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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]

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]

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]

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]

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: 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]

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]

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]

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]

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]

Objectives: Currently used risk scores for type 2 diabetes mellitus (T2DM) clearly underestimate cardiovascular risk in type 1 diabetes (T1DM). Hence, there is a need to develop novel and specific risk-estimation tools for this population. We aimed to assess the relationship between the Steno Type 1 Risk Engine (ST1RE) and arterial stiffness (AS), and to identify potential cut-off points of interest in clinical practice. Design and methods: A total of 179 patients with T1DM (50.8% men, mean age 41.2±13.1 years), without established cardiovascular disease, were evaluated for clinical and anthropometric data (including classical cardiovascular risk factors), and AS measured by aortic pulse-wave velocity (aPWV). The ST1RE was used to estimate 10-year cardiovascular risk and patients were classified into 3 groups: low- (<10%; n = 105), moderate- (10–20%; n = 53) and high-risk (≥20%; n = 21). Results: When compared with the low- and moderate-risk groups, patients in the high-risk group were older, had higher prevalence of hypertension, dyslipidemia and insulin-resistance, and had higher body-mass index and HbA1c. aPWV increased in parallel with estimated cardiovascular risk (6.4±1.0, 8.4±1.3 and 10.3±2.6m/s; p<0.001). As an evaluation of model performance, the C-statistic of aPWV was 0.914 (95% confidence interval [CI]:0.873–0.950) for predicting moderate/high-risk and 0.879 (95%CI:0.809–0.948) for high-risk, according to the ST1RE. The best cut-off points of aPWV were 7.3m/s (sensitivity:86%, specificity:83%) and 8.7m/s (sensitivity:76%, specificity:86%) for moderate/high- and high-risk, respectively. Conclusions: AS is highly correlated with the scores obtained from the ST1RE. We have identified two cut-off points of AS that can clearly discriminate moderate/high- and high-risk T1DM patients, which could be of great value in clinical practice. [ABSTRACT FROM AUTHOR]

Background: There has been a growing interest in understanding the effects of social networks on health-related behaviour, with a particular backdrop being the emerging prominence of complexity or systems science in public health. Social network interventions specifically use or alter the characteristics of social networks to generate, accelerate, or maintain health behaviours. We conducted a systematic review and meta-analysis to investigate health behaviour outcomes of social network interventions.Methods and Findings: We searched eight databases and two trial registries from 1990 to May 28, 2019, for English-language reports of randomised controlled trials (RCTs) and before-and-after studies investigating social network interventions for health behaviours and outcomes. Trials that did not specifically use social networks or that did not include a comparator group were excluded. We screened studies and extracted data from published reports independently. The primary outcome of health behaviours or outcomes at ≤6 months was assessed by random-effects meta-analysis. Secondary outcomes included those measures at >6-12 months and >12 months. This study is registered with the International Prospective Register of Systematic Reviews, PROSPERO: CRD42015023541. We identified 26,503 reports; after exclusion, 37 studies, conducted between 1996 and 2018 from 11 countries, were eligible for analysis, with a total of 53,891 participants (mean age 32.4 years [SD 12.7]; 45.5% females). A range of study designs were included: 27 used RCT/cluster RCT designs, and 10 used other study designs. Eligible studies addressed a variety of health outcomes, in particular sexual health and substance use. Social network interventions showed a significant intervention effect compared with comparator groups for sexual health outcomes. The pooled odds ratio (OR) was 1.46 (95% confidence interval [CI] 1.01-2.11; I2 = 76%) for sexual health outcomes at ≤6 months and OR 1.51 (95% CI 1.27-1.81; I2 = 40%) for sexual health outcomes at >6-12 months. Intervention effects for drug risk outcomes at each time point were not significant. There were also significant intervention effects for some other health outcomes including alcohol misuse, well-being, change in haemoglobin A1c (HbA1c), and smoking cessation. Because of clinical and measurement heterogeneity, it was not appropriate to pool data on these other behaviours in a meta-analysis. For sexual health outcomes, prespecified subgroup analyses were significant for intervention approach (p < 0.001), mean age of participants (p = 0.002), and intervention length (p = 0.05). Overall, 22 of the 37 studies demonstrated a high risk of bias, as measured by the Cochrane Risk of Bias tool. The main study limitations identified were the inclusion of studies of variable quality; difficulty in isolating the effects of specific social network intervention components on health outcomes, as interventions included other active components; and reliance on self-reported outcomes, which have inherent recall and desirability biases.Conclusions: Our findings suggest that social network interventions can be effective in the short term (<6 months) and longer term (>6 months) for sexual health outcomes. Intervention effects for drug risk outcomes at each time point were not significant. There were also significant intervention effects for some other health outcomes including alcohol misuse, well-being, change in HbA1c, and smoking cessation. [ABSTRACT FROM AUTHOR]

Background & aims: In patients at metabolic risk, nonalcoholic fatty liver disease is a strong and highly prevalent predictor for type 2 diabetes. Its assessment in clinical practice is not easy but the fatty liver index (FLI) could be used as a surrogate. Here, we studied the association between the FLI and the conversion to new-onset diabetes (NOD) or prediabetes reversion in patients with prediabetes. Methods: The IT-DIAB observational study included 389 individuals with prediabetes, defined as fasting plasma glucose (FPG) between 110 and 125 mg/dL. NOD conversion was defined as a first FPG value ≥ 126 mg/dL and prediabetes reversion as a first FPG value < 110 mg/dL. The associations of both events with baseline FLI were studied separately using multivariate Cox models. Results: After a median follow-up of 3.9 years (range 0.1–6.1), 138 individuals (35.5%) converted to NOD. FLI was associated with a higher risk of NOD conversion (unadjusted HR per SD = 1.54, 95%CI 1.27–1.86, p<0.0001), even after multiple adjustment on FPG, HbA1c and diabetes risk score (adjusted HR per SD 1.31, 95%CI 1.07–1.61, p = 0.008). FLI was also associated with prediabetes reversion: adjusted HR per SD = 0.85, 95%CI 0.75–0.96, p = 0.0077. Changes in FLI were significantly associated with changes in FPG during follow-up (p<0.0001). When compared to a full model including the diabetes risk score, FPG, HbA1C and FLI, only HbA1C added a significant prediction information (AUROC: 72.8% for full model vs 69.4% for the model without HbA1C; p = 0.028), while the removal of FLI to the full model did not alter its predictive value (AUROC 72.2%). The predictive value for NOD conversion was not significantly better for HOMA-IR compared to FLI (AUROC: 69.3 vs 63.7%, p = 0.067). Conclusions: FLI is a simple, practical score to further stratify the risk of conversion to NOD or the possibility of prediabetes reversion in clinical practice, independently of classical glucose parameters. Trial registration: ClincialTrials.gov number and . [ABSTRACT FROM AUTHOR]

