Helicobacter pylori and Its Treatment Impact on Immune-Mediated Ocular Diseases.

PURPOSE: Helicobacter pylori (HP), which colonizes exclusively in the gastrointestinal tract, has been reported to dysregulate the immune response and gives rise to several extra-gastrointestinal autoimmune disorders. However, the relationship between HP and immune-mediated ocular diseases remains ambiguous. This study aims to clarify the association between immune-mediated ocular diseases and HP infection, as well as the impact of HP treatment on the incidence of immune-mediated ocular diseases. METHODS: This is a retrospective population-based study using National Health Insurance Research Database in Taiwan. Patients with newly diagnosed peptic ulcer disease or HP infection between 2009 and 2015 were identified as HP group and compared to the non-HP group with one-to-one exact matching. Moreover, the incident risk of immune-mediated ocular diseases and its two subgroups (ocular surface and orbital inflammation group, intraocular inflammation group) were compared in HP patients with or without treatment. RESULTS: A total of 1,030,119 subjects in the non-HP group and 1,030,119 patients in the HP group were enrolled. The incidence rate of immune-mediated ocular diseases was significantly higher in the HP group (95% confidence interval (CI): 2.534-2.547). The incident rate ratio was significantly higher in HP with treatment than without treatment (HR: 1.654, 95% CI: 1.641-1.668). The Cox proportional hazards regression model demonstrated a significantly increased HR of immune-mediated ocular diseases in HP treated group (HR: 2.265, 95% CI: 2.024-2.534) and less increased HR in HP non-treated group (HR: 1.427, 95% CI: 1.273-1.598) when comparing to non-HP group. Subgroup analysis demonstrated a significantly higher incidence rate of ocular surface and orbital inflammation as well as intraocular inflammation in the HP group. CONCLUSION: This study illustrated a higher incidence of immune-mediated ocular diseases in HP infection, and a heightened risk following HP eradication.

Effect of Heart Rate Variability Biofeedback on Cardiac Autonomic Activation and Diabetes Self-Care in Patients with Type II Diabetes Mellitus.

In type 2 diabetes mellitus (T2DM), decreased autonomic activation and heightened negative emotions may worsen glycemic control. This study investigated the effects of heart rate variability biofeedback (HRVB) on autonomic activation, negative emotions, diabetes self-care, and glycemic control in patients with T2DM. A total of 61 participants with T2DM were assigned to either the HRVB group (n = 30; 62.67 ± 7.28 years; 14 females) or the control group (n = 31; 63.39 ± 6.96 years; 14 females). Both groups received the treatment as usual, and the HRVB group received 60 min of HRVB sessions weekly for 6 weeks. Participants completed psychological questionnaires, a resting electrocardiogram (ECG), and breathing rate assessments at pre- and post-tests. Heart rate variability (HRV) indices were derived from ECG data, and glycated hemoglobin (HbA1c) levels were collected from the electronic medical records. The analysis revealed significant Group × Time interaction effects on HRV indices, breathing rate, depression symptoms, and diabetes self-care behavior. The HRVB group demonstrated higher HRV indices, lower breathing rate, and improved diabetes self-care behavior compared to the control group. Moreover, the HRVB group showed enhanced HRV indices and diabetes self-care behavior, as well as reduced breathing rate and depression in the post-test compared to the pre-test. However, there was no significant interaction effect on HbA1c levels. Six sessions of HRVB proved effective as a complementary therapy for T2DM, enhancing HRV indices, alleviating depressive symptoms, and promoting better diabetes self-care behaviors.

Inter-Relations between Dietary Patterns and Glycemic Control-Related Biomarkers on Risk of Retinopathy in Type 2 Diabetes.

Diabetic retinopathy (DR), which can cause vision loss, may progress faster with poor glycemic control and oxidative stress. This study aims to examine how dietary patterns and glycemic control biomarkers relate to retinopathy risk in type 2 diabetes patients. In this study, we enrolled diabetic patients with retinopathy (DR) (n = 136) and without retinopathy (no DR) (n = 466) from a cohort of participants in the "Blood Pressure Control to Reduce the Risk of Type 2 Diabetic Nephropathy Study". Hemoglobin A1c (HbA1c) and malondialdehyde were defined as elevated when their levels reached ≥8.5% and ≥2/3 (16.2 µm), respectively. Dietary data were collected by a food frequency questionnaire. Dietary patterns were identified by factor analysis. Elevated HbA1c was significantly correlated with increased risk of DR (OR: 2.12, 95% CI: 1.14-3.93, p = 0.017). In subjects with a high animal protein and processed food dietary pattern (≥highest tertile score) or a low vegetable intake pattern (

Impact of comorbidities on the serological response to COVID-19 vaccination in a Taiwanese cohort.

