Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer.

PURPOSE: The combination of fulvestrant with alpelisib, a PI3K inhibitor, improves progression-free survival in metastatic hormone receptor-positive, PIK3CA-mutant breast cancer. This study describes the incidence, risk factors, and treatment of alpelisib-associated hyperglycemia. METHODS: Patients with metastatic breast cancer who received alpelisib from 2013 to 2021 at Memorial Sloan Kettering Cancer Center were included in this retrospective study. Alpelisib prescription dates and patient/tumor characteristics were abstracted from medical records. Risk factors associated with hyperglycemia and alpelisib dose reduction/discontinuation were evaluated using Pearson's χ2 tests. RESULTS: Among 247 patients, baseline median body mass index was 25.4 kg/m2 and median hemoglobin A1c (HbA1c) was 5.5%. A total of 152 patients (61.5%) developed any-grade hyperglycemia and 72 patients (29.2%) developed grade 3-4 hyperglycemia; median time to onset was 16 days. A total of 100 patients (40.5%) received alpelisib on a clinical trial; rates of hyperglycemia were significantly higher in patients treated as standard care versus on a clinical trial (any-grade hyperglycemia 80.3% vs. 34.0%, grade 3-4 hyperglycemia 40.2% vs. 13.0%, p < .001). Baseline HbA1c was significantly associated with development of hyperglycemia (p < .001) and alpelisib dose reduction/discontinuation (p = .015). Among those who developed hyperglycemia, 101 (40.9%) received treatment, most commonly with metformin. A total of 49 patients (19.8%) were referred to an endocrinologist, which was associated with SGLT2 inhibitor prescription (p = .007). CONCLUSIONS: Rates of hyperglycemia among patients treated with alpelisib as standard care were significantly higher than patients treated on clinical trials. Elevated baseline HbA1c is associated with alpelisib-induced hyperglycemia and requiring dose modification. Optimization of glycemic status before alpelisib initiation should become routine practice.

Docking study, molecular dynamic, synthesis, anti-α-glucosidase assessment, and ADMET prediction of new benzimidazole-Schiff base derivatives.

The control of postprandial hyperglycemia is an important target in the treatment of type 2 diabetes mellitus (T2DM). As a result, targeting α-glucosidase as the most important enzyme in the breakdown of carbohydrates to glucose that leads to an increase in postprandial hyperglycemia is one of the treatment processes of T2DM. In the present work, a new class of benzimidazole-Schiff base hybrids 8a-p has been developed based on the potent reported α-glucosidase inhibitors. These compounds were synthesized by sample recantations, characterized by 1H-NMR, 13C-NMR, FT-IR, and CHNS elemental analysis, and evaluated against α-glucosidase. All new compounds, with the exception of inactive compound 8g, showed excellent inhibitory activities (60.1 ± 3.6-287.1 ± 7.4 µM) in comparison to acarbose as the positive control (750.0 ± 10.5). Kinetic study of the most potent compound 8p showed a competitive type of inhibition (Ki value = 60 µM). In silico induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the title new compounds over the active site of α-glucosidase. In silico druglikeness analysis and ADMET prediction of the most potent compounds demonstrated that these compounds were druglikeness and had satisfactory ADMET profile.

Assessment of In Vitro Tests as Predictors of the Antioxidant Effects of Insulin, Metformin, and Taurine in the Brain of Diabetic Rats.

