Escherichia coli and Pichia pastoris: microbial cell-factory platform for -full-length IgG production.

Owing to the unmet demand, the pharmaceutical industry is investigating an alternative host to mammalian cells to produce antibodies for a variety of therapeutic and research applications. Regardless of some disadvantages, Escherichia coli and Pichia pastoris are the preferred microbial hosts for antibody production. Despite the fact that the production of full-length antibodies has been successfully demonstrated in E. coli, which has mostly been used to produce antibody fragments, such as: antigen-binding fragments (Fab), single-chain fragment variable (scFv), and nanobodies. In contrast, Pichia, a eukaryotic microbial host, is mostly used to produce glycosylated full-length antibodies, though hypermannosylated glycan is a major challenge. Advanced strategies, such as the introduction of human-like glycosylation in endotoxin-edited E. coli and cell-free system-based glycosylation, are making progress in creating human-like glycosylation profiles of antibodies in these microbes. This review begins by explaining the structural and functional requirements of antibodies and continues by describing and analyzing the potential of E. coli and P. pastoris as hosts for providing a favorable environment to create a fully functional antibody. In addition, authors compare these microbes on certain features and predict their future in antibody production. Briefly, this review analyzes, compares, and highlights E. coli and P. pastoris as potential hosts for antibody production.

Fc-Independent Protection from SARS-CoV-2 Infection by Recombinant Human Monoclonal Antibodies.

The use of passively-administered neutralizing antibodies is a promising approach for the prevention and treatment of SARS-CoV-2 infection. Antibody-mediated protection may involve immune system recruitment through Fc-dependent activation of effector cells and the complement system. However, the role of Fc-mediated functions in the efficacious in-vivo neutralization of SARS-CoV-2 is not yet clear, and it is of high importance to delineate the role this process plays in antibody-mediated protection. Toward this aim, we have chosen two highly potent SARS-CoV-2 neutralizing human monoclonal antibodies, MD65 and BLN1 that target distinct domains of the spike (RBD and NTD, respectively). The Fc of these antibodies was engineered to include the triple mutation N297G/S298G/T299A that eliminates glycosylation and the binding to FcγR and to the complement system activator C1q. As expected, the virus neutralization activity (in-vitro) of the engineered antibodies was retained. To study the role of Fc-mediated functions, the protective activity of these antibodies was tested against lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice, when treatment was initiated either before or two days post-exposure. Antibody treatment with both Fc-variants similarly rescued the mice from death reduced viral load and prevented signs of morbidity. Taken together, this work provides important insight regarding the contribution of Fc-effector functions in MD65 and BLN1 antibody-mediated protection, which should aid in the future design of effective antibody-based therapies.

[Factors associated with quality of life in 747 patients with type 2 diabetes in Tongzhou District and Shunyi District of Beijing].

OBJECTIVE: To investigate the situation of quality of life in patients with type 2 diabetes and its associated factors. METHODS: Questionnaires, physical examination and glycated hemoglobin test were conducted in 747 patients with type 2 diabetes. Hemoglobin A1c (HbA1c) was a proxy for glycemic control, diabetes specific quality of life scale (DSQL) score was a proxy for quality of life. Factors associa-ted with DSQL were analyzed by multiple linear regression and structural equation modeling (SEM). RESULTS: A total of 747 patients were included in this study. The mean HbA1c level was (7.1±1.2)%, with 35.1% reaching the target (262/747). There were significant differences in disease duration, me-dication and use of insulin, smoking, and body mass index (BMI) between the two groups with good and poor glycemic control (P < 0.05). The total score of DSQL was 44.92±13.32, in which average phy-siological factors were the highest, then followed by scores of psychological factors. Multiple linear regression showed that monthly household income, comorbidities, depression, duration of illness, insulin, hospitalization, and self-efficacy were significantly associated with the total score of DSQL (P < 0.05). SEM showed that blood glucose control was significantly associated with the scores of physical factors (0.166), psychological factors (0.076), and social factors (0.124) of DSQL, respectively. Depression had effects on the physical factors (0.342), psychological factors (0.217), and treatment factors (0.050) of DSQL (P < 0.05). CONCLUSION: Glycemic control in our study is relatively poor but the quality of life remains well. More attention should be paid to patients who are male, with long diagnosis duration, poor medication adherence, smoking, with depression and with low diabetes-related skills. In practice, health practitioners should be aware of psychological needs of patients, and offer mental health education to patients and their families, in order to help patients manage blood glucose and improve their quality of life.

Higher glucagon-to-insulin ratio is associated with elevated glycated hemoglobin levels in type 2 diabetes patients.

