Differential association of body mass index on glycemic control in type 1 diabetes.

BACKGROUND: In contrast to type 2 diabetes, the association of body mass index (BMI) with glycemic control in type 1 diabetes (T1D) remains unclear. We investigated the relationship between BMI and average HbA1c levels in subjects with T1D. METHOD: In this multi-centre observational study, we analysed 719 subjects with T1D aged ≥18 years. Average HbA1c levels over 18 months and other clinical and laboratory parameters were evaluated. RESULTS: The mean age and duration of diabetes at baseline were 41.5 ± 13.9 and 11.3 ± 8.7 years, respectively. A U-shaped correlation between BMI and 18-month average HbA1c levels was documented by a spline curve. Based on this finding, subjects were divided into three groups according to BMI (group I, <21; group II, 21-23; and group III, ≥23 kg/m2 ). In group I, the BMI negatively correlated with average HbA1c (r = -0.172, p = 0.011), while a positive relationship was observed (r = 0.162, p = 0.012) in group III. Average HbA1c levels were lower and the proportion of individuals with well-controlled glycemia (HbA1c <7%) were increased in the higher BMI tertile group among subjects with group I as well as in the lower BMI tertile group among subjects with group III BMI. After adjustment with additional covariates in the multiple regression model, these associations between BMI and HbA1c levels according to the different BMI ranges remained significant. CONCLUSIONS: In Korean subjects with T1D, an inverse relationship of BMI with HbA1c levels was observed in the low BMI group, while a positive correlation was shown in the high BMI group. Copyright © 2016 John Wiley & Sons, Ltd.

The Paradoxical Effects of AMPK on Insulin Gene Expression and Glucose-Induced Insulin Secretion.

The activation of AMP-activated protein kinase (AMPK) is known to repress the expression of the insulin gene and glucose-stimulated insulin secretion (GSIS). However, the mechanisms by which this occurs, as well as the effects of AMPK activation on glucolipotoxicity-induced ß-cell dysfunction, have not been elucidated. To investigate the effects of 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR) and peroxisome proliferator-activated receptorγ-coactivator-1α (PGC-1α) on ß-cell-specific genes under glucolipotoxic conditions, we performed real-time PCR and measured insulin secretion by primary islets. To study these effects in vivo, we administered AICAR for 10 days (1 mg/g body weight) to 90% pancreatectomized hyperglycemic mice. The exposure of isolated rat and human islets to glucolipotoxic conditions and the overexpression of PGC-1α suppressed insulin and NEUROD1 mRNA expression. However, the expression of these genes was preserved by AICAR treatment and by PGC-1α inhibition. Exposure of isolated islets to glucolipotoxic conditions for 3 days decreased GSIS, which was also well maintained by AICAR treatment and by PGC-1α inhibition. The administration of AICAR to 90% pancreatectomized hyperglycemic mice improved glucose tolerance and insulin secretion. These results indicate that treatment of islets with an AMPK agonist under glucolipotoxic conditions protects against glucolipotoxicity-induced ß-cell dysfunction. A better understanding of the functions of molecules such as PGC-1α and AMPK, which play key roles in intracellular fuel regulation, could herald a new era for the treatment of patients with type 2 diabetes mellitus by providing protection against glucolipotoxicity.

Triglyceride glucose index, a marker of insulin resistance, is associated with coronary artery stenosis in asymptomatic subjects with type 2 diabetes.

