Glucocorticoid-Induced Hypokalemic Periodic Paralysis after Short-Term Use of Tenofovir with Hypophosphatemia: A Case Report.

Hypokalemic periodic paralysis (HPP) is a neuromuscular disorder associated with muscular dysfunction caused by hypokalemia. There are various causes of HPPs and rarely, HPP appears to be relevant to tenofovir or glucocorticoid treatment. There have been several case reports of tenofovir-related nephrotoxicity or tenofovir-induced HPP. However, a case report of glucocorticoid-induced HPP in a patient using tenofovir temporarily has not been reported. Herein, we report a case of glucocorticoid-induced HPP with short-term use of tenofovir. A 28-year-old man visited the emergency room with decreased muscle power in all extremities (2/5 grade). In their past medical history, the patient was treated with tenofovir for two months for a hepatitis B virus infection. At the time of the visit, the drug had been discontinued for four months. The day before visiting the emergency room, betamethasone was administered at a local clinic for herpes on the lips. Laboratory tests showed hypokalemia, hypophosphatemia, and mild metabolic acidosis. However, urinalysis revealed no abnormal findings. Consequently, it can be postulated that this patient developed HPP by glucocorticoids after taking tenofovir temporarily. This is the first case report of glucocorticoid-induced HPP in a patient using tenofovir. Clinicians who prescribe tenofovir should be aware of HPP occurring when glucocorticoids are used.

Dipeptide YA is Responsible for the Positive Effect of Oyster Hydrolysates on Alcohol Metabolism in Single Ethanol Binge Rodent Models.

Accumulative alcohol hangovers cause liver damage through oxidative and inflammatory stress. Numerous antioxidant and anti-inflammatory reagents have been developed to reduce alcohol hangovers, but these reagents are still insignificant and have limitations in that they can cause liver toxicity. Oyster hydrolysate (OH), another reagent that has antioxidant and anti-inflammatory activity, is a product extracted through an enzymatic hydrolysis process from oysters (Crassostrea gigas), which can be easily eaten in meals. This study was aimed at determining the effects of OH on alcohol metabolism, using a single high dose of ethanol (EtOH) administered to rodents, by monitoring alcohol metabolic enzymes, oxidative stress signals, and inflammatory mediators. The effect of tyrosine-alanine (YA) peptide, a main component of OH, on EtOH metabolism was also identified. In vitro experiments showed that OH pretreatment inhibited EtOH-induced cell death, oxidative stress, and inflammation in liver cells and macrophages. In vivo experiments showed that OH and YA pre-administration increased alcohol dehydrogenase, aldehyde dehydrogenase, and catalase activity in EtOH binge treatment. In addition, OH pre-administration alleviated CYP2E1 activity, ROS production, apoptotic signals, and inflammatory mediators in liver tissues. These results showed that OH and YA enhanced EtOH metabolism and had a protective effect against acute alcohol liver damage. Our findings offer new insights into a single high dose of EtOH drinking and suggest that OH and YA could be used as potential marine functional foods to prevent acute alcohol-induced liver damage.

Psychological Development during Medical School Clerkship: Relationship to Resilience.

OBJECTIVE: The authors investigated changes in medical students' defenses during clerkship and examined the effects of these changes on students' resilience. METHODS: Between 2012 and 2014, all year-2 preclinical students (N = 249) at Gyeongsang National University Medical School were asked to participate. Those who agreed to participate (N = 237) completed the Korean version of the Defense Style Questionnaire (K-DSQ) and the Connor-Davidson resilience scale-10 (CD-RISC-10). After clerkship, students who proceeded to year 4 in 2 years (n = 187 (93 females), aged 24-38 years (mean, 28.9 ± 2.8 years)) completed the K-DSQ, CD-RISC-10, and the Korean version of the Hospital Anxiety and Depression Scale (K-HADS) in September 2014, 2015, and 2016. RESULTS: The use of adaptive (W = 11,603.5, p < 0.001, r = 0.39) and self-inhibiting (W = 10,901.5, p < 0.001, r = 0.32) styles increased significantly after clerkship. A multiple linear regression analysis showed that changes in adaptive defense styles (B = 1.336, SE = 0.386, ß = 0.218, p = 0.001) during clerkship were significantly related to resilience after adjusting for age, sex, depression, and anxiety. CONCLUSIONS: Both positive personality development and maladaptive changes in defenses were evident. An increase in the adaptive defense style score was related to resilience.

