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Several models for the long-term development of T2DM already exist, focusing on the dynamics of the interaction between glycemia, insulinemia and β-cell mass. Current models consider representative (fasting or daily average) glycemia and insulinemia as characterizing the compensation state of the subject at some instant in slow time. This implies that only these representative levels can be followed through time and that the role of fast glycemic oscillations is neglected. An improved model (DPM15) for the long-term progression of T2DM is proposed, introducing separate peripheral and hepatic (liver and kidney) insulin actions. The DPM15 model no longer uses near-equilibrium approximation to separate fast and slow time scales, but rather describes, at each step in slow time, a complete day in the life of the virtual subject in fast time. The model can thus represent both fasting and postprandial glycemic levels and describe the effect of interventions acting on insulin-enhanced tissue glucose disposal or on insulin-inhibited hepatic glucose output, as well as on insulin secretion and β-cell replicating ability. The model can simulate long-term variations of commonly used clinical indices (HOMA-B, HOMA-IR, insulinogenic index) as well as of Oral Glucose Tolerance or Euglycemic Hyperinsulinemic Clamp test results. The model has been calibrated against observational data from the Diabetes Prevention Program study: it shows good adaptation to observations as a function of very plausible values of the parameters describing the effect of such interventions as Placebo, Intensive LifeStyle and Metformin administration. [ABSTRACT FROM AUTHOR]

Recently, we observed a 15% decrease in the incidence of type 1 diabetes (T1D) in Australian 0-4-year-old children following the introduction of RV vaccination [[2], [3]], suggesting that RV vaccination could contribute to the primary prevention of this autoimmune disease. Australian surveillance data [[11]] show that the prevalence of RV G3 strains increased slightly along with an increase in strain diversity in the post-RV vaccine era, but G3 remains a minor component of disease-causing RV strains. RV was prevalent in nurseries, and the change to rooming-in would have altered the timing of exposure to RV, delaying it until later in the first year of life when, based on NOD mouse studies [[17]-[19]], RV might promote rather than retard development of diabetes. [Extracted from the article]

Background: Disparities in type 2 diabetes (T2D) care provision and clinical outcomes have been reported in the last 2 decades in the UK. Since then, a number of initiatives have attempted to address this imbalance. The aim was to evaluate contemporary data as to whether disparities exist in glycaemic control, monitoring, and prescribing in people with T2D.Methods and Findings: A T2D cohort was identified from the Royal College of General Practitioners Research and Surveillance Centre dataset: a nationally representative sample of 164 primary care practices (general practices) across England. Diabetes healthcare provision and glucose-lowering medication use between 1 January 2012 and 31 December 2016 were studied. Healthcare provision included annual HbA1c, renal function (estimated glomerular filtration rate [eGFR]), blood pressure (BP), retinopathy, and neuropathy testing. Variables potentially associated with disparity outcomes were assessed using mixed effects logistic and linear regression, adjusted for age, sex, ethnicity, and socioeconomic status (SES) using the Index of Multiple Deprivation (IMD), and nested using random effects within general practices. Ethnicity was defined using the Office for National Statistics ethnicity categories: White, Mixed, Asian, Black, and Other (including Arab people and other groups not classified elsewhere). From the primary care adult population (n = 1,238,909), we identified a cohort of 84,452 (5.29%) adults with T2D. The mean age of people with T2D in the included cohort at 31 December 2016 was 68.7 ± 12.6 years; 21,656 (43.9%) were female. The mean body mass index was 30.7 ± SD 6.4 kg/m2. The most deprived groups (IMD quintiles 1 and 2) showed poorer HbA1c than the least deprived (IMD quintile 5). People of Black ethnicity had worse HbA1c than those of White ethnicity. Asian individuals were less likely than White individuals to be prescribed insulin (odds ratio [OR] 0.86, 95% CI 0.79-0.95; p < 0.01), sodium-glucose cotransporter-2 (SGLT2) inhibitors (OR 0.68, 95% CI 0.58-0.79; p < 0.001), and glucagon-like peptide-1 (GLP-1) agonists (OR 0.37, 95% CI 0.31-0.44; p < 0.001). Black individuals were less likely than White individuals to be prescribed SGLT2 inhibitors (OR 0.50, 95% CI 0.39-0.65; p < 0.001) and GLP-1 agonists (OR 0.45, 95% CI 0.35-0.57; p < 0.001). Individuals in IMD quintile 5 were more likely than those in the other IMD quintiles to have annual testing for HbA1c, BP, eGFR, retinopathy, and neuropathy. Black individuals were less likely than White individuals to have annual testing for HbA1c (OR 0.89, 95% CI 0.79-0.99; p = 0.04) and retinopathy (OR 0.82, 95% CI 0.70-0.96; p = 0.011). Asian individuals were more likely than White individuals to have monitoring for HbA1c (OR 1.10, 95% CI 1.01-1.20; p = 0.023) and eGFR (OR 1.09, 95% CI 1.00-1.19; p = 0.048), but less likely for retinopathy (OR 0.88, 95% CI 0.79-0.97; p = 0.01) and neuropathy (OR 0.88, 95% CI 0.80-0.97; p = 0.01). The study is limited by the nature of being observational and defined using retrospectively collected data. Disparities in diabetes care may show regional variation, which was not part of this evaluation.Conclusions: Our findings suggest that disparity in glycaemic control, diabetes-related monitoring, and prescription of newer therapies remains a challenge in diabetes care. Both SES and ethnicity were important determinants of inequality. Disparities in glycaemic control and other areas of care may lead to higher rates of complications and adverse outcomes for some groups. [ABSTRACT FROM AUTHOR]

Background and aims: Many countries lack resources to identify patients at risk of developing Type 2 diabetes mellitus (diabetes). We aimed to develop and validate a diabetes risk score based on easily accessible clinical data. Methods: Prospective study including 5277 participants (55.0% women, 51.8±10.5 years) free of diabetes at baseline. Comparison with two other published diabetes risk scores (Balkau and Kahn clinical, respectively 5 and 8 variables) and validation on three cohorts (Europe, Iran and Mexico) was performed. Results: After a mean follow-up of 10.9 years, 405 participants (7.7%) developed diabetes. Our score was based on age, gender, waist circumference, diabetes family history, hypertension and physical activity. The area under the curve (AUC) was 0.772 for our score, vs. 0.748 (p<0.001) and 0.774 (p = 0.668) for the other two. Using a 13-point threshold, sensitivity, specificity, positive and negative predictive values (95% CI) of our score were 60.5 (55.5–65.3), 77.1 (75.8–78.2), 18.0 (16.0–20.1) and 95.9 (95.2–96.5) percent, respectively. Our score performed equally well or better than the other two in the Iranian [AUC 0.542 vs. 0.564 (p = 0.476) and 0.513 (p = 0.300)] and Mexican [AUC 0.791 vs. 0.672 (p<0.001) and 0.778 (p = 0.575)] cohorts. In the European cohort, it performed similarly to the Balkau score but worse than the Kahn clinical [AUC 0.788 vs. 0.793 (p = 0.091) and 0.816 (p<0.001)]. Diagnostic capacity of our score was better than the Balkau score and comparable to the Kahn clinical one. Conclusion: Our clinically-based score shows encouraging results compared to other scores and can be used in populations with differing diabetes prevalence. [ABSTRACT FROM AUTHOR]

Gastric emptying (GE) can be either delayed or accelerated in diabetes mellitus (DM). However, most research has focused on delayed GE mediated by a chronic hyperglycemic condition in DM. As such, the function of GE in the early stages of DM is not well understood. Interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal tract. In the present study, we investigated changes in GE and ICC networks in the early stages of DM using a streptozotocin-induced type 1 diabetic mouse model. The changes in GE were measured by the 13C-octanoic acid breath test. ICC networks were immunohistochemically detected by an antibody for c-Kit, a specific marker for ICC. Our results showed that GE in type 1 DM was significantly accelerated in the early stages of DM (2–4 weeks after onset). In addition, acute normalization of blood glucose levels by a single administration of insulin did not recover normal GE. ICC networks of the gastric antrum were significantly increased in DM and were not affected by the acute normalization of blood glucose. In conclusion, our results suggest that GE is accelerated in the early stages of DM, and it is associated with increased ICC networks. This mechanism may help to clarify a link between the onset of DM and GE disorders. [ABSTRACT FROM AUTHOR]

Purpose: To investigate if there are differences in macular capillaries between black and white subjects using optical coherence tomography angiography (OCTA) and identify potential factors underlying the epidemiologically-based higher vulnerability of black populations to diabetic retinopathy (DR). Methods: This prospective, observational cross-sectional study included 93 eyes of 47 healthy subjects with no medical history and ocular history who self-identified as black or white and were matched for age, sex, refractive error, and image quality. Subjects underwent OCTA imaging (RTVue-XR Avanti) of the superficial (SCP) and deep (DCP) capillary plexuses and choriocapillaris. AngioAnalytics was used to analyze vessel density (VD) and choriocapillaris % blood flow area (BFA) in the 1mm-diameter fovea, parafovea, and 3mm-diameter circular area including the fovea and parafovea (3x3mm image). Foveal avascular zone (FAZ) was also analyzed. Linear mixed models were used to evaluate for differences between the study groups. Results: Compared to the white subjects in this study, black subjects were found to have: lower foveal VD in the SCP (p<0.05); lower VD in the parafovea and in the 3x3mm image in the DCP (p<0.05); larger FAZ in SCP and DCP (p<0.05); and decreased choriocapillary BFA in the area underlying the fovea, parafovea, and 3x3mm image (p<0.05). Conclusion: In our study, our black subjects had decreased macular capillary vasculature compared to matched white subjects, even in early adulthood and the absence of any systemic or ocular conditions. To our knowledge, this is the first report showing that retinal and choriocapillary vascular differences may contribute to racial disparities in vulnerability to DR. [ABSTRACT FROM AUTHOR]

Background: The extent of medication adherence in patients with type 2 diabetes mellitus (T2DM) several years after starting treatment with hypoglycemic agents remains unknown. Most previous work on medication adherence targeting this group of patients has been undertaken across a single year or is questionnaire based. This study aimed to determine medication adherence status and factors affecting adherence 3 years after initiation of hypoglycemic agents, using a nationwide medical claim-based database in Japan. Methods: This retrospective study was conducted on data from 884 subjects with T2DM to better understand medication adherence, the effects of polypharmacy, and other factors. We also investigated the effects of medication nonadherence on hemoglobin A1c levels. Proportion of days covered was defined as the number of days for which a hypoglycemic agent was prescribed and in the patient’s possession to the number of days in the observation period. A proportion of days covered ≥0.8 were considered adherent, and those with a value <0.8 as nonadherence. Polypharmacy was defined as taking ≥5 medications. Results: Of the 884 patients investigated, 440 were considered adherent during the study period. Significant factors related to adherence included number of medications (3 or 4, or ≥5), male sex, age 50–<60 years, and total number of visits ≥17. Medication adherence was also a factor related to patients with hemoglobin A1c values < 7.0% at the end of the observation period. Conclusions: We surveyed medication adherence for 3 years with post medication initiation, and found that subjects aged 50–<60 years, those with ≥3 concomitant medications, and those with a total number of visits ≥17 were more likely to be adherent and persistent, and more likely to continue their hypoglycemic agents. A high degree of medication adherence was found to have a positive influence on hemoglobin A1c levels. [ABSTRACT FROM AUTHOR]