BACKGROUND/AIMS: The importance of α-cell dysfunction in the pathogenesis of type 2 diabetes has re-emerged recently. However, data on whether relative glucagon excess is present in clinical settings are scarce. We aimed to investigate associations between glucagon-to-insulin ratio and various metabolic parameters. METHODS: A total of 451 patients with type 2 diabetes naïve to insulin treatment were recruited. Using glucagon-to-insulin ratio, we divided subjects into quartiles according to both fasting and postprandial glucagon-to-insulin ratios. RESULTS: The mean age of the subjects was 58 years, with a mean body mass index of 25 kg/m2 . The patients in the highest quartile of glucagon-to-insulin ratio had higher glycated hemoglobin (HbA1c) levels. HbA1c levels were positively correlated with both fasting and postprandial glucagon-to-insulin ratios. Subjects in the highest quartile of postprandial glucagon-to-insulin ratio were more likely to exhibit uncontrolled hyperglycemia, even after adjusting for confounding factors (odds ratio, 2.730; 95% confidence interval, 1.236 to 6.028; p for trend < 0.01). CONCLUSION: Hyperglucagonemia relative to insulin could contribute to uncontrolled hyperglycemia in type 2 diabetes patients.

Investigating the Association Between Baseline Characteristics (HbA1c and Body Mass Index) and Clinical Outcomes of Fast-Acting Insulin Aspart in People with Diabetes: A Post Hoc Analysis.

INTRODUCTION: The aim of this study was to investigate the association between baseline characteristics [HbA1c and body mass index (BMI)] and the effect of mealtime fast-acting insulin aspart (faster aspart) relative to insulin aspart (IAsp) or basal-only insulin therapy on several efficacy and safety outcomes in people with diabetes. METHODS: Post hoc analysis of three randomised phase 3a trials in people with type 1 diabetes (T1D; onset 1) and type 2 diabetes (T2D; onset 2 and 3). Participants (N = 1686) were stratified according to baseline BMI (< 25 kg/m2, 25-< 30 kg/m2, ≥ 30 kg/m2) or HbA1c (≤ 58 mmol/mol, > 58-< 64 mmol/mol, ≥ 64 mmol/mol; ≤ 7.5%, > 7.5-< 8.0%, ≥ 8.0%). RESULTS: In participants with T2D, the estimated treatment difference for change in HbA1c was similar for all BMI and HbA1c subgroups. No major differences between treatments were observed in risk of overall hypoglycaemia or insulin dose across subgroups. In participants with T1D, change in HbA1c was similar across BMI and HbA1c subgroups, and no major differences between treatments were observed for severe or blood glucose-confirmed hypoglycaemia across subgroups. Total daily insulin dose (U/kg) was similar across all baseline HbA1c groups and the BMI < 25 kg/m2 and 25-30 kg/m2 groups, but was significantly lower with mealtime faster aspart compared with IAsp in the BMI > 30 kg/m2 subgroup. CONCLUSIONS: In participants with T1D and T2D, treatment differences (for change in HbA1c and overall hypoglycaemia) between mealtime faster aspart and insulin comparators were similar to the corresponding overall analysis across baseline HbA1c and BMI subgroups. The finding of a lower total daily insulin dose in participants with obesity (BMI > 30 kg/m2) and T1D treated with faster aspart, versus those treated with IAsp, may warrant further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01831765 (onset 1); NCT01819129 (onset 2); NCT01850615 (onset 3). FUNDING: Novo Nordisk A/S, Søborg, Denmark.

[Glycemic control and its associated factors in children and adolescents with type 1 diabetes mellitus].

Objective: To explore the factors associated with glycemic control in children and adolescents with type 1 diabetes mellitus (T1DM) treated with continuous subcutaneous insulin infusion (CSII). Methods: Subjects were enrolled from the Guangdong Type 1 Diabetes Translational Medicine Study between June 2011 and August 2017. Patients with T1DM aged less than 18 years and treated with CSII for at least 6 months were included. Demographic data and clinical information on self-monitoring of blood glucose (SMBG), glycosylated hemoglobin (HbA1c) and insulin treatment were collected. Participants were categorized based on HbA1c levels as sufficient control group (HbA1c<7.5% ) and insufficient control group ( HbA1c≥7.5%). A multivariate logistic regression model was used to examine the factors associated with glycemic control. Results: A total of 142 participants (76 females, 66 males) with a median age of 13.0 (9.9, 15.0) years and a median disease duration of 3.0 (1.6, 5.0) years were enrolled. HbA1c was (8.2±2.0)% and 41.55%(59/142) of patients achieved the target for HbA1c. The frequency of SMBG was 5.0 (2.0, 8.0) and 3.0 (1.0, 4.0) tests per day (P<0.001), and the frequency of hypoglycemia was 2.0 (0.8, 4.0) and 1.0 (0, 2.0) times per week (P=0.003) in sufficient control group and insufficient control group, respectively. Sufficient glycemic control (HbA1c <7.5%) was associated with the frequency of SMBG (OR=1.238, 95% CI: 1.088-1.409, P=0.001). Conclusion: A higher frequency of SMBG is one of the key factors to achieve sufficient glycemic control among children and adolescents with T1DM treated with CSII.

