Sodium-glucose cotranspor ter 2 (SGLT2) inhibitors in nephrolithiasis: should we "gliflozin" patients with kidney stone disease? / Inibidores de cotransportadores sódio-glicose-2 (SGLT2) na nefrolitíase - devemos "gliflozinar" os litiásicos?

ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?

RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?

Natural Physiological Changes During Pregnancy.

Pregnancy causes physiological changes that support the growing fetus and get the mother ready for labor and delivery. Some of these modifications affect biochemical levels; they are normally stable, while others could imitate symptoms of illness. It is critical to distinguish between pathology associated with disease and typical physiological changes. This review article focuses on the significant changes that occur throughout a typical pregnancy.

Novel 4th-generation phytase improves broiler growth performance and reduces woody breast severity through modulation of muscle glucose uptake and metabolism.

The objective of the present study was to determine the effect of a novel (4th generation) phytase supplementation as well as its mode of action on growth, meat quality, and incidence of muscle myopathies. One-day old male broilers (n = 720) were weighed and randomly allocated to 30 floor pens (24 birds/pen) with 10 replicate pens per treatment. Three diets were fed from hatch to 56- days-old: a 3-phase corn-soy based diet as a positive control (PC); a negative control (NC) formulated to be isocaloric and isonitrogenous to the PC and with a reduction in Ca and available P, respectively; and the NC supplemented with 2,000 phytase units per kg of diet (NC + P). At the conclusion of the experiment, birds fed with NC + P diet were significantly heavier and had 2.1- and 4.2-points better feed conversion ratio (FCR) compared to birds offered NC and PC diets, respectively. Processing data showed that phytase supplementation increased live weight, hot carcass without giblets, wings, tender, and skin-on drum and thigh compared to both NC and PC diets. Macroscopic scoring showed that birds fed the NC + P diet had lower woody breast (WB) severity compared to those fed the PC and NC diets, however there was no effect on white striping (WS) incidence and meat quality parameters (pH, drip loss, meat color). To delineate its mode of action, iSTAT showed that blood glucose concentrations were significantly lower in birds fed NC + P diet compared to those offered PC and NC diets, suggesting a better glucose uptake. In support, molecular analyses demonstrated that the breast muscle expression (mRNA and protein) of glucose transporter 1 (GLUT1) and glucokinase (GK) was significantly upregulated in birds fed NC + P diet compared to those fed the NC and PC diets. The expression of mitochondrial ATP synthase F0 subunit 8 (MT-ATP8) was significantly upregulated in NC + P compared to other groups, indicating intracellular ATP abundance for anabolic pathways. This was confirmed by the reduced level of phosphorylated-AMP-activated protein kinase (AMPKα1/2) at Thr172 site, upregulation of glycogen synthase (GYS1) gene and activation of mechanistic target of rapamycin and ribosomal protein S6 kinase (mTOR-P70S6K) pathway. In conclusion, this is the first report showing that in-feed supplementation of the novel phytase improves growth performance and reduces WB severity in broilers potentially through enhancement of glucose uptake, glycolysis, and intracellular ATP production, which used for muscle glycogenesis and protein synthesis.

U-shaped relationship between fasting blood glucose and urinary albumin-to-creatinine ratio in the general United States population.

Objective: The current controversy surrounding the association between fasting blood glucose (FBG) and albuminuria necessitates further investigation. Hence, the primary objective of this study was to examine the relationship between FBG and urinary albumin-to-creatinine ratio (UACR). Methods: A cohort of complete data from National Health and Nutrition Examination Survey (NHANES) participants (1999-2020) was analyzed. Linear regression analyses and a generalized additive model explored the association between FBG and UACR. Furthermore, the stability of this relationship across different populations was assessed. Results: The study involved a total of 20,264 participants who were identified as U.S. citizens. By employing linear regression analysis, a statistically significant relationship was observed between elevated FBG levels and an increase in UACR (P<0.0001). Additionally, using a generalized additive model analysis, a U-shaped correlation between FBG and UACR was identified. Further examination using threshold effect analysis indicated a turning point for FBG at 5.44 mmol/L. A noteworthy finding in multiple populations is the consistent U-shaped association between FBG and UACR, except for individuals with serum uric acid levels ≥420 µmol/L and those who refrain from alcohol consumption. Conclusion: The general U.S. population has a U-shaped nonlinear relationship between FBG and UACR.

