Association between gastrectomy and the risk of type 2 diabetes in gastric cancer survivors: a nationwide cohort study.

AIM: Postprandial glycemic fluctuations after gastrectomy are seen in patients with gastric cancer but, no studies have investigated the association between gastrectomy and type 2 diabetes mellitus (T2DM) in gastric cancer survivors. This study aimed to elucidate the relationship between gastrectomy (total or subtotal) and incident T2DM. In addition, we explored whether vitamin B12 supplementation modulates this risk among patients who have undergone total gastrectomy. METHODS: In this large nationwide population-based retrospective cohort study using the National Health Insurance Service database of South Korea, we identified patients aged >20 years who underwent gastrectomy from 2008 to 2015 (n=150,074) and age- and sex-matched controls without gastrectomy (n=301,508). A Cox proportional hazards model was used. RESULTS: During the median follow-up duration of 4.4 years after the 2-year time lag after gastrectomy, of the 78,006 subjects, 4,597 (5.9%) developed T2DM. Compared with matched controls, the adjusted hazard ratio (AHR[95% confidence interval]) for T2DM of patients with total gastrectomy was 1.34[1.23;1.47]. The corresponding AHR after subtotal gastrectomy was 0.81[0.76;0.86]. Among the patients with total gastrectomy, the risk of T2DM was significantly increased in those who did not receive any vitamin B12 supplementation (AHR=1.60[1.33;1.92]), whereas the risk of T2DM was lower (close to being statistically significant) in those who received continuous vitamin B12 supplementation after gastrectomy (AHR=0.70[0.49;1.01]). CONCLUSION: These results show a significantly reduced risk of T2DM in gastric cancer patients undergoing subtotal gastrectomy and a significantly increased risk of T2DM in gastric cancer patients undergoing total gastrectomy, which is mitigated by continuous vitamin B12 supplementation.

Glycaemic Status and Risk of Abdominal Aortic Aneurysm: A Nationwide Cohort Study of Four Million Adults using Korean National Health Screening Data.

OBJECTIVE: This retrospective cohort study aimed to confirm the previously reported inverse association between diabetes mellitus (DM) and abdominal aortic aneurysm (AAA) using large population based data. It also investigated the associations between AAA and impaired fasting glucose (IFG) and new onset DM (not yet treated). METHODS: A representative dataset was obtained from the Korean National Health Insurance Service. Participants who were aged ≥ 50 years and received a national health examination in 2009 were included and followed until 31 December 2019. Glycaemic status was defined based on fasting plasma glucose level and the relevant diagnostic codes. AAA was ascertained using medical facility use records with relevant diagnostic codes or aneurysm repair surgery. A Cox proportional hazards model was used to examine the association between glycaemic status and AAA, with adjustment for confounders. Additionally, the interactions between glycaemic status and subgroups based on baseline characteristics were examined. RESULTS: The study population comprised 4 162 640 participants. Participants with IFG or DM were significantly more likely to be male, older, and have comorbidities compared with normoglycaemic participants at baseline. The incidence of AAA was lower in participants with IFG or DM compared with normoglycaemic participants. The AAA risk was lower in patients with DM than in patients with IFG, and decreased linearly according to glycaemic status: the adjusted hazard ratio was 0.88 (95% confidence interval [CI] 0.85 - 0.91) for IFG, 0.72 (95% CI 0.67 - 0.78) for newly diagnosed DM, 0.65 (95% CI 0.61 - 0.69) for DM duration < 5 years, and 0.47 (95% CI 0.44 - 0.51) for DM duration ≥ 5 years compared with the normoglycaemia group. Both IFG and DM were related to reduced AAA risk in all subgroups, suggesting an independent association. CONCLUSION: Both IFG and DM, even when not treated with antihyperglycaemic medication, were associated with a lower incidence of AAA. The AAA risk decreased linearly according to DM duration.

Metabolic dysfunction-associated fatty liver disease and heavy alcohol consumption increase mortality:A nationwide study.

