Resilience, self-efficacy and diabetes distress on self-management behaviours in patients newly diagnosed with type 2 diabetes: A moderated mediation analysis.

AIM: To examine (1) the mediating role of self-efficacy between resilience and self-management behaviours and (2) the moderating role of diabetes distress on the relationship between self-efficacy and self-management behaviours in patients newly diagnosed with type 2 diabetes. DESIGN: Cross-sectional design. METHODS: Totally, 195 patients newly diagnosed with type 2 diabetes for more than 5 months but less than 18 months were recruited from three endocrine clinics in Taiwan through convenience sampling. Self-reported questionnaires including demographic and disease characteristics, resilience, self-efficacy and self-management behaviours were used to collect data from October 2020 to May 2021. Moderated mediation analysis was performed by Hayes's PROCESS macro. RESULT: According to bootstrapping results, the indirect effect of resilience on self-management was significant, although the direct effect of resilience on self-management was not. Participants were categorized into with and without diabetes distress groups. The results of moderated mediation analysis indicated self-efficacy significantly correlated with self-management behaviours in participants without diabetes distress, although self-efficacy did not significantly correlate with self-management in participants with diabetes distress. CONCLUSION: The association of resilience with self-management behaviours was fully mediated through self-efficacy with diabetes distress moderating the relationship between self-efficacy and self-management behaviours in patients newly diagnosed with type 2 diabetes. IMPACT: Improving resilience could enhance self-efficacy leading to possible improvement in self-management behaviour, although improving self-efficacy might not benefit self-management behaviours for those with high levels of diabetes distress. Healthcare providers need to first assess and address the diabetes distress before intervening to improve self-efficacy to enhance self-management behaviours in patients newly diagnosed with type 2 diabetes. PATIENT OR PUBLIC CONTRIBUTION: When designing this study, two patients newly diagnosed with diabetes were consulted about the importance of self-management behaviours for them personally.

Character Strengths Use in Diabetes Self-management Scale: Development and psychometric testing.

AIMS: To develop and psychometrically test Character Strengths Use in Diabetes Self-management Scale in people with type 2 diabetes. DESIGN: Cross-sectional design. METHODS: Based on literature reviews and examination by experts, a 20-item scale was developed and administered to 350 participants with type 2 diabetes who were enrolled from two endocrine clinics by convenience sampling in Taiwan. Item analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), concurrent and predictive validity as well as reliability were used to examine the psychometric characteristics of the scale. Data were collected from November 2021 to March 2022. RESULTS: EFA and CFA supported a 12-item scale with three factors, namely learning proactively, taking on challenges and thinking positively, fit the data well. The total score of the 12-item scale significantly and positively correlated with diabetes-specific quality of life, and significantly and negatively correlated with baseline and 9-month haemoglobin A1c levels. Cronbach's α for overall scale and subscales ranged between .78 and .91. CONCLUSION: The 12-item Character Strengths Use in Diabetes Self-management Scale demonstrated satisfactory validity and reliability in people with type 2 diabetes. IMPACT: Nurses could apply this new scale to identify the degree of using character strengths in self-management in people with type 2 diabetes; accordingly, character strength-based interventions could be provided to improve self-management in such patients with diabetes. Furthermore, the 12-item Character Strengths Use in Diabetes Self-management Scale has the potential to be used to measure the effectiveness of strength-based interventions in people with Type 2 diabetes. PATIENT OR PUBLIC CONTRIBUTION: Five patients with type 2 diabetes were invited to take the original 20-item scale to evaluate the clarity, readability and comprehensiveness of the 20 items.

LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1.

