How should anti-hypertensive medications be adjusted before screening for primary aldosteronism?

Anti-hypertensive medications may affect plasma renin activity and/or plasma aldosterone concentration, misleading the interpretation of the aldosterone-to-renin ratio when screening for primary aldosteronism. The Task Force of Taiwan PA recommends that, when necessary, using α-adrenergic receptor blocking agents, centrally acting α-adrenergic agonists, and/or non-dihydropyridine calcium channel blockers should be considered to control blood pressure before screening for PA. We recommend temporarily holding ß-adrenergic receptor blocking agents, mineralocorticoid receptor antagonists, dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and all diuretics before screening for PA. Further large-scale randomized controlled studies are required to confirm the recommendations.

Who needs to be screened for primary aldosteronism?

The prevalence of patients with primary aldosteronism (PA) is about 5%-15% in hypertensive patients, and it is common cause of secondary hypertension in clinical practice. Two major causes of PA are noted, namely bilateral adrenal hyperplasia and aldosterone-producing adenoma, and the general diagnosis is based on three steps: (1) screening, (2) confirmatory testing, and (3) subtype differentiation (Figure 1). The recommendation for screening patients is at an increased risk of PA, here we focus on which patients should be screened for PA, not only according to well-established guidelines but for potential patients with PA. We recommend screening for 1) patients with resistant or persistent hypertension, 2) hypertensive patients with hypokalemia (spontaneous or drug-induced), 3) young hypertensive patients (age <40 years), and 4) all hypertensive patients with a history of PA in first-degree relatives. Moreover, we suggest screening for 1) hypertensive patients themselves or first-degree relatives with early target organ damage, such as stroke and other diseases, 2) all hypertensive patients with a concurrent adrenal incidentaloma, 3) hypertensive patients with obstructive sleep apnea, 4) hypertensive patients with atrial fibrillation unexplained by structural heart defects and/or other conditions resulting in the arrhythmia, 5) hypertensive patients with anxiety and other psychosomatic symptoms, and 6) hypertensive patients without other comorbidities to maintain cost-effectiveness.

2022 Taiwan clinical multicenter expert consensus and recommendations for thyroid radiofrequency ablation.

Radiofrequency ablation (RFA) is a minimally invasive management strategy that has been widely applied for benign and recurrent malignant thyroid lesions as an alternative to surgery in Taiwan. Members of academic societies for specialists in interventional radiology, endocrinology, and endocrine surgery collaborated to develop the first consensus regarding thyroid RFA in Taiwan. The modified Delphi method was used to reach a consensus. Based on a comprehensive review of recent and valuable literature and expert opinions, the recommendations included indications, pre-procedural evaluations, procedural techniques, post-procedural monitoring, efficacy, and safety, providing a comprehensive review of the application of RFA. The consensus effectively consolidates advice regarding thyroid RFA in clinical practice for local experts.

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.

Gut Microbiota and Bile Acids Mediate the Clinical Benefits of YH1 in Male Patients with Type 2 Diabetes Mellitus: A Pilot Observational Study.

Our previous clinical trial showed that a novel concentrated herbal extract formula, YH1 (Rhizoma coptidis and Shen-Ling-Bai-Zhu-San), improved blood glucose and lipid control. This pilot observational study investigated whether YH1 affects microbiota, plasma, and fecal bile acid (BA) compositions in ten untreated male patients with type 2 diabetes (T2D), hyperlipidemia, and a body mass index ≥ 23 kg/m2. Stool and plasma samples were collected for microbiome, BA, and biochemical analyses before and after 4 weeks of YH1 therapy. As previous studies found, the glycated albumin, 2-h postprandial glucose, triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were significantly improved after YH1 treatment. Gut microbiota revealed an increased abundance of the short-chain fatty acid-producing bacteria Anaerostipes and Escherichia/Shigella. Furthermore, YH1 inhibited specific phylotypes of bile salt hydrolase-expressing bacteria, including Parabacteroides, Bifidobacterium, and Bacteroides caccae. Stool tauro-conjugated BA levels increased after YH1 treatment. Plasma total BAs and 7α-hydroxy-4-cholesten-3-one (C4), a BA synthesis indicator, were elevated. The reduced deconjugation of BAs and increased plasma conjugated BAs, especially tauro-conjugated BAs, led to a decreased glyco- to tauro-conjugated BA ratio and reduced unconjugated secondary BAs. These results suggest that YH1 ameliorates T2D and hyperlipidemia by modulating microbiota constituents that alter fecal and plasma BA compositions and promote liver cholesterol-to-BA conversion and glucose homeostasis.

