The joint impact of burnout and neurotic personality on career satisfaction and intention to leave among health workers during the first 2 years of COVID-19.

PURPOSE: The purpose of the study is to examine the psychological impact of COVID-19 on health workers' career satisfaction and intention to leave the health profession, with neurotic personality type as a moderator. DESIGN/METHODOLOGY/APPROACH: A total of 277 health workers in two public hospitals in Ghana were included in this study. Purposive and convenience sampling techniques were adopted for the study, focusing on eight departments that were involved in the management of COVID-19 cases. Validated instruments were used to measure burnout, intention to leave, neurotic personality and career satisfaction. Using AMOS and partial least squares structural equation modeling (PLS-SEM), various techniques were employed to analyze mediating and moderating mechanisms. FINDINGS: The departments had staff sizes ranging from 19 to 40, with 67% female and 33% male, with an average age of 31. Nurses accounted for the majority of responses (67.8%), followed by physicians (13.9%), sonographers (0.9%), lab technicians (0.9%) and other respondents (16.5%). The study found that health workers' level of burnout during COVID-19 had a positive effect on their intention to leave the health profession. Career satisfaction does not mediate this relationship; however, career satisfaction negatively influences the intention to leave the health profession. A neurotic personality does not moderate this relationship. ORIGINALITY/VALUE: This study provides validation of burnout and intention to leave among health workers in Ghana during COVID-19 and supports the proposition that threats to resources (burnout) and having a resource (career satisfaction) have effects on the intention to leave one's profession.

Immobilization of Thiol-Modified Horseradish Peroxidase on Gold Nanoparticles Enhances Enzyme Stability and Prevents Proteolytic Digestion.

The specificity and efficiency of enzyme-mediated reactions have the potential to positively impact many biotechnologies; however, many enzymes are easily degraded. Immobilization on a solid support has recently been explored to improve enzyme stability. This study aims to gain insights and facilitate enzyme adsorption onto gold nanoparticles (AuNPs) to form a stable bioconjugate through the installation of thiol functional groups that alter the protein chemistry. In specific, the model enzyme, horseradish peroxidase (HRP), is thiolated via Traut's reagent to increase the robustness and enzymatic activity of the bioconjugate. This study compares HRP and its thiolated analog (THRP) to deduce the impact of thiolation and AuNP-immobilization on the enzyme activity and stability. HRP, THRP, and their corresponding bioconjugates, HRP-AuNP and THRP-AuNP, were analyzed via UV-vis spectrophotometry, circular dichroism, zeta potential, and enzyme-substrate kinetics assays. Our data show a 5-fold greater adsorption for THRP on the AuNP, in comparison to HRP, that translated to a 5-fold increase in the THRP-AuNP bioconjugate activity. The thiolated and immobilized HRP exhibited a substantial improvement in stability at elevated temperatures (50 °C) and storage times (1 month) relative to the native enzyme in solution. Moreover, HRP, THRP, and their bioconjugates were incubated with trypsin to assess the susceptibility to proteolytic digestion. Our results demonstrate that THRP-AuNP bioconjugates maintain full enzymatic activity after 18 h of incubation with trypsin, whereas free HRP, free THRP, and HRP-AuNP conjugates are rendered inactive by trypsin treatment. These results highlight the potential for protein modification and immobilization to substantially extend enzyme shelf life, resist protease digestion, and enhance biological function to realize enzyme-enabled biotechnologies.

Road crossing behavior and preferences among pedestrians: From the lens of the theory of interpersonal behavior.

OBJECTIVE: As a major safety intervention, infrastructural facilities such as footbridges, underpasses or signals are provided for pedestrians to remove their direct interactions with vehicles and consequently ensure safe crossing as they attempt to cross roadways. Interestingly, it is evident that even within the proximity of footbridges or underpasses, some individuals are more willing to take the risk of crossing at-grade even where there are no signals or crosswalk markings to separate their movement from vehicles. These crossing alternatives may have different utilization depending on location and road user types. Therefore, sustainable crossing facilities are needed to meet pedestrian needs. This study attempts to investigate the factors that influence pedestrians to avoid provided footbridges and engage in at-grade crossing behaviors. METHODS: The crossing point preference is an interpersonal behavior which is a multifaceted and complex phenomenon involving conscious (intentions) and subconscious (habits) factors. This study employs Triandis' Theory of Interpersonal Behavior (TIB) as a theoretical framework and structural equation modeling to achieve study objectives. Pedestrians were intercepted randomly and socio-demographics, trip characteristics and perceptions data collected through a stated preference survey. RESULTS: Perceived consequence, affect, and social factors were found as significant antecedents of at-grade crossing intentions. Habits and facilitating conditions significantly moderate the impact of crossing intentions on actual at-grading crossing behavior. Pedestrians' perceived consequence was found to significantly mediate the impact of social factors and affective factors on intention to cross at-grade. Apart from gender, age, satisfaction with footbridge features, work trips, and crossing frequency were all significant determinants of actual crossing at-grade behavior. CONCLUSIONS: The study findings can help road safety agencies provide acceptable sustainable facilities that will be used by pedestrians to ensure that the purpose of investments toward pedestrian crossing safety is achieved. Effective road safety education and awareness campaigns on negative consequences of crossing at-grade, while highlighting the benefits of using provided footbridges are suggested to be undertaken by government agencies.

