Diabetes self-management education on the sustainability of metabolic control in type 2 diabetes patients: Diabetes share care program in Taiwan.

BACKGROUND: Diabetes self-management education (DSME) improves glycemic and metabolic control. However, the frequency, duration and sustainability of DSME for improving metabolic control have not been well studied. METHODS: The Diabetes Share Care Program (DSCP) stage 1 provided DSME every 3 months. If participants entering DSCP stage 1 ≥ 2 years and HbA1c < 7%, they can be transferred to stage 2 (DSME frequency: once a year). Three-to-one matching between DSCP stage 1 and stage 2 groups based on the propensity score method to match the two groups in terms of HbA1c and diabetes duration. We identified 311 people living with type 2 diabetes in DSCP stage 1 and 86 in stage 2 and evaluated their metabolic control and healthy behaviors annually for 5 years. RESULTS: In the first year, HbA1c in the DSCP stage 2 group was significantly lower than that in the stage 1 group. In the first and the fifth years, the percentage of patients achieving HbA1c < 7% was significantly higher in the DSCP stage 2 group than the stage 1 group. There was no significant difference in other metabolic parameters between the two groups during the 5-year follow-up. Self-monitoring of blood glucose (SMBG) frequency was associated with a reduced HbA1c after 5 years (95% CI: -0.0665 to -0.0004). CONCLUSION: We demonstrated sustainable effects of at least 2-year DSME on achieving better glycemic control for at least 1 year. SMBG contributed to improved glycemic control. The results may be applied to the reimbursement strategy in diabetes education.

Distinctive gene expression patterns in pregnancy-associated breast cancer.

Pregnancy-associated breast cancer (PABC) is diagnosed during pregnancy or within 1 year postpartum, but the unique aspects of its etiology and pathogenesis have not been fully elucidated. This study aimed to ascertain the molecular mechanisms of PABC to facilitate diagnosis and therapeutic development. The Limma package was used to characterize the differentially expressed genes in PABC as compared to non-pregnancy-associated breast cancer (NPABC) and normal breast tissue. A total of 871 dysregulated genes were identified in the PABC versus NPABC groups and 917 in the PABC versus normal groups, with notable differences in the expression of MAGE and CXCL family genes. The dysregulated genes between the PABC and normal groups were mainly associated with signal transduction and immune response, while Kyoto Encyclopedia of Genes and Genomes analysis revealed that the dysregulated genes were enriched in immune-related pathways, including the major histocompatibility complex (MHC) class II protein complex, the type I interferon signaling pathway, regulation of α-ß T-cell proliferation, and the T-cell apoptotic process. Through protein-protein interaction network construction, CD44 and BRCA1 were identified as prominent hub genes with differential expression in PABC versus NPABC. Furthermore, a cluster with eleven hub genes was identified in PABC versus normal adjacent tissues, of which the expression of EGFR, IGF1, PTGS2, FGF1, CAV1, and PLCB1 were verified to be differentially expressed in an independent cohort of PABC patients. Notably, IGF1, PTGS2, and FGF1 were demonstrated to be significantly related to patient prognosis. Our study reveals a distinctive gene expression pattern in PABC and suggests that IGF1, PTGS2, and FGF1 might serve as biomarkers for diagnosis and prognosis of PABC.

The Different Molecular Code in Generation of Dopaminergic Neurons from Astrocytes and Mesenchymal Stem Cells.

Transplantation of exogenous dopaminergic (DA) neurons is an alternative strategy to replenish DA neurons that have lost along the course of Parkinson's disease (PD). From the perspective of ethical acceptation, the source limitations, and the intrinsic features of PD pathology, astrocytes (AS) and mesenchymal stem cells (MSCs) are the two promising candidates of DA induction. In the present study, we induced AS or MSCs primary culture by the combination of the classical transcription-factor cocktails Mash1, Lmx1a, and Nurr1 (MLN), the chemical cocktails (S/C/D), and the morphogens SHH, FGF8, and FGF2 (S/F8/F2); the efficiency of induction into DA neurons was further analyzed by using immunostaining against the DA neuronal markers. AS could be efficiently converted into the DA neurons in vitro by the transcriptional regulation of MLN, and the combination with S/C/D or S/F8/F2 further increased the conversion efficiency. In contrast, MSCs from umbilical cord (UC-MSCs) or adipose tissue (AD-MSCs) showed moderate TH immunoreactivity after the induction with S/F8/F2 instead of with MLN or S/C/D. Our data demonstrated that AS and MSCs held lineage-specific molecular codes on the induction into DA neurons and highlighted the unique superiority of AS in the potential of cell replacement therapy for PD.