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.

Risk factors of first and recurrent genitourinary tract infection in patients with type 2 diabetes treated with SGLT2 inhibitors: A retrospective cohort study.

AIMS: This retrospective study investigated the risk factors of sodium-glucose cotransporter 2 inhibitors (SGLT2i) -related genitourinary tract infection (GUTI). METHODS: We used longitudinal claims data from May 2016 to December 2017 from the Chang Gung Research Database. Diabetic patients who used SGLT2i were included. The baseline characteristics risk factors between patients who had GUTI and no GUTI were analyzed. RESULTS: There were 428(3.43%) patients with the first occurrence of urinary tract infection (UTI) and 5(0.04%) patients with genital tract infection (GTI). Female patients aged ≥ 65 years with HbA1c ≥ 9%, eGFR < 60 ml/min/1.73 m2, urine albumin/creatinine ratio (UACR) level ≥30 mg/g, dyslipidemia, diabetic microvascular complications and mood disorder had a higher risk of having the first occurrence of UTI. There was no significant risk factor of GTI. 117 UTI and 3 GTI patients received SGLT2i rechallenging. The recurrent UTI rate was 28.2% and no recurrent GTI was diagnosed. The risk factors included CHD, eGRF < 45 ml/min/1.73 m2, and mood disorder (OR, 95% CI: 4.39, 1.15-16.74; 4.11, 1.51-11.19; 5.93, 1.39-25.34, respectively). CONCLUSIONS: In diabetic patients who had underlying disease of eGRF < 45 ml/min/1.73 m2, CHD, and mood disorder had higher risk of recurrent UTI after rechallenging SGLT2i.

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.

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.

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.

Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy.

The regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium extract (EE) on skeletal muscle as represented by differentiated C2C12 cells. Here we demonstrated that EE and ICA stimulated C2C12 myotube hypertrophy by activating several, including IGF-1 signal pathways. C2C12 myotube hypertrophy was demonstrated by enlarged myotube and increased myosin heavy chains (MyHCs). In similar to IGF-1, EE/ICA activated key components of the IGF-1 signal pathway, including IGF-1 receptor. Pre-treatment with IGF-1 signal pathway specific inhibitors such as picropodophyllin, LY294002, and rapamycin attenuated EE induced myotube hypertrophy and MyHC isoform overexpression. In a different way, EE induced MHyC-S overexpression can be blocked by AMPK, but not by mTOR inhibitor. On the level of transcription, EE suppressed myostatin and MRF4 expression, but did not suppress atrogenes MAFbx and MuRF1 like IGF-1 did. Differential regulation of MyHC isoform and atrogenes is probably due to inequivalent AKT and AMPK phosphorylation induced by EE and IGF-1. These findings suggest that EE/ICA stimulates pathways partially overlapping with IGF-1 signaling pathway to promote myotube hypertrophy.

Alterations of Gut Microbiota in Patients With Graves' Disease.

