Using the Diabetes Care System for a County-Wide Hepatitis C Elimination: An Integrated Community-Based Shared Care Model in Taiwan.

INTRODUCTION: Despite the serious risks of diabetes with hepatitis C virus (HCV) infection, this preventable comorbidity is rarely a priority for HCV elimination. We aim to examine how a shared care model could eliminate HCV in patients with diabetes (PwD) in primary care. METHODS: There were 27 community-based Diabetes Health Promotion Institutes in each township/city of Changhua, Taiwan. PwD from these institutes from January 2018 to December 2020 were enrolled. HCV screening and treatment were integrated into diabetes structured care through collaboration between diabetes care and HCV care teams. Outcome measures included HCV care continuum indicators. Township/city variation in HCV infection prevalence and care cascades were also examined. RESULTS: Of the 10,684 eligible PwD, 9,984 (93.4%) underwent HCV screening, revealing a 6.18% (n = 617) anti-HCV seroprevalence. Among the 597 eligible seropositive individuals, 507 (84.9%) completed the RNA test, obtaining 71.8% positives. Treatment was initiated by 327 (89.8%) of 364 viremic patients, and 315 (86.5%) completed it, resulting in a final cure rate of 79.4% (n = 289). Overall, with the introduction of antivirals in this cohort, the prevalence of viremic HCV infection dropped from 4.44% to 1.34%, yielding a 69.70% (95% credible interval 63.64%-77.03%) absolute reduction. DISCUSSION: Although HCV prevalence varied, the care cascades achieved consistent results across townships/cities. We have further successfully implemented the model in county-wide hospital-based diabetes clinics, eventually treating 89.6% of the total PwD. A collaborative effort between diabetes care and HCV elimination enhanced the testing and treatment in PwD through an innovative shared care model.

The association between arterial stiffness and tongue manifestations of blood stasis in patients with type 2 diabetes.

BACKGROUND: Diabetes mellitus (DM) is a hypercoagulable state and is associated with highly increased risk of vascular complications. In the theory of traditional Chinese medicine (TCM), these vascular complications are classified as blood stasis. Diagnosis of the tongue plays an important role in TCM; a bluish tongue, petechiae, and engorged sublingual collateral vessels are manifestations of blood stasis. This study aimed to characterize the tongue manifestations of blood stasis and derive a relationship between blood stasis and vascular disorders in patients with type 2 DM. METHOD: We conducted a cross-sectional study of 140 patients with type 2 DM, and compared demography, laboratory, physical examination, ankle brachial index(ABI), brachial-ankle pulse wave velocity (ba-PWV), and tongue manifestation datas. An automatic tongue diagnosis system was used to capture tongue images and characterize clinical tongue manifestations. RESULTS: A bluish or petechiae tongue was assoicated with a significant decrease in high-density lipoprotein level, and bluish tongue was associated with significant increase in blood triglyceride in patients with type 2 DM. On assessing arterial stiffness, patients with a petechiae tongue had a higher ba-PWV for both sides (L:1938.41 ± 469.54 cm/sec v.s.1723.99 ± 302.16, p = 0.02; R:1937.28 ± 405.55 v.s.1741.99 ± 325.82, p = 0.03). CONCLUSION: Blood stasis, particularly a tongue with petechiae, may be associated with arterial stiffness in patients with type 2 DM. Furthermore, tongue diagnosis could detect blood stasis relevant to DM and could serve as a feasible predictor for DM.

Analysis of target organs of Houttuynia cordata: A study on the anti-inflammatory effect of upper respiratory system.