CD34+ cells maintain vascular homeostasis and predict cardiovascular outcomes. We previously evaluated the association of CD34+ cells with cardiovascular disease (CVD) events over 23 months, but long-term CVD outcomes in relation to levels of CD34+ cells in patients on maintenance hemodialysis are unclear. Herein, we analyzed the long-term predictive potential levels of CD34+ cells for CVD outcomes and all-cause mortality. Between March 2005 and May 2005, we enrolled 215 patients on maintenance hemodialysis at Nagoya Kyoritsu Hospital and followed them up to 12.8 years. According to the CD34+ cell counts, patients were classified into the lowest, medium, and highest tertiles. Levels of CD34+ cells were analyzed in association with four-point major adverse CV events (MACEs), CVD death, and all-cause mortality. In univariate analysis age, smoking habit, lower geriatric nutrition risk index, lower calcium × phosphate product, and lower intact parathyroid hormone were significantly associated with the lowest tertile. Whereas, in multivariate analysis, age and smoking habit were significantly associated with the lowest tertile. Among 139 (64.7%) patients who died during a mean follow-up period of 8.0 years, 39 (28.1%) patients died from CVD. Patients in the lowest tertile had a significantly lower survival rate than those in the medium and highest tertiles (p ≤ 0.001). Using multivariable analyses, the lowest tertile was significantly associated with four-point MACEs (hazard ratio 1.80, p = 0.023) and CVD death (hazard ratio 2.50, p = 0.011). In conclusion, our long-term observational study revealed that a low level of CD34+ cells in the circulation predicts CVD outcomes among patients on maintenance hemodialysis. [ABSTRACT FROM AUTHOR]

The profiles of polytraumatized patients in intensive care units were characterized. Serum and salivary markers were compared with normality between Classes I and II of APACHE II and between periods of hospitalization; these results were correlated. This was a prospective study on saliva charts and collection (n = 70). Profile: male, 27 years old, blunt traumas and collisions. Serum parameters with normality: decrease in pH, creatinine at admission to Class I, and at 48 and 72 hours in both classes; K+ at 48 h in Class II; Ca+ on admission in both classes and at 72 h in Class I. Increase in urea at 72 h in Class II, glucose at all times and in all classes, and Ca+ at 48 h in both classes. Class II had high Na+ at 48 and 72 h compared to Class I. In Class I, creatinine reduction occurred in 48 h and 72 h compared to admission and an increase of Ca+ at 48 h with admission. In Class II, pH and Na+ increased at 48 h and 72 h compared to admission. K+ decreased from admission to 48 h and increased from 48 h to 72 h. Urea increased from 48 to 72 hours. Creatinine decreased from admission to 48 and 72 hours. Ca+ increased from admission to 48 hours and decreased from 48 to 72 hours. There was an increase in the saliva levels in both classes and times in relation to normality. There was an increase in urea at admission, glucose at 72 h, and Ca+ at 48 h in Class II compared with Class I. Class I urea increased from admission to 48 h and Ca+ decreased from admission to 48 h. Class II urea decreased from 48 h to 72 h. Strong or very strong positive correlation was identified between blood and creatinine saliva at all times and regular and negative Ca+ at 72 h. This study provides evidence that salivary and serum biomarkers can be used together to monitor the evolution of the clinical symptoms of ICU patients. [ABSTRACT FROM AUTHOR]

Introduction: While Kedah has recorded the highest prevalence of diabetes among all the states in Malaysia, the information on the practice and effectiveness of disease management in public health institutions remains limited. This study aimed to evaluate the management and glycemic control of patients with type-2 diabetes mellitus (T2DM) at the primary care level in Kedah. Methods: All T2DM patients, who made at least one visit to any of the 58 public health clinics in Kedah during August 2016 and July 2017, were included in this study. The sample was selected from the National Diabetes Registry using the stratified random sampling method. The information on the demographic and clinical characteristics, laboratory findings and pharmacological treatment was gathered from medical records of patients. The differences in mean HbA1C levels across subgroups of each variable were tested using the general linear model. The evaluation of the appropriateness of treatment was performed based on the recommendations of the latest Clinical Practice Guidelines for T2DM. Results: The patients (n = 23,557) were mainly female (63.4%), of Malay ethnicity (80.1%) and middle-aged (62.2%), with a mean duration of T2DM of 6.2±7.16 years. Only 15.6% of them had a HbA1C level <6.5%, and 28.6% did not have their HbA1C levels tested over the 12-month period. Yet, the underutilization of combination treatment (≥2 antidiabetic agents) and insulin in the patients with a poor glycemic control was evident. Retinopathy emerged as the most prevalent diabetes-related complication (12.6%). Along with those with a longer duration of T2DM, the patients who were younger, female and of Indian ethnicity were found to generally have a poorer glycemic control. Conclusion: This study discloses the suboptimal T2DM management at the primary care level in Kedah, which warrants a statewide plan for improvement. [ABSTRACT FROM AUTHOR]

Background: Diabetes is the most common comorbidity of necrotizing fasciitis (NF), but the effect of stress-induced hyperglycemia (SIH) on diabetic patients with NF has never been investigated. The aim of this study was to assess whether SIH, as determined by the glycemic gap between admission glucose levels and A1C-derived average glucose levels, predicts adverse outcomes in diabetic patients hospitalized with NF. Methods: We retrospectively reviewed the glycemic gap and clinical outcomes in 252 diabetic patients hospitalized due to NF from 2011 to 2018 in a single medical center in Taiwan. A receiver operating characteristic (ROC) curve was used to analyze the optimal cutoff values for predicting adverse outcomes. Univariate and multivariate logistic regression analyses were employed to identify significant predictors of adverse outcomes. Results: In total, 194 diabetic NF patients were enrolled. Compared with patients without adverse outcomes, patients with adverse outcomes had significantly higher glycemic gaps, Acute Physiology and Chronic Health Evaluation (APACHE) II scores and C-reactive protein (CRP) levels; lower albumin and hemoglobin levels; greater incidence of limb loss; and longer hospital and intensive care unit stays. The glycemic gap positively correlates with the laboratory risk indicator for NF scores, APACHE II scores and CRP levels. A glycemic gap of 146 mg/dL was the optimal cutoff value for predicting adverse outcomes using the ROC curve. Compared with patients with glycemic gaps ≤146 mg/dL, those with glycemic gaps >146 mg/dL had higher APACHE II scores and incidence rates of adverse outcomes, especially bacteremia and acute kidney injury. Multivariate analysis revealed that a glycemic gap >146 mg/dL and APACHE II score >15 were independent predictors of adverse outcomes, while the presence of hyperglycemia at admission was not. Conclusions: An elevated glycemic gap was significantly independently associated with adverse outcomes in diabetic NF patients. Further prospective studies are warranted to validate the role of the glycemic gap in NF patients with diabetes. [ABSTRACT FROM AUTHOR]

The Model for End-Stage Liver Disease (MELD) score has been successfully used to prioritize patients on the United States liver transplant waiting list since its adoption in 2002. The United Network for Organ Sharing (UNOS)/Organ Procurement Transplantation Network (OPTN) allocation policy has evolved over the years, and notable recent changes include Share 35, inclusion of serum sodium in the MELD score, and a ‘delay and cap’ policy for hepatocellular carcinoma (HCC) patients. We explored the potential of a registrant’s change in 30-day MELD scores (ΔMELD30) to improve allocation both before and after these policy changes. Current MELD and ΔMELD30 were evaluated using cause-specific hazards models for waitlist dropout based on US liver transplant registrants added to the waitlist between 06/30/2003 and 6/30/2013. Two composite scores were constructed and then evaluated on UNOS data spanning the current policy era (01/02/2016 to 09/07/2018). Predictive accuracy was evaluated using the C-index for model discrimination and by comparing observed and predicted waitlist dropout probabilities for model calibration. After the change to MELD-Na, increased dropout associated with ΔMELD30 jumps is no longer evident at MELD scores below 30. However, the adoption of Share 35 has potentially resulted in discrepancies in waitlist dropout for patients with sharp MELD increases at higher MELD scores. Use of the ΔMELD30 to add additional points or serve as a potential tiebreaker for patients with rapid deterioration may extend the benefit of Share 35 to better include those in most critical need. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) increases the risk of adverse maternal and neonatal outcomes, and optimization of glycemic control during pregnancy can help mitigate risks associated with diabetes. However, studies seldom focus precisely on maternal blood glucose level prior to pregnancy. We aimed to evaluate the associations between preconception blood fasting plasma glucose (FPG) level and subsequent pregnancy outcomes.Methods and Findings: We conducted a population-based retrospective cohort study among 6,447,339 women aged 20-49 years old who participated in National Free Pre-Pregnancy Checkups Project and completed pregnancy outcomes follow-up between 2010 and 2016 in China. During the preconception health examination, serum FPG concentration was measured, and self-reported history of DM was collected. Women were classified into three groups (normal FPG group: FPG < 5.6 mmol/L and no self-reported history of DM; impaired fasting glucose [IFG]: FPG 5.6-6.9 mmol/L and no self-reported history of DM; and DM: FPG ≥ 7.0 mmol/L or self-reported history of DM). The primary outcomes were adverse pregnancy outcomes, including spontaneous abortion, preterm birth (PTB), macrosomia, small for gestational age infant (SGA), birth defect, and perinatal infant death. Logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI) after adjusting for confounding variables. The mean age of women was 25.24 years, 91.47% were of Han nationality, and 92.85% were from rural areas. The incidence of DM and IFG was 1.18% (76,297) and 13.15% (847,737), respectively. Only 917 (1.20%) women reported a history of DM (awareness of their DM status), of whom 37.28% (337) had an elevated preconception FPG level (≥ 5.6 mmol/L), regarded as noncontrolled DM. A total of 1,005,568 (15.60%) women had adverse pregnancy outcomes. Compared with women with normal FPG, women with IFG had higher risks of spontaneous abortion (OR 1.08; 95% CI 1.06-1.09; P < 0.001), PTB (1.02; 1.01-1.03; P < 0.001), macrosomia (1.07; 1.06-1.08; P < 0.001), SGA (1.06; 1.02-1.10; P = 0.007), and perinatal infant death (1.08; 1.03-1.12; P < 0.001); the corresponding ORs for women with DM were 1.11 (95% CI 1.07-1.15; P < 0.001), 1.17 (1.14-1.20; P < 0.001), 1.13 (1.09-1.16; P < 0.001), 1.17 (1.04-1.32; P = 0.008), and 1.59 (1.44-1.76; P < 0.001). Women with DM also had a higher risk of birth defect (OR 1.42; 95% CI 1.15-1.91; P = 0.002). Among women without self-reported history of DM, there was a positive linear association between FPG levels and spontaneous abortion, PTB, macrosomia, SGA, and perinatal infant death (P for trend <0.001, <0.001, <0.001, 0.001, <0.001). Information about hypoglycemic medication before or during pregnancy was not collected, and we cannot adjust it in the analysis, which could result in underestimation of risks. Data on 2-hour plasma glucose level and HbA1c concentration were not available, and the glycemic control status was evaluated according to FPG value in women with DM.Conclusions: Women with preconception IFG or DM had higher risk of adverse pregnancy outcomes, including spontaneous abortion, PTB, macrosomia, SGA, and perinatal infant death. Preconception glycemic control through appropriate methods is one of the most important aspects of preconception care and should not be ignored by policy makers. [ABSTRACT FROM AUTHOR]

