Asymptomatic subjects with diabetes have a comparable risk of coronary artery disease to Non-diabetic subjects presenting chest pain: a 4-year community-based prospective study

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background Although diabetes mellitus is an important risk factor of coronary artery disease (CAD), routine screening for CAD is not recommended for asymptomatic diabetic patients. We assessed the impact of chest pain on CAD risk according to the presence or absence of diabetes mellitus. Methods We investigated the future CAD event rate in subjects with and without chest pain according to the presence or absence of diabetes in a prospective large-scale community-based study in Korea. Results Among 8,574 subjects (4,032 men and 4,542 women) without a history of CAD, 0.8% and 2.2% of non-diabetic and diabetic subjects, respectively, reported newly developed CAD events during 4 years of follow-up. Although the presence of chest pain at baseline was also significantly associated with an increased risk of CAD of more than 2-fold in both non-diabetic and diabetic subjects (P < 0.01), the risk of future CVD event in asymptomatic diabetic patients was not significantly different from that in non-diabetic subjects with chest pain (hazard ratio, 0.907; 95% confidence interval, 0.412 – 1.998). Conclusions The CAD event rate of asymptomatic subjects with diabetes was comparable to that of non-diabetic subjects reporting chest pain. Considering the high risk of CAD in asymptomatic diabetic patients, more clinical trials aimed at formulating strategies to screen asymptomatic diabetic subjects should be carried out

Peripheral arterial endothelial dysfunction predicts future cardiovascular events in diabetic patients with albuminuria: a prospective cohort study

Background Reactive hyperemia-peripheral arterial tonometry (RH-PAT) is a noninvasive and simple test for evaluating the endothelial function. There has been sparse evidence on the usefulness of the RH-PAT index (RHI) in predicting future cardiovascular diseases among diabetic patients. Methods Asymptomatic diabetic patients with albuminuria were selected; their medical history and laboratory findings were evaluated every 3 to 4 months, respectively. The primary outcome was a composite of three-point major adverse cardiovascular events (3-point MACE): death from cardiovascular causes, acute coronary events, or nonfatal stroke. On the contrary, secondary outcomes included a composite of 3-point MACE, hospitalization for heart failure, or chronic kidney disease (CKD) progression. RHI was measured using the Endo-PAT2000 at the baseline. RHI < 1.67 was considered to indicate peripheral endothelial dysfunction (PED). Results In total, 149 subjects were included (mean age, 61.8 ± 9.2 years; duration of diabetes was 12 years). During the follow-up period (median, 49.7 months), of the 149 subjects, primary outcomes were detected in 12 (1 [2.3%] and 11 [10.5%] of those without and with PED, respectively). The presence of PED in baseline measurements significantly increased both primary and secondary outcomes, following adjustment for age, sex, hypertension, glycated hemoglobin, low-density lipoprotein cholesterol, triglyceride, systolic blood pressure, baseline estimated glomerular filtration rate, overt proteinuria, duration of diabetes, premedical history of ischemic events, anti-platelet agents, and smoking history (hazard ratio [HR]: 10.95; 95% confidence interval CI 1.00–119.91 for the primary outcome; HR, 4.12; 95% CI 1.37–12.41 for secondary outcome). In addition, PED could predict secondary outcomes independent of the risk score according to the American College of Cardiology/American Heart Association (HR: 3.24; 95% CI 1.14–9.17). Conclusions PED can independently predict future cardiovascular events among diabetic patients with albuminuria.This study was supported by Health Connect Research Fund (No. 16-2013-87)

Efficacy evaluation of combination vaccine of recombinant C-terminal fragments of ApxIA, ApxIIA and ApxIIIA in piglets

The efficacy of the combination vaccine of the individual C-terminal fragments of ApxIA, ApxIIA and ApxIIIA of Actinobacillus pleuropneumoniae (APP) was evaluated in piglets. Twenty piglets were divided equally into 2 groups (n=10). All piglets were intramuscularly primed at 4 week-of-age (0 week post prime inoculation (WPPI)) and were intramuscularly boosted at 6 week-of-age (2 WPPI). Group A piglets were inoculated with sterile PBS and group B piglets were inoculated with the combination vaccine. Concentrations of each of the C-terminal fragment-specific IgG as determined by ELISA were significantly higher in group B than in group A from 2 WPPI until the end of this study. Clinical signs were observed from only 10% of group B piglets after the challenge with the mixture of APP serotypes 1, 2 and 5 at 4 WPPI, while 50% of group A piglets were protected against APP infections. Overall, intramuscular inoculation with the vaccine candidate can efficiently protect piglets against APP infection

Gene–diet interaction analysis using novel weighted food scores discovers the adipocytokine signaling pathway associated with the development of type 2 diabetes