Blood glucose monitoring devices for type 1 diabetes: a journey from the food and drug administration approval to market availability.

Blood glucose monitoring constitutes a pivotal element in the clinical management of Type 1 diabetes (T1D), a globally escalating metabolic disorder. Continuous glucose monitoring (CGM) devices have demonstrated efficacy in optimizing glycemic control, mitigating adverse health outcomes, and augmenting the overall quality of life for individuals afflicted with T1D. Recent progress in the field encompasses the refinement of electrochemical sensors, which enhances the effectiveness of blood glucose monitoring. This progress empowers patients to assume greater control over their health, alleviating the burdens associated with their condition, and contributing to the overall alleviation of the healthcare system. The introduction of novel medical devices, whether derived from existing prototypes or originating as innovative creations, necessitates adherence to a rigorous approval process regulated by the Food and Drug Administration (FDA). Diverse device classifications, stratified by their associated risks, dictate distinct approval pathways, each characterized by varying timelines. This review underscores recent advancements in blood glucose monitoring devices primarily based on electrochemical sensors and elucidates their regulatory journey towards FDA approval. The advent of innovative, non-invasive blood glucose monitoring devices holds promise for maintaining stringent glycemic control, thereby preventing T1D-associated comorbidities, and extending the life expectancy of affected individuals.

CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer.

CYP3A5 is a cytochrome P450 (CYP) enzyme that metabolizes drugs and contributes to drug resistance in cancer. However, it remains unclear whether CYP3A5 directly influences cancer progression. In this report, we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal adenocarcinoma. Multi-omics analysis showed that CYP3A5 knockdown results in a decrease in various glucose-related metabolites through its effect on glucose transport. A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP, a negative regulator of GLUT1. Notably, CYP3A5-generated reactive oxygen species were proved to be responsible for attenuating the AKT-4EBP1-TXNIP signaling pathway. CYP3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic cancer. Taken together, our results, for the first time, reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target.

Correlation Between Thyroid-Related Hormones and Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients with Normal Thyroid Function: A Retrospective Study.

Purpose: To investigate the correlation between thyroid-related hormones and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM). Patients and Methods: Patients with T2DM admitted to our hospital between January 2023 and June 2023 were retrospectively analyzed. The patients were divided into DR and non-diabetic retinopathy (NDR) groups according to whether DR occurred. Thyroid function-related hormones (TSH, FT3, and FT4), blood glucose indices (FBG and HbA1c), and blood lipid indices (HDL-C, LDL-C, TC, and TG) of the two groups were analyzed by univariate and multivariate logistic regression to explore the risk factors for DR. Pearson correlation analysis and multiple stepwise regression analysis were used to investigate the correlation of TSH or FT3 with FBG, HbA1c, and TG in DR patients. Results: Of the 286 patients with T2DM included in this study, 101 (35.31%) developed DR and 185 (64.69%) did not. High TG, FBG, HbA1c, and TSH and low FT3 levels were independent risk factors for DR in T2DM patients. TSH positively correlated with TG, whereas FT3 negatively correlated with TG and HbA1c in T2DM patients with DR. Conclusion: Higher TSH and lower FT3 in T2DM patients with normal thyroid function may affect glucose and lipid metabolism, thereby increasing the risk of DR.

Sugar signals pedal the cell cycle!