Introduction: Metabolic risk factors for cardiovascular disease (CVD) warrant significant public health concern globally. This study aims to utilise the regional database of a major laboratory network to describe the geographic distribution pattern of eight different cardiometabolic risk factors (CMRFs), which in turn can potentially generate hypotheses for future research into locality specific preventive approaches. Method: A cross-sectional design utilising de-identified laboratory data on eight CMRFs including fasting blood sugar level (FBSL); glycated haemoglobin (HbA1c); total cholesterol (TC); high density lipoprotein (HDL); albumin creatinine ratio (ACR); estimated glomerular filtration rate (eGFR); body mass index (BMI); and diabetes mellitus (DM) status was used to undertake descriptive and spatial analyses. CMRF test results were dichotomised into ‘higher risk’ and ‘lower risk’ values based on existing risk definitions. Australian Census Statistical Area Level 1 (SA1) were used as the geographic units of analysis, and an Empirical Bayes (EB) approach was used to smooth rates at SA1 level. Choropleth maps demonstrating the distribution of CMRFs rates at SA1 level were produced. Spatial clustering of CMRFs was assessed using Global Moran’s I test and Local Indicators of Spatial Autocorrelation (LISA). Results: A total of 1,132,016 test data derived from 256,525 individuals revealed significant geographic variation in the distribution of ‘higher risk' CMRF findings. The populated eastern seaboard of the study region demonstrated the highest rates of CMRFs. Global Moran’s I values were significant and positive at SA1 level for all CMRFs. The highest spatial autocorrelation strength was found among obesity rates (0.328), and the lowest for albuminuria (0.028). LISA tests identified significant High-High (HH) and Low-Low (LL) spatial clusters of CMRFs, with LL predominantly in the less populated northern, central and southern regions of the study area. Conclusion: The study describes a range of CMRFs with different distributions in the study region. The results allow generation of hypotheses to test in future research concerning location specific population health approaches. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes are at high risk of drug therapy problems (DTPs), as they are receiving multiple medications. To date, studies regarding DTPs in patients with diabetes in Ethiopia are limited. The aim of this study was to assess prevalence of DTPs, medication adherence and treatment satisfaction of patients with diabetes at Tikur Anbessa Specialized Hospital (TASH). Method: A cross-sectional study was conducted on randomly selected 418 participants who fulfilled the inclusion criteria. Data were collected using structured questionnaire and patients’ chart review. Cipolle’s classification system was used to determine DTPs. Modified Morisky’s Adherence Scale (MMAS-8) was used to measure patients’ adherence to their medication. Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) patient satisfaction assessment questionnaire was used to assess patients’ treatment satisfaction. Results: A total of 207 DTPs in 177 (42.3%) of participants were identified. Commonly identified DTPs were dosage too low (58, 28.0%), ineffective drug therapy (54, 26.1%), and need additional drug therapy (52, 25.1%). Factors associated with DTPs were female gender (Adjusted Odds Ratio [AOR] = 2.31,95% CI:1.30–4.12); ≥3comorbidities (AOR = 3.61, 95% CI:1.19–10.96); ever married (AOR = 2.58,95% CI:1.23–5.48); type 2 diabetes (AOR = 5.62, 95% CI:1.21–26.04); non-adherence (AOR = 5.26,95% CI:2.51–11.04) and residence out of Addis Ababa (AOR = 0.30, 95% CI:0.12–0.73). Twenty four percent of participants were non-adherent to their drug therapies. Factors associated with non-adherence were diabetes complications (AOR = 2.00, 95% CI: 1.2–3.32), the female gender (AOR = 1.67, 95%CI: 1.01–2.8) and level of education (AOR = 0.42, 95%CI: 0.18–0.96). Eighty one percent of participants were satisfied with the current treatment. Conclusion: A significant proportion of patients were satisfied with their treatment and a quarter of the study participants were non-adherent to their medications at TASH diabetic clinic. However, DTPs were considerably higher among the study participants. Hence, future interventions targeting prevention and resolution of DTPs deemed to be necessary. [ABSTRACT FROM AUTHOR]

Objective: Although previous studies have reported a negative relationship between serum bilirubin concentration and the development of diabetes mellitus (DM), the relationship between bilirubin and insulin resistance has not been thoroughly assessed. This study was designed to determine the relationships between bilirubin, body fat distribution, and adipose tissue inflammation in patients with type 2 DM and the effect of bilirubin in an obese animal model. Method: Body fat distribution was measured using an abdominal dual bioelectrical impedance analyzer in patients with type 2 DM. We also measured glycemic control, lipid profile, serum bilirubin concentration and other clinical characteristics, and determined their relationships with body fat distribution. In the animal study, biliverdin (20 mg/kg daily) was orally administered to high-fat diet (HFD)-induced obese (DIO) mice for 2 weeks, after which intraperitoneal insulin tolerance testing was performed. Then, adipocyte area, adipocytokine expression, and macrophage polarization were evaluated in epididymal adipose tissues. Results: In the clinical study, univariate analysis showed that a lower bilirubin concentration was significantly correlated with higher body mass index, waist circumference, triglyceride, uric acid, creatinine, visceral fat area and lower HDL-C. In multivariate analyses, bilirubin concentration significantly correlated with diastolic blood pressure, creatinine, and visceral fat area. However, there was no association between bilirubin concentration and subcutaneous fat area. In the animal study, DIO mice treated with biliverdin had smaller adipocytes than untreated DIO mice and biliverdin improved HFD-induced insulin resistance. Biliverdin treatment reversed the higher gene expression of Cd11c, encoding an M1 macrophage marker, and Tnfa, encoding the proinflammatory cytokine tumor necrosis factor-α, in the adipose tissues of DIO mice. These data suggest biliverdin administration alleviates insulin resistance by ameliorating inflammation and the dysregulation of adipocytokine expression in adipose tissues of DIO mice. Conclusions: Bilirubin may protect against insulin resistance by ameliorating visceral obesity and adipose tissue inflammation. [ABSTRACT FROM AUTHOR]

To identify pathways between stress indicators and adverse pregnancy outcomes, we applied a nonparametric graph-learning algorithm, PC-KCI, to data from an observational prospective cohort study. The Measurement of Maternal Stress study (MOMS) followed 744 women with a singleton intrauterine pregnancy recruited between June 2013 and May 2015. Infant adverse pregnancy outcomes were prematurity (<37 weeks' gestation), infant days spent in hospital after birth, and being small for gestational age (percentile gestational weight at birth). Maternal adverse pregnancy outcomes were pre-eclampsia, gestational diabetes, and gestational hypertension. PC-KCI replicated well-established pathways, such as the relationship between gestational weeks and preterm premature rupture of membranes. PC-KCI also identified previously unobserved pathways to adverse pregnancy outcomes, including 1) a link between hair cortisol levels (at 12–21 weeks of pregnancy) and pre-eclampsia; 2) two pathways to preterm birth depending on race, with one linking Hispanic race, pre-gestational diabetes and gestational weeks, and a second pathway linking black race, hair cortisol, preeclampsia, and gestational weeks; and 3) a relationship between maternal childhood trauma, perceived social stress in adulthood, and low weight for gestational age. Our approach confirmed previous findings and identified previously unobserved pathways to adverse pregnancy outcomes. It presents a method for a global assessment of a clinical problem for further study of possible causal pathways. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) patients are predisposed to several diabetes-related complications. Dysregulation of the haemostatic mechanisms have been implicated. There are however no current studies assessing the levels and activity of protein C (PC), protein S (PS), and antithrombin III (AT III), which are essential in haemostatic regulation, in a single cohort of T2DM patients. This study evaluated the effect of poorly-managed T2DM on the levels and activity of PC, PS, and AT III. Methods: This cross-sectional study was conducted at the Diabetes Clinic, Cocoa Clinic in Kumasi, Ghana. A total of 242 T2DM patients, comprising 152 patients with poorly-managed diabetes and 90 well-managed diabetes patients, were recruited for the study. Fasting blood glucose, liver function tests and lipid profile were performed for each respondent. Glycated haemoglobin (HbA1c) was estimated by turbidimetric inhibition immunoassay. The levels and activity of PC, PS and AT III were measured by solid phase sandwich ELISA method. Results: There was a negative correlation between HbA1c and the levels and activity of PC, PS and AT III. The levels and activity of PC [(5.78 vs 4.64 μg/ml, p<0.0001) and (42.22 vs 36.21 U/ml, p = 0.01) respectively], PS [(22.55 vs 20.29 μg/ml, p = 0.010) and (235.94 vs 211.67 U/ml, p<0.0001) respectively] and AT III [(16.28 vs 14.41μg/ml, p<0.0001) and (176.01 vs 160.09 U/ml, p = 0.03) respectively] were significantly increased in patients with well-managed T2DM compared to the poorly-managed diabetes patients. Likewise, the levels and activity of PC, PS, and AT III was higher among T2DM patients using statins than patients who were statin-naïve. Among patients with well-managed T2DM, those who were on statins had significantly higher levels and activities of PC, PS, and AT III compared to well-managed T2DM patients not on statins. However, there no statistically significant differences between the level and activity of PC, PS, and AT III among poorly-managed T2DM patients with respect to statin status. Conclusion: Poorly-managed type 2 diabetes mellitus is associated with reduced levels and activity of PC, PS and AT III compared to well-managed T2DM. Though use of statins may improve the levels and activity of the PC, PS and AT III in T2DM, their effect is limited in the presence of poorly-controlled T2DM. Proper management of diabetes is essential to reduce the likelihood of thrombotic events among T2DM patients. [ABSTRACT FROM AUTHOR]

