Asociación entre Glucemia inestable, tiempo de estancia y mortalidad de pacientes en estado críticos: Estudio de cohorte / Associação Entre Glicemia Instável, Tempo de Permanência e Mortalidade de Pacientes Críticos: Estudo de Coorte / Relationships between unstable Glycemia, Hospital Length Of Stay, and mortality In Critically Ill patients: A cohort study

Resumen Introducción: El control y la evaluación de los niveles glucémicos de pacientes en estado críticos es un desafío y una competencia del equipo de enfermería. Por lo que, determinar las consecuencias de esta durante la hospitalización es clave para evidenciar la importancia del oportuno manejo. Objetivo: Determinar la asociación entre la glucemia inestable (hiperglucemia e hipoglucemia), el resultado de la hospitalización y la duración de la estancia de los pacientes en una unidad de cuidados intensivos. Metodología: Estudio de cohorte prospectivo realizado con 62 pacientes a conveniencia en estado crítico entre marzo y julio de 2017. Se recogieron muestras diarias de sangre para medir la glucemia. Se evaluó la asociación de la glucemia inestable con la duración de la estancia y el resultado de la hospitalización mediante ji al cuadrado de Pearson. El valor de p<0.05 fue considerado significativo. Resultados: De las 62 personas participantes, 50 % eran hombres y 50 % mujeres. La edad media fue de 63.3 años (±21.4 años). La incidencia de glucemia inestable fue del 45.2 % y se asoció con una mayor duración de la estancia en la UCI (p<0.001) y una progresión a la muerte como resultado de la hospitalización (p=0.03). Conclusión: Entre quienes participaron, la glucemia inestable se asoció con una mayor duración de la estancia más prolongada y con progresión hacia la muerte, lo que refuerza la importancia de la actuación de enfermería para prevenir su aparición.

Resumo Introdução: O controle e avaliação dos níveis glicêmicos em pacientes críticos é um desafio e uma competência da equipe de enfermagem. Portanto, determinar as consequências da glicemia instável durante a hospitalização é chave para evidenciar a importância da gestão oportuna. Objetivo: Determinar a associação entre glicemia instável (hiperglicemia e hipoglicemia), os desfechos hospitalares e o tempo de permanência dos pacientes em uma unidade de terapia intensiva. Métodos: Um estudo de coorte prospectivo realizado com 62 pacientes a conveniência em estado crítico entre março e julho de 2017. Foram coletadas amostras diariamente de sangue para medir a glicemia. A associação entre a glicemia instável com o tempo de permanência e o desfecho da hospitalização foi avaliada pelo teste qui-quadrado de Pearson. O valor de p <0,05 foi considerado significativo. Resultados: Das 62 pessoas participantes, 50% eram homens e 50% mulheres. A idade média foi de 63,3 anos (±21,4 anos). A incidência de glicemia instável foi de 45,2% e se associou a um tempo de permanência mais prolongado na UTI (p <0,001) e uma progressão para óbito como desfecho da hospitalização (p = 0,03). Conclusão: Entre os participantes, a glicemia instável se associou a um tempo mais longo de permanência e com progressão para óbito, enfatizando a importância da actuação da equipe de enfermagem para prevenir sua ocorrência.

Abstract Introduction: The control and evaluation of glycemic levels in critically ill patients is a challenge and a responsibility of the nursing team; therefore, determining the consequences of this during hospitalization is key to demonstrate the importance of timely management. Objective: To determine the relationship between unstable glycemia (hyperglycemia and hypoglycemia), hospital length of stay, and the hospitalization outcome of patients in an Intensive Care Unit (ICU). Methods: A prospective cohort study conducted with 62 critically ill patients by convenience sampling between March and July 2017. Daily blood samples were collected to measure glycemia. The correlation of unstable glycemia with the hospital length of stay and the hospitalization outcome was assessed using Pearson's chi-square. A p-value <0.05 was considered significant. Results: Among the 62 patients, 50% were male and 50% were female. The mean age was 63.3 years (±21.4 years). The incidence of unstable glycemia was 45.2% and was associated with a longer ICU stay (p<0.001) and a progression to death as a hospitalization outcome (p=0.03). Conclusion: Among critically ill patients, unstable glycemia was associated with an extended hospital length of stay and a progression to death, emphasizing the importance of nursing intervention to prevent its occurrence.

Rest-activity rhythm disruption and metabolic health in schizophrenia: a cross-sectional actigraphy study of community-dwelling people living with schizophrenia and non-psychiatric comparison participants.