Using routine HbA1c measurements in stroke and the associations of dysglycaemia with stroke outcomes.

AIMS: Diabetes is a major risk factor for stroke. We aimed to investigate the prevalence of diabetes and pre-diabetes within a stroke cohort and examine the association of glycaemia status with mortality and morbidity. METHODS: Inpatients aged ≥54 who presented with a diagnosis of stroke had a routine HbA1c measurement as part of the Austin Health Diabetes Discovery Initiative. Additional data were attained from hospital databases and Australian Stroke Clinical Registry. Outcomes included diabetes and pre-diabetes prevalence, length of stay, 6-month and in-hospital mortality, 28-day readmission rates, and 3-month modified Rankin scale score. RESULTS: Between July 2013 and December 2015, 610 patients were studied. Of these, 31% had diabetes while 40% had pre-diabetes. Using multivariable regression analyses, the presence of diabetes was associated with higher odds of 6-month mortality (OR = 1.90, p = 0.022) and higher expected length of stay (IRR = 1.29, p = 0.004). Similarly, a higher HbA1c was associated with higher odds of 6-month mortality (OR = 1.27, p = 0.005) and higher expected length of stay (IRR = 1.08, p = 0.010). CONCLUSIONS: 71% of this cohort had diabetes or pre-diabetes. Presence of diabetes and higher HbA1c were associated with higher 6-month mortality and length of stay. Further research is necessary to determine if improved glycaemic control may improve stroke outcomes.

A systematic review of non-genetic predictors and genetic factors of glycated haemoglobin in type 1 diabetes one year after diagnosis.

Type 1 diabetes (T1D) results from autoimmune destruction of the pancreatic ßcells. Although all T1D patients require daily administration of exogenous insulin, their insulin requirement to achieve good glycaemic control may vary significantly. Glycated haemoglobin (HbA1c) level represents a stable indicator of glycaemic control and is a reliable predictor of long-term complications of T1D. The purpose of this article is to systematically review the role of non-genetic predictors and genetic factors of HbA1c level in T1D patients after the first year of T1D, to exclude the honeymoon period. A total of 1974 articles published since January 2011 were identified and 78 were finally included in the analysis of non-genetic predictors. For genetic factors, a total of 277 articles were identified and 14 were included. The most significantly associated factors with HbA1c level are demographic (age, ethnicity, and socioeconomic status), personal (family characteristics, parental care, psychological traits...) and features related to T1D (duration of T1D, adherence to treatment …). Only a few studies have searched for genetic factors influencing HbA1c level, most of which focused on candidate genes using classical genetic statistical methods, with generally limited power and incomplete adjustment for confounding factors and multiple testing. Our review shows the complexity of explaining HbA1c level variations, which involves numerous correlated predictors. Overall, our review underlines the lack of studies investigating jointly genetic and non-genetic factors and their interactions to better understand factors influencing glycaemic control for T1D patients.

Dietary Fiber Intake and Type 2 Diabetes Mellitus: An Umbrella Review of Meta-analyses.

OBJECTIVE: The purpose of this study was to review previously published meta-analyses on the effectiveness of dietary fiber on type 2 diabetes. METHODS: An umbrella review of all published meta-analyses was performed. A PubMed search from January 1, 1980, to April 30, 2017, was conducted using the following search strategy: (fiber OR glucan OR psyllium) AND (meta-analysis OR systematic review). Only English-language publications that provided quantitative statistical analysis on type 2 diabetes, fasting blood glucose concentrations, or glycosylated hemoglobin were retrieved. RESULTS: Sixteen meta-analyses were retrieved for inclusion in this umbrella review. In the meta-analyses comparing highest versus lowest dietary fiber intake, there was a statistically significant reduction in the relative risk (RR) of type 2 diabetes (RR = 0.81-0.85), with the greatest benefit coming from cereal fibers (RR = 0.67-0.87). However, statistically significant heterogeneity was observed in all of these meta-analyses. In the meta-analyses of supplementation studies using ß-glucan or psyllium fibers on type 2 diabetic participants, statistically significant reductions were identified in both fasting blood glucose concentrations and glycosylated hemoglobin percentages. CONCLUSION: This review suggests that those consuming the highest amounts of dietary fiber, especially cereal fiber, may benefit from a reduction in the incidence of developing type 2 diabetes. There also appears to be a small reduction in fasting blood glucose concentration, as well as a small reduction in glycosylated hemoglobin percentage for individuals with type 2 diabetes who add ß-glucan or psyllium to their daily dietary intake.