Background: Asians are predisposed to a lean heart failure (HF) phenotype. Data on the 'obesity paradox', reported in Western populations, are scarce in Asia and have only utilised the traditional classification of body mass index (BMI). We aimed to investigate the association between obesity (defined by BMI and abdominal measures) and HF outcomes in Asia.Methods and Findings: Utilising the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry (11 Asian regions including Taiwan, Hong Kong, China, India, Malaysia, Thailand, Singapore, Indonesia, Philippines, Japan, and Korea; 46 centres with enrolment between 1 October 2012 and 6 October 2016), we prospectively examined 5,964 patients with symptomatic HF (mean age 61.3 ± 13.3 years, 26% women, mean BMI 25.3 ± 5.3 kg/m2, 16% with HF with preserved ejection fraction [HFpEF; ejection fraction ≥ 50%]), among whom 2,051 also had waist-to-height ratio (WHtR) measurements (mean age 60.8 ± 12.9 years, 24% women, mean BMI 25.0 ± 5.2 kg/m2, 7% HFpEF). Patients were categorised by BMI quartiles or WHtR quartiles or 4 combined groups of BMI (low, <24.5 kg/m2 [lean], or high, ≥24.5 kg/m2 [obese]) and WHtR (low, <0.55 [thin], or high, ≥0.55 [fat]). Cox proportional hazards models were used to examine a 1-year composite outcome (HF hospitalisation or mortality). Across BMI quartiles, higher BMI was associated with lower risk of the composite outcome (ptrend < 0.001). Contrastingly, higher WHtR was associated with higher risk of the composite outcome. Individuals in the lean-fat group, with low BMI and high WHtR (13.9%), were more likely to be women (35.4%) and to be from low-income countries (47.7%) (predominantly in South/Southeast Asia), and had higher prevalence of diabetes (46%), worse quality of life scores (63.3 ± 24.2), and a higher rate of the composite outcome (51/232; 22%), compared to the other groups (p < 0.05 for all). Following multivariable adjustment, the lean-fat group had higher adjusted risk of the composite outcome (hazard ratio 1.93, 95% CI 1.17-3.18, p = 0.01), compared to the obese-thin group, with high BMI and low WHtR. Results were consistent across both HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]; pinteraction = 0.355). Selection bias and residual confounding are potential limitations of such multinational observational registries.Conclusions: In this cohort of Asian patients with HF, the 'obesity paradox' is observed only when defined using BMI, with WHtR showing the opposite association with the composite outcome. Lean-fat patients, with high WHtR and low BMI, have the worst outcomes. A direct correlation between high WHtR and the composite outcome is apparent in both HFpEF and HFrEF.Trial Registration: Asian Sudden Cardiac Death in HF (ASIAN-HF) Registry ClinicalTrials.gov Identifier: NCT01633398. [ABSTRACT FROM AUTHOR]

Fragmentation of mitochondrial network has been implicated in many neurodegenerative, renal, and metabolic diseases. However, a quantitative measure of the microscopic parameters resulting in the impaired balance between fission and fusion of mitochondria and consequently the fragmented networks in a wide range of pathological conditions does not exist. Here we present a comprehensive analysis of mitochondrial networks in cells with Alzheimer’s disease (AD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), optic neuropathy (OPA), diabetes/cancer, acute kidney injury, Ca2+ overload, and Down Syndrome (DS) pathologies that indicates significant network fragmentation in all these conditions. Furthermore, we found key differences in the way the microscopic rates of fission and fusion are affected in different conditions. The observed fragmentation in cells with AD, HD, DS, kidney injury, Ca2+ overload, and diabetes/cancer pathologies results from the imbalance between the fission and fusion through lateral interactions, whereas that in OPA, PD, and ALS results from impaired balance between fission and fusion arising from longitudinal interactions of mitochondria. Such microscopic difference leads to major disparities in the fine structure and topology of the network that could have significant implications for the way fragmentation affects various cell functions in different diseases. [ABSTRACT FROM AUTHOR]

A microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi living in different niches of the human body, which plays an essential role in many metabolic functions. Modifications in the microbiota composition can lead to several diseases, including metabolic disorders. The aim of this study was to analyze the prevalence of four viruses which can cause persistent infections–Epstein-Barr virus (EBV), human papillomavirus (HPV), cytomegalovirus (CMV), and herpes simplex virus type 1 (HSV-1) in patients with diabetes mellitus type 2 (DM2). Blood, saliva and oral swabs were collected from all the study participants. The nested-PCR technique was used to detect the viral DNA. DNA of at least one virus was detected in 71.1% of diabetic patients and in 30% of individuals without diabetes. In patients with diabetes EBV DNA was detected the most frequently (25.4%), followed by HPV– 19.1%, HSV– 10.4% and CMV– 5.2%. A higher percentage of EBV+HPV co-infection was found among men (30.8%). EBV DNA was statistically more often detected in patients living in rural areas (53.7%), while HPV (91.5%) and EBV+HPV co-infection (22.2%) prevailed among patients from urban areas. In patients with a DM2 history longer than 10 years viral infection was detected more frequently. The prevalence of EBV, HPV and the EBV+HPV co-infection was significantly higher in diabetic patients than in individuals without diabetes. The frequency of these infections depended on the duration of the disease (DM2). [ABSTRACT FROM AUTHOR]

Background and objectives: There have been limited studies regarding the association between glomerular hyperfiltration (GHF) and restrictive spirometry pattern (RSP) in Korean adults. Methods: We used data of 23,189 adults from the Korea National Health and Nutritional Examination Survey 2009–2015 with a complete data set including spirometry, serum creatinine, and anthropometric measurements. Spirometry data included the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). We defined GHF as the >90th percentile of age & sex adjusted estimated glomerular filtration rate (eGFR), and RSP was defined as an FVC <80%-predicted value and an FEV1/FVC ratio ≥0.7. Results: Participants with RSP showed higher blood pressure, fasting glucose, and triglyceride, reduced high density lipoprotein cholesterol, and central obesity, which resulted in a higher prevalence of metabolic syndrome (MetS) compared to those without RSP. Multivariate logistic regression revealed that the odds for RSP were significantly increased with an increased number of MetS components. In addition, increased eGFR was associated with decreased FVC, showing an inverted J-shaped relationship in a multivariate generalized additive model analysis. In the multivariate logistic regression analysis, the adjusted odds ratio and 95% confidence interval of GHF for RSP was 1.184 (1.026–1.368, P = 0.021), which was evident in groups without metabolic disorders. Conclusions: We concluded that GHF was associated with increased odds for RSP, particularly in groups without metabolic disorders. Further prospective studies are needed to confirm our study results. [ABSTRACT FROM AUTHOR]

Objective: Thresholds defining medication adherence are rarely evidence-based. A threshold of 0.8 is typically presumed to achieve improved outcomes. We aimed to assess the optimal threshold of adherence to lipid-lowering drugs (LLD) in predicting cardiovascular-related (CV) outcomes in patients with hypertension. Design: Cohort study of new users of LLDs. Setting: Comprehensive healthcare administrative databases of the province of Alberta (Canada) from 2008 to 2016. Participants: Patients with hypertension, who were new users of LLDs. Patients who had the outcomes prior to the initiation of LLD were excluded. Main outcomes measures: Hospitalization for acute coronary syndrome (ACS)/stroke, CV-related mortality and all-cause mortality. Statistical analysis: Adherence to LLDs was assessed as the proportion of days covered (PDC) by any LLD, from drug initiation to censoring, outcome, or study end. Three methods were used to assess the threshold: Contal and O'Quigley method, minimum distance method, and Youden's J index. Cox regressions were used to assess the risk associated with each method-specific threshold and Akaike information criteria were used to retain the optimal threshold after adjustment. Results: 52229 patients were included; 4.0% were hospitalized for ACS/stroke, 3.4% died, and 1.3% died from CV-related cause. In predicting ACS/stroke, CV-related and all-cause mortality, the optimal adherence threshold was 0.52 (range: 0.51–0.54), 0.79 (0.45–0.87), and 0.84 (0.79–0.89), respectively. These results were consistent among patients aged ≥ 65 years (n = 19804). However, the results varied among those aged < 65 years, where the incidence rates of outcomes were low. Conclusion: In new-users of LLDs with hypertension, approximately 50% days covered by LLDs may be enough to prevent long-term occurrence of ACS, or stroke. However, a threshold near 0.80 may be needed to prevent or reduce the risk of all-cause or CV-related mortality. [ABSTRACT FROM AUTHOR]

Background: The evidence for vitamin D and other agents that experimentally modulate T regulatory cells (Tregs) for the treatment of patients with autoimmune or allergic diseases has not been established. Objective: We have undertaken a systematic review of randomised controlled trials to assess the efficacy of vitamin D, vitamin A, niacin and short-chain fatty acids in enhancing absolute Treg numbers and phenotypes in patients with inflammatory or autoimmune disease. Methods: This systematic review was conducted using a predefined protocol (PROSPERO International prospective register of systematic reviews, ID = CRD42016048648/ CRD42016048646). Randomised controlled trials of patients with inflammatory or autoimmune disease or healthy participants which compared either oral vitamin D or vitamin A or short-chain fatty acids with control or placebo and measured the absolute concentration of proportion of Tregs were eligible for inclusion. Searches of electronic databases (CENTRAL, MEDLINE, EMBASE, CINAHL, PUBMED and Web of Science) identified eight eligible independent trials (seven autoimmune disease trials, one trial of healthy subjects). Data were extracted by two reviewers and the risk of study bias was assessed using Cochrane Collaboration methodology. Results: Planned meta-analysis was not possible due to the heterogeneous nature of the studies. Nevertheless, in five trials of autoimmune disorders which measured the proportion of Tregs, a higher proportion was observed in the vitamin D group compared to controls at 12 months in all but one trial. In the trial of healthy subjects, a significant difference was reported, with a higher percentage of Tregs observed in the vitamin D group (at 12 weeks, mean 6.4% (SD 0.8%) (vitamin D) vs 5.5% (1.0%) (placebo). There were no trials to assess the efficacy of vitamin A, niacin and short-chain fatty acids in enhancing absolute Treg numbers. Conclusions: Vitamin D supplementation may increase Treg/CD3 ratios in both healthy individuals and patients with autoimmune disorders and may increase Treg function. There remains a need for further suitably powered clinical studies aimed at enhancing Treg numbers and/or function. [ABSTRACT FROM AUTHOR]

Objectives: Traits of metabolic syndrome (MetS) and biomarkers of inflammation and endothelial dysfunction were examined. We investigated the differences of various biomarkers among individuals with or without Mets in a gender-specific manner. The gender-specific associations between E-selectin and MetS were further evaluated. Methods: A total of 205 patients were recruited from the outpatient clinics of Tri-Service General Hospital, Taipei, Taiwan. Inclusion criteria were age between 20–75 years and BMI < 35 kg/m2. Demographic, anthropometric and MetS index data were compared between genders. Markers of inflammation and endothelial dysfunction were compared between individuals with or without MetS by gender. Results: Age-adjusted E-selectin values showed significant positive correlations with BMI, waist-hip ratio, fasting plasma glucose, systolic and diastolic blood pressure, triglycerides, TNF-α, hsCRP and ICAM-1, and inverse correlation with HDL cholesterol. E-selectin levels were positively correlated with numbers of MetS components in females (P < 0.001) but not in males (P = 0.125). Conclusions: Increased E-selectin levels are significantly associated with increased MetS risk in females, but not in males. [ABSTRACT FROM AUTHOR]

Aims: To explore actions and motivations for self-management practices of Pacific adults following diagnosis of end stage renal disease (ESRD). Methods: Focused ethnography using in-depth interviews with 16 Pacific people on haemodialysis for diabetic ESRD, in Auckland, New Zealand. Study participants were of Samoan, Cook Islander, Tongan, Niuean, or Tokelauan ethnicity and aged between 30 to 69 years old. Thematic analysis was used to code and identify emergent themes. Results: All participants assumed active responsibility for their self-management following their diagnosis of ESRD. They reported positive differences in their current self-management behaviours, compared to pre-ESRD diagnosis. In the face of their terminal diagnosis, participant’s motivations to self-manage their health were fuelled by hope; the hope to live long enough to change their family legacy of diabetes and ESRD. To achieve this, there was a dependency upon family members as a resource for self-management support. Yet at the same time, family members also had health concerns (including diabetes), and several participants themselves were carers for sick or elderly family members. Conclusion: The growing number of members (within family units) progressing from moderate to late-stage diabetes raises concerns about the sustainability of future family support in Pacific families in New Zealand with histories of diabetes, ESRD, and other chronic diseases. While the burden upon informal carers (family) has been well documented throughout the past few decades, the dynamics of bi-directional carer support between (two or more) sick family members and their families have had less exposure. This has potentially significant implications for Pacific peoples in New Zealand, considering the increases in diabetes prevalence within their families. [ABSTRACT FROM AUTHOR]