STUDY OBJECTIVES: People living with schizophrenia (PLWS) have increased physical comorbidities and premature mortality which may be linked to dysregulated rest-activity rhythms (RARs). This study aimed to compare RARs between PLWS and non-psychiatric comparison participants (NCs); examine the relationships of RARs with age, sleep, metabolic and physical health outcomes; and, among PLWS, relationships of RARs with illness-related factors. METHODS: The study sample included 26 PLWS and 36 NCs, assessed with wrist-worn actigraphy to compute RAR variables and general sleep variables. Participants completed assessments for clinical symptoms, physical health, sleep quality, medication use, and assays for fasting glycosylated hemoglobin (HbA1c) levels. We examined group differences in RAR and sleep variables, relationships of RAR variables with metabolic and physical health measures, and, among PLWS, relationships between RAR variables and illness-related measures. RESULTS: PLWS had significantly shorter active periods, lower relative amplitude, and lower mean activity during their most active 10 hours compared to the NCs (Cohen's d=.79, .58, and .62; respectively). PLWS had poorer sleep quality, greater mean percent sleep, less wake after sleep onset, and higher total sleep time (TST) variability compared to NCs. PLWS had higher rates of antidepressant, anxiolytic, and antipsychotic medication use compared to NCs, which may have impacted sleep quality and objective sleep measures. Across both groups, more fragmented and variable RARs were associated with higher HbA1c levels (ηp2=0.10) and worse physical health (ηp2=0.21). Among PLWS, RARs were correlated with TST (rs=.789, p<0.01) and percent sleep (rs=.509, p<0.05), but not with age, sleep quality, or other illness-related factors. CONCLUSIONS: RARs provide unique information about sleep and activity for PLWS and have the potential for targeted interventions to improve metabolic health and mortality.

Associations between cardiometabolic indices and the risk of diabetic kidney disease in patients with type 2 diabetes.

BACKGROUND: This study was designed to assess the associations between emerging cardiometabolic indices-the atherogenic index of plasma (AIP), the stress hyperglycemia ratio (SHR), the triglyceride-glucose (TyG) index, and the homeostasis model assessment of insulin resistance (HOMA-IR)-and the incidence of diabetic kidney disease (DKD) in type 2 diabetes (T2D) patients. METHODS: We consecutively enrolled 4351 T2D patients. The AIP, SHR, TyG index, and HOMA-IR were calculated from baseline parameters. DKD was defined as a urine albumin/creatinine ratio > 30 mg/g or an eGFR < 60 mL/min per 1.73 m. All participants were categorized into tertiles based on the cardiometabolic indices. Multivariate logistic regression models, restricted cubic splines, and receiver operating characteristic (ROC) curves were used for analysis. RESULTS: A total of 1371 (31.5%) patients were diagnosed with DKD. A restricted cubic spline showed a J-shaped association of the AIP and TyG index with DKD, a log-shaped association between HOMA-IR and DKD, and a U-shaped association between the SHR and DKD incidence. Multivariate logistic regression revealed that individuals in the highest tertile of the four cardiometabolic indices had a significantly greater risk of DKD than did those in the lowest tertile (AIP: OR = 1.08, 95% CI = 1.02-1.14, P = 0.005; SHR: OR = 1.42, 95% CI = 1.12-1.81, P = 0.004; TyG index: OR = 1.86, 95% CI = 1.42-2.45, P < 0.001; HOMA-IR: OR = 2.24, 95% CI = 1.52-3.30, P < 0.001). The receiver operating characteristic curves showed that the HOMA-IR score was better than other indices at predicting the risk of DKD, with an optimal cutoff of 3.532. CONCLUSIONS: Elevated AIP, SHR, TyG index and HOMA-IR are associated with a greater risk of DKD in patients with T2D. Among these indices, the HOMA-IR score demonstrated the strongest association with and predictive value for DKD incidence.

Effects of the stress hyperglycemia ratio on long-term mortality in patients with triple-vessel disease and acute coronary syndrome.

AIMS: Risk assessment for triple-vessel disease (TVD) remain challenging. Stress hyperglycemia represents the regulation of glucose metabolism in response to stress, and stress hyperglycemia ratio (SHR) is recently found to reflect true acute hyperglycemic status. This study aimed to evaluate the prognostic value of SHR and its role in risk stratification in TVD patients with acute coronary syndrome (ACS). METHODS: A total of 3812 TVD patients with ACS with available baseline SHR measurement were enrolled from two independent centers. The endpoint was cardiovascular mortality. Cox regression was used to evaluate the association between SHR and cardiovascular mortality. The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) II (SSII) was used as the reference model in the model improvement analysis. RESULTS: During a median follow-up of 5.1 years, 219 (5.8%) TVD patients with ACS suffered cardiovascular mortality. TVD patients with ACS with high SHR had an increased risk of cardiovascular mortality after robust adjustment for confounding (high vs. median SHR: adjusted hazard ratio 1.809, 95% confidence interval 1.160-2.822, P = 0.009), which was fitted as a J-shaped pattern. The prognostic value of the SHR was found exclusively among patients with diabetes instead of those without diabetes. Moreover, addition of SHR improved the reclassification abilities of the SSII model for predicting cardiovascular mortality in TVD patients with ACS. CONCLUSIONS: The high level of SHR is associated with the long-term risk of cardiovascular mortality in TVD patients with ACS, and is confirmed to have incremental prediction value beyond standard SSII. Assessment of SHR may help to improve the risk stratification strategy in TVD patients who are under acute stress.