Diabetes plays an important role in the complex relationship between chronic kidney disease (CKD) and cardiovascular disease. This retrospective observational study compared the influence of estimated glomerular filtration rate (eGFR) and proteinuria on the risk of major adverse cardiovascular event (MACE; myocardial infarction or stroke) in CKD patients with and without diabetes. Data were from a linked database of UK electronic health records. Individuals with CKD and no prior MACE were classified as type 1 diabetes (T1DM; n = 164), type 2 diabetes (T2DM; n = 9,711), and non-diabetes (non-DM; n = 75,789). Monthly updated time-dependent Cox proportional hazard models were constructed to calculate adjusted hazard ratios (aHRs) for progression to MACE from first record of abnormal eGFR or proteinuria (index date). In non-DM, aHRs (95% CIs) by baseline eGFR category (referent G2) were G1: 0.70 (0.55–0.90), G3a: 1.28 (1.20–1.35), G3b: 1.64 (1.52–1.76), G4: 2.19 (1.98–2.43), and G5: 3.12 (2.44–3.99), and by proteinuria category (referent A1) were A2: 1.13 (1.00–1.28), A2/3 (severity indeterminable): 1.58 (1.28–1.95), and A3: 1.64 (1.38–1.95). In T2DM, aHRs were G1: 0.98 (0.72–1.32), G3a: 1.18 (1.03–1.34), G3b: 1.31 (1.12–1.54), G4: 1.87 (1.53–2.29), G5: 2.87 (1.82–4.52), A2: 1.22 (1.04–1.42), A2/3: 1.45 (1.17–1.79), and A3: 1.82 (1.53–2.16). Low numbers in T1DM precluded analysis. Modelling T2DM and non-DM together, aHRs were, respectively, G1: 3.23 (2.38–4.40) and 0.70 (0.55–0.89); G2: 3.18 (2.73–3.70) and 1.00 (referent); G3a: 3.65 (3.13–4.25) and 1.28 (1.21–1.36); G3b: 4.01 (3.40–4.74) and 1.65 (1.54–1.77); G4: 5.78 (4.70–7.10) and 2.21 (2.00–2.45); G5: 9.00 (5.71–14.18) and 3.14 (2.46–4.00). In conclusion, reduced eGFR and proteinuria were independently associated with increased risk of MACE regardless of diabetes status. However, the risk of MACE in the same eGFR state was 4.6–2.4 times higher in T2DM than in non-DM. [ABSTRACT FROM AUTHOR]

Background: Frequency of insulin pen use, despite its higher costs, is increasing to substitute the traditional use of insulin vials. This study aims to report insulin pen use frequency and its associated factors among participants of the STEPS survey 2016 in Iran, which was conducted based on the World Health Organization (WHO) STEPS methodology. Methods: In this cross-sectional study, 19,503 (mean age of 46.03±0.13) out of 30,541 participants of the Iran STEPS survey were included (Inclusion criteria: aged >25 years old and availability of their demographic, clinical, and laboratory results for serum glucose, HbA1c, and lipid profile). Clinical and demographic characteristics, a frequency of use of each diabetes mellitus treatment type, and the association of insulin pen use with health outcomes are reported using descriptive analysis and propensity score modeling. Results: There were 1,999(10.85%) individuals diagnosed with diabetes in the population, while 1,160(56.87%) cases were taking antihyperglycemic treatments. In this subset, 240(21.14%) individuals administered insulin with or without using oral agents at the same time. 52.28% of participants who were under insulin therapy used insulin pens. None of the socioeconomic determinants, including gender (p-value = 0.11), type of residential areas (p-value = 0.52), years of schooling (p-value = 0.27), wealth index (p-value = 0.19), marital status (p-value = 0.37), and insurance types (p-value = 0.72) were significantly different among groups using insulin pens and insulin vials. Moreover, in the propensity score modeling, pen usage was not associated with a lower heart attack and ischemic stroke histories, systolic blood pressure, serum lipid profile, blood glucose, or HbA1c levels. Conclusion: Results showed that the use of the higher-costing insulin pens compared to traditional vials and syringes is not associated with improved glycemic control and better lipid profile in our sample. Future studies are needed to confirm these findings and to compare other aspects of insulin pen use, including adherence to treatment and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Objectives: Despite growing evidence of the impact of smoking on diabetes complications, people with type 2 diabetes still smoke at high rates and little is known about the specific barriers to quit smoking in this group. The purpose of this article is to explore the perception of smoking, and motivation and barriers to quit among smokers with type 2 diabetes. This exploratory study will help designing a smoking cessation intervention tailored to the needs of people with type 2 diabetes. We hypothesize both that living with diabetes and gender may raise additional difficulties to quit smoking. Setting: The qualitative exploratory research included ten in-depth semi-structured individual interviews and five focus groups conducted in an Ambulatory Care University Hospital in Switzerland. The thematic analysis was conducted with a gender-sensitive focus. Participants: Both current and former smokers recruited from the ambulatory clinic and the community took part in the qualitative interviews. We restricted the analysis to 21 current smokers only. Results: The sample included 12 men and 9 women with type 2 diabetes, having a mean age of 59.4 years, who had diabetes for an average of 9 years with a mean HbA1c of 7.4%. We found that harmful effects of tobacco were superficially understood, and participants used several patterns of thinking to minimize the risks. The relation between tobacco and diabetes was poorly known. Readiness to change was related to personal self-image and meaningful engagement in life and social relationships. Barriers could be organized into three groups: dependence, psychological habits and social barriers. Barriers were markedly shaped by gender and living with diabetes. Conclusions: Results suggest that “one -fits-all” smoking cessation interventions do not satisfy the needs of type 2 diabetic smokers. Personalized smoking cessation interventions should be preferred and should pursue positive psychological outcomes addressing contextual factors. [ABSTRACT FROM AUTHOR]

Gastrin is a peptide hormone, which in combination with other factors such as TGFα, EGF or GLP-1, is capable of increasing beta cell mass and lowering blood glucose levels in adult diabetic mice. In humans, administration of a bolus of gastrin alone induces insulin secretion suggesting that gastrin may target islet cells. However, whether gastrin alone is sufficient to exert an effect on isolated human islets has been controversial and the mechanism remained poorly understood. Therefore, in this study we started to examine the effects of gastrin alone on cultured adult human islets. Treatment of isolated human islets with gastrin I for 48 h resulted in increased expression of insulin, glucagon and somatostatin transcripts. These increases were significantly correlated with the levels of donor hemoglobin A1c (HbA1c) but not BMI or age. In addition, gastrin treatment resulted in increased expression of PDX1, NKX6.1, NKX2.2, MNX1 and HHEX in islets from donors with HbA1c greater than 42 mmol/mol. The addition of YM022, an antagonist of the gastrin receptor cholecystokinin B receptor (CCKBR), together with gastrin eliminated these effects, verifying that the effects of gastrin are mediated through CCKBR.CCKBR is expressed in somatostatin-expressing delta cells in islets from all donors. However, in the islets from donors with higher HbA1c (greater than 42 mmol/mol [6.0%]), cells triple-positive for CCKBR, somatostatin and insulin were detected, suggesting a de-differentiation or trans-differentiation of endocrine cells. Our results demonstrate a direct effect of gastrin on human islets from prediabetic or diabetic individuals that is mediated through CCKBR+ cells. Further, our data imply that gastrin may be a potential treatment for diabetic patients. [ABSTRACT FROM AUTHOR]

Background: In Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes. Methods: Forty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation. Results: At week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of β cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial. Conclusions: This pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and β-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification. [ABSTRACT FROM AUTHOR]

Background: Based on the association of common GLIS3 variants with various forms of diabetes and the biological role of GLIS3 in beta-cells, we sequenced GLIS3 in non-diabetic and diabetic Danes to investigate the effect of rare missense variants on glucose metabolism. Methods: We sequenced 53 patients with maturity-onset diabetes of the young (MODY), 5,726 non-diabetic participants, 2,930 patients with newly diagnosed type 2 diabetes and 206 patients with glutamic acid decarboxylase antibody (GADA) -positive diabetes. Results: In total we identified 86 rare (minor allele frequency < 0.1%) missense variants. None was considered causal for the presence of MODY. Among patients with type 2 diabetes, we observed a higher prevalence of rare GLIS3 missense variants (2.5%) compared to non-diabetic individuals (1.8%) (odds ratio of 1.37 (interquartile range:1.01–1.88, p = 0.04)). A significantly increased HbA1c was found among patients with type 2 diabetes and with GADA-positive diabetes carrying rare GLIS3 variants compared to non-carriers of rare GLIS3 variants with diabetes (p = 0.02 and p = 0.004, respectively). One variant (p.I28V) was found to have a minor allele frequency of only 0.03% among patients with type 2 diabetes compared to 0.2% among non-diabetic individuals suggesting a protective function (odds ratio of 0.20 (interquartile range: 0.005–1.4, p = 0.1)), an effect which was supported by publically available data. This variant was also associated with a lower level of fasting plasma glucose among non-diabetic individuals (p = 0.046). Conclusion: Rare missense variants in GLIS3 associates nominally with increased level of HbA1c and increased risk of developing type 2 diabetes. In contrast, the rare p.I28V variant associate with reduced level of fasting plasma glucose and may be protective against type 2 diabetes. [ABSTRACT FROM AUTHOR]

