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The Western Journal of Emergency... Nov 2023Euglycemic diabetic ketoacidosis (DKA) (glucose <250 milligrams per deciliter (mg/dL) has increased in recognition since introduction of sodium-glucose co-transporter 2...
INTRODUCTION
Euglycemic diabetic ketoacidosis (DKA) (glucose <250 milligrams per deciliter (mg/dL) has increased in recognition since introduction of sodium-glucose co-transporter 2 (SGLT2) inhibitors but remains challenging to diagnose and manage without the hyperglycemia that is otherwise central to diagnosing DKA, and with increased risk for hypoglycemia with insulin use. Our objective was to compare key resource utilization and safety outcomes between patients with euglycemic and hyperglycemic DKA from the same period.
METHODS
This is a retrospective review of adult emergency department patients in DKA at an academic medical center. Patients were included if they were >18 years old, met criteria for DKA on initial laboratories (pH ≤7.30, serum bicarbonate ≤18 millimoles per liter [mmol/L], anion gap ≥10), and were managed via a standardized DKA order set. Patients were divided into euglycemic (<250 milligrams per deciliter [mg/dL]) vs hyperglycemic (≥250 mg/dL) cohorts by presenting glucose. We extracted and analyzed patient demographics, resource utilization, and safety outcomes. Etiologies of euglycemia were obtained by manual chart review. For comparisons between groups we used independent-group -tests for continuous variables and chi-squared tests for binary variables, with alpha 0.05.
RESULTS
We identified 629 patients with DKA: 44 euglycemic and 585 hyperglycemic. Euglycemic patients had milder DKA on presentation (higher pH and bicarbonate, lower anion gap; < 0.05) and lower initial glucose (195 vs 561 mg/dL, < 0.001) and potassium (4.3 vs 5.3 mmol/L, < 0.001). Etiologies of euglycemia were insulin use prior to arrival (57%), poor oral intake with baseline insulin use (29%), and SGLT2 inhibitor use (14%). Mean time on insulin infusion was shorter for those with euglycemic DKA: 13.5 vs 19.4 hours, = 0.003. Mean times to first bicarbonate >18 mmol/L and first long-acting insulin were similar. Incidence of hypoglycemia (<70 mg/dL) while on insulin infusion was significantly higher for those with euglycemic DKA (18.2 vs 4.8%, = 0.02); incidence of hypokalemia (<3.3 mmol/L) was 27.3 vs 19.1% ( = 0.23).
CONCLUSION
Compared to hyperglycemic DKA patients managed in the same protocolized fashion, euglycemic DKA patients were on insulin infusions 5.9 hours less, yet experienced hypoglycemia over three times more frequently. Future work can investigate treatment strategies for euglycemic DKA to minimize adverse events, especially iatrogenic hypoglycemia.
Topics: Adult; Humans; Adolescent; Diabetic Ketoacidosis; Bicarbonates; Insulin; Hypoglycemia; Glucose; Diabetes Mellitus
PubMed: 38165186
DOI: 10.5811/westjem.60361 -
Medical Science Monitor : International... Jul 2023BACKGROUND Human visceral adipose tissue (VAT), now identified as an endocrine organ, plays a significant role in impaired fasting glucose and diabetes through the...