The Emergency Medicine Education and Research by Global Experts (EMERGE) Network: Challenges and Lessons Learned.

INTRODUCTION: The Emergency Medicine Education and Research by Global Experts (EMERGE) network was formed to generate and translate evidence to improve global emergency care. We share the challenges faced and lessons learned in establishing a global research network. METHODS: We describe the challenges encountered when EMERGE proposed the development of a global emergency department (ED) visit registry. The proposed registry was to be a six-month, retrospective, deidentified, minimal dataset of routinely collected variables, such as patient demographics, diagnosis, and disposition. RESULTS: Obtaining reliable, accurate, and pertinent data from participating EDs is challenging in a global context. Barriers experienced ranged from variable taxonomies, need for language translation, varying site processes for curation and transfer of deidentified data, navigating institution- and country-specific data protection regulations, and substantial variation in each participating institution's research infrastructure including training in research-related activities. We have overcome many of these challenges by creating detailed data-sharing agreements with bilateral regulatory oversight agreements between EMERGE and participating EDs, developing relationships with and training health informaticians at each site to ensure secure transfer of deidentified data, and formalizing an electronic transfer process ensuring data privacy. CONCLUSION: We believe that networks like EMERGE are integral to providing the necessary platforms for education, training, and research collaborations for emergency care. We identified substantial challenges in data sharing and variation in local sites' research infrastructure and propose potential approaches to address these challenges.

A Global Survey of Emergency Department Responses to the COVID-19 Pandemic.

INTRODUCTION: Emergency departments (ED) globally are addressing the coronavirus disease 2019 (COVID-19) pandemic with varying degrees of success. We leveraged the 17-country, Emergency Medicine Education & Research by Global Experts (EMERGE) network and non-EMERGE ED contacts to understand ED emergency preparedness and practices globally when combating the COVID-19 pandemic. METHODS: We electronically surveyed EMERGE and non-EMERGE EDs from April 3-June 1, 2020 on ED capacity, pandemic preparedness plans, triage methods, staffing, supplies, and communication practices. The survey was available in English, Mandarin Chinese, and Spanish to optimize participation. We analyzed survey responses using descriptive statistics. RESULTS: 74/129 (57%) EDs from 28 countries in all six World Health Organization global regions responded. Most EDs were in Asia (49%), followed by North America (28%), and Europe (14%). Nearly all EDs (97%) developed and implemented protocols for screening, testing, and treating patients with suspected COVID-19 infections. Sixty percent responded that provider staffing/back-up plans were ineffective. Many sites (47/74, 64%) reported staff missing work due to possible illness with the highest provider proportion of COVID-19 exposures and infections among nurses. CONCLUSION: Despite having disaster plans in place, ED pandemic preparedness and response continue to be a challenge. Global emergency research networks are vital for generating and disseminating large-scale event data, which is particularly important during a pandemic.

Bicycle ownership and utilization in Tamale Metropolis; influencing factors and impacts to sustainable transport.