RKIP phosphorylation-dependent ERK1 activation stimulates adipogenic lipid accumulation in 3T3-L1 preadipocytes overexpressing LC3.

3T3-L1 preadipocytes undergo adipogenesis in response to treatment with dexamethaxone, 1-methyl-3-isobutylxanthine, and insulin (DMI) through activation of several adipogenic transcription factors. Many autophagy-related proteins are also highly activated in the earlier stages of adipogenesis, and the LC3 conjugation system is required for formation of lipid droplets. Here, we investigated the effect of overexpression of green fluorescent protein (GFP)-LC3 fusion protein on adipogenesis. Overexpression of GFP-LC3 in 3T3-L1 preadipocytes using poly-l-lysine-assisted adenoviral GFP-LC3 transduction was sufficient to produce intracellular lipid droplets. Indeed, GFP-LC3 overexpression stimulated expression of some adipogenic transcription factors (e.g., C/EBPα or ß, PPARγ, SREBP2). In particular, SREBP2 was highly activated in preadipocytes transfected with adenoviral GFP-LC3. Also, phosphorylation of Raf kinase inhibitory protein (RKIP) at serine 153, consequently stimulating extracellular-signal regulated kinase (ERK)1 activity, was significantly increased during adipogenesis induced by either poly-l-lysine-assisted adenoviral GFP-LC3 transduction or culture in the presence of dexamethasone, 1-methyl-3-isobutylxanthine, and insulin. Furthermore, RKIP knockdown promoted ERK1 and PPARγ activation, and significantly increased the intracellular accumulation of triacylglycerides in DMI-induced adipogenesis. In conclusion, GFP-LC3 overexpression in 3T3-L1 preadipocytes stimulates adipocyte differentiation via direct modulation of RKIP-dependent ERK1 activity.

Depletion of p18/LAMTOR1 promotes cell survival via activation of p27(kip1) -dependent autophagy under starvation.

The MAPK and mTOR signal pathways in endosomes or lysosomes play a crucial role in cell survival and death. They are also closely associated with autophagy, a catabolic process highly regulated under various cellular stress or nutrient deprivation. Recently we have isolated a protein, named p18/LAMTOR1, that specifically regulates the ERK or mTOR pathway in lysosomes. p18/LAMTOR1 also interacts with p27(kip1) . Here we examined how p18/LAMTOR1 plays a role in autophagy under nutrient deprivation. The p18(+/+) MEF cells were more susceptible to cell death under starvation or in the presence of AICAR in comparison with p18(-/-) MEF cells. Cleavage of caspase-3 was increased in p18(+/+) MEF cells under starvation, and phosphorylation at the threonine 198 of p27(kip1) was highly elevated in starved p18(-/-) MEF cells. Furthermore, LC3-II formation and other autophagy-associated proteins were largely increased in p18-deficient cells, and suppression of p27(kip1) expression in p18(-/-) MEF cells mitigated starvation-induced cell death. These data suggest that ablation of p18/LAMTOR1 suppresses starvation-induced cell death by stimulating autophagy through modulation of p27(kip1) activity.

Attenuation by a Vigna nakashimae extract of nonalcoholic fatty liver disease in high-fat diet-fed mice.

A Vigna nakashimae (VN) extract has been shown to have antidiabetic and anti-obesity effects. However, the mechanism underlying the effect of a VN extract on hepatic inflammation and endoplasmic reticulum (ER) stress remains unclear. In the present study, we investigated how a VN extract protects against the development of non-alcoholic fatty liver disease (NAFLD). A VN extract for 12 weeks reduced the body weight, serum metabolic parameters, cytokines, and hepatic steatosis in high-fat diet (HFD)-fed mice. A VN extract decreased HFD-induced hepatic acetyl CoA carboxylase and glucose transporter 4 expressions. In addition to the levels of high-mobility group box 1 and receptor for advanced glycation, the hepatic expression of ATF4 and caspase-3 was also reduced by a VN extract. Thus, these data indicate that a chronic VN extract prevented NAFLD through multiple mechanisms, including inflammation, ER stress, and apoptosis in the liver.

