Linagliptin and cardiovascular outcomes in type 2 diabetes after acute coronary syndrome or acute ischemic stroke.

BACKGROUND: The cardiovascular safety and efficacy of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-world cohort study was to evaluate the cardiovascular outcomes of linagliptin in patients with T2DM after ACS or AIS. METHODS: An open observational noncrossover retrospective cohort study was conducted between June 1, 2012 and December 31, 2013 utilizing Taiwan National Health Insurance Research Database. A total of 1203 patients with T2DM after ACS or AIS were selected as the study cohort. Cardiovascular safety and efficacy of linagliptin were evaluated by comparing outcomes of 401 subjects receiving linagliptin after ACS or AIS to 802 matched control subjects not receiving any incretin-based therapy after ACS or AIS. The primary composite outcome included cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke. RESULTS: The primary composite outcome after 15-month follow-up was 7% (28 patients) in the linagliptin group compared with 6.1% (49 patients) in the control group [hazard ratio (HR) 1.06; 95% confidence interval (CI) .66-1.68]. The linagliptin group also had similar risks of all-cause mortality, hospitalization for heart failure, percutaneous coronary intervention and coronary artery bypass grafting compared to the control group in terms of the secondary outcomes. CONCLUSIONS: In T2DM patients after ACS or AIS, treatment with linagliptin was not associated with increased risks of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke.

Novel and Advanced Ultrasound Techniques for Thyroid Thermal Ablation.

Thyroid radiofrequency ablation and microwave ablation are widely adopted minimally invasive treatments for diverse thyroid conditions worldwide. Fundamental skills such as the trans-isthmic approach and the moving shot technique are crucial for performing thyroid ablation, and advanced techniques, including hydrodissection and vascular ablation, improve safety and efficacy and reduce complications. Given the learning curve associated with ultrasound-guided therapeutic procedures, operators need training and experience. While training models exist, limited attention has been given to ultrasound maneuvers in ablation needle manipulation. This article introduces two essential maneuvers, the zigzag moving technique and the alienate maneuver, while also reviewing the latest ultrasound techniques in thyroid ablation, contributing valuable insights into this evolving field.

Prognostic significance of pituitary tumour-transforming gene-binding factor (PBF) expression in papillary thyroid carcinoma.

BACKGROUND: Pituitary tumour-transforming gene (PTTG)-binding factor (PBF), originally known as PTTG1 interacting protein (PTTG1IP), has been found to be significantly increased in well-differentiated thyroid cancer and independently associated with early tumour recurrence. OBJECTIVE: To assess the prognostic significance of PBF expression in a large cohort of papillary thyroid carcinoma (PTC) patients with a long-term follow-up. DESIGN AND PATIENTS: Retrospective analysis of PBF expression in PTC cases at different stages and correlate it with various clinicopathological parameters and patient survival. Subjects included 153 patients who received a thyroid operation for PTC at Chang Gung Memorial Hospital between 1991 and 2000. All patients had a complete follow-up till the end of 2010. MEASUREMENTS: Immunohistochemical study for PBF expression on tissue sections from tumour specimens. Bond automated machine (Leica Microsystems, Germany) with a polyclonal rabbit anti-PBF antibody (LifeSpan BioSciences, LS-C118942, Seattle, WA, USA) was used. SPSS 13.0 for Windows (SPSS Inc, Chicago, IL, USA) was used for all statistical analyses. RESULTS: High PBF expression was significantly correlated with age (P = 0·0298), distant metastases at diagnosis (P = 0·0139), tumour multicentricity (P = 0·0035), TNM stage (P = 0·0103), locoregional recurrence (P = 0·0410) and disease-specific mortality (P = 0·0064). The expression level of PBF was significantly correlated with disease-specific survival (P = 0·0065). Cox regression analysis showed that age, tumour size and PBF expression were independent prognostic indicators (P = 0·0097, P = 0·0021 and P = 0·0179). CONCLUSION: PBF expression may be a promising biomarker for prognostic and therapeutic purpose. More large-scale studies are needed to clarify its potential usefulness.