BACKGROUND Human visceral adipose tissue (VAT), now identified as an endocrine organ, plays a significant role in impaired fasting glucose and diabetes through the deregulated metabolism and adipogenesis of visceral adipocytes in obesity. Our study focuses on exploring the link between inflammation, oxidative stress, and glucose metabolism-associated genes with corresponding miRNAs in human visceral adipocytes and VAT from individuals with glucose metabolism disorders. MATERIAL AND METHODS We examined the expression of ATM, NFKB1, SOD2, INSR, and TIGAR, along with their related miRNAs using PCR, in two contexts:1 - During the three-stage visceral adipogenesis under normal glucose levels (5.5 millimoles), intermittent, and chronic hyperglycemia (30 millimoles).2 - In visceral adipose tissue from subjects (34 F, 18 M) with normal glucose metabolism, impaired fasting glucose, and type 2 diabetes mellitus. RESULTS Both chronic and intermittent hyperglycemia similarly influenced ATM, NFKB1, TIGAR, SOD2, INSR gene expression in visceral adipocytes, with corresponding changes in a few tested miRNAs (eg, let-7g-5p, miR-145-5p, miR-21-5p). Anthropometric and biochemical parameters led us to focus on female subjects. Our results showed transactivation of NFKB1, TIGAR, miR-10b-5p, miR-132-3p, miR-20a-5p, miR-21-5p, and miR-26a-5p exclusively in type 2 diabetes mellitus. Upregulated molecules (excluding miR-10b-5p and miR-20a-5p) positively correlated with glucose metabolism markers. CONCLUSIONS The genes studied may undergo miRNA interferences and hyperglycemic memory in visceral adipocytes under hyperglycemic conditions. VAT from women with type 2 diabetes mellitus, but not with impaired fasting glucose, showed transactivated miRNAs and a molecular dysregulation of TIGAR and NFKB1, possibly enhancing inflammation, oxidative stress, and disrupted glucose metabolism. These findings highlight the epigenetic and molecular disturbances in VAT related to glucose metabolism abnormalities. However, additional research is necessary to further understand their biological significance.
Topics: Humans; Female; MicroRNAs; Diabetes Mellitus, Type 2; Intra-Abdominal Fat; Inflammation; Hyperglycemia; Glucose; Oxidative Stress; Adipose Tissue
PubMed: 37422695
DOI: 10.12659/MSM.939299 -
Metallomics : Integrated Biometal... Feb 2019Gadolinium-based contrast agents (GBCAs) are widely used with clinical magnetic resonance imaging (MRI), and 10 s of millions of doses of GBCAs are administered annually... (Review)
Review
Gadolinium-based contrast agents (GBCAs) are widely used with clinical magnetic resonance imaging (MRI), and 10 s of millions of doses of GBCAs are administered annually worldwide. GBCAs are hydrophilic, thermodynamically stable and kinetically inert gadolinium chelates. In clinical MRI, 5-10 millimoles of Gd ion is administered intravenously and the GBCA is rapidly eliminated intact primarily through the kidneys into the urine. It is now well-established that the Gd3+ ion, in some form(s), is partially retained in vivo. In patients with advanced kidney disease, there is an association of Gd retention with nephrogenic systemic fibrosis (NSF) disease. However Gd is also retained in the brain, bone, skin, and other tissues in patients with normal renal function, and the presence of Gd can persist months to years after the last administration of a GBCA. Regulatory agencies are restricting the use of specific GBCAs and inviting health care professionals to evaluate the risk/benefit ratio prior to using GBCAs. Despite the growing number of studies investigating this issue both in animals and humans, the biological distribution and the chemical speciation of the residual gadolinium are not fully understood. Is the GBCA retained in its intact form? Is the Gd3+ ion dissociated from its chelator, and if so, what is its chemical form? Here we discuss the current state of knowledge regarding the issue of Gd retention and describe the analytical and spectroscopic methods that can be used to investigate the Gd speciation. Many of the physical methods that could be brought to bear on this problem are in the domain of bioinorganic chemistry and we hope that this review will serve to inspire this community to take up this important problem.
Topics: Contrast Media; Gadolinium; Magnetic Resonance Imaging; Molecular Structure
PubMed: 30516229
DOI: 10.1039/c8mt00302e -
JAMA Network Open Dec 2022There have been major advances in insulin delivery and formulations over the past several decades. It is unclear whether these changes have resulted in improved glycemic...
IMPORTANCE
There have been major advances in insulin delivery and formulations over the past several decades. It is unclear whether these changes have resulted in improved glycemic control for patients with diabetes.
OBJECTIVE
To characterize trends and disparities in glycemic control and severe hyperglycemia in US adults with diabetes using insulin.
DESIGN, SETTING, AND PARTICIPANTS
This serial population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) between 1988-1994 and 1999-2020. Participants were nonpregnant US adults aged 20 years or older who had a diagnosis of diabetes and were currently using insulin.
