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Background: We aimed to investigate the association of hepatic steatosis with liver fibrosis and to assess the interactive effects of hepatic steatosis and insulin resistance on liver fibrosis in a nationally representative sample of United States adults.Methods: We conducted a cross-sectional analysis using data from National Health and Nutrition Examination Survey 2017 to 2018, which for the first time included transient elastography to assess liver stiffness and hepatic steatosis. We evaluated the association between hepatic steatosis (using controlled attenuation parameter [CAP]) and clinically significant liver fibrosis (defined as liver stiffness ≥7.5 kPa) using logistic regression with an interaction term for hepatic steatosis and insulin resistance (defined as homeostatic model assessment of insulin resistance ≥3.0).Results: Among adults undergoing transient elastography (n=2,023), 45.9% had moderate or greater hepatic steatosis and 11.3% had clinically significant liver fibrosis. After adjustment for demographic and metabolic factors, the odds of significant liver fibrosis increased as CAP score rose (odds ratio, 1.35 per standard deviation increment; 95% confidence interval, 1.11 to 1.64). We detected a significant interaction effect between CAP score and insulin resistance on the probability of significant liver fibrosis (P=0.016 for interaction). The probability of significant liver fibrosis increased in the presence of insulin resistance with increasing CAP score, while those without insulin resistance had low probability of significant liver fibrosis, even with high CAP scores.Conclusion: Individuals with hepatic steatosis had higher odds of fibrosis when insulin resistance was present. Our findings emphasize the importance of the metabolic aspects of the disease on fibrosis risk and suggest a need to better identify patients with metabolic associated fatty liver disease.

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.

To compare the efficacy and safety of adding low-dose lobeglitazone (0.25 mg/day) or standard-dose lobeglitazone (0.5 mg/day) to patients with type 2 diabetes mellitus (T2DM) with inadequate glucose control on metformin and dipeptidyl peptidase (DPP4) inhibitor therapy.In this phase 4, multicentre, double-blind, randomized controlled, non-inferiority trial, patients with T2DM insufficiently controlled by metformin and DPP4 inhibitor combination therapy were randomized to receive either low-dose or standard-dose lobeglitazone. The primary endpoint was non-inferiority of low-dose lobeglitazone in terms of glycaemic control, expressed as the difference in mean glycated haemoglobin levels at week 24 relative to baseline values and compared with standard-dose lobeglitazone, using 0.5% non-inferiority margin.At week 24, the mean glycated haemoglobin levels were 6.87 ± 0.54% and 6.68 ± 0.46% in low-dose and standard-dose lobeglitazone groups, respectively (p = .031). The between-group difference was 0.18% (95% confidence interval 0.017-0.345), showing non-inferiority of the low-dose lobeglitazone. Mean body weight changes were significantly greater in the standard-dose group (1.36 ± 2.23 kg) than in the low-dose group (0.50 ± 1.85 kg) at week 24. The changes in HOMA-IR, lipid profile and liver enzyme levels showed no significant difference between the groups. Overall treatment-emergent adverse events (including weight gain, oedema and hypoglycaemia) occurred more frequently in the standard-dose group.Adding low-dose lobeglitazone to metformin and DPP4 inhibitor combination resulted in a non-inferior glucose-lowering outcome and fewer adverse events compared with standard-dose lobeglitazone. Therefore, low-dose lobeglitazone might be one option for individualized strategy in patients with T2DM.

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: 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 ...

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: 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.

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.

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 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. Electronic supplementary material The online version of this article (doi:10.1186/s12911-017-0507-4) contains supplementary material, which is available to authorized users.

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.

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.

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.

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

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.

Objective Fatty liver is associated with insulin resistance-related diseases, such as dyslipidemia, obesity, and type 2 diabetes. The aim of this study was to evaluate the association of dyslipidemia with fatty liver and assess the differences in these associations according to the degree of hepatic steatosis. Methods A total of 2,462 subjects (1,679 men and 783 women) who underwent a comprehensive health check-up (including abdominal computed tomography) from January 2010 to December 2013 were enrolled at Samsung Changwon Hospital Healthcare Center. The liver attenuation index (LAI), defined as the difference between mean hepatic and splenic attenuation, was used to assess the degree of hepatic steatosis. An LAI below 5 Hounsfield units was defined as fatty liver. Results We found that 32.2% of the study subjects had fatty liver. Serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG), and fasting blood glucose concentrations and glycated hemoglobin (HbA1c percentage) were significant greater in the fatty liver group compared with the non-fatty liver group, while serum high-density lipoprotein cholesterol (HDL-C) was significantly lower in the fatty liver group. Subjects with fatty liver had 1.7-fold greater risk of dyslipidemia than those without fatty liver after adjusting for age, sex, body mass index (BMI), and HbA1c. When individuals with fatty liver were analyzed by tertiles of LAI values, LDL-C, TG, fasting glucose, BMI, and HbA1c concentrations increased while HDL-C decreased with decreasing LAI tertiles. Compared with LAI tertile 3, the risk for dyslipidemia significantly increased with adjusted odds ratios of 1.42, and 1.81 in tertiles 2 and 1, respectively. Conclusion Fatty liver was significantly associated with dyslipidemia and this association varied according to the degree of hepatic steatosis.

