changes in SMI over 1 year after additionally adjusting for baseline SMI and glycometabolic parameters. Conclusions An increase in relative skeletal muscle mass over time has a potential preventive effect on developing metabolic syndrome, independently of baseline skeletal muscle mass and glycometabolic parameters. Electronic supplementary material The online version of this article (10.1186/s12933-018-0659-2) contains supplementary material, which is available to authorized users.

Aims To evaluate whether variable fatty liver status over time influence the risk of type 2 diabetes differently. Methods We analyzed the data from 7849 subjects without type 2 diabetes who underwent comprehensive health check-ups annually for 5 years. All subjects had an abdominal ultrasonography annually. The risk of incident diabetes was assessed in individuals with sustained non-alcoholic fatty liver disease (NAFLD), individuals with changed fatty liver status (intermittent NAFLD group), and individuals who did not have NAFLD (never NAFLD group) during the study period. A subgroup analysis was done in subjects of the intermittent NAFLD group. Incident diabetes was compared according to the number of time diagnosed as NAFLD by annual ultrasonography. Results During the mean follow-up of 4 years, subjects in the sustained NAFLD group had a HR of 1.50 (95% CI 1.13–1.98) for the development of diabetes compared with those in the never NAFLD group, whereas the risk was not higher in the intermittent NAFLD group (HR 0.99, 95% CI 0.76–1.31). When compared with the intermittent NAFLD group, multivariable adjusted HR for incident diabetes was 1.50 (95% CI 1.20–1.89) in the sustained NAFLD group. As the number of times diagnosed as NAFLD increased, the proportion of subjects who developed diabetes also increased (p = .002). Conclusions The presence of fatty liver was differentially associated with incident diabetes based on its duration. The persistence of fatty liver status is an important factor for an independent association between NAFLD and incident diabetes.

We examined the association between changes in serum calcium levels with the incidence of type 2 diabetes mellitus (T2DM) in apparently healthy South Korean subjects.A retrospective longitudinal analysis was conducted with subjects who had participated in comprehensive health check-ups at least four times over a 7-year period (between 2006 and 2012). In total, 23,121 subjects were categorized into tertiles based on changes in their albumin-adjusted serum calcium levels. Multivariate Cox regression models were fitted to assess the association between changes in serum calcium levels during follow-up and the relative risk of diabetes incidence.After a median follow-up of 57.4months, 1,929 (8.3%) new cases of T2DM occurred. Simple linear regression analysis showed serum calcium level changes correlated positively with changes in HbA1c and fasting plasma glucose (FPG) levels (B=5.72, p0.001 for FPG; B=0.13, p0.001 for HbA1c). An increase in albumin-adjusted serum calcium levels during follow-up was related to an increased risk of T2DM. After adjustment for potential confounders, the risk of T2DM was 1.6 times greater for subjects whose albumin-adjusted serum calcium levels were in the highest change tertile during follow-up than for subjects whose levels were in the lowest tertile (HR 1.65, 95% CI 1.44-1.88, P0.001).The elevation of albumin-adjusted serum calcium levels was associated with an increased risk of T2DM, independent of baseline glycemic status.

Metabolically healthy obese is the designation for a subgroup of obese individuals with normal metabolic features. However, metabolically healthy obese individuals are prone to developing metabolic syndrome. Serum triiodothyronine (T3) levels are associated with various metabolic risk factors including obesity. Therefore, this longitudinal study aimed to explore the possible correlation between serum T3 concentration and the onset of MetS in metabolically healthy obese persons. A retrospective analysis of 992 euthyroid metabolically healthy obese subjects who underwent yearly health checkups over 6 years was performed. The risk of developing MetS was analyzed according to baseline T3 concentration, as both tertiles and continuous values, using Cox regression analysis. Serum T3 concentration at the end of the study was further analyzed according to the final metabolic phenotype. The incidence of MetS was 464 cases (46.8%) during a median 3.3 years of follow-up (3168.2 person-years). The hazard ratio for incident MetS enhanced with increasing T3 concentration in both the crude and adjusted models. Higher baseline serum T3 levels were associated with unfavorable metabolic parameters. However, over the course of the study, serum T3 concentration significantly increased in subjects who sustained metabolically healthy phenotypes compared to baseline value, while it significantly decreased in the subjects who developed MetS. Serum T3 concentrations exhibit distinct associations with development of metabolic syndrome in euthyroid metabolically healthy obese persons, but its increment during follow-up maintained metabolically healthy state. These findings suggest that serum T3 modulation might be an adaptive process to protect against metabolic deterioration.