BACKGROUND: The effects of excessive alcohol consumption on the prognosis of metabolic dysfunction-associated fatty liver disease (MAFLD) remain unclear. We investigated all-cause and cause-specific mortality according to the amount of alcohol consumed by Asian individuals with MAFLD. METHODS: This nationwide retrospective study included 996,508 adults aged 40-79 years who underwent health check-ups between 2009 and 2012. Participants were categorized by the alcohol consumption-non-alcohol, moderate alcohol, and heavy alcohol group (≥ 30 g/day for men, ≥ 20 g/day for women) and by the combination of the presence or absence of MAFLD. Hepatic steatosis was defined as the fatty liver index ≥ 30. Cox analyses were used to analyze the association between alcohol consumption and MAFLD and all-cause and cause-specific mortality. RESULTS: MAFLD significantly increased all-cause, liver-, and cancer-related mortality. Individuals with both MAFLD and heavy alcohol consumption expressed the highest mortality risk in liver-related mortality compared to non-MAFLD and non-alcohol group (adjusted hazard ratio (HR), 9.8; 95% confidence interval (CI), 8.20-12.29). Regardless of MAFLD, heavy alcohol consumption increased the risk of liver- and cancer-related mortality. CONCLUSIONS: MAFLD and heavy alcohol consumption increased all-cause, liver-, and cancer-related mortality. Heavy alcohol consumption and MAFLD synergistically increase liver-related mortality.

Clinical Characteristics, Diagnosis, and Treatment of Thyroid Stimulating Hormone-Secreting Pituitary Neuroendocrine Tumor (TSH PitNET): A Single-Center Experience.

BACKGRUOUND: Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity. METHODS: A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared. RESULTS: Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered. CONCLUSION: The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.

Association between total cholesterol levels and all-cause mortality among newly diagnosed patients with cancer.

We aimed to determine the association between cholesterol values and the risk of all-cause mortality in newly diagnosed patients with cancer in a large-scale longitudinal cohort. Newly diagnosed patients with cancer were reviewed retrospectively. Cox proportional hazards regression models determined the association between baseline levels of total cholesterol (TC), triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol and the risk of all-cause mortality. A restricted cubic spline curve was used to identify the association between total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol with the risk of death on a continuous scale and to present the lowest values of lipid measurements associated with death. The median follow-up duration of the study was 5.77 years. Of the 59,217 patients with cancer, 12,624 patients were expired. The multivariable adjusted hazard ratio (aHR) for all-cause mortality in patients with cancer with 1st-5th (≤ 97 mg/dL) and 96th-100th (> 233 mg/dL) in TC levels was 1.54 (95% CI 1.43-1.66) and 1.28 (95% CI 1.16-1.41), respectively, compared to 61st-80th (172-196 mg/dL). The TC level associated with the lowest mortality risk in the multivariable model was 181 mg/dL. In comparison with LDL-C levels in the 61st-80th (115-136 mg/dL), the multivariable aHR for all-cause mortality in cancer patients with LDL-C levels in the 1st-5th (≤ 57 mg/dL) and 96th-100th (> 167 mg/dL) was 1.38 (95% CI 1.14-1.68) and 0.94 (95% CI 0.69-1.28), respectively. The 142 mg/dL of LDL cholesterol showed the lowest mortality risk. We demonstrated a U-shaped relationship between TC levels at baseline and risk of mortality in newly diagnosed patients with cancer. Low LDL levels corresponded to an increased risk of all-cause death.

Protective effects of metformin in the pro-inflammatory cytokine induced intestinal organoids injury model.