Glucagon like peptide 1 receptor agonists: a therapy for diabetes management / Agonistas del receptor péptido 1 similar al glucagon: una terapia para el control de la diabetes

Abstract Introduction: Glucagon-like peptide 1 agonists inhibit glucose-dependent glucagon secretion, decrease gastric emptying and appetite through neural mechanisms, contribute to glucose regulation and show reduction in glycated hemoglobin A. Methods: A bibliographic search was made on Medline® about pharmacology of the agonist glucagon-like peptide-1 receptor, Liraglutide, Lixisenatide, Albiglutide, Exenatide, Exenatide with long-acting release. Results: The GLP1 receptor agonist are agents involved with glycemic balance, weight loss induction and are associated with lower risk of hypoglycemia. They have shown efficacy in the treatment of hypoglycemia in patients with type-2 diabetes. Conclusions: GLP1 receptor agonist are part of the therapies for diabetes that have shown benefits in metabolic control, effectiveness in weight reduction and changes in glycated hemoglobin. More studies are needed to evaluate its long-term safety.

Resumen Introducción: Los agonistas del péptido 1 similar al glucagón inhiben la secreción del glucagón dependiente de glucosa, también disminuyen el vaciamiento gástrico y el apetito a través de mecanismos neurales contribuyen a la regulación de la glucosa y muestran reducción en la hemoglobina A glicada. Métodos: Búsqueda bibliográfica en Medline sobre la farmacología de los agonistas del receptor del péptido 1 similar al glucagón: liraglutide, lixisenatide, albiglutide, exenatide, exenatide con liberación de acción prolongada. Resultados: Los agonistas del receptor del péptido 1 similar al glucagón son agentes involucrados con el equilibrio glucémico, inducen pérdida de peso, se asocian a un menor riesgo de hipoglucemias y han mostrado eficacia en el tratamiento de la hiperglucemia en pacientes con diabetes tipo 2. Conclusiones: Los agonistas del receptor del péptido 1 similar al glucagón forman parte de las terapias para la diabetes que han mostrado beneficios en el control metabólico, efectividad en la reducción de peso y cambios en la hemoglobina A glicosilada. Aún faltan estudios que evalúen su seguridad a largo plazo.

Improvement of Glycosylated Hemoglobin in Patients with Type 2 Diabetes Mellitus under Insulin Treatment by Reimbursement for Self-Monitoring of Blood Glucose.

BACKGROUND: In Korea, the costs associated with self-monitoring of blood glucose (SMBG) for patients with type 2 diabetes mellitus (T2DM) under insulin treatment have been reimbursed since November 2015. We investigated whether this new reimbursement program for SMBG has improved the glycemic control in the beneficiaries of this policy. METHODS: Among all adult T2DM patients with ≥3 months of reimbursement (n=854), subjects without any changes in anti-hyperglycemic agents during the study period were selected. The improvement of glycosylated hemoglobin (HbA1c) was defined as an absolute reduction in HbA1c ≥0.6% or an HbA1c level at follow-up <7%. RESULTS: HbA1c levels significantly decreased from 8.5%±1.3% to 8.2%±1.2% during the follow-up (P<0.001) in all the study subjects (n=409). Among them, 35.5% (n=145) showed a significant improvement in HbA1c. Subjects covered under the Medical Aid system showed a higher prevalence of improvement in HbA1c than those with medical insurance (52.2% vs. 33.3%, respectively, P=0.012). In the improvement group, the baseline HbA1c (P<0.001), fasting C-peptide (P=0.016), and daily dose of insulin/body weight (P=0.024) showed significant negative correlations with the degree of HbA1c change. Multivariate analysis showed that subjects in the Medical Aid system were about 2.5-fold more likely to improve in HbA1c compared to those with medical insurance (odds ratio, 2.459; 95% confidence interval, 1.138 to 5.314; P=0.022). CONCLUSION: The reimbursement for SMBG resulted in a significant improvement in HbA1c in T2DM subjects using insulin, which was more prominent in subjects with poor glucose control at baseline or covered under the Medical Aid system.

Impact of Diabetes Mellitus on Outcomes in Patients Supported With Left Ventricular Assist Devices: A Single Institutional 9-Year Experience.