Hyperglycemia-induced oxidative stress is an intrinsic feature of diabetes mellitus and a recognized causative factor of complications associated with the disease. As a result, compounds possessing antioxidant properties are commonly investigated as possible ways of minimizing and even preventing diabetes-related oxidative stress. On these premises, the present study was carried out to investigate the antioxidant properties of metformin (MET), a common oral hypoglycemic agent, of taurine (TAU), a sulfonic acid compound with known antioxidant benefits in diabetes, and of insulin (INS), a standard antidiabetic serving as a reference compound, by using in vitro and in vivo tests. A battery of seven in vitro tests was used to assess antioxidant/antiradical activity. The addition of a treatment compound led to a mean percentage decrease of values for free radical/lipid peroxidation (LPO) that ranged from very high (82%) with INS to moderate (43%) with MET) and to low (31%) with TAU. Combining MET with TAU leads to an improvement of the effect seen with MET alone (46%). By contrast, under the same conditions, N-acetylcysteine, a known antioxidant, was more potent (92%) than any of the test compounds. In vivo studies were conducted using rats made diabetic with streptozotocin and treated with daily doses of INS, MET, TAU, and MET-TAU for 6 weeks. Among the test compounds, the greatest hypoglycemic effect was attained with INS (>90% decrease), followed by MET (~70% decrease), with TAU providing only a modest effect (-30% decrease). Unexpectedly, however, all three compounds reduced the diabetic values for brain LPO, nitric oxide, antioxidant enzymes, glutathione, and glutathione-related enzymes to values that varied in extent within a narrow range (<12% from one another). On the other hand, pairing MET with TAU led to a small enhancement (<10%) of the effects seen with MET alone. In short, while in vitro tests for antioxidant/antiradical activity suggest marked differences in potency for INS, MET, and TAU as a result of different structures, changes in the values of indices of oxidative stress affected by these compounds in the brain of diabetic rats varied within a rather narrow range. Also, the present results suggest that although hyperglycemia is an important determinant of the oxidative stress of diabetes, other factors may be involved since a weak hypoglycemic like TAU demonstrated in vivo antioxidant actions that were comparable to those of more potent hypoglycemic agents like INS and MET.

Changes in glycaemic control of oral anti-diabetic medications assessed by continuous glucose monitors among patients with type 2 diabetes: a protocol of network meta-analysis.

BACKGROUND: Continuous glucose monitors (CGMs) can measure interstitial fluid glucose levels to provide comprehensive real-time glucose profile among people with type 2 diabetes. These can accurately detect glucose levels, hyperglycaemia and hypoglycaemia events compared with conventional self-monitoring. Increased application of CGMs provides a valuable opportunity to evaluate glucose control on oral anti-diabetic medications. This review will compare the efficacy and safety of oral anti-diabetic medications among patients with type 2 diabetes, evaluated by CGM. METHODS: The following databases will be searched: Cochrane Library, PubMed, EMBASE, CINAHL, PsycINFO, Scopus and grey literature (ClinicalTrials.gov, PsycEXTRA, ProQuest Dissertations, Google Scholar and Theses Global) for the identification of studies. The review will include and summarise evidence from randomised clinical trials that use CGMs for blood glucose management in adults (aged ≥ 18 years), published in English between January 2000 and May 2021 without any restrictions of countries. Reference list of all selected articles will independently be screened to identify additional studies left out in the initial search. Primary outcomes will be HbA1c (≤ 7.0%), time spent with hypoglycaemia (< 70 mg/dl) or hyperglycaemia (≥ 180 mg/dl). Secondary outcomes will be change in weight, blood pressure and related comorbidities (cardiovascular mortality, heart failure events, myocardial infarction and stroke). Study selection, data extraction and quality assessment will be conducted independently by at least two reviewers. A third reviewer will determine and resolve discrepancies. At least two independent reviewers will cross-check data synthesis. The quality of evidence of the review will be assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Tool. DISCUSSION: The review is anticipated to provide up to date evidence for further studies and clinic practices regarding glycaemic control, hypoglycaemia, and hyperglycaemia issues. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION: PROSPERO CRD42020188399 .

Combination therapy of bioactive compounds with acarbose: A proposal to control hyperglycemia in type 2 diabetes.

Type 2 diabetes (T2D) is a chronic metabolic disease with a high impact on public health and social welfare. Hyperglycemia is a characteristic of T2D that leads to different complications. Acarbose (ACB) reduces hyperglycemia by inhibiting α-amylase (AMY) and α-glucosidase (GLU) enzymes. However, ACB causes low adherence to treatment by patients with diabetes due to its side effects. Consequently, reducing the side effects produced by ACB without compromising its efficacy is a challenge in treating T2D. Bioactive compounds (BC) are safe and could decrease the side effects compared to antidiabetic drugs such as ACB. Nevertheless, their efficacy alone concerning that drug is unknown. The scientific advances have been directed toward searching for new approaches, such as combination therapies between BC and ACB. This review analyzes the combined therapy of BC (extracts or isolates) with ACB in inhibiting AMY and GLU as a proposal to control hyperglycemia in T2D. PRACTICAL APPLICATION: Postprandial hyperglycemia is one most typical signs of type 2 diabetes, and it can have significant consequences, including cardiovascular problems. Acarbose has side effects that lead to the abandonment of treatment. Bioactive compounds in extracts or isolated forms have become a viable option for controlling hyperglycemia without side effects, but their administration alone is insufficient. The scientific advances of acarbose/bioactive compound combination therapy as a proposal for controlling hyperglycemia in T2D were analyzed. The findings suggested that bioactive compounds combined with acarbose are effective when they function synergistically or additively; however, they are not recommended in therapy when they have an antagonistic effect.