Pathogenesis of inflammatory bowel disease (IBD) accompanies disrupted intestinal tight junctions. However, many approaches of therapeutics for IBD are focused only on anti-inflammatory effects and most cellular experiments are based on two-dimensional cell lines which have insufficient circumstances of intestine. Thus, here, we used three-dimensional structure intestinal organoids to investigate effects of metformin in the in vitro IBD condition. In this study, we focused on both tight junctions and the levels of inflammatory cytokines. Metformin enhances the intestinal barrier in injured intestine via upregulation of AMP-activated protein kinase, dysfunction of which contributes to the pathogenesis of intestinal diseases. We aim to investigate the effects of metformin on cytokine-induced injured intestinal organoids. Tumor necrosis factor-alpha (TNF-α) was used to induce intestinal injury in an organoid model, and the effects of metformin were assessed. Cell viability and levels of inflammatory cytokines were quantified in addition to tight junction markers. Furthermore, 4 kDa FITC-dextran was used to assess intestinal permeability. The upregulation of inflammatory cytokine levels was alleviated by metformin, which also restored the intestinal epithelium permeability in TNF-α-treated injury organoids. We confirmed that claudin-2 and claudin-7, representative tight junction markers, were also protected by metformin treatment. This study confirms the protective effects of metformin, which could be used as a therapeutic strategy for inflammatory intestinal diseases.

Association between lipid variability and the risk of mortality in cancer patients not receiving lipid-lowering agents.

Aim: We investigated the association between total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride (TG) variability and cancer patient mortality risk. Methods: We retrospectively analyzed 42,539 cancer patients who were not receiving lipid-lowering agents and who had at least three TC measurements within 2 years of their initial cancer diagnosis. Using a multivariable Cox regression model, the risk of mortality was evaluated. Results: In multivariable analysis, Q2 (adjusted hazard ratio [aHR]: 1.32, 95% confidence interval (CI): 1.24-1.41), Q3 (aHR: 1.66, 95% CI: 1.56-1.76), and Q4 (aHR: 1.96, 95% CI: 1.84-2.08) of coefficient of variation (CV) in TC were significantly associated with mortality risk compared to Q1, showing a linear association between higher TC variability and mortality (P for trend<0.001). Q2 (aHR: 1.34, 95% CI: 1.06-1.77), Q3 (aHR: 1.40, 95% CI: 1.06-1.85), and Q4 (aHR: 1.50, 95% CI: 1.14-1.97) were all significantly associated with a higher risk of death compared to Q1 in multivariable Cox regression for the association between CV in LDL and all-cause mortality (P for trend=0.005). Conclusion: In cancer patients who do not receive lipid-lowering agents, high variability in total cholesterol and LDL cholesterol levels was found to pose significant role in mortality risk.

Anti-cancer effects of metformin in a 3D co-culture model of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) presents with condensed stroma that contributes to its high invasive capability. Although metformin adjuvant treatment has been suggested to improve the survival times of patients with PDAC, the mechanism responsible for that benefit has been investigated only in two-dimensional cell lines. We assessed the anti-cancer effect of metformin in a three-dimensional (3D) co-culture model to quantify the migration behavior of patient-derived PDAC organoids and primary pancreatic stellate cells (PSCs). At a concentration of 10 µM, metformin reduced the migratory ability of the PSCs by downregulating the expression of matrix metalloproteinase-2 (MMP2). In the 3D direct co-cultivation of PDAC organoids and PSCs, metformin attenuated the transcription of cancer stemness-related genes. The reduced stromal migratory ability of PSCs was associated with the downregulation of MMP2, and MMP2 knockdown in PSCs reproduced their attenuated migratory ability. The anti-migration effect of a clinically relevant concentration of metformin was demonstrable in a 3D indirect co-culture model of PDAC consisting of patient-derived PDAC organoids and primary human PSCs. The metformin suppressed PSC migration via MMP2 downregulation and attenuated cancer stemness factors. Furthermore, oral administration of metformin (30 mg/kg) strikingly suppressed the growth of PDAC organoids xenograft in immunosuppressed mice. These results indicate metformin could offer the potential approach as an effective therapeutic drug for PDAC.

Extracellular Vesicles Derived from Three-Dimensional-Cultured Human Umbilical Cord Blood Mesenchymal Stem Cells Prevent Inflammation and Dedifferentiation in Pancreatic Islets.