Corrigendum: Ankle-Brachial Index Is Independently Associated With Cardiovascular Outcomes and Foot Ulcers in Asian Patients With Type 2 Diabetes Mellitus.

[This corrects the article DOI: 10.3389/fendo.2021.752995.].

Successful Applications of Food-Assisted and -Simulated Training Model of Thyroid Radiofrequency Ablation.

Background: Radiofrequency ablation (RFA) for benign thyroid nodules is one kind of scarless treatment for symptomatic or cosmetic benign thyroid nodules. However, how to train RFA-naive physicians to become qualified operators for thyroid RFA is an important issue. Our study aimed to introduce a successful training model of thyroid RFA. Materials and Methods: We used a food-assisted and -simulated training model of thyroid RFA. Chicken hearts were simulated into thyroid nodules, three-layer pork meats were simulated into peri-thyroid structure, and gel bottles were simulated into trachea, respectively. Successful training ablations were defined as chicken hearts that were fully cooked. After repeating training ablations of chicken hearts at least 100 times with the nearly 100% success rates for three young trainees, they served as the first assistant for the real procedures of thyroid RFA and then were qualified to perform thyroid RFA on real patients under the supervision of one experienced interventional radiologist. Results: 23 real patients who received RFA and follow-up at least 6 months after treatment were included in Linkou Chang Gung Memorial Hospital from January 1, 2020 to October 1, 2021. Three young endocrinologists performed thyroid RFA independently. The outcomes were volume reduction rate (VRR), major complications and minor complications. The median VRR at 12 months was 82.00%, two major complications were transient hoarseness, and three minor complications were wound pain. All complications were completely recovered within three days. Conclusions: For young and RFA-native physicians without any basic skills of echo-guided intervention, this food-assisted and -simulated training model of thyroid RFA was useful for medical training and education.

Regimen comprising GLP-1 receptor agonist and basal insulin can decrease the effect of food on glycemic variability compared to a pre-mixed insulin regimen.

BACKGROUND: Increasing evidence suggests that glucagon-like peptide 1 (GLP-1) receptor agonists (RA) can stabilize glycemic variability (GV) and interfere with eating behavior. This study compared the impact of insulin, GLP-1 RA, and dietary components on GV using professional continuous glucose monitoring (CGM). METHODS: Patients with type 2 diabetes underwent CGM before and after switching from a twice-daily pre-mixed insulin treatment regimen to a GLP-1 RA (liraglutide) plus basal insulin regimen. The dietary components were recorded and analyzed by a certified dietitian. The interactions between the medical regimen, GV indices, and nutrient components were analyzed. RESULTS: Sixteen patients with type 2 diabetes were enrolled in this study. No significant differences in the diet components and total calorie intake between the two regimens were found. Under the pre-mixed insulin regimen, for increase in carbohydrate intake ratio, mean amplitude of glucose excursion (MAGE) and standard deviation (SD) increased; in contrast, under the new regimen, for increase in fat intake ratio, MAGE and SD decreased, while when the protein intake ratio increased, the coefficient of variation (CV) decreased. The impact of the food intake ratio on GV indices disappeared under the GLP-1 RA regimen. After switching to the GLP-1 RA regimen, the median MAGE, SD, and CV values decreased significantly. However, the significant difference in GV between the two regimens decreased during the daytime. CONCLUSION: A GLP-1 RA plus basal insulin regimen can stabilize GV better than a regimen of twice-daily pre-mixed insulin, especially in the daytime, and can diminish the effect of food components on GV.

Evaluation of recurrence risk in patients with papillary thyroid cancer through tumor-node-metastasis staging: A single-center observational study in Taiwan.