IntroductionThe influence of dietary patterns measured using Recommended Food Score (RFS) with foods with high amounts of antioxidant nutrients for Type 2 diabetes (T2D) was analyzed. Our analysis aims to find associations between dietary patterns and T2D and conduct a gene-diet interaction analysis related to T2D.MethodsData analyzed in the current study were obtained from the Korean Genome and Epidemiology Study Cohort. The dietary patterns of 46 food items were assessed using a validated food frequency questionnaire. To maximize the predictive power of the RFS, we propose two weighted food scores, namely HisCoM-RFS calculated using the novel Hierarchical Structural Component model (HisCoM) and PLSDA-RFS calculated using Partial Least Squares-Discriminant Analysis (PLS-DA) method.ResultsBoth RFS (OR: 1.11; 95% CI: 1.03- 1.20; P = 0.009) and PLSDA-RFS (OR: 1.10; 95% CI: 1.02-1.19, P = 0.011) were positively associated with T2D. Mapping of SNPs (P &lt; 0.05) from the interaction analysis between SNPs and the food scores to genes and pathways yielded some 12 genes (CACNA2D3, RELN, DOCK2, SLIT3, CTNNA2, etc.) and pathways associated with T2D. The strongest association was observed with the adipocytokine signalling pathway, highlighting 32 genes (STAT3, MAPK10, MAPK8, IRS1, AKT1-3, ADIPOR2, etc.) most likely associated with T2D. Finally, the group of the subjects in low, intermediate and high using both the food scores and a polygenic risk score found an association between diet quality groups with issues at high genetic risk of T2D.ConclusionA dietary pattern of poor amounts of antioxidant nutrients is associated with the risk of T2D, and diet affects pathway mechanisms involved in developing T2D

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

Insulin-sensitizing effects of exercise on adiponectin and retinol-binding protein-4 concentrations in young and middle-aged women

CONTEXT: Exercise training enhances insulin sensitivity. Changes in retinol-binding protein-4 (RBP4) and adiponectin levels are linked to insulin resistance. OBJECTIVE: We tested whether the insulin-sensitizing effect of exercise is associated with age-related changes in circulating RBP4 and adiponectin levels in women. DESIGN, SUBJECTS, AND INTERVENTION: We studied 36 healthy young (22.4 +/- 2.8 yr) and 38 middle-aged (59.8 +/- 5.9 yr) women. All subjects performed 60 min of aerobic exercise three times per week for 10 wk at about 70% maximal exercise capacity. RESULTS: After a 10-wk training program, maximal exercise capacity was significantly increased in both young and middle-aged women, suggesting increased oxidative capacity. Insulin sensitivity was also improved, as indicated by decreases in plasma insulin levels and homeostasis model assessment for insulin resistance index. Serum adiponectin and RBP4 concentrations were increased and decreased more in older than younger women, respectively (P < 0.01). Concurrently, circulating transthyretin levels were also decreased in older subjects in response to exercise training. The older women showed higher correlations between changes in adiponectin or RBP4 levels and obesity indices or metabolic parameters than the younger group. When subjects showing increasing adiponectin or decreasing RBP4 levels were classified as responders, there were higher correlations between these changes in responders than in nonresponders. CONCLUSIONS: We conclude that the mechanism for the insulin-sensitizing effects of exercise could involve increased adiponectin and reduced RBP4 levels in exercise-trained women. These data suggest that alterations in circulating RBP4 and adiponectin levels could play an important role in regulating insulin sensitivity

Partial Deletion of Perk Improved High-Fat Diet-Induced Glucose Intolerance in Mice

Although pancreatic endoplasmic reticulum kinase (PERK) is indispensable to beta cells, low-dose PERK inhibitor improved glucose- stimulated insulin secretion (GSIS) and hyperglycemia in diabetic mice. Current study examined if partial deletion of Perk (Perk+/-) recapitulated the effects of PERK inhibitor, on the contrary to the complete deletion. Perk+/- mice and wild-type controls were fed with a high-fat diet (HFD) for 23 weeks. Glucose tolerance was evaluated along with serum insulin levels and islet morphology. Perk+/- mice on normal chow were comparable to wild-type mice in various metabolic features. HFD-induced obesity was not influenced by Perk reduction; however, HFD-induced glucose intolerance was significantly improved since 15-week HFD. HFD-induced compromises in GSIS were relieved by Perk reduction, accompanied by reductions in phosphorylated PERK and activating transcription factor 4 (ATF4) in the islets. Meanwhile, HFD-induced islet expansion was not significantly affected. In summary, partial deletion of Perk improved glucose tolerance and GSIS impaired by diet-induced obesity, without changes in body weights or islet mass

Permanent Pacemaker for Syncope after Heart Transplantation with Bicaval Technique

Sinus node dysfunction occurs occasionally after heart transplantation and may be caused by surgical trauma, ischemia to the sinus node, rejection, drug therapy, and increasing donor age. However, the timing and indication of permanent pacemaker insertion due to sinus node dysfunction following heart transplantation is contentious. Here, we report a case of a permanent pacemaker insertion for syncope due to sinus arrest after heart transplantation, even with a bicaval technique, which has been known to associate with few incidences of sinus node dysfunction