PURPOSE: Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a fast-growing incidence in recent decades. HOTAIR as a long non-coding RNA has been shown to be highly expressed in papillary thyroid cancer tissues with only a limited understanding of its functional roles and downstream regulatory mechanisms in papillary thyroid cancer cells. METHODS: We applied three thyroid cancer cell lines (MDA-T32, MDA-T41 and K1) to investigate the phenotypic influence after gain or loss of HOTAIR. The Cancer Genome Atlas (TCGA) database were utilised to select candidate genes possibly regulated by HOTAIR with validation in the cellular system and immunohistochemical (IHC) staining of PTC tissues. RESULTS: We observed HOTAIR was highly expressed in MDA-T32 cells but presents significantly decreased levels in MDA-T41 and K1 cells. HOTAIR knockdown in MDA-T32 cells significantly suppressed proliferation, colony formation, migration with cell cycle retardation at G1 phase. On the contrary, HOTAIR overexpression in MDA-T41 cells dramatically enhanced proliferation, colony formation, migration with cell cycle driven toward S and G2/M phases. Similar phenotypic effects were also observed as overexpressing HOTAIR in K1 cells. To explore novel HOTAIR downstream mechanisms, we analyzed TCGA transcriptome in PTC tissues and found DLX1 negatively correlated to HOTAIR, and its lower expression associated with reduced progression free survival. We further validated DLX1 gene was epigenetically suppressed by HOTAIR via performing chromatin immunoprecipitation. Moreover, IHC staining shows a significantly stepwise decrease of DLX1 protein from normal thyroid tissues to stage III PTC tissues. CONCLUSIONS: Our study pointed out that HOTAIR is a key regulator of cellular malignancy and its epigenetic suppression on DLX1 serves as a novel biomarker to evaluate the PTC disease progression.

Augmented CCL5/CCR5 signaling in brown adipose tissue inhibits adaptive thermogenesis and worsens insulin resistance in obesity.

Chemokine (C-C motif) ligand 5 (CCL5) and CCR5, one of its receptors have been reported to be highly expressed in white adipose tissue (WAT) and are associated with the progression of inflammation and the development of insulin resistance in obese humans and mice. However, the role of CCL5/CCR5 signaling in obesity-associated dysregulation of energy metabolism remains unclear. Here, we demonstrate that global CCL5/CCR5 double knockout (DKO) mice have higher cold stress-induced energy expenditure and thermogenic function in brown adipose tissue (BAT) than wildtype (WT) mice. DKO mice have higher cold stress-induced energy expenditure and thermogenic function in BAT than WT mice. KEGG pathway analysis indicated that deletion of CCL5/CCR5 further facilitated the cold-induced expression of genes related to oxidative phosphorylation (OxPhos) and lipid metabolic pathways. In primary brown adipocytes of DKO mice, the augmentation of CL-316243-stimulated thermogenic and lipolysis responses was reversed by co-treatment with AMPKα1 and α2 short interfering RNA (siRNA). Overexpression of BAT CCL5/CCR5 genes by local lentivirus injection in WT mice suppressed cold stress-induced lipolytic processes and thermogenic activities. In contrast, knockdown of BAT CCL5/CCR5 signaling further up-regulated AMPK phosphorylation as well as thermogenic and lipolysis responses to chronic adrenergic stimuli and subsequently decreased level of body weight gain. Chronic knockdown of BAT CCL5/CCR5 signaling improved high-fat diet (HFD)-induced insulin resistance in WT mice. It is suggested that obesity-induced augmentation of adipose tissue (AT) CCL5/CCR5 signaling could, at least in part, suppress energy expenditure and adaptive thermogenesis by inhibiting AMPK-mediated lipolysis and oxidative metabolism in thermogenic AT to exacerbate the development of obesity and insulin resistance.

Adipose Tissue-Derived CCL5 Enhances Local Pro-Inflammatory Monocytic MDSCs Accumulation and Inflammation via CCR5 Receptor in High-Fat Diet-Fed Mice.