BACKGROUND: Many patients with papillary thyroid cancer (PTC) demonstrate satisfactory outcomes. However, 8%-28% of patients with PTC show tumor recurrence, which may affect prognosis. Therefore, identifying factors associated with tumor recurrence in patients with PTC may be helpful to refine therapeutic strategies. METHODS: To identify factors associated with PTC recurrence, we retrospectively reviewed demographic features (sex and age), operation method, image character, serum thyroglobulin (Tg), accumulated radioactive iodine (I-131) therapeutic dose, I-131 uptake, and metastases at diagnosis in 829 patients with PTC. Patients were grouped into early (stage I and II; n = 698) and advanced (stage III and IV; n = 131) tumor-node-metastasis (TNM) stages. Recurrence rate, mortality rate, risk factors of recurrence, recurrent free survival and overall survival curve were compared between two groups. RESULTS: Patients in the early stage demonstrated a lower recurrence rate (7.2%) than did those in the advanced stage (28.2%, p < 0.05). The mortality rate of patients with recurrence in the advanced stage was higher than that of those in the early stage (51.4% vs. 12.0%). The major impact factors on tumor recurrence in early TNM stage were distant metastasis and lymph node metastasis, while in advanced TNM stage were distant metastasis, male gender, total thyroidectomy with limited lymph node dissection, and a high serum Tg level. CONCLUSIONS: Strategies to monitor tumor recurrence might be refined according to the TNM stages of PTC patients.

Pyogenic liver abscess caused by Pseudomonas aeruginosa: clinical analysis of 20 cases.

BACKGROUND: There are few reports of Pseudomonas aeruginosa liver abscess (PALA) in the literature, and clinical information regarding its risk factors, route of transmission, and clinical course remains limited. METHODS: The medical records of 1076 patients with pyogenic liver abscess treated at Chang Gung Memorial Hospital were reviewed. RESULTS: Twenty of the patients whose records were analyzed had PALA. Mortality was 20%. Five patients with PALA, diagnosed immediately following an intra-abdominal surgical or endoscopic procedure, were classified as group A. The latent phase for the development of PALA in this group was less than 3 weeks. The remaining 15 patients were further subgrouped into group B (n = 8), with a traceable intra-abdominal procedure, and group C (n = 7), with no history of an invasive intra-abdominal procedure. The latent period in patients in group B varied from 6 weeks to 3.7 y. The absence of multidrug resistance in P. aeruginosa isolates from group C suggests the community-acquired nature of the infection in this group. Risk factor analysis showed that the incidence of hepatobiliary co-morbidities was high in all the groups (100%, 88%, and 71% in groups A, B, and C, respectively). The rates of co-infection with human gastrointestinal tract flora were 20%, 50%, and 71% in groups A, B, and C, respectively. CONCLUSIONS: PALA may be found in subjects without conventional risk factors for P. aeruginosa infection. In addition to patients with a preceding contaminated procedure, those with hepatobiliary co-morbidities form another high-risk group for this condition.

Effects of a novel short-term continuous subcutaneous insulin infusion program evaluated by continuous glucose monitoring on young adult type 1 diabetic patients in Taiwan.

The aim of this study is to evaluate the effectiveness of blood sugar control by a short-course reinforcement program, consisting of using continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) for young adult type 1 diabetic patients. Twenty-six pump-naïve type 1 diabetic patients were successively enrolled in two years. The mean disease duration was 13 years and the mean HbA1c was 8.8 %. Initially, a 3-day course of CGM was used to evaluate the baseline glycemic status of the subjects, followed by 6-day intensive insulin adjustment by CSII therapy. Thereafter, a second course of CGM was performed to evaluate the effectiveness of our outcomes in comparison to the initial measurements. All participants received necessary education and instruction as required throughout the course of the program. The glucose variability as measured by standard deviation of plasma glucose and mean amplitude of glucose excursion decreased significantly (67.8 ± 2.7 to 52.0 ± 1.8 mg/dL and 140.4 ± 6.5 to 105.5 ± 5.3 mg/dL, p < 0.001). The hypoglycemic events noted per patient were reduced by 46.4% (p = 0.003) and occurred significantly less often during nocturnal periods (-63.2%, p = 0.002). Following the adjustment, the mean daily insulin requirement was reduced by 28.05% (from 0.82 to 0.59 IU/kg) and the new proportion of 40% as basal insulin was found. The short-term CSII program provided significant improvement in blood sugar control for type 1 diabetic patients, by reducing hypoglycemic events, glucose excursion, and insulin dosage in our examined subjects.