The study seeks to identify bicycle ownership and ridership and gain insights into how demographics, perceptions and experiences of respondents influenced the status of cycling in Tamale Metropolis. Earlier studies have focused on examining the determinants of utility cycling among adults in the same metropolis, but this study assesses cycling from a broader perspective in terms of demographics, barriers, and promotional strategies. A cross-sectional survey was carried out with 500 semi-structured questionnaires through mainly a face-to-face approach. Five trained survey assistants administered the questionnaires within demarcated zones in the metropolis and tracked participants by geographic information system. Binary logistic regression, chi-squared test and descriptive statistics were employed in the analysis of the data. Out of the 439 valid questionnaires, bicycle ownership and ridership were 56% and 78% respectively. Gender and occupation were significant in owning and riding bicycles, where p < 0.05. Males and the non-income earners (i.e., students, apprentices and unemployed) were more likely to ride and own bicycles. Cycling was prevalent among low-income individuals and in households where bicycles were available. The major motivation of bicycle riders was affordability. Age was statistically insignificant to owning or riding bicycles since every age group cycled as much. Despite the existing infrastructure provision for cycling and its associated benefits, there is a latent desire to shift from bicycles by 85% of the riders. A chi-square test conducted revealed that the desire to shift from bicycle use was independent of one's gender, age and occupation, but associated with bicycle ownership. Moreover, speed, fatigue endured in riding and inadequate infrastructure were mentioned as part of the factors that discourage cycling. This study, therefore, recommends government interventions such as a reduction in bicycle cost, and the introduction of electric bicycles to meet the respondents' transport needs of speed and travelling with less fatigue.

Pathogenic Mechanisms of Prediabetes in Obese vs. Very Obese African American Women: Implications for Diabetes Prevention.

BACKGROUND: The influence of obesity on the development of prediabetes among African American women (AAW) remains uncertain. Thus, we investigated whether the pathogenic mechanisms of prediabetes differ in obese (OB, BMI<35 kg/m2) and very obese (VOB, BMI>35 kg/m2) AAW. SUBJECTS/METHODS: We recruited 26-OB and 41-VOB, AAW with prediabetes, mean age (46.3 ± 10.3 years), A1C (5.9 ± 0.4%) and BMI (38.3 ± 8.2 kg/m2). OGTT and FSIVGT were performed in each subject. Body composition (% body fat) was measured using DEXA. Si, Sg acute insulin response to glucose (AIRg) and disposition index (DI) were calculated using minimal model method. RESULTS: Mean BMI (32.6 ± 1.9 vs. 42.8 ± 5.5 kg/m2) and %body fat (44.7 ± 2.0 vs. 49.6 ± 2.2%) were significantly (p = 0.0001) lower in OB vs VOB. Mean fasting and post-glucose challenge, (glucose, insulin, c-peptide) levels were significantly (p = 0.03-0.0001) lower in OB vs VOB. Mean Si and Sg was not different. Mean AIRg tended to be higher (808 ± 776 vs. 535 ± 443 (x min [uU/L] -1), p = 0.106) whereas DI was greater (1999 ± 1408 vs. 1511 ± 1033, (×10-2 x min-1), p = 0.01) in OB vs VOB subjects. CONCLUSION: We found that OB and VOB AAW had similar Si and Sg, but VOB showed attenuated AIRg and DI. These parameters should be considered when developing primary prevention programs in AAW with prediabetes.

Assessing the predictive accuracy of oral glucose effectiveness index using a calibration model.

PURPOSE: Current reference methods for measuring glucose effectiveness (GE) are the somatostatin pancreatic glucose clamp and minimal model analysis of frequently sampled intravenous glucose tolerance test (FSIVGTT), both of which are laborious and not feasible in large epidemiological studies. Consequently, surrogate indices derived from an oral glucose tolerance test (OGTT) to measure GE (oGE) have been proposed and used in many studies. However, the predictive accuracy of these surrogates has not been formally validated. In this study, we used a calibration model analysis to evaluate the accuracy of surrogate indices to predict GE from the reference FSIVGTT (SgMM). METHODS: Subjects (n = 123, mean age 48 ± 11 years; BMI 35.9 ± 7.3 kg/m2) with varying glucose tolerance (NGT, n = 37; IFG/IGT, n = 78; and T2DM, n = 8) underwent FSIVGTT and OGTT on two separate days. Predictive accuracy was assessed by both root mean squared error (RMSE) of prediction and leave-one-out cross-validation-type RMSE of prediction (CVPE). RESULTS: As expected, insulin sensitivity, SgMM, and oGE were reduced in subjects with T2DM and IFG/IGT when compared with NGT. Simple linear regression analyses revealed a modest but significant relationship between oGE and SgMM (r = 0.25, p < 0.001). However, using calibration model, measured SgMM and predicted SgMM derived from oGE were modestly correlated (r = 0.21, p < 0.05) with the best fit line suggesting poor predictive accuracy. There were no significant differences in CVPE and RMSE among the surrogates, suggesting similar predictive ability. CONCLUSIONS: Although OGTT-derived surrogate indices of GE are convenient and feasible, they have limited ability to robustly predict GE.