Implementation of an Electronic Clinical Decision Support System for the Early Recognition and Management of Dysglycemia in an Inpatient Mental Health Setting Using CogStack: Protocol for a Pilot Hybrid Type 3 Effectiveness-Implementation Randomized Controlled Cluster Trial.

BACKGROUND: Severe mental illnesses (SMIs), including schizophrenia, bipolar affective disorder, and major depressive disorder, are associated with an increased risk of physical health comorbidities and premature mortality from conditions including cardiovascular disease and diabetes. Digital technologies such as electronic clinical decision support systems (eCDSSs) could play a crucial role in improving the clinician-led management of conditions such as dysglycemia (deranged blood sugar levels) and associated conditions such as diabetes in people with a diagnosis of SMI in mental health settings. OBJECTIVE: We have developed a real-time eCDSS using CogStack, an information retrieval and extraction platform, to automatically alert clinicians with National Health Service Trust-approved, guideline-based recommendations for dysglycemia monitoring and management in secondary mental health care. This novel system aims to improve the management of dysglycemia and associated conditions, such as diabetes, in SMI. This protocol describes a pilot study to explore the acceptability, feasibility, and evaluation of its implementation in a mental health inpatient setting. METHODS: This will be a pilot hybrid type 3 effectiveness-implementation randomized controlled cluster trial in inpatient mental health wards. A ward will be the unit of recruitment, where it will be randomly allocated to receive either access to the eCDSS plus usual care or usual care alone over a 4-month period. We will measure implementation outcomes, including the feasibility and acceptability of the eCDSS to clinicians, as primary outcomes, alongside secondary outcomes relating to the process of care measures such as dysglycemia screening rates. An evaluation of other implementation outcomes relating to the eCDSS will be conducted, identifying facilitators and barriers based on established implementation science frameworks. RESULTS: Enrollment of wards began in April 2022, after which clinical staff were recruited to take part in surveys and interviews. The intervention period of the trial began in February 2023, and subsequent data collection was completed in August 2023. Data are currently being analyzed, and results are expected to be available in June 2024. CONCLUSIONS: An eCDSS can have the potential to improve clinician-led management of dysglycemia in inpatient mental health settings. If found to be feasible and acceptable, then, in combination with the results of the implementation evaluation, the system can be refined and improved to support future successful implementation. A larger and more definitive effectiveness trial should then be conducted to assess its impact on clinical outcomes and to inform scalability and application to other conditions in wider mental health care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04792268; https://clinicaltrials.gov/study/NCT04792268. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49548.

Effect of glycotoxicity and lipotoxicity on carbohydrate antigen 19 - 9 in the patients with diabetes.

OBJECTIVES: In comparison to the subjects without diabetes, a greater concentration of serum carbohydrate antigen 19 - 9 (CA 19 - 9) was observed in the subjects with diabetes. Nevertheless, since the occurrence of abnormal CA 19 - 9 is not widespread among the whole diabetic population, this phenomenon has not attracted enough attention. The prevalence of abnormal CA 19 - 9 in hospitalized patients with diabetes was the focus of our research. METHOD: A total of 385 subjects with diabetes and 200 controls were enrolled and all had been tested the CA19-9 levels. Cases of cancers were excluded through examination and followup for 1 year. RESULTS: We found that the rate of patients with abnormal CA19-9 level was 8.3%. The rate of patients with abnormal CA19-9 level was 14.0% in the HbA1c ≥ 9% group, and 3.0% in the HbA1c < 9% group, 2.5% in the control group. There was no significant difference in the HbA1c < 9% group and the control group. A significant correlation between serum CA19-9 and both HbA1c and total cholesterol was observed, yet no difference in CRP level was observed between subjects with normal CA19-9 level and subjects with abnormal CA19-9 level. However, a significant difference in fasting C-peptide levels was observed between the two groups, p = 0.039. CONCLUSION: The percentage of patients with diabetes exhibiting elevated CA19-9 level is 14% in the HbA1c ≥ 9% diabetic patients, much higher than expected. The underlying mechanism may be related to islet injury caused by glycotoxicity and lipotoxicity. STRENGTHS AND LIMITATIONS OF THE STUDY: We studied the rate of hospitalized diabetic patients with elevated CA 19 - 9 which were characterized with poorly controlled blood glucose. We found that the elevation of CA 19 - 9 was unexpectedly high in diabetic inpatients without development to cancer. The limitation of this study is that the underlying mechanism is not sufficiently studied.

RNA-seq analysis-based study on the effects of gestational diabetes mellitus on macrosomia.

