The impact of diabetes status on total and site-specific cancer risk in the elderly population: A nationwide cohort study.

AIMS: We aimed to evaluate the association of prediabetes, diabetes, and diabetes duration with risk of total and site-specific cancer in the Korean population aged 65 years and above. METHODS: This study included 1,232,173 subjects aged ≥ 65 years who underwent a general health screening program. Diabetes status was categorized as normal glucose tolerance, impaired fasting glucose, new-onset diabetes, diabetes duration of < 5 years, and diabetes duration of ≥ 5 years. Cox proportional hazards models were used to investigate the association of diabetes status with cancer risk. RESULTS: The risk of total cancer increased as diabetes status worsened, as did the risks of liver, biliary, and pancreatic cancer. Risks of liver, biliary, and pancreatic cancer were significantly higher in subjects aged 65-74 years than in those aged ≥ 75 years. The relationship of diabetes status with overall cancer incidence was found to significantly interact with sex. Among subjects with diabetes, the risks of liver and lung cancer were significantly higher in men than in women regardless of diabetes duration. CONCLUSIONS: Diabetes status is associated with increased risk of cancer in the elderly. There are age and sex differences in the risk of total and site-specific cancers, including liver, biliary, and pancreatic cancer. This study highlights the importance of cancer screening for elderly subjects with diabetes.

Impacts of gender and lifestyle on the association between depressive symptoms and cardiovascular disease risk in the UK Biobank.

We investigated the effects of gender and lifestyle on the association between frequency of depressive symptoms and CVD risk. The UK Biobank is a national prospective cohort study that recruited 502,505 participants aged 40-69 years between 2006 and 2010. Participants without CVD were classified as having low, moderate, high, or very high frequency of depressive symptoms according to the number of days they felt depressed in a 2-week period. UKBB data include self-reported questionnaires covering lifestyle behaviors such as smoking, physical activity, eating habits, and sleep duration. The primary outcomes included incident CVD including coronary artery disease, ischemic stroke, hemorrhagic stroke, peripheral artery disease, atrial fibrillation/flutter, and heart failure. Cox proportional hazard models were used to evaluate the effects of gender and lifestyle on the association of frequency of depressive symptoms and CVD risk. During a median follow-up of 8.9 years, 27,394 (6.3%) developed CVD. The frequency of depressive symptoms increased the risk of CVD according to low, moderate, high, and very high frequency of depressive symptoms (P for trend < 0.001). The adjusted CVD risk was 1.38-fold higher for participants with very high frequency of depressive symptoms compared to those with low frequency of depressive symptoms (HR 1.38, 95% CI 1.24-1.53, P < 0.001). The correlation between frequency of depressive symptoms and CVD risk was more remarkable in females than in males. In participants with high or very high frequency of depressive symptoms, the individual lifestyle factors of no current smoking, non-obesity, non-abdominal obesity, regular physical activity, and appropriate sleep respectively was associated with lower CVD risk by 46% (HR 0.54, 95% CI 0.48-0.60, P < 0.001), 36% (HR 0.64, 95% CI 0.58-0.70, P < 0.001), 31% (HR 0.69, 95% CI 0.62-0.76, P < 0.001), 25% (HR 0.75, 95% CI 0.68-0.83, P < 0.001), and 22% (HR 0.78, 95% CI 0.71-0.86, P < 0.001). In this large prospective cohort study, a higher frequency of depressive symptoms at baseline was significantly associated with increased risk of CVD in the middle-aged population, and this relationship was prominent in women. In the middle-aged population with depressive symptoms, engaging in a healthier lifestyle could prevent CVD risk.

Lactobacillus paracasei ATG-E1 improves particulate matter 10 plus diesel exhaust particles (PM10D)-induced airway inflammation by regulating immune responses.