Assessment of the Effectiveness of a Protocol to Manage Dexamethasone-Induced Hyperglycemia Among Hospitalized Patients With COVID-19.

OBJECTIVE: Well-controlled glucose levels (ie, 70-180 mg/dL) have been associated with lower mortality from COVID-19. The addition of dexamethasone to COVID-19 treatment protocols has raised concerns about the potential negative consequences of dexamethasone-induced hyperglycemia. METHODS: We developed a protocol to guide the management of dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19. Two of the 4 medical teams managing patients with COVID-19 at a tertiary center in Saudi Arabia used the protocol and the other 2 teams continued to manage hyperglycemia at the discretion of the treating physicians (protocol and control groups, respectively). The glycemic control and clinical outcomes in 163 patients hospitalized with COVID-19 and dexamethasone-induced hyperglycemia between July 5th and September 30th, 2020, were retrospectively compared between the 2 groups. RESULTS: Compared to the control group, the protocol group had higher proportions of patients with well-controlled glucose across all premeals and bedtime glucose readings throughout the hospital stay. The differences in glycemic control between the 2 groups were statistically significant for fasting glucose on days 4, 5, and the discharge day; prelunch glucose on the discharge day; predinner glucose on days 3, 5, and the discharge day; and bedtime glucose on day 1 (all P < .05). After adjusting for age, sex, nationality, body mass index, Charlson score, and diabetes status, patients in the protocol group were more likely to have well-controlled glucose levels compared with those in the control group. Moreover, the in-hospital mortality was significantly lower in the protocol group (12.93%) compared to the control group (29.93%) (P < .01). CONCLUSION: The implementation of a protocol to manage dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19 resulted in more patients achieving well-controlled glucose levels and was associated with lower mortality from COVID-19.

Black Patients with Ischemic Stroke and Hyperglycemia have Worse outcome than Whites if given Intensive Glucose Control.

BACKGROUND: Hyperglycemia is common after acute ischemic stroke and is associated with worse outcome, but intensive glucose control has not improved outcome. There is also a racial disparity in outcome after stroke, with Black patients more likely to have functional impairment than whites. We aimed to evaluate if there were racial differences in outcomes in acute ischemic stroke patients treated with intensive glucose control. METHODS: We performed a post-hoc analysis of the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial to determine if Black patients had worse functional outcome than whites and if standard versus intensive glucose control modified that association. We included non-Hispanic white and Black patients. The primary outcome was excellent functional outcome (90-day modified Rankin Score of 0-1). To account for patient clustering by study site, we fit mixed-effects logistic regression models to our outcome and tested the interaction of treatment and race. RESULTS: We included 895 patients, of which 304 (34%) were Black and 591 (66%) were white. The rate of excellent outcome was 31.6% in Black patients versus 41.0% in white patients (p=0.006). After adjusting for potential confounders, the odds ratio for excellent outcome in Black patients was 0.54 (95% CI 0.38-0.77). The interaction term between treatment and race was significant (p=0.067). In the intensive treatment arm, Black patients had a predicted probability of excellent outcome of 26.4% (20.1-32.8) versus 42.7% (37.6-47.9) for white patients (p<0.001), while in the standard treatment arm the difference was not significant. CONCLUSIONS: Black patients with acute ischemic stroke and hyperglycemia had worse functional outcome at 90 days than white patients, particularly if given intensive glucose control. These findings are from a post-hoc analysis and may be confounded, thus warrant additional study.

Hyperglycemia requiring insulin during acute lymphoblastic leukemia induction chemotherapy is associated with increased adverse outcomes and healthcare costs.