Background: Both the mother and the infant are negatively impacted by macrosomia. Macrosomia is three times as common in hyperglycemic mothers as in normal mothers. This study sought to determine why hyperglycemic mothers experienced higher macrosomia. Methods: Hematoxylin and Eosin staining was used to detect the placental structure of normal mother(NN), mothers who gave birth to macrosomia(NM), and mothers who gave birth to macrosomia and had hyperglycemia (DM). The gene expressions of different groups were detected by RNA-seq. The differentially expressed genes (DEGs) were screened with DESeq2 R software and verified by qRT-PCR. The STRING database was used to build protein-protein interaction networks of DEGs. The Cytoscape was used to screen the Hub genes of the different group. Results: The NN group's placental weight differed significantly from that of the other groups. The structure of NN group's placenta is different from that of the other group, too. 614 and 3207 DEGs of NM and DM, respectively, were examined in comparison to the NN group. Additionally, 394 DEGs of DM were examined in comparison to NM. qRT-PCR verified the results of RNA-seq. Nucleolar stress appears to be an important factor in macrosomia, according on the results of KEGG and GO analyses. The results revealed 74 overlapped DEGs that acted as links between hyperglycemia and macrosomia, and 10 of these, known as Hub genes, were key players in this process. Additionally, this analysis believes that due of their close connections, non-overlapping Hubs shouldn't be discounted. Conclusion: In diabetic mother, ten Hub genes (RPL36, RPS29, RPL8 and so on) are key factors in the increased macrosomia in hyperglycemia. Hyperglycemia and macrosomia are linked by 74 overlapping DEGs. Additionally, this approach contends that non-overlapping Hubs shouldn't be ignored because of their tight relationships.

Carotenoid pattern intake and relation to metabolic status, risk and syndrome, and its components - divergent findings from the ORISCAV-LUX-2 survey.

Carotenoids are generally associated with health-beneficial effects; however, their intake patterns related to metabolic syndrome (MetS) and its components remains controversial. This cross-sectional study investigated associations between dietary intakes of individual carotenoids, fruits and vegetables, and the MetS and its components. Dietary intakes of 1346 participants of the ORISCAV-LUX-2 study were investigated by a 174 item-food frequency questionnaire, and carotenoid intake was determined by linking findings using mainly the USDA food databases. Components of MetS and complementary variables, including anthropometric (BMI, waist-circumferences, waist-hip ratio) and biological parameters (triglycerides, HDL-c, fasting blood glucose, blood pressure), were measured. Logistic (for MetS) and linear multivariable regression models (including assessing MetS as scores) adjusted for various confounders were created. α-and ß-Carotene, as well as lutein+zeaxanthin, were inversely associated with MetS (also when it was measured on a continuous scale), reducing the odds for MetS by up to 48%. However, lycopene, phytoene and phytofluene were rather positively associated with MetS scores and its components, though these adverse effects disappeared, at least for lycopene, when controlling for intakes of tomato-based convenience foods, in line with indicating a rather unhealthy/Westernized diet. All these associations remained significant when including fruits and vegetables as confounders, suggesting that carotenoids were related to MetS independently from effects within fruits and vegetables. Thus, a high intake of carotenoids was bidirectionally associated with MetS, its severity, risk, and its components, depending on the type of carotenoid. Future investigations are warranted to explore the inverse role that tomato-based carotenoids appear to suggest in relation to the MetS.

Q-Score Complements the Time in Range in the Evaluation of Short-Term Glycemic Control.

BACKGROUND AND AIMS: The Q-Score is a single-number composite metric that is constructed based on the following components: central glycemic tendency, hyperglycemia, hypoglycemia, and intra- and interday variability. Herein, we refined the Q-Score for the screening and analysis of short-term glycemic control using continuous glucose monitoring (CGM) profiles. METHODS: Continuous glucose monitoring profiles were obtained from noninterventional, retrospective cross-sectional studies. The upper limit of the Q-Score component hyperglycemia' that is, the time above target range (TAR), was adjusted from 8.9 to 10 mmol/L (n = 1562 three-day-sensor profiles). A total of 302 people with diabetes mellitus treated with intermittent CGM for ≥14 days were enrolled. The time to stability was determined via correlation-based analysis. RESULTS: There was a strong correlation between the Q-Scores of the two TARs, that is, 8.9 and 10 mmol/L (Q-ScoreTAR10 = -0.03 + 1.00 Q-ScoreTAR8.9, r = .997, p < .001). The times to stability of the Q-Score and TIR were 10 and 12 days, respectively. The Q-Score was correlated with fructosamine concentrations, the glucose management indicator (GMI), the time in range (TIR), and the glycemic risk index (GRI) (r = .698, .887, -.874, and .941), respectively. The number of Q-Score components above the target increased as the TIR decreased, from two (1.7 ± 0.9) in CGM profiles with a TIR between 70% and 80% to four (3.9 ± 0.5) in the majority of the CGM profiles with a TIR below 50%. A conversion matrix between the Q-Score and glycemic indices was developed. CONCLUSIONS: The Q-Score is a tool for assessing short-term glycemic control. The Q-Score can be translated into clinician opinion using the GRI.

Antioxidative and Anti-inflammatory Effects of Plant-derived Hypoglycemic Medicines: An In vivo/In vitro Systematic Review.