BACKGROUND: Diabetes mellitus (DM) is a risk factor for morbidity and mortality in patients with heart failure. The effect of DM on post-left ventricular assist device (LVAD) implantation outcomes is unclear. This study sought to investigate whether patients with DM had worse outcomes than patients without DM after LVAD implantation and whether LVAD support resulted in a better control of DM. METHODS AND RESULTS: We retrospectively reviewed 341 consecutive adults who underwent implantation of LVAD from 2007 to 2016. Patient characteristics and adverse events were studied and compared between patients with and without DM. One hundred thirty-one patients (38%) had DM. Compared with patients without DM, those with DM had higher rates of ischemic cardiomyopathy, LVAD implantation as destination therapy, and increased baseline body mass index. In a proportional hazards (Cox) model with adjustment for relevant covariates and median follow-up of 16.1 months, DM was associated with increased risk of all-cause mortality (hazard ratio, 1.73; 95% confidence interval: 1.18-2.53; P=0.005) and increased risk of nonfatal LVAD-related complications, including a composite of stroke, pump thrombosis, and device infection (hazard ratio, 2.1; 95% confidence interval: 1.35-3.18; P=0.001). Preoperative hemoglobin A1c was not significantly associated with mortality or adverse events among patients with DM. LVAD implantation resulted in a remarkable decrease in hemoglobin A1c levels (7.4±1.9 pre-LVAD versus 6.0±1.5 and 6.3±1.4 after 3 and 12 months post-LVAD, respectively; P<0.0001) and a significant reduction in requirements of DM medications. CONCLUSIONS: DM is associated with increased rates of all-cause mortality and major adverse events despite favorable glycemic control after LVAD implantation.

Glycated Hemoglobin and All-Cause Mortality in Korean Type 2 Diabetes.

The purpose of this study was to evaluate the association between glycated hemoglobin (HbA1c) and all-cause mortality in type 2 diabetes mellitus. We conducted a community-based prospective cohort study of 352 type 2 diabetic patients aged 30-92 who participated in a community diabetes complications screening program in Gokseng-gun, Jeollanamdo, Korea. HbA1c levels were categorized as <6.5%, 6.5-6.9%, 7.0-7.9%, 8.0-8.9% and ≥9.0%. Patients were followed up on for a mean of 6.9 years. The Cox proportional hazards model was used to evaluate the relationship between HbA1c levels and all-cause mortality. During the mean follow-up period of 6.9 years, 77 patients (21.9%) died. A J-shaped association was found between HbA1c and all-cause mortality, with the lowest mortality at 6.5-6.9% of HbA1c levels. Compared to patients with HbA1c of 6.5-6.9%, patients with <6.5%, 7.0-7.9%, 8.0-8.9% and ≥9.0% had an adjusted hazard ratio (95% confidence interval) for all-cause mortality of 1.71 (0.76-3.84), 1.23 (0.53-2.82), 1.32(0.51-3.44) and 2.66 (1.01-7.02), respectively. We found a J-shaped association between glycated hemoglobin and all-cause mortality in Korean type 2 diabetic patients.

Diabetes and CKD in the United States Population, 2009-2014.

BACKGROUND AND OBJECTIVES: Diabetes is an important cause of CKD. However, among people with diabetes, it is unclear to what extent CKD is attributable to diabetes itself versus comorbid conditions, such as advanced age and hypertension. We examined associations of diabetes with clinical manifestations of CKD independent of age and BP and the extent to which diabetes contributes to the overall prevalence of CKD in the United States. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a cross-sectional study of 15,675 participants in the National Health and Nutrition Examination Surveys from 2009 to 2014. Diabetes was defined by use of glucose-lowering medications or hemoglobin A1c ≥6.5%. eGFR was calculated using the CKD Epidemiology Collaboration formula, and albumin-to-creatinine ratio was measured in single-void urine samples. We calculated the prevalence of CKD manifestations by diabetes status as well as prevalence ratios, differences in prevalence, and prevalence attributable to diabetes using binomial and linear regression, incorporating data from repeat eGFR and urine albumin-to-creatinine ratio measurements to estimate persistent disease. RESULTS: For participants with diabetes (n=2279) versus those without diabetes (n=13,396), the estimated prevalence of any CKD (eGFR<60 ml/min per 1.73 m2; albumin-to-creatinine ratio ≥30 mg/g, or both) was 25% versus 5.3%, respectively; albumin-to-creatinine ratio ≥30 mg/g was 16% versus 3.0%, respectively; albumin-to-creatinine ratio ≥300 mg/g was 4.6% versus 0.3%, respectively; eGFR<60 ml/min per 1.73 m2 was 12% versus 2.5%, respectively; and eGFR<30 ml/min per 1.73 m2 was 2.4% versus 0.4%, respectively (each P<0.001). Adjusting for demographics and several aspects of BP, prevalence differences were 14.6% (P<0.001), 10.8% (P<0.001), 4.5% (P<0.001), 6.5% (P<0.001), and 1.8% (P=0.004), respectively. Approximately 24% (95% confidence interval, 19% to 29%) of CKD among all United States adults was attributable to diabetes after adjusting for demographics. CONCLUSIONS: Diabetes is strongly associated with both albuminuria and reduced GFR independent of demographics and hypertension, contributing substantially to the burden of CKD in the United States.