Objectives: The association of obstructive sleep apnea (OSA) with hypothalamic pituitary adrenal (HPA) axis activation has not been fully understood from results of previous studies using hormonal assessments. We aimed to investigate the relationship between adrenal size, a potential marker reflecting HPA axis activity, and sleep parameters related to OSA. Methods: We retrospectively reviewed data on 284 consecutive adult patients aged 20 to 80 y who had undergone polysomnography and abdominal computed tomography (CT). OSA was defined as none/mild (apnea-hypopnea index [AHI] <15, n = 75), moderate (AHI 15 to 30, n = 80), and severe OSA (AHI ≥30, n = 129). Widths of adrenal body and limbs were measured by abdominal CT. Results: Adrenal size was greater in participants with severe OSA than in those with none/mild or moderate OSA (adrenal body width: 6.03 mm, none/mild OSA; 6.09 mm, moderate OSA; 6.78 mm, severe OSA; p <0.001; adrenal limb width: 3.75 mm, none/mild OSA; 3.95 mm, moderate OSA; 4.26 mm, severe OSA, p <0.001). Multivariate regression analysis showed that not the 3% oxygen desaturation index and time of SpO2 <90% but a higher arousal index was the only determinant factor for increased adrenal limb width (β = 0.27, p <0.001) after adjusting for other variables that could affect adrenal size. Neither the arousal index nor hypoxic parameters were associated with adrenal body width. Conclusions: Results indicated that adrenal glands may enlarge in response to longstanding sleep fragmentation, suggesting the involvement of OSA in HPA axis augmentation. [ABSTRACT FROM AUTHOR]

Asprosin is a counter-regulatory hormone to insulin which plays a role in fasting. It may therefore also play a role in hypoglycaemia unawareness, which has been subsequently examined in this pilot study. Intravenous glucose tolerance test was used to induce controlled hyperglycemia whereas a hyperinsulinemic clamp test was used to induce a controlled hypoglycaemia in 15 patients with diabetes type 1, with and without hypoglycaemia unawareness. Changes in asprosin plasma levels did not differ between patients with and without hypoglycaemia unawareness. However, nine patients with insulin resistance as well as higher liver stiffness values and low-density lipoprotein but lower high-density lipoprotein levels did not show the expected increase in asprosin plasma levels during hypoglycemia. Therefore, insulin resistance and alterations in liver structure, most likely early stages of non-alcoholic fatty liver disease, seem to be relevant in type 1 diabetes and do not only lead to elevated plasma levels of asprosin, but also to a blunted asprosin response in hypoglycemia. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate whether different levels of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) in prediabetes are associated with hyperfiltration. Methods: A prospective cohort of 2,022 individuals aged 30–74 years took part in the PREDAPS Study. One cohort of 1,184 participants with prediabetes and another cohort of 838 participants with normal FPG and normal HbA1c were followed for 5 years. Hyperfiltration was defined as an estimated glomerular filtration rate (eGFR) above the age- and gender-specific 95th percentile for healthy control participants, while hypofiltration was defined as an eGFR below the 5th percentile. The prevalence of hyperfiltration was compared for different levels of prediabetes: level 1 of prediabetes: FPG <100 mg/dL plus HbA1c 5.7–6.0% or FPG 100–109 mg/dL plus HbA1c < 5.7%; level 2 of prediabetes: FPG <100 mg/dL plus HbA1c 6.1–6.4% or FPG 100–109 mg/dL plus HbA1c 5.7–6.0% or FPG 110–125 mg/dL plus HbA1c <5.7% and level 3 of prediabetes: FPG 100–109 mg/dL plus HbA1c 6.1–6.4% or FPG 110–125 mg/dL plus HbA1c 5.7–6.4%. Results: The participants with hyperfiltration were significantly younger, had a higher percentage of active smokers, and lower levels of hemoglobin and less use of ACEIs or ARBs. Only level 3 prediabetes based on FPG 100–109 mg/dL plus HbA1c 6.1–6.4% or FPG 110–125 mg/dL plus HbA1c 5.7–6.4% had a significantly higher odds ratio (OR) of hyperfiltration (OR 1.69 (1.05–2.74); P < 0.001) compared with no prediabetes (FPG < 100 mg/dL and HbA1c < 5.7%) after adjustment for different factors. The odds ratios for different levels of HbA1c alone in prediabetes increased progressively, but not significantly. Conclusions: Level 3 of prediabetes based on FPG 100–109 mg/dL plus HbA1c 6.1–6.4% or FPG 110–125 mg/dL plus HbA1c 5.7–6.4% had a significantly higher OR of hyperfiltration compared with participants without prediabetes. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is associated with substantial cardiovascular morbidity. Atrial fibrillation (AF) is a prevalent arrhythmia that increases the risk of both stroke and cardiovascular mortality. Information about the mortality risk among patients with advanced CKD and new-onset AF (NAF) in the presence and absence of dialysis is important. However, the association between advanced CKD and NAF in patients with and without dialysis is unclear. Objective: To investigate long-term outcomes of the association between advanced CKD and NAF in patients with and without dialysis. Methods: We conducted a nested case-control study based on the National Health Insurance Program in Taiwan. Each participant aged 20 years and older who had CKD with dialysis from 2000 to 2013 was assigned to the dialysis group, whereas sex-, age-, CKD duration-, and index date-matched participants without dialysis were randomly selected and assigned to the non-dialysis group. We used the Cox regression model to estimate the hazard ratio (HR) with the 95% confidence interval (CI) for mortality in CKD patients with combined dialysis and NAF. Patients with neither NAF nor dialysis served as the reference group. Results: We identified 3,673 dialysis cases and 7,346 Non-dialysis matched controls for enrolment in the study. The crude mortality rates were 3.3 (95% CI: 3.1–3.5), 10.98 (95% CI: 9.3–13.0), 9.2 (95% CI: 8.7–10.0), and 18.0 (95% CI: 15.4–21.2) in the [Non-dialysis, non-NAF], [Non-dialysis, NAF], [Dialysis, non-NAF], and [Dialysis, NAF] groups, respectively. After adjustment for age, gender, and co-morbidities, the aHRs were 2.0 (95% CI: 1.7–2.3), 2.7 (95% CI: 2.5–2.9), and 3.5 (95% CI: 2.9–4.1) in the [Non-Dialysis, NAF], [Dialysis, non-NAF], and [Dialysis, NAF] groups compared with the [Non-Dialysis, non-NAF] group, respectively. The Kaplan-Meier survival curves showed the highest mortality risk in the [Dialysis, NAF] group among the study groups. Patients with concurrent peritoneal dialysis and AF had the highest mortality risk: aHR = 4.3 (95% CI: 2.3–8.0). However, there was a relatively lower effect of NAF on mortality in patients on dialysis than in patients who were not. Conclusions: Patients with advanced CKD and NAF had a significantly increased risk of mortality. Dialysis is not risky for patients with concurrent CKD and NAF. Dialysis offers a sufficient survival benefit to be considered as a standard treatment, as indicated by the superior physical status of patients on dialysis. [ABSTRACT FROM AUTHOR]

We previously reported that allogeneic, intraperitoneally administered “Neo-Islets,” composed of cultured pancreatic islet cells co-aggregated with high numbers of immunoprotective and cytoprotective Adipose-derived Stem Cells, reestablished, through omental engraftment, redifferentiation and splenic and omental up-regulation of regulatory T-cells, normoglycemia in autoimmune Type-1 Diabetic Non-Obese Diabetic (NOD) mice without the use of immunosuppressive agents or encapsulation devices. Based on these observations, we are currently testing this Neo-Islet technology in an FDA guided pilot study (INAD 012–776) in insulin-dependent, spontaneously diabetic pet dogs by ultrasound-guided, intraperitoneal administration of 2x10e5 Neo-Islets/kilogram body weight to metabolically controlled (blood glucose, triglycerides, thyroid and adrenal functions) and sedated animals. We report here interim observations on the first 4 canine Neo-Islet-treated, insulin-dependent pet dogs that are now in the early to intermediate-term follow-up phase of the planned 3 year study (> 6 months post treatment). Current results from this translational study indicate that in dogs, Neo-Islets appear to engraft, redifferentiate and physiologically produce insulin, and are rejected by neither auto- nor allo-immune responses, as evidenced by (a) an absent IgG response to the allogeneic cells contained in the administered Neo-Islets, and (b) progressively improved glycemic control that achieves up to a 50% reduction in daily insulin needs paralleled by a statistically significant decrease in serum glucose concentrations. This is accomplished without the use of anti-rejection drugs or encapsulation devices. No adverse or serious adverse events related to the Neo-Islet administration have been observed to date. We conclude that this minimally invasive therapy has significant translational relevance to veterinary and clinical Type 1 diabetes mellitus by achieving complete and at this point partial glycemic control in two species, i.e., diabetic mice and dogs, respectively. [ABSTRACT FROM AUTHOR]

Objective: Previous reports have highlighted the suboptimal utilization and prescription of statin therapy among patients with type 2 diabetes mellitus (T2DM) in the Malaysian clinical practice. This study aims to test the impact of a pharmacist-led academic detailing program on improving the overall statin therapy prescribing in Malaysian hospital and primary care settings. Methods: As a quasi-experimental design with a control group and pre-tests., we examined 1,598 medical records of T2DM subjects in six healthcare facilities in the state of Pahang, Malaysia. In all study sites, there was a pre and post-intervention assessment of the percentage of appropriate statin therapy prescribing that complied with the clinical guidelines with no potential safety issues. The intervention was an academic detailing program offered to the health care providers in three study sites, while the other three sites served as the control group. A comparison of the overall percentage of appropriate statin therapy prescribing before and after the academic detailing was performed in all intervention and control sites. Results: Overall, 797 medical records were examined in the pre-intervention phase, and 801 records were evaluated in the post-intervention phase. The academic detailing program was associated with a statistically significant difference in the proportion of appropriate statin therapy prescribing between the post-intervention phase compared to the pre-intervention phase (n = 246, 61.7% versus n = 188, 47.1%), p = 0.001. Whereas, the appropriate statin therapy prescribing in the control study sites experienced a modest change from 53.8% (214/398) to 56.7% (228/402), p = 0.220. The academic detailing showed significant increases in the proportions of appropriate statin therapy prescribing in both hospital and primary care settings. Conclusions: The academic detailing program was found to be significantly associated with a positive impact on the overall statin therapy prescribing among patients with T2DM in Malaysian hospital and primary care settings. [ABSTRACT FROM AUTHOR]