BACKGROUND: The activation of oxidative stress and inflammatory conditions has been associated with acceleration in diabetes (DM) onset and complications. Despite various anti-DM medications, there is a growing trend to discover inexpensive and effective treatments with low adverse effects from plants as one of the promising sources for drug development. OBJECTIVE: This study aimed to systematically investigate the simultaneous anti-inflammatory and antioxidant effects of plant-derived hypoglycemic medicines in diabetic experimental models. METHODS: The search terms consisted of "diabetes", "herbal medicine", "antioxidant", "Inflammatory biomarker", and their equivalents among PubMed, Scopus, Web of Science, and Cochrane Library databases up to 17 August 2021. RESULTS: Throughout the search of databases, 201 eligible experimental studies were recorded. The results showed that the most commonly assessed inflammatory and oxidative stress biomarkers were tumor necrosis factor (TNF)-α, interleukin (IL) 6, IL-1ß, IL-10, malondialdehyde (MDA), and nitric oxide (NO). The activity of antioxidant enzymes, including superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were assessed in the present review. Among herbal treatments, Trigonella foenum-graecum L., Centella asiatica (L.) Urb., Vitis vinifera L., and Moringa oleifera Lam. were most commonly used for diabetic complications. Due to the dispersion of the treatments, meta-analysis was not applicable. CONCLUSION: Our findings showed that the application of different plant-derived hypoglycemic treatments in animal models improved diabetes and its complications, as well as modulated concomitant inflammatory and oxidative stress biomarkers. These findings suggest that plant-based antidiabetic medicines and food supplements have the potential to manage diabetes and its complications.

Aquaporins enriched in endothelial vacuole membrane regulate the diameters of microvasculature in hyperglycemia.

BACKGROUND: In patients with diabetic microvascular complications, decreased perfusion or vascular occlusion, caused by reduced vascular diameter, is a common characteristic that will lead to insufficient blood supply. Yet, the regulatory mechanism and effective treatment approach remain elusive. METHODS AND RESULTS: Our initial findings revealed a notable decrease in the expression of human AQP1 in both diabetic human retina samples (49 healthy vs. 54 diabetic samples) and high-glucose-treated human retinal microvascular endothelial cells. Subsequently, our investigations unveiled a reduction in vascular diameter and compromised perfusion within zebrafish embryos subjected to high glucose treatment. Further analysis indicated a significant downregulation of two aquaporins, aqp1a.1 and aqp8a.1, which are highly enriched in ECs and are notably responsive to hyperglycemic conditions. Intriguingly, the loss of function of aqp1a.1 and/or aqp8a.1 resulted in a reduction of intersegmental vessel diameters, effectively mirroring the phenotype observed in the hyperglycemic zebrafish model.The overexpression of aqp1a.1/aqp8a.1 in zebrafish ECs led to notable enlargement of microvascular diameters. Moreover, the reduced vessel diameters resulting from high-glucose treatment were effectively rescued by the overexpression of these aquaporins. Additionally, both aqp1a.1 and apq8a.1 were localized in the intracellular vacuoles in cultured ECs as well as the ECs of sprouting ISVs, and the loss of Aqps caused the reduction of those vacuoles, which was required for lumenization. Notably, while the loss of AQP1 did not impact EC differentiation from human stem cells, it significantly inhibited vascular formation in differentiated ECs. CONCLUSION: EC-enriched aquaporins regulate the diameter of blood vessels through an intracellular vacuole-mediated process under hyperglycemic conditions. These findings collectively suggest that aquaporins expressed in ECs hold significant promise as potential targets for gene therapy aimed at addressing vascular perfusion defects associated with diabetes.

Retinal thickness changes in preobese and obese patients without hyperglycemia: Optical coherence tomography study.

PURPOSE: To evaluate retinal thickness changes by optical coherence tomography in preobese and obese patients without hyperglycemia. METHODS: This comparative cross-sectional study was conducted on 55 normal (18.5-24.9 kg/m2), 42 preobese (25-29.9 kg/m2), 34 obese (>30 kg/m2), a total of 131, according to body mass index (BMI) value at the time of examination. All participants were examined in the internal medicine department and fasting serological biochemical and lipid tests were performed, and those with hyperglycemia were excluded from the study. All participants underwent a full ophthalmological examination and sectoral examination of the retina with optical coherence tomography. RESULTS: The study included 55 right eyes of 55 normal, 42 of 42 preobese, and 34 of 34 obese, age- and sex-matched participants, without hyperglycemia. The mean BMI of the normal group was 22.3 ± 1.3, 26.8 ± 1.3 in the preobese group, and 33.2 ± 4.2 in the obese group. Central foveal thickness (normal 229.8 ± 20.1 µm, preobese 234.7 ± 18.8 µm and obese 222.0 ± 23.4 µm, P:0.031) and mean inferior (normal 280.7 ± 55.8 µm, preobese 296.7 ± 11.1 µm and obese 285.3 ± 9.9 µm) thickness in the 3 mm The Early Treatment Diabetic Retinopathy Study (ETDRS) circle was significantly higher in the preobese group and significantly lower in the obese group. Mean nasal, temporal, and superior thickness in the 3 mm ETDRS circle and peripapillary retinal nerve fiber layer was higher in the preobese group and lower in the obese group but this difference was statistically not significant. CONCLUSION: The fact that preobesity, which is not accompanied by hyperglycemia, causes an increase in the thickness of the central macular regions and obesity causes thinning of the retina, supports that lipid metabolism in the body alone can affect retinal thickness changes and retinal neurodegeneration.