Acute pancreatitis induced by methimazole treatment in a 51-year-old korean man: a case report.

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.

Exendin-4 Improves Nonalcoholic Fatty Liver Disease by Regulating Glucose Transporter 4 Expression in ob/ob Mice.

Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been known to reverse hepatic steatosis in ob/ob mice. Although many studies have evaluated molecular targets of Ex-4, its mechanism of action on hepatic steatosis and fibrosis has not fully been determined. In the liver, glucose transporter 4 (GLUT4) is mainly expressed in hepatocytes, endothelial cells and hepatic stellate cells (HSCs). In the present study, the effects of Ex-4 on GLUT4 expression were determined in the liver of ob/ob mice. Ob/ob mice were treated with Ex-4 for 10 weeks. Serum metabolic parameters, hepatic triglyceride levels, and liver tissues were evaluated for hepatic steatosis. The weights of the whole body and liver in ob/ob mice were reduced by long-term Ex-4 treatment. Serum metabolic parameters, hepatic steatosis, and hepatic fibrosis in ob/ob mice were reduced by Ex-4. Particularly, Ex-4 improved hepatic steatosis by enhancing GLUT4 via GLP-1R activation in ob/ob mice. Ex-4 treatment also inhibited hepatic fibrosis by decreasing expression of connective tissue growth factor in HSCs of ob/ob mice. Our data suggest that GLP-1 agonists exert a protective effect on hepatic steatosis and fibrosis in obesity and type 2 diabetes.

The Efficacy of Treatment Intensification by Quadruple Oral Therapy Compared to GLP-1RA Therapy in Poorly Controlled Type 2 Diabetes Mellitus Patients: A Real-world Data Study.

We compared the glycemic efficacy of treatment intensification between quadruple oral antidiabetic drug therapy and once-weekly glucagon-like peptide-1 receptor agonist (GLP-1RA)-based triple therapy in patients with poorly controlled type 2 diabetes mellitus refractory to triple oral therapy. For 24 weeks, changes in glycosylated hemoglobin (HbA1c) from baseline were compared between the two treatment groups. Of all 96 patients, 50 patients were treated with quadruple therapy, and 46 were treated with GLP-1RA therapy. Reductions in HbA1c for 24 weeks were comparable (in both, 1.1% reduction from baseline; P=0.59). Meanwhile, lower C-peptide level was associated with a lower glucose-lowering response of GLP-1RA therapy (R=0.3, P=0.04) but not with quadruple therapy (R=-0.13, P=0.40). HbA1c reduction by GLP-1RA therapy was inferior to that by quadruple therapy in the low C-peptide subgroup (mean, -0.1% vs. -1.3%; P=0.04). Treatment intensification by switching to quadruple oral therapy showed similar glucose-lowering efficacy to weekly GLP-1RA-based triple therapy. Meanwhile, the therapeutic response was affected by C-peptide levels in the GLP-1RA therapy group but not in the quadruple therapy group.

Dyslipidemia Is a Risk Factor for Hypothyroidism in Women: A Longitudinal Cohort Study from South Korea.