BACKGROUND: Hyperglycemia is a complication of induction chemotherapy in 10%-50% of pediatric patients with acute lymphoblastic leukemia (ALL). Though hyperglycemia in ALL patients is usually transient, it may be associated with adverse health outcomes. However, the risk factors for and consequences of hyperglycemia are poorly understood. We hypothesized that hyperglycemia significant enough to require insulin therapy during induction chemotherapy would be associated with increased morbidity and mortality in pediatric ALL patients during induction chemotherapy and in subsequent care. METHODS: We abstracted clinical and resource utilization data from the Pediatric Health Information System (PHIS) database utilizing ICD-9 codes and medication charges. We used logistic regression analysis to predict the development of hyperglycemia. The effects of hyperglycemia on binary and count adverse outcomes following induction chemotherapy were modeled using mixed-effect regression models. RESULTS: An increased risk of hyperglycemia requiring insulin was associated with older age, female sex, higher risk group and trisomy 21. Patients on insulin for hyperglycemia had increased mortality following induction chemotherapy. These patients were more likely to have subsequent infectious complications, need for bone marrow transplant, and risk of disease relapse. They also had greater length of inpatient stay, higher cost of care, and were more likely to require intensive care unit admission during induction chemotherapy. CONCLUSIONS: Hyperglycemia requiring insulin during induction chemotherapy in pediatric ALL is associated with an increased risk of short-term and long-term complications. Prospective studies are needed to analyze formal screening, preventive measures, and optimal management practices for hyperglycemia during ALL induction chemotherapy.

Diabetes Technology in the Inpatient Setting for Management of Hyperglycemia.

In past decades, a rapid evolution of diabetes technology led to increased popularity and use of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) in the ambulatory setting for diabetes management, and recently, the artificial pancreas became available. Efforts to translate this technology to the hospital setting have shown accuracy and reliability of CGM, safety of CSII in appropriate populations, improvement of inpatient glycemic control with computerized glycemic management systems, and feasibility of inpatient CGM-CSII closed-loop systems. Several ongoing studies are focusing on continued translation of this technology to improve glycemic control and outcomes in hospitalized patients.

Comparison of clinical pharmacy specialists and usual care in outpatient management of hyperglycemia in Veterans Affairs medical centers.

PURPOSE: The results of a study to assess the effectiveness and safety of hyperglycemia management provided by clinical pharmacy specialists (CPSs) versus usual care in outpatients with diabetes from 53 Veterans Affairs (VA) medical centers are reported. METHODS: An historical cohort study of outpatients with baseline glycosylated hemoglobin (HbA1c) values of >9% who were referred to a CPS for management of hyperglycemia and primary care patients who were not referred to a CPS was conducted. The primary outcomes were change in HbA1c over time and time to reach an HbA1c value of <8%. Secondary outcomes included the number of visits to achieve an HbA1c value of <8%, proportion of patients with an HbA1c value of <6% who were receiving secretagogues, and proportion of patients with serious hypoglycemia. RESULTS: After propensity score matching by baseline characteristics, there were 12,327 patients in each group. The mean ± S.D. number of visits to reach an HbA1c value of <8% was 2.46 ± 1.58 in the pharmacist-managed group and 1.82 ± 1.27 with usual care (p < 0.001). The proportion of patients with an HbA1c value of <6% who were receiving secretagogues was 39.9% with pharmacist-managed care and 38.6% with usual care (p = 0.73). Serious hypoglycemia was noted in 4.3% of pharmacist-managed patients and 3.1% of usual care patients (p < 0.001). CONCLUSION: Data from 53 VA medical centers revealed that CPSs managed the care of ambulatory care patients with hyperglycemia as well as primary care providers.

Inequalities in glycemic control in childhood onset type 2 diabetes in England and Wales-A national population-based longitudinal study.