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb. (HC) is a traditional anti-pyretic herb that is classified as the lung meridian in traditional Chinese medicine. However, no articles have explored the main organs responsible for the anti-inflammatory activities of HC. AIM OF THE STUDY: The aim of the study was to investigate the meridian tropism theory of HC in lipopolysaccharide (LPS)-induced pyretic mice, as well as to identify the underlying mechanisms. MATERIALS AND METHODS: Transgenic mice carrying the luciferase gene driven by nuclear factor-κB (NF-κB) were intraperitoneally injected with LPS and orally administered standardized concentrated HC aqueous extract. The phytochemicals present in the HC extract were analyzed using high-performance liquid chromatography. In vivo and ex vivo luminescent imaging from transgenic mice was used to investigate the meridian tropism theory and anti-inflammatory effects of HC. Microarray analysis of gene expression patterns was used to elucidate the therapeutic mechanisms of HC. RESULTS: HC extract was found to contain phenolic acids, such as protocatechuic acid (4.52%) and chlorogenic acid (8.12%), as well as flavonoids like rutin (2.05%) and quercitrin (7.73%). The bioluminescent intensities induced by LPS in the heart, liver, respiratory system, and kidney were significantly suppressed by HC, while the maximal decrease (about 90% reduction) of induced luminescent intensity was observed in the upper respiratory tract. These data suggested that upper respiratory system might be the target for HC anti-inflammatory abilities. HC affected the processes involved in innate immunity, such as chemokine-mediated signaling pathway, inflammatory response, chemotaxis, neutrophil chemotaxis, and cellular response to interleukin-1 (IL-1). Moreover, HC significantly reduced the proportions of p65-stained cells and the amount of IL-1ß in trachea tissues. CONCLUSION: Bioluminescent imaging coupled with gene expression profile was used to demonstrate the organ selectivity, anti-inflammatory effects, and therapeutic mechanisms of HC. Our data demonstrated for the first time that HC displayed lung meridian-guiding effects and exhibited great anti-inflammatory potential in the upper respiratory tract. The NF-κB and IL-1ß pathways were associated with the anti-inflammatory mechanism of HC against LPS-provoked airway inflammation. Moreover, chlorogenic acid and quercitrin might be involved in the anti-inflammatory properties of HC.

Association between smoking and glycemic control in men with newly diagnosed type 2 diabetes: a retrospective matched cohort study.

BACKGROUND: Longitudinal data on the association between smoking and glycemic control in men with newly diagnosed type 2 diabetes (T2DM) is scarce. Therefore, this study aimed to examine the extent of the association between smoking and glycemic control in this population. METHODS: The retrospective cohort study identified 3044 eligible men with T2DM in a medical centre in Taiwan between 2002 and 2017. Smokers (n = 757) were matched 1:1 with non-smokers using propensity score-matching. All of them were followed for one year. Glycated haemoglobin (HbA1c) levels were measured at 0, 3, 6, 9, and 12 months after enrolment. Generalised estimating equations were used to assess smoking status-by-time interaction to determine the difference in HbA1c reduction between the two cohorts. All analyses were performed in 2020. RESULTS: The estimated maximal difference in HbA1c reduction between smokers and non-smokers was 0.33% (95% CI, 0.05-0.62%) at 3 months of follow-up. For patients with body mass index (BMI) <25 kg/m2, the difference in HbA1c reduction between smokers and non-smokers was much larger (0.74%, 95% CI, 0.35-1.14%) than in those with a higher BMI. CONCLUSIONS: Our findings show that smoking was independently associated with unfavourable glycemic control among men with newly diagnosed T2DM, and such a detrimental association could be stronger in men with a lower BMI.

The novel anti-inflammatory activity of mcIRBP from Momordica charantia is associated with the improvement of diabetic nephropathy.