EXPOSURES
Diabetes diagnosis and use of insulin.
MAIN OUTCOMES AND MEASURES
Trends in glycemic control (glycated hemoglobin [HbA1c] level <7%) and severe hyperglycemia (HbA1c level >10%; to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01; to convert to millimoles per mole, multiply by 10.93 and subtract by 23.50) overall and by age, race and ethnicity, and indicators of socioeconomic status were evaluated using logistic regression. Analyses incorporated sample weights to account for oversampling of certain populations and survey nonresponse.
RESULTS
There were 2482 participants with diabetes using insulin included in the analyses (mean [SD] age, 59.8 [0.4] years); 51.3% were men, 7.0% were Mexican American individuals, 17.9% were non-Hispanic Black individuals, and 65.2% were non-Hispanic White individuals. From 1988-1994 to 2013-2020, the proportion of patients with diabetes who received insulin and achieved glycemic control did not significantly change, from 29.2% (95% CI, 22.6%-36.8%) to 27.5% (95% CI, 21.7%-34.2%). Mexican American adults who received insulin were less likely than non-Hispanic White adults to achieve glycemic control, and disparities increased during the study period. The proportion of adults with severe hyperglycemia did not significantly change and was 14.6% (95% CI, 12.0-17.5) in 2013-2020. Adults who were Mexican American or non-Hispanic Black, were uninsured, or had low family income had the highest prevalence of severe hyperglycemia.
CONCLUSIONS AND RELEVANCE
In this population-based cross-sectional study of NHANES data over the past 3 decades, glycemic control stagnated and racial and ethnic disparities increased among US adults with diabetes who received insulin. Efforts to improve access to insulin may optimize glycemic control and reduce disparities in this population.
Topics: Male; Adult; Humans; Middle Aged; Female; Insulin; Nutrition Surveys; Glycated Hemoglobin; Cross-Sectional Studies; Glycemic Control; Diabetes Mellitus; Insulin, Regular, Human; Hyperglycemia
PubMed: 36538330
DOI: 10.1001/jamanetworkopen.2022.47656 -
JAMA Cardiology May 2019For patients with chronic kidney disease (CKD), hyperkalemia is common, associated with fatal arrhythmias, and often asymptomatic, while guideline-directed monitoring of...
IMPORTANCE
For patients with chronic kidney disease (CKD), hyperkalemia is common, associated with fatal arrhythmias, and often asymptomatic, while guideline-directed monitoring of serum potassium is underused. A deep-learning model that enables noninvasive hyperkalemia screening from the electrocardiogram (ECG) may improve detection of this life-threatening condition.
OBJECTIVE
To evaluate the performance of a deep-learning model in detection of hyperkalemia from the ECG in patients with CKD.
DESIGN, SETTING, AND PARTICIPANTS
A deep convolutional neural network (DNN) was trained using 1 576 581 ECGs from 449 380 patients seen at Mayo Clinic, Rochester, Minnesota, from 1994 to 2017. The DNN was trained using 2 (leads I and II) or 4 (leads I, II, V3, and V5) ECG leads to detect serum potassium levels of 5.5 mEq/L or less (to convert to millimoles per liter, multiply by 1) and was validated using retrospective data from the Mayo Clinic in Minnesota, Florida, and Arizona. The validation included 61 965 patients with stage 3 or greater CKD. Each patient had a serum potassium count drawn within 4 hours after their ECG was recorded. Data were analyzed between April 12, 2018, and June 25, 2018.
EXPOSURES
Use of a deep-learning model.
MAIN OUTCOMES AND MEASURES
Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity, with serum potassium level as the reference standard. The model was evaluated at 2 operating points, 1 for equal specificity and sensitivity and another for high (90%) sensitivity.