Background: Hypothyroidism is a risk factor for dyslipidemia. We explored whether dyslipidemia is a risk factor for hypothyroidism. Methods: We performed a retrospective analysis of data from a longitudinal cohort study of South Korean adults who underwent medical examination and ≥4 biochemical assessments of thyroid function. The primary outcome was hypothyroidism (thyrotropin [TSH] >4.2 mU/L), and the secondary outcome was severe subclinical hypothyroidism (SCH; TSH ≥10.0 mU/L and normal free thyroxine [fT4] level) or overt hypothyroidism (OH; total triiodothyronine <80 ng/dL and/or fT4 < 0.93 ng/dL and high TSH values). The association of baseline dyslipidemia status with subsequent hypothyroidism was evaluated using Kaplan-Meier curves with the log-rank test and Cox proportional hazards regression models (for the entire population and respective genders). Subgroup analyses according to age (<40 and ≥40 years) and body-mass index (BMI; <23, 23-25, and ≥25 kg/m2) were performed according to gender. Results: We included 1665 participants. During a median follow-up period of 61.0 months, 24.3% (404/1665) individuals developed hypothyroidism. Among these, 36 participants (2.1%) had severe SCH or OH. Excluding patients with a first abnormal TSH level at last follow-up, 44.5% (126/283) of the patients with hypothyroidism had spontaneous TSH normalization. In respective multivariate analyses, dyslipidemia at baseline was independently associated with development of hypothyroidism in women (adjusted hazard ratio [HR] = 2.05 [1.31-3.19], p = 0.002), but not in men (adjusted HR = 1.00 [0.77-1.30], p = 0.991). In women, the presence of dyslipidemia at baseline was associated with development of severe SCH or OH (adjusted HR = 5.33 [1.41-20.12], p = 0.014). In women, respective associations according to age and BMI were as follows: age <40 years, adjusted HR = 2.90 (1.34-6.26, p = 0.007); age ≥40 years, adjusted HR = 1.85 (1.08-3.14, p = 0.023); BMI <23 kg/m2, adjusted HR = 1.68 (0.82-3.43, p = 0.151); BMI = 23-25 kg/m2, adjusted HR = 2.17 (0.93-5.07, p = 0.071); and BMI ≥25 kg/m2, adjusted HR = 2.82 (1.16-6.86, p = 0.022). Conclusions: In Korean adults, dyslipidemia was associated with development of hypothyroidism in women. Our findings require confirmation.

α-lipoic acid prevents non-alcoholic fatty liver disease in OLETF rats.

BACKGROUND: Insulin resistance, oxidative stress, inflammation and innate immune system activation contribute to the development of non-alcoholic fatty liver disease (NAFLD) through steatosis and inflammation in the liver. The powerful antioxidant α-lipoic acid (ALA) has been shown to improve insulin sensitivity and suppress inflammatory responses. This study explores how ALA administration protects against NAFLD. METHODS: Otsuka Long-Evans Tokushima Fatty (OLETF) rats were divided into two groups (treated with 200 mg/kg/day of ALA or untreated) at 12 weeks of age and sacrificed at 28 weeks of age. RESULTS: Serum levels of insulin, free fatty acids, total cholesterol, triglyceride, leptin, IL-6 and blood glucose were decreased in ALA-treated rats. Serum adiponectin levels were higher in ALA-treated rats. ALA treatment decreased the expression of sterol regulatory element binding protein-1 and acetyl CoA carboxylase, and increased glucose transporter-4 expression in the livers of OLETF rats. Expression of the antioxidant enzymes heme oxygenase-1 and Cu/Zn-superoxide dismutase was increased in the livers of ALA-treated rats. The lipid peroxidation marker 4-hydroxynonenal was decreased in the liver of ALA-treated rats. Proteins associated with innate immune activation (Toll-like receptor-4 and high-mobility group protein box-1) and inflammatory markers (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and cyclooxygenase-2) were decreased in the livers of ALA-treated rats. CONCLUSIONS: Chronic ALA supplementation prevents NAFLD through multiple mechanisms by reducing steatosis, oxidative stress, immune activation and inflammation in the liver.

Mitigation of H2O2-induced autophagic cell death by propofol in H9c2 cardiomyocytes.

Autophagy, a self-eating process, is responsible for degradation of long-lived proteins and damaged cellular proteins/organelles. Double-membrane autophagosomes, formed during the process, engulf proteins/organelles and fuse with lysosomes to degrade the contents. It is important to maintain cell homeostasis and many physiological processes including cellular responses to oxidative stress. Oxidative stress induced by myocardial infarction is a major factor of heart failures. In this study, we examined how propofol modulates hydrogen peroxide (H(2)O(2))-induced autophagic cell death in H9c2 cardiomyocytes. H(2)O(2) dramatically induced cell death, which was similarly reduced in the presence of either propofol or autophagy inhibitors (e.g., wortmannin), suggesting that propofol has a protective effect in H(2)O(2)-induced autophagic cell death. Acidic autophagic vacuoles were elevated in H(2)O(2)-treated H9c2 cells, but they were largely decreased in the presence of propofol. Furthermore, many autophagy-related proteins such as LC3-II, ATG proteins, p62, AMPK, and JNK were activated in H(2)O(2)-treated H9c2 cells and were significantly deactivated in the presence of propofol. These results show that propofol regulates oxidative stress-induced autophagic cell death in cardiomyocytes. We further suggest that propofol can act as a cardioprotectant in heart diseases.