Diabetic nephropathy is an inflammatory immune disorder accompanying diabetes. A trypsin inhibitor of Momordica charantia, mcIRBP, is an abundant 68 amino acid residue protein that interacts with the insulin receptor. Here the long-term effects of mcIRBP on the improvement of diabetic nephropathy were determined. Type 2 diabetic mice (db/db) were given mcIRBP administered orally for 12 consecutive weeks. Histological changes relating to the kidney were evaluated using Periodic Acid Schiff and Sirius Red staining. The mcIRBP-affected gene expression profile in the kidney was determined using RNA-Seq. The renoprotective mechanism of mcIRBP was elucidated based on ex vivo imaging and immunohistochemistry staining. Data showed that the administration of mcIRBP significantly decreased fasting blood glucose and glycated hemoglobin A1c (HbA1c) levels by 61% and 27.92%, respectively, suggesting that mcIRBP exhibited HbA1c-lowering abilities in diabetic mice. RNA sequencing (RNA-Seq) analysis showed that the majority of the mcIRBP-affected biological pathways were associated with inflammation and immunity, and the nuclear factor-κB (NF-κB) signaling pathway was significantly affected by mcIRBP. Ex vivo imaging showed that mcIRBP significantly decreased NF-κB-driven bioluminescence in the kidney by 46 ± 23%. The levels of the renal function indices, Evans blue dye content, fibrosis lesions, and cytokine expression were significantly decreased by mcIRBP, suggesting that mcIRBP improved vascular leakage and the pathological and inflammatory characteristics of diabetic nephropathy. This is the first study reporting that, in addition to blood glucose regulation, mcIRBP can act as a novel renoprotective and anti-inflammatory polypeptide, thereby improving diabetic nephropathy in db/db mice. In addition, this study suggested that there was a potential medicinal use of mcIRBP for the management of diabetes and its complications.

Correction: The novel anti-inflammatory activity of mcIRBP from Momordica charantia is associated with the improvement of diabetic nephropathy.

Correction for 'The novel anti-inflammatory activity of mcIRBP from Momordica charantia is associated with the improvement of diabetic nephropathy' by Pei-Yung Liao et al., Food Funct., 2022, DOI: 10.1039/d1fo03620c.

A gastro-resistant peptide from Momordica charantia improves diabetic nephropathy in db/db mice via its novel reno-protective and anti-inflammatory activities.

Diabetic nephropathy (DN), a principal diabetic microvascular complication, is a chronic inflammatory immune disorder. A gastro-resistant peptide mcIRBP-9 from Momordica charantia has shown modulation of blood glucose homeostasis in diabetic mice. Here we conducted a long-term experiment to evaluate the therapeutic effects and mechanisms of mcIRBP-9 on DN. Type 2 diabetic mice (db/db mice) were orally given mcIRBP-9 once daily for 12 consecutive weeks. The amelioration of DN was evaluated by renal function indexes, vascular leakage, and pathological lesions. Possible effective mechanisms of mcIRBP-9 on DN were analyzed by gene expression profiles. A pharmacokinetic study in rats was carried out to evaluate the oral bioavailability of mcIRBP-9. Our data showed that mcIRBP-9 was able to enter systemic circulation in rats after oral administration. In comparison with mock, long-term administration of mcIRBP-9 significantly decreased blood glucose (572.25 ± 1.55 mg dL-1vs. 213.50 ± 163.39 mg dL-1) and HbA1c levels (13.58 ± 0.30% vs. 8.23 ± 2.98%) and improved the survival rate (85.7% vs. 100%) in diabetic mice. mcIRBP-9 ameliorated DN by reducing renal vascular leakage and histopathological changes. mcIRBP-9 altered the pathways involved in inflammatory and immune responses, and the nuclear factor-κB played a central role in the regulation of mcIRBP-9-affected pathways. Moreover, mcIRBP-9 improved the inflammatory characteristic of DN in diabetic and non-diabetic mice. In conclusion, mcIRBP-9 displayed a novel anti-inflammatory activity and exhibited a reno-protective ability in addition to controlling the blood glucose and HbA1c levels. These findings suggested the role of mcIRBP-9 from M. charantia as a nutraceutical agent for diabetes and subsequent DN.

Self-monitoring of blood glucose in association with glycemic control in newly diagnosed non-insulin-treated diabetes patients: a retrospective cohort study.

