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Background Despite the well-recognized health benefits of fresh fruit consumption, there is still substantial uncertainty about its potential effects on glycemic control in patients with type 2 diabetes mellitus (T2DM). Methods We examined the association of fresh fruit consumption and glycemic control in patients with T2DM using data from the 6th Korea National Health and Nutrition Examination Survey. The study sample was divided into three groups based on weekly fruit consumption frequency for the analysis. Results Patients with the highest fruit intake were older than those in the other two groups, and women were more likely to consume fruits in general. Being a current smoker and weekly alcohol intake also showed negative correlations according to the fruit intake tertiles. Fruit consumption was positively correlated with better hemoglobin A1c (HbA1c) levels. Moreover, patients in the highest tertile of fruit intake were 3.48 times more likely to be in good glycemic control defined as HbA1c

Background Fatty liver is associated with increased risk of developing type 2 diabetes. We aimed to evaluate whether the severity of hepatic steatosis is associated with incident diabetes. Methods We conducted a longitudinal analysis using data from 1,798 participants who underwent a comprehensive health checkup and abdominal computed tomography (CT). We assessed the association between baseline liver attenuation value on non-contrast CT images and risk of incident diabetes. All the participants were categorized into three groups based on the baseline liver attenuation value on non-contrast CT images: without hepatic steatosis (>57 Hounsfield unit [HU]), mild hepatic steatosis (41–57 HU), and moderate to severe hepatic steatosis (≤40 HU). Results During a median follow-up period of 5 years, 6.0% of the study participants progressed to diabetes. The incidence of diabetes was 17.3% in the moderate to severe hepatic steatosis group, 9.0% in the mild steatosis group, and 2.9% in those without hepatic steatosis. In a multivariate adjustment model, as compared with participants without hepatic steatosis, those with moderate to severe steatosis had a hazard ratio (HR) of 3.24 (95% confidence interval [CI], 1.64 to 4.2) for the development of diabetes, and those in the mild steatosis group had a HR of 2.33 (95% CI, 1.42 to 3.80). One standard deviation decrease in mean CT attenuation values of the liver was associated with a 40% increase in the development of diabetes (multivariate adjusted HR, 1.40; 95% CI, 1.2 to 1.63). Conclusion We found a positive association between severity of hepatic steatosis and risk of incident diabetes. Greater severity of steatosis was associated with a higher risk of incident diabetes.

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.

ABSTRACT 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.

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

BackgroundIt 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.MethodsIn 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.ResultsAfter 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

BackgroundDifferentiated 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.MethodsThis 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.ResultsThe 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.ConclusionThe 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.

BackgroundSerum 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.MethodsIn 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.ResultsDuring 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).ConclusionHigher 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.

Abstract 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.

Abstract 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.

BackgroundAn 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.MethodsWe 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.ResultsA 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.ConclusionThere 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.

Abstract After publication of the original article [1] it was noted that both the figures and captions and relating to Figs. 1 and 2 had been interchanged.

BackgroundRecent 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.MethodsA 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.ResultsOf 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.

BackgroundMetabolic 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.MethodsA 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).ResultsThe 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.ConclusionMetS is a significant risk factor for the development of CVD although its impact varies between sexes.

BackgroundPrimary hypophysitis causes varying degrees of endocrine dysfunction and mass effect. The natural course and best treatment have not been well established.MethodsMedical records of 22 patients who had been diagnosed with primary hypophysitis between January 2001 and March 2013 were retrospectively reviewed. Based on the anatomical location, we classified the cases as adenohypophysitis (AH), infundibuloneurohypophysitis (INH), and panhypophysitis (PH). Clinical presentation, endocrine function, pathologic findings, magnetic resonance imaging findings, and treatment courses were reviewed.ResultsAmong 22 patients with primary hypophysitis, 81.8% (18/22) had involvement of the posterior pituitary lobe. Two patients of the AH (2/3, 66.6%) and three patients of the PH (3/10, 30%) groups initially underwent surgical mass reduction. Five patients, including three of the PH (3/10, 33.3%) group and one from each of the AH (1/3, 33.3%) and INH (1/9, 11.1%) groups, initially received high-dose glucocorticoid treatment. Nearly all of the patients treated with surgery or high-dose steroid treatment (9/11, 82%) required continuous hormone replacement during the follow-up period. Twelve patients received no treatment for mass reduction due to the absence of acute symptoms and signs related to a compressive mass effect. Most of them (11/12, 92%) did not show disease progression, and three patients recovered partially from hormone deficiency.ConclusionDeficits of the posterior pituitary were the most common features in our cases of primary hypophysitis. Pituitary endocrine defects responded less favorably to glucocorticoid treatment and surgery. In the absence of symptoms related to mass effect and with the mild defect of endocrine function, it may not require treatment to reduce mass except hormone replacement.