The C-C chemokine motif ligand 5 (CCL5) and its receptors have recently been thought to be substantially involved in the development of obesity-associated adipose tissue inflammation and insulin resistance. However, the respective contributions of tissue-derived and myeloid-derived CCL5 to the etiology of obesity-induced adipose tissue inflammation and insulin resistance, and the involvement of monocytic myeloid-derived suppressor cells (MDSCs), remain unclear. This study used CCL5-knockout mice combined with bone marrow transplantation (BMT) and mice with local injections of shCCL5/shCCR5 or CCL5/CCR5 lentivirus into bilateral epididymal white adipose tissue (eWAT). CCL5 gene deletion significantly ameliorated HFD-induced inflammatory reactions in eWAT and protected against the development of obesity and insulin resistance. In addition, tissue (non-hematopoietic) deletion of CCL5 using the BMT method not only ameliorated adipose tissue inflammation by suppressing pro-inflammatory M-MDSC (CD11b+Ly6G-Ly6Chi) accumulation and skewing local M1 macrophage polarization, but also recruited reparative M-MDSCs (CD11b+Ly6G-Ly6Clow) and M2 macrophages to the eWAT of HFD-induced obese mice, as shown by flow cytometry. Furthermore, modulation of tissue-derived CCL5/CCR5 expression by local injection of shCCL5/shCCR5 or CCL5/CCR5 lentivirus substantially impacted the distribution of pro-inflammatory and reparative M-MDSCs as well as macrophage polarization in bilateral eWAT. These findings suggest that an obesity-induced increase in adipose tissue CCL5-mediated signaling is crucial in the recruitment of tissue M-MDSCs and their trans-differentiation to tissue pro-inflammatory macrophages, resulting in adipose tissue inflammation and insulin resistance.

Determinants of fear of falling in older adults with diabetes.

OBJECTIVES: To identify the important determinants of FoF among older adults with diabetes in endocrine clinics based on demographic and illness characteristics, physical function and capability, psychosocial and cognitive factors. METHODS: A cross-sectional study was conducted on 240 older adults with Type 2 diabetes who were recruited by convenience sampling. Self-reported questionnaires, medical records as well as physical function and capability tests were used to collect the data. Multiple linear regression was used to identify the important determinants of FoF. RESULT: Diabetes distress, sarcopenia levels, TUG results, and HbA1c levels were significant determinants of FoF. These determinants uniquely explained 14%, 9%, 4%, and 2% of the variance in FoF respectively. CONCLUSION: Beside sarcopenia and dynamic balance being known as significantly associated with FoF in a general older population, diabetes distress and HbA1c levels should also be considered in designing interventions to improve FoF among older adults with diabetes.

Predictors of abnormality in thallium myocardial perfusion scans for type 2 diabetes.

Type 2 diabetes mellitus (T2DM) increases coronary artery disease (CAD) risk. In this study, we used T2DM clinical variables to predict abnormality in thallium-201 myocardial perfusion scans (Th-201 scans). These clinical variables were summed stress score (SSS), summed rest score, and summed difference score (SDS), with data obtained from 368 male and 428 female participants with T2DM. Multiple linear regression results were as follows. In male participants, body mass index (BMI) and creatinine (Cr) were associated with SSS (ß = 0.224, p < 0.001; ß = 0.140, p = 0.022, respectively), and only BMI was associated with SDS (ß = 0.174, p = 0.004). In female participants, BMI and high-density lipoprotein cholesterol level were associated with SSS (ß = 0.240, p < 0.001; ß = - 0.120, p = 0.048, respectively), and only BMI was correlated with SDS (ß = 0.123, p = 0.031). Our multivariate logistic regression indicated that in male and female participants, BMI was the only independent indicator of high SSS (SSS ≥ 9). In this study, we demonstrated that male patients have a higher SSS and SDS than female patients do in Th-201 scans for T2DM in a Chinese population. For male and female patients, BMI was the strongest predictor of abnormality in Th-201 scans. Our results can help clinicians identify patients with T2DM at high risk of CAD.

High-Molecular-Weight Hyaluronic Acid Inhibits IL-1ß-Induced Synovial Inflammation and Macrophage Polarization through the GRP78-NF-κB Signaling Pathway.

Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid (HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, was suggested to contribute to the hyperplasia of synovial cells in OA. However, it was still unclear whether HMW-HA affected macrophage polarization through GRP78. Therefore, we aimed to identify the effect of HMW-HA in primary synovial cells and macrophage polarization and to investigate the role of GRP78 signaling. We used IL-1ß to treat primary synoviocytes to mimic OA, and then treated them with HMW-HA. We also collected conditioned medium (CM) to culture THP-1 macrophages and examine the changes in the phenotype. IL-1ß increased the expression of GRP78, NF-κB (p65 phosphorylation), IL-6, and PGE2 in primary synoviocytes, accompanied by an increased macrophage M1/M2 polarization. GRP78 knockdown significantly reversed the expression of IL-1ß-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1ß culture. Finally, the synovial fluid from OA patients revealed significantly decreased IL-6 and PGE2 levels after the HMW-HA treatment. Our study elucidated a new form of signal transduction for HMW-HA-mediated protection against synovial inflammation and macrophage polarization and highlighted the involvement of the GRP78-NF-κB signaling pathway.