Assessment of Glycemia Risk Index and Standard Continuous Glucose Monitoring Metrics in a Real-World Setting of Exercise in Adults With Type 1 Diabetes: A Post-Hoc Analysis of the Type 1 Diabetes and Exercise Initiative.

BACKGROUND: Standardized reporting of continuous glucose monitoring (CGM) metrics does not provide extra weighting for very high or very low glucose, despite their distinct clinical significance, and thus may underestimate glycemic risk in people with type 1 diabetes (T1D) during exercise. Glycemia Risk Index (GRI) is a novel composite metric incorporating clinician-validated extra weighting for glycemic extremes, which may provide a novel summary index of glycemia risk around exercise. METHODS: Adults (≥18 years) in the T1D EXercise Initiative study wore CGM and activity trackers for four weeks. For this analysis, exercise days were defined as 24 hours following ≥20 minutes of exercise, with no other exercise in the 24-hour period. Sedentary days were defined as any 24 hours with no recorded exercise within that period or the preceding 24 hours. Linear mixed-effects regression was used to evaluate exercise effects on GRI and CGM metrics within 24 hours postexercise. RESULTS: In 408 adults with T1D with >70% CGM and activity data, GRI on exercise (N = 3790) versus sedentary days (N = 1865) was significantly lower (mean [SD]: 29.9 [24.0] vs 34.0 [26.1], respectively, absolute mean difference -1.70 [-2.73, -0.67], P < .001), a ~5% reduction in glycemic risk. Percent time in range (TIR; 70-180 mg/dL) increased on exercise days (absolute mean difference 2.67 [1.83, 3.50], P < .001), as did time below range (TBR; relative mean difference 1.17 [1.12, 1.22], P < .001), while time above range (TAR) decreased (relative mean difference 0.84 [0.79, 0.88], P < .001). CONCLUSIONS: Glycemia Risk Index improved on exercise versus sedentary days, despite increased TBR, which is weighted most heavily in the GRI calculation, due to a robust reduction in TAR.

Treatment with systemic corticosteroid versus placebo for exacerbations of COPD: A systematic review and meta-analysis.

BACKGROUND: For the treatment of COPD exacerbations, systemic corticosteroids are recommended in addition to short-acting bronchodilators. Although there have been several systemic reviews, many of the included studies were conducted before 2007 and a re-evaluation has not been performed since 2014. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety profile of systemic corticosteroids in patients with COPD during exacerbations. METHODS: We searched relevant randomized control trials (RCTs) and analyzed the treatment failure, relapse, lung function, improvement in PaO2 and PaCO2, dyspnea, quality of life (QOL), length of stay in hospital and adverse events including hyperglycemia and mortality as the outcomes of interest. RESULTS: We identified a total of 12 RCTs (N = 1336). Systemic corticosteroids significantly reduced the treatment failure (odds ratios; OR 0.41, 95% confidence intervals; CI 0.25 to 0.67) and hospital length of stay (mean difference; MD -1.57 days, 95% CI -2.36 to -0.78) and improved FEV1 (MD 0.18 L, 95% CI 0.08 to 0.28) and dyspnea (transitional dyspnea index; MD 1.90, 95% CI 0.26 to 3.54) in COPD exacerbations compared to placebo. However, systemic corticosteroids were associated with a significantly higher incidence of adverse events (OR 1.83, 95% CI 1.25 to 2.69) and hyperglycemia (OR 2.94, 95% CI 1.68 to 5.14). CONCLUSIONS: In patients with moderate and severe COPD and severe obstructive impairment during exacerbations, systemic corticosteroids cause more adverse events, including hyperglycemia, than placebo but significantly reduce the treatment failure and hospital length of stay and improve FEV1 and dyspnea.

Prandial Insulins: A Person-Centered Choice.