Ankle-Brachial Index Is Independently Associated With Cardiovascular Outcomes and Foot Ulcers in Asian Patients With Type 2 Diabetes Mellitus.

Background and Aims: The ankle-brachial index (ABI) is an efficient tool for objectively documenting the presence of lower-extremity peripheral arterial disease (PAD). The predictive factors of cardiovascular events and diabetic foot ulcer were not clear from the ABI examination in Taiwanese patients with type 2 diabetes mellitus (DM). Methods: We enrolled 482 patients with type 2 DM who regularly visited the outpatient department of Chang Gung Memorial Hospital and received ABI as well as brachial-ankle pulse wave velocity (ba-PWV) examinations from 2010 to 2017. Age, gender, PAD symptoms, comorbidities, family history of chronic diseases, lifestyle (smoking, alcohol consumption, and exercise), height, weight, waist circumference, monofilament testing and foot ulcer status were studied. Results: There were 104 (22%) patients (mean age, 67.8 years) with the ABI <1.0. These patients with low ABI (ABI<1.0) had a significantly older age (p=0.001), higher delta PWV (p<0.001), higher rates of stroke (p=0.007), myocardial infarction (p=0.016), and foot ulcer (p=0.039). In a multivariable analysis model, the adjusted odds ratio (aOR) for myocardial infarction, stroke, and foot ulcers associated with low ABI were 1.219 (0.397-3.743, p=0.729), 1.204 (0.556-2.610, p=0.638), and 2.712 (1.199-6.133, p=0.017), respectively. The patients with low PWV (PWV<1400 cm/s) were significantly younger (p<0.001) and had a lower rate of hypertension (p<0.001), and higher percentages of stroke (p=0.027) and dialysis (p=0.041) family history. Conclusions: Low ABI was associated with cardiovascular events and diabetic foot ulcer independently in patients with type 2 DM.

Evaluation of Disease Complications Among Adults With Type 1 Diabetes and a Family History of Type 2 Diabetes in Taiwan.

Importance: Patients with type 1 diabetes (T1D) and a family history of type 2 diabetes (T2D) appear to be at a high risk of diabetes complications and other cardiovascular diseases. However, estimates of individual risks in patients in Taiwan are largely unavailable or unreliable. Objective: To evaluate the risk of diabetes complications and major adverse cardiovascular events (MACEs) in patients with T1D with a family history of T2D. Design, Setting, and Participants: A population-based cohort study used the Taiwan National Health Insurance Research Database. Participants included all individuals registered in that database on December 31, 2017, and followed up since March 1, 1995. The data were analyzed from December 6, 2018, to December 5, 2019. Exposure: Patients with T1D and a family history of T2D were evaluated. Main Outcomes and Measures: The prevalence and hazard ratios (HRs) of diabetes complications and other cardiovascular diseases in patients with T1D were analyzed. The MACEs were identified by diagnostic or procedural codes and heritability was formulated by the registry data of beneficiaries. Results: Of 27 370 965 individuals included in the database, 11 237 (mean [SD] age, 22.7 [14.4] years; 54% were female) had T1D. The crude prevalence of T1D was 0.04%, with a female to male ratio of 1.22: 1. The adjusted HRs in individuals who had a first-degree relative with T2D were 2.61 (95% CI, 1.32-5.16) for MACEs at an age at diagnosis of less than 20 years. Adjusted HRs were 1.44 (95% CI, 1.27-1.64) for diabetic neuropathy, 1.28 (95% CI, 1.12-1.47) for retinopathy, and 1.24 (95% CI, 1.06-1.47) for neuropathy at all ages of diagnosis. Conclusions and Relevance: In this study of patients in Taiwan with T1D, having relatives with T2D was associated with an increase in the individual risks of developing diabetes complications. Patients with T1D and a family history of T2D might have more complications and require close management.