Effectiveness of Quality Improvement Strategies for the Management of CKD: A Meta-Analysis.

BACKGROUND AND OBJECTIVES: Quality improvement interventions have enhanced care for other chronic illnesses, but their effectiveness for patients with CKD is unknown. We sought to determine the effects of quality improvement strategies on clinical outcomes in adult patients with nondialysis-requiring CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a systematic review of randomized trials, searching Medline and the Cochrane Effective Practice and Organization of Care database from January of 2003 to April of 2015. Eligible studies evaluated one or more of 11 prespecified quality improvement strategies, and prespecified study outcomes included at least one process of care measure, surrogate outcome, or hard clinical outcome. We used a random effects model to estimate the pooled risk ratio (RR; dichotomous data) or the mean difference (continuous data). RESULTS: We reviewed 15 patient-level randomized trials (n=3298 patients), and six cluster-randomized trials (n=30,042 patients). Quality improvement strategies reduced dialysis incidence (seven trials; RR, 0.85; 95% confidence interval [95% CI], 0.74 to 0.97) and LDL cholesterol concentrations (four trials; mean difference, -17.6 mg/dl; 95% CI, -28.7 to -6.5), and increased the likelihood that patients received renin-angiotensin-aldosterone system inhibitors (nine trials; RR, 1.16; 95% CI, 1.06 to 1.27). We did not observe statistically significant effects on mortality, cardiovascular events, eGFR, glycated hemoglobin, and systolic or diastolic BP. CONCLUSIONS: Quality improvement interventions yielded significant beneficial effects on three elements of CKD care. Estimates of the effectiveness of quality improvement strategies were limited by study number and adherence to quality improvement principles. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_09_06_CJASNPodcast_17_10.mp3.

[Diabetes Screening in Patients with Macrovascular Coronary Disease: Are the New European Guidelines a Step Backwards?] / Rastreio da Diabetes em Doentes com Doença Macrovascular Coronária: As Novas Guidelines Europeias são um Retrocesso?

BACKGROUND: The new European guidelines on diabetes mellitus and cardiovascular diseases propose that the FINnish Diabetes RIsk SCore should be used to evaluate the risk of diabetes mellitus and that diabetes mellitus screening in coronary artery disease patients should be based on fasting glucose and HbA1c. The 2 hour oral glucose tolerance test, recommended for all pts in the previous guidelines, is now only recommended for 'inconclusive' cases. We aimed to evaluate this new strategy. MATERIAL AND METHODS: Fasting glucose, HbA1c and glucose tolerance test (75 g, 2h) were prospectively evaluated in a consecutive group of pts with coronary artery disease. ADA criteria (both glucose tolerance test and HbA1c) were used to define diabetes mellitus and pre-diabetes mellitus. Diabetes mellitus risk was evaluated according to the FINnish Diabetes RIsk SCore. RESULTS: A total of 135 patients were included (mean age 62.3 +/- 13.1 years, 99 males). Glucose tolerance test and HbA1c together diagnosed 18 (13.3%) new cases of diabetes mellitus and 77 (57.0%) patients with pre-diabetes mellitus. Fasting glucose + HbA1c (guidelines strategy) identified 12/18 patients with diabetes mellitus (Sens 66.7%; negative predictive value 95.1%; Kappa 0.78; p < 0.0001) and 83/95 patients with glucose anomalies (pre- diabetes mellitus + diabetes mellitus) (Sens 87.4%; negative predictive value 76.9%). Performing glucose tolerance test in the 29 patients with an elevated FINnish Diabetes RIsk SCore would allow identifying 15/18 patients with diabetes mellitus (Sens 83.3%; negative predictive value 97.5%; Kappa 0.85; p < 0.0001) and 86/95 patients with glucose anomalies (Sens 90.5%; negative predictive value 81.6%). DISCUSSION: Although this strategy improved the screening accuracy, one in each six patients with diabetes mellitus would still remain undiagnosed, as compared to measuring HbA1c and performing an glucose tolerance test in all patients. CONCLUSION: Using the FINnish Diabetes RIsk SCore to select candidates to additional glucose tolerance test improves the accuracy for identifying diabetic patients, as compared with fasting glucose + HbA1c alone. However, 1/6 patients diabetes mellitus is still left undiagnosed with this strategy proposed by the current guidelines.