The benefits of self-monitoring of blood glucose (SMBG) on glycemic control among type 2 diabetes (T2DM) patients not receiving insulin remains controversial. This study aimed to examine the association between SMBG and glycemic control in these patients. This retrospective longitudinal study enrolled 4987 eligible patients from a medical center in Taiwan. Data were collected from electronic medical records at 0 (baseline), 3, 6, 9, and 12 (end-point) months after enrollment. Patients were assigned to the early SMBG group or to the non-user group depending on whether they performed SMBG at baseline. Differences in glycated hemoglobin (HbA1c) reduction between groups at each time-point were assessed using SMBG group-by-time interaction in generalized estimating equations models, which were established using backward elimination method for multivariate regression analysis. Subgroup analyses for patients using non-insulin and insulin secretagogues were performed additionally. The estimated maximal difference in HbA1c reduction between groups (early SMBG users vs. non-users) was 0.55% at 3 months. Subgroup analyses showed maximal differences of 0.61% and 0.52% at 3 months in the non-insulin and insulin secretagogues groups, respectively. SMBG group-by-time interaction was statistically significant at 3 months and lasted for 12 months. The finding suggests that performing SMBG at disease onset was positively associated with better glycemic control in newly diagnosed non-insulin-treated T2DM patients, regardless whether non-insulin secretagogues or insulin secretagogues were used.

Predictors of treatment failure during the first year in newly diagnosed type 2 diabetes patients: a retrospective, observational study.

BACKGROUND: Diabetes patients who fail to achieve early glycemic control may increase the future risk of complications and mortality. The aim of the study was to identify factors that predict treatment failure (TF) during the first year in adults with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: This retrospective cohort study conducted at a medical center in Taiwan enrolled 4,282 eligible patients with newly diagnosed T2DM between 2002 and 2017. Data were collected from electronic medical records. TF was defined as the HbA1c value >7% at the end of 1-year observation. A subgroup analysis of 2,392 patients with baseline HbA1c ≥8% was performed. Multivariable logistic regression analysis using backward elimination was applied to establish prediction models. RESULTS: Of all study participants, 1,439 (33.6%) were classified as TF during the first year. For every 1% increase in baseline HbA1c, the risk of TF was 1.17 (95% CI 1.15-1.20) times higher. Patients with baseline HbA1c ≥8% had a higher rate of TF than those with HbA1c <8% (42.0 vs 23.0%, p < 0.001). Medication adherence, self-monitoring of blood glucose (SMBG), regular exercise, gender (men), non-insulin treatment, and enrollment during 2010-2017 predicted a significant lower risk of TF in both of the primary and subgroup models. CONCLUSIONS: Newly diagnosed diabetes patients with baseline HbA1c ≥8% did have a much higher rate of TF during the first year. Subgroup analysis for them highlights the important predictors of TF, including medication adherence, performing SMBG, regular exercise, and gender, in achieving glycemic control.

A convenient diagnostic tool for discriminating adult-onset glutamic acid decarboxylase antibody-positive autoimmune diabetes from type 2 diabetes: a retrospective study.

BACKGROUND: The glutamic acid decarboxylase antibody (GADA) test, commonly used to diagnose autoimmune diabetes, is not cost-effective in areas of low prevalence. The aim of this study was to develop a convenient tool to discriminate adult-onset GADA-positive autoimmune diabetes from type 2 diabetes (T2DM) in patients with newly diagnosed diabetes. METHODS: This retrospective cross-sectional study, conducted at Changhua Christian Hospital in Taiwan, collected electronic medical record data from January 2009 to December 2018. Patients were divided into a case group (GADA+, n = 152) and a reference group (T2DM, n = 358). Variables that differed significantly between the groups were subjected to receiver operator characteristic analysis to establish cutoff values. Discriminant function analysis was then employed to discriminate the two groups. RESULTS: At the onset of diabetes, the GADA+ group was younger, with lower body mass index (BMI), higher hemoglobin A1c (HbA1c), higher high-density lipoprotein cholesterol (HDL-C), and lower total cholesterol and triglycerides (TG). Five major factors were identified to form the linear discriminant functions: BMI, age at onset, TG, HDL-C, and HbA1c. BMI < 23 kg/m2 was the most important factor, followed by TG < 98 mg/dL, HDL-C ≥ 46 mg/dL, age at onset < 30 years, and HbA1c ≥ 8.6%. The overall accuracy of the linear discriminant functions was 87.1%, with 84.2% sensitivity and 88.3% specificity. CONCLUSIONS: Routine tests in diabetes care were used to establish a convenient, low-cost tool that may assist in the early identification of adult-onset GAD+ autoimmune diabetes in clinical practice.