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.

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.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.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).Increase in serum albumin concentration might protect against early glycemic deterioration and progression to type 2 diabetes even in subjects without MetS.

BackgroundTo determine whether an internet-based mentoring program can improve glycemic control in subjects with type 1 diabetes mellitus (T1DM).MethodsSubjects with T1DM on intensive insulin therapy and with hemoglobin A1c (HbA1c) ≥8.0% were randomized to mentored (glucometer transmission with feedback from mentors) or control (glucometer transmission without feedback) groups and were examined for 12 weeks. Five mentors were interviewed and selected, of which two were T1DM patients themselves and three were parents with at least one child diagnosed with T1DM since more than 5 years ago.ResultsA total of 57 T1DM adult subjects with a mean duration after being diagnosed with diabetes of 7.4 years were recruited from Samsung Medical Center. Unfortunately, the mentored group failed to show significant improvements in HbA1c levels or other outcomes, including the quality of life, after completion of the study. However, the mentored group monitored their blood glucose (1.41 vs. 0.30) and logged into our website (http://ubisens.co.kr/) more frequently (20.59 times vs. 5.07 times) than the control group.ConclusionA 12-week internet-based mentoring program for T1DM patients with inadequate glycemic control did not prove to be superior to the usual follow-up. However, the noted increase in the subjects' frequency of blood glucose monitoring may lead to clinical benefits.

BackgroundSerum albumin has been suggested to be associated with insulin resistance. We evaluated the association between serum albumin concentration and insulin resistance. We also investigated whether serum albumin level has an independent effect on the development of diabetes.MethodsIn our study, 9,029 subjects without diabetes, who underwent comprehensive health check-ups annually for 5 years, were categorized into tertiles based on their serum albumin levels at baseline. The odds ratio (OR) for the prevalence of insulin resistance, defined as the top quartile of homeostasis model assessment of insulin resistance and the presence of impaired fasting glucose and nonalcoholic fatty liver disease, was evaluated cross-sectionally. Also, the hazard ratio (HR) for incident diabetes was estimated longitudinally, according to the baseline albumin tertiles using Cox proportional hazard analysis respectively.ResultsFrom the lowest to the highest tertile of albumin, the multivariable-adjusted ORs of insulin resistance increased significantly in both men and women. During the mean follow-up period of nearly 4 years, 556 (6.1%) subjects progressed to diabetes. The multivariable-adjusted HR (95% confidence interval [CI]) of diabetes in men were 1, 1.09 (95% CI, 0.86 to 1.40), and 1.10 (95% CI, 0.86 to 1.41), respectively, from the lowest to the highest tertiles of baseline albumin. Corresponding values for women were 1, 1.21 (95% CI, 0.66 to 2.21), and 1.06 (95% CI, 0.56 to 2.02), respectively.ConclusionOur study showed that increased serum albumin level was associated with insulin resistance. However, serum albumin did not have an independent effect on the development of diabetes.

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.

BackgroundDiabetes 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.MethodsWe 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.ResultsAmong 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