We aimed to investigate the clinical factors affecting the therapeutic effectiveness of the sodium–glucose cotransporter-2 inhibitor empagliflozin in patients with type 2 diabetes mellitus (T2DM). We reviewed the medical records of 374 T2DM patients aged between 20 and 75 years who were prescribed empagliflozin 10 mg or 25 mg as add-on therapy for more than 90 consecutive days. Changes in hemoglobin A1c (HbA1c) from baseline levels and the reduction in body weights of the study participants were assessed. We found that younger patients (≤ 50 years), patients with the highest levels of HbA1c (>9%) at baseline, patients with an estimated glomerular filtration rate (eGFR) of >90 mL/min/1.73 m2, and patients with a shorter duration of T2DM (< 10 years) were more likely to exhibit a better glycemic response. Multivariate linear regression analysis revealed that a shorter duration of T2DM, higher baseline levels of HbA1c, and higher eGFR were positively associated with HbA1c reduction. Higher BMI and lower HbA1c levels were predictors of a more significant reduction in body weight among patients taking empagliflozin. The glucose-lowering effect of empagliflozin was more evident in T2DM patients with higher baseline HbA1c levels, better renal function, and shorter duration of T2DM. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis and advanced fibrosis in particular is the strongest predictor of liver-related outcomes and mortality among nonalcoholic steatohepatitis (NASH) patients. Understanding prevalence and predictors of NASH with advanced fibrosis is critical for healthcare resource planning. Using a large U.S. clinical laboratory database from 10/1/2017-9/30/2018, adults negative for hepatitis B and hepatitis C and after excluding for alcoholic liver disease and pregnancy were evaluated for prevalence of F3 and F4 fibrosis using a systematic algorithm of five fibrosis-4 (FIB-4) criteria: Criteria 1 (≥F3: >2.67), Criteria 2 (2.674.12), Criteria 3 (2.673.15), Criteria 4 (3.253.5), Criteria 5 (3.254.12). Metabolic co-morbidities evaluated included decreased high density lipoprotein (<40 mg/dL men, <50 mg/dL women), high triglycerides (≥150 mg/dL), elevated hemoglobin A1C (≥6.5%). Parallel analyses of patients with specific NAFLD/NASH ICD-9/10 codes from 10/1/2013-9/30/2018 were performed. Multivariate logistic regression models evaluated for predictors of ≥F3 fibrosis. Among patients with NAFLD/NASH ICD-9/10 codes, ≥F3 prevalence ranged from 4.35% - 6.90%, and F4 prevalence ranged from 2.52%– 3.67%. Increasing metabolic co-morbidities was associated with higher risk of ≥F3 fibrosis. Compared to NASH patients without metabolic co-morbidities, NASH with four concurrent metabolic co-morbidities had higher risk of ≥F3 (OR 1.56, 95% CI 1.40–1.73, p<0.001). In summary, prevalence of NASH with advanced fibrosis among U.S. adults was as high as 6.90% and prevalence of NASH with cirrhosis was as high as 3.67%, representing 5.18 million and 2.75 million, respectively, when using an estimate of 75 million U.S. adults with NAFLD. Co-morbid metabolic abnormalities were associated with higher risk of advanced fibrosis among NASH patients. [ABSTRACT FROM AUTHOR]

Since both retinopathy and nephropathy are major diabetic microvascular complications, we investigated whether severity of diabetic retinopathy (DR) has adverse effects on renal function and albuminuria in the patients with type 2 diabetes mellitus (DM). We screened 2,197 adult patients with type 2 DM who had undergone fundus exam between August 2006 and February 2014. Among them, 1,592 subjects with available serial renal function and albuminuria measurement were included in the analysis. DR status was classified as no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). The risk of CKD progression was assessed according to DR severity. A total of 384 (24.1%) had NPDR and 202 (12.7%) had PDR at either eye. The mean follow-up period was 5.6±2.1 years. DR was associated with lower body mass index, lower plasma hemoglobin, lower serum albumin level, longer duration of DM, poorer control of blood sugar, lower estimated glomerular filtration rate (eGFR), and greater amount of albuminuria. Interestingly, baseline DR severity was associated with faster renal function decline and greater albuminuria progression. In multivariate analysis, NPDR had 2.9 times and PDR had 16.6 times higher risk for CKD progression. Our findings showed that baseline DR severity is a prognostic factor for future CKD progression in type 2 DM patients. Therefore, clinicians must evaluate DR severity at the first visit and closely monitor renal function and albuminuria in the subjects with severe DR. [ABSTRACT FROM AUTHOR]

Aims: The aim of the present study was to investigate the major determinants of diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D), considering the traditional and newly discovered risk factors, including hypoglycaemia and glycemic variability. Methods: This retrospective case-control study was conducted in a tertiary care hospital in Taiwan. A total of 2,837 patients with T2D were recruited, medical history and biochemical data were obtained, and patients were screened for DPN using the Michigan Neuropathy Screening Instrument (MNSI). DPN was defined as an MNSI exam score > 2. A stepwise selection of variables was used based on the Akaike Information Criterion (AIC) and the Schwarz Criterion (SC). Multivariate analysis was performed using the identified variables obtained from the stepwise selection. Results: Among the recruited patients, 604 (21.3%) were found to have DPN. 275 patients with DPN were selected because of longer follow up period before enrollment and complete data of glycemic parameters, and paired with 351 patients with T2D without DPN and matched for age, gender, and diabetes duration. The results of the stepwise selection showed that the presence of moderately and severely increased albuminuria yielded the lowest values of AIC and SC, which indicate the best predictive performance. Multivariate analysis demonstrated that moderately and severely increased albuminuria and greater long-term glycemic variability significantly increased the risk of DPN, with a corresponding odds ratio of 1.85 and 1.61 (95%confidence intervals of 1.25–2.73and1.02–2.55, respectively), after adjusted for hypoglycaemia and types of diabetes treatment. Conclusions: Albuminuria is a potent predictor of DPN, and greater long-term glycemic variabilityis clearly associated with DPN in adults with T2D. These findings indicate that, in addition to achieve average blood glucose control, screening for albuminuria and reducing blood glucose fluctuations might be useful for improving diabetic microvascular complications. [ABSTRACT FROM AUTHOR]

Introduction: Liver transplant (LT) recipients have limited understanding of post-transplant chronic kidney disease (CKD) despite an excellent pre-existing framework of transplant care. This pilot study examined the efficacy and feasibility of a tailored educational and goal-setting tool in improving CKD knowledge among LT recipients with early-stage CKD. Methods: In this prospective cohort study, we administered the CKD educational and goal-setting tool to 81 LT recipients between 7/1/2016 and 12/31/2017. We excluded patients with simultaneous liver-kidney transplantation, eGFR<30 ml/min, non-English speaking, on hemodialysis or listed for kidney transplantation. The pre- and post-education knowledge scores were compared using a paired t-test. Linear regression was used to assess the independent predictors of change in knowledge score. Results: Mean age was 56.3 years, 69.1% were males, 85.2% were Caucasians and mean eGFR was 61.2 ± 20.0 ml/min. The CKD educational and goal-setting tool improved the CKD knowledge scores among LT recipients (pre: 71.8 ± 16.6%, post: 83.3 ± 10.4%; p<0.001). In an adjusted model (r2 = 0.75), those with lower pre-education knowledge scores had the most improvement in their post-education knowledge scores (β = -83.2; p<0.001). Two-thirds stated their most important self-management goal and reported motivation to follow this goal. Time spent for the CKD education was approximately 15 minutes. Conclusions: A simple LT-specific patient educational and goal-setting tool effectively improved CKD knowledge. Implementation of this tailored intervention will improve CKD awareness and may promote goal-setting in the target population. [ABSTRACT FROM AUTHOR]