BACKGROUND/AIMS: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control COVID-19 pandemic. The serological response to COVID-19 vaccination in Taiwanese patients with different comorbidities is elusive. METHODS: Uninfected subjects who received 3 doses of mRNA vaccines (BNT162b2 [Pfizer-BioNTech, BNT] and mRNA-1273 [Moderna]), viral vector-based vaccines (ChAdOx1-S (AZD1222, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine) were prospectively enrolled. The SARS-CoV-2-IgG spike antibody level was determined within three months after the 3rd dose of vaccination. The Charlson Comorbidity Index (CCI) was applied to determine the association between vaccine titers and underlying comorbidities. RESULTS: A total of 824 subjects were enrolled in the current study. The proportions of CCI scores of 0-1, 2-3 and > 4 were 52.8% (n = 435), 31.3% (n = 258) and 15.9% (n = 131), respectively. The most commonly used vaccination combination was AZ-AZ-Moderna (39.2%), followed by Moderna-Moderna-Moderna (27.8%). The mean vaccination titer was 3.11 log BAU/mL after a median of 48 days after the 3rd dose. Factors associated with potentially effective neutralization capacity (IgG level ≥ 4160 AU/mL) included age ≥ 60 years (odds ratio [OR]/95% confidence interval [CI]: 0.50/0.34-0.72, P < 0.001), female sex (OR/CI: 1.85/1.30-2.63, P = 0.001), Moderna-Moderna-based vaccination (compared to AZ-AZ-based vaccination, OR/CI: 6.49/3.90-10.83, P < 0.001), BNT-BNT-based vaccination (compared to AZ-AZ-based vaccination, OR/CI: 7.91/1.82-34.3, P = 0.006) and a CCI score ≥ 4 (OR/CI: 0.53/0.34-0.82, P = 0.004). There was a decreasing trend in antibody titers with increasing CCI scores (trend P < 0.001). Linear regression analysis revealed that higher CCI scores (ß: - 0.083; 95% CI: - 0.094-0.011, P = 0.014) independently correlated with low IgG spike antibody levels. CONCLUSIONS: Subjects with more comorbidities had a poor serological response to 3 doses of COVID-19 vaccination.

Using Machine Learning for the Risk Factors Classification of Glycemic Control in Type 2 Diabetes Mellitus.

Several risk factors are related to glycemic control in patients with type 2 diabetes mellitus (T2DM), including demographics, medical conditions, negative emotions, lipid profiles, and heart rate variability (HRV; to present cardiac autonomic activity). The interactions between these risk factors remain unclear. This study aimed to use machine learning methods of artificial intelligence to explore the relationships between various risk factors and glycemic control in T2DM patients. The study utilized a database from Lin et al. (2022) that included 647 T2DM patients. Regression tree analysis was conducted to identify the interactions among risk factors that contribute to glycated hemoglobin (HbA1c) values, and various machine learning methods were compared for their accuracy in classifying T2DM patients. The results of the regression tree analysis revealed that high depression scores may be a risk factor in one subgroup but not in others. When comparing different machine learning classification methods, the random forest algorithm emerged as the best-performing method with a small set of features. Specifically, the random forest algorithm achieved 84% accuracy, 95% area under the curve (AUC), 77% sensitivity, and 91% specificity. Using machine learning methods can provide significant value in accurately classifying patients with T2DM when considering depression as a risk factor.

Novel Smart Assistance System for Arteriosclerosis Evaluation.