Particulate matter (PM) exposure can adversely affect respiratory function. Probiotics can alleviate the inflammatory responses in respiratory diseases. We examined the protective effects of Lactobacillus paracasei ATG-E1 isolated from the feces of a newborn baby against airway inflammation in a PM10 plus diesel exhaust particle (DEP) (PM10D)-induced airway inflammation model. BALB/c mice were exposed to PM10D by intranasal injection three times at 3-day intervals for 12 days, and L. paracasei ATG-E1 was administered orally for 12 days. Analysis of immune cell population and expression of various inflammatory mediators and gut barrier-related genes were determined in bronchoalveolar lavage fluid (BALF), lung, peyer's patch, and small intestine. A histological analysis of the lungs was performed. In addition, the in vitro safety and their safety in genomic analyses were examined. L. paracasei ATG-E1 was found to be safe in vitro and by genomic analysis. L. paracasei ATG-E1 suppressed neutrophil infiltration and the number of CD4+, CD4+CD69+, CD62L-CD44+high, CD21/35+B220+, and Gr-1+CD11b+ cells, as well as the expression of inflammatory mediators, including chemokine (C-X-C motif) ligand (CXCL)-1, macrophage inflammatory protein (MIP)-2, interleukin (IL)-17a, tumor necrosis factor (TNF)-α, and IL-6 in BALF and lungs in PM10D-induced airway inflammation. It protected against histopathological damage in the lungs of mice with PM10D-induced airway inflammation. L. paracasei ATG-E1 concomitantly increased the expression levels of the gut barrier function-related genes occludin, claudin-1, and IL-10 in the small intestine, with an increased number of CD4+ and CD4+CD25+ immune cells in the peyer's patch. L. paracasei ATG-E1 suppressed immune activation and airway inflammatory responses in the airways and lungs by restoring the lung damage by PM10D. It also regulated intestinal immunity and ameliorated the gut barrier function in the ileum. These results indicate the potential of L. paracasei ATG-E1 as an protective and therapeutic agent against airway inflammation and respiratory diseases.

Sulfur Metabolism of the Gut Microbiome and Colorectal Cancer: The Threat to the Younger Generation.

Colorectal cancer diagnosed in individuals under 50 years old is called early-onset colorectal cancer (EOCRC), and its incidence has been rising worldwide. Simultaneously occurring with increasing obesity, this worrisome trend is partly explained by the strong influence of dietary elements, particularly fatty, meaty, and sugary food. An animal-based diet, the so-called Western diet, causes a shift in dominant microbiota and their metabolic activity, which may disrupt the homeostasis of hydrogen sulfide concentration. Bacterial sulfur metabolism is recognized as a critical mechanism of EOCRC pathogenesis. This review evaluates the pathophysiology of how a diet-associated shift in gut microbiota, so-called the microbial sulfur diet, provokes injuries and inflammation to the colonic mucosa and contributes to the development of CRC.

Comparison of Operational Definition of Type 2 Diabetes Mellitus Based on Data from Korean National Health Insurance Service and Korea National Health and Nutrition Examination Survey.

BACKGROUND: We evaluated the validity and reliability of the operational definition of type 2 diabetes mellitus (T2DM) based on the Korean National Health Insurance Service (NHIS) database. METHODS: Adult subjects (≥40 years old) included in the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2017 were merged with those from the NHIS health check-up database, producing a cross-sectional dataset. We evaluated the sensitivity, specificity, accuracy, and agreement of the NHIS criteria for defining T2DM by comparing them with the KNHANES criteria as a standard reference. RESULTS: In the study population (n=13,006), two algorithms were devised to determine from the NHIS dataset whether the diagnostic claim codes for T2DM were accompanied by prescription codes for anti-diabetic drugs (algorithm 1) or not (algorithm 2). Using these algorithms, the prevalence of T2DM was 14.9% (n=1,942; algorithm 1) and 20.8% (n=2,707; algorithm 2). Good reliability in defining T2DM was observed for both algorithms (Kappa index, 0.73 [algorithm 1], 0.63 [algorithm 2]). However, the accuracy (0.93 vs. 0.89) and specificity (0.96 vs. 0.90) tended to be higher for algorithm 1 than for algorithm 2. The validity (accuracy, ranging from 0.91 to 0.95) and reliability (Kappa index, ranging from 0.68 to 0.78) of defining T2DM by NHIS criteria were independent of age, sex, socioeconomic status, and accompanied hypertension or dyslipidemia. CONCLUSION: The operational definition of T2DM based on population-based NHIS claims data, including diagnostic codes and prescription codes, could be a valid tool to identify individuals with T2DM in the Korean population.