Cell cycle involves the sequential and reiterative progression of important events leading to cell division. Progression through a specific phase of the cell cycle is under the control of various factors. Since the cell cycle in multicellular eukaryotes responds to multiple extracellular mitogenic cues, its study in higher forms of life becomes all the more important. One such factor regulating cell cycle progression in plants is sugar signalling. Because the growth of organs depends on both cell growth and proliferation, sugars sensing and signalling are key control points linking sugar perception to regulation of downstream factors which facilitate these key developmental transitions. However, the basis of cell cycle control via sugars is intricate and demands exploration. This review deals with the information on sugar and TOR-SnRK1 signalling and how they manoeuvre various events of the cell cycle to ensure proper growth and development.

A Novel Mechanistic Model for Future Research in the Elements of the ERAS Program in Patients With Sickle Cell Disease.

Enhanced recovery after surgery (ERAS) is a patient-centered, evidence-based, multidisciplinary team-developed approach to a surgical stress response that is implemented to optimize physiological function and facilitate recovery for the best possible outcomes from surgery. Although there are currently well-known published guidelines for the perioperative management of patients with sickle cell disease, there are currently no specific and evidencebased ERAS protocols that address the needs of these patients. A novel mechanistic model has recently been found that could change ERAS protocols for patients with sickle cell disease with regard to a current preoperative carbohydrate loading drink recommendation, nutrition and intravenous fluid management. ERAS has great benefits for most patient populations, but emerging research suggests that patients with sickle cell disease may process and respond differently to varying concentrations of serum glucose and serum cations (hyperglycemia and hypertonic states). This adverse response involves actin, a cytoskeletal protein, in the red blood cell and how increased hemoglobin glycosylation may lead to a malfunction in this protein and a transition to vaso-occlusive crises in patients with sickle cell disease. Further research is warranted with this new mechanistic model to develop more meticulous and customized perioperative management plans to address risk mitigation in patients with sickle cell disease.

Mast Cells are Dependent on Glucose Transporter 1 (GLUT1) and GLUT3 for IgE-mediated Activation.

Mast cells (MCs) are known to have a pathological impact in a variety of settings, in particular in allergic conditions. There is also limited evidence implicating MCs in diabetes, raising the possibility that MC function may be influenced by alterations in glucose levels. However, it is not known whether MCs are directly affected by elevated glucose concentrations. Moreover, it is not known which glucose transporters that are expressed by MCs, and whether MCs are dependent on glucose transporters for activation. Here we addressed these issues. We show that MCs express high levels of both glucose transporter 1 (GLUT1/Slc2A1) and GLUT3 (Slc2A3). Further, we show that the inhibition of either GLUT1 or GLUT3 dampens both MC degranulation and cytokine induction in response to IgE receptor crosslinking, and that combined GLUT1 and GLUT3 inhibition causes an even more pronounced inhibition of these parameters. In contrast, the inhibition of GLUT1 or GLUT3, or combined GLUT1 and GLUT3 inhibition, had less impact on the ability of the MCs to respond to activation via compound 48/80. Elevated glucose concentrations did not affect MC viability, and had no stimulatory effect on MC responses to either IgE receptor crosslinking or compound 48/80. Altogether, these findings reveal that MCs are strongly dependent on glucose transport via GLUT1 and/or GLUT3 for optimal responses towards IgE-mediated activation, whereas MC functionality is minimally affected by elevated glucose levels. Based on these findings, antagonists of GLUT1 and GLUT3 may be considered for therapeutic intervention in allergic conditions.

Why have SGLT2 Inhibitors Failed to Achieve the Desired Success in COVID-19?