It is unclear whether extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) have a direct protective effect on pancreatic islets. In addition, whether culturing MSCs in three dimensions (3D) instead of a monolayer (2D) can induce changes in the cargo of EVs that facilitate the polarization of macrophages into an M2 phenotype has not been investigated. We sought to determine whether EVs from MSCs cultured in 3D can prevent inflammation and dedifferentiation in pancreatic islets and, if so, whether the protective effect is superior to that of EVs from 2D MSCs. Human umbilical cord blood- (hUCB-) MSCs cultured in 3D were optimized according to cell density, exposure to hypoxia, and cytokine treatment based on the ability of the hUCB-MSC-derived EVs to induce the M2 polarization of macrophages. Islets isolated from human islet amyloid polypeptide (hIAPP) heterozygote transgenic mice were cultured in serum-deprived conditions with hUCB-MSC-derived EVs. EVs derived from 3D hUCB-MSCs had more abundant microRNAs involved in M2 polarization of macrophages and had an enhanced M2 polarization ability on macrophages, which was optimized when the 3D culture condition was 2.5 × 104 cells per spheroid without preconditioning with hypoxia and cytokine exposure. When islets isolated from hIAPP heterozygote transgenic mice were cultured in serum-deprived conditions with hUCB-MSC-derived EVs, the EVs derived from 3D hUCB-MSCs suppressed the expression of proinflammatory cytokines and caspase-1 in pancreatic islets and increased the proportion of M2-polarized islet-resident macrophages. They improved glucose-stimulated insulin secretion, reduced the expression of Oct4 and NGN3, and induced the expression of Pdx1 and FoxO1. The greater suppression of IL-1ß, NLRP3 inflammasome, caspase-1, and Oct4 and induction of Pdx1 and FoxO1 were found in islets cultured with the EVs derived from 3D hUCB-MSCs. In conclusion, EVs derived from 3D hUCB-MSCs optimized for M2 polarization attenuated nonspecific inflammation and preserved ß-cell identity of pancreatic islets.

Fatty Liver and Risk of Head and Neck Cancer in Type 2 Diabetes Mellitus: A Nationwide Cohort Study.

This study is aimed at investigating the association between NAFLD and the risk of HNC separately based on cancer site using a large population-based cohort of patients with T2DM. The data used in this population-based retrospective cohort study were provided by the Korean National Health Insurance Service. The Cox proportional hazards model was used to estimate multivariable adjusted hazard ratios and 95% CIs for the association of the fatty liver index (FLI) and the risk of HNC. During the mean 6.9 years of follow-up, approximately 25.4% of the study cohort had NAFLD, defined as an FLI ≥60. A total of 3543 HNC cases were identified. Overall, patients with a higher FLI had a significantly higher risk of HNC in the oral cavity, pharynx, and larynx compared with patients with an FLI <30. An association was not observed between salivary gland cancer and FLI. There was no association between obesity and HNC. However, obese patients showed a lower risk of cancer for the oral cavity (p = 0.040), pharynx (p = 0.009), and larynx (p < 0.001) than non-obese patients with the same FLI level. Neither obesity nor smoking affected the association between FLI- and HNC-risk in stratified analyses. In T2DM patients, NAFLD was associated with an increased risk of developing HNC in the oral cavity, pharynx, and larynx, but not in the salivary gland.

Association between Cholesterol Level and the Risk of Hematologic Malignancy According to Menopausal Status: A Korean Nationwide Cohort Study.

Recent studies have revealed the possible association between serum cholesterol levels and hematologic malignancy (HM). However, limited information is available about how reproductive factors interact with this association. Therefore, we investigated the roles of serum cholesterol in the risk of HM according to the menopausal status. We finally identified 1,189,806 premenopausal and 1,621,604 postmenopausal women who underwent a national health screening program in 2009 using data from the Korean National Health Insurance Service database. Overall, 5449 (0.19%) developed HM. Among postmenopausal women, the inverse associations were observed between total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) levels, and the risk of overall HM. In premenopausal women, the highest quartile of HDL-C was associated with a reduced risk of HM compared with the lowest quartile of HDL-C consistent with results in postmenopausal women (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] [0.68-0.95]), whereas the highest quartile of triglyceride (TG) showed an increased risk of HM compared to the lowest quartile of TG, (aHR 1.22, 95% CI [1.02,1.44]) only in premenopausal women. Our finding suggests that lipid profiles are differently associated with HM risk by menopausal status.