Risk of severe hypoglycemic events from amiodarone-sulfonylureas interactions: A population-based nested case-control study.

PURPOSE: To evaluate whether concomitant use of amiodarone and sulfonylureas is associated with an increased risk of serious hypoglycemia. METHODS: We conducted two nested case-control studies by analyzing the Taiwan National Health Insurance Research Database from 2008 to 2013 among diabetic patients continuously receiving sulfonylureas. Cases were defined as patients with severe hypoglycemia and those with a composite outcome of severe hypoglycemia, altered consciousness, and fall-related fracture in the first and second study, respectively. In both studies, each case was individually matched up to 10 randomly-selected controls. Conditional logistic regressions were employed to estimate odds ratios (ORs). RESULTS: We identified 1343 cases and 11 597 controls as well as 2848 cases of composite events and 24 808 controls among 46 317 sulfonylurea users. Concurrent use of amiodarone with sulfonylureas was associated with a 1.56-fold (95% CI: 0.98-2.46) increased risk of severe hypoglycemia, despite not statistically significant. Notably, an approximately 2-fold increased risk of severe hypoglycemia was observed with amiodarone therapy lasting for >180 days (adjusted OR: 2.08; 95% CI: 1.01-4.30) or at a daily dose greater than 1 defined daily dose (adjusted OR: 2.21; 95% CI: 1.25-3.91) when concurrently administrating sulfonylureas. A significantly increased risk of hypoglycemia-related composite events was also found with amiodarone concurrently used with sulfonylureas (adjusted OR: 1.59; 95% CI: 1.13-2.24). CONCLUSIONS: Concurrent use of amiodarone and sulfonylureas is associated with an increased risk of serious hypoglycemia among diabetic patients, with an elevated risk for amiodarone used in a long-term or at a high daily dose.

Cilostazol inhibits hyperglucose-induced vascular smooth muscle cell dysfunction by modulating the RAGE/ERK/NF-κB signaling pathways.

BACKGROUND: Increasing evidence suggests that high glucose (HG) causes abnormalities in endothelial and vascular smooth muscle cell function (VSMC) and contributes to atherosclerosis. Receptor for advanced glycation end-products (RAGE) has been linked to the pathogenesis of both the macrovascular and microvascular complications of diabetes. Cilostazol is used to treat diabetic vasculopathy by ameliorating HG-induced vascular dysfunction. OBJECTIVES: In this study, we investigated whether the cilostazol suppression of HG-induced VSMC dysfunction is through RAGE signaling and its possible regulation mechanism. METHOD: We investigated the effect of HG and cilostazol on RAGE signaling in A7r5 rat VSMCs. Aortic tissues of streptozotocin (STZ) diabetic mice were also collected. RESULTS: Aortic tissue samples from the diabetic mice exhibited a significantly decreased RAGE expression after cilostazol treatment. HG increased RAGE, focal adhesion kinase (FAK), matrix metalloproteinase-2 (MMP-2), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions, and was accompanied with increased reactive oxygen species (ROS), cell proliferation, adhesion and migration. Cilostazol significantly reversed HG-induced RAGE, ROS, downstream gene expressions and cell functions. RAGE knockdown significantly reversed the expressions of HG-induced vasculopathy related gene expressions and cell functions. Cilostazol with RAGE knockdown had additive effects on downstream ERK/NF-κB signaling pathways, gene expressions and cell functions of A7r5 rat VSMCs in HG culture. CONCLUSIONS: Both in vitro and in vivo experimental diabetes models showed novel signal transduction of cilostazol-mediated protection against HG-related VSMC dysfunction, and highlighted the involvement of RAGE signaling and downstream pathways.