Early conversion to everolimus was assessed in kidney transplant recipients participating in the Eurotransplant Senior Program (ESP), a population in whom data are lacking. The SENATOR multicenter study enrolled 207 kidney transplant recipients undergoing steroid withdrawal at week 2 post-transplant (ClinicalTrials.gov [NCT00956293]). At week 7, patients were randomized (1:2 ratio) to continue the previous calcineurin inhibitor (CNI)-based regimen with mycophenolic acid (MPA) and cyclosporine or switch to a CNI-free regimen with MPA, everolimus (5–10 ng/mL) and basiliximab at weeks 7 and 12, then followed for 18 weeks to month 6 post-transplant. The primary endpoint was estimated GFR (eGFR). At week 7, 77/207 (37.2%) patients were randomized (53 everolimus, 24 control). At month 6, eGFR was comparable: 36.5±10.8ml/min with everolimus versus 42.0±13.0ml/min in the control group (p = 0.784). Discontinuation due to adverse events occurred in 27.8% of everolimus-treated patients and 0.0% of control patients (p = 0005). Efficacy profiles showed no difference. In conclusion, eGFR, safety and efficacy outcomes at month 6 post-transplant showed no difference between groups. The everolimus group experienced a higher rate of discontinuation due to adverse events. However, the high rate of non-randomization is highly relevant, indicating this to be a somewhat unstable patient population regardless of treatment. [ABSTRACT FROM AUTHOR]

Objective: To explore clinical factors associated with bacterial translocation in Japanese patients with type 2 diabetes mellitus (T2DM). Methods: The data of 118 patients with T2DM were obtained from two previous clinical studies, and were retrospectively analyzed regarding the clinical parameters associated with bacterial translocation defined as detection of bacteremia and levels of plasma lipopolysaccharide binding protein (LBP), the latter of which is thought to reflect inflammation caused by endotoxemia. Results: LBP level was not significantly different between patients with and without bacteremia. No clinical factors were significantly correlated with the detection of bacteremia. On the other hand, plasma LBP level was significantly correlated with HbA1c (r = 0.312), fasting blood glucose (r = 0.279), fasting C-peptide (r = 0.265), body mass index (r = 0.371), high-density lipoprotein cholesterol (r = -0.241), and inflammatory markers (high-sensitivity C-reactive protein, r = 0.543; and interleukin-6, r = 0.456). Multiple regression analysis identified body mass index, HbA1c, high-sensitivity C-reactive protein, and interleukin-6 as independent determinants of plasma LBP level. Conclusion: The plasma LBP level was similar in patients with and without bacteremia. While both bacteremia and LBP are theoretically associated with bacterial translocation, the detection of bacteremia was not associated with LBP level in T2DM. [ABSTRACT FROM AUTHOR]

This study aimed to assess the renopreventive effect of enalapril and/or paricalcitol on streptozotocin (STZ) diabetes-induced nephropathy and to elucidate their mechanisms of action through investigation of the effects on renal oxidative stress, antioxidant defense system and expressions of TNF-α, p53, caspase-3, and Bcl-2. Diabetes mellitus was induced in fasting male Wistar rats by single intraperitoneal injection of STZ (45 mg /kg b.w.) dissolved in citrate buffer (pH 4.5). Ten days after STZ injection, the diabetic rats were treated with enalapril (25 mg/l of drinking water) and/or paricalcitol (8 μg/kg b.w. per os) dissolved in 5% DMSO daily for 4 weeks. The obtained data revealed that the treatment of diabetic Wistar rats with enalapril and/or paricalcitol led to significant decreases in the elevated serum urea, uric acid, creatinine, sodium and potassium levels; thereby reflecting the improvement of the impaired kidney function. The deteriorated kidney lipid peroxidation, GSH content and GST and catalase activities in diabetic rats were significantly ameliorated as a result of treatment with enalapril and/or paricalcitol. The elevated fasting and post-prandial serum glucose levels and the lowered serum insulin and C-peptide levels were also improved. The treatment with enalapril and paricalcitol in combination was the most potent in decreasing the elevated serum glucose levels. Moreover, the treatment of diabetic rats successfully prevented the diabetes-induced histopathological deleterious changes of kidney and islets of Langerhans of pancreas. In association, the immunohistochemically detected pro-inflammatory cytokine, TNF-α, and apoptotic mediators, p53 and caspase-3, were remarkably decreased in kidney of diabetic rats as a result of treatment while the expression of anti-apoptotic protein Bcl-2 was increased. Based on these findings, it can be concluded that enalapril and paricalcitol alone or in combination can prevent STZ diabetes-induced nephropathy through amelioration of the glycemic state and antioxidant defense system together with the suppression of oxidative stress, inflammation and apoptosis. However, the treatment of diabetic rats with enalapril and paricalcitol in combination has no further significant improvement effects on renal function and damage when compared with enalapril or paclitaxel treated diabetic groups. [ABSTRACT FROM AUTHOR]

Purpose: To investigate intraocular pressure (IOP) readings by non-contact tonometry (NCT) and Goldmann applanation tonometry (GAT) for patients with different degrees of bilateral tearing. Methods: In this study, we reviewed the medical charts of patients complaining of different degrees of bilateral tearing. The tear meniscus height (TMH) and IOP with NCT and GAT were measured. In each patient, a comparison of IOP readings between the eye with lower TMH and the contralateral eye with higher TMH was evaluated. The TMH was graded as follows: grade 1 (low): TMH < 0.2 mm; grade 2 (moderate): 0.2 mm ≤ TMH < 0.6 mm; grade 3 (high): TMH ≥ 0.6 mm. Subsequently, a comparison of IOP readings among eyes with low, moderate, and high TMH was also performed. Results: A total of 120 eyes of 60 patients were enrolled. When comparing the two eyes of a patient, the eye with higher TMH showed higher NCT readings and larger difference in IOP readings between the two tonometries than the eye with lower TMH (P < 0.001 and P < 0.001, respectively). When TMH was classified into grades according to the degree, the high TMH eyes showed higher NCT readings than did the low and moderate TMH eyes (P < 0.001 and P = 0.001, respectively). In addition, the high TMH eyes showed a larger difference in IOP readings between the two tonometries than did the low and moderate TMH eyes (P < 0.001 and P < 0.001, respectively). Conclusion: Eyes with higher TMH showed higher NCT readings and a larger difference in IOP between the two tonometries (NCT and GAT) than those with lower TMH. In patients with tearing, the NCT value may be inaccurate, so it is necessary to measure the GAT. [ABSTRACT FROM AUTHOR]

Background: An assessment of bone strength based on bone mineral density (BMD) underestimates the risk of fracture in patients with diabetes mellitus (T2DM). However, using the trabecular bone score (TBS) for estimating bone microarchitecture, previous studies showed that bone fragility is associated with deterioration of the microstructure concomitantly with decreased BMD. This study was conducted to clarify which of these skeletal-related factors had a more prominent relationship with bone fragility. Research design and methods: A retrospective cross-sectional study was performed at Shimane University Hospital. A total of 548 Japanese patients with T2DM [257 postmenopausal women and 291 men aged over 50 years] were included. TBS of the spine was computed from dual-energy X-ray absorptiometry images obtained from BMD measurements. Results: Vertebral fractures (VFs) were identified in 74 (28.8%) women and 115 (39.5%) men. A relationship between BMD and VFs was observed in the limited subgroup of women with a BMD T-score ≤-1.0. According to multivariate logistic regression analysis, low TBS was significantly correlated with prevalent VFs, independent of BMD in both genders, except for men with a BMD T-score > -1.0. The decision tree showed that the priority factor for determining VFs was TBS, not BMD. Conclusion: Spinal microarchitecture represented by TBS was a more dominant skeletal factor for bone fragility than the decrease in bone mass, independent of BMD, in patients with T2DM. This observation suggests that loss of structural bone quality was crucial underlying pathogenesis for bone brittleness in these populations, regardless of gender. An integrated assessment of bone strength by BMD and TBS would help diagnose diabetic osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Despite dietary recommendations of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, n-3 and n-6 PUFAs and their interplay in relation to diabetes risk remain debated. Importantly, data among pregnant women are scarce. We investigated individual plasma phospholipid n-3 and n-6 PUFAs in early to midpregnancy in relation to subsequent risk of gestational diabetes mellitus (GDM).Methods and Findings: Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (n = 2,802), individual plasma phospholipid n-3 and n-6 PUFAs levels were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used, adjusting for major risk factors for GDM. After adjusting for covariates, individual n-3 eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were inversely correlated with insulin-resistance markers, whereas individual n-6 dihomo-gamma-linolenic acid (DGLA) was positively correlated with insulin-resistance markers. At GW 15-26, a standard deviation (SD) increase in total n-3 PUFAs and individual n-3 DPA was associated with a 36% (adjusted odds ratio 0.64; 95% CI 0.42-0.96; P = 0.042) and 33% (0.67; 95% CI 0.45-0.99; P = 0.047) lower risk of GDM, respectively; however, the significance did not persist after post hoc false-discovery rate (FDR) correction (FDR-corrected P values > 0.05). Associations between total n-6 PUFAs and GDM were null, whereas associations with individual n-6 PUFAs were differential. Per SD increase, gamma-linolenic acid (GLA) at GWs 10-14 and DGLA at GWs 10-14 and 15-26 were significantly associated with a 1.40- to 1.95-fold higher risk of GDM, whereas docosatetraenoic acid (DTA) at GW 15-26 was associated with a 45% (0.55; 95% CI 0.37-0.83) lower risk of GDM (all FDR-corrected P values < 0.05). Null associations were observed for linoleic acid (LA) in either gestational window in relation to risk of GDM. Women with high (≥median) n-3 PUFAs and low (Conclusions: Our findings may suggest a potential role of primarily endogenously metabolized plasma phospholipid n-6 PUFAs including GLA, DGLA, and DTA in early to midpregnancy in the development of GDM. Null findings on primarily diet-derived n-3 EPA and DHA and n-6 LA do not provide strong evidence to suggest a beneficial role in prevention of GDM, although not excluding the potential benefit of EPA and DHA on glucose-insulin homeostasis given the inverse associations with insulin-resistance markers. Our findings highlight the importance of assessing individual circulating PUFAs to investigate their distinct pathophysiologic roles in glucose homeostasis in pregnancy. [ABSTRACT FROM AUTHOR]