Graves' disease (GD) is a systemic autoimmune disease characterized by hyperthyroidism. Evidence suggests that alterations to the gut microbiota may be involved in the development of autoimmune disorders. The aim of this study was to characterize the composition of gut microbiota in GD patients. Fecal samples were collected from 55 GD patients and 48 healthy controls. Using 16S rRNA gene amplification and sequencing, the overall bacterial richness and diversity were found to be similar between GD patients and healthy controls. However, principal coordinate analysis and partial least squares-discriminant analysis showed that the overall gut microbiota composition was significantly different (ANOSIM; p < 0.001). The linear discriminant analysis effect size revealed that Firmicutes phylum decreased in GD patients, with a corresponding increase in Bacteroidetes phylum compared to healthy controls. In addition, the families Prevotellaceae, and Veillonellaceae and the genus Prevotella_9 were closely associated with GD patients, while the families Lachnospiraceae and Ruminococcaceae and the genera Faecalibacterium, Lachnospira, and Lachnospiraceae NK4A136 were associated with healthy controls. Metagenomic profiles analysis yielded 22 statistically significant bacterial taxa: 18 taxa were increased and 4 taxa were decreased. Key bacterial taxa with different abundances between the two groups were strongly correlated with GD-associated clinical parameters using Spearman's correlation analysis. Importantly, the discriminant model based on predominant microbiota could effectively distinguish GD patients from healthy controls (AUC = 0.825). Thus, the gut microbiota composition between GD patients and healthy controls is significantly difference, indicating that gut microbiota may play a role in the pathogenesis of GD. Further studies are needed to fully elucidate the role of gut microbiota in the development of GD.

Association between serum bilirubin levels and progression of albuminuria in Taiwanese with type 2 diabetes mellitus.

BACKGROUND: To investigate the association between serum bilirubin (BIL) levels and the progression of albuminuria in type 2 diabetic Taiwanese. METHODS: Longitudinal data from January 2001 to June 2015 were retrospectively reviewed from Chang Gung Memorial Hospital in Taiwan. A total of 2877 type 2 diabetic patients with normal total BIL levels were divided into 4 groups according to BIL, with the highest BIL in the fourth group. The urinary albumin/creatinine ratio (UACR) trend and progression, as well as other laboratory measurements, were evaluated among the four groups. The cumulative incidence and Cox proportional hazard model analysis were performed to examine the relationship between BIL and the risk of albuminuria progression (AUPr). RESULTS: The mean duration of follow-up was 1.5 years (±1.37 years). The mean patient age, glycosylated hemoglobin level, and duration of diabetes were 62.52 years, 7.9%, and 3.94 years, respectively. A significant correlation was observed between BIL and both the UACR at baseline (P < 0.001) and the cumulative incidence of AUPr (log-rank test, P = 0.031). Hazard ratio (HR) analysis revealed that patients in the fourth BIL quartile had the lowest HR risk of AUPr among the four groups (adjusted HR = 0.70; 95% Confidence Interval = 0.56-0.89, P < 0.05). CONCLUSIONS: Higher serum BIL levels are associated with a lower risk of AUPr in type 2 diabetes patients in Taiwan.

Primary lung cancer with radioiodine avidity: A thyroid cancer cohort study.

BACKGROUND: A proportion of lung cancers show sodium/iodide symporter (NIS) expression. Lung cancers with NIS expression may uptake radioiodine (RAI) and show RAI-avid lesions on RAI scan for differentiated thyroid cancer (DTC) surveillance. AIM: To investigate the possibility of RAI uptake by lung cancer in a cohort with thyroid cancer. METHODS: RAI-avid lung cancers were analyzed using a prospectively maintained database of patients with thyroid cancer who were registered at a medical center between December 1, 1976 and May 28, 2018. NIS expression in lung cancer was assessed using immunohistochemical staining. RESULTS: Of the 5000 patients with thyroid cancer from the studied dataset, 4602 had DTC. During follow-up, 33 patients developed primary lung cancer. Of these patients, nine received an iodine-131 (131I) scan within 1 year before the diagnosis of lung cancer. One of these nine lung cancers was RAI-avid. NIS expression was evaluated, and three of the eight available lung cancers revealed NIS expression. The proportions of lung cancer cells with NIS expression were 60%, 15%, and 10%. The RAI-avid lung cancer had the highest level of expression (60%). The RAI-avid lung cancer had a spiculated border upon single-photon emission computed tomography/computed tomography, which led to an accurate diagnosis. CONCLUSION: A proportion of lung cancer demonstrates NIS expression and is RAI-avid. Clinicians should be aware of this possibility in the interpretation of RAI scintigraphy.