Targetted inhibition of CD74 attenuates adipose COX-2-MIF-mediated M1 macrophage polarization and retards obesity-related adipose tissue inflammation and insulin resistance.

Adipose tissue (AT) inflammation is crucial to the development of obesity-associated insulin resistance. Our aim was to investigate the contribution of cyclooxygenase-2 (COX-2)/macrophage migration inhibitory factor (MIF)-mediated cross-talk between hypertrophic adipocytes and macrophages to the etiology of AT inflammation and the involvement of CD74 using human SGBS adipocytes, THP-1 macrophages and mice fed a high-fat (HF) diet. The MIF and CD74 mRNA levels in the adipocytes and stromal vascular cells (SVCs) of white fat were highly correlated with body weight (BW), homeostatic model assessment for insulin resistance (HOMA-IR), and adipose macrophage marker expression levels, especially those in SVCs. COX-2 inhibition suppressed the elevation of MIF production in HF white adipocytes as well as palmitate and hypoxic-treated SGBS adipocytes. Treatment of adipocytes transfected with shCOX-2 and siMIF or subjected to MIF depletion in the medium reversed the pro-inflammatory responses in co-incubated THP-1 cells. Inhibition of NF-κB activation reversed the COX2-dependent MIF secretion from treated adipocytes. The targetted inhibition of macrophage CD74 prevented M1 macrophage polarization in the above co-culture model. The COX-2-dependent increases in CD74 gene expression and MIF release in M1-polarized macrophages facilitated the expression of COX-2 and MIF in co-cultured SGBS adipocytes. CD74 shRNA intravenous injection suppressed HF-induced AT M1 macrophage polarization and inflammation as well as insulin resistance in mice. The present study suggested that COX-2-mediated MIF secretion through NF-κB activation from hypertrophic and hypoxic adipocytes as well as M1 macrophages might substantially contribute to the phenotypic switch of AT macrophages through CD74 in obesity. Inhibition of CD74 could attenuate AT inflammation and insulin resistance in the development of HF diet-induced obesity.

Osteoporosis as the Female-Specific Risk Factor for Dynapenia in Elderly Patients with Type 2 Diabetes.

Aims: Dynapenia is a noteworthy health issue contributing to increased risk of falling, but its co-occurrence with osteoporosis in elderly individuals with type 2 diabetes mellitus (T2DM) has not been well explored. Therefore, this study aimed to establish the association between osteoporosis and dynapenia, focusing on T2DM females due to their high prevalence of osteoporosis and fragility. Methods: We conducted a cross-sectional study to recruit a total of 103 T2DM patients (43 males and 60 females), aged between 50 and 80 years with median 68.0 years. Dual-energy X-ray absorptiometry (DXA) and dominant hand grip strength measurements were performed to define body composition, osteoporosis, and dynapenia in a sex-specific manner. Results: Higher prevalence of dynapenia and dyna-osteoporosis was observed in female T2DM patients with a significantly positive correlation between osteoporosis and dynapenia even after adjustment of body mass index (BMI). By performing a multivariate logistic regression analysis, both BMI and osteoporosis were identified as risk predictors for the development of dynapenia in female T2DM patients with odds ratios (95% CIs) of 1.234 (1.029-1.480) and 4.883 (1.352-17.630), respectively. Conclusions: Our results point out there is high, female-specific co-occurrence of osteoporosis and dynapenia in T2DM patients. Moreover, having osteoporosis and increased BMI might boost the risk of dynapenia in elderly females with T2DM.

Exploring the link between metformin use and adhesive capsulitis of the shoulder: a retrospective cohort study in Taiwan.