Association between serum ferritin levels and colorectal cancer risk in Korea.

BACKGROUND/AIMS: The concentration of serum ferritin, a storage form of iron, may be associated with carcinogenesis in various cancers. There are only limited studies on the relationship between serum ferritin levels and colorectal cancer (CRC) risk, especially in the Asian population. This study aimed to analyze the association between CRC incidence and serum ferritin levels. METHODS: This was a national cohort study that used health checkup and insurance claims data of the Korean population. CRC incidence according to the serum ferritin level was analyzed during 2008-2018 in 17,116 participants. RESULTS: The hazard ratio (HR) of CRC incidence decreased as serum ferritin levels increased (Q1: HR, 1.000 [95% confidence interval [CI], reference]; Q2: HR, 0.811 [95% CI, 0.558 to 1.178]; Q3: HR, 0.654 [95% CI, 0.442 to 0.968]; Q4: HR, 0.443 [95% CI, 0.285 to 0.687]; p = 0.0026). In subgroup analysis, 40 to 64 years of age, sex, body mass index of < 25 kg/ m2, presence of metabolic syndrome, absence of diabetes mellitus, and absence of anemia had HRs of < 0.5 (95% CI) in the highest quartiles compared with that in the lowest quartiles. CONCLUSION: This study shows an inverse association between serum ferritin and CRC risk. Serum ferritin measurement can aid in identifying young adults requiring active CRC screening.

Duration of diabetes mellitus and risk of kidney and bladder cancer: a longitudinal nationwide cohort study.

Previous studies have suggested that diabetes mellitus (DM) may increase the risk of kidney and bladder cancer; however, little is known about the duration of DM. We aimed to analyze the risk of kidney and bladder cancer according to the duration of DM in a longitudinal nationwide cohort. This study was conducted in a cohort of 9,773,462 participants ≥ 20 years old who underwent a National Health Examination in 2009 and were followed up until December 2017. Cox-proportional hazard models were used to evaluate the risk of kidney and bladder cancer in relation to the duration of DM. During follow-up (mean 7.3 years), kidney and bladder cancer occurred in 11,219 and 13,769 participants, respectively. DM was associated with an increased risk of kidney and bladder cancer (hazard ratio (HR), 95% confidence interval (95% CI); 1.14, 1.09-1.20 and 1.23, 1.17-1.28, respectively). Compared to fasting glucose < 100 mg/dL, impaired fasting glucose (IFG) and longer DM duration were associated with increased risks (HR, 95% CI): IFG (1.05, 1.01-1.10), new-onset DM (1.13, 1.03-1.24), DM < 5 years (1.11, 1.02-1.20), and DM ≥ 5 years (1.25, 1.15-1.36) in kidney cancer; IFG (1.05, 1.01-1.09), new-onset DM (1.10, 1.01-1.19), DM < 5 years (1.26, 1.18-1.35), and DM ≥ 5 years (1.34, 1.26-1.43) in bladder cancer, respectively. Our findings suggest that the subjects with IFG and longer duration of DM had a higher risk for kidney and bladder cancer than those without DM.

An affinity for brainstem microglia in pediatric high-grade gliomas of brainstem origin.