Using Deep Convolutional Neural Networks for Enhanced Ultrasonographic Image Diagnosis of Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) from follicular epithelial cells is the most common form of thyroid cancer. Beyond the common papillary thyroid carcinoma (PTC), there are a number of rare but difficult-to-diagnose pathological classifications, such as follicular thyroid carcinoma (FTC). We employed deep convolutional neural networks (CNNs) to facilitate the clinical diagnosis of differentiated thyroid cancers. An image dataset with thyroid ultrasound images of 421 DTCs and 391 benign patients was collected. Three CNNs (InceptionV3, ResNet101, and VGG19) were retrained and tested after undergoing transfer learning to classify malignant and benign thyroid tumors. The enrolled cases were classified as PTC, FTC, follicular variant of PTC (FVPTC), Hürthle cell carcinoma (HCC), or benign. The accuracy of the CNNs was as follows: InceptionV3 (76.5%), ResNet101 (77.6%), and VGG19 (76.1%). The sensitivity was as follows: InceptionV3 (83.7%), ResNet101 (72.5%), and VGG19 (66.2%). The specificity was as follows: InceptionV3 (83.7%), ResNet101 (81.4%), and VGG19 (76.9%). The area under the curve was as follows: Incep-tionV3 (0.82), ResNet101 (0.83), and VGG19 (0.83). A comparison between performance of physicians and CNNs was assessed and showed significantly better outcomes in the latter. Our results demonstrate that retrained deep CNNs can enhance diagnostic accuracy in most DTCs, including follicular cancers.

Renal and Glucose-Lowering Effects of Empagliflozin and Dapagliflozin in Different Chronic Kidney Disease Stages.

Objective: The objective of this study was to investigate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on renal function in different stages of chronic kidney disease (CKD). Design and Methods: We conducted a retrospective cohort study using longitudinal claims data from May 2016-December 2017 from the Chang Gung Research Database. Patients who used one of the three types of SGLT2 inhibitor available at Chang Gung Memorial Hospital, namely empagliflozin 10 mg/tab (Empa10), empagliflozin 25 mg/tab (Empa25), and dapagliflozin 10 mg/tab (Dapa), were included, with the same number of matched non-users. Analysis of variance was used for continuous variables and the chi-square test was applied for categorical variables. Differences in data between two groups were analyzed using an independent t-test, and the basic data before and after treatment were analyzed using generalized estimating equation (GEE). The association among renal function changes was analyzed using a Cox proportional hazards model, with the results presented as unadjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results: Among the 7,624 SGLT2 inhibitor users, 1,696 patients used Empa10, 2,654 used Empa25, and 3,274 used Dapa. Compared with non-users, dapagliflozin had the lowest risk of estimated glomerular filtration rate (eGFR) decrease over 40% from baseline within 1 year (HR 0.36, 95% CI 0.25-0.51). By using the ICD-10-CM code N179, the acute kidney injury (AKI)-related hospitalization rate was lower in Empa10 and Dapa users than in non-users (HR 0.65, 95% CI 0.49-0.86). Conclusion: Lower risk of eGFR decrease over 40% and AKI-related hospitalization was found in all SGLT2 inhibitor users across the different CKD stages.

Diagnostic value of adrenal iodine-131 6-beta-iodomethyl-19-norcholesterol scintigraphy for primary aldosteronism: a retrospective study at a medical center in North Taiwan.