The preventability of trauma-related death at a tertiary hospital in Ghana: a multidisciplinary panel review approach.

INTRODUCTION: The purpose of the study was to determine the preventable trauma-related death rate (PDR) at Komfo Anokye Teaching Hospital in Kumasi, Ghana three years after initiation of an Emergency Medicine (EM) residency. METHOD: This was a retrospective, cross-sectional study. A multidisciplinary panel of physicians completed a structured implicit review of clinical data for trauma patients who died during the period 2011 to 2012. The panel judged the preventability of each death and the nature of inappropriate care. Categories were definitely preventable (DP), possibly preventable (PP), and not preventable (NP). RESULTS: 1) The total number of cases was forty-five; 36 cases had adequate data for review. Subjects were predominately male; road traffic injury (RTI) was the leading mechanism of injury. Four cases (11.1%) were DP, 14 cases (38.9%) were PP and 18 (50%) were NP. Hemorrhage was the leading cause of death (39%). Among DP/PP deaths there were 37 instances of inappropriate care. Delay in surgical intervention was the predominate event (50%). 2) The PDR for this study was 50% (0.95 CI, 33.7%-66.3%). CONCLUSION: Fifty percent of trauma deaths were DP/PP. Multiple episodes of varying types of inappropriate care occurred. More efficient surgical evaluation and appropriate treatment of hemorrhage could reduce trauma morality. Large amounts of missing and incomplete clinical data suggest considerable selection bias. A major implication of this study is the importance of having a robust, prospective trauma registry to collect clinical information to increase the number of cases for review.

Gender, blood pressure, and cardiovascular and renal outcomes in adults with hypertension from the Systolic Blood Pressure Intervention Trial.

BACKGROUND: To determine if the effects of intensive lowering of systolic blood pressure (goal of less than 120 mmHg) versus standard lowering (goal of less than 140 mmHg) upon cardiovascular, renal, and safety outcomes differed by gender. METHODS: Nine thousand three hundred and sixty-one men and women aged 50 years or older with systolic blood pressure of 130 mmHg or greater, taking 0-4 antihypertensive medications, and with increased risk of cardiovascular disease, but free of diabetes, were randomly assigned to either a systolic blood pressure target of less than 120 mmHg (intensive treatment) or a target of less than 140 mmHg (standard treatment). The primary composite outcome encompassed incident myocardial infarction, heart failure, other acute coronary syndromes, stroke, or cardiovascular-related death. All-cause mortality, renal outcomes, and serious adverse events were also assessed. RESULTS: Compared with the standard treatment group, the primary composite outcome in the intensive treatment group was reduced by 16% [hazard ratio 0.84 (0.61-1.13)] in women, and by 27% in men [hazard ratio 0.73 (0.59-0.89), P value for interaction between treatment and gender is 0.45]. Similarly, the effect of the intensive treatment on individual components of the primary composite outcome, renal outcomes, and overall serious adverse events was not significantly different according to gender. CONCLUSION: In adults with hypertension but not with diabetes, treatment to a systolic blood pressure goal of less than 120 mmHg, compared with a goal of less than 140 mmHg, resulted in no heterogeneity of effect between men and women on cardiovascular or renal outcomes, or on rates of serious adverse events.ClinicalTrials.gov number, NCT01206062.

Influence of metabolic syndrome and race on the relationship between intensive blood pressure control and cardiovascular outcomes in the SPRINT cohort.

AIMS: To determine whether baseline metabolic syndrome (MetS) modifies the effect of intensive blood pressure control on cardiovascular (CV) outcomes, and whether the effects varied by race/ethnicity. METHODS: We performed post hoc analyses among non-Hispanic black, non-hispanic white and Hispanic participants, with and without MetS, in the Systolic Blood Pressure Intervention Trial (SPRINT), who were randomized to a systolic blood pressure (SBP) target of <120 mm Hg (intensive group, N = 4544) or an SBP target of <140 mm Hg (standard group, N = 4553). The median follow-up was 3.26 years. The primary outcome was the composite of the first occurrence of myocardial infarction, stroke, heart failure, non-myocardial infarction acute coronary syndrome or CV death. RESULTS: Overall, 3521/9097 participants (38.7%) met the criteria for MetS at baseline. Baseline characteristics were similar in the two SBP target groups within each MetS subgroup, except body mass index was slightly higher in the standard arm of the MetS subgroup (33.3 ± 5.6 vs 33.0 ± 5.3 kg/m2 ; P < .01), but were similar across treatment arms in the non-MetS subgroup. The hazard ratio for the primary outcome was similarly reduced in participants with or without baseline MetS: 0.75 (95% confidence interval [CI] 0.57, 0.96) and 0.71 (95% CI 0.57, 0.87), respectively (adjusted P value for treatment by subgroup interaction = .98). Similarly, there was no evidence of treatment × MetS subgroup interaction for all-cause mortality (adjusted interaction P value = .98). The findings were also similar across race/ethnic subgroups. CONCLUSIONS: In this analysis the CV benefit of intensive SBP control did not differ among participants by baseline MetS status, regardless of race/ethnicity.