Personality traits and emotional status affecting academic achievements of medical students: testifying mediating effect of learning strategies.

PURPOSE: The purpose of this study is to identify possible causal relationships among personality traits, emotional status, learning strategies, and academic achievements of medical students and to testify mediating effect of learning strategies in these relationships. METHODS: The study subjects are 424 medical students in the academic year of 2020 at the Gyeongsang National University, Jinju, Korea. Using the Multi-dimensional Learning Strategy Test-II, we assessed the students' academic achievements with personality traits, emotional status, and learning strategies. This study employed Structural Equation Modelling to explore the causal relationships among the latent variables. RESULTS: In the path model, personality traits directly affected academic achievements (ß=0.285, p<0.05) and indirectly affected academic achievements via emotional status (ß=0.063, p<0.01) and via learning strategies (ß=0.244, p<0.05), respectively. Further, personality traits indirectly affected academic achievements via emotional status first and learning strategies next (ß=0.019, p<0.05). Personality traits indirectly affected academic achievements through three multiple paths in the model (ß=0.326, p<0.05). Learning strategies partially mediated the relationship between personality traits and academic achievements as well as the relationship between emotional status and academic achievements of medical students. CONCLUSION: Study findings proved constructing the causal relationships among personality traits, emotional status, learning strategies, and academic achievements of medical students, thus supporting our hypotheses. Early habits of self-regulated learning are essential for the successful academic achievements of medical students. Therefore, medical students should know how to regulate personality traits and control emotional status, significantly affecting learning strategies.

The impact of the COVID-19 pandemic on outpatients of internal medicine and pediatrics: A descriptive study.

ABSTRACT: This study analyzed the changes in the number of outpatients and disease presentation during the entirety of 2020, the period of COVID-19 pandemic.The average annual number of outpatient visits between 2017 and 2019 (before COVID-19) and the total number of outpatient visits in 2020 (COVID-19 period) were compared. Diagnostic codes were identified during 2 periods to analyze changes in the number of outpatient visits according to disease and month.The average annual number of outpatient visits was 47,105 before, and 40,786 during the COVID-19 pandemic, with a decrease of 13.4%. The number of outpatient visits in internal medicine decreased by 10.2% during the COVID-19 pandemic and tended to rebound during the second half of the year. However, the number of outpatient visits in the pediatric department decreased by 37.5% overall throughout the COVID-19 period and continued to decline in the second half of the year. The number of outpatients with infectious diseases decreased significantly (35.9%) compared to noninfectious diseases (cancer, 5.0%; circulatory disease, 4.1%). In addition, the number of outpatient visits due to viral diseases continued to decline, while the incidence of bacterial diseases increased rapidly in the second half of the year.This study confirmed that the number of outpatient visits due to bacterial or viral infections decreased throughout the COVID-19 crisis. Therefore, expanding public health and telemedicine services is necessary to prevent secondary health problems caused by essential medical use restrictions.

Neuroprotective Effects of Nicotinamide against MPTP-Induced Parkinson's Disease in Mice: Impact on Oxidative Stress, Neuroinflammation, Nrf2/HO-1 and TLR4 Signaling Pathways.