BACKGROUND: Not much is known about glycaemic-control trajectories in childhood-onset type 2 diabetes (T2D). We investigated characteristics of children and young people (CYP) with T2D and inequalities in glycemic control. METHODS: We studied 747 CYP with T2D, <19 years of age in 2009-2016 (from the total population-based National Pediatric Diabetes Audit [>95% diabetes cases in England/Wales]). Linear mixed-effects modeling was used to assess socioeconomic and ethnic differences in longitudinal glycated hemoglobin (HbA1c ) trajectories during 4 years post-diagnosis (3326 HbA1c data points, mean 4.5 data points/subject). Self-identified ethnicity was grouped into six categories. Index of Multiple Deprivation (a small geographical area-level deprivation measure) was grouped into SES quintiles for analysis. RESULTS: Fifty-eight percent were non-White, 66% were female, and 41% were in the most disadvantaged SES quintile. Mean age and HbA1c at diagnosis were 13.4 years and 68 mmol/mol, respectively. Following an initial decrease between diagnosis and end of year 1 (-15.2 mmol/mol 95%CI, -19.2, -11.2), HbA1c trajectories increased between years 1 and 3 (10 mmol/mol, 7.6, 12.4), followed by slight gradual decrease subsequently (-1.6 mmol/mol, -2, -1.1). Compared to White CYP, Pakistani children had higher HbA1c at diagnosis (13.2 mmol/mol, 5.6-20.9). During follow-up, mixed-ethnicity and Pakistani CYP had poorer glycemic control. Compared to children in the most disadvantaged quintile, those in the most advantaged had lower HbA1c at diagnosis (-6.3 mmol, -12.6, -0.1). Differences by SES remained during follow-up. Mutual adjustment for SES and ethnicity did not substantially alter the above estimates. CONCLUSIONS: About two-thirds of children with childhood-onset T2D were non-White, female adolescents, just under half of whom live in the most disadvantaged areas of England and Wales. Additionally, there are substantial socioeconomic and ethnic inequalities in diabetes control.

Glycemic control outcomes of manual and computerized insulin titration protocols: a systematic review protocol.

OBJECTIVE: The object of this systematic review is to determine the effectiveness of computerized insulin titration protocols compared to manual insulin titration protocols for glycemic control in hospitalized adult patients. INTRODUCTION: Hyperglycemia is common during acute illness, and current recommendations for patients with altered glucose metabolism is the use of intravenous insulin therapy. Due to the narrow therapeutic index of insulin, euglycemia is difficult to achieve and requires frequent dose titrations and blood glucose checks. Dose titrations can be accomplished through the use of manual or computerized insulin titration protocols. INCLUSION CRITERIA: This review will consider studies that compare manual and computerized insulin titration protocols for hospitalized adult patients requiring intravenous insulin therapy for hyperglycemia. Studies must have considered one or more glycemic control outcomes. METHODS: This systematic review will use the JBI methodology for evidence of effectiveness. The search will be limited to studies published in English from 1984, as this was the approximate year that the first pilot study of a computerized titration protocol was implemented. The databases to be searched include: Cochrane Central Register of Controlled Trials, CINAHL, PubMed, Embase, Health Technology Assessments and Ovid Healthstar. The trial registers to be searched include: US National Library of Medicine (ClinicalTrials.gov). The search for unpublished studies will include ProQuest Dissertations and Theses, and MedNar. Retrieval of full-text studies, assessment of methodological quality and data extraction will be performed independently by two reviewers. Meta-analysis will be performed if possible, and a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Summary of Findings presented. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019142776.

Amelioration of diabetic nephropathy using pomegranate peel extract-stabilized gold nanoparticles: assessment of NF-κB and Nrf2 signaling system.

BACKGROUND: Diabetic nephropathy (DN), an end-stage renal disorder, has posed a menace to humankind globally, because of its complex nature and poorly understandable intricate mechanism. In recent times, functional foods as potential health benefits have been gaining attention of consumers and researchers alike. Rich in antioxidants, the peel and seed of pomegranate have previously demonstrated protection against oxidative-stress-related diseases, including cardiovascular disorders, diabetes, and cancer. PURPOSE: This study was designed to investigate the ameliorative role of pomegranate peel extract-stabilized gold nanoparticle (PPE-AuNP) on streptozotocin (STZ)-induced DN in an experimental murine model. METHODS: Following the reduction methods, AuNP was prepared using the pomegranate peel ellagitannins and characterized by particle size, physical appearance, and morphological architecture. Modulatory potential of PPE-AuNP was examined through the plethora of biochemical and high throughput techniques, flow cytometry, immunoblotting, and immunofluorescence. RESULTS: The animals treated with PPE-AuNP markedly reduced the fasting blood glucose, renal toxicity indices, and serum TC and TG in a hyperglycemic condition. As evident from an increased level of plasma insulin level, PPE-AuNP normalized the STZ-induced pancreatic ß-cell dysfunction. The STZ-mediated suppression of endogenous antioxidant response was restored by the PPE-AuNP treatment, which reduced the generation of LPO as well as iROS. Furthermore, the hyperglycemia-mediated augmentation of protein glycation, followed by the NOX4/p-47phox activation, diminished with the application of PPE-AuNP. The histological and immunohistochemical findings showed the protective efficacy of PPE-AuNP in reducing STZ-induced glomerular sclerosis and renal fibrosis. In addition, it reduced proinflammatory burden through the modulation of the MAPK/NF-κB/STAT3/cytokine axis. Simultaneously, PI3K/AKT-guided Nrf2 activation was evident upon the PPE-AuNP application, which enhanced the antioxidant response and maintained hyperglycemic homeostasis. CONCLUSION: The findings indicate that the use of PPE-AuNPs might act as an economic therapeutic remedy for alleviating DN.

