Combined Administration of Pravastatin and Metformin Attenuates Acute Radiation-Induced Intestinal Injury in Mouse and Minipig Models.

Radiation-induced gastrointestinal (GI) damage is one of the critical factors that serve as basis for the lethality of nuclear accidents or terrorism. Further, there are no Food and Drug Administration-approved agents available to mitigate radiation-induced intestinal injury. Although pravastatin (PS) has been shown to exhibit anti-inflammatory and epithelial reconstructive effects following radiation exposure using mouse and minipig models, the treatment failed to improve the survival rate of high-dose irradiated intestinal injury. Moreover, we previously found that metformin (MF), a common drug used for treating type 2 diabetes mellitus, has a mitigating effect on radiation-induced enteropathy by promoting stem cell properties. In this study, we investigated whether the combined administration of PS and MF could achieve therapeutic effects on acute radiation-induced intestinal injury in mouse and minipig models. We found that the combined treatment markedly increased the survival rate and attenuated histological damage in a radiation-induced intestinal injury mouse model, in addition to epithelial barrier recovery, anti-inflammatory effects, and improved epithelial proliferation with stem cell properties. Furthermore, in minipig models, combined treatment with PS and MF ameliorates gross pathological damage in abdominal organs and attenuated radiation-induced intestinal histological damage. Therefore, the combination of PS and MF effectively alleviated radiation-induced intestinal injury in the mouse and minipig models. We believe that the combined use of PS and MF is a promising therapeutic approach for treating radiation-induced intestinal injury.

Metformin Protects the Intestinal Barrier by Activating Goblet Cell Maturation and Epithelial Proliferation in Radiation-Induced Enteropathy.

Radiotherapy or accidental exposure to high-dose radiation can cause severe damage to healthy organs. The gastrointestinal (GI) tract is a radiation-sensitive organ of the body. The intestinal barrier is the first line of defense in the GI tract, and consists of mucus secreted by goblet cells and a monolayer of epithelium. Intestinal stem cells (ISCs) help in barrier maintenance and intestinal function after injury by regulating efficient regeneration of the epithelium. The Wnt/ß-catenin pathway plays a critical role in maintaining the intestinal epithelium and regulates ISC self-renewal. Metformin is the most widely used antidiabetic drug in clinical practice, and its anti-inflammatory, antioxidative, and antiapoptotic effects have also been widely studied. In this study, we investigated whether metformin alleviated radiation-induced enteropathy by focusing on its role in protecting the epithelial barrier. We found that metformin alleviated radiation-induced enteropathy, with increased villi length and crypt numbers, and restored the intestinal barrier function in the irradiated intestine. In a radiation-induced enteropathy mouse model, metformin treatment increased tight-junction expression in the epithelium and inhibited bacterial translocation to mesenteric lymph nodes. Metformin increased the number of ISCs from radiation toxicity and enhanced epithelial repair by activating Wnt/ß-catenin signaling. These data suggested that metformin may be a potential therapeutic agent for radiation-induced enteropathy.

Screening for Atrial Fibrillation Using a Smartphone-Based Electrocardiogram in Korean Elderly.

Atrial fibrillation (AF) is responsible for 10-20% of cerebral infarctions. Several mobile devices have been developed to screen for AF and studies of AF screening have been conducted in several countries to evaluate the applicability of these mobile devices. In this tradition, we conducted a community-based AF screening using an automated single-lead electrocardiogram (SL-ECG). This survey examined 2,422 participants in a community dementia screening program who were aged 60 years or older in the preliminary study, and 5,366 participants at 9 Senior Welfare Centers aged 60 years or older in the expanded study. AF screening was conducted using an automated SL-ECG (Kardia Mobile, AliveCor, Mountain View, CA, USA). AF was confirmed with a 12-lead electrocardiogram in subjects classified as having AF on the SL-ECG. In the preliminary study, of the 2,422 subjects, 124 had AF on the SL-ECG. The prevalence of AF was 3.0% (95% confidence interval [CI]: 2.4-3.8). The positive predictive value (PPV) of SL-ECG was 58.9% (95% CI: 50.1-67.1). Of the subjects diagnosed with AF, 65.8% (95% CI: 54.3-75.6) were newly diagnosed. In an expanded study, of the 5,366 subjects, 289 had AF on SL-ECG. The prevalence was 2.6% (95% CI: 2.2-3.1) and PPV of SL-ECG was 48.8% (95% CI: 43.1-54.5). In this community-based AF screening, we found that AF is underdiagnosed and undertreated. These results suggest that the early detection of AF using mobile devices is needed in Korea.