Aim Serum albumin concentration is associated with both type 2 diabetes and metabolic syndrome (MetS). We sought to investigate whether baseline serum albumin and change in serum albumin could be independent risk factors for prediabetes in subjects without MetS. We further examined the effect of serum albumin on progression to overt diabetes in subjects who developed prediabetes. Methods Among 10,792 participants without diabetes and MetS who consecutively underwent yearly health check-ups over six years, 9,807 subjects without incident MetS were enrolled in this longitudinal retrospective study. The risk of developing prediabetes (impared fasting glucose or hemoglobin A1c) was analyzed according to baseline and percent change in serum albumin concentration using Cox regression analysis. Serial changes in serum albumin concentration were measured from baseline to one year before prediabetes diagnosis, and then from the time of prediabetes diagnosis to progression to overt diabetes or final follow-up. Results A total of 4,398 incident cases of prediabetes developed during 35,807 person-years (median 3.8 years). The hazard ratio for incident prediabetes decreased as percent change in serum albumin concentration (quartiles and per 1%) increased in a crude and fully adjusted model. However, baseline serum albumin concentration itself was not associated with prediabetic risk. Serum albumin levels kept increasing until the end of follow-up in prediabetic subjects who returned to normal glycemic status, whereas these measures did not change in prediabetic subjects who developed type 2 diabetes. Serum albumin concentration measured at the end of follow-up was the highest in the regression group, compared to the stationary (p = 0.014) or progression groups (p = 0.009). Conclusions Increase in serum albumin concentration might protect against early glycemic deterioration and progression to type 2 diabetes even in subjects without MetS.

Background: Metabolic syndrome (MetS) is a condition characterized by a cluster of metabolic disorders and is associated with increased risk of cardiovascular disease (CVD). This study analyzed data from the Korean Health and Genome Study to examine the impact of MetS on CVD. Methods: A total of 8,898 subjects (4,241 males and 4,657 females), 40 to 69 years of age, were enrolled and evaluated for the development of new onset CVD from 2001 to 2012 (median 8.1 years of follow-up). Results: The prevalence of MetS at baseline was 22.0% (932/4,241) and 29.7% (1,383/4,657) in males and females, respectively. MetS was associated with increased risk of coronary heart disease (CHD; hazard ratio (HR), 1.818; 95% confidence interval (CI), 1.312 to 2.520 in males; HR, 1.789; 95% CI, 1.332 to 2.404 in females) and CVD (HR, 1.689; 95% CI, 1.295 to 2.204 in males; HR, 1.686; 95% CI, 1.007 to 2.192 in females). Specifically, MetS was associated with risk of future stroke in females only (HR, 1.486; 95% CI, 1.007 to 2.192). Among MetS components, abdominal obesity and hypertension were independent predictors of both CHD and CVD. In addition, a higher number of MetS components correlated with higher CVD risk. Conclusion: MetS is a significant risk factor for the development of CVD although its impact varies between sexes.