BACKGROUND: Insulin resistance is one of the most important contributing factors to cardiovascular disease. This study aimed to investigate the association between coronary artery stenosis (CAS) and triglyceride glucose index (TyG index), a simple insulin resistance marker, in asymptomatic subjects with type 2 diabetes. METHODS: We recruited asymptomatic adults with type 2 diabetes but without previous history of coronary heart disease (n = 888). Significant CAS was defined as maximum intraluminal stenosis ≥70 % by coronary CT angiography. TyG index was calculated as log [fasting triglycerides (mg/dl) x fasting glucose (mg/dl)/2]. RESULTS: Mean age was 63.8 ± 9.5 and 58.9 % of the subjects were men. We analyzed the participants according to the tertile of TyG index. The TyG index was correlated with HOMA-IR (r = 0.397, P < 0.001), and subjects with higher tertile of TyG index were younger but showed worse clinical and metabolic parameters. The prevalence of CAS was higher in subjects with higher tertile of TyG compared with those with lower tertile of TyG (14 % vs. 7.8 %, P = 0.022). On multiple regression analysis, the highest tertile of TyG index was an independent risk factor for CAS after adjustment for other confounders (odds ratio, 3.19 [95 % CI, 1.371-7.424]). Subgroup analysis showed that TyG index showed more significant association with CAS in patients with risk factors such as old age, longer duration of diabetes, poor glycemic control, no statin use, and male gender. CONCLUSION: Higher TyG index is associated with increased risk of CAS in asymptomatic subjects with type 2 diabetes, particularly when they have risk factors for cardiovascular disease. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials. gov with the registration number of NCT02070926 in Feb 23, 2014.

Identifying subgroups of obesity using the product of triglycerides and glucose: the Korea National Health and Nutrition Examination Survey, 2008-2010.

OBJECTIVE: To determine whether the TyG index, a product of the levels of triglycerides and glucose, may be a valuable marker for identifying metabolically obese but normal weight (MONW) or metabolically healthy but obese (MHO) individuals. DESIGN AND SUBJECTS: A total of 17 029 nondiabetic subjects (7185 men and 9844 women) were selected from the Korea National Health and Nutrition Examination Survey conducted in 2008-2010. Individuals with a normal body mass index (BMI) (≥18·5 and <23 kg/m(2) ) and the highest quartile of the homoeostasis model assessment of insulin resistance (HOMA-IR) were classified as MONW. Individuals with obesity (BMI ≥25 kg/m(2) ) and the lowest quartile of HOMA-IR were classified as MHO. MEASUREMENTS: The TyG index was calculated as ln[fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. RESULTS: The levels of the TyG index paralleled with various metabolic risk parameters. The index was significantly higher in the MONW group and lower in the MHO group when compared with the non-MONW group and the non-MHO group, respectively. The odds ratios (ORs) of being categorized into the MONW group were approximately fourfold higher in the highest vs lowest quartiles of the TyG index (3·999: 95% CI, 2·508-6·376 in men; 4·737: 95% CI, 3·418-6·565 in women) among normal weight subjects. Conversely, there was a stepwise decrease in the OR of being categorized into the MHO group across the TyG index quartiles among obese subjects. CONCLUSIONS: These data highlight the value of the TyG index in discriminating those subjects with higher risks of metabolic diseases.

Successful xenotransplantation with re-aggregated and encapsulated neonatal pig liver cells for treatment of mice with acute liver failure.

BACKGROUND: Hepatocyte transplantation is a promising therapy for acute liver failure. Cell therapy using xenogeneic sources has emerged as an alternative treatment for patients with organ failure due to the shortage of transplantable human organs. The purpose of this study was to improve the survival of mice with acute liver failure by transplanting encapsulated neonatal pig re-aggregated liver cells (NPRLC). METHODS: Liver injury was induced in C57/BL6 male mice by the injection of 600 mg/kg of acetaminophen. Xenogeneic liver cells were isolated from a neonatal pig and processed via re-aggregation and encapsulation to improve the efficiency of the xenogeneic liver cell transplantation. The neonatal pig liver showed abnormal lobule structure. Isolated cells were re-aggregated and intraperitoneally transplanted into acute liver failure mice models. RESULTS: Re-aggregated cells showed significantly enhanced viability and significantly greater synthesis of albumin and urea than cells cultured in monolayers. Further, we observed improved serum levels of ALT/AST, and the survival rate of mice with acute liver failure was improved by the intraperitoneal transplantation of encapsulated hepatocytes (48,000 equivalent (Eq) per mouse). CONCLUSIONS: This study shows that using encapsulated NPRLCs improves the efficacy of xenogeneic liver cell transplantation for the treatment of mice with acute liver failure. Therefore, this may be a good strategy for bridge therapy for the treatment of acute liver failure in humans.

A randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes.