The influence of I-131 therapy on FDG uptake in differentiated thyroid cancer.

OBJECTIVE: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) [or PET/computed tomography (CT)] is more likely to show false-negative results when it is performed shortly after chemotherapy and/or radiotherapy because of "metabolic stunning". The present study aimed to evaluate the influence of I-131 therapy on FDG uptake and the detection of recurrence or metastasis of differentiated thyroid cancer (DTC). METHODS: We retrospectively enrolled 16 consecutive FDG-PET/CT studies which had been performed in patients with DTC with elevated thyroglobulin (TG) but negative I-131 whole-body scan. All studies were performed under L: -thyroxine suppression. The patients were divided into groups A and B for PET/CT performed within 4 months of I-131 therapy or no such therapy, respectively. Each lesion identified on PET/CT was characterized using a 5-point scale by visual analysis: 0 = definitely benign, 1 = probably benign, 2 = equivocal, 3 = probably malignant, and 4 = definitely malignant. The maximum standardized uptake value (SUV max) in each lesion was also measured for semiquantitative analysis. We compared the visual grading and SUV max of the lesion of highest FDG uptake between groups A and B. RESULTS: For visual analysis, group B had significantly more patients with an uptake score of 3 or 4 than group A (80% vs. 17%, P = 0.01). In addition, there were significantly more equivocal results from group A than from group B (67% vs. 10%, P = 0.02). If the patients with the highest uptake scores of 2, 3, and 4 were considered to be positive for local recurrence or metastasis, there would be no significant difference between the positive rates of groups A and B (83% vs. 90%, P = 0.7). However, the mean SUV max of positive results was significantly lower for group A than for group B (3.1 +/- 0.9 and 6.6 +/- 3.5, respectively, P = 0.02). CONCLUSIONS: The preliminary results suggested that FDG uptake in DTC may be negatively influenced by I-131 therapy within 4 months, resulting in lower FDG uptake and more equivocal results. Further studies are necessary to determine whether it is secondary to "metabolic stunning" caused by I-131 therapy.

Metabolic control with insulin pump therapy: preliminary experience.

BACKGROUND: The benefits of insulin pump therapy on the metabolic control of both type 1 and type 2 diabetes have been reported. Such reports have prompted our interest to investigate the long-term metabolic effects of insulin pump therapy at our institution. METHODS: We retrospectively analyzed the management of type 1 and type 2 diabetic patients who began extended insulin pump therapy at Changhua Christian Hospital between November 2004 and October 2007. One-way ANOVA and post hoc analysis were used to compare baseline glycosylated hemoglobin (HbA1C) values with subsequent values. RESULTS: We studied 12 patients who were on continuous subcutaneous insulin infusion (CSII) therapy at the time of data collection. Mean duration of CSII therapy was 2.3 years. A reduction in HbA1C was found after administering CSII, which was sustained after 1, 2 and 3 years of therapy (7.0%, 6.7% and 6.6%, respectively), with statistical significance (p<0.05). No incidence of severe hypoglycemia or diabetic ketoacidosis occurred during the treatment period. CONCLUSION: Our preliminary experience demonstrated the effectiveness of insulin pump therapy for both type 1 and type 2 diabetic patients. The reduction in their HbA1C values was both statistically and clinically significant. This treatment should be considered for patients poorly controlled by subcutaneous insulin injection therapy.

Nailfold capillary abnormalities are associated with type 2 diabetes progression and correlated with peripheral neuropathy.