Iodine in iodinated contrast agents (ICAs) interferes with radioactive iodine treatment (RAIT) and diagnostic scans in patients with differentiated thyroid carcinoma (DTC) because it can compete with ¹³¹I. Published guidelines recommend delaying RAIT for three to four months in patients who have been exposed to ICA. Spot urinary iodine concentration is a useful marker to reflect the body iodine pool. We investigated the impact of ICAs administered at preoperative computed tomography (CT) scan on the body iodine pool to determine the proper time interval between preoperative CT and RAIT in DTC patients.We performed a retrospective review of 1023 patients with DTC who underwent a preoperative CT scan with ICA, total thyroidectomy, and one week of low-iodine diet in preparation for RAIT. Urine iodine excretion (UIE) was measured in spot urine by inductively coupled plasma mass spectrometry and reported both in simple concentration (μg/L) and divided by gram creatinine (μg/gCr). Patients were divided into five groups by time interval in days between preoperative CT scan and spot urine iodine measurement (A, 31-60 [n=29]; B, 61-90 [n=155]; C, 91-120 [n=546]; D, 121-150 [n=226]; E, 151-180 [n=67]).The median (interquartile range) of UIE (μg/gCr) in each group was 44.4 (27.7-73.2) in group A, 33.3 (22.8-64.7) in group B, 32.7 (20.8-63.0) in group C, 32.0 (20.6-67.0) in group D, and 30.4 (19.6-70.8) in group E. There was no significant difference between group A and the remaining groups (p0.05) Also, the proportion of patients who achieved the appropriate UIE for RAIT according to our hospital's cutoff (≤66.2 μg/gCr) was not different between groups (A, 72.4%; B, 76.1%; C, 77.5%; D, 74.8%; E, 74.6%) (p=0.78).This study shows that a UIE of one month after preoperative CT scan with ICA was not higher than that of six months after CT scan in patients who underwent total thyroidectomy for DTC. Thus, current guidelines that recommend delay of RAIT for three to four months after CT scan with ICA should be revisited and future studies to clarify the appropriate time interval between CT scan with ICA and RAIT are warranted.

The aim of this study was to evaluate the changes in the masticatory functions of complete dentures before and after the insertion of a LOCATOR attachment. The mixing ability index with a two-colored paraffin wax cube was used to quantify masticatory performance. In addition, degree of satisfaction with the treatment was assessed using a visual analog scale. The mixing ability index for the implant-retained overdentures and the complete dentures were calculated (−0.03 ± 1.38 and −2.10 ± 1.57, respectively), as were the visual analog scales of the implant-retained overdentures and the complete dentures (8.9 ± 1.5 and 4.3 ± 1.7, respectively). The paired t test revealed significant improvements (P < .001).

Role of impaired suppression of glucagon secretion in the pathogenesis of pancreatic cancer-associated diabetes has been suggested. We examined the correlation between glucagon/insulin ratio (G/I) after glucose challenge and hemoglobin A1C (A1C) in subjects with and without pancreatic cancer. Data were gathered from a preoperative screening 75-g oral glucose tolerance test in patients who would eventually undergo pancreatic resection. A multiple linear regression analysis was conducted using the following covariates: age, body mass index, hemoglobin, glucose and insulin levels at the corresponding time points, indices of insulin resistance, duration of diabetes, insulinogenic index, and use of glucose-lowering drugs. In subject group with pancreatic cancer (n = 45), but not in subject group without pancreatic cancer (n = 101), participants with A1C ≥6.5 % had significantly higher glucagon levels, lower insulin levels, and higher G/I ratios after the glucose challenge than those of the subjects with A1C

Background The ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1) has been reported to be associated with metabolic syndrome (MetS) and insulin resistance (IR). Non-HDL-C is regarded as a surrogate marker for apoB in routine clinical practice. However, it is unclear whether the ratio of non-HDL-C to HDL-C is an equal or a better predictor than the apoB/apoA1 ratio for the identification of MetS and IR. Methods We performed a retrospective study of 41,821 Korean adults who participated in a routine health screening examination. Anthropometry, fasting glucose, fasting insulin, HOMA-IR, CRP, lipid profiles, apoB, and apoA1 were measured. Results To compare the predictive value for MetS between different lipid ratios, we analyzed the ROC curves of apoB/apoA1 and non-HDL-C/HDL-C ratios. ROC analysis showed that the AUCs of non-HDL-C/HDL-C (0.75 [95% CI=0.74–0.76] in men and 0.84 [95% CI=0.83–0.85] in women) were significantly higher than those of apoB/apoA1 (0.66 [95% CI=0.65–0.67] in men and 0.77 [95% CI=0.76–0.78] in women). The non-HDL-C/HDL-C ratio also showed a significantly stronger association with HOMA-IR than the apoB/apoA1 ratio. The optimal cutoff value of the non-HDL-C/HDL-C ratio for detection of MetS in men was 3.39, with a sensitivity of 66.7% and a specificity of 71.8%, whereas the optimal ratio cutoff value in women was 2.89, with a sensitivity of 75.7% and a specificity of 78.1%. Conclusions Our findings indicate that the non-HDL-C/HDL-C ratio is a better marker than the apoB/apoA1 ratio for identifying IR and MetS in Koreans.