The risk of adhesive capsulitis of shoulder in diabetic patients taking metformin has not been evaluated. We aimed for evaluating the relative risk of adhesive capsulitis of shoulder in diabetic patients taking metformin at the level of the whole country population. We conducted a retrospective cohort study using a national health insurance database in Taiwan from 2000 to2015. We used International Classification of Diseases, Ninth Revision, to categorise the medical condition for study group and comparison group. We used Cox proportional hazard regression analyses to determined adjusted hazard ratios (aHRs) of adhesive capsulitis of shoulder between study and comparison group after adjusting for sex, age, and comorbidities.Among 30,412 diabetic patients using metformin, 3020 patients were diagnosis with adhesive capsulitis of shoulder during follow up. Of the 121,648 patients without the use of metformin, 11,375 patients developed adhesive capsulitis of shoulder. Adhesive capsulitis of shoulder risk was elevated in patients taking metformin than in non-metformin group (adjusted hazard ratio [HR] 1.179, 95% confidence interval [95% CI] 1.022 to 1.268; p = 0.039). Risk of adhesive capsulitis of shoulder among the diabetic patients taking metformin was higher than those did not taking metformin.

Optimizing lipid control in Taiwanese diabetic patients: A collaborative consensus by the Diabetes Association of the Republic of China (Taiwan) and the Taiwanese Association of Diabetes Educators.

We present an in-depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low-density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence-based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.

The role of traditional Chinese medicine on fracture surgery, hospitalization, and total mortality risks in diabetic patients with osteoporosis.

BACKGROUND: Studies have confirmed that osteoporosis has been considered as one of the complications of diabetes, and the health hazards to patients are more obvious. This study is mainly based on the Taiwan National Health Insurance Database (TNHID). Through the analysis of TNHID, it is shown that the combined treatment of traditional Chinese medicine (TCM) medicine in patients of diabetes with osteoporosis (T2DOP) with lower related risks. METHODS: According to the study design, 3131 patients selected from TNHID who received TCM treatment were matched by 1-fold propensity score according to gender, age, and inclusion date as the control group. Cox proportional hazards analyzes were performed to compare fracture surgery, hospitalization, and all-cause mortality during a mean follow-up from 2000 to 2015. RESULTS: A total of 1055/1469/715 subjects (16.85%/23.46%/11.42%) had fracture surgery/inpatient/all-cause mortality of which 433/624/318 (13.83%/19.93%/10.16%) were in the TCM group) and 622/845/397 (19.87%/26.99%/12.68%) in the control group. Cox proportional hazards regression analysis showed that subjects in the TCM group had lower rates of fracture surgery, inpatient and all-cause mortality (adjusted HR = 0.467; 95% CI = 0.225-0.680, P<0.001; adjusted HR = 0.556; 95% CI = 0.330-0.751, P<0.001; adjusted HR = 0.704; 95% CI = 0.476-0.923, P = 0.012). Kaplan-Meier analysis showed that the cumulative risk of fracture surgery, inpatient and all-cause mortality was significantly different between the case and control groups (all log-rank p<0.001). CONCLUSION: This study provides longitudinal evidence through a cohort study of the value of integrated TCM for T2DOP. More research is needed to fully understand the clinical significance of these results.

Pharmacokinetics and Safety of Long-Acting Release Formulations of Pasireotide (SOM230) in a Male Population Who Are Hyperendemic Hepatitis B/C and Chronic Kidney Disease: An Open-Label, Phase I Study.

BACKGROUND: In patients with kidney or hepatic diseases, an increment of circulating pasireotide is also expected. Therefore, this open-label, phase I study aimed to evaluate the pharmacokinetic profiles and safety of subcutaneous (SC) and long-acting release (LAR) intramuscular injections of pasireotide in male Taiwanese volunteers who are hyperendemic hepatitis B/C and chronic kidney disease (CKD). METHODS: A total of 45 male volunteers were randomized to receive one of nine treatment sequences, involving a single subcutaneous injection of 300, 600, or 900 µg pasireotide, a multiple SC injection of the same dosage of pasireotide [300, 600, or 900 µg, twice daily (b.i.d.) for 4 days and a single dose for 1 day], and a single dose of 20, 40, or 60 mg LAR pasireotide intramuscular injection. The pasireotide SC and LAR formulations were prepared and supplied to the study center by Novartis. Pharmacokinetic parameters were assessed from both formulations. All adverse events that occurred in participants throughout the study period, including abnormalities in fasting levels of glucose, insulin, and glucagon, as well as laboratory measurements and electrocardiograms, were recorded. RESULTS: Analysis of plasma concentration over time revealed a rapid absorption of pasireotide, with a maximal concentration at 0.5 h after SC injection(s) of pasireotide (300-900 µg). Following a single dose of pasireotide LAR (20-60 mg), a sustained release was observed following an initial increase on day 1, a plateau around day 20, and a decline over the next 7 weeks. CONCLUSIONS: Both pasireotide formulations showed dose-proportional pharmacokinetics and 300-900 µg of SC pasireotide and 20-60 mg LAR pasireotide treatment showed favorable safety profiles and was well-tolerated when administered in male Taiwanese volunteers who are hyperendemic hepatitis B/C and CKD.