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).

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 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.

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.

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 Some studies have reported that delayed heart rate recovery (HRR) after exercise is associated with incident type 2 diabetes mellitus (T2DM). This study aimed to investigate the longitudinal association of delayed HRR following a graded exercise treadmill test (GTX) with the development of T2DM including glucose-associated parameters as an adjusting factor in healthy Korean men. Material and methods Analyses including fasting plasma glucose, HOMA-IR, HOMA-β, and HbA1c as confounding factors and known confounders were performed. HRR was calculated as peak heart rate minus heart rate after a 1-min rest (HRR 1). Cox proportional hazards model was used to quantify the independent association between HRR and incident T2DM. Results During 9082 person-years of follow-up between 2006 and 2012, there were 180 (10.1%) incident cases of T2DM. After adjustment for age, BMI, systolic BP, diastolic BP, smoking status, peak heart rate, peak oxygen uptake, TG, LDL-C, HDL-C, fasting plasma glucose, HOMA-IR, HOMA-β, and HbA1c, the hazard ratios (HRs) [95% confidence interval (CI)] of incident T2DM comparing the second and third tertiles to the first tertile of HRR 1 were 0.867 (0.609–1.235) and 0.624 (0.426–0.915), respectively (p for trend=0.017). As a continuous variable, in the fully-adjusted model, the HR (95% CI) of incident T2DM associated with each 1 beat increase in HRR 1 was 0.980 (0.960–1.000) (p=0.048). Conclusions This study demonstrated that delayed HRR after exercise predicts incident T2DM in men, even after adjusting for fasting glucose, HOMA-IR, HOMA-β, and HbA1c. However, only HRR 1 had clinical significance.

Adipocyte fatty acid-binding protein (FABP4) is abundantly expressed in adipocytes and plays a role in glucose homeostasis. We analysed the relationship between serum FABP4 levels and the progression of metabolic syndrome in healthy adults.A total of 465 subjects were selected from participants in a medical check-up programme at a Health Promotion Center. Baseline serum FABP4 levels were measured, and the subjects were evaluated for the presence of metabolic syndrome (MetS) according to the recommendations of the American Heart Association/National Heart, Lung, and Blood Institute. The subjects were re-evaluated 4 years later. Baseline FABP4 concentrations were significantly higher in subjects with MetS than in those without MetS (P0.001). At the 4-year follow-up, subjects in the highest FABP4 tertile at baseline exhibited higher values for body mass index, fat mass and percent body fat, as well as blood pressure, fasting glucose, total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol, insulin, homeostasis model assessment of insulin resistance, monocyte chemoattractant protein-1 and tumor necrosis factor-α levels (all P0.05). The subjects with higher FABP4 levels had lower HDL-cholesterol concentrations (P0.05). After adjustment for age, sex, change in percent body fat and baseline values for other metabolic and inflammatory parameters, FABP4 levels at baseline were shown to be strongly associated with the development of MetS by year 4 (odds ratio (OR), 5.75; 95% confidence interval (CI), 2.71-12.23 for highest tertile vs. lowest tertile, P0.001)Baseline serum FABP4 levels appear to be a significant predictor for the future development of MetS, independent of pro-inflammatory cytokines.

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.

Objective There is some evidence that lung function and chronic kidney disease (CKD) may be related. We evaluated the impact of lung function on the development of CKD in a large-scale longitudinal study. Method Retrospective longitudinal analyses were conducted among subjects who participated in comprehensive health check-ups at least four times during 7 years (between 2006 and 2012). We investigated the development of CKD during the follow-up period according to lung function status. Results Ten thousand one hundred and twenty-eight individuals (mean age =51.2 years) without CKD at baseline were enrolled. During the mean follow-up of 5 years (58.5±14.4 months), 167 of the 10 128 subjects (1.6%) developed CKD. Multivariable Cox proportional hazards analyses adjusting for age, sex, body mass index, systolic blood pressure, fasting glucose, estimated glomerular filtration rate, uric acid, triglycerides, serum albumin, and the presence of diabetes and hypertension revealed that a decrease of 10% in the forced expiratory volume in 1s (FEV1)/forced vital capacity (FVC) ratio was associated with a 35% increase in the development of CKD during the follow-up. The incidence of CKD was higher in those with an FEV1/FVC ratio