Aims/Introduction To evaluate whether hemoglobin A1c (HbA1c) levels are affected by hemoglobin level and gender. Materials and Methods A cross-sectional analysis was carried out in a sample of 87,284 non-diabetic Koreans without anemia who participated in comprehensive health check-ups between January and December 2009 at the Kangbuk Samsung Hospital Total Healthcare Center in Seoul, Korea. We categorized men and women separately according to fasting plasma glucose and hemoglobin level to carry out the analysis. Results HbA1c increased steadily with increasing fasting plasma glucose level. Both men and women with lower hemoglobin had significantly higher HbA1c at a given fasting glucose level, and this result was consistent across the fasting glucose quintiles within the non-diabetic range. Women had a lower mean hemoglobin value compared with men, and women had higher HbA1c levels at a given fasting glucose level consistently across the fasting glucose deciles. There was also a gender-specific association between age and HbA1c (P

Aims/Introduction Small dense low-density lipoprotein (sdLDL) has been suggested to be a potential risk factor for cardiovascular diseases (CVD). Materials and Methods We carried out a prospective nested case–control study in the Korean Health and Genome Study. Participants were men and women aged 40–69 years who developed CVD (n = 313), and were matched by age and sex to controls who remained free of CVD (n = 313) during the 8-years follow-up period (from 2001 to 2009). LDL subfractions were analyzed in frozen samples collected from the 626 participants using polyacrylamide tube gel electrophoresis. Results Patients with CVD had a significantly higher glycated hemoglobin level compared with the controls (5.72 vs 5.56). The proportion of patients with diabetes mellitus (DM) was higher in those who developed CVD during follow up (8.0% vs 1.9%). The frequency of CVD according to each tertile of LDL particle size and the number of metabolic syndrome components did not differ significantly. In the multivariate analysis, DM (odds ratio 4.244, 95% confidence interval 1.693–10.640, P = 0.002) was the only independent predictive factor of CVD. LDL particle size was not associated with the risk for future CVD. Conclusions Small dense LDL might not be a significant predictor of CVD in this Korean community-based prospective cohort study.

Background A Personal Health Record (PHR) is an online application that allows patients to access, manage, and share their health data. PHRs not only enhance shared decision making with healthcare providers, but also enable remote monitoring and at-home-collection of detailed data. The benefits of PHRs can be maximized in insulin dose adjustment for patients starting or intensifying insulin regimens, as frequent self-monitoring of glucose, self-adjustment of insulin dose, and precise at-home data collection during the visit-to-visit period are important for glycemic control. The aim of this study is to examine the efficacy and safety of insulin dose adjustment based on a smartphone PHR application in patients with diabetes mellitus (DM) and to confirm the validity and stability of an information and communication technology (ICT)-based centralized clinical trial monitoring system. Methods This is a 24-week, open-label, randomized, multi-center trial. There are three follow-up measures: baseline, post-intervention at week 12, and at week 24. Subjects diagnosed with type 1 DM, type 2 DM, and/or post-transplant DM who initiate basal insulin or intensify their insulin regimen to a basal-bolus regimen are included. After education on insulin dose titration and prevention for hypoglycemia and a 1-week acclimation period, subjects are randomized in a 1:1 ratio to either an ICT-based intervention group or a conventional intervention group. Subjects in the conventional intervention group will save and send their health information to the server via a PHR application, whereas those in ICT-based intervention group will receive additional algorithm-based feedback messages. The health information includes level of blood glucose, insulin dose, details on hypoglycemia, food diary, and step count. The primary outcome will be the proportion of patients who reach an optimal insulin dose within 12 weeks of study enrollment, without severe hypoglycemia or unscheduled clinic visits. Discussion This clinical trial will reveal whether insulin dose adjustment based on a smartphone PHR application can facilitate the optimization of insulin doses in patients with DM. In addition, the process evaluation will provide information about the validity and stability of the ICT-based centralized clinical trial monitoring system in this research field. Trial registration Clinicaltrials.gov NCT 03112343 . Registered on 12 April 2017.