Introdução: As novas recomendações europeias de diabetes mellitus tipo 2 e doença cardiovascular sugerem que o risco de diabetes mellitus tipo 2 deve ser avaliado através do score de risco FINnish Diabetes RIsk SCore e que o rastreio de diabetes mellitus tipo 2 na população com doença arterial coronária deve ser efetuado apenas com a glicemia plasmática em jejum e a HbA1, remetendo a prova de tolerância oral à glicose para os casos 'inconclusivos'. Pretendemos avaliar os resultados desta estratégia, que difere da previamente defendida nas guidelines. Material e Métodos: A glicemia plasmática em jejum, HbA1c e a prova de tolerância oral à glicose (75 g, 2 horas) foram avaliadas prospectivamente num grupo de doentes consecutivos submetidos a intervenção coronária percutânea, sendo usada a classificação da ADA para pré-diabetes mellitus tipo 2 e diabetes mellitus tipo 2. O risco de diabetes foi avaliado de acordo com o FINnish Diabetes RIsk SCore. Resultados: Foram incluídos 135 doentes (idade média 62,3 +/- 13,1 anos; 99 homens). Usando a prova de tolerância oral à glicose e a HbA1c, foram diagnosticados 18 (13,3%) novos casos de diabetes mellitus tipo 2 e 77 (57,0%) casos de pré-diabetes mellitus tipo 2. A glicemia plasmática em jejum + HbA1c identificou 12/18 doentes com diabetes mellitus tipo 2 (Sens 66,7%; valor preditivo negativo 95,1%; Kappa 0,78; p < 0,0001) e 83 do total (pré-diabetes mellitus tipo 2/ diabetes mellitus tipo 2) de 95 doentes com distúrbios da glucose (Sens 87,4%; valor preditivo negativo 76,9%). Realizar adicionalmente prova de tolerância oral à glicose nos 29 doentes com um FINnish Diabetes RIsk SCore elevado permitiu diagnosticar 15/18 doentes com diabetes mellitus (Sens 83,3%; valor preditivo negativo 97,5%; Kappa 0,85; p < 0,0001) e 86/95 dos doentes com distúrbios da glucose (Sens 90,5%; valor preditivo negativo 81,6%). Discussão: Apesar da melhoria diagnóstica, um em cada seis doentes com diabetes mellitus tipo 2 não seria diagnosticado por esta estratégia. Conclusão: A utilização do FINnish Diabetes RIsk SCore como forma de selecionar os doentes candidatos a rastreio com prova de tolerância oral à glicose melhora a capacidade diagnóstica, quando comparada com a simples avaliação da glicemia plasmática em jejum e da HbA1c. No entanto, um em cada seis doentes com diabetes mellitus tipo 2 não é identificado com esta metodologia.

Disglucemia en el paciente crítico: evidencia actual y perspectivas futuras / Dysglycemia in the critically ill patient: current evidence and future perspectives

RESUMEN La disglucemia en el paciente crítico (hiperglucemia, hipoglucemia, variabilidad de la glucemia y el tiempo en rango) es un marcador de severidad de la enfermedad crítica asociada a mayor mortalidad. Sin embargo, dicho impacto parece atenuarse en los pacientes con diabetes mellitus, en particular en aquellos con mal control glucémico premórbido lo cual ha sido denominado "paradoja de la diabetes". Este fenómeno determina que en los nuevos protocolos de control de la glucemia deban ser contemplados los valores de hemoglobina glucosilada (HbA1c) al ingreso a unidad de cuidados intensivos, siendo necesarios nuevos rangos de glucemia objetivos según los valores de la HbA1c. En tal sentido, la HbA1c surge como una herramienta sencilla que permite obtener información de utilidad terapéutica y valor pronóstico en la unidad de cuidados intensivos.

ABSTRACT Dysglycemia in critically ill patients (hyperglycemia, hypoglycemia, glycemic variability and time in range) is a biomarker of disease severity and is associated with higher mortality. However, this impact appears to be weakened in patients with previous diabetes mellitus, particularly in those with poor premorbid glycemic control; this phenomenon has been called "diabetes paradox". This phenomenon determines that glycated hemoglobin (HbA1c) values should be considered in choosing glycemic control protocols on admission to an intensive care unit and that patients' target blood glucose ranges should be adjusted according to their HbA1c values. Therefore, HbA1c emerges as a simple tool that allows information that has therapeutic utility and prognostic value to be obtained in the intensive care unit.

[Utility of hemoglobin A1c for diagnosing metabolic syndrome in Chinese subjects over 50 years old].