BACKGROUND: Primary aldosteronism (PA) is a common cause of secondary hypertension. Among the many leading causes of PA, the two most frequent are, bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenomas (APA). Since a solitary APA may be cured surgically, but BAH needs lifelong pharmacologic therapy, confirmation is mandatory before surgery. We herein sought to determine the diagnostic value of iodine-131 6-beta-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy to distinguish BAH from APA. PATIENTS AND METHODS: Patients clinically suspected of PA from March 2000 to October 2016 were retrospectively analyzed. A total of 145 patients, including 74 postunilateral adrenalectomy and seven postradiofrequency ablation for adrenal mass, were reviewed. All patients received NP-59 adrenal scintigraphy prior to surgery. The accuracy of the NP-59 adrenal scintigraphy was confirmed by the pathologic findings and postoperative outcomes. RESULTS: Among 81 patients receiving interventional procedures for adrenal mass, adenoma was eventually diagnosed in 72 patients according to their pathologic results, with 60 unilaterally and seven bilaterally localized lesions by NP-59 scintigraphy; nevertheless, there were five negative findings initially. The sensitivity, specificity, and positive predictive value of NP-59 scintigraphy for APA detection were therefore 83.3, 44.4, and 92.3%, respectively. Moreover, single-photon emission computed tomography/computed tomography scan increased the sensitivity and specificity, but not the positive predictive value (85.0, 60.0, and 89.5%) of NP-59 scintigraphy in this study. CONCLUSION: NP-59 adrenal scintigraphy is a useful imaging test to detect APA. Lateralization by this modality prior to surgical intervention may reduce the need for such invasive procedures as adrenal venous sampling.

Impact of Carbohydrate on Glucose Variability in Patients with Type 1 Diabetes Assessed Through Professional Continuous Glucose Monitoring: A Retrospective Study.

INTRODUCTION: The aim of this study was to objectively analyze the correlation between dietary components and blood glucose variation by means of continuous glucose monitoring (CGM). METHODS: Patients with type 1 diabetes mellitus (T1DM) who received CGM to manage their blood glucose levels were enrolled into the study, and the components of their total caloric intake were analyzed. Glycemic variation parameters were calculated, and dietary components, including percentages of carbohydrate, protein and fat in the total dietary intake, were analyzed by a dietitian. The interaction between parameters of glycemic variability and dietary components was analyzed. RESULTS: Sixty-one patients with T1DM (33 females, 28 males) were enrolled. The mean age of the participants was 34.7 years, and the average duration of diabetes was 14 years. Glycated hemoglobin before CGM was 8.54%. Participants with a carbohydrate intake that accounted for < 50% of their total caloric intake had a longer DM duration and a higher protein and fat intake than did those with a carbohydrate intake that accounted for ≥ 50% of total caloric intake, but there was no between-group difference in total caloric intake per day. The group with a carbohydrate intake that accounted for < 50% of their total caloric intake also had lower nocturnal continuous overlapping net glycemic action (CONGA) 1, - 2 and - 4 values. The percentage of protein intake had a slightly negative correlation with mean amplitude of glycemic excursions (MAGE) (r = - 0.286, p < 0.05) and a moderately negative correlation with coefficient of variation (CV) (r = 0.289, p < 0.05). One additional percentage of protein calories of total calories per day decreased the MAGE to 4.25 mg/dL and CV to 0.012 (p < 0.05). The optimal dietary protein percentage for MAGE < 140 mg/dL was 15.13%. The performance of predictive models revealed the beneficial effect of adequate carbohydrate intake on glucose variation when combined with protein consumption. CONCLUSIONS: Adequate carbohydrate consumption-but not more than half the daily total calories-combined with protein calories that amount to approximately 15% of the daily caloric intake is important for glucose stability and beneficial for patients with T1DM.

Dietary factors associated with hyperuricemia in adults.