Nicotinamide (NAM) is the amide form of niacin and an important precursor of nicotinamide adenine dinucleotide (NAD), which is needed for energy metabolism and cellular functions. Additionally, it has shown neuroprotective properties in several neurodegenerative diseases. Herein, we sought to investigate the potential protective mechanisms of NAM in an intraperitoneal (i.p) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model (wild-type mice (C57BL/6N), eight weeks old, average body weight 25-30 g). The study had four groups (n = 10 per group): control, MPTP (30 mg/kg i.p. for 5 days), MPTP treated with NAM (500 mg/kg, i.p for 10 days) and control treated with NAM. Our study showed that MPTP increased the expression of α-synuclein 2.5-fold, decreased tyrosine hydroxylase (TH) 0.5-fold and dopamine transporters (DAT) levels up to 0.5-fold in the striatum and substantia nigra pars compacta (SNpc), and impaired motor function. However, NAM treatment significantly reversed these PD-like pathologies. Furthermore, NAM treatment reduced oxidative stress by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) between 0.5- and 1.0-fold. Lastly, NAM treatment regulated neuroinflammation by reducing Toll-like receptor 4 (TLR-4), phosphorylated nuclear factor-κB, tumor (p-NFκB), and cyclooxygenase-2 (COX-2) levels by 0.5- to 2-fold in the PD mouse brain. Overall, these findings suggest that NAM exhibits neuroprotective properties and may be an effective therapeutic agent for PD.

Oyster broth concentrate and its major component taurine alleviate acute alcohol-induced liver damage.

Our previous study showed that oyster hydrolysate (OH) protected against the liver damage caused by a single instance of ethanol (EtOH) binge drinking. Oyster broth concentrate (OBC) was discovered in the process of searching for a different substance derived from oysters (Crassostrea gigas) with economic value. OBC is a by-product of boiling oysters at 95°C for 3 min. In this study, we investigated the effects of OBC and its major component taurine on blood and liver tissues obtained from a single-EtOH-binge-drinking mouse model. The preadministration of OBC enhanced EtOH metabolism by increasing the activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and catalase. In addition, the preadministration of OBC reduced cytochrome P450 2E1 (CYP2E1) activity, reactive oxygen species (ROS) generation, Ca2+ concentrations, apoptotic signals, and inflammatory mediators in liver tissues. The reduction of apoptotic and inflammatory signals by OBC resulted from the downregulation of endoplasmic reticulum (ER) stress molecules and NF-κB activity. Taurine administration showed similar effects to OBC. These results show that OBC protected against acute EtOH-induced liver damage through the action of taurine. Our findings suggest that OBC could be an economically valuable substance and a functional food with hepatoprotective effects.

Antioxidant and Anti-Inflammatory Effects of Citrus Flavonoid Hesperetin: Special Focus on Neurological Disorders.

Neurodegenerative disorders have emerged as a serious health issue in the current era. The most common neurodegenerative disorders are Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). These diseases involve progressive impairment of neurodegeneration and memory impairment. A wide range of compounds have been identified as potential neuroprotective agents against different models of neurodegeneration both in vivo and in vitro. Hesperetin, a flavanone class of citrus flavonoid, is a derivative of hesperidin found in citrus fruits such as oranges, grapes, and lemons. It has been extensively reported that hesperetin exerts neuroprotective effects in experimental models of neurodegenerative diseases. In this systematic review, we have compiled all the studies conducted on hesperetin in both in vivo and in vitro models of neurodegeneration. Here, we have used an approach to lessen the bias in each study, providing a least biased, broad understanding of findings and impartial conclusions of the strength of evidence and the reliability of findings. In this review, we collected different papers from a wide range of journals describing the beneficial effects of hesperetin on animal models of neurodegeneration. Our results demonstrated consistent neuroprotective effects of hesperetin against different models of neurodegeneration. In addition, we have summarized its underlying mechanisms. This study provides the foundations for future studies and recommendations of further mechanistic approaches to conduct preclinical studies on hesperetin in different models.

Metabolic Stress Alters Antioxidant Systems, Suppresses the Adiponectin Receptor 1 and Induces Alzheimer's Like Pathology in Mice Brain.