DAMP-modulating nanoparticle for successful pancreatic islet and stem cell transplantation.

Cell therapy is targeted at many organs, but locally or systemically delivered cells are shortly able to survive resulting from the immune/inflammation reactions and irregular cell targeting. Here we explore the multimodal nanoparticle having anti-inflammation and magnetic guidance for successful cell transplantation. We design magnetic resonance (MR)-active glycyrrhizin-chitosan coated superparamagnetic iron oxide nanoparticle (SPIO@Chitosan-GL) to inhibit release of inflammatory damage-associated molecular pattern (DAMP) protein and to offer noninvasive monitoring after intrahepatic transplantation of pancreatic islets and mesenchymal stem cell (MSC) spheroids. Intracellular delivered SPIO@Chitosan-GL is not cytotoxic to pancreatic islets and MSC spheroids and attenuate DAMP release from them. Also, therapeutic cells labeled with SPIO@Chitosan-GL are magnetically localized to the intended lobe of liver during transplantation procedure. If necessary, partial hepatectomy can be performed to remove the localized therapeutic cells for protection of the remaining liver lobes from systemic inflammation. Therapeutically, the cells selectively localized in the liver can treat blood glucose in diabetic mice to normal levels with DAMP modulation, and are visualized using in vivo MR imaging for over 4 weeks. Collectively, DAMP-modulating SPIO@Chitosan-GL can be used in multimodal nanomedince for attenuating the inflammation reaction by transplanted cells and for noninvasively long-term monitoring of transplanted cells.

Obesity-Independent Association between Glycemic Status and the Risk of Hematologic Malignancy: A Nationwide Population-Based Longitudinal Cohort Study.

There have been conflicting results regarding the association between diabetes and the risk of hematologic malignancies, and its interaction with obesity is unknown. This study determined the risk of hematologic malignancies according to the glycemic status in a population-based study involving health screening 9,774,625 participants. The baseline glycemic status of the participants was categorized into no diabetes, impaired fasting glucose (IFG), newly detected diabetes, diabetes duration <5 years, and diabetes duration ≥5 year groups. The risks of overall and specific hematologic malignancies were estimated using a Cox regression analysis. During a median follow up of 7.3 years, 14,733 hematologic malignancies developed. The adjusted hazard ratio (aHR) for the risk of all the hematologic malignancies was 0.99 (95% confidence interval (CI) 0.95-1.02) for IFG, 0.99 (95% CI 0.91-1.08) for newly detected diabetes, 1.03 (95% CI 0.96-1.11) for diabetes duration <5 years, and 1.11 (95% CI 1.03, 1.20) for diabetes duration ≥5 year groups. The association was independent from obesity. The risk of non-Hodgkin's lymphoma (NHL) increased according to the progression of dysglycemia towards a longer diabetes duration, while Hodgkin's lymphoma did not. This study in Korea demonstrated diabetes to be associated with an increased risk of hematologic malignancies independent of obesity. The NHL risk increased with the diabetes duration.

Early mortality and cardiovascular disease, varied association with body mass index and its changes in insulin-treated diabetes: a nationwide study.

