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.

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.

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.

Effects of Anti-Helicobacter pylori Therapy on Incidence of Autoimmune Diseases, Including Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Helicobacter pylori induces immune tolerance and is associated with a lower risk for immune-mediated disorders, such as autoimmune and inflammatory bowel diseases (IBD). We aimed to determine the effects of treatment for H pylori infection on the incidence of autoimmune disease and IBD. METHODS: We collected data from the National Health Insurance Research Database in Taiwan on patients younger than 18 years old without a prior diagnosis of autoimmune disease or IBD. Patients with peptic ulcer disease (PUD) with treatment of H pylori infection (PUD+HPRx), PUD without H pylori treatment (PUD-HPRx), a urinary tract infection (UTI) treated with cephalosporin, or without PUD (controls) were matched for age, sex, insurance, and Charlson's comorbidity index score. RESULTS: Of the 1 million patients we collected data from in 2005, we included 79,181 patients in the study. We compared the effects of treatment for H pylori infection on the risk of autoimmunity or IBD and found that PUD+HPRx has the highest adjusted hazard risk (aHR) for autoimmunity or IBD (aHR, 2.36), compared to PUD-HPRx (aHR, 1.91) or UTI (aHRs, 1.71) (P < .001). The increased risk of autoimmune disease was not completely accounted for by antibiotic therapy alone, because PUD+HPRx had a higher aHR than UTI (P < .001). A small but significant increase in mortality was observed in the PUD+HPRx cohort (aHR, 1.11; P = .001). CONCLUSION: In an analysis of data from the National Health Insurance Research Database in Taiwan, we found that treatment for H pylori infection is associated with a significant increase in the risk for autoimmune disease, including IBD.

Diabetes-related kidney, eye, and foot disease in Taiwan: An analysis of nationwide data from 2005 to 2014.

BACKGROUND/PURPOSE: Patients with diabetes have a higher risk of developing chronic complications and cause a huge burden to the public health care system as well as on patients and their families. We studied these diabetic complications about kidney, eye and peripheral vascular diseases to understand their prevalence and distributions in a national survey. METHODS: We analyzed diabetic complications using National-Health-Insurance claims filed from 2005 to 2014. We used this database to evaluate their developments of kidney, eye, and peripheral vascular diseases according to the International-Classification-of-Diseases, Ninth Revision using clinical modification diagnosis codes. RESULTS: The prevalence of diabetic kidney disease (DKD) significantly increased from 10.49% to 17.92% from 2005 to 2014. The prevalence rate of diabetic foot significantly decreased from 1.34% to 1.05% from 2005 to 2014, and the rate of severe infection also significantly decreased from 50.69% to 45.85%. The amputation rate significantly decreased from 24.91% to 17.47% among all patients with diabetic foot. CONCLUSION: In this study, the trends in DKD and dialysis prevalence were similar to those of the 2012 report. The rate of increase in dialysis prevalence is lower in this study than in the 2012 report. The prevalence of diabetic foot, severe infection, and amputation in this report exhibited significantly decreasing trends. This improvement may be attributable to care from multidisciplinary teams. We should dedicate more resources to our prevention program of DKD and retinopathy to further improve outcomes in the future.

Statin therapy prevents the onset of Parkinson disease in patients with diabetes.

OBJECTIVE: We studied the association between the statin dosage and the risk of Parkinson disease (PD) in diabetic patients in Taiwan. METHODS: One million patients were randomly sampled from a National Health Insurance (NHI) database and followed from 2001 to 2008. Diabetic patients were screened by diagnosis of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and statin dosage was determined according to the NHI pharmacy database. PD was diagnosed on the basis of ICD-9-CM codes and anti-Parkinson medication use. Statin users was classified by statin dose-duration-day > 28 and matched with nonusers of statins using a coarsened exact matching method. There were 50,432 patients, and half of them were statin users. We examined the risk of PD between statin users and nonusers of statins and further tested the trends of the relative risk between the statin dosage and PD. RESULTS: The PD incidence rate was lower in statin users than in nonusers of statins. The crude hazard ratio of PD incidence in statin users was 0.65 (95% confidence interval [CI] = 0.57-0.74) in females and 0.60 (95% CI = 0.51-0.69) in males compared with nonusers of statins. After Cox regression analysis, all statins except lovastatin exerted protective effects on PD incidence and had a significant dose-dependent trend. INTERPRETATION: In Taiwanese diabetic patients, the risk of PD is lower in statin users than in nonusers of statins. Statin users, except lovastatin users, are dose-dependently associated with a decreased incidence of PD compared with nonusers of statins. This finding provides a new indication for statin beyond lipid control and cardiovascular events in diabetic patients. Ann Neurol 2016;80:532-540.