Oxidative stress and insulin resistance play major roles in numerous neurodegenerative diseases, including Alzheimer's disease (AD). A high-fat diet induces obesity-associated oxidative stress, neuronal insulin resistance, microglial activation, and neuroinflammation, which are considered important risk factors for neurodegeneration. Obesity-related metabolic dysfunction is a risk factor for cognitive decline. The present study aimed to elucidate whether chronic consumption of a high-fat diet (HFD; 24 weeks) can induce insulin resistance, neuroinflammation, and amyloid beta (Aß) deposition in mouse brains. Male C57BL/6N mice were used for a high-fat diet (HFD)-induced pre-clinical model of obesity. The protein expression levels were examined via Western blot, immunofluorescence, and the behavior analysis was performed using the Morris water maze test. To obtain metabolic parameters, insulin sensitivity and glucose tolerance tests were performed. We found that metabolic perturbations from the chronic consumption of HFD elevated neuronal oxidative stress and insulin resistance through adiponectin receptor (AdipoR1) suppression in HFD-fed mice. Similarly, our in vitro results also indicated that knockdown of AdipoR1 in the embryonic mouse hippocampal cell line mHippoE-14 leads to increased oxidative stress in neurons. In addition, HFD markedly increased neuroinflammatory markers' glial activation in the cortex and hippocampus regions of HFD mouse brains. More importantly, we observed that AdipoR1 suppression increased the amyloidogenic pathway both in vivo and in vitro. Furthermore, deregulated synaptic proteins and behavioral deficits were observed in the HFD mouse brains. Taken together, our findings suggest that excessive consumption of an HFD has a profound impact on brain function, which involves the acceleration of cognitive impairment due to increased obesity-associated oxidative stress, insulin resistance, and neuroinflammation, which ultimately may cause early onset of Alzheimer's pathology via the suppression of AdipoR1 signaling in the brain.

Predictive Performance of Glycated Hemoglobin for Incident Diabetes Compared with Glucose Tolerance Test According to Central Obesity.

BACKGROUND: To examine whether glycated hemoglobin (HbA1c) test would be a suitable screening tool for detecting high-risk subjects for diabetes compared to oral glucose tolerance test (OGTT) according to accompanied central obesity. METHODS: In this prospective population-based cohort study, both OGTT and HbA1c tests were performed and continued every 2 years up to 12 years among individuals with non-diabetic state at baseline (aged 40 to 69 years, n=7,512). Incident diabetes was established by a doctor, HbA1c ≥6.5%, and/or fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-hour postprandial glucose (2hPG) level based on OGTT ≥200 mg/dL. Discriminative capacities of high HbA1c (≥5.7%) versus high 2hPG (≥140 mg/dL) for predicting incident diabetes were compared using Cox-proportional hazard regression and C-index. RESULTS: During the median 11.5 years of follow-up period, 1,341 (17.6%) developed diabetes corresponding to an incidence of 22.1 per 1,000 person-years. Isolated high 2hPG was associated with higher risk for incident diabetes (hazard ratio [HR], 4.29; 95% confidence interval [CI], 3.56 to 5.17) than isolated high HbA1c (HR, 2.79; 95% CI, 2.40 to 3.26; P<0.05). In addition, high 2hPG provided better discriminatory capacity than high HbA1c (C-index 0.79 vs. 0.75, P<0.05). Meanwhile, in subjects with central obesity, the HR (3.95 [95% CI, 3.01 to 5.18] vs. 2.82 [95% CI, 2.30 to 3.46]) and discriminatory capacity of incident diabetes (C-index 0.75 vs. 0.75) between two subgroups became comparable. CONCLUSION: Even though the overall inferior predictive capacity of HbA1c test than OGTT, HbA1c test might plays a complementary role in identifying high risk for diabetes especially in subjects with central obesity with increased sensitivity.

Hypoglycemic efficacy and safety of Momordica charantia (bitter melon) in patients with type 2 diabetes mellitus.

INTRODUCTION: Momordica charantia (bitter melon) is widely used for its glucose-lowering effects. This study was conducted to assess the efficacy and safety of M. charantia as an adjuvant treatment in patients with type 2 diabetes. METHODS: We performed a randomized, placebo-controlled study. Blood glucose levels, lipid profile, and adverse events were investigated after 12 weeks of treatment. Ninety subjects were included in the final analysis for glucose lowering efficacy of bitter melon. RESULTS: There were no differences in age, sex, or glycated hemoglobin (HbA1c) levels between the bitter melon extract and placebo groups. After treatment with bitter melon extract for 12 weeks, the HbA1c levels of the bitter melon and placebo groups remained unchanged; however, the average fasting glucose level of the bitter melon group decreased (p = 0.014). No serious adverse events were reported during the treatment period. CONCLUSIONS: Our data showed that bitter melon has effects of glucose lowering in patients with type 2 diabetes.