SummaryObjective Although papillary thyroid microcarcinoma (PTMC) has a favourable long-term prognosis, disease recurrence after initial treatment remains a problem and controversy exists regarding the role of radioactive iodine (RAI) ablation in PTMC. We performed this study to evaluate the effect of RAI ablation on disease recurrence in patients with PTMC. Patients and Methods Between 1994 and 2004, 2579 patients underwent thyroid surgery for thyroid cancer at Samsung Medical Center. Among these patients, 704 patients with PTMC presumed disease-free after initial treatment were followed up for disease recurrence (median, 64 months; range, 1–185 months). Patients with PTMC with microscopic extrathyroidal extension, cervical lymph node metastases or multifocality were considered to be in the intermediate-risk group for recurrence. Results Disease recurrence was found in six patients at a median of 29 months (range, 10–70 months) after initial treatment; all six patients with recurrent tumours had received RAI treatment after total thyroidectomy. Disease-related mortality was not observed, even after recurrence. Based on a Cox regression model considering the standardized inverse probability of treatment weight (IPTW) within each propensity score stratum of patients with a similar likelihood of having received RAI ablation, the likelihood ratio for recurrence did not differ between the RAI ablation group and no RAI group (P = 0·17). When we performed a subgroup analysis considering only patients with PTMC at intermediate-risk for recurrence, RAI ablation again did not have a significant effect on recurrence (P = 0·79). Conclusions Radioactive iodine ablation after total thyroidectomy in low- and intermediate-risk patients with PTMC did not prevent recurrent tumours. Future randomized, controlled, multicenter prospective trials involving a larger sample of patients followed-up for a longer duration are warranted to confirm our findings.

Background: Tumor necrosis factor (TNF)-α is associated with insulin resistance and systemic inflammatory responses. The aim of this study was to investigate the relationship between TNF-α and the development of nonalcoholic fatty liver disease (NAFLD) in a longitudinal study. Methods: Three hundred and sixty-three apparently healthy subjects (mean age, 40.5±6.1 years; male, 57.6%) without NAFLD were enrolled in 2003. Anthropometric and laboratory measurements were performed. The participants were grouped into tertiles according to their serum TNF-α levels from samples taken in 2003. At a 4-year follow-up, we compared the odds ratios (ORs) of the development of NAFLD according to the tertiles of TNF-α levels measured in 2003. Results: At the 4-year follow-up, the cumulative incidence of NAFLD was 29.2% (106/363). The group that developed NAFLD had higher levels of TNF-α than those in the group without NAFLD (3.65±1.79 pg/mL vs. 3.15±1.78 pg/mL; P=0.016). When the 2003 serum TNF-α levels were categorized into tertiles: incidence of NAFLD observed in 2007 was significantly higher with increasing tertiles (22.6%, 35.8%, and 41.5%, respectively; P

We report the case of a 36-year-old woman who presented with headache, fever, and amenorrhea. Laboratory analysis revealed hypopituitarism and autoimmune thyroiditis, while a cerebrospinal fluid study suggested concurrent aseptic meningitis. A magnetic resonance image (MRI) scan revealed a 1.0×0.9 cm cystic mass enlarging the sella turcica. Surgical resection via an endoscopic transsphenoidal route was performed. The histological finding of the excised tissue revealed foamy histiocytes with vacuolated cytoplasm, supporting the diagnosis of xanthomatous hypophysitis. Although a residual soft lesion was observed on the MRI image postoperatively, the patient's headache and fever improved. Ten months after surgery, the patient complained of visual impairment and headache, and the residual mass had enlarged into the suprasellar area. High dose (500 mg intravenous) methylprednisolone was administered for 3 days. During the methylprednisolone pulse therapy, the patient's visual acuity and headache improved. A follow-up MRI taken after methylprednisolone therapy showed a marked mass reduction. Our case supports an autoimmune pathophysiology for xanthomatous hypophysitis and suggests that high dose glucocorticoid therapy as a treatment option.

This study was conducted to investigate whether baseline lung function or change in lung function is associated with the development of metabolic syndrome (MS) in Koreans. We analyzed clinical and laboratory data from 3,768 Koreans aged 40-60 years who underwent medical check-ups over a six-year period between 2006 and 2012. We calculated the percent change in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) over the study period. We tested for an association between baseline lung function or lung function change during the follow-up period and the development of MS. The 533 subjects (14.1%) developed MS after the six-year follow-up. The baseline FVC and FEV1 were not different between the subjects who developed MS after six years and the subject without MS after six years. The percent change in FVC over six years in subjects who developed MS after six years was higher than that in subjects who did not develop MS (-5.75 [-10.19 --1.17], -3.29 [-7.69-1.09], respectively, P = 0.001). The percent change in FVC over six years was associated with MS development after adjusting for age, sex, body mass index (BMI), glucose, HDL, triglyceride, waist circumferences (WC), and systolic blood pressure. However, these association was not significant after adjusting for change of BMI and change of WC over six years (P = 0.306). The greater change in vital capacity over six years of follow-up was associated with MS development, predominantly due to obesity and abdominal obesity. The prospective study is needed to determine the relationship between lung function decline and MS.