The aim of this study was to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes in a double-blind randomized placebo-controlled study. A total of 109 patients were randomized to 100 mg (n=37) or 200 mg (n=33) anagliptin twice daily or placebo (n=39). The primary objective was to alter HbA1c levels from baseline at a 24-week endpoint. The overall baseline mean age and body mass index were 56.20 ± 9.77 years and 25.01 ± 2.97 kg/m(2), respectively, and the HbA1c level was of 7.14 ± 0.69 %. Anagliptin at 100 mg and 200 mg produced significant reductions in HbA1c (-0.50 ± 0.45 % and -0.51 ± 0.55%, respectively), and the placebo treatment resulted in an increase in HbA1c by 0.23 ± 0.62 %. Both doses of anagliptin produced significant decreases in fasting plasma glucose (-0.53 ± 1.25 mmol/L and -0.72 ± 1.25 mmol/L, respectively) and the proinsulin/insulin ratio (-0.04 ± 0.15 and -0.07 ± 0.18, respectively) compared with placebo. No meaningful body weight changes from baseline were observed in three groups. Plasma dipeptidyl peptidase (DPP)-4 activity was significantly inhibited after 24 weeks of anagliptin treatment, and >75% and >90% inhibitions were observed during the meal tolerance tests with 100 mg and 200 mg anagliptin, respectively. The incidences of adverse or serious adverse events were similar among the three study groups. Twice-daily anagliptin therapy effectively inhibited DPP-4 activity and improved glycemic control and was well-tolerated in patients with type 2 diabetes.

Reversal of Hypoglycemia Unawareness with a Single-donor, Marginal Dose Allogeneic Islet Transplantation in Korea: A Case Report.

Pancreatic islet transplantation is a physiologically advantageous and minimally invasive procedure for the treatment of type 1 diabetes mellitus. Here, we describe the first reported case of successful allogeneic islet transplantation alone, using single-donor, marginal-dose islets in a Korean patient. A 59-yr-old patient with type 1 diabetes mellitus, who suffered from recurrent severe hypoglycemia, received 4,163 islet equivalents/kg from a single brain-death donor. Isolated islets were infused intraportally without any complications. The immunosuppressive regimen was based on the Edmonton protocol, but the maintenance dosage was reduced because of mucositis and leukopenia. Although insulin independence was not achieved, the patient showed stabilized blood glucose concentration, reduced insulin dosage and reversal of hypoglycemic unawareness, even with marginal dose of islets and reduced immunosuppressant. Islet transplantation may successfully improve endogenous insulin production and glycemic stability in subjects with type 1 diabetes mellitus.

My Wife Is My Insurance Policy: Household Bargaining and Couples' Purchase of Long-Term Care Insurance.

This paper examines household decisions over long-term care insurance (LTCI) purchases through a bargaining lens. Long-term care insurance purchase is a discrete decision around which spouses' interests may diverge substantially. The cost of buying LTCI is typically borne by both spouses, but the benefits of LTCI go disproportionately to women, who are more likely to need long-term care for themselves, and to benefit from the asset protection and other support LTCI offers in the event their husband needs care. Using panel data on married couples ages 50-75 from the US Health and Retirement Study (HRS), we test and find support for the hypothesis that spouses' relative bargaining power is related to LTCI purchase decisions. In particular, when husbands have final say in household decisions, LTCI coverage is less likely. The findings suggest that spouse's relative bargaining power matters for health care choices and, therefore, for the welfare of older men and women.

Generation of iPSC-derived insulin-producing cells from patients with type 1 and type 2 diabetes compared with healthy control.