Several cross-sectional studies reported that serum bilirubin concentrations had an inverse association with type 2 diabetes mellitus (T2DM) prevalence. The aim of the current study was to investigate the relationship between percentage change in bilirubin levels (PCB) and incident risk of T2DM using a longitudinal model.22,084 participants who received regular health check-ups between 2006 and 2012 were enrolled. Multivariable-adjusted Cox regression models were used to determine the hazard ratio (HR) of incident T2DM based on PCB. PCB was determined by subtracting baseline serum bilirubin level (BB) from the bilirubin level at the end of follow-up or a year before the last date of diagnosis, dividing by BB and multiplying by 100. Compared to non-diabetics, BB was lower in the diabetic group at the initial visit. There were 20,098 participants without T2DM at the initial visit; 1253 new cases occurred during follow-up. As PCB increased, T2DM incidence also increased (P 0.001). After adjusting for confounders, the HR of incident T2DM in the highest PCB quartile was 2.08 (95% confidence interval [CI] 1.76-2.46). This trend remained significant when PCB was analyzed as a continuous variable (HR for 1-SD increment, 1.25; 95% CI 1.19-1.31). Additional analysis comparing the rate of PCB during the follow-up period revealed that the serum bilirubin level of the Incident T2DM group increased before T2DM development and decreased rapidly thereafter compared to others (P 0.001).Bilirubin level increment over time is associated with T2DM development.

The concept of subclinical Cushing’s syndrome stands on the presence of adrenocorticotropic hormone-independent subclinical hypercortisolism without a clear Cushingoid phenotype and may be observed in patients with an incidentally found adrenal adenoma [1]. Kim et al. [2] found that the prevalence of subclinical Cushing’s syndrome in Korean patients with adrenal incidentaloma was 7.1% (19 of 268 patients), which suggests that subclinical hypercortisolism is commonly found in patients with this disorder. Moreover, the presence of subclinical hypercortisolism in these patients was also associated with an increased prevalence of cardiovascular disease risk factors such as diabetes and hypertension [2]. As findings shown in Kim’s study, subclinical hypercortisolism is the most common hormonal abnormality in patients with adrenal incidentaloma [3] and even a very low excess of cortisol in patients with subclinical Cushing’s syndrome may contribute to the development of metabolic disorders such as obesity, diabetes, hypertension, and osteoporosis [1,4]. Thus, there has been a recent rise in interest regarding the diagnosis and management of subclinical Cushing’s syndrome. A recent study by Di Dalmazi et al. [5] observed that the incidences of cardiovascular events and mortality were higher in patients with subclinical Cushing’s syndrome compared to those with non-secreting adrenal incidentalomas over a mean followup period of 7.5 years. These authors suggested that this difference might be attributable to the relationship between subclinical cortisol excess and cardiovascular disease risk factors. The finding that subclinical hypercortisolism can harm patients implies that the management of subclinical Cushing’s syndrome would be a beneficial strategy to mitigate the effects of this disease. However, there is insufficient evidence to conclude which management strategy may be most effective [1]. To date, the majority of studies investigating this issue have been conducted using retrospective and cross-sectional designs with small sample sizes and a variety of definitions. Only one prospective study has been published showing that laparoscopic adrenalectomy is more beneficial than conservative management for the improvement of cardiovascular disease risk factors [6]. Thus, it is necessary to conduct a high-quality prospective study of the long-term outcomes of patients with subclinical Cushing’s syndrome, including their natural histories and the impending complications and/or risk factors. Furthermore, prospective studies should evaluate the effects of different management strategies on cardiovascular disease events and mortality in patients with adrenal incidentaloma and subclinical Cushing’s syndrome [1,6]. Currently, a multicenter, randomized, controlled prospective study assessing the long-term metabolic effects of adrenalectomy in Korean patients with adrenal incidentalomas and subclinical Cushing’s syndrome is underway (Clinicaltrial. gov: NCT01383420). The findings of this study will provide further insight into the effects of the management of subclinical Cushing’s syndrome on metabolic disorders.

OBJECTIVE We aimed to evaluate the effects of carnitine-orotate complex in patients with nonalcoholic fatty liver disease (NAFLD) and diabetes. RESEARCH DESIGN AND METHODS Eight hospitals in Korea participated in this randomized, controlled, double-blind trial of patients with diabetes and NAFLD. Seventy-eight patients were randomly assigned in a 1:1 ratio to receive carnitine-orotate complex (824 mg, three times daily) or matching placebo. The primary study outcome was decline in alanine aminotransferase (ALT) to the normal range. Secondary study outcomes were change in ALT, radiological hepatic steatosis, parameters for anthropometry, liver function, lipid profiles, and glycemic control. Hepatic steatosis was assessed using Hounsfield units on noncontrast computed tomography (CT) imaging with hepatic attenuation. RESULTS After 12 weeks of treatment, compared with placebo group, carnitine-orotate complex–treated participants had a significantly higher rate of normalization of serum ALT level (17.9% vs. 89.7%, P < 0.001). On hepatic CT analysis, participants treated with carnitine-orotate complex showed an increased liver attenuation index (0.74 ± 8.05 vs. 6.21 ± 8.96, P < 0.008). A significant decrease in HbA1c was observed in the carnitine-orotate complex group (−0.33 ± 0.82% [−3.6 ± 9.0 mmol/mol], P = 0.007), but no significant change was seen in the placebo group. CONCLUSIONS Treatment with carnitine-orotate complex improves serum ALT and may improve hepatic steatosis as assessed by CT in patients with diabetes and NAFLD. Further studies using more advanced magnetic resonance imaging and liver histology as an end point are needed to assess its efficacy in NAFLD.