Kynurenine/Tryptophan Ratio Predicts Angiotensin Receptor Blocker Responsiveness in Patients with Diabetic Kidney Disease.

Albuminuria is a measurement and determinant factor for diabetic kidney disease (DKD). Angiotensin receptor blocker (ARB) is recommended for albuminuria in DKD with variable response. To find surrogate markers to predict the therapeutic effect of ARB, we carried out a prospective study to correlate plasma metabolites and the progression of renal function/albuminuria in DKD patients. A total of 56 type 2 diabetic patients with various stages of chronic kidney disease and albuminuria were recruited. ARB was prescribed once albuminuria was established. Urinary albumin-to-creatinine ratio (UACR) was determined before and six months after ARB treatment, with a ≥30% reduction of UACR considered an ARB responder. Plasma levels of 145 metabolites were measured before ARB treatment; only those associated with albuminuria were selected and compared between ARB responders and non-responders. Both lower tryptophan (Trp ≤ 46.75 µmol/L) levels and a higher kynurenine/tryptophan ratio (KTR ≥ 68.5 × 10-3) were significantly associated with macroalbuminuria (MAU), but only KTR (≥54.7 × 10-3) predicts ARB responsiveness (sensitivity 90.0%, specificity 50%) in MAU. Together, these data suggest that the kynurenine/tryptophan ratio predicts angiotensin receptor blocker responsiveness in patients with diabetic kidney disease.

Long-term therapeutic outcomes of papillary thyroid carcinoma with concomitant hyperparathyroidism: A single center case-control study.

BACKGROUND: Papillary thyroid carcinoma occasionally presents with concomitant hyperparathyroidism; however, the clinical significance has not been well established. This study aimed to evaluate the long-term cancer prognosis following a multimodality therapy. METHODS: We conducted a case-control study using prospectively maintained data from a medical center thyroid cancer database between 1980 and 2013. The study cohort comprised patients with concomitant papillary thyroid carcinoma and hyperparathyroidism. Patients with papillary thyroid carcinoma only were matched using the propensity score method. Therapeutic outcomes, including the non-remission rate of papillary thyroid carcinoma and patient mortality, were compared. RESULTS: We identified 27 study participants from 2537 patients with papillary thyroid carcinoma, with 10 patients having primary hyperparathyroidism and 17 having renal hyperparathyroidism. Eighty-five percent of the cohort was found to have tumor-node-metastasis stage I disease. During a mean follow-up of 7.7 years, we identified 3 disease non-remission and 4 mortality events. The non-remission risk did not increase (hazard ratio [HR], 1.66; 95% confidence interval [CI], 0.43-6.40; p = 0.47); however, the overall mortality risk significantly increased (HR, 4.43; 95% CI, 1.11-17.75; p = 0.04). All mortality events were not thyroid cancer related, including two identified cardiovascular diseases. CONCLUSIONS: Patients with papillary thyroid carcinoma who present with concomitant hyperparathyroidism are usually diagnosed at an early cancer stage with compatible therapeutic outcomes. However, hyperparathyroidism-related comorbidity may decrease long-term survival.

Similar Cardiovascular Outcomes Between Insulin Detemir and Insulin Glargine In Type 2 Diabetic Patients With Extremely Atherosclerotic Cardiovascular Disease Risks.