RESULTS
Of the total 1 638 546 ECGs, 908 000 (55%) were from men. The prevalence of hyperkalemia in the 3 validation data sets ranged from 2.6% (n = 1282 of 50 099; Minnesota) to 4.8% (n = 287 of 6011; Florida). Using ECG leads I and II, the AUC of the deep-learning model was 0.883 (95% CI, 0.873-0.893) for Minnesota, 0.860 (95% CI, 0.837-0.883) for Florida, and 0.853 (95% CI, 0.830-0.877) for Arizona. Using a 90% sensitivity operating point, the sensitivity was 90.2% (95% CI, 88.4%-91.7%) and specificity was 63.2% (95% CI, 62.7%-63.6%) for Minnesota; the sensitivity was 91.3% (95% CI, 87.4%-94.3%) and specificity was 54.7% (95% CI, 53.4%-56.0%) for Florida; and the sensitivity was 88.9% (95% CI, 84.5%-92.4%) and specificity was 55.0% (95% CI, 53.7%-56.3%) for Arizona.
CONCLUSIONS AND RELEVANCE
In this study, using only 2 ECG leads, a deep-learning model detected hyperkalemia in patients with renal disease with an AUC of 0.853 to 0.883. The application of artificial intelligence to the ECG may enable screening for hyperkalemia. Prospective studies are warranted.
Topics: Aged; Aged, 80 and over; Algorithms; Arrhythmias, Cardiac; Artificial Intelligence; Deep Learning; Electrocardiography; Female; Humans; Hyperkalemia; Male; Mass Screening; Middle Aged; Neural Networks, Computer; Prevalence; Renal Insufficiency, Chronic; Retrospective Studies; Sensitivity and Specificity
PubMed: 30942845
DOI: 10.1001/jamacardio.2019.0640 -
Proceedings of the National Academy of... Sep 2022Saturn's moon Enceladus has a potentially habitable subsurface water ocean that contains canonical building blocks of life (organic and inorganic carbon, ammonia,...
Saturn's moon Enceladus has a potentially habitable subsurface water ocean that contains canonical building blocks of life (organic and inorganic carbon, ammonia, possibly hydrogen sulfide) and chemical energy (disequilibria for methanogenesis). However, its habitability could be strongly affected by the unknown availability of phosphorus (P). Here, we perform thermodynamic and kinetic modeling that simulates P geochemistry based on recent insights into the geochemistry of the ocean-seafloor system on Enceladus. We find that aqueous P should predominantly exist as orthophosphate (e.g., HPO), and total dissolved inorganic P could reach 10 to 10 mol/kg HO, generally increasing with lower pH and higher dissolved CO, but also depending upon dissolved ammonia and silica. Levels are much higher than <10 mol/kg HO from previous estimates and close to or higher than ∼10 mol/kg HO in modern Earth seawater. The high P concentration is primarily ascribed to a high (bi)carbonate concentration, which decreases the concentrations of multivalent cations via carbonate mineral formation, allowing phosphate to accumulate. Kinetic modeling of phosphate mineral dissolution suggests that geologically rapid release of P from seafloor weathering of a chondritic rocky core could supply millimoles of total dissolved P per kilogram of HO within 10 y, much less than the likely age of Enceladus's ocean (10 to 10 y). These results provide further evidence of habitable ocean conditions and show that any oceanic life would not be inhibited by low P availability.
Topics: Ammonia; Carbon; Carbon Dioxide; Hydrogen Sulfide; Minerals; Oceans and Seas; Phosphates; Phosphorus; Silicon Dioxide; Water
PubMed: 36122219
DOI: 10.1073/pnas.2201388119 -
JAMA Pediatrics Mar 2015Recent national data suggest there were improvements in serum lipid concentrations among US children and adolescents between 1988 and 2010 but an increase in or stable...
IMPORTANCE
Recent national data suggest there were improvements in serum lipid concentrations among US children and adolescents between 1988 and 2010 but an increase in or stable blood pressure (BP) during a similar period.
OBJECTIVE
To describe the prevalence of and trends in dyslipidemia and adverse BP among US children and adolescents.
DESIGN
The National Health and Nutrition Examination Survey, a cross-sectional survey.
SETTING
Noninstitutionalized US population.