BACKGROUND/OBJECTIVES: We investigated the hazards of cardiovascular diseases (CVDs) and all-cause death during follow-up according to baseline body mass index (BMI) and percent change in BMI among adults with insulin-treated diabetes. SUBJECTS/METHODS: Using the Korean National Health Insurance Service datasets (2002-2017), the hazards of myocardial infarction (MI), stroke, and all-cause mortality during follow-up were analyzed according to baseline BMI and percent change in BMI among adults with insulin-treated diabetes and without baseline CVD and/or malignancy (N = 44,055). RESULTS: At baseline, 67.3% of total subjects were either obese or overweight. During a mean 3.8 years, 1,081 MI and 1,562 stroke cases developed; 2,847 deaths occurred over a mean 3.9 years. Compared with normal weight, overweight and obesity were associated with lower hazards of outcomes [hazard ratio (95% CI): 0.836 (0.712-0.981), 0.794 (0.687-0.917) for MI; 0.829 (0.726-0.946), 0.772 (0.684-0.870) for stroke; 0.740 (0.672-0.816), 0.666 (0.609-0.728) for death, respectively]. Underweight was associated with a higher hazard of all-cause death during follow-up [hazard ratio (95% CI): 2.035 (1.695-2.443)]. When the group with minimum absolute value for percent change in BMI was set as a reference, the relative reduction in BMI was associated with increased hazards of MI, stroke, and all-cause death, and relative increase in BMI was associated with increased hazards of stroke and all-cause death during follow-up. CONCLUSIONS: Among adults with insulin-treated diabetes, a high prevalence of overweight and obesity was observed, and baseline BMI category was inversely associated with CVD incidence and all-cause death during follow-up. Both weight loss and gain were associated with increased CVD incidence and all-cause death during follow-up, showing a U-shaped relationship between weight change and outcome. Stable body weight might be a predictor of a lower risk of CVDs and premature death among individuals with insulin-treated diabetes.

Urinary Free Metanephrines for Diagnosis of Pheochromocytoma and Paraganglioma.

BACKGROUND: Pheochromocytoma and paraganglioma (PPGL) is diagnosed through biochemical confirmation of excessive catecholamines in urine and plasma. Recent technological developments have allowed us to measure urinary free metanephrines; however, the diagnostic accuracy of these new methods and the diagnostic cutoff values have not been evaluated. METHODS: This is a retrospective study of 595 subjects, including 71 PPGL cases and 524 controls. PPGL was based on pathological confirmation. Subjects with no evidence of PPGL over 2 years were included in the control group. RESULTS: Urinary free metanephrines yielded similar area under the curve (AUC) to urinary fractionated metanephrines and plasma free metanephrines. However, urinary free normetanephrine yielded a better AUC than did urinary fractionated normetanephrine. The optimal cutoff for urinary free metanephrine and normetanephrine corrected for urinary creatinine yielded 97.2% sensitivity and 98.1% specificity. CONCLUSION: Urinary free metanephrines are a reliable method for diagnosing PPGL in Asian populations compared with existing biochemical methods.

Protective effect of a novel clinical-grade small molecule necrosis inhibitor against oxidative stress and inflammation during islet transplantation.

Inhibition of mitochondrial reactive oxygen species (ROS) and subsequent damage-associated molecular patterns (DAMPs)-induced inflammatory responses could be a novel target in clinical islet transplantation. We investigated the protective effects of NecroX-7, a novel clinical-grade necrosis inhibitor that specifically targets mitochondrial ROS, against primary islet graft failure. Islets from heterozygote human islet amyloid polypeptide transgenic (hIAPP+/- ) mice and nonhuman primates (NHPs) were isolated or cultured with or without NecroX-7 in serum-deprived medium. Supplementation with NecroX-7 during hIAPP+/- mouse islet isolation markedly increased islet viability and adenosine triphosphate content, and attenuated ROS, transcription of c-Jun N-terminal kinases, high mobility group box 1, interleukin-1beta (IL-1 ß ), IL-6, and tumor necrosis factor-alpha. Supplementation of NecroX-7 during serum-deprived culture also protected hIAPP+/- mouse and NHP islets against impaired viability, serum deprivation-induced ROS, proinflammatory response, and accumulation of toxic IAPP oligomer. Supplementation with NecroX-7 during isolation or serum-deprived culture of hIAPP+/- mouse and NHP islets also improved posttransplant glycemia in the recipient streptozotocin-induced diabetic hIAPP-/- mice and BALB/c-nu/nu mice, respectively. In conclusion, pretransplant administration of NecroX-7 during islet isolation and serum-deprived culture suppressed mitochondrial ROS injury, generation of DAMPs-induced proinflammatory responses, and accumulation of toxic IAPP oligomers ex vivo, and improved posttransplant glycemia in vivo.

Risk of end-stage renal disease from chronic kidney disease defined by decreased glomerular filtration rate in type 1 diabetes: A comparison with type 2 diabetes and the effect of metabolic syndrome.