Background: High-grade gliomas (HGG) in children have a devastating prognosis and occur in a remarkable spatiotemporal pattern. Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPG), typically occur in mid-childhood, while cortical HGGs are more frequent in older children and adults. The mechanisms behind this pattern are not clear. Methods: We used mouse organotypic slice cultures and glial cell cultures to test the impact of the microenvironment on human DIPG cells. Comparing the expression between brainstem and cortical microglia identified differentially expressed secreted proteins. The impact of some of these proteins on DIPGs was tested. Results: DIPGs, pediatric HGGs of brainstem origin, survive and divide more in organotypic slice cultures originating in the brainstem as compared to the cortex. Moreover, brainstem microglia are better able to support tumors of brainstem origin. A comparison between the two microglial populations revealed differentially expressed genes. One such gene, interleukin-33 (IL33), is highly expressed in the pons of young mice and its DIPG receptor is upregulated in this context. Consistent with this observation, the expression levels of IL33 and its receptor, IL1RL1, are higher in DIPG biopsies compared to low-grade cortical gliomas. Furthermore, IL33 can enhance proliferation and clonability of HGGs of brainstem origin, while blocking IL33 in brainstem organotypic slice cultures reduced the proliferation of these tumor cells. Conclusions: Crosstalk between DIPGs and the brainstem microenvironment, in particular microglia, through IL33 and other secreted factors, modulates spatiotemporal patterning of this HGG and could prove to be an important future therapeutic target.

Adherence to healthy lifestyle behaviors as a preventable risk factor for severe hypoglycemia in people with type 2 diabetes: A longitudinal nationwide cohort study.

AIMS/INTRODUCTION: We investigated the associations between a combination of lifestyle factors and changes to these factors and the subsequent risk of severe hypoglycemia (SH) in type 2 diabetes patients. MATERIALS AND METHODS: Individuals with adult type 2 diabetes who underwent consecutive 2-year interval health screening programs from 2009 to 2012 from the Korean National Health Insurance Service database were included and followed up until 2018. Information on history of smoking status, alcohol consumption and physical activity, as well as changes to these factors, was obtained. The primary outcome was incident SH. RESULTS: Of the 1,490,233 type 2 diabetes patients, 30,539 (2.1%) patients developed SH. Current smokers and heavy drinkers had increased risk of SH, compared with non-smokers and non-drinkers, respectively (hazard ratio 1.28, 95% confidence interval 1.23-1.34; hazard ratio 1.22, 95% confidence interval 1.15-1.30). However, regular physical activity was associated with reduced SH risk (hazard ratio 0.79, 95% confidence interval 0.77-0.82). A combination of unhealthy lifestyle habits was associated with increased SH risk in a dose-dependent fashion (P for trend <0.001). Compared with participants without changes in their unhealthy lifestyles, participants who improved lifestyles had decreased risk of SH. CONCLUSIONS: Greater adherence to healthy lifestyle factors and any improvement in unhealthy lifestyle habits were associated with a substantially lower risk of SH in individuals with type 2 diabetes.

Association of weight change following smoking cessation with the risk of tuberculosis development: A nationwide population-based cohort study.

BACKGROUND: Smoking or weight loss is a risk of tuberculosis (TB) development. However, the impact of weight change after smoking cessation on the occurrence of TB remains elusive. We aimed to determine the relationship between weight change after smoking cessation and the risk of TB development. METHODS: We conducted a population-based cohort study using the national database in Republic of Korea. Of the 10,490,491 subjects who underwent health check-up in 2009, we enrolled 9,953,124 subjects without a previous TB history and followed them until 2017. We divided all study participants into the following three groups: never, former, and current smokers. The primary endpoint was newly developed TB. RESULTS: Among 9,953,124 subjects analyzed, 5,922,845 (59.5%) were never smokers, 1,428,209 (14.4%) were former smokers, and 2,602,080 (26.1%) were current smokers. The risk of TB development was significantly higher in current smokers than in never smokers (adjusted hazard ratio (aHR) 1.158; 95% confidence interval [CI] 1.131-1.186). Among current smokers, individuals who stopped smoking and maintained weight after baseline evaluation had a significantly lower risk of TB development compared with those who continued to smoke (aHR 0.771; 95% CI 0.741-0.892). However, even after smoking cessation, individuals who lost weight were at a significantly higher risk of TB development compared with those who continued to smoke (aHR 1.327; 95% CI 1.119-1.715). CONCLUSIONS: Our findings suggest that smoking is a risk factor for TB and weight maintenance (neither gaining or losing) after quitting smoking might reduce the risk of TB development.