Association of serum vitamin D and parathyroid hormone with subclinical atherosclerotic phenotypes: The Dong-gu Study.

BACKGROUND: Although previous studies reported an association between serum vitamin D and parathyroid hormone (PTH) with carotid atherosclerosis or arterial stiffness, these were inconsistent. We examined the independent association between serum vitamin D and PTH with multiple subclinical markers of atherosclerosis. METHODS: A total of 8,217 subjects who participated in the Dong-gu Study in Korea were included in the final analysis. The carotid artery structure, including intima-media thickness (IMT), plaques, and luminal diameter, was evaluated using a high-resolution B-mode ultrasound. The brachial-ankle pulse wave velocity (baPWV) was determined using an automatic waveform analysis device, and the mean of the left and right baPWV was used. RESULTS: The PTH concentration was positively associated with carotid luminal diameter and baPWV, but not with carotid IMT and plaques. The mean carotid luminal diameter of individuals with PTH levels in the second, third, and fourth quartiles was significantly larger compared with those in the first quartile (P-trend < 0.01). The mean baPWV of individuals with PTH levels in the fourth quartile was significantly greater than those with PTH levels in the first quartile (P-trend = 0.01). However, there was no significant association between vitamin D and any atherosclerotic phenotypes, including carotid IMT, plaques, luminal diameter, and baPWV. CONCLUSION: This suggests that PTH might affect the development of atherosclerosis by altering vascular compliance.

A Gender-Specific Association between Self-Reported Snoring and Hemoglobin A1c Levels in a General Population without Type 2 Diabetes Mellitus.

PURPOSE: We explored whether a gender difference was evident in terms of the associations of snoring with hemoglobin A1c (HbA1c) and homeostatic model assessment-insulin resistance (HOMA-IR) levels in a healthy population without type 2 diabetes mellitus (DM). MATERIALS AND METHODS: We analyzed 2706 males and 4080 females who participated in the baseline survey of the Namwon Study. In terms of self-reported snoring frequency, participants were classified as non-snorers or occasional (1-3 days/week), frequent (4-6 days/week), or constant (7 days/week) snorers. Participants with DM, defined as a fasting blood glucose level ≥126 mg/dL and/or use of insulin or hypoglycemic medication, were excluded from the analysis. RESULTS: In females, the fully adjusted mean (95% confidence interval) HbA1c levels in non-snorers and in occasional, frequent, and constant snorers were 5.53% (5.47-5.59%), 5.53% (5.47-5.59%), 5.57% (5.49-5.64%), and 5.57% (5.51-5.64%), respectively, reflecting a dose-response relationship (p trend=0.004). Compared with female non-snorers, the risk of an elevated HbA1c level (top quintile, ≥5.9%) in constant snorers remained significant (odds ratio 1.30, 95% confidence interval 1.02-1.66) after full adjustment. In addition, in females, a significant linear trend in HbA1c level odds ratio by increased snoring frequency was apparent (p trend=0.019 in model 3). In contrast, no significant association between snoring frequency and HbA1c level was identified in males. No significant association between snoring frequency and HOMA-IR was detected in either gender. CONCLUSION: We discovered a gender-specific association between snoring and HbA1c level in a healthy, community-dwelling population free of DM.

Association between Serum 25-hydroxyvitamin D Levels and Type 2 Diabetes in Korean Adults.