Thyroid hormones are important regulators of glucose homeostasis. However, the association between thyroid hormones within the reference range and type 2 diabetes mellitus (T2DM) remains unclear. The aim of this study was to clarify the incidence of T2DM according to the baseline levels and changes of thyrotropin (TSH) and thyroid hormones (free thyroxine and triiodothyronine) in euthyroid subjects.Among the participants who consecutively underwent thyroid function tests between 2006 and 2012 through a yearly health checkup program, 6235 euthyroid subjects (3619 men and 2616 women) without T2DM were enrolled in the study. The change in each hormone was calculated by subtracting the baseline value from the level at the end of follow-up or one year before the diagnosis of diabetes.During 25,692 person-years of follow-up, there were 229 new cases of T2DM. After full adjustment for potential confounders including HbA1c and fasting glucose in Cox proportional hazards models, the individuals in the highest tertile of TSH change (2.5-4.2 μIU/mL) had a greater risk of incident T2DM (hazard ratio [HR] = 1.44 [confidence interval (CI) 1.04-1.98], p = 0.027) in comparison with individuals in the lowest tertile (-4.1 to -0.5 μIU/mL). Simultaneously, the highest tertile of triiodothyronine change (16.3-104.7 ng/dL) and free thyroxine change (0.2-1.6 ng/dL) conferred protective effects against diabetes (HR = 0.60 [CI 0.43-0.85], p = 0.002, and HR = 0.34 [CI 0.24-0.48], p 0.001, respectively) compared with those in the lowest tertile (-76.5 to -1.8 ng/dL and -0.6 to 0.0 ng/dL, respectively). These associations remained significant when each of the hormones was analyzed as a continuous variable. However, baseline levels or tertiles of TSH and thyroid hormones were not associated with the risk of diabetes.Individual changes in TSH and thyroid hormones, even within the normal reference range, were an additional risk factor of incident T2DM.

Introduction Non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of the metabolic syndrome (MetS), with insulin resistance as the common pathophysiology. In a current longitudinal cohort study, we evaluated the separate and combined effects of MetS and NAFLD on incident diabetes risk. Methods Participants were categorized into four groups on the basis of the presence of NAFLD and MetS at baseline (i.e., with NAFLD, with MetS, with both, or without either). We compared the development of diabetes among these four groups. Results During the mean follow up of 4 years, 435 of the 7849 participants (5.5%) developed diabetes. The age, sex, and smoking-adjusted risk of incident diabetes was higher in the NAFLD only group (HR 1.51, 95% CI 1.14–1.99), MetS only group (HR 2.82, 95% CI 2.01–3.95), and both group (HR 5.45, 95% CI 4.32–6.82) compared with the group of neither. When compared with the NAFLD only group, the adjusted HR for incident diabetes was 1.87 (95% CI 1.29–2.72) in the MetS only group and 3.62 (95% CI 2.74–4.77) in both group. Among individuals with MetS, the presence of NAFLD showed a significant increase in risk of incident diabetes even after further adjustment for MetS components including fasting glucose, TG, BMI, systolic BP, and HDL-C (HR 1.53, 95% CI 1.09–2.16). Conclusion The presence of NAFLD further increased the risk of incident diabetes in individuals with metabolic syndrome. Our results suggest that the coexistence of NAFLD has an additive effect on the development of diabetes in individuals with MetS.