Diabetes mellitus (DM) is associated with a state of chronic hyperglycemia with a highly increased risk of vascular complications. The current study aimed to investigate microcirculation abnormalities in patients with type 2 DM and those with pre-DM using nailfold videocapillaroscopy (NVC) and evaluate the possible correlation with microvascular complications.A total of 115 patients with type 2 DM, 41 patients with pre-DM, and 37 healthy subjects without diabetes were enrolled. All subjects underwent NVC to evaluate capillary density, length, morphology, distribution, presence of enlarged loops or hemorrhages, and blood flow. NVC score was used to quantitate the aforementioned characteristics.Patients with type 2 DM showed significantly increased alterations including reduced capillary length (29.6%), irregular distribution (35.7%), and abnormal morphology (59.1%), while the corresponding NVC scores were comparable to those of control subjects. In addition, subjects with pre-DM had a significantly higher NVC score and greater alterations in distribution (26.8%) and morphology (48.8%) than control subjects. NVC score was positively correlated with diabetic peripheral neuropathy (DPN) and the number of microvascular complications.NVC identified a high frequency of microcirculation abnormalities in subjects with pre-DM or type 2 DM compared to those in the control group. NVC score was also capable of detecting microvascular complications in patients with type 2 DM and was correlated with DPN and the number of microvascular complications.

Diabetes with pyogenic liver abscess--A perspective on tongue assessment in traditional Chinese medicine.

BACKGROUND: This novel study provides a time series analysis of tongue features extracted from a diabetic patient with pyogenic liver abscess (PLA), treated with the integration of western medicine and traditional Chinese medicine (TCM). The features, namely, tongue color, tongue fur thickness and fur color, identified from a series of tongue images taken every two days, exhibit significant transitions matching closely with the progression of disease. These tongue features could serve as effective, non-intrusive indices for different progression stages of diabetes with PLA. CASE PRESENTATION: A 76-year-old male diabetic patient was admitted for hyperglycemic hyperosmolar state. Intermittent fever and abdominal discomfort were noted. After performing abdominal computed tomography and laboratory studies, the results indicated pyeogenic liver abscess, Klebsiella pneumoniae ssp. pneumoniae related. As PLA progressed, the patient suffered spiking fever and right upper abdominal pain. Tongue examination revealed features with red tongue, white-yellow and thick fur. After receiving pigtail catheter drainage, the fever subsided and the pus-like fluid was drained smoothly. During the course of this process, gradually dwindled tongue fur witnessed through periodic tongue examination coincides consistently with laboratory data, namely, body temperature, fasting plasma glucose and plasma glucose level gathered. CONCLUSION: This is the first time series analysis of applying tongue examination to the progression of a specific disease. Through a series of tongue images taken periodically, tongue color, tongue fur thickness and fur color are identified to closely linked to the progression of diabetes with PLA, as indicated by data gathered through means of plasma glucose and abdominal sonographic follow-ups. Based on this promising finding, our future study will further extend the application of tongue assessment to evaluate the tongue characteristics of diabetic patients.

Efficacy and safety of valsartan in hypertensive Taiwanese patients: post-marketing surveillance study.

OBJECTIVE: To evaluate the efficacy and safety of valsartan in Taiwanese patients with essential hypertension. METHODS: This 12-week multi-center, open-label, observational, post-marketing surveillance study enrolled 2046 hypertensive patients who were prescribed valsartan 80 or 160 mg as monotherapy or in combination with other antihypertensives based on clinical judgment. The primary endpoint was the incidence rate of dizziness with valsartan 160 mg monotherapy or combination therapy at Week 4. Secondary endpoints included the blood-pressure-lowering efficacy and the overall safety and tolerability of valsartan at Weeks 4 and 12. RESULTS: The monotherapy and combination groups had comparable baseline characteristics. At Week 4, monotherapy was found non-inferior to combination for incidence rate of dizziness (monotherapy, 9.25%; combination, 10%; difference in incidence of dizziness, 0.75%; 95% CI - 0.61% to 2.12%; non-inferiority margin, -1.33%;WaldTest approach). Greater blood pressure (BP) reduction was noted atWeek 12 than atWeek 4.The antihypertensive effect was greater with combination therapy and the 160-mg dose. BP control (systolic <140 mmHg or diastolic <90 mmHg) was achieved in 80-90% patients.Valsartan was well tolerated; most commonly reported adverse events included dizziness, headache, constipation and cough. CONCLUSION: Valsartan is an effective treatment option for essential hypertension in Taiwanese patients.