Background: The inflammatory contribution to type 2 diabetes (T2D) has suggested new therapeutic targets using biologic drugs designed for rheumatoid arthritis (RA). On this basis, we aimed at investigating whether interleukin-1 (IL-1) inhibition with anakinra, a recombinant human IL-1 receptor antagonist, could improve both glycaemic and inflammatory parameters in participants with RA and T2D compared with tumour necrosis factor (TNF) inhibitors (TNFis).Methods and Findings: This study, designed as a multicentre, open-label, randomised controlled trial, enrolled participants, followed up for 6 months, with RA and T2D in 12 Italian rheumatologic units between 2013 and 2016. Participants were randomised to anakinra or to a TNFi (i.e., adalimumab, certolizumab pegol, etanercept, infliximab, or golimumab), and the primary end point was the change in percentage of glycated haemoglobin (HbA1c%) (EudraCT: 2012-005370-62 ClinicalTrial.gov: NCT02236481). In total, 41 participants with RA and T2D were randomised, and 39 eligible participants were treated (age 62.72 ± 9.97 years, 74.4% female sex). The majority of participants had seropositive RA disease (rheumatoid factor and/or anticyclic citrullinated peptide antibody [ACPA] 70.2%) with active disease (Disease Activity Score-28 [DAS28]: 5.54 ± 1.03; C-reactive protein 11.84 ± 9.67 mg/L, respectively). All participants had T2D (HbA1c%: 7.77 ± 0.70, fasting plasma glucose: 139.13 ± 42.17 mg). When all the enrolled participants reached 6 months of follow-up, the important crude difference in the main end point, confirmed by an unplanned ad interim analysis showing the significant effects of anakinra, which were not observed in the other group, led to the study being stopped for early benefit. Participants in the anakinra group had a significant reduction of HbA1c%, in an unadjusted linear mixed model, after 3 months (β: -0.85, p < 0.001, 95% CI -1.28 to -0.42) and 6 months (β: -1.05, p < 0.001, 95% CI -1.50 to -0.59). Similar results were observed adjusting the model for relevant RA and T2D clinical confounders (male sex, age, ACPA positivity, use of corticosteroids, RA duration, T2D duration, use of oral antidiabetic drug, body mass index [BMI]) after 3 months (β: -1.04, p < 0.001, 95% CI -1.52 to -0.55) and 6 months (β: -1.24, p < 0.001, 95% CI -1.75 to -0.72). Participants in the TNFi group had a nonsignificant slight decrease of HbA1c%. Assuming the success threshold to be HbA1c% ≤ 7, we considered an absolute risk reduction (ARR) = 0.42 (experimental event rate = 0.54, control event rate = 0.12); thus, we estimated, rounding up, a number needed to treat (NNT) = 3. Concerning RA, a progressive reduction of disease activity was observed in both groups. No severe adverse events, hypoglycaemic episodes, or deaths were observed. Urticarial lesions at the injection site led to discontinuation in 4 (18%) anakinra-treated participants. Additionally, we observed nonsevere infections, including influenza, nasopharyngitis, upper respiratory tract infection, urinary tract infection, and diarrhoea in both groups. Our study has some limitations, including open-label design and previously unplanned ad interim analysis, small size, lack of some laboratory evaluations, and ongoing use of other drugs.Conclusions: In this study, we observed an apparent benefit of IL-1 inhibition in participants with RA and T2D, reaching the therapeutic targets of both diseases. Our results suggest the concept that IL-1 inhibition may be considered a targeted treatment for RA and T2D.Trial Registration: The trial is registered with EU Clinical Trials Register, EudraCT Number: 2012-005370-62 and with ClinicalTrial.gov, number NCT02236481. [ABSTRACT FROM AUTHOR]

Background: The Developmental Origins of Health and Disease (DOHaD) hypothesis postulates that exposures during early life, such as maternal dietary intake during pregnancy, may have a lifelong impact on the individual's susceptibility to diseases. The individual's own lifestyle habits are obviously an additional factor, but we have only limited knowledge regarding how it may interact with prenatal exposures in determining later disease. To gain further insight into these potentially complex relationships, we examined the longitudinal association between maternal diet quality during pregnancy and diet quality in early adolescence in a contemporary cohort.Methods and Findings: From 1996 to 2003, the Danish National Birth Cohort (DNBC) was established. Women from across the country were enrolled, and dietary intake in midpregnancy was assessed concurrently with a 360-item food frequency questionnaire (FFQ) (https://www.dnbc.dk/-/media/arkiv/projekt-sites/dnbc/kodeboeger/dnbc-food-frequency-questionnaire/dnbc-food-frequency-questionnaire-pdf.pdf?la=en). During 2013-2018, dietary intake was assessed at age 14 years with a 150-item FFQ (https://www.dnbc.dk/-/media/arkiv/projekt-sites/dnbc/kodeboeger/ffq-14/dnbc-ffq-14-english-translation.pdf?la=en) in the DNBC children. Among the 19,582 mother-offspring pairs included in the analyses, the mean age (±standard deviation [SD]) was 30.7 (±4.1) years and 14.0 (±0.0) years for mothers and offspring, respectively. The majority of both mothers (67%) and offspring (76%) were classified as normal weight. For both questionnaires, a Healthy Eating Index (HEI) was developed as an indicator for diet quality based on current Danish Food-Based Dietary Guidelines (FBDG) including eight components: fruits and vegetables, fish, dietary fibres, red meat, saturated fatty acids (SFAs), sodium, sugar-sweetened beverages (SSBs), and added sugar. The HEI score was divided into quartiles; individuals in the highest quartile represented those with the most optimal diet. The maternal HEI score was correlated positively with offspring HEI score (Pearson r = 0.22, p < 0.001). A log-linear binomial model was used to estimate the relative risk of the offspring being in the highest quartile of HEI at age 14 years if the mother was ranked in quartile 4 during pregnancy. Results showed that offspring born to mothers who were in the highest HEI quartile during pregnancy were more likely themselves to be located in the highest HEI quartile at age 14 years (risk ratio [RR]: 2.1, 95% confidence interval [CI]: 2.0, 2.3, p < 0.001). Adjusting for maternal prepregnancy body mass index (BMI), parity, education, alcohol intake, physical activity, smoking, and breastfeeding, as well as offspring total energy intake and sex, did not influence the effect estimates. The limitations of our study include that some attrition bias towards more healthy participants was observed when comparing participants with nonparticipants. Bias in the FFQ method may also have resulted in underrepresentation of adolescents with poorer diet quality.Conclusions: In this study using data from a large national birth cohort, we observed that maternal diet quality during pregnancy was associated with diet quality of the offspring at age 14 years. These findings indicate the importance of separating early dietary exposures from later dietary exposures when studying dietary aetiologies of diseases postulated to have developmental origins such as, for instance, obesity or asthma in observational settings. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate which clinical and metabolic tests offer optimal accuracy and acceptability to help diagnose diabetes among a large sample of people with serious mental illness in receipt of antipsychotic medication. Methods: A prospective observational study design of biochemical and clinical factors was used. Biochemical measures were fasting glucose, insulin and lipids, oral glucose tolerance testing (OGTT), hemoglobin A1c, and insulin resistance assessed with the homeostatic model (HOMA-IR) were determined in a consecutive cohort of 798 adult psychiatric inpatients receiving antipsychotics. Clinical variables were gender, age, global assessment of functioning (GAF), mental health clinicians’ global impression (CGI), duration of severe mental illness, height, weight, BMI and waist/hip ratio. In addition, we calculated the risk using combined clinical predictors using the Leicester Practice Risk Score (LPRS) and the Topics Diabetes Risk Score (TDRS). Diabetes was defined by older criteria (impaired fasting glucose (IFG) or OGTT) as well as2010 criteria (IFG or OGTT or Glycated haemoglobin (HBA1c)) at conventional cut-offs. Results: Using the older criteria, 7.8% had diabetes (men: 6.3%; women: 10.3%). Using the new criteria, 10.2% had diabetes (men: 8.2%, women: 13.2%), representing a 30.7% increase (p = 0.02) in the prevalence of diabetes. Regarding biochemical predictors, conventional OGTT, IFG, and HbA1c thresholds used to identify newly defined diabetes missed 25%, 50% and 75% of people with diabetes, respectively. The conventional HBA1c cut-point of ≥6.5% (48 mmol/mol) missed 7 of 10 newly defined cases of diabetes while a cut-point of ≥5.7% improved sensitivity from 44.4% to up to 85%. Specific algorithm approaches offered reasonable accuracy. Unfortunately no single clinical factor was able to accurately rule-in a diagnosis of diabetes. Three clinical factors were able to rule-out diabetes with good accuracy namely: BMI, waist/hip ratio and height. A BMI < 30 had a 92% negative predictive value in ruling-out diabetes. Of those not diabetic, 20% had a BMI ≥ 30. However, for complete diagnosis a specific biochemical protocol is still necessary. Conclusions: Patients with SMI maintained on antipsychotic medication cannot be reliably screened for diabetes using clinical variables alone. Accurate assessment requires a two-step algorithm consisting of HBA1c ≥5.7% followed by both FG and OGTT which does not require all patients to have OGTT and FG. [ABSTRACT FROM AUTHOR]

Purpose: To determine the characteristics of diabetic macular edema (DME) patients refractory to intravitreal bevacizumab (IVB) treatments and an additional dexamethasone implant. Methods: We classified 119 DME patients according to whether or not they are responsive to 3 consecutive monthly anti-VEGF treatments and/or an additional dexamethasone implant. We compared their concentrations of IL (interleukin)-1β, IL-8, IL-10, IL-17, placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) in the aqueous humor as well as their optical coherence tomography (OCT) findings, and baseline characteristics. We used logistic regression analyses to identify preoperative factors related to refractoriness to treatments. Results: Of 119 treatment-naïve DME patients, 50 (42.02%) patients showed responsiveness [central subfield thickness (CST) < 300μm] after 3 IVBs, and 59 (49.58%) patients showed responsiveness after an additional dexamethasone implant, but 10 (8.40%) patients showed CST 300 ≥ μm even after both treatments. Refractory DME patients showed significantly higher number of hyperreflective foci (HF) in the OCT and higher average level of aqueous IL-1β at baseline (p<0.001 and p = 0.042, respectively). In the logistic regression analysis, higher number of HF in the OCT was associated with the refractoriness to both treatments (odds ratio [OR]: 7.03, p = 0.007) Conclusions: Higher number of HF in the OCT at the initial visit was associated with poor responses to IVBs and an additional dexamethasone implant. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have been successful in identifying genetic variants associated with complex diseases. However, association analyses between genotypes and phenotypes are not straightforward due to the complex relationships between genetic and environmental factors. Moreover, multiple correlated phenotypes further complicate such analyses. To resolve this complexity, we present an analysis using structural equation modeling (SEM). Unlike current methods that focus only on identifying direct associations between diseases and genetic variants such as single-nucleotide polymorphisms (SNPs), our method introduces the effects of intermediate phenotypes, which are related phenotypes distinct from the target, into the systematic genetic study of diseases. Moreover, we consider multiple diseases simultaneously in a single model. The procedure can be summarized in four steps: 1) selection of informative SNPs, 2) extraction of latent variables from the selected SNPs, 3) investigation of the relationships among intermediate phenotypes and diseases, and 4) construction of an SEM. As a result, a quantitative map can be drawn that simultaneously shows the relationship among multiple SNPs, phenotypes, and diseases. In this study, we considered two correlated diseases, hypertension and type 2 diabetes (T2D), which are known to have a substantial overlap in their disease mechanism and have significant public health implications. As intermediate phenotypes for these diseases, we considered three obesity-related phenotypes—subscapular skin fold thickness, body mass index, and waist circumference—as traits representing subcutaneous adiposity, overall adiposity, and abdominal adiposity, respectively. Using GWAS data collected from the Korea Association Resource (KARE) project, we applied the proposed SEM process. Among 327,872 SNPs, 24 informative SNPs were selected in the first step (p<1.0E-05). Ten latent variables were generated in step 2. After an exploratory analysis, we established a path diagram among phenotypes and diseases in step 3. Finally, in step 4, we produced a quantitative map with paths moving from specific SNPs to hypertension through intermediate phenotypes and T2D. The resulting model had high goodness-of-fit measures (χ2 = 536.52, NFI = 0.997, CFI = 0.998, GFI = 0.995, AGFI = 0.993, RMSEA = 0.012). [ABSTRACT FROM AUTHOR]