The study aims to describe the distribution of patients with type 2 diabetes (T2D) by care plan and to highlight determinants of underuse and overuse of integrated care (IC). This cross-sectional study included all T2D patients resident in Reggio Emilia on 31/12/2015 based on the population-based diabetes registry. Eligibility for IC requires good glycaemic control, no rapid insulin, no kidney failure and no diabetes complications. We calculated the proportion of IC underuse and overuse and adjusted prevalence estimate using multivariate logistic regression. Determinants were age, sex, citizenship, district of residence and time since diagnosis. Of 29,776 patients, 15,364 (51.6%) were in diabetes clinic plan, 9851 (33.1%) in IC plan and 4561 (15.3%) not in any care plan (i.e., in Other group). There were 10,906 (36.6%) patients eligible for IC, of whom 1000 in Other group. When we adjusted for all covariates and restricted the analysis to patients included in care plans, the proportion of those eligible for IC plan but cared for in diabetes clinic plan (i.e. underuse of IC) was 28% (n = 3028/9906; 95%CI 27–29). Similarly, the proportion of those not eligible for IC but cared for in IC plan (i.e. overuse of IC) was 11% (n = 1720/11,896; 95%CI 10–11).The main determinant of both IC underuse and overuse was the district of residence. Foreign status was associated with underuse (37%; 95%CI 33–43), while old age (≥80 years) with both underuse (36%; 95%CI 0.33–0.38) and overuse (23%; 95%CI 22–25). The criterion for suspension of IC plan most frequently found was renal failure, followed by hospitalization for diabetes-related complications. Patients are more often allocated to more specialized settings than not. Healthcare provider-related factors are the main determinants of inappropriate setting allocation. [ABSTRACT FROM AUTHOR]

Aims/Hypothesis: Early recognition of those at high risk for diabetes as well as diabetes itself can permit preventive management, but many Americans with diabetes are undiagnosed. We sought to determine whether routinely available outpatient random plasma glucose (RPG) would be useful to facilitate the diagnosis of diabetes. Methods: Retrospective cohort study of 942,446 U.S. Veterans without diagnosed diabetes, ≥3 RPG in a baseline year, and ≥1 primary care visit/year during 5-year follow-up. The primary outcome was incident diabetes (defined by diagnostic codes and outpatient prescription of a diabetes drug). Results: Over 5 years, 94,599 were diagnosed with diabetes [DIAB] while 847,847 were not [NONDIAB]. Baseline demographics of DIAB and NONDIAB were clinically similar, except DIAB had higher BMI (32 vs. 28 kg/m2) and RPG (150 vs. 107 mg/dl), and were more likely to have Black race (18% vs. 15%), all p<0.001. ROC area for prediction of DIAB diagnosis within 1 year by demographic factors was 0.701, and 0.708 with addition of SBP, non-HDL cholesterol, and smoking. These were significantly less than that for prediction by baseline RPG alone (≥2 RPGs at/above a given level, ROC 0.878, p<0.001), which improved slightly when other factors were added (ROC 0.900, p<0.001). Having ≥2 RPGs ≥115 mg/dl had specificity 77% and sensitivity 87%, and ≥2 RPGs ≥130 mg/dl had specificity 93% and sensitivity 59%. For predicting diagnosis within 3 and 5 years by RPG alone, ROC was reduced but remained substantial (ROC 0.839 and 0.803, respectively). Conclusions: RPG levels below the diabetes “diagnostic” range (≥200 mg/dl) provide good discrimination for follow-up diagnosis. Use of such levels–obtained opportunistically, during outpatient visits–could signal the need for further testing, allow preventive intervention in high risk individuals before onset of disease, and lead to earlier identification of diabetes. [ABSTRACT FROM AUTHOR]

Background: The prevalence of non-communicable diseases (NCDs) is rising in low- and middle-income countries (LMICs). Self-management, which enables patients to better manage their health, presents a potentially-scalable means of mitigating the growing burden of NCDs in LMICs. Though the effectiveness of self-management interventions in high-income countries is well-documented, the use of these strategies in LMICs has yet to be thoroughly summarized. Objective: The purpose of this scoping review is to summarize the nature and effectiveness of past interventions that have enabled the self-management of NCDs in LMICs. Methods: Using the scoping review methodology proposed by Arksey and O’Malley, PubMed was searched for relevant articles published between January 2007 and December 2018. The implemented search strategy comprised three major themes: self-management, NCDs and LMICs. Results: Thirty-six original research articles were selected for inclusion. The selected studies largely focused on the self-management of diabetes (N = 21), hypertension (N = 7) and heart failure (N = 5). Most interventions involved the use of short message service (SMS, N = 17) or phone calls (N = 12), while others incorporated educational sessions (N = 10) or the deployment of medical devices (N = 4). The interventions were generally effective and often led to improvements in physiologic indicators, patient self-care and/or patient quality of life. However, the studies emphasized results in small populations, with little indication of future scaling of the intervention. Furthermore, the results indicate a need for further research into the self-management of cardiovascular diseases, as well as for the co-management of diabetes and cardiovascular disease. Conclusions: Self-management appears to be an effective means of improving health outcomes in LMICs. Future strategies should include patients and clinicians in all stages of design and development, allowing for a focus on long-term sustainability, scalability and interoperability of the intervention in the target setting. [ABSTRACT FROM AUTHOR]

Background: The incidence of type 2 diabetes (T2DM) in children has increased dramatically. However, limited published information is known about the glycemic control and lipid outcomes in pediatric T2DM outside of clinical trials. Objectives: To determine the glycemic control and lipid measure outcomes at one and three- year follow-up in children with T2DM. Methods: A retrospective electronic medical record review of children with T2DM at the Children’s Hospital of Alabama over a 12-year period. Results: There were 301 patients with a diagnosis of T2DM who had a 1-year follow-up visit, of which 184 also had a 3-year follow-up. Most patients (78%) received either insulin with metformin or insulin alone at diagnosis. At one year, 37% of the cohort achieved ‘optimal glycemic control’ (HbA1C ≤6.5%) and 58% of patients achieved durable glycemic control (HbA1C ≤8%). Optimal glycemic control was seen in 48 patients at 3 years. The patients treated with insulin (alone or in combination with metformin) tended to have higher HbA1C at diagnosis, but had improved lipid and glycemic outcomes at follow-up. The group treated with insulin along with metformin had significant improvements in non-HDL, HDL and TC/HDL ratios. The effects of insulin treatment on glycemic control at 3 years were not statistically significant. Conclusion: With the current modality of treatment, only a minority of patients achieve optimal glycemic control at 1 and 3 years of follow-up. Studies are warranted to further elucidate the optimal therapies in the management of pediatric T2DM. [ABSTRACT FROM AUTHOR]