Effects of combined traditional Chinese medicine therapy in patients of lower limbs injuries with osteoporosis: A retrospective paired cohort study.

Studies have confirmed that the health hazards of patients with lower limb injuries combined with osteoporosis are more obvious. This study is mainly based on the Taiwan National Health Insurance Database, and through big data analysis, it shows that the combined treatment of traditional Chinese medicine (TCM) is helpful to the health of patients with lower limb injuries combined with osteoporosis. A total of 9989 combined TCM-treated patients and 19,978 2:1 sex-, age-, and index-year-matched controls who did not receive TCM treatment were selected from the Taiwan National Health Insurance Database. Cox proportional hazards analyzes were performed to compare fracture surgery, inpatient, and all-cause mortality during a mean follow-up period of 17 years. A total of 5406/8601/2564 enrolled-subjects (14.11%/25.46%/5.53%) had fracture surgery/inpatient/all-cause mortality, including 1409/2543/552 in the combined TCM group (14.11%/25.46%/5.53%) and 3997/6058/2012 in the control group (20.01%/30.32%/10.07%). Cox proportional hazard regression analysis showed a lower rate of fracture surgery, inpatient and all-cause mortality for subjects in the combined TCM group (adjusted hazard ratios [HR] = 0.723; 95% confidence intervals [CI] = 0.604-0.810, P < .001; adjusted hazard ratios [HR] = 0.803; 95% CI = 0.712-0.950, P = .001; adjusted HR = 0.842; 95% CI = 0.731-0.953, P = .007, respectively). After 10 years of follow-up, the cumulative incidence of fracture surgery in patients combining TCM treatment seems to be half of that without combining TCM treatment those are shown in Kaplan-Meier analysis with statistically significant (log rank, P < .001, P < .001, and P = .010, respectively). This study hopes to provide clinicians with the option of combined TCM treatment for patients of lower limbs injuries combined with osteoporosis, so that such patients will be associate with a lower risk of fracture surgery, inpatient or all-cause mortality.

DFATs derived from infrapatellar fat pad hold advantage on chondrogenesis and adipogenesis to evade age mediated influence.

Background: Dedifferentiated fat cells (DFATs) are highly homogeneous and multipotent compared with adipose-derived stromal cells (SCs). Infrapatellar fat pad (IFP)-SCs have advanced chondrogenic potency; however, whether IFP-DFATs could serve as better cell material remains unclear. Here, we aimed to examine the influence of age and body mass index (BMI) on the features of IFPs and IFP-derived cells (IFP-SCs and IFP-DFATs) with exploration of the clinical utilization of IFP-DFATs. Methods: We collected IFPs with isolation of paired IFP-SCs and IFP-DFATs from individuals aged 65 years and older with distinct body weights who underwent total knee replacement for osteoarthritis (OA). Flow cytometry was used to characterize the cellular immunophenotypes. Adipogenesis and chondrogenesis were performed in vitro. Real-time qPCR, western blotting, and Oil Red O or Alcian blue staining were performed to evaluate inflammation, adipogenesis, and chondrogenesis. RNA sequencing and Seahorse analyses were conducted to explore the underlying mechanisms. Results: We found that IFPs from old or normal-weight individuals with knee OA were pro-inflammatory, and that interleukin-6 (IL-6) signaling was associated with multiple immune-related molecules, whereas IFP-derived cells could escape the inflammatory properties. Aging plays an important role in diminishing the chondrogenic and adipogenic abilities of IFP-SCs; however, this effect was avoided in IFP-DFATs. Generally, IFP-DFATs presented a steady state of chondrogenesis (less influenced by age) and consistently enhanced adipogenesis compared to paired IFP-SCs in different age or BMI groups. RNA sequencing and Seahorse analysis suggested that the downregulation of eukaryotic initiation factor 2 (EIF2) signaling and enhanced mitochondrial function may contribute to the improved cellular biology of IFP-DFATs. Conclusions: Our data indicate that IFP-DFATs are superior cell material compared to IFP-SCs for cartilage differentiation and adipogenesis, particularly in advanced aging patients with knee OA. The translational potential of this article: These results provide a novel concept and supportive evidence for the use of IFP-DFATs for cell therapy or tissue engineering in patients with knee OA. Using Ingenuity Pathway Analysis (IPA) of RNA-seq data and Seahorse analysis of mitochondrial metabolic parameters, we highlighted that some molecules, signaling pathways, and mitochondrial functions are likely to be jointly coordinated to determine the enhanced biological function in IFP-DFATs.