Assessment of the efficacy and safety of a protocol to manage glucocorticoid-induced hyperglycemia in diabetic patients during hospital stay. / Evaluación de la eficacia y la seguridad de un protocolo de manejo de pacientes con diabetes descompensada por glucocorticoides durante la hospitalización.

INTRODUCTION: There are no agreed protocols on hospital management of hyperglycemic decompensation induced by pharmacological doses of glucocorticoids (GCs). The study objective was to assess the efficacy and safety of an insulin therapy protocol specific for patients treated with glucocorticoids (CP) as compared to a general protocol (GP) in diabetes decompensation secondary to glucocorticoids. Materials and methods An experimental study in patients with glucocorticoids-induced decompensated diabetes admitted to a respiratory ward including a non-randomized control group. Two protocols (CP and GP), both based on basal-bolo insulin regimens, but with different insulin doses and distribution, were compared. The difference in mean blood glucose (MBG) levels between both protocols was measured during hospital stay, as was the risk of having MBG levels > 200mg/dL, adjusted for potential confounding factors (related to patients and to the glucocorticoid therapy used). RESULTS: A total of 131 patients were included, 60 assigned to the GP and 71 to the CP groups. Seventy-four percent of patients had been admitted due to COPD exacerbation. There was a significant difference in the total daily insulin dose used between the CP and GP groups (29.4 vs. 57.4 IU; P<.0001). The adjusted difference in MBG levels (CP-GP) was -14.8 (95% CI, -26.2 to -3.3) mg/dL. Patients in the CP group had a lower adjusted risk of having MBG levels >200mg/dL during hospital admission (OR=0.31; 95% CI, 0.11-0.91; P=.033). There were no differences in the risk of severe hypoglycemia between the CP and GP groups (0% vs. 1.4%; P=.36). CONCLUSIONS: The study protocol has been shown to decrease MBG levels in patients with glucocorticoids-induced decompensation of diabetes during hospital admission without compromising their safety.

Prevalence, Correlates and Management of Hyperglycemia in Diabetic Non-critically Ill Patients at a Tertiary Care Center in Lebanon.

BACKGROUND: Diabetes Mellitus is a chronic metabolic disease that affects 387 million people around the world. Episodes of hyperglycemia in hospitalized diabetic patients are associated with poor clinical outcomes and increased morbidity and mortality. Therefore, prevention of hyperglycemia is critical to decrease the length of hospital stay and to reduce complications and readmissions. OBJECTIVE: The study aims to examine the prevalence of hyperglycemia and assess the correlates and management of hyperglycemia in diabetic non-critically ill patients. METHODS: The study was conducted on the medical wards of a tertiary care teaching hospital in Lebanon. A retrospective chart review was conducted from January 2014 until September 2015. Diabetic patients admitted to Internal Medicine floors were identified. Descriptive analysis was first carried out, followed by a multivariable analysis to study the correlates of hyperglycemia occurrence. RESULTS: A total of 235 medical charts were reviewed. Seventy percent of participants suffered from hyperglycemia during their hospital stay. The identified significant positive correlates for inpatient hyperglycemia, were the use of insulin sliding scale alone (OR=16.438 ± 6.765-39.941, p=0.001) and the low frequency of glucose monitoring. Measuring glucose every 8 hours (OR= 3.583 ± 1.506-8.524, p=0.004) and/or every 12 hours (OR=7.647 ± 0.704-79.231, p=0.0095) was associated with hyperglycemia. The major factor perceived by nurses as a barrier to successful hyperglycemia management was the lack of knowledge about appropriate insulin use (87.5%). CONCLUSION: Considerable mismanagement of hyperglycemia in diabetic non-critically ill patients exists; indicating a compelling need for the development and implementation of protocol-driven insulin order forms a comprehensive education plan on the appropriate use of insulin.