Background: The Philippines is ranked 3rd globally for tuberculosis incidence (554/100,000 population). The tuberculosis ward at San Lazaro Hospital, Manila receives 1,800–2,000 admissions of acutely unwell patients per year with high mortality. Objectives of this prospective cohort study were to quantify the association of under-nutrition (primary) and diabetes (secondary) with inpatient mortality occurring between 3–28 days of hospital admission in patients with suspected or previously diagnosed TB. Methods and results: We enrolled 360 adults (≥18 years); 348 were eligible for the primary analysis (alive on day 3). Clinical, laboratory, anthropometric and enhanced tuberculosis diagnostic data were collected at admission with telephone tracing for mortality up to 6 months post-discharge. In the primary analysis population (mean age 45 years, SD = 15.0 years, 70% male), 58 (16.7%) deaths occurred between day 3–28 of admission; 70 (20.1%) between day 3 and discharge and documented total post-day 3 mortality including follow-up was 96 (27.6%). In those in whom it could be assessed, body mass index (BMI) ranged from 11.2–30.6 kg/m2 and 141/303 (46.5%) had moderate/severe undernutrition (BMI<17 kg/m2). A sex-specific cut-off for mid-upper arm circumference predictive of BMI<17 kg/m2 was associated with inpatient Day 3–28 mortality in males (AOR = 5.04, 95% CI: 1.50–16.86; p = 0.009; p = 0.032 for interaction by sex). The inability to stand for weight/height for BMI assessment was also associated with mortality (AOR = 5.59; 95% CI 2.25–13.89; p<0.001) as was severe compared to normal/mild anaemia (AOR = 9.67; 95% CI 2.48–37.76; p<0.001). No TB specific variables were associated with Day 3–28 mortality, nor was diabetes (HbA1c ≥6.5% or diabetes treatment). Similar effects were observed when the same multivariable model was applied to confirmed TB patients only and to the outcome of all post-day 3 in-patient mortality. Conclusion: This research supports the use of mid-upper arm circumference for triaging acutely unwell patients and the design and testing of nutrition-based interventions to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: In 2017, more than 1.1 million children were living with type 1 diabetes mellitus (T1DM) globally. The goal in paediatric diabetes therapy is reaching optimal glycaemic control as early as possible in order to avoid complications and early mortality without compromising the quality of life (QoL) of children. Several different insulin regimens are available for T1DM patients to reach this goal. Aims: This review set out to analyse whether continuous subcutaneous insulin infusion (CSII) regimens are superior to multiple daily injection (MDI) therapy in T1DM youth regarding QoL. Additionally, it assessed glycaemic control and adverse events as secondary outcomes and discussed potential future public health implications and justifications for using CSII as a first-line therapy in diabetic youth. Methods: A systematic review and random effects meta-analysis was performed on studies investigating the association between QoL and diabetes treatment regimen. Differences in adverse event rates between groups were analysed using a Mann-Whitney U test. Lastly, differences in glycaemic control were assessed using a random effects meta-analysis. Results: QoL and glycaemic control was significantly better in CSII subjects at baseline and follow-up. No significant differences in adverse events were found between study groups. No significant changes over time could be shown for either QoL or glycaemic control. Conclusion: CSII proved to provide similar or slightly better outcomes in all analysed fields. This is consistent with previous research. However, to make credible recommendations, better-designed studies are needed to investigate the impact of CSII in children. [ABSTRACT FROM AUTHOR]

Background: Data are lacking from physical activity (PA) trials with long-term follow-up of both objectively measured PA levels and robust health outcomes. Two primary care 12-week pedometer-based walking interventions in adults and older adults (PACE-UP and PACE-Lift) found sustained objectively measured PA increases at 3 and 4 years, respectively. We aimed to evaluate trial intervention effects on long-term health outcomes relevant to walking interventions, using routine primary care data.Methods and Findings: Randomisation was from October 2012 to November 2013 for PACE-UP participants from seven general (family) practices and October 2011 to October 2012 for PACE-Lift participants from three practices. We downloaded primary care data, masked to intervention or control status, for 1,001 PACE-UP participants aged 45-75 years, 36% (361) male, and 296 PACE-Lift participants, aged 60-75 years, 46% (138) male, who gave written informed consent, for 4-year periods following randomisation. The following new events were counted for all participants, including those with preexisting diseases (apart from diabetes, for which existing cases were excluded): nonfatal cardiovascular, total cardiovascular (including fatal), incident diabetes, depression, fractures, and falls. Intervention effects on time to first event post-randomisation were modelled using Cox regression for all outcomes, except for falls, which used negative binomial regression to allow for multiple events, adjusting for age, sex, and study. Absolute risk reductions (ARRs) and numbers needed to treat (NNTs) were estimated. Data were downloaded for 1,297 (98%) of 1,321 trial participants. Event rates were low (<20 per group) for outcomes, apart from fractures and falls. Cox hazard ratios for time to first event post-randomisation for interventions versus controls were nonfatal cardiovascular 0.24 (95% confidence interval [CI] 0.07-0.77, p = 0.02), total cardiovascular 0.34 (95% CI 0.12-0.91, p = 0.03), diabetes 0.75 (95% CI 0.42-1.36, p = 0.34), depression 0.98 (95% CI 0.46-2.07, p = 0.96), and fractures 0.56 (95% CI 0.35-0.90, p = 0.02). Negative binomial incident rate ratio for falls was 1.07 (95% CI 0.78-1.46, p = 0.67). ARR and NNT for cardiovascular events were nonfatal 1.7% (95% CI 0.5%-2.1%), NNT = 59 (95% CI 48-194); total 1.6% (95% CI 0.2%-2.2%), NNT = 61 (95% CI 46-472); and for fractures 3.6% (95% CI 0.8%-5.4%), NNT = 28 (95% CI 19-125). Main limitations were that event rates were low and only events recorded in primary care records were counted; however, any underrecording would not have differed by intervention status and so should not have led to bias.Conclusions: Routine primary care data used to assess long-term trial outcomes demonstrated significantly fewer new cardiovascular events and fractures in intervention participants at 4 years. No statistically significant differences between intervention and control groups were demonstrated for other events. Short-term primary care pedometer-based walking interventions can produce long-term health benefits and should be more widely used to help address the public health inactivity challenge.Trial Registrations: PACE-UP isrctn.com ISRCTN98538934; PACE-Lift isrctn.com ISRCTN42122561. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the incidence trends of type 1 diabetes diagnosed with ketoacidosis in Saxony, Germany from 1999 to 2016. Methods: The population based Childhood Diabetes Registry of Saxony comprising valid data for all children aged 0–14 years diagnosed with type 1 diabetes from1999 to 2016 were used for the analyses. Direct age-standardized incidence rates were calculated and the effects of age, sex, calendar year, home districts and family history of any types of diabetes on the incidence were modelled using Poisson regression. Trend analyses for standard rate ratios of children with moderate and severe diabetic ketoacidosis versus children with type 1 diabetes with non-diabetic ketoacidosis were performed using join point regression. Results: The rate of ketoacidosis at the time of the type 1 diabetes diagnosis was high with 35.2% during the entire observation period in Saxony. The Poisson regression analysis indicated a statistically significant increased occurrence of diabetic ketoacidosis for younger age-groups, but no statistically significant differences between boys and girls. The join point trend analyses show that the proportion of severe and moderate ketoacidosis is increasing disproportionally to the increase in incidence of type 1 diabetes over the years. Conclusion: Due to the observed increasing incidence of diabetes as well of diabetic ketoacidosis, an educational prevention campaign is needed in Saxony as soon as possible to aid pediatricians, general physicians as well as general public to identify the early signs of type 1 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the effectiveness of a care management intervention in improving self-management behavior in multimorbid patients with type 2 diabetes; care was delivered by medical assistants in the context of a primary care network (PCN) in Germany. Methods: This study is an 18-month, multi-center, two-armed, open-label, patient-randomized parallel-group superiority trial (ISRCTN 83908315). The intervention group received the care management intervention in addition to the usual care. The control group received usual care only. The primary outcome was the change in self-care behavior at month 9 compared to baseline. The self-care behavior was measured with the German version of the Summary of Diabetes Self-Care Activities Measure (SDSCA-G). A multilevel regression analysis was applied. Results: We assigned 495 patients to intervention (n = 252) and control (n = 243). At baseline, the mean age was 68 ±11 years, 47.8% of the patients were female and the mean HbA1c was 7.1±1.2%. The primary analysis showed no statistically significant effect, but a positive trend was observed (p = 0.206; 95%-CI = -0.084; 0.384). The descriptive analysis revealed a significantly increased sum score of the SDSCA-G in the intervention group over time (P = 0.012) but not in the control group (p = 0.1973). Conclusion: The sum score for self-care behavior markedly improved in the intervention group over time. However, the results of our primary analysis showed no statistically significant effect. Possible reasons are the high baseline performance in our sample and the low intervention fidelity. The implementation of this care management intervention in PCNs has the potential to improve self-care behavior of multimorbid patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Burden, phenotype and risk-factors of lung function defects in successfully treated tuberculosis cases are unclear. Methods: We performed spirometry with bronchodilators in new drug-sensitive adult (≥18 years) pulmonary tuberculosis cases during the 12 months following successful treatment in India. Airflow obstruction was defined as pre-bronchodilator FEV1/FVC<5th percentile of Global Lung Initiative mixed-ethnicity reference (lower limit of normal [LLN]). Chronic obstructive pulmonary disease (COPD) was defined as post-bronchodilator FEV1/FVC