For alternative sources of ß cells, patient-specific induced pluripotent stem cells (iPSCs) could be promising, as cells derived from the "self" allow autologous transplantation. However, only a few studies have investigated insulin-producing cells (IPCs) using iPSCs of patients with type 1 diabetes (T1D). In this study, we generated IPCs using iPSCs derived from patients with T1D and type 2 diabetes (T2D) and compared them with IPCs from a non-diabetic (ND) individual. To facilitate differentiation of human iPSCs into IPCs, we induced PDX-1 gene expression using Ad-PDX-1/VP16. IPCs derived from T1D- and T2D-specific iPSCs expressed islet-specific markers such as Pdx-1, MafA, Beta2/NeuroD, and insulin, similar to IPCs derived from ND-specific iPSCs. In addition, IPCs derived from T1D- and T2D-specific iPSCs showed comparable glucose-stimulated insulin secretion as IPCs derived from ND-specific iPSCs. These results suggest the potential for autologous transplantation using patient-specific iPSCs in patients with T1D and T2D. This study was clinically significant because the majority of people with diabetes have T2D and insulin secretion declines over time in T2D. To the best of our knowledge, this is the first study to generate and simultaneously compare IPCs from ND-, T1D-, and T2D-specific iPSCs.

South Korean time trade-off values for EQ-5D health states: modeling with observed values for 101 health states.

OBJECTIVES: This study establishes the South Korean population-based preference weights for EQ-5D based on values elicited from a representative national sample using the time trade-off (TTO) method. METHODS: The data for this paper came from a South Korean EQ-5D valuation study where 1307 representative respondents were invited to participate and a total of 101 health states defined by the EQ-5D descriptive system were directly valued. Both aggregate and individual level modeling were conducted to generate values for all 243 health states defined by EQ-5D. Various regression techniques and model specifications were also examined in order to produce the best fit model. Final model selection was based on minimizing the difference between the observed and estimated value for each health state. RESULTS: The N3 model yielded the best fit for the observed TTO value at the aggregate level. It had a mean absolute error of 0.029 and only 15 predictions out of 101 had errors exceeding 0.05 in absolute magnitude. CONCLUSIONS: The study successfully establishes South Korean population-based preference weights for the EQ-5D. The value set derived here is based on a representative population sample, limiting the interpolation space and possessing better model performance. Thus, this EQ-5D value set should be given preference for use with the South Korean population.

Metabolic health is more closely associated with decrease in lung function than obesity.

OBJECTIVE: Previous studies have evaluated the link between metabolic syndrome and obesity with impaired lung function, however findings have been controversial. We aimed to compare lung function among subjects with different metabolic health and obesity status. METHODS: Total 10,071 participants were evaluated at the Health Promotion Center in Seoul St. Mary's Hospital between January 2012 and December 2014. Being metabolically healthy was defined as having fewer than three of the following risk factors: high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol and abdominal obesity. Obesity status was defined as body mass index (BMI) higher than 25 kg/m2. Analyses of pulmonary function were performed in four groups divided according to metabolic health and obesity: metabolically healthy non-obese (MHNO), metabolically health obese (MHO), metabolically unhealthy non-obese (MUHNO), and metabolically unhealthy obese (MUHO). RESULTS: Metabolically unhealthy subjects were more prone to decreased lung function compared with their metabolically healthy counterparts, regardless of obesity status. When multinomial logistic regression analysis was performed according to quartiles of forced vital capacity (FVC) or forced expiratory volume in 1 second (FEV1) (% pred), after adjusting for age, sex, and smoking status, odds ratio (OR) for the lowest FVC and FEV1 (% pred) quartiles were significantly higher in MUHO subjects (1.788 [95% CI, 1.531-2.089] and 1.603 [95% CI, 1.367-1.881]) and lower in MHO subjects (0.768 [95% CI, 0.654-0.902] and 0.826 [95% CI, 0.700-0.976]) with MHNO group as the reference, when OR for highest FVC and FEV1 quartiles were considered as 1.0. CONCLUSION: Metabolic health is more closely associated with impaired lung function than obesity.

Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: We evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin. METHODS: A total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita, n=65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb, n=66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment, n=34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24. RESULTS: The add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (P<0.001 vs. baseline) decrease in glycosylated hemoglobin (HbA1c) at week 16, while changes in HbA1c were insignificant in the Met+Sita group (-0.09%±0.10%, P=0.113). After 8 weeks of triple combination therapy, HbA1c levels were comparable between Met+Sita and Met+Sita+Acarb group (7.66%±0.13% vs. 7.47%±0.12%, P=0.321). Acarbose add-on therapy demonstrated suppressed glucagon secretion (area under the curve of glucagon, 4,726.17±415.80 ng·min/L vs. 3,314.38±191.63 ng·min/L, P=0.004) in the absence of excess insulin secretion during the meal tolerance tests at week 16 versus baseline. The incidence of adverse or serious adverse events was similar between two groups. CONCLUSION: In conclusion, a 16-week acarbose add-on therapy to metformin and sitagliptin, effectively lowered HbA1c without significant adverse events. Acarbose might be a good choice as a third-line therapy in addition to metformin and sitagliptin in Korean subjects with T2DM who have predominant postprandial hyperglycemia and a high carbohydrate intake.