OBJECTIVES: Although diet has long been assumed to be associated with hyperuricemia, the association between diet and hyperuricemia remains to be verified. METHODS: The Nutrition and Health Survey in Taiwan (NAHSIT) implemented between 1993 and 1996 was a nationwide survey using a stratified multistage sampling design. A food frequency questionnaire (FFQ), 24-hour diet recall, and blood samples were utilized. Hyperuricemia was defined as serum urate >7.7 mg/dL for men and >6.6 mg/dL for women. RESULTS: In total, 2176 adults, 987 (45%) men and 1189 (55%) women, were recruited. Mean serum urate was 6.81 +/- 1.66 mg/dL (range, 2.5-16.8 mg/dL) and 5.47 +/- 1.55 mg/dL (range, 1.4-11.5 mg/dL) for men and women, respectively. Multiple logistic regression analysis indicated that beer consumption in both the FFQ and the 24-hour diet recall were significantly associated with hyperuricemia in men after adjusting for age, total caloric intake, body mass index, and geographic area. In FFQ, the adjusted odds ratio was 1.49 for men who imbibed 0.1 to 11.6 g ethanol (<1 standard drink) daily and 1.56 for men who imbibed > or =11.7 g ethanol (> or =1 standard drink) daily, when compared with that for men who did not drink beer (P = 0.035). In the 24-hour diet recall, the adjusted odds ratio for men who drank <5 cans of beer daily was 1.13, and for men who drank > or =5 cans daily was 1.28 when compared with that for men who did not drink beer (P = 0.003). CONCLUSIONS: This cross-sectional survey demonstrated that beer intake is independently associated with increased risk of hyperuricemia in men. Restricted beer intake may help prevent hyperuricemia in the population. The finding of elevated mean serum urate levels over recent decades warrants further study.

Coadministration of DPP-4 inhibitor and insulin therapy does not further reduce the risk of cardiovascular events compared with DPP-4 inhibitor therapy in diabetic foot patients: a nationwide population-based study.

BACKGROUND: The effect of combined insulin and dipeptidyl peptidase-4 inhibitor (DPP4i) therapy on major adverse cardiovascular events (MACEs) in patients with diabetic foot is unclear. METHODS: We conducted this nationwide cohort study using longitudinal claims data obtained from the Taiwan National Health Insurance program and included 19,791 patients with diabetic foot from 2007 to 2014. Patients receiving DPP4i-based therapy and/or insulin-based therapy after a diagnosis of diabetic foot were categorized into combined, DPP4i- or insulin-based groups, respectively. The risk of MACEs including nonfatal myocardial infarction, nonfatal stroke, cardiac death, and heart failure was assessed using Cox proportional hazards analysis and propensity score matching. RESULTS: Among the 19,791 patients with diabetic foot (mean age, 58.8 years [SD, 12.5]; men, 51.2%), 6466 received DPP4i-based therapy, 1925 received insulin-based therapy, and 11,400 received combined DPP4i and insulin therapy. The DPP4i-based and insulin-based groups had a lower risk of MACEs (HR 0.53, 95% CI 0.50-0.57 DPP4i only; HR 0.89, 95% CI 0.81-0.97 insulin only) than the combined group. After propensity score matching, the incidence of all complications in the DPP4i-based group was still significantly lower than that in the combined group (HR 0.55, 95% CI 0.51-0.59 for MACEs; HR 0.32, 95% CI 0.24-0.42 for nonfatal myocardial infarction; HR 0.70, 95% CI 0.63-0.78 for nonfatal stroke; HR 0.22, 95% CI 0.13-0.38 for cardiac death; HR 0.22, 95% CI 0.19-0.25 for any death; HR 0.16, 95% CI 0.13-0.20 for amputation). In the diabetic foot patients with end-stage renal disease (ESRD), the benefit of a lower incidence of MACEs in the DPP4i-based group disappeared (HR 0.77, 95% CI 0.58-1.08). CONCLUSIONS: This study demonstrated that the patients with diabetic foot receiving DPP4i-based therapy had a lower risk of MACEs than those receiving combined therapy with DPP4i and insulin, but that the effect disappeared in those with concurrent ESRD.

Moderate- to high-intensity statins for secondary prevention in patients with type 2 diabetes mellitus on dialysis after acute myocardial infarction.