Thyroid function is known to influence glucose metabolism, and thyroid-stimulating hormone is the most useful parameter in screening for thyroid dysfunction. Therefore, the aim of this study was to investigate the incidence of type 2 diabetes according to baseline thyroid-stimulating hormone level and thyroid-stimulating hormone change in euthyroid subjects. We identified and enrolled 17,061 euthyroid subjects without diabetes among participants who had undergone consecutive thyroid function tests between 2006 and 2012 as a part of yearly health check-up program. Thyroid-stimulating hormone changes were determined by subtracting baseline thyroid-stimulating hormone level from thyroid-stimulating hormone level at 1 year before diagnosis of diabetes or at the end of follow-up in subjects who did not develope diabetes. During 84,595 person-years of follow-up, there were 956 new cases of type 2 diabetes. Cox proportional hazards models showed the risk of incident type 2 diabetes was significantly increased with each 1 μIU/mL increment in TSH after adjustment for multiple confounding factors (hazard ratio = 1.13, 95% confidence interval: 1.07–1.20, P

BackgroundSeveral cross-sectional studies have reported that thyroid hormone levels are associated with cardiovascular risk markers and metabolic syndrome (MetS) even in euthyroid subjects. However, the prognostic role of serum thyroid hormone levels in the risk of incident MetS has not been elucidated.AimWe aimed to investigate the associations of baseline serum thyroid hormone levels with the development of MetS in healthy subjects.MethodsThis 6-year, cross-sectional, longitudinal and follow-up study was conducted in 12 037 euthyroid middle-aged subjects without MetS subjected to comprehensive health examinations. Subjects were grouped according to total triiodothyronine (T3) quartiles. The hazard ratio (HR) for the development of MetS according to T3 quartiles was estimated using Cox proportional hazards model.ResultsDuring the 6-year period, 3544 incident cases of MetS (29%) were identified. The proportion of subjects with incident MetS increased across the T3 quartiles (Pfor trend P ConclusionIn euthyroid middle-aged subjects, serum T3 levels are associated with increased risk for future development of MetS.

BACKGROUND Diabetes self-management education has an important role in diabetes management. The efficacy of education has been proven in several randomized trials. However, the status of diabetes education programs in real Korean clinical practice has not yet been evaluated in terms of patient compliance with the education prescription. METHODS We retrospectively analyzed clinical and laboratory data from all patients who were ordered to undergo diabetes education during 2009 at Samsung Medical Center, Seoul, Korea (n=2,291). After excluding ineligible subjects, 588 patients were included in the analysis. RESULTS Among the 588 patients, 433 received education. The overall compliance rate was 73.6%, which was significantly higher in the subjects with a short duration or living in a rural area compared to those with a long duration (85.0% vs. 65.1%, respectively; P

Background/Aims: We have a limited understanding of the effect of nonalcoholic fatty liver disease (NAFLD) on the de-velopment of type 2 diabetes. Methods: The study subjects included male who had received biennial medical check-ups between 2005 and 2009 and who had been diagnosed with fatty liver disease. The subjects with sustained NAFLD (FL, n=107) and sustained non-NAFLD (NFL, n=1,054) were followed to determine the development of type 2 diabetes. Results: In the FL group, there were more subjects with impaired fasting glucose (IFG), type 2 diabetes and high HOMA-IR than there were in the NFL group during the 5-year follow-up period (32.7 vs. 17.6%, 1.9 vs. 0.3%, 17.9 vs. 5.2% respectively, p

Background: We aimed to examine the relationship between iron status and hypertension as few studies have addressed this. Methods: We analyzed the association between ferritin/total iron-binding capacity (TIBC) and the subsequent development of hypertension. A total of 8,580 men who visited the Health Promotion Center for a medical checkup in 2005 were followed-up after 4 years. Results: Of the 8,580 men who were not hypertensive at baseline, 818 were found to be hypertensive at the 4-year follow-up. Compared with those who remained normotensive, these hypertensive subjects had higher levels of ferritin and TIBC at baseline, but had no significant difference in iron levels. After adjustment for age and body mass index (BMI), the odds ratios (OR) was substantially higher for new hypertension (OR 1.54, 95% confidence intervals (CIs) 1.26-1.88; P for trend