Introduction: Individuals with functional impairments or chronic diseases are often in need of assistance in their daily lives. For these individuals it is essential to find novel, cost-effective solutions to meet their needs. Service dogs are dogs that are specially trained to assist individuals with functional impairments and may be able to improve these individuals’ quality of life at a reasonable cost, i.e. be cost effective. Cost-effectiveness analyses are used to illustrate the cost of an intervention in relation to its effects and provide important input to decision-makers when setting priorities. Aim: The aim of this study is to assess the cost effectiveness of a certified physical service dog and a diabetes alert dog compared to a regular companion dog. Method: Costs, life years and quality-adjusted life years were estimated over a 10-year time horizon using a decision-analytic model built upon evidence from the”service and hearing dog project”. The primary outcome was the incremental cost-effectiveness ratio expressed as cost per gained quality-adjusted life year. The analysis was conducted from a societal perspective. Costs and effects were discounted with 3% per annum and reported in USD. Results: Compared to a regular companion dog, a physical service dog is cost saving [-6,000 USD] and gives the dog owner more quality-adjusted life years [0.28]. The diabetes alert dog is also cost effective in comparison with a regular companion dog [-4,500 USD, 0.06 QALYs]. Conclusion: This study indicates that a certified service dog is cost saving in comparison with a regular companion dog for individuals with functional impairments or chronic diseases. The uncertainty of the analysis implies that further studies are needed in order to confirm these results. Nevertheless, physical service dogs and diabetes alert dogs show potential to be a valuable support and decision analytic models are useful tools to provide this information. [ABSTRACT FROM AUTHOR]

Aims: We aimed to provide reference values for speckle-tracking derived systolic and diastolic myocardial deformation markers, and to determine their relation with age, sex, and cardiovascular risk factors. Methods and results: The Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study recruited a representative sample of the population of Würzburg, Germany, aged 30–79 years. In a sample of 1818 participants (52% female, mean age 54±12 years) global longitudinal peak systolic strain (GL-PSS, n = 1218), systolic (GL-SSR, n = 1506), and early (GL-EDSR, n = 1506) and late diastolic strain rates (GL-LDSR, n = 1500) were derived from 2D speckle tracking analysis. From a subgroup of 323 individuals without any cardiovascular risk factor, sex- and age-specific reference values were computed. GL-PSS, GL-SSR, and GL-EDSR were associated with sex, GL-EDSR decreased and GL-LDSR increased with age. In the total sample, dyslipidemia was associated with altered GL-PSS, GL-SSR, and GL-EDSR in women but not in men, whereas obesity was associated with less favorable GL-PSS and GL-EDSR in either sex. Hypertension impacted more adversely on systolic and diastolic myocardial deformation in women compared to men (all p<0.01). Conclusion: The female myocardium appeared more vulnerable to high blood pressure and dyslipidemia when compared to men, while obesity was associated with adverse myocardial deformation in either sex. The reference values for echocardiographic myocardial deformation provided for a non-diseased population and their here reported associations with cardiovascular risk factors will inform future observational and intervention studies regarding i) effect sizes and power calculation, ii) cross-study comparisons, and iii) categorization of myocardial deformation in specific patient groups. [ABSTRACT FROM AUTHOR]

Context: Multiple factors contribute to sexual dysfunction in men with obesity. Sex hormone levels are commonly abnormal in men with obesity and this abnormality is often the focus of management in clinical practice. The role of small fibre neuropathy in obesity-related sexual dysfunction is not well established. Objective: We aimed to investigate the relationship between sexual function, sex hormone levels and small nerve fibre morphology in men with severe obesity. Materials and methods: A prospective study of 29 men with severe obesity was undertaken. Sexual function was assessed using the European Male Ageing Study Sexual Function Questionnaire. Small nerve fibre morphology was quantified using corneal confocal microscopy. Sex hormone levels were measured by mass spectrophotometry. Results: Erectile dysfunction was present in 72% of the cohort with a higher prevalence of diabetes among the symptomatic group (88% vs 38%, p = 0.006). Corneal nerve fibre length (CNFL) and corneal nerve fibre density (CNFD) were both significantly lower in participants with erectile dysfunction compared to those without (p = 0.039 and p = 0.048 respectively). The erectile function score correlated with CNFL (r = -0.418, p = 0.034) and CNFD (r = -0.411, p = 0.037). Total testosterone and calculated free testosterone levels did not differ significantly between men with or without erectile dysfunction (median 8.8 nmol/L vs 9.0 nmol/L, p = 0.914; and median 176 pmol/L vs 179 pmol/L, p = 0.351 respectively), infrequent sexual thoughts (median 8.1 nmol/L vs 9.2 nmol/L, p = 0.650; and median 184 pmol/L, vs 176 pmol/L, p = 0.619 respectively) and decreased morning erections (median 9.0 nmol/L vs 8.8 nmol/L, p = 0.655; and median 170 pmol/L vs 193 pmol/L, p = 0.278 respectively). Conclusion: Sexual dysfunction is highly prevalent in men with severe obesity. We found an association between small fibre neuropathy with erectile dysfunction with presence of diabetes a likely a significant contributing factor. We found no associations between testosterone levels with sexual symptoms (including frequency of sexual thoughts). The influence of small nerve fibre neuropathy on response to therapeutic interventions and whether interventions that improve small fibre neuropathy can improve erectile function in this population merits further study. [ABSTRACT FROM AUTHOR]

Oxidative stresses intensify the progression of diabetes-related behavioural changes and testicular injuries. Graviola (Annona muricata), a small tree of the Annonaceae family, has been investigated for its protective effects against diabetic complications, oxidative stress, and neuropathies. This study was planned to investigate the effects of graviola on behavioural alterations and testicular oxidative status of streptozotocin (STZ; 65 mg/kg)-induced diabetic rats. Forty adult male Wistar rats were equally allocated into four groups: control (received normal saline 8 ml/kg orally once daily), diabetic (received normal saline orally once daily), graviola (GR; received 100 mg/kg/day; orally once daily), and diabetic with graviola (Diabetic+GR; received 100 mg/kg/day; once daily). Behavioural functions were assessed using standard behavioural paradigms. Also, oxidative statuses of testis were evaluated. Results of behavioural observations showed that diabetes induced depression-like behaviours, reduction of exploratory and locomotor activities, decreased memory performance, and increased stress-linked behaviours. These variations in diabetic rats were happened due to oxidative stress. Interestingly, treatment of diabetic rats with graviola for four weeks alleviated all behavioural changes due to diabetes. Also, rats in graviola-treated groups had greater testicular testosterone and estradiol levels compared with diabetic rats due to significant rise in testicular acetyl-CoA acetyltransferase 2 expression. In the same context, graviola enhanced the antioxidant status of testicular tissues by significantly restoring the testicular glutathione and total superoxide dismutase that fell during diabetes. In addition, Graviola significantly decreased the expression of apoptotic (Bax) and inflammatory (interleukin-1β) testicular genes. In conclusion, these data propose that both the hypoglycemic and antioxidative potential of graviola are possible mechanisms that improve behavioural alterations and protect testis in diabetic animals. Concomitantly, further clinical studies in human are required to validate the current study. [ABSTRACT FROM AUTHOR]

The difficulty in obtaining as well as maintaining weight loss, together with the impairment of metabolic control in conditions like diabetes and cardiovascular disease, may represent pathological situations of inadequate neural communication between the brain and peripheral organs and tissues. Innervation of adipose tissues by peripheral nerves provides a means of communication between the master metabolic regulator in the brain (chiefly the hypothalamus), and energy-expending and energy-storing cells in the body (primarily adipocytes). Although chemical and surgical denervation studies have clearly demonstrated how crucial adipose tissue neural innervation is for maintaining proper metabolic health, we have uncovered that adipose tissue becomes neuropathic (ie: reduction in neurites) in various conditions of metabolic dysregulation. Here, utilizing both human and mouse adipose tissues, we present evidence of adipose tissue neuropathy, or loss of proper innervation, under pathophysiological conditions such as obesity, diabetes, and aging, all of which are concomitant with insult to the adipose organ as well as metabolic dysfunction. Neuropathy is indicated by loss of nerve fiber protein expression, reduction in synaptic markers, and lower neurotrophic factor expression in adipose tissue. Aging-related adipose neuropathy particularly results in loss of innervation around the tissue vasculature, which cannot be reversed by exercise. Together with indications of neuropathy in muscle and bone, these findings underscore that peripheral neuropathy is not restricted to classic tissues like the skin of distal extremities, and that loss of innervation to adipose may trigger or exacerbate metabolic diseases. In addition, we have demonstrated stimulation of adipose tissue neural plasticity with cold exposure, which may ameliorate adipose neuropathy and be a potential therapeutic option to re-innervate adipose and restore metabolic health. [ABSTRACT FROM AUTHOR]

This study aimed to examine the macrophage phenotype and its relationship to renal function and histological changes in human DN and the effect of TREM-1 on high-glucose-induced macrophage activation. We observed that in renal tissue biopsies, the expression of CD68 and M1 was apparent in the glomeruli and interstitium, while accumulation of M2 and TREM-1 was primarily observed in the interstitium. The numbers of CD68, M1, and M2 macrophages infiltrating in the DN group were increased in a process-dependent manner compared with the control group, and the intensities of the infiltrates were proportional to the rate of subsequent decline in renal function. M1 macrophages were recruited into the kidney at an early stage (I+IIa) of DN. The M1-to-M2 macrophage ratio peaked at this time, whereas M2 macrophages predominated at later time points (III) when the percentage of M1/M2 macrophages was at its lowest level. In an in vitro study, we showed that under high glucose conditions, macrophages began to up-regulate their expression of TREM-1, M1, and marker iNOS and decreased the M2 marker MR. However, the above effects of high-glucose were abolished when TREM-1 expression was inhibited by TREM-1 siRNA. In conclusion, our study demonstrated that there was a positive correlation between the M1/M2 activation state and the progress of DN, and TREM-1 played an important role in high-glucose-induced macrophage phenotype transformation. [ABSTRACT FROM AUTHOR]

Purpose: Data for elucidating post-kidney transplantation (KT) acute pancreatitis (AP) risk are limited and no large-scale cohort study has investigated the impact of AP after KT. Method: Data from Taiwan National Health Insurance (NHI) Research Database (NHIRD) were calculated through the method of propensity score matching to compare the pancreatitis risk in patients with and without KT. Results: The overall pancreatitis incidence rates were 1.71 and 0.61 per 1,000 person-years in the KT and non-KT groups, respectively and corresponding adjusted HR (aHR [95% CI]) for pancreatitis was 2.48 (1.51–4.09) in the KT group. In the multivariable model, AP risk was higher in transplant patients with alcohol-related illnesses (aHR: 3.78, 95% CI: 1.32–10.8), gall stone disease (aHR: 3.53, 95% CI: 1.48–8.44), or past history of pancreatitis (aHR: 10.3, 95% CI: 5.08–20.8). Of note, recurrent AP risk was significantly higher in the KT group (aHR: 8.19, 95% CI: 2.89–23.2). Patients with post-KT AP demonstrated shorter patient and allograft survival than did those without (both P < 0.001, respectively). Conclusion: In conclusion, KT recipients are very likely to be associated with AP. Moreover, their inferior outcomes are strongly associated with post-KT AP. [ABSTRACT FROM AUTHOR]