Synergistic association between underweight and type 2 diabetes on the development of laryngeal cancer: a national population-based retrospective cohort study.

BACKGROUND: Although cigarette smoking is the most significant risk factor for laryngeal cancer, other risk factors might also be associated with the development of laryngeal cancer. We investigated whether underweight and type 2 diabetes are associated with laryngeal cancer in a Korean population. METHODS: A total of 9,957,059 participants (≥20 years) without prior history of cancer who underwent a National Health Insurance Service health checkup in 2009 were followed up until December 31, 2018. Newly diagnosed laryngeal cancer was identified using claim data, and underweight was defined as body mass index (BMI) < 18.5 kg/m2. A Cox proportional-hazards models with multivariable adjustment were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs). RESULTS: During the median follow-up period of 8.3 years, 3504 cases of laryngeal cancer occurred. Underweight was associated with increased risk of laryngeal cancer after adjusting for potential confounders (HR: 1.43, 95% CI: 1.22-1.69) compared to those who were not underweight. Underweight and type 2 diabetes were synergistically associated with higher risk of laryngeal cancer (HR: 2.33, 95% CI: 1.54-3.51), compared to those without either condition. This relationship was stronger in those with an age < 65 years (HR: 3.33, 95% CI: 1.88-5.87) and alcohol consumption (HR: 2.72, 95% CI: 1.64-4.53). CONCLUSIONS: These results suggest that underweight may be a significant risk factor for laryngeal cancer and that underweight and type 2 diabetes might synergistically increase the risk of laryngeal cancer.

Impaired Lung Function and Lung Cancer Incidence: A Nationwide Population-Based Cohort Study.

BACKGROUND: It is unclear whether the presence of minimal lung function impairment is an independent risk factor for the development of lung cancer in general populations. METHODS: We conducted a population-based cohort study using nationally representative data from the Korean National Health and Nutrition Examination Survey and the Korean National Health Insurance Service. RESULTS: Of 20,553 participants, 169 were diagnosed with lung cancer during follow-up (median, 6.5 years). Participants with obstructive lung function impairment had increased risk of lung cancer (aHR: 2.51; 95% CI: 1.729-3.629) compared with those with normal lung function. The lower was the quartile or decile of forced expiratory volume in one second (FEV1) or the FEV1/forced vital capacity (FVC) ratio, the significantly higher was the incidence rate of lung cancer (p for trend < 0.0001). With FEV1 values in the lowest quartile (Q4), the incidence of lung cancer was significantly increased regardless of FVC (FEV1 Q4 and FVC values in the higher three quartiles Q1-3: aHR 1.754; 95% CI 1.084-2.847, FEV1 Q4 and FVC Q4: aHR 1.889; 95% CI 1.331-2.681). CONCLUSION: Our findings suggest that minimal lung function impairment, as expressed by lower FEV1 or FEV1/FVC value, may be associated with increased risk of lung cancer.

Cumulative obesity exposure increases the risk of kidney cancer: a longitudinal nationwide cohort study.

Obesity is one of the most important prognostic factors of kidney cancer. However, little is known regarding the cumulative impacts of obesity on kidney cancer risk. We aimed to analyze the dose- and time-dependent impact of obesity on kidney cancer risk using the Korean National Health Insurance System database. This longitudinal nationwide cohort study used data from the Korean National Health Insurance System database between 2012 and 2013. In total, 3,102,240 participants who received annual health examination more than four times consecutively were included in the final analysis. The primary endpoint was newly diagnosed kidney cancer according to the dose- and time-dependent impact of obesity. Dose-dependent impact was measured using body mass index (BMI) and waist circumference (WC), and time-dependent impact was measured using general and abdominal cumulative obesity exposure (gCOE and aCOE). COE was defined as the number of years since obesity diagnosis during the exposure period. We identified 1,831 participants with newly diagnosed kidney cancer (median follow-up: 4.3 years). The hazard ratios (HRs) for kidney cancer increased significantly alongside BMI and WC. The HRs for kidney cancer increased significantly in the higher gCOE groups (P for trend <0.001) as follows: 1 (1.33, 95% confidence intervals: 1.10-1.60), 2 (1.33, 1.08-1.63), 3 (1.55, 1.30-1.85), and 4 (1.82, 1.64-2.03) years. Similar trends were observed for aCOE (P for trend <0.001) as follows: 1 (1.42, 1.23-1.64), 2 (1.71, 1.46-2.02), 3 (1.76, 1.48-2.08), and 4 (2.11, 1.84-2.42) years. Risks of kidney cancer related to COE were much more pronounced in participants with the following characteristics: younger than 65 years old, male gender, diabetes, hypertension, and dyslipidemia. Longer COE was associated with an increased risk of kidney cancer in the Korean population. Participants with prolonged obesity and metabolic syndrome need active surveillance for kidney cancer.