BACKGROUND: We estimated the end-stage renal disease (ESRD) risk of chronic kidney disease (CKD) in patients with type 1 diabetes (T1D). The ESRD risk of CKD in patients with T1D was compared with that of CKD in patients without diabetes and with type 2 diabetes (T2D). We also evaluated the predictive value of metabolic syndrome (MetS) for ESRD development in CKD patients with T1D. MATERIALS AND METHODS: The Korean National Health Insurance Service datasets of preventive health check-ups from 2009 to 2016 were used. The risk of incident ESRD was analysed according to the presence and type of diabetes in CKD (defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) patients aged 20 years or older. Incident ESRD risk according to the presence of MetS was calculated among adult patients with CKD and T1D. RESULTS: During 10 701 375.84 person-years of follow-up, 43 693 cases of ESRD developed. Hazard ratios (HRs) for incident ESRD from CKD in the T1D group were 2.580 (95% confidence interval [CI], 2.336-2.849) and 9.267 (95% CI, 8.378-10.251) compared with T2D and nondiabetes groups, respectively. In CKD patients with T1D, the presence of MetS increased incident ESRD risk by an HR of 2.023 (95% CI, 1.501-2.727). CONCLUSIONS: The presence of diabetes increases the risk for ESRD development from CKD. Furthermore, patients with T1D have a higher risk for ESRD incidence from CKD than do patients with T2D in a Korean population. MetS may be a useful predictor for ESRD in CKD patients with T1D.

The Protective Effects of Increasing Serum Uric Acid Level on Development of Metabolic Syndrome.

BACKGROUND: It 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. METHODS: In 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. RESULTS: After 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 <0.001) and 1.000 (0.843 to 1.186), 0.744 (0.615 to 0.900), and 0.684 (0.557 to 0.840) in female (P for trend <0.001), respectively. As a continuous variable in the fully-adjusted model, each one-standard deviation increase in percent change in SUA level was associated with an HR (95% CI) for incident MetS of 0.944 (0.906 to 0.982) in male (P=0.005) and 0.851 (0.801 to 0.905) in female (P<0.001). CONCLUSION: The current study demonstrated that increasing SUA level independently protected against the development of MetS, suggesting a possible role of SUA as an antioxidant in the pathogenesis of incident MetS.

Increased Risk of Osteoporosis in Gastric Cancer Survivors Compared to General Population Control: A Study with Representative Korean Population.

PURPOSE: Although several studies have suggested that osteoporosis is common in survivors of gastric cancer (GC), no study to date has directly assessed the risk for osteoporosis in GC survivors compared to matched controls. Thus, we aimed to investigate the relative risk for osteoporosis in survivors of GC compared to general population. MATERIALS AND METHODS: We used the Korea National Health and Nutrition Examination Survey data (2008-2011). Patients with a history of GC (n=94) were defined as case among 8,142 individuals over 50 years old who were evaluated by dual-energy X-ray absorptiometry. Controls (n=470) were matched to cases by age and sex in a 1:5 ratio. Osteopenia (-2.5 < T-score < -1.0) and osteoporosis (T-score ≤ -2.5) were defined. RESULTS: The prevalence of osteoporosis in GC survivors was 30.2%, which was significantly greater than that of controls (19.7%). In total, GC survivors had a 3.7-fold increased risk for osteoporosis compared to controls (p=0.021). In addition, the risk for osteoporosis of the total proximal femur total (TF) and femur neck (FN) was significantly increased among GC survivors compared to controls (adjusted relative risk, 4.64; 95% confidence interval, 1.16 to 18.6 in TF and adjusted relative risk, 3.58; 95% confidence interval, 1.19 to 10.8 in FN). Furthermore, we found sub-optimal daily calcium intake and mean serum levels of 25-hydroxy-vitamin D in both groups. CONCLUSION: GC survivors are at significantly increased risk for osteoporosis, especially in the femur. Clinically, our finding supports the importance of screening bone health and adequate nutrient supplementation in survivors of GC.