Disparities in Cardiovascular Disease and Type 2 Diabetes Risk Factors in Blacks and Whites: Dissecting Racial Paradox of Metabolic Syndrome.

Cardiovascular diseases (CVD) remain as the leading cause of mortality in the western world and have become a major health threat for developing countries. There are several risk factors that account for the CVD and the associated mortality. These include genetics, type 2 diabetes (T2DM), obesity, physical inactivity, hypertension, and abnormal lipids and lipoproteins. The constellation of these risk factors has been termed metabolic syndrome (MetS). MetS varies among racial and ethnic populations. Thus, race and ethnicity account for some of the differences in the MetS and the associated CVD and T2DM. Furthermore, the relationships among traditional metabolic parameters and CVD differ, especially when comparing Black and White populations. In this regard, the greater CVD in Blacks than Whites have been partly attributed to other non-traditional CVD risk factors, such as subclinical inflammation (C-reactive protein), homocysteine, increased low-density lipoprotein oxidation, lipoprotein a, adiponectin, and plasminogen activator inhibitor-1, etc. Thus, to understand CVD and T2DM differences in Blacks and Whites with MetS, it is essential to explore the contributions of both traditional and non-traditional CVD and T2DM risk factors in Blacks of African ancestry and Whites of Europoid ancestry. Therefore, in this mini review, we propose that non-traditional risk factors should be integrated in defining MetS as a predictor of CVD and T2DM in Blacks in the African diaspora in future studies.

Ethnic differences in glucose effectiveness and disposition index in overweight/obese African American and white women with prediabetes: A study of compensatory mechanisms.

OBJECTIVE: Prediabetes, a major precursor of type 2 diabetes, varies among ethnic populations. Therefore, we compared the pathophysiologic mechanisms of prediabetes in overweight/obese African American (AA) and White American (WA) women. SUBJECTS AND METHODS: We recruited 95 women (67 AA, 28 WA) with prediabetes. Standard OGTT and FSIVGTT were performed in each subject. Insulin sensitivity (Si), glucose effectiveness (Sg), beta cell function (acute insulin response to glucose (AIRg) and disposition index (DI: Si×AIRg) were calculated using Bergman's Minmod. RESULTS: Mean BMI was greater in AA vs WA with prediabetes (38.3±8.2vs 34.6±8.5kg/m2, p=0.05). Mean fasting serum glucose, and insulin levels were lower in AA vs WA. Similarly, mean peak serum glucose levels were lower while peak insulin levels were higher at 30 and 60minutes in AA vs WA. In contrast, mean fasting and peak serum c-peptide levels at 60 and 90minutes were significantly lower in AA vs WA. Mean AIRg was higher but not significantly different in AA vs WA (633±520.92 vs 414.8±246.8, p=0.193). Although, Si (2.93±3.25vs 44 2.50±1.76 (×10-4×min-1 [µU/ml]-1), p=0.448) was not different, DI was significantly higher in AA vs WA (1381±1126 vs 901.9±477.1, p=0.01). In addition, mean Sg was significantly higher in AAvs WA (2.51±1.17 vs 1.97±0.723 (×10-2/min), p=0.02). CONCLUSIONS: We found that in overweight/obese prediabetic AA and WA women with similar Si, the mean Sg and DI were significantly higher in AA. We conclude that the pathophysiologic mechanisms of prediabetes differ in the overweight/obese AA and WA women.

Peripheral insulin resistance rather than beta cell dysfunction accounts for geographical differences in impaired fasting blood glucose among sub-Saharan African individuals: findings from the RODAM study.