PARTICIPANTS
Children and adolescents aged 8 to 17 years with measured lipid concentrations (n = 1482) and BP (n = 1665).
MAIN OUTCOMES AND MEASURES
Adverse concentrations of total cholesterol (TC) (≥ 200 mg/dL), high-density lipoprotein cholesterol (HDL-C) (<40 mg/dL), and non-HDL-C (≥ 145 mg/dL) (to convert TC, HDL-C, and non-HDL-C to millimoles per liter, multiply by 0.0259) and high or borderline BP were examined. Definitions of BP were informed by the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. Analyses of linear trends in dyslipidemias and BP were conducted overall and separately by sex across 7 periods (1999-2000, 2001-2002, 2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012).
RESULTS
In 2011-2012, 20.2% (95% CI, 16.3-24.6) of youths had an adverse concentration of TC, HDL-C, or non-HDL-C and 11.0% (95% CI, 8.8-13.4) had either high or borderline BP. The prevalences of adverse concentrations decreased between 1999-2000 and 2011-2012 for TC (10.6% [95% CI, 8.3-13.2] vs 7.8% [95% CI, 5.7-10.4]; P = .006), HDL-C (17.9% [95% CI, 15.0-21.0] vs 12.8% [95% CI, 9.8-16.2]; P = .003), and non-HDL-C (13.6% [95% CI, 11.3-16.2] vs 8.4% [95% CI, 5.9-11.5]; P < .001). There was a decrease in high BP between 1999-2000 (3.0% [95% CI, 2.0-4.3]) and 2011-2012 (1.6% [95% CI, 1.0-2.4]) (P = .003). There was no change from 1999-2000 to 2011-2012 in borderline high BP (7.6% [95% CI, 5.8-9.8] vs 9.4% [95% CI, 7.2-11.9]; P = .90) or either high or borderline high BP (10.6% [8.4-13.1] vs 11.0% [95% CI, 8.8-13.4]; P = .26).
CONCLUSIONS AND RELEVANCE
In 2011-2012, approximately 1 in 5 children and adolescents aged 8 to 17 years had an adverse lipid concentration of TC, HDL-C, or non-HDL-C and slightly more than 1 in 10 had either borderline high or high BP. The prevalence of dyslipidemia modestly decreased between 1999-2000 and 2011-2012, but either high or borderline high BP remained stable. The reasons for these trends require further study.
Topics: Adolescent; Blood Pressure; Child; Cross-Sectional Studies; Dyslipidemias; Female; Humans; Hypertension; Lipids; Male; Nutrition Surveys; Prevalence; United States
PubMed: 25599372
DOI: 10.1001/jamapediatrics.2014.3216 -
Journal of the American Society of... Oct 2022Harmful glucose exposure and absorption remain major limitations of peritoneal dialysis (PD). We previously showed that inhibition of sodium glucose cotransporter 2 did...
BACKGROUND
Harmful glucose exposure and absorption remain major limitations of peritoneal dialysis (PD). We previously showed that inhibition of sodium glucose cotransporter 2 did not affect glucose transport during PD in rats. However, more recently, we found that phlorizin, a dual blocker of sodium glucose cotransporters 1 and 2, reduces glucose diffusion in PD. Therefore, either inhibiting sodium glucose cotransporter 1 or blocking facilitative glucose channels by phlorizin metabolite phloretin would reduce glucose transport in PD.
METHODS
We tested a selective blocker of sodium glucose cotransporter 1, mizagliflozin, as well as phloretin, a nonselective blocker of facilitative glucose channels, in an anesthetized Sprague-Dawley rat model of PD.
RESULTS
Intraperitoneal phloretin treatment reduced glucose absorption by >30% and resulted in a >50% higher ultrafiltration rate compared with control animals. Sodium removal and sodium clearances were similarly improved, whereas the amount of ultrafiltration per millimole of sodium removed did not differ. Mizagliflozin did not influence glucose transport or osmotic water transport.
CONCLUSIONS
Taken together, our results and previous results indicate that blockers of facilitative glucose channels may be a promising target for reducing glucose absorption and improving ultrafiltration efficiency in PD.