OBJECTIVE: The cardiovascular outcomes of insulin detemir 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-life cohort study was to evaluate the cardiovascular outcomes of insulin detemir (IDet) versus insulin glargine (IGlar) in T2DM patients after ACS or AIS. METHODS: A retrospective cohort study was conducted between June 1, 2005, and December 31, 2013, utilizing the Taiwan National Health Insurance Research Database. A total of 3,129 ACS or AIS patients were eligible for the analysis. Clinical outcomes were evaluated by comparing 1,043 subjects receiving IDet with 2,086 propensity score-matched subjects who received IGlar. The primary composite outcome included cardiovascular (CV) death, nonfatal myocardial infarction (MI) and nonfatal stroke. RESULTS: The primary composite outcome occurred in 322 patients (30.9%) in the IDet group and 604 patients (29.0%) in the IGlar group (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.95 to 1.32) with a mean follow-up of 2.4 years. No significant differences were observed for CV death (HR, 1.09; 95% CI, 0.86 to 1.38), nonfatal MI (HR, 0.88; 95% CI, 0.66 to 1.19), and nonfatal stroke (HR, 1.15; 95% CI, 0.97 to 1.35). There were similar risks of all-cause mortality, hospitalization for heart failure and revascularization between the IDet group and the IGlar group (P = .647, .115, and .390 respectively). CONCLUSION: Compared with IGlar, in T2DM patients after ACS or AIS, IDet was not associated with increased risks of CV death, nonfatal MI, or nonfatal stroke. ABBREVIATIONS: ACS = acute coronary syndrome; AIS = acute ischemic stroke; ASCVD = atherosclerotic cardiovascular disease; CI = confidence interval; CV = cardiovascular; DKA = diabetic ketoacidosis; HHF = hospitalization for heart failure; HHS = hyperosmolar hyperglycemic state; HR = hazard ratio; IDet = insulin detemir; IGlar = insulin glargine; MI = myocardial infarction; NHIRD = National Health Insurance Research Database; PCI = percutaneous coronary intervention; PSM = propensity score matching; T2DM = type 2 diabetes mellitus.

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.

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.

Association of stiff-person syndrome with autoimmune endocrine diseases.

BACKGROUND: Stiff-person syndrome (SPS) and its subtype, stiff limb syndrome (SLS), are rare neurological disorders characterized by progressive muscular rigidity and spasms. Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the production of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter of the central nervous system. SPS is an autoimmune disease triggered by anti-glutamic acid decarboxylase antibody (anti-GAD Ab). Clinically, anti-GAD Ab is associated with SPS, type 1 diabetes mellitus (T1DM), and other autoimmune diseases. AIM: To investigate the link of autoimmune endocrine disorders with anti-GAD Ab in SPS subjects. METHODS: This retrospective study was approved by the Institutional Review Board of Chang Gung Memorial Hospital, Taiwan. We collected the patients with SPS from January 2001 to June 2018. By reviewing 14 patients from medical records, we analyzed the clinical findings with coexisting autoimmune diseases, particularly diabetes mellitus and thyroid disease, which are associated with anti-GAD antibody titers or other immunological test results (anti-thyroid peroxidase and anti-nuclear antibodies). We also evaluated malignancies, major complications, and reported treatment to improve symptoms. Anti-GAD antibodies were measured using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). The cut-off values of these tests are < 1 U/mL and < 5 U/mL, respectively. RESULTS: The median age of all patients was 39.3 (range, 28.0-54.0) years with a median follow-up period of 6.0 (2.7-13.3) years. Five (35.7%) patients were female; twelve (85.7%) were diagnosed with classic SPS and two (14.3%) with SLS. The median age of onset of symptoms was 35.0 (26.0-56.0) years with a median follow-up duration of 9.0 (2.1-14.9) years in the classic SPS group; the SLS group had a median age of onset of 46.7 years and a shorter follow-up duration of 4.3 years. Among nine classic SPS patients who underwent the anti-GAD Ab test, three were anti-GAD Ab seropositive and each of these three patients also had T1DM, latent autoimmune diabetes in adults, and autoimmune thyroid disease, respectively. In contrast, other rare autoimmune diseases co-existed in six anti-GAD Ab seronegative SPS patients. None of the SLS patients had additional autoimmune diseases. CONCLUSION: While typical clinical symptoms are crucial for the diagnosis of SPS, the presence of anti-GAD autoantibody may consolidate the diagnosis and predict the association with other autoimmune diseases.