RBM4a-SRSF3-MAP4K4 Splicing Cascade Constitutes a Molecular Mechanism for Regulating Brown Adipogenesis.

An increase in mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) reportedly attenuates insulin-mediated signaling which participates in the development of brown adipose tissues (BATs). Nevertheless, the effect of MAP4K4 on brown adipogenesis remains largely uncharacterized. In this study, results of a transcriptome analysis (also referred as RNA-sequencing) showed differential expressions of MAP4K4 or SRSF3 transcripts isolated from distinct stages of embryonic BATs. The discriminative splicing profiles of MAP4K4 or SRSF3 were noted as well in brown adipocytes (BAs) with RNA-binding motif protein 4-knockout (RBM4-/-) compared to the wild-type counterparts. Moreover, the relatively high expressions of authentic SRSF3 transcripts encoding the splicing factor functioned as a novel regulator toward MAP4K4 splicing during brown adipogenesis. The presence of alternatively spliced MAP4K4 variants exerted differential effects on the phosphorylation of c-Jun N-terminal protein kinase (JNK) which was correlated with the differentiation or metabolic signature of BAs. Collectively, the RBM4-SRSF3-MAP4K4 splicing cascade constitutes a novel molecular mechanism in manipulating the development of BAs through related signaling pathways.

RBM4-Nova1-SRSF6 splicing cascade modulates the development of brown adipocytes.

Alternative splicing (AS) is a pivotal mechanism for the expansion of gene diversity, which determines the cellular fate or specification. However, the effect of AS networks on brown adipogenesis has not been comprehensively investigated. In this study, we identified the discriminative splicing profiles of RNA-binding motif protein 4a-knockout (RBM4a-/-) brown adipocytes (BAs) and compared them with those of their wild-type counterparts through deep RNA-sequencing. Among these candidates, RBM4a ablation enhanced the relative level of exon 4-excluded neuro-oncological ventral antigen 1 (Nova1-4) transcripts, which were predominantly generated in embryonic BAs. By contrast, most of the Nova1 transcripts were exon 4-included (Nova1+4) in mature BAs. The Nova1 isoforms exhibited differential effects on repressing the development of BAs. Moreover, overexpression of Nova1 proteins reduced the serine/arginine splicing factor 6 (SRSF6) level by enhancing the generation of intron 2-included (SRSF6+intron 2) transcripts, which are a putative candidate of the AS-coupled nonsense-mediated decay mechanism. Furthermore, we observed the positive effect of SRSF6 on BA development. These results highlight the hierarchical role of RBM4a in an AS cascade that manipulates brown adipogenesis.

Assessment of Blood Glucose Regulation and Safety of Resistant Starch Formula-Based Diet in Healthy Normal and Subjects With Type 2 Diabetes.

To evaluate the effects of the new resistant starch (RS) formula, PPB-R-203, on glucose homeostasis in healthy subjects and subjects with type 2 diabetes.A cohort consisting of 40 healthy participants received test and control diets and was checked for up to 3 hours post-meal. A randomized, 2-regimen, cross-over, comparative study was conducted in 44 subjects with type 2 diabetes and glycemic control was assessed with a continuous glucose monitoring system.In healthy participants, serum glucose values and incremental areas under the glucose curves (AUC) were significantly lower in the PPB-R-203 than the control group (P < 0.05). In patients with type 2 diabetes, mean blood glucose concentrations for subjects on the control regimen were higher than those for subjects on the PPB-R-203-based regimen (7.9 ±â€Š1.7, 95% confidence interval [CI] 7.4-8.4 vs 7.4 ±â€Š1.6, 95% CI 6.9-7.9 mmol/L, respectively; P = 0.023). AUCs for total blood glucose and hyperglycemia (glucose >10 mmol/L) were also reduced for subjects on the PPB-R-203-based regimen as compared with those on control regimen (total blood glucose: 16.2 ±â€Š4.0, 95% CI 14.9-17.4 vs 18.7 ±â€Š4.0, 95% CI 17.6-20.1, P < 0.001; hyperglycemia: 4.9 ±â€Š5.7, 95% CI 3.1-6.6 vs 6.3 ±â€Š6.4, 95% CI 4.3-8.3 mmol/L × day, P = 0.021). However, AUC measurements for hypoglycemia (glucose <3.9 mmol/l) were not statistically significant.A PPB-R-203-based diet reduced postprandial hyperglycemia in patients with type 2 diabetes without increasing the risk of hypoglycemia or glucose excursion.

Effects of high-dose phytoestrogens on circulating cellular microparticles and coagulation function in postmenopausal women.