Efficacies of Stem Cell Therapies for Functional Improvement of the ß Cell in Patients with Diabetes: A Systematic Review of Controlled Clinical Trials.

BACKGROUND AND OBJECTIVES: This study was performed to investigate whether stem cell therapy enhances ß cell function by meta-analysis with proper consideration of variability of outcome measurements in controlled trial of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) patients. METHODS: A systematic search was performed from inception to January 2018 in PubMed, EMBASE, and Cochrane databases. ß cell function was assessed by stimulated C-peptide, fasting C-peptide, normal glycosylated hemoglobin levels (HbA1C), and exogenous insulin dose patterns. The quality of the studies were assessed by both the Cochrane Collaboration's Risk of Bias (ROB) for Randomized controlled trials and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) for non-randomized controlled trials. RESULTS: From the selected final 15 articles, total of 16 trials were analyzed. There were 6 T1DM trials (total 153 cases) and 10 T2DM trials (total 457 cases). In T2DM patients, the changes in stimulated C-peptide, HbA1c, and exogenous insulin dose versus baseline showed a favorable pattern with a significant heterogeneity in stem cell therapy. In T1DM, there was no significant difference between control group and stem cell therapy group in three indicators except for HbA1c. Most of the studies were rated as having high risk of bias in the quality assessment. CONCLUSIONS: The stem cell therapy for DM patients is not effective in T1DM but seems to be effective in improving the ß cell function in T2DM. However the observed effect should be interpreted with caution due to the significant heterogeneity and high risk of bias within the studies. Further verification through a rigorously designed study is warranted.

Study Time after School and Habitual Eating Are Associated with Risk for Obesity among Overweight Korean Children: A Prospective Study.

OBJECTIVE: To investigate behavioral factors that contribute to the development of obesity among overweight children. METHODS: Among a community sample of 884 children aged 9-13 years, 833 children completed a baseline and 1-year follow-up examination that included anthropometrics, physical fitness, and behavioral factors. RESULTS: During the follow-up period, BMI for most children with normal weight or obesity did not change. However, among overweight children (n = 100), about one-third developed obesity (n = 26), while the others were categorized as normal weight (n = 32) or overweight (n = 42) after 1 year. Characteristics of overweight children at baseline and follow-up were analyzed. Those who developed obesity showed a notable increase in blood pressure as well as in BMI, waist circumference, and body fat over 1 year. At baseline, this group spent more time studying after school compared to overweight children who did not develop obesity, while there were no differences in time spent viewing television or engaging in vigorous physical activity. Eating outside the home, fast food consumption, and habitual eating in the absence of hunger were more common at baseline in those who did versus those who did not develop obesity. After adjusting for age, sex, and BMI, spending more time studying after school and habitual eating without hunger were associated with the development of obesity. CONCLUSION: Among Korean overweight children, study time after school and habitual eating without hunger were associated with an increased risk for development of obesity.

DNA Methylation Profiles of Blood Cells Are Distinct between Early-Onset Obese and Control Individuals.