The association of obstructive sleep apnea and renal outcomes-a systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to summarize the association of obstructive sleep apnea (OSA) with renal outcome. METHODS: Our study followed the PRISMA guidelines. Two independent reviewers searched for relevant articles in the databases of Pubmed, the Web of Science and CENTRAL, and conducted study selection and quality assessment. A random-effect model was used to estimate the effects. RESULTS: total of 1240 articles were initially identified (Pubmed = 568, Web of Science = 640, CENTRAL = 32). After removal of duplicate articles (n = 415) and irrelevant articles (n = 788), 37 were selected for full-text review, and 18 were finally included in the analysis. Overall, patients diagnosed with OSA were found to have a higher odds ratio (OR) of a poorer renal outcome, with a pooled OR of 1.77 (95% C.I.: 1.37­2.29). The significant association between OSA and a poorer renal outcome was not affected by the medical condition of diabetes mellitus (DM). In addition, we found that OSA was consistently associated with higher albuminuria/proteinuria and a lower estimated glomerular filtration rate (eGFR), with a pooled OR of 1.84 (95% C.I.: 1.24­2.73) and 1.60 (95% C.I.: 1.19­2.16), respectively. A greater OSA severity was also found to be related to a higher OR, with a mild group OR of 1.45 (95% C.I.: 1.19­1.77) and a moderate and severe group OR of 2.39 (95% C.I.: 1.96­2.90). CONCLUSIONS: Our study demonstrated that OSA is significantly associated with poorer renal function.

Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved.

Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. "Stimulated by retinoic acid 6" (STRA6), one retinol-binding protein 4 receptor, was recently identified to regulate retinoid homeostasis. Here, we observed that L5 suppressed STRA6 cascades [STRA6, cellular retinol-binding protein 1 (CRBP1), RARs, retinoid X receptor α, and retinol, RA], but L5 simultaneously induced apoptosis and fibrosis (TGFß1, Smad2, collagen 1, hydroxyproline, and trichrome) in kidneys of L5-injected mice and L5-treated renal tubular cells. These L5-induced changes of STRA6 cascades, renal apoptosis, and fibrosis were reversed in kidneys of LOX1(-/-) mice. LOX1 RNA silencing and inhibitor of c-Jun N-terminal kinase and p38MAPK rescued the suppression of STRA6 cascades and apoptosis and fibrosis in L5-treated renal tubular cells. Furthermore, crbp1 gene transfection reversed downregulation of STRA6 cascades, apoptosis, and fibrosis in L5-treated renal tubular cells. For mimicking STRA6 deficiency, efficient silencing of STRA6 RNA was performed and was found to repress STRA6 cascades and caused apoptosis and fibrosis in L1-treated renal tubular cells. In summary, this study reveals that electronegative L5 can cause kidney apoptosis and fibrosis via the suppression of STRA6 cascades, and implicates that STRA6 signaling may be involved in dyslipidemia-mediated kidney disease.

Association of Serum Uric Acid Concentration with Diabetic Retinopathy and Albuminuria in Taiwanese Patients with Type 2 Diabetes Mellitus.

Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN) during their lifetime. In clinical studies, serum uric acid concentration has been found to be associated with DR and DN. The goal of this study was to evaluate the relationship between the increases in serum uric acid level and the severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded serum uric acid concentration, the severity of DR, and the severity of albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385 patients with type 2 DM. In multivariate logistic regression analysis, a high uric acid concentration was a risk factor for albuminuria (odds ratio (OR), 1.227; 95% confidence interval (CI) = 1.015-1.482; p = 0.034) and DR (OR, 1.264; 95% CI = 1.084-1.473; p = 0.003). We also demonstrated that there was a higher concentration of serum uric acid in the patients with more severe albuminuria and DR. In conclusion, an increased serum uric acid level was significantly correlated with the severity of albuminuria and DR in Taiwanese patients with type 2 DM.

Statin, calcium channel blocker and Beta blocker therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes.

BACKGROUND: It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether the strong association between tuberculosis and diabetes mellitus is independent from the influence of hypertension and dyslipidemia, and its treatment in elderly Taiwanese patients. METHODS: A total of 27,958 patients aged more than 65 years were identified from the National Health Insurance Research Database (NIHRD) in 1997 and were followed from 1998 to 2009. The demographic characteristics between the patients with and without diabetes were analyzed using the χ2 test. A total of 13,981 patients with type 2 diabetes were included in this study. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risk of tuberculosis. RESULTS: After adjusting for age, sex, other co-morbidities and medications, calcium channel blocker, beta blocker and statin users had a lower independent association, with risk ratios of 0.76 (95% CI, 0.58-0.98), 0.72 (95% CI, 0.58-0.91) and 0.76 (95% CI, 0.60-0.97), respectively. CONCLUSION: Calcium channel blocker, beta blocker and statin therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes.