Objective: To evaluate glycated hemoglobing A1c (HbA1c) in diagnosing metabolic syndrome (MS) in Chinese subjects aged over 50 years. Methods: A community-based cross-sectional survey was conducted between October 2010 and January 2011 in Shipai community, Guangzhou. A total of 1 494 subjects aged over 50 years were investigated. Questionnaire survey and physical examination were performed among all participants. Fasting blood samples were obtained to measure plasma glucose (FPG), blood lipids and HbA1c. MS was defined by the criteria of International Diabetes Federation (IDF), National Cholesterol Education Program-Adult Treatment Panel Ⅲ (ATP Ⅲ)(2005) and Chinese Diabetes Society (CDS), respectively. Receiver operating characteristic (ROC) curves were plotted to explore the accuracy of HbA1c for diagnosing MS. Results: After excluding subjects with missing data, the remaining 1 473 subjects had a median age of 61 years (55-68 years). An HbA1c threshold of 6.1% yielded the highest combination of sensitivity (52.1%) and specificity (84.3%) for diagnosing MS. Using HbA1c≥5.7% as definition of dysglycemia, the prevalence of MS (IDF), MS (ATP Ⅲ) and MS (CDS) were 48.7%, 57.1% and 50.8%, respectively. The κ coefficients were 0.853, 0.768 and 0.730, respectively. Using HbA1c≥6.1% as definition of dysglycemia, the prevalences of MS (IDF), MS (ATP Ⅲ) and MS (CDS) were 41.2%, 45.8% and 39.1%, respectively. The κ coefficients were 0.923, 0.880 and 0.881, respectively. The optimal HbA1c threshold with the highest level of agreement according to IDF, ATP Ⅲ and CDS criteria were 6.1%, 6.3% and 6.3%, respectively. Conclusions: An HbA1c threshold of 6.1% showed a high specificity for diagnosing MS in Chinese subjects aged over 50 years in community-based setting. The optimal HbA1c threshold may vary according to different criteria and populations.

Is glycemia control in Canadians with diabetes individualized? A cross-sectional observational study.

OBJECTIVE: Diabetes guidelines recommend individualized glycemic targets: tighter control in younger, healthier patients and consideration of more moderate control in the elderly and those with coexisting illnesses. Our objective was to examine whether glycemic control varied by age and comorbidities in Canadian primary care. RESEARCH DESIGN AND METHODS: Cross-sectional study using data from the electronic medical records of 537 primary care providers across Canada; 30 416 patients with diabetes, aged 40 or above, with at least one encounter and one hemoglobin A1c (HbA1c) measurement between 1 January 2012 and 31 December 2013. The outcome was the most recent HbA1c, categorized into three levels of control: tight (<7.0% or <53 mmol/mol), moderate (7.0%-8.5%, 53 mmol/mol-69.5 mmol/mol) and uncontrolled (>8.5% or >69.5 mmol/mol). We adjusted for several factors associated with glycemic control including treatment intensity. RESULTS: Younger patients (aged 40-49) were more likely to have moderate as opposed to tight control than the older patients (aged 80+) (OR 1.28; 95% CI 1.11 to 1.49, p=0.001). The youngest were also more likely to have uncontrolled as opposed to moderately controlled glycemia (OR 3.39; 95% CI 2.75 to 4.17, p<0.0001). Patients with no or only one comorbidity were more likely to have moderate as opposed to tight control than those with three or more comorbidities (OR 1.66;95% CI 1.46 to 1.90, p<0.0001). CONCLUSIONS: Levels of glycemic control, given age and comorbidities appear to differ from guideline recommendations. Research is needed to understand these discrepancies and develop methods to assist providers in personalizing glycemic targets.

Dietetic and educational interventions improve clinical outcomes of diabetic and obese clients with mental impairment.

AIM: The aim of this study was to evaluate the effect of dietetic and educational interventions provided to clients with type 2 diabetes (with or without obesity) or obesity-only residing in supported residential facilities and characterised by mental impairment. METHODS: A retrospective audit involving the retrieval of information from medical records and databases was undertaken to evaluate the effect of dietetic and educational interventions. Clinical outcomes were weight, body mass index and glycosylated haemoglobin (HbA1c) levels. RESULTS: A total of 91 clients were included, 47 with type 2 diabetes (with or without obesity) and 44 with obesity-only. All but one had schizophrenia, an intellectual disability or another psychological condition. After interventions, the diabetic subgroup demonstrated significant decreases in weight (mean [SD] initial = 101.5 [20.7], final = 97.8 [20.6] kg, P = 0.001) and body mass index (mean [SD] initial = 35.8 [8.1], final = 34.4 [7.8] kg/m2 , P = 0.001) and a non-significant decrease in HbA1c over time. The obesity-only subgroup showed no significant change in outcomes. Factors significantly negatively impacting at least one outcome included the presence of schizophrenia (P ≤ 0.017) and refusal of intervention(s) (P ≤ 0.048), whereas a significant positive impact was seen for a greater total number of visits to a dietitian or diabetes educator (P ≤ 0.024). CONCLUSIONS: These results provide evidence to support the effectiveness of dietetic and educational interventions for this vulnerable client group.