AIMS/HYPOTHESIS: The aim of this study was to assess the extent to which insulin resistance and beta cell dysfunction account for differences in impaired fasting blood glucose (IFBG) levels in sub-Saharan African individuals living in different locations in Europe and Africa. We also aimed to identify determinants associated with insulin resistance and beta cell dysfunction among this population. METHODS: Data from the cross-sectional multicentre Research on Obesity and Diabetes among African Migrants (RODAM) study were analysed. Participants included Ghanaian individuals without diabetes, aged 18-96 years old, who were residing in Amsterdam (n = 1337), Berlin (n = 502), London (n = 961), urban Ghana (n = 1309) and rural Ghana (n = 970). Glucose and insulin were measured in fasting venous blood samples. Anthropometrics were assessed during a physical examination. Questionnaires were used to assess demographics, physical activity, smoking status, alcohol consumption and energy intake. Insulin resistance and beta cell function were determined using homeostatic modelling (HOMA-IR and HOMA-B, respectively). Logistic regression analysis was used to study the contribution of HOMA-IR and inverse HOMA-B (beta cell dysfunction) to geographical differences in IFBG (fasting glucose 5.6-6.9 mmol/l). Multivariate linear regression analysis was used to identify determinants associated with HOMA-IR and inverse HOMA-B. RESULTS: IFBG was more common in individuals residing in urban Ghana (OR 1.41 [95% CI 1.08, 1.84]), Amsterdam (OR 3.44 [95% CI 2.69, 4.39]) and London (OR 1.58 [95% CI 1.20 2.08), but similar in individuals living in Berlin (OR 1.00 [95% CI 0.70, 1.45]), compared with those in rural Ghana (reference population). The attributable risk of IFBG per 1 SD increase in HOMA-IR was 69.3% and in inverse HOMA-B was 11.1%. After adjustment for HOMA-IR, the odds for IFBG reduced to 0.96 (95% CI 0.72, 1.27), 2.52 (95%CI 1.94, 3.26) and 1.02 (95% CI 0.78, 1.38) for individuals in Urban Ghana, Amsterdam and London compared with rural Ghana, respectively. In contrast, adjustment for inverse HOMA-B had very minor impact on the ORs of IFBG. In multivariate analyses, BMI (ß = 0.17 [95% CI 0.11, 0.24]) and waist circumference (ß = 0.29 [95%CI 0.22, 0.36]) were most strongly associated with higher HOMA-IR, whereas inverse HOMA-B was most strongly associated with age (ß = 0.20 [95% CI 0.16, 0.23]) and excess alcohol consumption (ß = 0.25 [95% CI 0.07, 0.43]). CONCLUSIONS/INTERPRETATION: Our findings suggest that insulin resistance, rather than beta cell dysfunction, is more important in accounting for the geographical differences in IFBG among sub-Saharan African individuals. We also show that BMI and waist circumference are important factors in insulin resistance in this population.

Exenatide substantially improves proinsulin conversion and cell survival that augment Ins2+/Akita beta cell function.

Proinsulin folding imperfections cause extensive beta-cell defects known in diabetes. Here, we investigated whether exenatide can alleviate such defects in proinsulin conversion, beta-cell survival, and insulin secretion, in the Ins2+/Akita beta-cells that have a spontaneous mutation (Cys 96 Tyr) in the insulin 2 gene caused dominant negative misfolding problem. 15 or 120 min exenatide administration substantially improves glucose-stimulated insulin secretion, marked in the secreted insulin levels and proinsulin/insulin ratio. This improvement is mainly due to enhanced conversion of proinsulin to insulin, having nothing to do with the prohormone convertase PC1/3 and PC2 levels. The 15 min improvement is calcium-independent. The 120 min improvement is linked to calcium and/or cAMP dependent mechanisms. This efficacy is validated during longer treatment and in Akita islets. Exenatide improves Ins2+/Akita beta-cell survival and Akita mouse's glucose tolerance. The results suggest a potential of incretin mimetics in alleviating defective proinsulin conversion and other proinsulin misfolding consequences.

Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial.