The efficacy and safety of combined GLP-1RA and basal insulin therapy among inadequately controlled T2D with premixed insulin therapy.

This study investigated the effect of a combination of glucagon-like peptide-1 receptor agonist (GLP-1 RA) and basal insulin (BI) in poorly controlled type 2 diabetes mellitus previously treated with premixed insulin. The possible therapeutic benefit of the subject is mainly hoped to provide a direction for optimizing treatment options to reduce the risk of hypoglycemia and weight gain. A single-arm, open-label study was conducted. The antidiabetic regimen was switched to GLP-1 RA plus BI to replace previous treatment with premixed insulin in type 2 diabetes mellitus subjects. After 3 months of treatment modification, GLP-1 RA plus BI was compared for superior outcomes by continuous glucose monitoring system. There were 34 subjects at the beginning, 4 withdrew due to gastrointestinal discomfort, and finally 30 subjects completed the trial, of which 43% were male; the average age was 58 ± 9 years old, and the average duration of diabetes was 12 ± 6 years, the baseline glycated hemoglobin level was 8.6 ± 0.9 %. The initial insulin dose of premixed insulin was 61 ± 18 units, and the final insulin dose of GLP-1 RA + BI was 32 ± 12 units (P < .001). Time out of range (from 59%-42%), time-in-range (from 39%-56%) as well as glucose variability index including standard deviation also improved, mean magnitude of glycemic excursions, mean daily difference and continuous population in continuous glucose monitoring system, continuous overall net glycemic action (CONGA). Also noted was a decrease in body weight (from 70.9 kg-68.6 kg) and body mass index (all P values < .05). It provided important information for physicians to decide to modify therapeutic strategy as individualized needs.

Gender-specific impacts of thigh skinfold thickness and grip strength for predicting osteoporosis in type 2 diabetes.

BACKGROUND: Diabetes with co-existing bone fragility or osteoporosis is common in elderly patients, whereas is frequently underestimated. METHODS: We conducted dual-energy x-ray absorptiometry (DXA) with 7-site skinfold (SF) and dominant hand grip strength measurements among patients with type 2 diabetes (T2DM) to assess their gender-specific associations. A total of 103 patients with T2DM (60 females and 43 males), aged between 50 and 80 years (median 68.0 years) were enrolled and 45 non-DM females were also included to compare with T2DM females. RESULTS: Our results revealed osteoporosis was negatively correlated with grip strength in both genders, negatively correlated with lean mass solely in males and negatively correlated with fat mass (particular the gynoid fat mass and thigh SF thickness) in females. Via performing multivariable stepwise logistic regression, we identified grip strength in both genders and thigh SF thickness in females as predictors for osteoporosis. Receiver operating characteristic curve analysis further disclosed 20.5 mm female thigh skinfold thickness, 18.1 kg female grip strength and 29.0 kg male grip strength as reasonable cutoff levels for predicting osteoporosis in the Taiwanese patients with T2DM. CONCLUSIONS: Patients with T2DM presented gender-specific associations between osteoporosis, body composition and grip strength. Grip strength and thigh SF thickness might serve as predictors for detection of osteoporosis in patients with T2DM.