Arteriosclerosis is a cardiovascular disease that can cause calcification, sclerosis, stenosis, or obstruction of blood vessels and may further cause abnormal peripheral blood perfusion or other complications. In clinical settings, several approaches, such as computed tomography angiography and magnetic resonance angiography, can be used to evaluate arteriosclerosis status. However, these approaches are relatively expensive and require an experienced operator and often the injection of a contrast agent. In this article, a novel smart assistance system based on near-infrared spectroscopy was proposed that can noninvasively assess blood perfusion and thus indicate arteriosclerosis status. In this system, a wireless peripheral blood perfusion monitoring device simultaneously monitors changes in hemoglobin parameters and the cuff pressure applied by a sphygmomanometer. Several indexes extracted from changes in hemoglobin parameters and cuff pressure were defined and can be used to estimate blood perfusion status. A neural network model for arteriosclerosis evaluation was constructed using the proposed system. The relationship between the blood perfusion indexes and arteriosclerosis status was investigated, and the neural network model for arteriosclerosis evaluation was validated. Experimental results indicated that the differences in many blood perfusion indexes for different groups were significant and that the neural network model could effectively evaluate arteriosclerosis status (accuracy = 80.26%). By using a sphygmomanometer, the model can be employed for simple arteriosclerosis screening and blood pressure measurements. The model offers real-time noninvasive measurement, and the system is relatively inexpensive and easy to operate.

Gut microbiota composition can reflect immune responses of latent tuberculosis infection in patients with poorly controlled diabetes.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB). Evidence has linked the DM-related dysbiosis of gut microbiota to modifiable host immunity to Mycobacterium tuberculosis infection. However, the crosslinks between gut microbiota composition and immunological effects on the development of latent TB infection (LTBI) in DM patients remain uncertain. METHODS: We prospectively obtained stool, blood samples, and medical records from 130 patients with poorly-controlled DM (pDM), defined as ever having an HbA1c > 9.0% within previous 1 year. Among them, 43 had LTBI, as determined by QuantiFERON-TB Gold in-Tube assay. The differences in the taxonomic diversity of gut microbiota between LTBI and non-LTBI groups were investigated using 16S ribosomal RNA sequencing, and a predictive algorithm was established using a random forest model. Serum cytokine levels were measured to determine their correlations with gut microbiota. RESULTS: Compared with non-LTBI group, the microbiota in LTBI group displayed a similar alpha-diversity but different beta-diversity, featuring decrease of Prevotella_9, Streptococcus, and Actinomyces and increase of Bacteroides, Alistipes, and Blautia at the genus level. The accuracy was 0.872 for the LTBI prediction model using the aforementioned 6 microbiome-based biomarkers. Compared with the non-LTBI group, the LTBI group had a significantly lower serum levels of IL-17F (p = 0.025) and TNF-α (p = 0.038), which were correlated with the abundance of the aforementioned 6 taxa. CONCLUSIONS: The study results suggest that gut microbiome composition maybe associated with host immunity relevant to TB status, and gut microbial signature might be helpful for the diagnosis of LTBI.

SGLT2 Inhibitor Canagliflozin Alleviates High Glucose-Induced Inflammatory Toxicity in BV-2 Microglia.

Patients with diabetes mellitus can experience hyperglycemia, which affects brain function and produces cognitive impairment or neurodegeneration. Neuroinflammation is an important cause of cognitive dysfunction. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antihyperglycemic agents that reportedly possess anti-inflammatory properties and may produce beneficial cognitive effects. We hypothesized that SGLT2 inhibitors alleviate hyperglycemia-related inflammation in brain immune cells. Cultured BV-2 microglia were exposed to high glucose (HG) in the absence or presence of SGLT2 inhibitors including canagliflozin (Cana), dapagliflozin (Dapa), empagliflozin (Empa), and ertugliflozin (Ertu). Afterward, we evaluated the cytotoxic and inflammatory responses by specific biochemical assays. Treatments with non-toxic Cana or Dapa, but not Empa or Ertu, inhibited proliferation without cell death. Only Cana rescued BV-2 microglia from HG-induced cytotoxicity, including apoptosis or autophagic degradation. None of SGLT2 inhibitors affected the HG-stimulated induction of stress proteins HO-1 and HSP70. Also, compared to the other three SGLT2 inhibitors, Cana was better at inhibiting HG-induced oxidative/inflammatory stress, as evidenced by its ability to repress proinflammatory factors (e.g., oxygen free radicals, iNOS, NLRP3, IL-1ß, and TNF-α) other than COX-2. Cana's action to alleviate HG insults was mediated not by altering SGLT2 protein expression, but by reducing HG-stimulated signaling activities of NFκB, JNK, p38, and PI3K/Akt pathways. Particularly, Cana imitated the effects of NFκB inhibitor on HG-induced iNOS and COX-2. Of the four SGLT2 inhibitors, Cana provided BV-2 microglia with the best protection against HG-induced inflammatory toxicity. Thus, Cana may help to reduce innate neuroimmune damage caused by hyperglycemia.