Topics: Rats; Animals; Sodium-Glucose Transporter 1; Dialysis Solutions; Glucose; Rats, Sprague-Dawley; Ultrafiltration; Phloretin; Phlorhizin; Peritoneal Dialysis; Biological Transport; Sodium; Peritoneum
PubMed: 35985816
DOI: 10.1681/ASN.2022040474 -
Nature Dec 2021Carbon capture and storage (CCS) is a key technology to mitigate the environmental impact of carbon dioxide (CO) emissions. An understanding of the potential trapping...
Carbon capture and storage (CCS) is a key technology to mitigate the environmental impact of carbon dioxide (CO) emissions. An understanding of the potential trapping and storage mechanisms is required to provide confidence in safe and secure CO geological sequestration. Depleted hydrocarbon reservoirs have substantial CO storage potential,, and numerous hydrocarbon reservoirs have undergone CO injection as a means of enhanced oil recovery (CO-EOR), providing an opportunity to evaluate the (bio)geochemical behaviour of injected carbon. Here we present noble gas, stable isotope, clumped isotope and gene-sequencing analyses from a CO-EOR project in the Olla Field (Louisiana, USA). We show that microbial methanogenesis converted as much as 13-19% of the injected CO to methane (CH) and up to an additional 74% of CO was dissolved in the groundwater. We calculate an in situ microbial methanogenesis rate from within a natural system of 73-109 millimoles of CH per cubic metre (standard temperature and pressure) per year for the Olla Field. Similar geochemical trends in both injected and natural CO fields suggest that microbial methanogenesis may be an important subsurface sink of CO globally. For CO sequestration sites within the environmental window for microbial methanogenesis, conversion to CH should be considered in site selection.
Topics: Bacteria; Carbon Dioxide; Geology; Groundwater; Methane; Temperature
PubMed: 34937895
DOI: 10.1038/s41586-021-04153-3 -
Surgical Endoscopy Oct 2023In metabolic surgery, hemorrhage is the most common major complication. This study investigated whether peroperative administration of tranexamic acid (TXA) reduced the... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
In metabolic surgery, hemorrhage is the most common major complication. This study investigated whether peroperative administration of tranexamic acid (TXA) reduced the risk of hemorrhage in patients undergoing laparoscopic sleeve gastrectomy (SG).
METHODS
In this double-blind randomized controlled trial, patients undergoing primary SG in a high-volume bariatric hospital were randomized (1:1) to receive 1500-mg TXA or placebo peroperatively. Primary outcome measure was peroperative staple line reinforcement using hemostatic clips. Secondary outcome measures were peroperative fibrin sealant use and blood loss, postoperative hemoglobin, heart rate, pain, major and minor complications, length of hospital stay (LOS), side effects of TXA (i.e., venous thrombotic event (VTE)) and mortality.
RESULTS
In total, 101 patients were analyzed and received TXA (n = 49) or placebo (n = 52). There was no statistically significant difference in hemostatic clip devices used in both groups (69% versus 83%, p = 0.161). TXA administration showed significant positive changes in hemoglobin levels (millimoles per Liter; 0.55 versus 0.80, p = 0.013), in heart rate (beats per minute; -4.6 versus 2.5; p = 0.013), in minor complications (Clavien-Dindo ≤ 2, 2.0% versus 17.3%, p = 0.016), and in mean LOS (hours; 30.8 versus 36.7, p = 0.013). One patient in the placebo-group underwent radiological intervention for postoperative hemorrhage. No VTE or mortality was reported.
CONCLUSION
This study did not demonstrate a statistically significant difference in use of hemostatic clip devices and major complications after peroperative administration of TXA. However, TXA seems to have positive effects on clinical parameters, minor complications, and LOS in patients undergoing SG, without increasing the risk of VTE. Larger studies are needed to investigate the effect of TXA on postoperative major complications.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Postoperative Hemorrhage; Double-Blind Method; Blood Loss, Surgical; Administration, Intravenous
PubMed: 37400687
DOI: 10.1007/s00464-023-10232-5