BACKGROUND: The role of incretin-based drugs in the treatment of patients with type 2 diabetes admitted to hospital has not been extensively assessed. In this study, we compared the safety and efficacy of a dipeptidyl peptidase-4 inhibitor (sitagliptin) plus basal insulin with a basal-bolus insulin regimen for the management of patients with type 2 diabetes in general medicine and surgery in hospitals. METHODS: We did a multicentre, prospective, open-label, non-inferiority randomised clinical trial (Sita-Hospital) in five hospitals in the USA, enrolling patients aged 18-80 years with type 2 diabetes and a random blood glucose concentration of 7·8-22·2 mmol/L who were being treated with diet or oral antidiabetic drugs or had a total daily insulin dose of 0·6 units per kg or less, admitted to general medicine and surgery services. We randomly assigned patients (1:1) to receive either sitagliptin plus basal glargine once daily (the sitagliptin-basal group) or a basal-bolus regimen with glargine once daily and rapid-acting insulin lispro or aspart before meals (the basal-bolus group) during the hospital stay. All other antidiabetic drugs were discontinued on admission. The randomisation was achieved by computer-generated tables with block stratification according to randomisation blood glucose concentrations (ie, higher or lower than 11·1 mmol/L). The primary endpoint of the trial was non-inferiority in mean differences between groups in their daily blood glucose concentrations during the first 10 days of therapy (point-of-care measurements; non-inferiority was deemed a difference <1 mmol/L). The safety endpoints included hypoglycaemia and uncontrolled hyperglycaemia leading to treatment failure. All participants who received at least one dose of study drug were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT01845831. FINDINGS: Between Aug 23, 2013, and July 27, 2015, we recruited 279 patients, and randomly assigned 277 to treatment; 138 to sitagliptin-basal and 139 to basal-bolus. The length of stay in hospital was similar for both groups (median 4 days [IQR 3-8] vs 4 [3-8] days, p=0·54). The mean daily blood glucose concentration in the sitagliptin-basal group (9·5 mmol/L [SD 2·7]) was not inferior to that in the basal-bolus group 9·4 mmol/L [2·7]) with a mean blood glucose difference of 0·1 mmol/L (95% CI -0·6 to 0·7). No deaths occurred in this trial. Treatment failure occurred in 22 patients (16%) in the sitagliptin-basal group versus 26 (19%) in the basal-bolus group (p=0·54). Hypoglycaemia occurred in 13 patients (9%) in the sitagliptin-basal group and in 17 (12%) in the basal-bolus group (p=0·45). No differences in hospital complications were noted between groups. Seven patients (5%) developed acute kidney injury in the sitagliptin-basal group and six (4%) in the basal-bolus group. One patient (0·7%) developed acute pancreatitis (in the basal-bolus group). INTERPRETATION: The trial met the non-inferiority threshold for the primary endpoint, because there was no significant difference between groups in mean daily blood glucose concentrations. Treatment with sitagliptin plus basal insulin is as effective and safe as, and a convenient alternative to, the labour-intensive basal-bolus insulin regimen for the management of hyperglycaemia in patients with type 2 diabetes admitted to general medicine and surgery services in hospital in the non-intensive-care setting. FUNDING: Merck.

Ethnic differences in serum lipids and lipoproteins in overweight/obese African-American and white American women with pre-diabetes: significance of NMR-derived lipoprotein particle concentrations and sizes.

OBJECTIVE: African-American women (AAW) suffer disproportionately from higher rates of cardiovascular disease (CVD) mortality compared with white American women (WAW), despite favorable lipid and lipoprotein profile. Therefore, we used nuclear magnetic resonance (NMR) to examine lipoprotein particle concentrations and sizes in overweight/obese AAW and WAW with pre-diabetes. PARTICIPANTS AND METHODS: We studied 69 AAW and 41 WAW, with mean age 46.5±11.3 years and body mass index (BMI) 37.8±6.4 kg/m(2). All participants completed standard oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIVGTT). Insulin sensitivity (Si) was calculated using MINIMOD method. Body composition was assessed using dual-energy X-ray absorptiometry (DEXA). Fasting blood was obtained for traditional lipids/lipoproteins and NMR-derived lipoprotein particle sizes and concentrations. RESULTS: We found that AAW with pre-diabetes were more obese (BMI 38.8±6.7 vs 36.0±5.4 kg/m(2), p=0.02) than WAW. Mean Si was not significantly different. However, the mean serum triglycerides were lower, whereas the high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (Apo A1) were significantly higher in AAW versus WAW. The large HDL particle concentration (6.1±3.1 vs 4.6±3.1 µmol/L, p=0.02) was significantly higher in AAW versus WAW. Mean total very low-density lipoprotein (VLDL) particle concentration was lower in AAW versus WAW (39.9±24.4 vs 59.2±25.6 nmol/L, p≤0.001). While mean total LDL particle concentrations were not different, mean small LDL particle concentrations were lower in AAW versus WAW (538.8±294.1 vs 638.4±266 nmol/L, p=0.07). CONCLUSIONS: We found a more favorable NMR-derived lipoprotein profile in AAW that extends the traditional antiatherogenic lipid/lipoprotein profiles. Clinically, these favorable lipid/lipoprotein profiles cannot explain the paradoxically higher CVD mortality in AAW than WAW and warrant further prospective outcome studies.