Framingham Risk Score Assessment in Subjects with Pre-diabetes and Diabetes: A Cross-Sectional Study in Korea.

BACKGROUND: This study aimed to evaluate cardiovascular risk in subjects with pre-diabetes and diabetes in Korea. METHODS: In this pan-Korean, non-interventional, cross-sectional study, data were collected from medical records of 10 hospitals between November 2013 and June 2014. Subjects (aged ≥40 years) with medical records of dysglycemia and documentation of total cholesterol level, high-density lipoprotein cholesterol level, systolic blood pressure, and smoking status in the past 6 months were included. The primary endpoint was to determine the Framingham risk score (FRS). The relationships between FRS and cardiovascular risk factors, glycated hemoglobin, and insulin usage were determined by multiple linear regression analyses. RESULTS: Data from 1,537 subjects with pre-diabetes (n=1,025) and diabetes (n=512) were analyzed. The mean FRS (mean±standard deviation) in subjects with pre-diabetes/diabetes was 13.72±8.77. FRS was higher in subjects with diabetes than pre-diabetes (P<0.001). FRS in men with pre-diabetes was comparable to that in women with diabetes (13.80±7.37 vs. 13.35±7.13). FRS was elevated in subjects who consumed alcohol (2.66, P=0.033) and with obesity-class II (6.10, P=0.015) among subjects with diabetes (n=199), and was elevated in patients with left ventricular hypertrophy (11.10, P=0.005), those who consumed alcohol (3.06, P=0.000), were pre-obese (3.21, P=0.002), or were obesity-class I (2.89, P=0.002) among subjects with pre-diabetes (n=306) in comparison to subjects without these coexisting risk factors. CONCLUSION: Overall, Korean subjects with pre-diabetes and diabetes have an increased cardiovascular risk, which is significantly higher in those subjects with diabetes than with pre-diabetes. The present data can be used to develop measures to prevent and manage cardiovascular complications in Koreans with impaired glucose metabolism.

Waist circumference, body mass index, and colorectal cancer risk according to diabetes status: A Korean nationwide population-based cohort study.

BACKGROUND AND AIM: We investigated the relationship of BMI and waist circumference with the risk of colorectal cancer (CRC) using a population-based cohort database and to explore the relationship of CRC with diabetes status. METHODS: Retrospective data (age >20 years) on anthropometric variables, blood parameters of fasting sugar, lipid levels, and blood pressure were collected from the National Health Insurance Corporation database between 2009 and 2012. Cox regression models were used to estimate hazard ratio (HR) and corresponding 95% confidence intervals (95% CI). RESULTS: Of the 23 121 360 people studied, 120 579 were diagnosed with CRC after a median follow-up period of 5.4 years. Both waist circumference and body mass index were positively associated with increased risk of CRC, regardless of age or sex. After mutual adjustment, only waist circumference was significantly associated with increased risk of CRC (HR = 1.275, 95% CI: 1.205-1.349). When the risk of CRC was compared according to diabetes status among people with the same waist circumference range, risk of CRC was higher for those with worse diabetes status. CONCLUSION: When waist circumference and body mass index were mutually adjusted, only waist circumference was associated with CRC risk. In addition, the risk of CRC is gradually higher in those with worsening diabetes, even if their waist circumferences are within the same range.