Serum bilirubin level was negatively associated with the prevalence of metabolic syndrome (MetS) in previous cross-sectional studies. However, bilirubin variance preceding the development of MetS has yet to be investigated. We aimed to determine the effect of change in bilirubin concentration on the risk of incident MetS in healthy Korean adults.We conducted a retrospective longitudinal study of subjects who had undergone at least four yearly health check-ups between 2006 and 2012. Of 24,185 total individuals who received annual check-ups, 11,613 non-MetS participants with a baseline bilirubin level not exceeding 34.2 μmol/l were enrolled. We evaluated the association between percent change in bilirubin and risk of incident MetS.During 55,407 person-years of follow-up, 2,439 cases of incident MetS developed (21.0%). Baseline serum bilirubin level clearly showed no association with the development of MetS in men but an independent significant inverse association in women which attenuated (hence may be mediated) by elevated homeostatic model assessment index 2 for insulin resistance (HOMA2-IR). However, increased risk for incident MetS was observed in higher percent change in bilirubin quartiles, with hazard ratios of 2.415 (95% CI 2.094-2.785) in men and 2.156 (95% CI 1.738-2.675) in women in the fourth quartile, compared to the lowest quartile, after adjusting for age, smoking status, medication history, alanine aminotransferase, uric acid, estimated glomerular filtration rate, fasting glucose, baseline diabetes mellitus prevalence, systolic blood pressure, waist circumference, and body mass index. The hazard ratios per one standard deviation increase in percent change in bilirubin as a continuous variable were 1.277 (95% CI 1.229-1.326) in men and 1.366 (95% CI 1.288-1.447) in women.Increases in serum bilirubin concentration were positively associated with a higher risk of incident MetS. Serum bilirubin increment might be a sensitive marker for the development of MetS.

BackgroundSmall dense low density lipoprotein (sdLDL) has recently emerged as an important risk factor of coronary heart disease.MethodsThe mean LDL particle size was measured in 203 patients with type 2 diabetes mellitus (T2DM) and 212 matched subjects without diabetes using polyacrylamide tube gel electrophoresis. Major vascular complications were defined as stroke, angiographically-documented coronary artery disease or a myocardial infarction. Peripheral vascular stenosis, carotid artery stenosis (≥50% in diameter) or carotid artery plaque were considered minor vascular complications. Overall vascular complications included both major and minor vascular complications.ResultsDiabetic patients had significantly smaller mean-LDL particle size (26.32 nm vs. 26.49 nm) and a higher percentage of sdLDL to total LDL compared to those of subjects without diabetes (21.39% vs. 6.34%). The independent predictors of sdLDL in this study were serum triglyceride level and body mass index (odds ratio [OR], 1.020 with P

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.

BackgroundWhether diabetic patients without a history of coronary heart disease (CHD) have the same risk of CHD events as non-diabetic patients with a history of CHD remains controversial. This study aimed to determine whether type 2 diabetes mellitus (T2DM) is a coronary heart disease (CHD) equivalent in the need for coronary revascularization procedures (RVs) in the Korean population.Methodology/principal findingsWe followed 2,168,698 subjects who had oral anti-diabetic drugs (OADs)-taking T2DM in 2008 and/or CHD in 2007-2008 (i.e., recent CHD). We used systematic datasets from the nationwide claims database of the Health Insurance Review and Assessment service of Korea, which is representative of the whole population of Korea, from January 2007 to December 2012. The primary study endpoint was the development of need for RVs (i.e., incident CHD) after January 2009 among three groups based on their status of T2DM and recent CHD, i.e., T2DM only, recent CHD only, and both T2DM and recent CHD. After adjustment for age and sex, patients with recent CHD only had 2.14 times the risk of incident CHD (95% CI, 2.11-2.18, PConclusions/significanceThis analysis of data from the nationwide claims database revealed that T2DM did not have a recent CHD equivalent risk in the Korean population. These results suggest that an appropriate strategy for the CHD risk stratification in diabetic patients should be adopted to manage this population.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a prevalent and rapidly increasing disease worldwide; however, no widely accepted screening models to assess the risk of NAFLD are available. Therefore, we aimed to develop and validate a self-assessment score for NAFLD in the general population using two independent cohorts.MethodsThe development cohort comprised 15676 subjects (8313 males and 7363 females) who visited the National Health Insurance Service Ilsan Hospital in Korea in 2008-2010. Anthropometric, clinical, and laboratory data were examined during regular health check-ups and fatty liver diagnosed by abdominal ultrasound. Logistic regression analysis was conducted to determine predictors of prevalent NAFLD and to derive risk scores/models. We validated our models and compared them with other existing methods using an external cohort (N = 66868).ResultsThe simple self-assessment score consists of age, sex, waist circumference, body mass index, history of diabetes and dyslipidemia, alcohol intake, physical activity and menopause status, which are independently associated with NAFLD, and has a value of 0-15. A cut-off point of ≥ 8 defined 58% of males and 36% of females as being at high-risk of NAFLD, and yielded a sensitivity of 80% in men (77% in women), a specificity of 67% (81%), a positive predictive value of 72% (63%), a negative predictive value of 76% (89%) and an AUC of 0.82 (0.88). Comparable results were obtained using the validation dataset. The comprehensive NAFLD score, which includes additional laboratory parameters, has enhanced discrimination ability, with an AUC of 0.86 for males and 0.91 for females. Both simple and comprehensive NAFLD scores were significantly increased in subjects with higher fatty liver grades or severity of liver conditions (e.g., simple steatosis, steatohepatitis).ConclusionsThe new non-laboratory-based self-assessment score may be useful for identifying individuals at high-risk of NAFLD. Further studies are warranted to evaluate the utility and feasibility of the scores in various settings.