BACKGROUND: Evidences support the benefits of moderate- to high-intensity statins for patients with acute myocardial infarction (AMI) except for those with type 2 diabetes mellitus (T2DM) on dialysis after AMI. This study was aimed to investigate the safety and efficacy of secondary prevention of cardiovascular diseases using moderate- to high-intensity statins in T2DM patients on dialysis after AMI. METHODS: A simulated prospective cohort study was conducted between January 1st, 2001 and December 31st, 2013 utilizing data from the Taiwan National Health Insurance Research Database. A total of 882 patients with T2DM on dialysis after AMI were selected as the study cohort. Cardiovascular efficacy and safety of moderate- to high-intensity statins were evaluated by comparing outcomes of 441 subjects receiving statins after AMI to 441 matched subjects not receiving statins after AMI. The primary composite outcome included cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke. RESULTS: The Kaplan-Meier event rate for the primary composite outcomes at 8 years was 30.2% (133 patients) in the statin group compared with 25.2% (111 patients) in the non-statin group (hazard ratio [HR], .98; 95% confidence interval [CI] .76-1.27). Significantly lower risks of non-fatal ischemic stroke (HR, .58; 95% CI .35-.98) and all-cause mortality (HR, .70; 95% CI .59-.84) were found in the statin group. CONCLUSIONS: In T2DM patients on dialysis after AMI, the use of moderate- to high-intensity statins has neutral effects on composite cardiovascular events but may reduce risks of non-fatal ischemic stroke and all-cause mortality.

The impact of nutritional status on treatment outcomes of patients with limb-threatening diabetic foot ulcers.

AIM: This study aimed to investigate the nutritional status of patients with limb-threatening diabetic foot ulcers (DFUs) and its impact on treatment outcomes. METHODS: A total of 478 consecutive patients (mean age, 65.4years) treated for limb-threatening DFUs were enrolled. Nutritional status assessment using the Mini Nutritional Assessment (MNA) and Geriatric Nutritional Risk Index (GNRI) was performed by three qualified dieticians within 48hours of admission. Limb-preservation outcomes were stratified into major lower extremity amputation (LEA) (above the ankle, n=33), minor LEA (distal to ankle, n=117) and no amputation (non-LEA, n=328). RESULTS: Most patients were identified as being at risk of malnutrition (70.5%) or malnourished (14.6%) (mean MNA score, 20.6±3.4). MNA scores decreased with increasing severity of LEA (mean, 21.1, 20.0, and 17.9, respectively; P for linear trend <0.001), associated inversely with the tendency to require LEA (P for linear trend was 0.001), and associated independently with both major and minor LEA outcomes (adjusted odds ratio [aOR]=0.80, 95% confidence interval [CI], 0.65-0.99, P=0.042 and aOR=0.89, 95% CI, 0.80-0.99, P=0.032, respectively). The predictive value was sustained in patients younger than age 65years. Though GNRI results had similar associations with outcomes, its predictive value was limited in minor LEA and younger population. CONCLUSIONS: Patients' nutritional status was shown to have significant influence on limb-preservation outcomes for limb-threatening DFUs. Nutritional assessment of this patient population using the MNA is recommended.

Glucose Variability and ß- Cell Response by GLP-1 Analogue added-on CSII for Patients with Poorly Controlled Type 2 Diabetes.

The effects of twice-daily GLP-1 analogue injections added on continuous subcutaneous insulin infusion (CSII) in patients with poorly controlled type 2 diabetes (T2DM) were unknown. After optimization of blood glucose in the first 3 days by CSII during hospitalization, patients with poorly controlled T2DM were randomized to receive CSII combined with injections of exenatide or placebo for another 3 days. A total of 51 patients (30 in exenatide and 21 in placebo groups) with mean A1C 11% were studied. There was no difference in mean glucose but a significant higher standard deviation of plasma glucose (SDPG) was found in the exenatide group (50.51 ± 2.43 vs. 41.49 ± 3.00 mg/dl, p = 0.027). The improvement of incremental area under the curve (AUC) of glucose and insulinogenic index (Insulin 0-peak/ Glucose 0-peak) in 75 g oral glucose tolerance test was prominent in the exenatide group (p < 0.01). The adiponectin level was significantly increased with exenatide added on (0.39 ± 0.32 vs. -1.62 ± 0.97 µg/mL, in exenatide and placebo groups, respectively, p = 0.045). In conclusion, the add-on of GLP-1 analogue to CSII increased glucose variability and the ß - cell response in patients with poorly controlled T2DM.