Boosting the detection performance of severe acute respiratory syndrome coronavirus 2 test through a sensitive optical biosensor with new superior antibody.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged in late 2019 leading to the COVID-19 disease pandemic that triggered socioeconomic turmoil worldwide. A precise, prompt, and affordable diagnostic assay is essential for the detection of SARS-CoV-2 as well as its variants. Antibody against SARS-CoV-2 spike (S) protein was reported as a suitable strategy for therapy and diagnosis of COVID-19. We, therefore, developed a quick and precise phase-sensitive surface plasmon resonance (PS-SPR) biosensor integrated with a novel generated anti-S monoclonal antibody (S-mAb). Our results indicated that the newly generated S-mAb could detect the original SARS-CoV-2 strain along with its variants. In addition, a SARS-CoV-2 pseudovirus, which could be processed in BSL-2 facility was generated for evaluation of sensitivity and specificity of the assays including PS-SPR, homemade target-captured ELISA, spike rapid antigen test (SRAT), and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Experimentally, PS-SPR exerted high sensitivity to detect SARS-CoV-2 pseudovirus at 589 copies/ml, with 7-fold and 70-fold increase in sensitivity when compared with the two conventional immunoassays, including homemade target-captured ELISA (4 × 103 copies/ml) and SRAT (4 × 104 copies/ml), using the identical antibody. Moreover, the PS-SPR was applied in the measurement of mimic clinical samples containing the SARS-CoV-2 pseudovirus mixed with nasal mucosa. The detection limit of PS-SPR is calculated to be 1725 copies/ml, which has higher accuracy than homemade target-captured ELISA (4 × 104 copies/ml) and SRAT (4 × 105 copies/ml) and is comparable with qRT-PCR (1250 copies/ml). Finally, the ability of PS-SPR to detect SARS-CoV-2 in real clinical specimens was further demonstrated, and the assay time was less than 10 min. Taken together, our results indicate that this novel S-mAb integrated into PS-SPR biosensor demonstrates high sensitivity and is time-saving in SARS-CoV-2 virus detection. This study suggests that incorporation of a high specific recognizer in SPR biosensor is an alternative strategy that could be applied in developing other emerging or re-emerging pathogenic detection platforms.

Predictive Value of HbA1c and Metabolic Syndrome for Renal Outcome in Non-Diabetic CKD Stage 1-4 Patients.

Glycated hemoglobin (HbA1c) levels are commonly used to indicate long-term glycemic control. An HbA1c level of 6.5−5.7% is defined as pre-diabetes and is proposed as a criterion for diagnosing metabolic syndrome (MetS). However, HbA1c levels can be affected by chronic kidney disease (CKD). Whether HbA1c is associated with clinical outcomes in nondiabetic CKD patients with or without MetS is still unknown. This study included 1270 nondiabetic CKD stage 1−4 Asian patients, divided by HbA1c and MetS. Through linear regression, HbA1c was positively associated with age, waist circumference, hemoglobin levels, and C-reactive protein and was negatively associated with malnutrition−inflammation. HbA1c levels were 5.5% (0.6%) and 5.7% (0.6%) in non-MetS and MetS, respectively (p < 0.001). In Cox regression, higher-level HbA1c was associated with worse composite renal outcome in MetS patients, but with better renal outcome in non-MetS patients: Hazard ratio (HR) (95% confidence interval [CI]) of HbA1c ≥5.7%, compared with HbA1c <5%, was 2.00 (1.06−3.78) in MetS and 0.25 (0.14−0.45) in non-MetS. An association between HbA1c and all-cause mortality was not found. In conclusion, higher HbA1c levels are associated with worse renal outcomes in nondiabetic CKD stage 1−4 patients modified by the presence of MetS.

Association of depression and parasympathetic activation with glycemic control in type 2 diabetes mellitus.