The SARS-CoV-2 virus emerged towards the end of 2019 and caused a major worldwide pandemic lasting at least 2 years, causing a disease called COVID-19. SARS-CoV-2 caused a severe infection with direct cellular toxicity, stimulation of cytokine release, increased oxidative stress, disruption of endothelial structure, and thromboinflammation, as well as angiotensin-converting enzyme 2 (ACE2) down-regulation-mediated renin-angiotensin system (RAS) activation. In addition to glucosuria and natriuresis, sodium-glucose transport protein 2 (SGLT2) inhibitors (SGLT2i) cause weight loss, a decrease in glucose levels with an insulin-independent mechanism, an increase in erythropoietin levels and erythropoiesis, an increase in autophagy and lysosomal degradation, Na+/H+-changer inhibition, prevention of ischemia/reperfusion injury, oxidative stress and they have many positive effects such as reducing inflammation and improving vascular function. There was great anticipation for SGLT2i in treating patients with diabetes with COVID-19, but current data suggest they are not very effective. Moreover, there has been great confusion in the literature about the effects of SGLT2i on COVID-19 patients with diabetes . Various factors, including increased SGLT1 activity, lack of angiotensin receptor blocker co-administration, the potential for ketoacidosis, kidney injury, and disruptions in fluid and electrolyte levels, may have hindered SGLT2i's effectiveness against COVID-19. In addition, the duration of use of SGLT2i and their impact on erythropoiesis, blood viscosity, cholesterol levels, and vitamin D levels may also have played a role in their failure to treat the virus. This article aims to uncover the reasons for the confusion in the literature and to unravel why SGLT2i failed to succeed in COVID-19 based on some solid evidence as well as speculative and personal perspectives.

A bout of aerobic exercise in the heat increases carbohydrate use but does not enhance the disposal of an oral glucose load, in healthy active individuals.

We investigated if a bout of exercise in a hot environment (HEAT) would reduce the postprandial hyperglycemia induced by glucose ingestion. The hypothesis was that HEAT stimulating glycogen use would increase the disposal of the ingested glucose (i.e., OGTT; 75 g of glucose). Separated by at least 1 week, nine young-healthy individuals underwent three trials after an overnight fast in a randomized order. Two trials included 50 min of pedaling at 58±5% VO2MAX either in a thermoneutral (21±1ºC; NEUTRAL) or in a hot environment (33±1ºC; HEAT) eliciting similar energy expenditure (503±101 kcals). These two trials were compared to a no-exercise trial (NO EXER). Twenty min after exercise (or rest), subjects underwent an OGTT, while carbohydrate oxidation (CHOxid, using indirect calorimetry) plasma blood glucose, insulin concentrations (i.e., [glucose], [insulin]), and double tracer glucose kinetics ([U- 13C] glucose ingestion and [6,6-2H2] glucose infusion) were monitored for 120 min. At rest, [glucose], [insulin], and rates of appearance/disappearance of glucose in plasma (glucose Ra/Rd) were similar among trials. During exercise, heart rate, tympanic temperature, [glucose], glycogen oxidation, and total CHOxid were higher during HEAT than NEUTRAL (i.e., 149±35 vs 124±31 µmol·kg-1·min-1, p=0.010). However, during the following OGTT glucose Rd was similar in HEAT and NEUTRAL (i.e., 25.1±3.6 vs 25.2±5.3 µmol·kg-1·min-1, p=0.981). Insulin sensitivity (i.e., ISIMATSUDA) only improved in NEUTRAL compared to NO EXER (10.1±4.6 vs 8.8±3.7 a.u.; p=0.044). In summary, stimulating carbohydrate use with exercise in a hot environment does not improve postprandial plasma glucose disposal or insulin sensitivity in a subsequent OGTT.

SMEK1 ablation promotes glucose uptake and improves obesity-related metabolic dysfunction via AMPK signaling pathway.