Previous studies have suggested that a vitamin D deficiency increases the risk of type 2 diabetes. This study evaluated the association between serum vitamin D levels and type 2 diabetes in Korean adults. This study included 9,014 subjects (3,600 males and 5,414 females) aged ≥50 years who participated in the Dong-gu Study. The subjects were divided into groups in whom the serum vitamin D level was severely deficient (<10 ng/mL), deficient (10 to <20 ng/mL), insufficient (20 to <30 ng/mL) and sufficient (≥30 ng/mL). Type 2 diabetes was defined by a fasting blood glucose level of ≥126 mg/dL and/or an HbA1c proportion of ≥6.5% and/or self-reported current use of diabetes medication. Multiple logistic regression was performed to evaluate the association between vitamin D status and type 2 diabetes. The age- and sex-adjusted prevalence of type 2 diabetes was 22.6%, 22.5% and 18.4% and 12.7% for severely deficient, deficient, insufficient, and sufficient, respectively. Multivariate modeling revealed that subjects with insufficient or sufficient vitamin D levels were at a lower risk of type 2 diabetes than were subjects with deficient vitamin D levels [odds ratio (OR), 0.82; 95% confidence interval (CI), 0.71-0.94 and OR, 0.51; 95% CI, 0.35-0.74, respectively]. Higher serum vitamin D levels were associated with a reduced risk of diabetes in Korean adults, suggesting that vitamin D may play a role in the pathogenesis of diabetes.

Association between Vitamin D Status and Risk of Peripheral Arterial Disease: The Dong-gu Study.

Low levels of vitamin D have been associated with increased cardiovascular disease risk. However, few studies have evaluated the association between vitamin D status and peripheral arterial disease (PAD). We therefore aimed to investigate whether low 25-hydroxyvitamin D (25(OH)D) levels were associated with increased risk of PAD in the Korean population. This cross-sectional study was conducted among 8,960 subjects aged 50 years or older without known myocardial infarction or stroke. PAD was defined by an ankle brachial blood pressure index <0.9. Multivariate logistic regression was used to evaluate the association between serum 25(OH)D levels and risk of PAD. Of the 8,960 subjects, 3.0% had PAD and the age and sex adjusted prevalence of PAD decreased with the increasing 25(OH)D quartile. After adjusting for potential confounders and parathyroid hormones, serum 25(OH)D levels were associated with a significantly decreased risk of PAD (OR for one SD increase, 0.98; 95% CI, 0.95-1.0, P for trend=0.040). Compared with the first 25(OH)D quartile, the odds of PAD were 0.86 (95% CI, 0.62-1.21), 0.67 (95% CI, 0.46-0.97), and 0.71 (95% CI, 0.49-1.04) for the second, third, and fourth quartiles, respectively. In this cross-sectional study, we found that low serum 25(OH)D levels were associated with an increased risk of PAD, independent of traditional cardiovascular risk factors and parathyroid hormone. Our findings suggest that low vitamin D levels may contribute to PAD in the Korean population.

Association of APOE Genotype with Bone Mineral Density in Men and Women: The Dong-gu and Namwon Studies.

Many studies have investigated relationships between APOE genotype and bone mineral density (BMD). However, the results of these studies have been inconsistent. Few studies have been carried out in Asian populations. We studied the relationship of the APOE gene polymorphism and BMD in two large population-based studies. The datasets included the Dong-gu Study (3575 men and 5335 women) and the Namwon Study (2310 men, 3512 women). Lumbar spine and femoral neck BMD were measured by dual-energy X-ray absorptiometry. APOE genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The APOE genotypes were classified into APOE E2 (E2/E2 and E2/E3), APOE E3 (E3/E3), and APOE E4 (E3/E4 and E4/E4). The genotype distribution of the study population was in Hardy-Weinberg equilibrium. There were no significant differences among APOE genotype groups in lumbar and femoral neck BMD in either cohort. Our data do not support the hypothesis that the APOE genotype is associated with BMD.