Spanish Diabetes Society (SED) recommendations for the pharmacologic treatment of hyperglycemia in type 2 diabetes: 2018 Update. / Recomendaciones de la Sociedad Española de Diabetes (SED) para el tratamiento farmacológico de la hiperglucemia en la diabetes tipo 2: Actualización 2018.

Type 2 diabetes mellitus (DM2) has become a problem of global dimensions by their high and growing prevalence worldwide and the personal and economic costs associated with it. Correct treatment can reduce mortality and associated complications. New concepts have recently been included in routine clinical practice and have changed the algorithm of DM2 pharmacological therapy. Therefore, the Spanish Society of Diabetes (SED) entrusted to the Working Group of Consensus and Clinical Guidelines an update of the 2010 document Recommendations for Pharmacological Treatment of Hyperglycemia in Diabetes type2. Novel aspects include nine characteristics to describe each drug group: efficiency, the risk of hypoglycemia, effects on body weight, the demonstrated effect in cardiovascular risk, nephroprotection, limitation of use in renal insufficiency, the rate of secondary effects, complexity and costs. Additionally, the document details combination options, and develop the start and adjustment of available injectable therapies.

Norbixin, an apocarotenoid derivative activates PPARγ in cardiometabolic syndrome: Validation by in silico and in vivo experimental assessment.

The increased prevalence of cardio-metabolic disorders worldwide prompted the exploration of new strategies for its treatment. Peroxisome Proliferator activated receptor (PPAR) play major role in regulation of lipid as well as glucose metabolism and thus, natural PPARγ activators seem to be drug of choice. AIMS: In the present work, we studied norbixin which is a natural apocarotenoid derivative for its agonistic activity for PPAR γ followed by in vivo studies for amelioration of cardio-metabolic syndrome (CMetS). MAIN METHODS: The methods include computational studies, TR-FRET binding analysis and in vivo studies on high fat diet induced rats. KEY FINDINGS: Molecular docking and molecular dynamics (MD) simulation studies showed that norbixin could be embedded into hydrophobic pocket of PPARγ and stable hydrogen bonding interactions were found with residues Glu273, Tyr327, Ser289, His323, His449 and Tyr473 of PPARγ. These results were substantiated by significant in vitro PPAR agonistic activity of norbixin in TR-FRET binding assay studies. The experimental results of norbixin in high fat diet induced CMetS in rats further confirmed that norbixin decreased insulin resistance (IR), hyperglycemia and dyslipidemia. These results were accompanied by reduced inflammatory marker hs-CRP as well as decreased oxidative stress and arterial pressure. The histopathology of heart sections also showed that norbixin could prevent the abnormal fibrotic changes in heart. Furthermore, PPARγ protein expressions were increased, whereas NF-κB expression was decreased by norbixin treatment in western blot studies. SIGNIFICANCE: These results validate norbixin as a novel PPARγ agonist and prove therapeutic potential of norbixin in treatment of CMetS.

Reducing Treatment Errors Through Point-of-Care Glucometer Configuration.