OBJECTIVE: Obesity has become a major risk of global public health. SMEK1 is also known as a regulatory subunit of protein phosphatase 4 (PP4). Both PP4 and SMEK1 have been clarified many metabolic functions, including regulating the hepatic gluconeogenesis and glucose transporter gene expression in yeast. Whether SMEK1 participates in obesity and the broader metabolic role in mammals is unknown. Thus we investigated the function of SMEK1 in white adipose tissue and glucose uptake. METHODS: GWAS/GEPIA/GEO database was used to analyze the correlation between SMEK1 and metabolic phenotypes/lipid metabolism related genes/obesity. Smek1 KO mice were generated to identify the role of SMEK1 in obesity and glucose homeostasis. Cell culture and differentiation of SVFs and 3T3-L1 were used to determine the mechanism. 2-NBDG was used to measure the glucose uptake. Compound C was used to confirm the role of AMPK. RESULTS: We elucidated that SMEK1 was correlated to obesity and adipogenesis. Smek1 deletion enhanced adipogenesis in both SVFs and 3T3-L1. Smek1 KO protected mice from obesity, had protective effects on metabolic disorders including insulin resistance and inflammation. Smek1 KO mice have lower level of fasting serum glucose, we found that SMEK1 ablation promoted glucose uptake by increased p-AMPKα(T172) and the transcription of Glut4, when the effect on AMPK-regulated glucose uptake was due to the PP4 catalytic subunits (PPP4C). CONCLUSION: Our findings reveal a novel role of SMEK1 in obesity and glucose homeostasis, providing a potential new therapeutic target for obesity and metabolic dysfunction.

Threshold of hyperglycaemia associated with mortality in critically ill patients: a multicentre, prospective, observational study using continuous glucose monitoring.

AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) provides comprehensive information on the exposure to dysglycaemia. This study aimed to investigate the threshold of hyperglycaemia related to mortality risk in critically ill patients using CGM technology. METHODS: A total of 293 adult critically ill patients admitted to intensive care units of five medical centres were prospectively included between May 2020 and November 2021. Participants wore intermittently scanned CGM for a median of 12.0 days. The relationships between different predefined time above ranges (TARs), with the thresholds of hyperglycaemia ranging from 7.8 to 13.9 mmol/l (140-250 mg/dl), and in-hospital mortality risk were assessed by multivariate Cox proportional regression analysis. Time in ranges (TIRs) of 3.9 mmol/l (70 mg/dl) to the predefined hyperglycaemic thresholds were also assessed. RESULTS: Overall, 66 (22.5%) in-hospital deaths were identified. Only TARs with a threshold of 10.5 mmol/l (190 mg/dl) or above were significantly associated with the risk of in-hospital mortality, after adjustment for covariates. Furthermore, as the thresholds for TAR increased from 10.5 mmol/l to 13.9 mmol/l (190 mg/dl to 250 mg/dl), the hazards of in-hospital mortality increased incrementally with every 10% increase in TARs. Similar results were observed concerning the associations between TIRs with various upper thresholds and in-hospital mortality risk. For per absolute 10% decrease in TIR 3.9-10.5 mmol/l (70-190 mg/dl), the risk of in-hospital mortality was increased by 12.1% (HR 1.121 [95% CI 1.003, 1.253]). CONCLUSIONS/INTERPRETATION: A glucose level exceeding 10.5 mmol/l (190 mg/dl) was significantly associated with higher risk of in-hospital mortality in critically ill patients.

Glycemic Variability and the Thickness of Retinal Layers in Cystic Fibrosis Patients with and without Cystic Fibrosis Related Diabetes.

PURPOSE: Patients with cystic fibrosis (CF) are at risk to develop CF related diabetes (CFRD) and subsequently even diabetic neuro- and/or vasculopathy. We sought to determine if there are typical signs of diabetes-related retinal alterations present in CF patients with preserved and impaired glycemic control. METHODS: During routine annual examination CF patients were offered an additional 7-day period of real time continuous glucose monitoring (rtCGM) and an ophthalmological examination including retinal optical coherence tomography (OCT). Patients were categorized according to the glycemic control, i.e. the results of an oral glucose tolerance test (OGTT) and rtCGM were taken into consideration. OCT data was analyzed by our previously published visual analysis software generating dedicated and spatially resolved deviation maps for visualization and quantification of differences in total retinal thickness and thickness of retinal nerve fiber layer (RNFL) as well as ganglion cell layer (GCL) in comparison to age-matched healthy controls and patients with either type 1 or type 2 diabetes mellitus. RESULTS: Results of the rtCGM and/or OGTT enabled discrimination between patients with normal glycemic control (CFNG; n = 6), with abnormal glycemic control (CFAG; n = 6) and overt CFRD (n = 4). OCT data indicates gradually increasing retinal thinning in all 3 groups, depending on the degree of glucose metabolism disorder compared to healthy controls. At the foveal region total retinal thickness and GCL thickness were significantly thinner in CFRD patients compared to CFNG patients (total retinal thickness: 260.4 µm (239.3-270.8) vs. 275.4 µm (254.3-289.5); GCL: 11.82 µm (11.16-15.25) vs. 17.30 µm (13.95-19.82); each p < 0.05). CONCLUSION: Although we investigated a rather small number of patients, we obtained evidence that intraretinal neurodegenerative changes occur in each of our subgroups (CFNG, CFAG, CFRD). Beyond this, our results favor the detrimental role of additional diabetes, as the deviations from healthy controls were most pronounced in the CFRD group and are similar to those seen in patients suffering from type 1 or type 2 diabetes.