AIM: Patients with type 2 diabetes mellitus exhibited autonomic nervous system (ANS) dysfunction and comorbidities with depressive or anxiety symptoms were related to poor glycemic control. Heart rate variability (HRV) converted from electrocardiogram (ECG) has been used as the ANS index. The study aimed to explore the associations between depression, anxiety, HRV, and glycemic control in patients with type 2 diabetes mellitus. METHODS: The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) questionnaires were used to assess depressive and anxiety symptoms in 647 patients with type 2 diabetes mellitus (mean age was 63 ± 10 years, 56 % males). The ECG raw signals were collected from a 5-min sitting and resting baseline and then transformed to HRV indices referring ANS activation. Blood glucose and lipid profiles including glycated hemoglobin (HbA1c), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride were obtained from the electronic medical records. RESULTS: Ninety-nine (15 %) participants had depressive symptoms and 59 (9 %) had anxiety symptoms. Depression and HbA1c were negatively correlated with parasympathetic activation. Depression and anxiety were positively correlated with sympathetic activation. After controlling for demographic data and lipid profiles, depression was a significant positive predictor for HbA1c levels; and HRV indices (lnLF and lnHF) were the significant negative predictors for HbA1c levels. Mediation effect analysis showed that depression was a mediator between parasympathetic activation and glycemic control. CONCLUSIONS: Lower parasympathetic activation and higher depressive symptoms may affect glycemic control in patients with type 2 diabetes mellitus. Intervention programs targeting to increase parasympathetic activities and reducing depression could be further tested for their effects on glycemic outcomes for potential clinical use.

Effects of Helicobacter pylori treatment on the incidences of autoimmune diseases and inflammatory bowel disease in patients with diabetes mellitus.

BACKGROUND: Helicobacter pylori infection is known to decrease the incidences of autoimmune diseases and inflammatory bowel disease(IBD). Our aim was investigating the effect of H. pylori treatment in diabetes mellitus(DM) patients. METHODS: Adults with newly-diagnosed H. pylori infection or peptic ulcer disease(PUD) within the general population and DM population were identified from the National Health Insurance Research Database of Taiwan from 2000-2010. 79,181 patients were assigned to the 3 groups: general population with PUD without H. pylori treatment(PUD-HPRx in general population), DM patients with PUD without H. pylori treatment(PUD-HPRx in DM), and DM patients with PUD who received H. pylori treatment(PUD+HPRx in DM). RESULTS: Higher incidences of autoimmune diseases and IBD were observed in the PUD+HPRx in DM group than in the PUD-HPRx in general population and PUD-HPRx in DM groups (autoimmune diseases = 5.14% vs 3.47% and 3.65%; IBD = 5.60% vs 3.17% and 3.25%; P<0.0001). A lower all-cause mortality was noted in the PUD+HPRx in DM group (HR: 0.937, P<0.001) than in the PUD-HPRx in DM group. Trends of a higher incidence of IBD and a lower mortality in younger patients in the PUD+HPRx in DM group compared with the PUD-HPRx in DM group were noted. CONCLUSIONS: The results revealed that H. pylori treatment increased the incidences of autoimmune diseases and IBD and decreased the all-cause mortality in the DM group with PUD. The effect was more significant in younger patients. This finding assists in realizing the influence of H. pylori treatment in the DM population.

Therapeutic DNA vaccine encoding CEMIP (KIAA1199) ameliorates kidney fibrosis in obesity through inhibiting the Wnt/ß-catenin pathway.

BACKGROUND: CEMIP is a novel risk factor of various cancers through activating Wnt/ß-catenin /epithelial-mesenchymal transition between epithelial cells and stroma. The chronic fibrosis commonly contributes renal carcinogenesis in patients with obesity. As there have very few choices of medicines targeting CEMIP. This study intended to design therapeutic DNA vaccines for nephropathy in obesity, through diminishing the CEMIP/Wnt1/ß-catenin pathway. METHOD: In an 8-week experiment, plasmid-encoding CEMIP was vaccinated into high-fat diet (HFD) or obesity mice in the first 4 weeks, and then vaccination was stopped for at least 4 weeks. Then, plasma and spleens were harvested to evaluate anti-CEMIP antibody synthesis and T-helper type 1 and 2 activation after vaccination. Kidneys were collected to investigate efficacy of CEMIP DNA vaccine on inhibiting HFD and obesity-induced fibrosis and Wnt1/ß-catenin pathway. To confirm that CEMIP crucially contributed towards fibrotic formation, CEMIP gene or siRNA transfection was performed in HK-2 cells under VLDL stimulation, or not. RESULTS: At the end point, anti-CEMIP antibody was successfully produced in the pcDNA 3.1-CEMIP vaccinated group, while Wnt1/ß-catenin signaling and fibrosis was inactive. Through VLDL stimulation and CEMIP overexpression, Wnt1/ß-catenin signaling and fibrosis significantly presented in vitro. Otherwise, anti-sera of CEMIP-vaccinated mice could inhibit the VLDL-induced Wnt1/ß-catenin/fibrosis pathway in HK-2 cells. Similarly, the silencing of CEMIP by siRNA ameliorated the Wnt1/ß-catenin pathway and fibrogenesis under VLDL stimulation. CONCLUSION: DNA vaccine targeting CEMIP/Wnt1/ß-catenin pathway plays a novel strategy in nephropathy. GENERAL SIGNIFICANCE: Immune therapy might provide a new therapeutic option on nephropathy of obesity.