BACKGROUND: Blood glucose (BG) testing is the most widely performed point-of-care (POC) test in a hospital setting. Multiple adverse events reported to the Food and Drug Administration (FDA) revealed that treatment decisions may be affected by information displayed on the POC glucometer's results screen. A randomized, crossover simulation study was conducted to compare two results screen configurations for ACCU-CHEK Inform II, a POC glucometer. METHODS: Prior to the study, a heuristic evaluation of the results screen configurations and a pilot study were conducted to select the two results screen configurations for comparison. At two multicampus medical centers, 66 nurse participants experienced two computer-based simulation scenarios that asked them to interpret glucometer readings and make treatment decisions for simulated patients with 32 mg/dL BG levels and subtle symptoms of hypoglycemia. One scenario displayed a numeric value ("32 mg/dL"), and the other displayed a range abbreviation, such as "RR LO" (out of reportable range; low). Treatment errors were recorded when the participant did not treat the hypoglycemic patient with glucose or when they administered insulin. RESULTS: When ACCU-CHEK Inform II displayed an "RR LO" reading, 10.6% of participants made a treatment error, including 6.7% of participants with prior training on the meaning of an "RR LO" reading. None of the participants made a treatment error when ACCU-CHEK Inform II displayed a "32 mg/dL" reading. CONCLUSION: Displaying a numeric BG reading eliminated potentially life-threating treatment errors caused by confusing range abbreviations. Manufacturers should consider these findings during future research and development of POC glucometers.

Real-world use of self-monitoring of blood glucose in people with type 2 diabetes: an urgent need for improvement.

AIMS: To assess use of self-monitoring of blood glucose (SMBG) in type 2 diabetes (T2DM) in the context of a continuous quality improvement initiative (AMD Annals). METHODS: 14 quality-of-care indicators were developed, including frequency of SMBG, fasting blood glucose (FBG), and post-prandial glucose (PPG) levels, and hypoglycemia and hyperglycemia episodes. Clinical data and SMBG values downloaded from any glucose meter were obtained from electronic medical records. The most frequently used glucose-lowering treatment regimens were identified and the indicators were assessed separately by regimen. RESULTS: Overall, 21 Italian centers and 13,331 patients (accounting for 35,657 HbA1c tests and 8.44 million SMBG values collected during 2014 and 2015) were included in the analysis; 11 therapeutic regimens were selected. Patients in regimens not including insulin performed 15-23 measurements per patient-month, those treated with basal insulin 32.1 tests/patient-month, and those treated with basal and short-acting insulin 53-58 tests/patient-month. In all treatment regimens, PPG measurements represented a minority of all tests; pre-breakfast measurements accounted for about 50% of all FBG values. Mean FBG levels exceeded 130 mg/dl in 49.3-88.3% of the cases in the different treatment regimens, while PPG levels were over 140 mg/dl in 46.7-81.0%. From 5.7 to 32.7%, patients in the different regimens had at least one episode of hypoglycemia (< 70 mg/dl), while from 3.7 to 47.7% had at least one episode of hyperglycemia (> 300 mg/dl). CONCLUSIONS: SMBG is underutilized in patients with T2DM treated or not with insulin. In all treatment groups, PPG is seldom investigated. Poor metabolic control and rates of hyper- and hypoglycemia deserve consideration in all treatment groups.

Incidence and management of postoperative hyperglycemia in patients undergoing insulinoma resection.

PURPOSE: It has been proposed that rebound hyperglycemia after resection of insulinoma indicates a biochemical cure. However, there is scant objective data in the literature on the rate and need for intervention in hyperglycemia in patients undergoing resection of insulinoma. The goal of our study was to evaluate the rate of postoperative hyperglycemia, any predisposing factors, and the need for intervention in a prospective cohort study of all patients undergoing routine glucose monitoring. METHODS: A retrospective analysis of 33 patients who had an insulinoma resected and who underwent routine postoperative monitoring of blood glucose (every hour for the first six hours then every four hours for the first 24 h) was performed. Hyperglycemia was defined as glucose greater than 180 mg/dL (10 mmol/l). RESULTS: Twelve patients (36%) developed hyperglycemia within 24 h (range 1-16 h). In patients with hyperglycemia, the mean maximum plasma glucose level was 221.5 mg/dL (range 97-325 mg/dL) (12.3 mmol/l), and four (33%) patients were treated with insulin. There was no significant difference in age, gender, body mass index (BMI), tumor size, biochemical profile, or surgical approach and extent of pancreatectomy between patients who developed hyperglycemia and those who did not. Pre-excision and post-excision intraoperative insulin levels were evaluated in 14 of 33 patients. The percentage decrease of the intraoperative insulin levels was not significantly different between patients who developed hyperglycemia and those who did not. All patients with postoperative hyperglycemia had normalization of their glucose levels, and none were discharged on anti-hyperglycemic agents. CONCLUSIONS: Hyperglycemia is common after insulinoma resection, and a subset of patients require transient treatment with insulin.