An update review of post-transplant diabetes mellitus: Concept, risk factors, clinical implications and management.

OBJECTIVE: Kidney transplantation is the gold standard therapeutic alternative for patients with end-stage renal disease; nevertheless, it is not without potential complications leading to considerable morbidity and mortality such as post-transplant diabetes mellitus (PTDM). This narrative review aims to comprehensively evaluate PTDM in terms of its diagnostic approach, underlying pathophysiological pathways, epidemiological data, and management strategies. METHODS: Articles were retrieved from electronic databases using predefined search terms. Inclusion criteria encompassed studies investigating PTDM diagnosis, pathophysiology, epidemiology, and management strategies. RESULTS: PTDM emerges as a significant complication following kidney transplantation, influenced by various pathophysiological factors including peripheral insulin resistance, immunosuppressive medications, infections, and proinflammatory pathways. Despite discrepancies in prevalence estimates, PTDM poses substantial challenges to transplant. Diagnostic approaches, including traditional criteria such as fasting plasma glucose (FPG) and HbA1c, are limited in their ability to capture early PTDM manifestations. Oral glucose tolerance test (OGTT) emerges as a valuable tool, particularly in the early post-transplant period. Management strategies for PTDM remain unclear, within sufficient evidence from large-scale randomized clinical trials to guide optimal interventions. Nevertheless, glucose-lowering agents and life style modifications constitute primary modalities for managing hyperglycemia in transplant recipients. DISCUSSION: The complex interplay between PTDM and the transplant process necessitates individualized diagnostic and management approaches. While early recognition and intervention are paramount, modifications to maintenance immunosuppressive regimens based solely on PTDM risk are not warranted, given the potential adverse consequences such as increased rejection risk. Further research is essential to refine management strategies and enhance outcomes for transplant recipients.

A Single-group, Clinical Interventional Study on the Effect of Iron Deficiency Anemia on Blood Glucose and Insulin Resistance in Women with Type II Diabetes.

AIMS: Iron deficiency anemia (IDA) is one of the disorders recently associated with an increase in insulin resistance (IR) and, consequently, diabetes mellitus (DM) affection by causing oxidative stress. In this study, we look at how IDA may contribute to developing type II diabetes mellitus (T2DM), controlling diabetes, and reducing IR in women with T2DM. METHODS: In this single group, clinical interventional study, we enrolled 40 women with T2DM and IDA. Before and after intervention with ferrous sulfate tablets, their blood glucose (BG) levels and IR levels were evaluated. This study was approved by the Ethics Committee of Qom University of Medical Sciences (ethics code: IR.MUQ.REC.1397.031) and registered at the Iranian Center for Clinical Trials (No. IRCT20170215032587N3). A significant level was considered p <0.05. RESULT: The mean age of patients was 48.18 ± 4.6 years, with 5.3-5.8 years duration of T2DM. After the intervention, the mean fasting blood glucose (FBG) level reached 198.53 ± 48.11 to 170.93 ± 37.41, which was significant (p <0.0001). Also, hemoglobin A1C level reached from 8.49 ± 0.9 to 7.96 ± 0.58, which was significant (p <0.0001). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) demonstrating a significant reduction of IR levels after intervention with ferrous sulfate tablets (p <0.018). CONCLUSIONS: IDA treatment in patients with T2DM can significantly reduce the BG and IR levels. To better control BG, checking iron status and its correction may provide better clinical outcomes in these patients. CLINICAL TRIAL REGISTRATION NUMBER: IRCT20170215032587N3.