Fibromyalgia (FM) is one of the most frequent generalized pain disorders with poorly understood neurobiological mechanisms. This condition accounts for an enormous proportion of healthcare costs. Despite extensive research, the etiology of FM is unknown and thus, there is no disease modifying therapy available for this condition. We show that most (if not all) patients with FM belong to a distinct population that can be segregated from a control group by their glycated hemoglobin A1c (HbA1c) levels, a surrogate marker of insulin resistance (IR). This was demonstrated by analyzing the data after introducing an age stratification correction into a linear regression model. This strategy showed highly significant differences between FM patients and control subjects (p < 0.0001 and p = 0.0002, for two separate control populations, respectively). A subgroup of patients meeting criteria for pre-diabetes or diabetes (patients with HbA1c values of 5.7% or greater) who had undergone treatment with metformin showed dramatic improvements of their widespread myofascial pain, as shown by their scores using a pre and post-treatment numerical pain rating scale (NPRS) for evaluation. Although preliminary, these findings suggest a pathogenetic relationship between FM and IR, which may lead to a radical paradigm shift in the management of this disorder. [ABSTRACT FROM AUTHOR]

Background: In patients with sepsis, an inflammatory response can lead to destruction of the glycocalyx. These alterations cause the progression of organ dysfunction. Destruction of the glycocalyx can also occur in chronic hyperglycemia. Glycated hemoglobin (HbA1c) is a reliable marker of premorbid hyperglycemia. We investigated the association between HbA1c level at admission and the degree of organ dysfunction progression 72 hours after admission and ICU mortality. Methods and findings: This study was a retrospective observational study. Logistic regression and correlation analyses were performed to evaluate the association between the HbA1c level and the degree of organ dysfunction progression 72 hours after ICU admission. We applied survival analysis to examine the association between HbA1c level and ICU mortality. A total of 90 patients were included in this study. The association between HbA1c level and degree of organ dysfunction progression was significant (r = 0.320; P = 0.002). Multivariable logistic regression analysis showed that high HbA1c level (≥6.5%) (OR, 2.98; 95% CI, 1.033–8.567; P = 0.043) were significant, independent predictors of severe organ dysfunction progression. Patients with an HbA1c level ≥6.5% exhibited significantly greater liver and kidney dysfunction progression 72 hours after ICU admission compared with those with an HbA1c level <6.5%. Kaplan-Meier analysis showed that the survival period was significantly shorter in patients with an HbA1c level ≥6.5% than in those with an HbA1c level <6.5% (P < 0.001). Multivariable Cox proportional hazard analysis showed that HbA1c level ≥6.5% (HR, 3.49; 95% CI, 1.802–6.760; P <0.001) were significant, independent predictors of ICU mortality. Conclusions: In patients with sepsis, the HbA1c level at ICU admission is associated with progression of organ dysfunction 72 hours later and with ICU mortality. It may be important to assess HbA1c level at ICU admission because it may be a predictor of ICU outcome. For patients with a high HbA1c level (≥6.5%), greater attention should be paid to the possibility of organ dysfunction progression. [ABSTRACT FROM AUTHOR]

The objective of the present study was to investigate the correlations between serum undercarboxylated osteocalcin (ucOC) or osteocalcin (OC) concentrations and %body fat, serum adiponectin and free-testosterone concentration, muscle strength and dose of exogenous insulin in patients with type 1 diabetes. We recruited 73 Japanese young adult patients with childhood-onset type 1 diabetes. All participants were receiving insulin replacement therapy. The correlations between logarithmic serum ucOC or OC concentrations and each parameter were examined. Serum ucOC and OC concentrations were inversely correlated with %body fat (r = -0.319, P = 0.007; r = -0.321, P = 0.006, respectively). Furthermore, multiple linear regression analyses were performed to determine whether or not serum ucOC or OC concentrations were factors associated with %body fat. Serum ucOC and OC concentrations remained significant factors even after adjusting for gender, HbA1c, body weight-adjusted total daily dose of insulin and duration of diabetes (β = -0.260, P = 0.027; β = -0.254, P = 0.031, respectively). However, serum ucOC and OC concentrations were not correlated with serum adiponectin or free-testosterone concentrations, muscle strength or dose of exogenous insulin. In conclusion, our study demonstrates the inverse correlation between serum ucOC or OC concentrations and body fat in patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Inflammation and oxidative stress are linked to type 2 diabetes mellitus (T2DM). In this work, we analyzed patients’ blood markers of antioxidant capacity, oxidative stress and inflammation in individuals with T2DM, in pre-diabetes state (pre-DM) and controls without diabetes. Patients were divided into three groups, according to glycated hemoglobin A1c (HbA1c): <7%, 7–9%, and >9%. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, total thiols, nitric oxide (•NO), tumor necrosis factor alpha (TNF-α) and intercellular adhesion molecule 1 (ICAM-1) levels of the individuals were measured. Plasma SOD activity was higher in T2DM subjects compared to the controls. While total thiols levels were lower in T2DM groups when compared to pre-DM, the values remained unchanged when compared to controls. ICAM-1 levels of T2DM groups were lower than in controls, while GPx activity, •NO, and TNF-α levels were similar among all groups. A positive correlation was found between SOD and HbA1c levels. Concluding, individuals with T2DM present altered SOD activity, total thiols, and ICAM-1 levels, which might contribute to further complications. There is a positive correlation between SOD activity and HbA1c levels. No apparent correlation exists between total thiols and ICAM-1 levels and with any other of the parameters evaluated in this study. [ABSTRACT FROM AUTHOR]