Associations of general obesity and central obesity with the risk of hepatocellular carcinoma in a Korean population: A national population-based cohort study.

Numerous previous studies have shown an association between general obesity and hepatocellular carcinoma (HCC). However, relatively few reports on the association of central obesity and HCC are available in Asian populations. Therefore, we investigated the association between WC representing central obesity and the risk of HCC in addition to BMI representing general obesity and the risk of HCC in Korea. A total of 10 505 818 participants who received the National Health Insurance Service (NHIS) health checkups in 2009 were screened for study eligibility, and 26 979 cases of HCC occurred during the 7.3 years of mean follow-up. General obesity increased the risk of HCC with hazard ratios (HRs) of 1.14 (95% CI, 1.11-1.18) for BMI 25.0-<30.0 kg/m2 and 1.52 (95% CI, 1.43-1.61) for BMI ≥30 kg/m2 compared to those whose BMI is within the normal range. Central obesity was also associated with a higher risk of HCC. For the participants with a WC ≥105 cm in men and WC ≥100 cm in women, the risk of HCC was higher than that of the reference group (HR = 1.69, 95% CI, 1.54-1.85). The HRs were 1.13 (95% CI, 1.07-1.19) for nonobese participants with central obesity, and 1.34 (95% CI, 1.30-1.38) for obese participants with central obesity compared to those without both conditions. Our findings suggest that the risk of HCC increases even more when general obesity is combined with central obesity. Moreover, central obesity is associated with the risk of HCC, regardless of general obesity.

Role of sirtuin-1 (SIRT1) in hypoxic injury in pancreatic ß-cells.

Islet transplantation (ITx) is being developed as a treatment for type 1 diabetes mellitus, but hypoxic damage to transplanted islet grafts is an important factor affecting successful transplantation. To investigate the role of sirtuin-1 (SIRT1) under hypoxic injury in INS-1 cells, one type of pancreatic ß-cell lines, we used SRT1720 and GW4064 for SIRT1 activation. The small interfering RNA SIRT1 (si-SIRT1) was used to suppress SIRT1 gene expression. We measured cell viability, apoptosis, and the levels of inflammatory cytokines, including tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and reactive oxygen species (ROS), under hypoxic conditions. Real-time PCR and Western blot analysis were performed. Cell viability was significantly reduced to 71% and 40% after 4 and 6 h of hypoxic conditions, respectively. Apoptosis increased significantly 2.8-fold and 5.3-fold after 4 and 6 h of hypoxia, respectively. SIRT1 expression was significantly reduced at the mRNA and protein levels during hypoxia. Hypoxic damage significantly increased the TNF-α, IL-6 and ROS levels in INS-1 cells. However, the reduced cell viability and increased inflammatory cytokines from hypoxic damage were ameliorated by SIRT1 activation in INS-1 cells. These results suggest that SIRT1 is a potential target for the protection of pancreatic ß-cells against hypoxic damage during ITx.

Fasting glucose level and all-cause or cause-specific mortality in Korean adults: a nationwide cohort study.

BACKGROUND/AIMS: Although people with diabetes have been shown to have higher mortality than people without diabetes, there is a lack of data on the association between fasting glucose (FG) levels and cause-specific mortality rates in the general population. METHODS: A total of 326,547 Korean adults over 20 years of age, who had received a health checkup between 2006 and 2008 were selected from the Korean National Health Insurance Service sample cohort dataset and followed until 2015. We estimated hazard ratios (HRs) of all-cause mortality and cause-specific mortality relative to various range of FG levels. All causes of death were classified according to International Classification of Diseases (ICD)-10 codes. RESULTS: During follow-up (mean, 8.5 years), a total of 13,536 deaths (mortality rate 4.89/1,000 person-year) occurred; 4,916 deaths from cancer, 2,133 from cardiovascular disease, 762 from infectious disease, 199 from renal disease, and 5,526 from other causes. The overall mortality rate increased with an increase in FG category (HR, 1.78; 95% confidence interval, 1.65 to 1.92; in the ≥ 160 mg/dL). In addition, a J-shaped associations was found between FG levels and all-cause mortality after adjustment for age, sex, smoking, drinking, physical activity, body mass index, diabetes mellitus medication, hypertension, and dyslipidemia. In particular, the risk of cancer-mortality with high FG levels was increased for men but not women. CONCLUSION: The risk of all-cause and cause-specific mortality showed the tendency to increase when the FG level was outside of the normal range, indicating a J-shaped relationship, in both men and women.