BACKGROUND/PURPOSE: Estrogen in hormone replacement therapy causes homeostatic changes. However, little is known regarding the safety of high-dose phytoestrogen on coagulation and hematological parameters in healthy postmenopausal women. This study evaluated the effects of high-dose soy isoflavone (300 mg/day) on blood pressure, hematological parameters, and coagulation functions including circulating microparticles in healthy postmenopausal women. METHODS: The original study is a 2-year prospective, double-blind, placebo-controlled study. In total, 431 postmenopausal women (from 3 medical centers) were randomly assigned to receive either high-dose isoflavone or placebo for 2 years. At baseline, 6 months, 1 year, and 2 years after treatment, blood pressure, body weight, liver function tests, hematological parameters, and lipid profiles were measured. The 1(st) year blood specimens of 85 cases of 144 eligible participants (from one of the three centers) were analyzed as D-dimer, von Willebrand factor antigen, factor VII, plasminogen activator inhibitor type 1, and circulating cellular microparticles, including the measurement of monocyte, platelet, and endothelial microparticles. RESULTS: In the isoflavone group, after 1 year, the changes in liver function tests, hematological parameters, and coagulation tests were not different from those of the control. Triglyceride levels were significantly lower after 6 months of isoflavone treatment than the placebo group, but the difference did not persist after 1 year. Endothelial microparticles increased steadily in both groups during the 1-year period but the trend was not affected by treatment. CONCLUSION: The results of the present study indicate that high-dose isoflavone treatment (300 mg/day) does not cause hematological abnormalities or activate coagulation factors.

Evaluating self-management behaviors of diabetic patients in a telehealthcare program: longitudinal study over 18 months.

BACKGROUND: Self-management is an important skill for patients with diabetes, and it involves frequent monitoring of glucose levels and behavior modification. Techniques to enhance the behavior changes of diabetic patients have been developed, such as diabetes self-management education and telehealthcare. Although the patients are engaged in self-management activities, barriers to behavior changes remain and additional work is necessary to address the impact of electronic media and telehealthcare on patient self-care behaviors. OBJECTIVE: The aims of this study were to (1) explore the behaviors of diabetic patients interacting with online applications, (2) determine the impact of a telehealthcare program among 7 self-care behaviors of the patients, and (3) determine the changes in glycosylated hemoglobin (HbA1c) levels. METHODS: A telehealthcare program was conducted to assist the patients with 7 self-care activities. The telehealthcare program lasted for 18 months and included the use of a third-generation mobile telecommunications glucometer, an online diabetes self-management system, and a teleconsultant service. We analyzed the data of 59 patients who participated in the telehealthcare program and 103 who did not. The behavioral assessments and the HbA1c data were collected and statistically analyzed to determine whether the telehealthcare services had an impact on the patients. We divided the 18-month period into 3 6-month intervals and analyzed the parameters of patients assisted by the telehealthcare service at different time points. We also compared the results of those who were assisted by the telehealthcare service with those who were not. RESULTS: There was a significant difference in monitoring blood glucose between the beginning and the end of the patient participation (P=.046) and between the overall period and the end of patient participation (P<.001). Five behaviors were significantly different between the intervention and control patients: being active (P<.001), healthy eating (P<.001), taking medication (P<.001), healthy coping (P=.02), and problem solving (P<.001). Monitoring of blood glucose was significantly different (P=.02) during the 6-12 month stage of patient participation between the intervention and control patients. A significant difference between the beginning and the 6-12 month stage of patient participation was observed for the mean value of HbA1c level (P=.02), and the differences between the overall HbA1c variability and the variability of each 6-month interval was also significant. CONCLUSIONS: Telehealthcare had a positive effect on diabetic patients. This study had enhanced blood glucose monitoring, and the patients in the program showed improvements in glycemic control. The self-care behaviors affect patient outcomes, and the changes of behavior require time to show the effects.

An architecture model for multiple disease management information systems.

Disease management is a program which attempts to overcome the fragmentation of healthcare system and improve the quality of care. Many studies have proven the effectiveness of disease management. However, the case managers were spending the majority of time in documentation, coordinating the members of the care team. They need a tool to support them with daily practice and optimizing the inefficient workflow. Several discussions have indicated that information technology plays an important role in the era of disease management. Whereas applications have been developed, it is inefficient to develop information system for each disease management program individually. The aim of this research is to support the work of disease management, reform the inefficient workflow, and propose an architecture model that enhance on the reusability and time saving of information system development. The proposed architecture model had been successfully implemented into two disease management information system, and the result was evaluated through reusability analysis, time consumed analysis, pre- and post-implement workflow analysis, and user questionnaire survey. The reusability of the proposed model was high, less than half of the time was consumed, and the workflow had been improved. The overall user aspect is positive. The supportiveness during daily workflow is high. The system empowers the case managers with better information and leads to better decision making.