Epidemiological characteristics of diabetic kidney disease in Taiwan.

Diabetic kidney disease (DKD) is a critical microvascular complication of diabetes. With the continuous increase in the prevalence of diabetes since 2000, the prevalence of DKD has also been increasing in past years. The prevalence of DKD among individuals with type 2 diabetes in Taiwan increased from 13.32% in 2000 to 17.92% in 2014. The cumulative incidence of DKD among individuals with type 1 diabetes in Taiwan was higher than 30% during 1999-2012. DKD is the leading cause of end-stage renal disease (ESRD), with a prevalence of approximately 45% in a population on chronic dialysis in Taiwan. Among individuals with type 2 diabetes, the prevalence of ESRD in the receipt of dialysis also increased from 1.32% in 2005 to 1.47% in 2014. Risk factors for DKD development are age, race, family history, hyperglycemia, hypertension, dyslipidemia, dietary patterns, and lifestyles. Prognostic factors that aggravate DKD progression include age, family history, sex, glycemic control, blood pressure (BP), microvascular complications, and atherosclerosis. This review summarizes updated information on the onset and progression of DKD, particularly in the Taiwanese population. Translating these epidemiological features is essential to optimizing the kidney care and improving the prognosis of DKD in Asian populations.

Clinical Outcomes and Oral Health-Related Quality of Life after Periodontal Treatment with Community Health Worker Strategy in Patients with Type 2 Diabetes: A Randomized Controlled Study.

Interventions engaging community health workers (CHW) for diabetes management aim to improve diabetes care and self-management behaviors among patients. We evaluated the effects of nonsurgical periodontal treatment (NSPT) with the CHW strategy on oral self-care behaviors, periodontal status and oral health-related quality of life (OHQoL) in patients with type 2 diabetes mellitus (T2DM). The participants were randomly assigned to experimental (EG; n = 35) and control (CG; n = 33) groups. All participants received NSPT, whereas the patients in the EG also received one-on-one 30 min lessons from a CHW over 4 weeks. The EG exhibited greater improvement in the probing pocket depth (ß = -0.2, effect size [ES] = 0.61) and clinical attachment level (ß = -0.2, ES = 0.59) at 1-month follow-up than the CG did. The ES increased over the 1-, 3- and 6-month follow-ups, indicating an increase in OHQoL (ES = 0.19, 0.60, and 0.62, respectively) in the EG. The patients in the EG were more likely to change their oral self-care behaviors than patients in the CG were. The NSPT with CHW strategy had a positive effect on 1-month periodontal treatment outcomes, long-term OHQoL and oral self-care behaviors in patients with T2DM.

Completion Rate and Safety of Programmatic Screening and Treatment for Latent Tuberculosis Infection in Elderly Patients With Poorly Controlled Diabetic Mellitus: A Prospective Multicenter Study.