Background: Many factors contribute to suboptimal diabetes control including insufficiently-intensive treatment and non-adherence to medication and lifestyle. Determining which of these is most relevant for individual patients is challenging. Patient engagement techniques may help identify contributors to suboptimal adherence and address barriers (using motivational interviewing) and help facilitate choices among treatment augmentation options (using shared decision-making). These methods have not been used in combination to improve diabetes outcomes. Objective: To evaluate the impact of a telephone-based patient-centered intervention on glycosylated hemoglobin (HbA1c) control for individuals with poorly-controlled diabetes. Design: Two-arm pragmatic randomized control trial within an explanatory sequential mixed-methods design. Subjects: 1,400 participants 18–64 years old with poorly-controlled type 2 diabetes. Intervention: The intervention was delivered over the telephone by a clinical pharmacist and consisted of a 2-step process that integrated brief negotiated interviewing and shared decision-making to identify patient goals and options for enhancing diabetes management. Main measures: The primary outcome was change in HbA1c. Secondary outcomes were medication adherence measures. Outcomes were evaluated using intention-to-treat principles; multiple imputation was used for missing values in the 12-month follow-up. We used information from pharmacist notes to elicit factors to potentially explain the intervention’s effectiveness. Key results: Participants had a mean age of 54.7 years (SD:8.3) and baseline HbA1c of 9.4 (SD:1.6). Change in HbA1c from baseline was -0.79 (SD:2.01) in the control arm and -0.75 (SD:1.76) in the intervention arm (difference:+0.04, 95%CI: -0.22, 0.30). There were no significant differences in adherence. In as-treated analyses, the intervention significantly improved diabetes control (-0.48, 95%CI: -0.91, -0.05). Qualitative findings provided several potential explanations for the findings, including insufficiently addressing patient barriers. Conclusions: A novel telephone-based patient-centered intervention did not improve HbA1c among individuals with poorly-controlled diabetes, though as-treated analyses suggest that the intervention was effective for those who received it. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Objective: Patients with persistent poorly-controlled diabetes mellitus (PPDM) despite engagement in clinic-based care are at particularly high risk for diabetes complications and costs. Understanding this population’s demographics, comorbidities and care utilization could guide strategies to address PPDM. We characterized factors associated with PPDM in a large sample of Veterans with type 2 diabetes. Methods: We identified a cohort of Veterans with medically treated type 2 diabetes, who received Veterans Health Administration primary care during fiscal years 2012 and 2013. PPDM was defined by hemoglobin A1c levels uniformly >8.5% during fiscal year (FY) 2012, despite engagement with care during this period. We used FY 2012 demographic, comorbidity and medication data to describe PPDM in relation to better-controlled diabetes patients and created multivariable models to examine associations between clinical factors and PPDM. We also constructed multivariable models to explore the association between PPDM and FY 2013 care utilization. Results: In our cohort of diabetes patients (n = 435,820), 12% met criteria for PPDM. Patients with PPDM were younger than better-controlled patients, less often married, and more often Black/African-American and Hispanic or Latino/Latina. Of included comorbidities, only retinopathy (OR 1.68, 95% confidence interval (CI): 1.63,1.73) and nephropathy (OR 1.26, 95% CI: 1.19,1.34) demonstrated clinically significant associations with PPDM. Complex insulin regimens such as premixed (OR 10.80, 95% CI: 10.11,11.54) and prandial-containing regimens (OR 18.74, 95% CI: 17.73,19.81) were strongly associated with PPDM. Patients with PPDM had higher care utilization, particularly endocrinology care (RR 3.56, 95% CI: 3.47,3.66); although only 26.4% of patients saw endocrinology overall. Conclusion: PPDM is strongly associated with complex diabetes regimens, although heterogeneity in care utilization exists. While there is evidence of underutilization, inadequacy of available care may also contribute to PPDM. Our findings should inform tailored approaches to meet the needs of PPDM, who are among the highest-risk, highest-cost patients with diabetes. [ABSTRACT FROM AUTHOR]

Objectives: To compare the biomedical health profile and morbidity of adult carers with non-carers. Methods: The North West Adelaide Health Study (NWAHS) is a representative population-based longitudinal biomedical cohort study of 4056 participants aged 18 years and over at Stage One. Informal (unpaid) carers were identified in Stage 3 of the project (2008–2010). Risk factors, chronic medical conditions and biomedical, health and demographic characteristics using self-report and blood measured variables were assessed. Data were collected through clinic visits, telephone interviews and self-completed questionnaires. Risk factors included blood pressure, cholesterol/lipids, body mass index (BMI), smoking and alcohol intake. Chronic medical conditions included cardiovascular and respiratory diseases, diabetes, and musculoskeletal conditions. Blood measured variables were routine haematology, biochemistry, Vitamin D, and the inflammatory biomarkers high sensitivity C-Reactive Protein (hs-CRP), Tumor Necrosis Factor alpha (TNFα) and Interleukin-6 (Il-6). Results: The prevalence of carers aged 40 years and over was 10.7%, n = 191. Carers aged 40 years and over were more likely to assess their health status as fair/poor and report having diabetes, arthritis, anxiety and depression. They also reported insufficient exercise and were found to have higher BMI compared with non-carers. Significant findings from blood measured variables were lower serum Vitamin D and haemoglobin. Male carers had raised diastolic blood pressure, higher blood glucose, lower haemoglobin and albumin levels and slightly elevated levels of the inflammatory biomarkers TNFα and hs-CRP. Discussion and conclusions: This study confirms informal carers had different biomedical profiles to non-carers that included some chronic physical illnesses. It identifies that both female and male carers showed a number of risk factors which need to be considered in future caregiver research, clinical guidelines and policy development regarding carer morbidity. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus that results in both tubular and glomerular injury. Low-grade inflammation and oxidative stress are two mechanisms known to drive the progression of DN. Nucleotide-binding leucine-rich repeat containing family member X1 (NLRX1) is an innate immune receptor, uniquely located in mitochondria, that has been found to regulate inflammatory responses and to dampen renal oxidative stress by regulating oxidative phosphorylation. For this reason, we investigated the role of NLRX1 in the development of DN in a Type 1 Diabetes mouse model. We analyzed the effect of NLRX1 deficiency on diabetes development and the accompanied renal damage, inflammation, and fibrosis. We found that multiple low doses of streptozotocin induced body weight loss, polydipsia, hyperglycemia, glycosuria, and a mild DN phenotype in wildtype and NLRX1-deficient mice, without significant differences between these mouse strains. Despite increased NLRX1 expression in diabetic wildtype mice, NLRX1 deficiency did not affect the diabetic phenotype induced by streptozotocin treatment, as reflected by similar levels of polyuria, microalbuminuria, and increased renal markers of oxidative stress and inflammation in wildtype and NLRX1-deficient mice. The present findings show that NLRX1 does not mediate the development of streptozotocin-induced diabetes and diabetic-induced nephropathy in mice after multiple low doses of streptozotocin. This data implies that, while NLRX1 can be triggered by cellular stress, its regulatory and functional effects may be dependent on the specific physiological conditions. In the case of DN, NLRX1 may be neither helpful nor harmful, but rather a marker of metabolic stress. [ABSTRACT FROM AUTHOR]

Introduction: Patients with diabetes mellitus type 2 (DM2) are at high risk for micro- and macrovascular disease. Here, we explore the degree of traditional risk factor control in the baseline visit of a cohort of DM2 outpatients. Methods: DIACORE (DIAbetes COhoRtE) is a prospective cohort study of 3000 adult DM2 outpatients. Here, we present results from the baseline visit. Sociodemographic and anthropometric variables, cardiovascular risk factors, comorbidities and medication were assessed by interview and medical exams. Serum-creatinine based estimated glomerular filtration rate (eGFRcrea) and urinary albumin-creatinine ratio (UACR) were determined for classification of chronic kidney disease (CKD). The proportion of patients with adequate control of traditional risk factors (blood pressure<140/90mmHg, HbA1c<7.5%, LDL<100mg/dl) was calculated in 2892 patients with non-missing data in 9 relevant variables within each KDIGO 2012 CKD class. Results: In the analyzed baseline data (n = 2892, 60.2% men), mean (standard deviation) values for age, DM2 duration and HbA1c were 65.3 (9.3) years, 10.3 (8.4) years and 6.9% (1.1) respectively. Of these 2892 patients, 18.7% had CKD stage 3 or higher, 25.7% had UACR≥30mg/g. Adequate blood pressure, HbA1c and LDL control was achieved in 55.7%, 78.5% and 34.4%, respectively. In 16.4% of patients (473), all three risk factors were below recommended targets. The proportion of adequate risk factor control was similar across KDIGO eGFRcrea classes. Adequate blood pressure and HbA1c control were significantly associated with lower UACR category without and with controlling for other risk factors (p<0.0001, p = 0.0002, respectively). Conclusion: In our study of patients with diabetes mellitus type 2, we observed a low level of risk factor control indicating potential for risk reduction. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a chronic disease that requires long-term therapy and regular check-ups to prevent complications. In this study, insurance claim data from the National Health Insurance Service (NHIS) of Korea were used to investigate insulin use in T2DM patients according to the economic status of patients and their access to primary physicians, operationally defined as the frequently used medical care providers at the time of T2DM diagnosis. A total of 91,810 participants were included from the NHIS claims database for the period between 2002 and 2013. The utilization pattern of insulin was set as the dependent variable and classified as one of the following: non-use of antidiabetic drugs, use of oral antidiabetic drugs only, or use of insulin with or without oral antidiabetic drugs. The main independent variables of interest were level of income and access to a frequently-visited physician. Multivariate Cox proportional hazards analysis was performed. Insulin was used by 9,281 patients during the study period, while use was 2.874 times more frequent in the Medical-aid group than in the highest premium group [hazard ratio (HR): 2.874, 95% confidence interval (CI): 2.588–3.192]. Insulin was also used ~50% more often in the patients managed by a frequently-visited physician than in those managed by other healthcare professionals (HR: 1.549, 95% CI: 1.434–1.624). The lag time to starting insulin was shorter when the patients had a low income and no frequently-visited physicians. Patients with a low level of income were more likely to use insulin and to have a shorter lag time from diagnosis to starting insulin. The likelihood of insulin being used was higher when the patients had a frequently-visited physician, particularly if they also had a low level of income. Therefore, the economic statuses of patients should be considered to ensure effective management of T2DM. Utilizing frequently-visited physicians might improve the management of T2DM, particularly for patients with a low income. [ABSTRACT FROM AUTHOR]