Obesity is a highly prevalent, chronic disorder that has been increasing in incidence in young patients. Both epigenetic and genetic aberrations may play a role in the pathogenesis of obesity. Therefore, in-depth epigenomic and genomic analyses will advance our understanding of the detailed molecular mechanisms underlying obesity and aid in the selection of potential biomarkers for obesity in youth. Here, we performed microarray-based DNA methylation and gene expression profiling of peripheral white blood cells obtained from six young, obese individuals and six healthy controls. We observed that the hierarchical clustering of DNA methylation, but not gene expression, clearly segregates the obese individuals from the controls, suggesting that the metabolic disturbance that occurs as a result of obesity at a young age may affect the DNA methylation of peripheral blood cells without accompanying transcriptional changes. To examine the genome-wide differences in the DNA methylation profiles of young obese and control individuals, we identified differentially methylated CpG sites and investigated their genomic and epigenomic contexts. The aberrant DNA methylation patterns in obese individuals can be summarized as relative gains and losses of DNA methylation in gene promoters and gene bodies, respectively. We also observed that the CpG islands of obese individuals are more susceptible to DNA methylation compared to controls. Our pilot study suggests that the genome-wide aberrant DNA methylation patterns of obese individuals may advance not only our understanding of the epigenomic pathogenesis but also early screening of obesity in youth.

Reliability and Validity of the Korean Version of the General-Food Craving Questionnaire-Trait for Children.

OBJECTIVE: The General-Food Craving Questionnaire-Trait (G-FCQ-T) is a validated, assessment scale for food craving. The aim of this study was to measure its reliability and validity for Korean children. METHODS: A total of 172 children (94 boys and 78 girls) were selected to fill out a set of questionnaires, including the G-FCQ-T, the Children's version of the Dutch Eating Behavior Questionnaire (DEBQ-C), and the Three-Factor Eating Questionnaire (TFEQ) in the Korean language. RESULTS: The internal consistency (Cronbach's alpha=0.933) and test-retest reliability (r=0.653) were satisfactory. The G-FCQ-T showed a significantly positive correlation with the DEBQ-C (r=0.560) and the TFEQ (r=0.397). The optimum cutoff score of the G-FCQ-T set by Receiver Operating Characteristics analysis was 51, with sensitivity and specificity of 0.833 and 0.825, respectively, for children. CONCLUSION: The G-FCQ-T showed good reliability and validity for assessing food craving for children and could become a practial instrument in clinical and research settings.

Factors associated with greater benefit of a national reimbursement policy for blood glucose test strips in adult patients with type 1 diabetes: A prospective cohort study.

AIMS/INTRODUCTION: We aimed to identify factors independently associated with greater benefit of a national reimbursement policy for blood glucose test strips in adult patients with type 1 diabetes, in terms of glycemic control and the rate of severe hypoglycemia. MATERIALS AND METHODS: This was a prospective cohort study of 466 adult patients with type 1 diabetes from five tertiary referral hospitals who registered for a national reimbursement program for blood glucose strips and were then followed-up for 12 months. Factors associated with a > 5% reduction in glycated hemoglobin (HbA1c) and decreased rate of severe hypoglycemia (SH) at 12 months from baseline were evaluated. RESULTS: At the end of the 12 months of follow up, 158 of 466 patients (33.9%) achieved >5% reduction in HbA1c, and 47 of 111 patients (42.3%) had a decreased rate of SH relative to baseline. Higher HbA1c (P < 0.001), lower total daily insulin dose at baseline (P = 0.048) and an increase in self-monitoring of blood glucose (SMBG) frequency during follow up (P = 0.001) were independently associated with >5% reduction in HbA1c. A higher SMBG frequency (P < 0.001), higher rate of SH at baseline (P = 0.029) and lack of hypoglycemic unawareness (P = 0.044) were independently associated with an increase in the frequency of SMBG during follow up. Higher SMBG frequency at baseline (P < 0.001) was independently associated with a decreased rate of SH. CONCLUSIONS: Several factors, including higher SMBG frequency at baseline, were independently associated with reduced HbA1c and a decreased rate of severe hypoglycemia, showing that patients with these characteristics derive the most benefit from reimbursement of blood glucose test strips.

Antifibrotic effect of rapamycin containing polyethylene glycol-coated alginate microcapsule in islet xenotransplantation.