BACKGROUND: Poor control of diabetes mellitus (DM) increases active tuberculosis (TB) risk. Understanding risk factors for latent TB infection (LTBI) in this population and intervention completion rates is crucial for policy making. METHODS: Under a collaborative multidisciplinary team consisting of public health professionals, endocrinologists, and pulmonologists, patients aged >45 years with poorly controlled DM (pDM), defined as having a glycated hemoglobin level of ≥9% within the preceding year, were enrolled by endocrinologists from 2 hospitals; these patients underwent LTBI screening by using QuantiFERON (QFT). Once-weekly isoniazid and rifapentine for 12 weeks (3HP) or daily isoniazid for 9 months (9H) was administered by pulmonologists. QFT-positivity predictors were evaluated using logistic regression. Completion rates and safety were also investigated. RESULTS: Among 980 patients with pDM (age: 64.2 ±â€…9.7 years), 261 (26.6%) were QFT-positive. Age, DM duration, chronic kidney disease stage ≥3, and dipeptidyl peptidase-4 inhibitor use, not using metformin, were associated with QFT-positivity. Preventive therapy (3HP: 138; 9H: 62) was administered in 200 (76.6%) QFT-positive patients. The completion rates of 3HP and 9H were 84.1% and 79.0%, respectively (P = .494). Nine (6.5%) and zero patients in the 3HP and 9H groups, respectively, developed systemic drug reactions (P = .059); 78.3% and 45.2% had ≥1 adverse drug reactions (P < .001); and post-treatment QFT conversion rates were 32% and 20%, respectively (P = .228). CONCLUSIONS: LTBI prevalence exceeds 25% in elderly patients with pDM. Under care from a collaborative multidisciplinary team, the completion rate of preventive therapy, regardless of regimen could approach, or even exceed 80% in this population.

Disruption of retinoid homeostasis induces RBP4 overproduction in diabetes: O-GlcNAcylation involved.

BACKGROUND: Retinol-binding protein 4 (RBP4) is elevated and associated with inflammation in metabolic diseases. Disruption of the retinol cascade and O-GlcNAcylation of the RBP4 receptor (STRA6) are found in diabetic kidneys. OBJECTIVES: We investigated whether the disruption of the retinol cascade induces RBP4 overproduction and if O-linked GlcNAc modification targets RBPR2 and contributes to the disruption of retinol cascades in diabetic livers. METHODS: Western blot or immunohistochemistry for RBPR2, CRBP1, LRAT, RALDH, RARα, RARγ, RXRα, RBP4, GFAT, OGT, OGA and inflammatory markers, as well as ELISA for RBP4, were performed in livers of db/db and ob/ob mice and high glucose-cultured hepatocytes. Immunoprecipitation and dual fluorescence staining were used to explore O-GlcNAc-modified RBPR2 and RBP4 binding activity on RBPR2. Transfection of the CRBP1 gene was done to verify whether a disrupted retinol cascade induces RBP4 overproduction. OGT silencing was done to investigate the association of O-GlcNAcylation with the disruption of retinol cascade. RESULTS: Disruption of retinol cascade, RBP4 overproduction, O-GlcNAcylation of RBPR2, decreased RBP4 binding activity on RBPR2 and inflammation were found in livers of db/db and ob/ob mice and high glucose-cultured hepatocytes. CRBP1 gene transfection reversed the suppression of the cellular retinol cascade and simultaneously attenuated the RBP4 overproduction and inflammation in high glucose-treated hepatocytes. The silencing of OGT reversed the disruption of the cellular retinol cascade, RBP4 overproduction and inflammation induced by high glucose in hepatocytes. CONCLUSIONS: This study indicates that the disruption of cellular retinol cascade is strongly associated with RBP4 overproduction and inflammation in diabetic livers. RBPR2 is one target for high glucose-mediated O-linked GlcNAc modification, which causes liver retinol dyshomeostasis.

Electronegative low-density lipoprotein of patients with metabolic syndrome induces pathogenesis of aorta through disruption of the stimulated by retinoic acid 6 cascade.

AIMS/INTRODUCTION: Electronegative low-density lipoprotein (L5) is the most atherogenic fraction of low-density lipoprotein and is elevated in people with metabolic syndrome (MetS), whereas the retinol-binding protein 4 receptor (stimulated by retinoic acid 6 [STRA6]) cascade is disrupted in various organs of patients with obesity-related diseases. Our objective was to investigate whether L5 from MetS patients capably induces pathogenesis of aorta through disrupting the STRA6 cascade. MATERIAL AND METHODS: We examined the in vivo and in vitro effects of L5 on the STRA6 cascade and aortic atherogenic markers. To investigate the role of this cascade on atherosclerotic formation, crbp1 transfection was carried out in vitro. RESULTS: This study shows that L5 activates atherogenic markers (p38 mitogen-activated protein kinases, pSmad2 and matrix metallopeptidase 9) and simultaneously suppresses STRA6 signals (STRA6, cellular retinol-binding protein 1, lecithin-retinol acyltransferase, retinoic acid receptor-α and retinoid X receptor-α) in aortas of L5-injected mice and L5-treated human aortic endothelial cell lines and human aortic smooth muscle cell lines. These L5-induced changes of the STRA6 cascade and atherogenic markers were reversed in aortas of LOX1-/- mice and in LOX1 ribonucleic acid-silenced human aortic endothelial cell lines and human aortic smooth muscle cell lines. Furthermore, crbp1 gene transfection reversed the disruption of the STRA6 cascade, the phosphorylation of p38 mitogen-activated protein kinases and Smad2, and the elevation of matrix metallopeptidase 9 in L5-treated human aortic endothelial cell lines. CONCLUSIONS: This study shows that L5 from MetS patients induces atherogenic markers by disrupting STRA6 signaling. Suppression of STRA6 might be one novel pathogenesis of aorta in patients with MetS.