Abdominal or visceral obesity is a well-known risk factor for metabolic diseases. However, whether abdominal obesity significantly affects plasma lipid profile during the development of type 2 diabetes has not been fully elucidated. We investigated the differences in plasma lipid concentrations in 63 participants categorized into six groups (middle-aged Korean men); Normal, Pre-diabetes (pre-DM), and Diabetes mellitus (DM) with or without abdominal obesity (AO or lean). The lipidomic profiles were determined by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sphingomyelin (SM) levels in plasma were significantly higher in the pre-DM with AO than in pre-DM with lean (p = 0.021). SM concentrations correlated positively with waist-to-hip ratio (WHR) (r = 0.256, p = 0.044), cholesteryl ester (CE) (r = 0.483, p < 0.0001), ceramide (r = 0.489, p < 0.0001) and plasmanyl phosphatidylcholine (PC) (r = 0.446, p < 0.0001). The present study found that pre-diabetic patients with AO were characterized by increased plasma concentrations of SM. Plasma SM levels in individuals with AO may be an early prognostic biomarker to better predict the progression toward type 2 diabetes and metabolic syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Intensive treatment aimed at achieving optimal metabolic control to prevent the development of chronic diabetic complications is often associated with an increased rate of hypoglycemic events. Hypoglycemia is believed to be responsible for acute fatal and nonfatal cardiovascular events likely as a consequence of the activation of pro-inflammatory and pro-atherothrombotic pathways. Hypoglycemia has been reported to influence the development of preclinical atherosclerosis. The present study was designed to prospectively evaluate whether hypoglycemia influences the function and the morphology of the arteries in subjects with type 2 diabetes without complications and uncontrolled diabetes. Material and methods: Seventy-six subjects underwent a noninvasive evaluation of carotid wall thickness and brachial artery function at baseline and after one year of treatment with the intent of obtaining optimal glycemic control. At the end of the observation time, subjects were divided in two groups: with hypoglycemia (H-group) or without hypoglycemia (C-group). Results: Baseline characteristic were comparable between groups. HbA1c significantly decreased in both groups, and fasting plasma glucose was only significant in the H-group. Subjects with hypoglycemia showed a significant reduction of carotid wall thickness after one-year of treatment (H-groups: right baseline 834±141 vs. 1-year 770±132 μ p<0.05; C-group: 757±162 vs. 767±135 μ p = ns). Endothelial function remained unchanged during the study for both groups. Discussion: The present findings demonstrate that hypoglycemia does not affect endothelial function. Furthermore, subjects who experience more hypoglycemia show significant reduction of carotid wall thickness. Optimal metabolic control should be pursued as soon as possible. [ABSTRACT FROM AUTHOR]

Background: The prevalence of diabetes is increasing rapidly in low- and middle-income countries (LMICs), urgently requiring detailed evidence to guide the response of health systems to this epidemic. In an effort to understand at what step in the diabetes care continuum individuals are lost to care, and how this varies between countries and population groups, this study examined health system performance for diabetes among adults in 28 LMICs using a cascade of care approach.Methods and Findings: We pooled individual participant data from nationally representative surveys done between 2008 and 2016 in 28 LMICs. Diabetes was defined as fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl), random plasma glucose ≥ 11.1 mmol/l (200 mg/dl), HbA1c ≥ 6.5%, or reporting to be taking medication for diabetes. Stages of the care cascade were as follows: tested, diagnosed, lifestyle advice and/or medication given ("treated"), and controlled (HbA1c < 8.0% or equivalent). We stratified cascades of care by country, geographic region, World Bank income group, and individual-level characteristics (age, sex, educational attainment, household wealth quintile, and body mass index [BMI]). We then used logistic regression models with country-level fixed effects to evaluate predictors of (1) testing, (2) treatment, and (3) control. The final sample included 847,413 adults in 28 LMICs (8 low income, 9 lower-middle income, 11 upper-middle income). Survey sample size ranged from 824 in Guyana to 750,451 in India. The prevalence of diabetes was 8.8% (95% CI: 8.2%-9.5%), and the prevalence of undiagnosed diabetes was 4.8% (95% CI: 4.5%-5.2%). Health system performance for management of diabetes showed large losses to care at the stage of being tested, and low rates of diabetes control. Total unmet need for diabetes care (defined as the sum of those not tested, tested but undiagnosed, diagnosed but untreated, and treated but with diabetes not controlled) was 77.0% (95% CI: 74.9%-78.9%). Performance along the care cascade was significantly better in upper-middle income countries, but across all World Bank income groups, only half of participants with diabetes who were tested achieved diabetes control. Greater age, educational attainment, and BMI were associated with higher odds of being tested, being treated, and achieving control. The limitations of this study included the use of a single glucose measurement to assess diabetes, differences in the approach to wealth measurement across surveys, and variation in the date of the surveys.Conclusions: The study uncovered poor management of diabetes along the care cascade, indicating large unmet need for diabetes care across 28 LMICs. Performance across the care cascade varied by World Bank income group and individual-level characteristics, particularly age, educational attainment, and BMI. This policy-relevant analysis can inform country-specific interventions and offers a baseline by which future progress can be measured. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy (DPN), the most common chronic complication of diabetes, has become an important public health crisis worldwide. Given that DPN is extremely difficult to treat, determining its risk factors and controlling it at an early stage is critical to preventing its serious consequences and the burden of social disease. Current studies suggest that the risk factors for diabetic peripheral neuropathy are the duration of diabetes, age, glycosylated hemoglobin A1c (HbA1c), diabetic retinopathy (DR), smoking, and body mass Index (BMI). However, most of the aforementioned studies are cross-sectional, and the sample sizes are very limited, so the strength of causal reasoning is relatively low. The current study systematically evaluated DPN’s influencing factors in patients with type 2 diabetes using evidence-based medicine. Overall, 16 included studies (14 cross-sectional studies and 2 case-control studies including 12,116 cases) that conformed to the present criteria were included in the final analysis. The results suggested that the duration of diabetes (MD 2.5, 95% CI 1.71~3.29), age (MD 4.00, 95% CI 3.05~4.95), HbA1c (MD 0.48, 95% CI 0.33~0.64), and DR (OR 2.34, 95% CI 1.74~3.16) are associated with significantly increased risks of DPN among diabetic patients, while BMI, smoking, total triglyceride (TG), and total cholesterol (TC) did not indicate any risks of increasing DPN. The findings provide a scientific basis for a further understanding of the causes of type 2 diabetes complicated with peripheral neuropathy and the improvement of preventive strategies. The next step is to conduct further high-quality prospective cohort studies to validate this paper’s findings. [ABSTRACT FROM AUTHOR]