Feasibility and Performance of Continuous Glucose Monitoring to Guide Computerized Insulin Infusion Therapy in Cardiovascular Intensive Care Unit.

BACKGROUND: We evaluated the feasibility of real-time continuous glucose monitoring (CGM) for titrating continuous intravenous insulin infusion (CII) to manage hyperglycemia in postoperative individuals in the cardiovascular intensive care unit and assessed their accuracy, nursing acceptance, and postoperative individual satisfaction. METHODS: Dexcom G6 CGM devices were applied to 59 postsurgical patients with hyperglycemia receiving CII. A hybrid approach combining CGM with periodic point-of-care blood glucose (POC-BG) tests with two phases (initial-ongoing) of validation was used to determine CGM accuracy. Mean and median absolute relative differences and Clarke Error Grid were plotted to evaluate the CGM accuracy. Surveys of nurses and patients on the use of CGMs experience were conducted and results were analyzed. RESULTS: In this cohort (mean age 64, 32% female, 32% with diabetes) with 864 paired POC-BG and CGM values analyzed, mean and median absolute relative difference between POC-BG and CGM values were 13.2% and 9.8%, respectively. 99.7% of paired CGM and POC-BG were in Zones A and B of the Clarke Error Grid. Responses from nurses reported CGMs being very or quite convenient (n = 28; 93%) and it was favored over POC-BG testing (n = 28; 93%). Majority of patients (n = 42; 93%) reported their care process using CGM as being good or very good. CONCLUSION: This pilot study demonstrates the feasibility, accuracy, and nursing convenience of adopting CGM via a hybrid approach for insulin titration in postoperative settings. These findings provide robust rationale for larger confirmatory studies to evaluate the benefit of CGM in postoperative care to improve workflow, enhance health outcomes, and cost-effectiveness.

Stevioside Ameliorates Palmitic Acid-Induced Abnormal Glucose Uptake via the PDK4/AMPK/TBC1D1 Pathway in C2C12 Myotubes.

BACKGROUND: Stevioside (SV) with minimal calories is widely used as a natural sweetener in beverages due to its high sweetness and safety. However, the effects of SV on glucose uptake and the pyruvate dehydrogenase kinase isoenzyme (PDK4) as an important protein in the regulation of glucose metabolism, remain largely unexplored. In this study, we used C2C12 skeletal muscle cells that was induced by palmitic acid (PA) to assess the effects and mechanisms of SV on glucose uptake and PDK4. METHODS: The glucose uptake of C2C12 cells was determined by 2-NBDG; expression of the Pdk4 gene was measured by quantitative real-time PCR; and expression of the proteins PDK4, p-AMPK, TBC1D1 and GLUT4 was assessed by Western blotting. RESULTS: In PA-induced C2C12 myotubes, SV could significantly promote cellular glucose uptake by decreasing PDK4 levels and increasing p-AMPK and TBC1D1 levels. SV could promote the translocation of GLUT4 from the cytoplasm to the cell membrane in cells. Moreover, in Pdk4-overexpressing C2C12 myotubes, SV decreased the level of PDK4 and increased the levels of p-AMPK and TBC1D1. CONCLUSION: SV was found to ameliorate PA-induced abnormal glucose uptake via the PDK4/AMPK/TBC1D1 pathway in C2C12 myotubes. Although these results warranted further investigation for validation, they may provide some evidence of SV as a safe natural sweetener for its use in sugar-free beverages to prevent and control T2DM.