PURPOSE OF REVIEW: Postprandial hyperglycemia, or elevated blood glucose after meals, is associated with the development and progression of various diabetes-related complications. Prandial insulins are designed to replicate the natural insulin release after meals and are highly effective in managing post-meal glucose spikes. Currently, different types of prandial insulins are available such as human regular insulin, rapid-acting analogs, ultra-rapid-acting analogs, and inhaled insulins. Knowledge about diverse landscape of prandial insulin will optimize glycemic management. RECENT FINDINGS: Human regular insulin, identical to insulin produced by the human pancreas, has a slower onset and extended duration, potentially leading to post-meal hyperglycemia and later hypoglycemia. In contrast, rapid-acting analogs, such as lispro, aspart, and glulisine, are new insulin types with amino acid modifications that enhance their subcutaneous absorption, resulting in a faster onset and shorter action duration. Ultra-rapid analogs, like faster aspart and ultra-rapid lispro, offer even shorter onset of action, providing better meal-time flexibility. The Technosphere insulin offers an inhaled route for prandial insulin delivery. The prandial insulins can be incorporated into basal-bolus, basal plus, or prandial-only regimens or delivered through insulin pumps. Human regular insulin, aspart, lispro, and faster aspart are recommended for management of hyperglycemia during pregnancy. Ongoing research is focused on refining prandial insulin replacement and exploring newer delivery methods. The article provides a comprehensive overview of various prandial insulin options and their clinical applications in the management of diabetes.

Association of persistent postoperative hyperglycemia with mortality after elective craniotomy.

OBJECTIVE: The influence of persistent postoperative hyperglycemia after craniotomy has not yet been explored. This study aimed to investigate the hypothesis that persistent postoperative hyperglycemia is associated with mortality in patients undergoing an elective craniotomy. METHODS: This study included adult patients (age ≥ 18 years) undergoing an elective craniotomy between January 2011 and March 2021 at the West China Hospital, Sichuan University. Peak daily blood glucose values measured within the first 7 days after craniotomy were collected. Persistent hyperglycemia was defined by two or more consecutive serum glucose levels of mild, moderate, or severe hyperglycemia. Normoglycemia, mild hyperglycemia, moderate hyperglycemia, and severe hyperglycemia were defined as glucose values of ≤ 6.1 mmol/L, > 6.1 and ≤ 7.8 mmol/L, > 7.8 and ≤ 10.0 mmol/L, and > 10.0 mmol/L, respectively. RESULTS: This study included 14,907 patients undergoing an elective craniotomy. In the multivariable analysis, both moderate (adjusted OR 3.76, 95% CI 2.68-5.27) and severe (adjusted OR 3.82, 95% CI 2.54-5.76) persistent hyperglycemia in patients were associated with higher 30-day mortality compared with normoglycemia. However, this association was not observed in patients with mild hyperglycemia (adjusted OR 1.32, 95% CI 0.93-1.88). Interestingly, this association was observed regardless of whether patients had preoperative hyperglycemia. There was no interaction between moderate or severe hyperglycemia and preexisting diabetes (p for interaction = 0.65). When postoperative peak blood glucose values within the first 7 days after craniotomy were evaluated as a continuous variable, for each 1-mmol/L increase in blood glucose, the adjusted OR of 30-day mortality was 1.17 (95% CI 1.14-1.21). Postoperative blood glucose (area under the curve [AUC] = 0.78) was superior to preoperative blood glucose (AUC = 0.65; p < 0.001) for predicting mortality. Moderate and severe persistent hyperglycemia in patients were associated with an increased risk of deep venous thrombosis (adjusted OR 3.20, 95% CI 2.31-4.42), pneumonia (adjusted OR 2.77, 95% CI 2.40-3.21), myocardial infarction (adjusted OR 4.38, 95% CI 3.41-5.61), and prolonged hospital stays (adjusted OR 1.43, 95% CI 1.29-1.59). CONCLUSIONS: In patients undergoing an elective craniotomy, moderate and severe persistent postoperative hyperglycemia were associated with an increased risk of mortality compared with normoglycemia, regardless of preoperative hyperglycemia.

Recommendations for management of diabetes and its complications during Hajj (Muslim Pilgrimage) - 2024 update.

Hajj is an obligatory duty for all healthy adult Muslims once in the lifetime subjected to the ability. Considering the 10.5 % global prevalence of diabetes coupled with the numbers of Muslims performing the Hajj, ∼ 1.8 million in 2023, it is estimated that Muslims with diabetes performing Hajj may exceed 340,000 this year. During Hajj the pattern and amount of their meal, fluid intake and physical activity are markedly altered. Many people with diabetes insist on doing the Hajj duty, thereby creating a medical challenge for themselves and their health care providers. It is therefore important that medical professionals be aware of the potential risks that may be associated with Hajj. People with diabetes may face many health hazards during Hajj including but not limited to the killer triad which might occur during Hajj: Hypoglycemia, Foot injury and Infections. Many precautions should be taken to prevent and treat these potentially serious complications. Risk stratification, medication adjustments, proper clinical assessment, and education before doing Hajj are crucial.

Effects of Simvastatin on Gene Expression and Alkaline Phosphatase Activity in the MG-63 Cell Line Treated With Hyperglycemia for Bone Regeneration.