Blood biomarkers of various dietary patterns correlated with metabolic indicators in Taiwanese type 2 diabetes.

BACKGROUND: Metabolic alterations correlate with adverse outcomes in type 2 diabetes. Dietary modification serves as an integral part in its treatment. OBJECTIVE: We examined the relationships among dietary patterns, dietary biomarkers, and metabolic indicators in type 2 diabetes (n = 871). DESIGN: Diabetic patients (n = 871) who provided complete clinical and dietary data in both 2008 and 2009 were selected from a cohort participating in a diabetic control study in Taiwan. Dietary data were obtained using a short, semiquantitative food frequency questionnaires, and dietary pattern identified by factor analysis. Multiple linear regressions were used to analyze the association between dietary biomarkers (ferritin, folate, and erythrocyte n-3 polyunsaturated fatty acids [n-3 PUFAs]) and metabolic control upon adjusting for confounders. RESULTS: Three dietary patterns (high-fat meat, traditional Chinese food-snack, and fish-vegetable) were identified. Ferritin correlated positively with high-fat meat factor scores (P for trend <0.001). Erythrocyte n-3 PUFAs (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA], n-3/n-6 PUFA ratio) correlated positively with fish-vegetable factor scores (all P for trends <0.001). Multiple linear regressions revealed a positive relationship between ferritin concentrations and fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and triglycerides, but a negative relationship with high-density lipoprotein cholesterol (HDL-C). Erythrocyte n-3 PUFA, EPA+DHA, and n-3/n-6 PUFA ratio were negatively linked to FPG, HbA1c, and triglycerides (all P < 0.05) and positively with HDL-C (though n-3/n-6 ratio marginally correlated). CONCLUSIONS: Ferritin and n-3 PUFA can serve as valid biomarkers for high-fat meat and fish-vegetable dietary patterns. Unlike ferritin, erythrocyte n-3 PUFA status was related to better glycemic and blood lipid profiles. Our results suggest that habitual consumption of diet pattern rich in fish and vegetables may contribute in part to a healthier metabolic profile in type 2 diabetes.

Periodontal Treatment Experience Associated with Oral Health-Related Quality of Life in Patients with Poor Glycemic Control in Type 2 Diabetes: A Case-Control Study.

Severe periodontitis is a risk factor for poor glycemic control. The appropriate medicaltreatment and plaque control of periodontitis positively affects blood-sugar control in diabetespatients. We aimed to identify the factors associated with glycemic control and examine theperiodontal treatment (PT) experience and oral health-related quality of life (OHQoL) for patientswith poor glycemic control in type 2 diabetes mellitus (T2DM). This multicenter case-control studyrecruited 242 patients with poor glycemic control and 198 patients with good glycemic control. Wecollected patients' information through face-to-face interviews using a structured questionnaire.The Oral Health Impact Profile-14 (OHIP-14) was used to measure OHQoL. Based on PT status, thepatients were classified into three groups: a non-periodontal disease group, a PT group, and a non-PT (NPT) group. Regression models were used to analyze the data. No interdental cleaning(adjusted odds ratio (aOR) = 1.78) and positive attitudes toward periodontal health (aOR = 1.11)were significantly more likely to be associated with poor glycemic control in patients with T2DM.The PT group had a significantly lower OHIP-14 score than the NPT group (6.05 vs. 9.02, p < 0.001),indicating a better OHQoL among patients with poorly controlled T2DM. However, the OHQoLdid not differ significantly in patients with well-controlled T2DM between the PT and NPT groups.This suggested that diabetic patients with poor glycemic control must improve periodontal carepractices and receive proper PT, if necessary, to improve their OHQoL.