Fasting plasma glucose level and the risk of open angle glaucoma: Nationwide population-based cohort study in Korea.

BACKGROUND: The level of fasting plasma glucose (FPG) is positively associated with intraocular pressure. Diabetes causes early structural changes of retina, especially on ganglion cell layer. In this regard, the FPG level itself may also show an independent association with open angle glaucoma (OAG) development in general population. Herein, we investigate the association of the FPG level with the incidence of OAG. METHODS: Using nationally representative data from the Korean National Health Insurance System, 374,376 subjects ≥40 years of age without OAG who underwent health examinations from 2009 to 2013 were enrolled and followed to the end of 2014. Incident cases of OAG using the International Classification of Diseases 10 codes and medication information were analyzed based on the levels of FPG. RESULTS: Subjects with the highest FPG level (≥160 mg/dL), compared with the lowest level (<80 mg/dL), showed a higher hazard ratio (HR) [2.189; 95% confidence interval (CI): 1.779-2.695; P for trend < 0.001] for OAG after adjustments for age and sex. This result persisted after further adjustments for the presence of type 2 diabetes, current smoking, drinking, and exercise habits, diastolic blood pressure, body mass index (BMI), and total cholesterol level (HR: 1.588; 95% CI: 1.268-1.989; P for trend < 0.001). The positive association between the FPG level and the incidence of OAG was distinct in subjects 40-64 years of age, those with a BMI <25 kg/m2, and those without hypertension (HR 2.022; 95% CI: 1.494-2.736; P for trend <0.001: HR 1.817; 95% CI: 1.372-2.407; P for trend < 0.001: HR 1.706; 95% CI: 1.180-2.467; P for trend <0.001, respectively). CONCLUSIONS: This nationwide population-based cohort study showed that the fasting glucose was associated with an increased risk of OAG. These findings suggest that subjects with high FPG levels require special attention when screening for glaucoma.

Site-specific cancer risk in patients with type 2 diabetes: a nationwide population-based cohort study in Korea.

BACKGROUND/AIMS: We aimed to evaluate site-specific cancer risk in diabetic patients and to investigate causal and temporal relationships by analyzing organ-specific cancer risk according to the duration of diabetes. METHODS: Using a database provided by the Korean National Health Insurance Service, we conducted a retrospective, population-based cohort study of adults aged ≥ 30 years from January 2005 to December 2013. To verify the possibility of detection bias or reverse causation, we compared hazard ratios (HRs) for each cancer according to the following duration of diabetes: less than 6 months, 6 months to 3 years, and more than 3 years. RESULTS: The incidence of overall cancer per 1,000 person-years was higher in patients with diabetes than in those without diabetes (20.36 vs. 10.83). The overall cancer risk according to the duration of diabetes was the highest within the first 6 months after diagnosis (HR, 2.03; 95% confidence interval [CI], 1.99 to 2.07), and the HR decreased with the duration of diabetes, ranging from 1.19 (95% CI, 1.18 to 1.21) between 6 months and 3 years to 1.12 (95% CI, 1.11 to 1.13) after 3 years. Both overall cancer risk and HR remained significantly higher in patients with diabetes than in those without diabetes. The risk for prostate cancer was higher in men with diabetes than in those without diabetes (HR, 1.12; 95% CI, 1.10 to 1.14). In women, the risk for endometrial cancer was significantly higher in patients with diabetes than in those without diabetes throughout the duration of diabetes. CONCLUSION: The risk for stomach, colorectum, liver, pancreas, and kidney cancer appeared to be higher in patients with diabetes than in those without diabetes regardless of the sex or duration of diabetes.