Racial Disparities in the Pathogenesis of Type 2 Diabetes and its Subtypes in the African Diaspora: A New Paradigm.

The global epidemic of diabetes has extended to the developing countries including Sub-Sahara Africa. In this context, blacks with type 2 diabetes in the African Diaspora continue to manifest 1.5-2 times higher prevalent rates than in their white counterparts. Previous studies have demonstrated that blacks with and without type 2 diabetes have alterations in hepatic and peripheral insulin sensitivity, beta-cell function, and hepatic insulin clearance as well as hepatic glucose dysregulation when compared to whites. In addition, non-diabetic blacks in the African Diaspora manifest multiple metabolic mediators that predict type 2 diabetes and its subtypes. These pathogenic modifiers include differences in subclinical inflammation, oxidative stress burden, and adipocytokines in blacks in the African Diaspora prior to clinical diagnosis. Consequently, blacks in the African Diaspora manifest subtypes of type 2 diabetes, including ketosis-prone diabetes and J type diabetes. Given the diversity of type 2 diabetes in blacks in the African Diaspora, we hypothesize that blacks manifest multiple early pathogenic defects prior to the diagnosis of type 2 diabetes and its subtypes. These metabolic alterations have strong genetic component, which appears to play pivotal and primary role in the pathogenesis of type 2 diabetes and its subtypes in blacks in the African Diaspora. However, environmental factors must also be considered as major contributors to the higher prevalence of type 2 diabetes and its subtypes in blacks in the African Diaspora. These multiple alterations should be targets for early prevention of type 2 diabetes in blacks in the African Diaspora.

Mathematical analysis of a model for glucose regulation.

Diabetes affects millions of Americans, and the correct identification of individuals afflicted with this disease, especially of those in early stages or in progression towards diabetes, remains an active area of research. The minimal model is a simplified mathematical construct for understanding glucose-insulin interactions. Developed by Bergman, Cobelli, and colleagues over three decades ago, this system of coupled ordinary differential equations prevails as an important tool for interpreting data collected during an intravenous glucose tolerance test (IVGTT). In this study we present an explicit solution to the minimal model which allows for separating the glucose and insulin dynamics of the minimal model and for identifying patient-specific parameters of glucose trajectories from IVGTT. As illustrated with patient data, our approach seems to have an edge over more complicated methods currently used. Additionally, we also present an application of our method to prediction of the time to baseline recovery and calculation of insulin sensitivity and glucose effectiveness, two quantities regarded as significant in diabetes diagnostics.

Glycemic variability during algorithmic titration of insulin among hospitalized patients with type 2 diabetes and heart failure.

AIMS: The objective of this study is to assess hypoglycemia and glycemic variability (GV) in hospitalized patients with and without heart failure (HF) exacerbation. METHODS: Hospitalized patients with type 2 diabetes (T2D) with (N=35) or without (N=16) HF who had hyperglycemia or significant insulin use were included. Subjects underwent continuous glucose monitoring during algorithmic titration of basal bolus insulin. RESULTS: HF subjects had lower glucose coefficient of variation ([CV], 31±12 vs. 22±8.2, p=0.02), lower Low Blood Glucose Index (LBGI) and less hypoglycemia (25% vs. 2.6%, p=0.02), but similar mean glucose and glycemic lability index as non-HF subjects on day 1, but not on day 2. Sensor CV was correlated with hypoglycemia (ρ 0.32, p=0.02), HF status (ρ -0.35, p=0.013), T2D duration (ρ 0.29, p=0.04), insulin use prior to admission (ρ 0.42, p=0.002) and catecholamine levels. After controlling for differences in age, HbA1c, hypoglycemia, catecholamine levels, QT interval, and beta blocker use, only HF and diabetes duration or insulin use prior to admission were independent predictors of CV. HF had less robust associations with LBGI in multivariable models. CONCLUSIONS: HF is not associated with increased GV or hypoglycemia risk during initial titration of insulin. Further research is needed to determine prognostic implications.