BACKGROUND: Recent studies report the importance of metabolic health beyond obesity. The aim of this study is to compare the risk for diabetes development according to different status of metabolic health and obesity over a median follow-up of 48.7 months. METHODS: 6,748 non-diabetic subjects (mean age 43 years) were divided into four groups according to the baseline metabolic health and obesity status: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUHNO) and metabolically unhealthy obese (MUHO). Being metabolically healthy was defined by having less than 2 components among the 5 components, that is, high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol and being in the highest decile of homeostasis model assessment-insulin resistance (HOMA-IR) index. Obesity status was assessed by body mass index (BMI) higher than 25 kg/m2. The development of diabetes was assessed annually from self-questionnaire, fasting glucose and HbA1c. RESULTS: At baseline, 45.3% of the subjects were MHNO, 11.3% were MHO, 21.7% were MUHNO, and 21.7% were MUHO. During a median follow-up of 48.7 months, 277 subject (4.1%) developed diabetes. The hazard ratio for diabetes development was 1.338 in MHO group (95% CI 0.67-2.672), 4.321 in MUHNO group (95% CI 2.702-6.910) and 5.994 in MUHO group (95% CI 3.561-10.085) when MHNO group was considered as the reference group. These results were similar after adjustment for the changes of the risk factors during the follow-up period. CONCLUSION: The risk for future diabetes development was higher in metabolically unhealthy subgroups compared with those of metabolically healthy subjects regardless of obesity status.

The effects of exendin-4 on Sirt1 expression as a mechanism of reducing fatty liver have not been previously reported. Therefore, we investigated whether the beneficial effects of exendin-4 treatment on fatty liver are mediated via Sirt1 in high-fat (HF) diet-induced obese C57BL/6J mice and related cell culture models. Exendin-4 treatment decreased body weight, serum free fatty acid (FA), and triglyceride levels in HF-induced obese C57BL/6J mice. Histological analysis showed that exendin-4 reversed HF-induced hepatic accumulation of lipids and inflammation. Exendin-4 treatment increased mRNA and protein expression of Sirt1 and its downstream factor, AMPK, in vivo and also induced genes associated with FA oxidation and glucose metabolism. In addition, a significant increase in the hepatic expression of Lkb1 and Nampt mRNA was observed in exendin-4-treated groups. We also observed increased expression of phospho-Foxo1 and GLUT2, which are involved in hepatic glucose metabolism. In HepG2 and Huh7 cells, mRNA and protein expressions of GLP-1R were increased by exendin-4 treatment in a dose-dependent manner. Exendin-4 enhanced protein expression of Sirt1 and phospho-AMPKα in HepG2 cells treated with 0.4 mM palmitic acid. We also found that Sirt1 was an upstream regulator of AMPK in hepatocytes. A novel finding of this study was the observation that expression of GLP-1R is proportional to exendin-4 concentration and exendin-4 could attenuate fatty liver through activation of Sirt1.

BACKGROUND: We evaluated the association of regular physical exercise with the presence of non-alcoholic fatty liver disease (NAFLD) and liver enzymes in relation to obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional analysis was conducted in 72,359 healthy Korean adults without diabetes who participated in a comprehensive health check-up. Subjects who have been exercising regularly (more than 3 times per week, at least for 30 minutes each time and for consecutive 3 month) were categorized into exercise group. All subjects were categorized into deciles based on their body mass index (BMI) and we estimated the odds ratios (ORs) for having NAFLD according to exercise regularity in each decile. The diagnosis of NAFLD was based on ultrasonography findings. Individuals with NAFLD (n = 19,921) were analyzed separately to evaluate ORs for having elevated liver enzymes based on regularity of exercise. The risk for NAFLD was significantly reduced in exercise group with age- and sex-adjusted ORs of 0.53-0.72 for all BMI deciles except at BMI categories of