Background Dental implants have become a widespread treatment option for replacing missing teeth. Adequate bone is required for the placement of dental implants, in the absence of which, augmentation by bone regeneration is done. Antiresorptive drugs are used as treatment procedures for bone regeneration. One such antiresorptive drug is simvastatin (SV), a 3-hydroxy-3-methylglutaryl coenzyme used to manage hyperlipidemia. It reduces serum cholesterol levels and has an advantageous effect on new bone formation. Various studies establish that SV stimulates bone morphogenetic protein (BMP)-2 expression and leads to bone formation. SV prevents the production of isoprenoids and mevalonate, which are essential for osteoclastogenesis and contribute to the bone-sparing effect.  Aim The aim of the study was to investigate the osteoregenerative activity of SV in the osteoblast-like cell models, MG-63 cell line, with hyperglycemic conditions. Methodology MG-63 cultures were established under high glucose concentrations during the experiments and cultured with SV concentrations of 1 µM and 3 µM. The quantification of the expression of the genes, namely, BMP-2 and osteocalcin (OCN) was done by real-time quantitative polymerase chain reaction (RTqPCR). The measurement of alkaline phosphatase activity in the SV-treated cells was also determined. Results According to the results of the study, SV had osteoprotective properties resulting from the inhibition of osteoclast stimulation and osteoinductive properties, facilitated by BMP-2 and OCN. In addition, SV at concentrations of 1 µM and 3 µM increased the gene expression of BMP-2 and OCN in the MG-63 cell line. Conclusion The results of this study demonstrated that SV had a significant and direct effect on osteogenesis in osteoblasts in vitro.

Association between stress hyperglycemia ratio and diabetes mellitus mortality in American adults: a retrospective cohort study and predictive model establishment based on machine learning algorithms (NHANES 2009-2018).

BACKGROUND: Stress hyperglycemia is a physiological response of the body under stress to make adaptive adjustments in response to changes in the internal environment. The stress hyperglycemia ratio (SHR) is a new indicator after adjusting the basal blood glucose level of the population. Previous studies have shown that SHR is associated with poor prognosis in many diseases, such as cardiovascular and cerebrovascular diseases and delirium in elderly patients. However, there are currently no studies on the correlation between SHR and the general U.S. POPULATION: The purpose of this study was to examine the association between SHR and adverse outcomes among adults in the United States in general. METHODS: Data on 13,315 follow-up cohorts were extracted from NHANES. The study population was divided into four groups according to quartiles of SHR. The primary outcomes were all-cause mortality and diabetes mellitus mortality. The relationship between SHR and outcomes was explored using restricted cubic splines, COX proportional hazards regression, Kaplan-Meier curves, and mediation effects. SHR is incorporated into eight machine learning algorithms to establish a prediction model and verify the prediction performance. RESULTS: A total of 13,315 individual data were included in this study. Restricted cubic splines demonstrated a "U-shaped" association between SHR and all-cause mortality and diabetes mellitus mortality, indicating that increasing SHR is associated with an increased risk of adverse events. Compared with lower SHR, higher SHR was significantly associated with an increased risk of all cause mortality and diabetes mellitus mortality (HR > 1, P < 0.05). The mediating effect results showed that the positively mediated variables were segmented neutrophils and aspartate aminotransferase, and the negatively mediated variables were hemoglobin, red blood cell count, albumin, and alanine aminotransferase. The ROC of the eight machine learning algorithm models are XGBoost (0.8688), DT (0.8512), KNN (0.7966), RF (0.8417), Logistic regression (0.8633), ENET (0.8626), SVM (0.8327) and MLP (0.8662). CONCLUSION: SHR can be used as a predictor of all cause mortality and diabetes mellitus mortality in the general adult population in the United States. Higher SHR is significantly associated with an increased risk of poor prognosis, especially in those aged < 65 years and in women.

Microglial SCAP deficiency protects against diabetes-associated cognitive impairment through inhibiting NLRP3 inflammasome-mediated neuroinflammation.

Hyperglycemia-induced pathological microglial responses and subsequent neuronal damage are notable characteristics of diabetes-associated cognitive impairment (DACI). Cholesterol accumulation in the brain is a prevalent consequence of diabetes mellitus (DM), exacerbating pathological microglial responses. Regarding disordered glucose and lipid metabolism, the Sterol Regulatory Element-Binding Protein (SREBP) cleavage-activating protein (SCAP), a cholesterol sensor, exhibits increased expression and abnormal translocation from the endoplasmic reticulum to the Golgi, amplifying the inflammatory response. Therefore, we hypothesized that overexpression of microglia-SCAP and cholesterol accumulation in DM mice could induce pathological microglial responses associated with DACI. Our type 2 DM mice model presented an abnormal increase in microglial SCAP expression. The functional loss of microglia-specific SCAP in DM mice improved cognitive impairment, neuronal synaptic plasticity deficits, and abnormal microglial responses. Mechanistically, the accumulated SCAP directly bound to and enhanced the activation of the microglial-specific inflammatory amplifier, NLRP3 inflammasome, in Golgi, thereby increasing pathological microglial responses and promoting neuronal damage. These findings indicate an important regulatory axis of microglial responses from SCAP to the NLRP3 inflammasome pathway in microglia. These underscore the crosstalk between cholesterol disorders and pathological microglial responses, offering a promising avenue for pharmaceutical interventions in DACI.