Traditional lipid measures are known to be associated with incident type 2 diabetes.Our objective was to assess the independent association between lipid profiles and the development of type 2 diabetes in nondiabetic Korean subjects over a 4-yr period.A total of 5577 Koreans without diabetes who underwent consecutive comprehensive health check-ups annually for 5 yr were enrolled. We measured concentrations of total cholesterol (TC), triglyceride (TG), apolipoprotein B (apoB), apolipoprotein A-I, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) and calculated lipid ratios. The association between incident type 2 diabetes and the initial values for lipid ratios and other lipoprotein components was examined.Over the course of 4 yr, 330 subjects (5.9%) developed type 2 diabetes. TC, LDL-C, TG, non-HDL, apoB, apoB to apolipoprotein A-I ratio, TC to HDL ratio, TG to HDL ratio, LDL to HDL ratio and apoB to HDL ratio were associated with incident type 2 diabetes in multivariate analysis after adjustment for age and gender. Of these, the ratio of TC to HDL and apoB to HDL showed a significant association with increased risk of type 2 diabetes, compared with other lipoprotein parameters: odds ratio (1.340, 95% confidence interval 1.166-1.538; and 1.338, 95% confidence interval 1.162-1.540), respectively. The odds ratio for the development of type 2 diabetes increased significantly as the tertiles of the baseline ratio of TC to HDL and apoB to HDL increased from the first to the third tertile.This study suggests that lipid and lipoprotein profiles can be independently associated with later development of type 2 diabetes in nondiabetic Korean adults in a longitudinal analysis.

Objective To evaluate the prevalence of and risk factors for diabetic retinopathy (DR) in Koreans with type II diabetes. Methods Subjects (400 male, 296 female) aged 30–65 years (mean 55.3 years) with hyperglycaemia (fasting plasma glucose ≥7.0 mmol/ml) or known diabetes (mean±SD duration 6.36±5.73 years) were enrolled in the Seoul Metro-City Diabetes Prevention Program (SMC-DPP) from September 2008 to September 2009. The severity of DR was diagnosed by grading fundus photographs taken from five standard fields per eye and categorised following the Early Treatment of Diabetic Retinopathy Study grading protocol. All participants underwent routine clinical and laboratory examinations to evaluate risk factors for DR. Results The overall prevalence of any type of DR was 18.7%. Logistic regression analyses showed that the following factors were significantly associated with DR after adjustment for age and gender, duration of diabetes, serum glycated haemoglobin A1c (HbA1c), mean arterial pressure, serum total cholesterol and serum triglycerides: duration of diabetes (OR 1.14, 95% CI 1.10 to 1.18, for 1 year increase), HbA1c (OR 1.49, 95% CI 1.20 to 1.85, for 1% increase), serum concentration of insulin (OR 0.87, 95% CI 0.81 to 0.94, for 1 μIU/ml increase), homoeostasis model assessment of insulin resistance (OR 0.06, 95% CI 0.01 to 0.29, for 10 unit increase), and presence of macroalbuminuria (OR 5.14, 95% CI 1.45 to 18.20, albumin to creatinine ratio >300 mg/g). Conclusions In addition to traditional risk factors, insulin resistance was associated with an increased risk of DR in Koreans with type 2 diabetes.

BACKGROUND: We performed a retrospective longitudinal study on the effects of changes in weight, body composition, and homeostasis model assessment (HOMA) indices on glycemic progression in subjects without diabetes during a four-year follow-up period in a community cohort without intentional intervention. METHODS: From 28,440 non-diabetic subjects who participated in a medical check-up program in 2004, data on anthropometric and metabolic parameters were obtained after four years in 2008. Body composition analyses were performed with a bioelectrical impedance analyzer. Skeletal muscle index (SMI, %) was calculated with lean mass/weight×100. Subjects were divided into three groups according to weight change status in four years: weight loss (≤-5.0%), stable weight (-5.0 to 5.0%), weight gain (≥5.0%). Progressors were defined as the subjects who progressed to impaired fasting glucose or diabetes. RESULTS: Progressors showed worse baseline metabolic profiles compared with non-progressors. In logistic regression analyses, the increase in changes of HOMA-insulin resistance (HOMA-IR) in four years presented higher odds ratios for glycemic progression compared with other changes during that period. Among the components of body composition, a change in waist-hip ratio was the strongest predictor, and SMI change in four years was a significant negative predictor for glycemic progression. Changes in HOMA β-cell function in four years was a negative predictor for glycemic progression. CONCLUSION: Increased interval changes in HOMA-IR, weight gain and waist-hip ratio was associated with glycemic progression during a four-year period without intentional intervention in non-diabetic Korean subjects.