Diabetes mellitus increases severity of thrombocytopenia in dengue-infected patients.

BACKGROUND: Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. METHODS: We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. RESULTS: Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54±51.69 vs. 86.58±63.4 (p≤0.001), 43.98±44.09 vs. 64.52±45.06 (p=0.002), 43.86±35.75 vs. 62.72±51.2 (p=0.012)). Diabetes mellitus, death, dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF) and increased glutamic-pyruvate transaminase (GPT) levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression ß of -13.981 (95% confidence interval (CI) -27.587, -0.374), -26.847 (95% CI -37.562, -16.132), and 0.054 (95% CI 0.015, 0.094) respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression ß of -2.947 (p=0.004), 2.801 (p=0.005), and -3.568 (p≤0.001), respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients. CONCLUSIONS: Dengue patients with diabetes tended to have more severe thrombocytopenia and were more likely to have DHF/DSS. Older age, hypoalbuminemia, and hypertriglyceridemia were independently associated with more severe thrombocytopenia in dengue patients.

Increased unbound retinol-binding protein 4 concentration induces apoptosis through receptor-mediated signaling.

The increase of apo-/holo-retinol-binding protein 4 (RBP4) concentrations has been found in subjects with renal dysfunction and even in diabetic patients with microalbuminuria. Holo-RBP4 is recognized to possess cytoprotective function. Therefore, we supposed that the relative increase in apo-RBP4 might induce cell damage. In this study, we investigated the signal transduction that activated apoptosis in response to the increase of apo-/holo-RBP4 concentration. We found that increase of apo-/holo-RBP4 concentration ratio delayed the displacement of RBP4 with "stimulated by retinoic acid 6" (STRA6), enhanced Janus kinase 2 (JAK2)/STAT5 cascade, up-regulated adenylate cyclase 6 (AC6), increased cAMP, enhanced JNK1/p38 cascade, suppressed CRBP-I/RARα (cellular retinol-binding protein/retinoic acid receptor α) expression, and led to apoptosis in HK-2 and human umbilical vein endothelial cells. Furthermore, STRA6, JAK2, STAT5, JNK1, or p38 siRNA and cAMP-PKA inhibitor reversed the repression of CRBP-I/RARα and apoptosis in apo-RBP4 stimulation. In conclusion, this study indicates that the increase of apo-/holo-RBP4 concentration may influence STRA6 signaling, finally causing apoptosis.

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.

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.

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.

Diabetes-related kidney, eye, and foot disease in Taiwan: an analysis of the nationwide data for 2000-2009.

BACKGROUND/PURPOSE: Diabetes is one of the leading causes of dialysis, blindness, and amputation worldwide. However, the prevalence of diabetes-related kidney, eye, and foot diseases has not been investigated in national surveys. METHODS: In this study, we reviewed data sets of the National Health Insurance claims for the years 2000-2009. In 2009, the total population of Taiwan was 23 million. We de-identified the data and then analyzed them on inpatients and outpatients with diabetes mellitus, kidney diseases, eye diseases, peripheral vascular diseases (PVDs), and diabetic foot according to the International Classification of Diseases, 9(th) Revision with Clinical Modification diagnosis codes. RESULTS: The prevalence of diabetic nephropathy increased from 13.32% in 2000 to 15.42% in 2009. The corresponding diabetes dialysis rate increased from 1.5% to 2.46% during the same period (p < 0.001). The prevalence rates of retinopathy and PVD also increased (from 6.17% to 8.91%; p = 0.002 and from 1.87 to 2.47; p < 0.001, respectively). More than 94% of the patients treated for diabetic foot in the hospital had an associated foot infection. The prevalence of in-hospital diabetic foot decreased from 1.68% to 1.02% during the years 2000-2009 (p < 0.001), while the rates of lower extremity amputation as the treatment outcome did not show improvement (mean amputation rate: 28.35%). CONCLUSION: During the years 2000-2009, patients with diabetes in Taiwan had an increased risk for kidney, eye, and PVDs. Multidisciplinary teams need to be set up for the treatment of complications related to diabetic foot, and preventions programs that are specifically designed to target these complications should now be made mandatory.

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.

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.