Islet microencapsulation is an attractive strategy for the minimization or avoidance of life-long immunosuppression after transplantation. However, the clinical implementation of this technique is currently limited by incomplete biocompatibility. Thus, the aim of the present study was to demonstrate the improved biocompatibility of rapamycin-containing polyethylene glycol (Rapa-PEG)-coating on alginate microcapsules containing xenogeneic islets. The Rapa-PEG-coating on the alginate layer was observed using scanning electron microscopy (SEM) and the molecular cut-off weight of the microcapsules was approximately 70 kDa. The viabilities of the alginate-encapsulated and Rapa-PEG-coated alginate-encapsulated islets were lower than the viability of the naked islets just after encapsulation, but these the differences diminished over time in culture dishes. Rapa-PEG-coating on the alginate capsules effectively decreased the proliferation of macrophage cells compared to the non-coating and alginate coating of xenogeneic pancreas tissues. Glucose-stimulated insulin secretion did not significantly differ among the groups prior to transplantation. The random blood glucose levels of diabetic mice significantly improved following the transplantation of alginate-encapsulated and Rapa-PEG-coated alginate-encapsulated islets, but there were no significant differences between these two groups. However, there was a significant decrease in the number of microcapsules with fibrotic cell infiltration in the Rapa-PEG-coated alginate microcapsule group compared to the alginate microcapsule group. In conclusion, Rapa-PEG-coating might be an effective technique with which to improve the biocompatibility of microcapsules containing xenogeneic islets. Copyright © 2015 John Wiley & Sons, Ltd.

An Internet-based health gateway device for interactive communication and automatic data uploading: Clinical efficacy for type 2 diabetes in a multi-centre trial.

Introduction The aim of this study was to improve the quality of diabetes control and evaluate the efficacy of an Internet-based integrated healthcare system for diabetes management and safety. Methods We conducted a large-scale, multi-centre, randomized clinical trial involving 484 patients. Patients in the intervention group ( n = 244) were treated with the Internet-based system for six months, while the control group ( n = 240) received the usual outpatient management over the same period. HbA1c, blood chemistries, anthropometric parameters, and adverse events were assessed at the beginning of the study, after three months, and the end of the study. Results There were no initial significant differences between the groups with respect to demographics and clinical parameters. Upon six-month follow-up, HbA1c levels were significantly decreased from 7.86 ± 0.69% to 7.55 ± 0.86% within the intervention group ( p < 0.001) compared to 7.81 ± 0.66% to 7.70 ± 0.88% within the control group. Postprandial glucose reduction was predominant. A subgroup with baseline HbA1c higher than 8% and good compliance achieved a reduction of HbA1c by 0.8 ± 1.05%. Glucose control and waist circumference reduction were more effective in females and subjects older than 40 years of age. There were no adverse events associated with the intervention. Discussion This e-healthcare system was effective for glucose control and body composition improvement without associated adverse events in a multi-centre trial. This system may be effective in improving diabetes control in the general population.

Physician-Directed Diabetes Education without a Medication Change and Associated Patient Outcomes.

BACKGROUND: When patients with diabetes mellitus (DM) are first referred to a hospital from primary health care clinics, physicians have to decide whether to administer an oral hypoglycemic agent (OHA) immediately or postpone a medication change in favor of diabetes education regarding diet or exercise. The aim of this study was to determine the effect of diabetes education alone (without alterations in diabetes medication) on blood glucose levels. METHODS: The study was conducted between January 2009 and December 2013 and included patients with DM. The glycosylated hemoglobin (HbA1c) levels were evaluated at the first visit and after 3 months. During the first medical examination, a designated doctor also conducted a diabetes education session that mainly covered dietary management. RESULTS: Patients were divided into those who received no diabetic medications (n=66) and those who received an OHA (n=124). Education resulted in a marked decrease in HbA1c levels in the OHA group among patients who had DM for <1 year (from 7.0%±1.3% to 6.6%±0.9%, P=0.0092) and for 1 to 5 years (from 7.5%±1.8% to 6.9%±1.1%, P=0.0091). Those with DM >10 years showed a slightly lower HbA1c target achievement rate of <6.5% (odds ratio, 0.089; P=0.0024). CONCLUSION: For patients who had DM for more than 5 years, higher doses or changes in medication were more effective than intensive active education. Therefore, individualized and customized education are needed for these patients. For patients with a shorter duration of DM, it may be more effective to provide initial intensive education for diabetes before prescribing medicines, such as OHAs.