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Up to 25% of patients with long COVID experience persistent night sweats. However, in most cases they remain untreated until they disappear on their own. Since SARS-CoV-2 is known to disrupt glucose homeostasis, we hypothesized that impaired mitochondria would result in faster glycogen depletion at night due to reduced ATP production yield, inducing adrenaline production ultimately leading to the onset of persistent night sweats. To test our hypothesis we investigated whether incorporating carbohydrates into the diet of three non-diabetic patients with long COVID before bedtime would have any effect decreasing their night sweats. Remarkably, after one week with the dietary intervention, the patients reported that their night sweats had completely disappeared. Therefore, we propose carbohydrate supplementation as an affordable solution for night sweats in long COVID patients.

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.

BACKGROUND: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. METHODS: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. RESULTS: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. CONCLUSION: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clini

BACKGROUND: The supraclavicular fossa is the dominant location for human brown adipose tissue (BAT). Activation of BAT promotes non-shivering thermogenesis by utilization of glucose and free fatty acids and has been the focus of pharmacological and non-pharmacological approaches for modulation in order to improve body weight and glucose homeostasis. Sympathetic neural control of supraclavicular BAT has received much attention, but its innervation has not been extensively investigated in humans. METHODS: Dissection of the cervical region in human cadavers was performed to find the distribution of sympathetic nerve branches to supraclavicular fat pad. Furthermore, proximal segments of the 4th cervical nerve were evaluated histologically to assess its sympathetic components. RESULTS: Nerve branches terminating in supraclavicular fat pad were identified in all dissections, including those from the 3rd and 4th cervical nerves and from the cervical sympathetic plexus. Histology of the proximal segments of the 4th cervical nerves confirmed tyrosine hydroxylase positive thin nerve fibers in all fascicles with either a scattered or clustered distribution pattern. The scattered pattern was more predominant than the clustered pattern (80% vs. 20%) across cadavers. These sympathetic nerve fibers occupied only 2.48% of the nerve cross sectional area on average. CONCLUSIONS: Human sympathetic nerves use multiple pathways to innervate the supraclavicular fat pad. The present finding serves as a framework for future clinical approaches to activate human BAT in the supraclavicular region.

Propionate is a microbial metabolite formed in the gastrointestinal tract, and it affects host physiology as a source of energy and signaling molecule. Despite the importance of propionate, the biochemical pathways responsible for its formation are not clear in all microbes. For the succinate pathway used during fermentation, a key enzyme appears to be missing-one that oxidizes ferredoxin and reduces NAD. Here we show that Rnf [ferredoxin-NAD+ oxidoreductase (Na+-transporting)] is this key enzyme in two abundant bacteria of the rumen (Prevotella brevis and Prevotella ruminicola). We found these bacteria form propionate, succinate, and acetate with the classic succinate pathway. Without ferredoxin:NAD+ oxidoreductase, redox cofactors would be unbalanced; it would produce almost equal excess amounts of reduced ferredoxin and oxidized NAD. By combining growth experiments, genomics, proteomics, and enzyme assays, we point to the possibility that these bacteria solve this problem by oxidizing ferredoxin and reducing NAD with Rnf [ferredoxin-NAD+ oxidoreductase (Na+-transporting)]. Genomic and phenotypic data suggest many bacteria may use Rnf similarly. This work shows the ferredoxin:NAD+ oxidoreductase activity of Rnf is important to propionate formation in Prevotella species and other bacteria from the environment, and it provides fundamental knowledge for manipulating fermentative propionate production.

Detection of small molecule metabolites (SMM), particularly those involved in energy metabolism using MALDI-mass spectrometry imaging (MSI), is challenging due to factors including ion suppression from other analytes present (e.g., proteins and lipids). One potential solution to enhance SMM detection is to remove analytes that cause ion suppression from tissue sections before matrix deposition through solvent washes. Here, we systematically investigated solvent treatment conditions to improve SMM signal and preserve metabolite localization. Washing with acidic methanol significantly enhances the detection of phosphate-containing metabolites involved in energy metabolism. The improved detection is due to removing lipids and highly polar metabolites that cause ion suppression and denaturing proteins that release bound phosphate-containing metabolites. Stable isotope infusions of [13C6]nicotinamide coupled to MALDI-MSI (Iso-imaging) in the kidney reveal patterns that indicate blood vessels, medulla, outer stripe, and cortex. We also observed different ATP:ADP raw signals across mouse kidney regions, consistent with regional differences in glucose metabolism favoring either gluconeogenesis or glycolysis. In mouse muscle, Iso-imaging using [13C6]glucose shows high glycolytic flux from infused circulating glucose in type 1 and 2a fibers (soleus) and relatively lower glycolytic flux in type 2b fiber type (gastrocnemius). Thus, improved detection of phosphate-containing metabolites due to acidic methanol treatment combined with isotope tracing provides an improved way to probe energy metabolism with spatial resolution in vivo.

Branched-chain amino acid (BCAA) metabolism is linked to glucose homeostasis, but the underlying signaling mechanisms are unclear. We find that gluconeogenesis is reduced in mice deficient of Ppm1k, a positive regulator of BCAA catabolism, which protects against obesity-induced glucose intolerance. Accumulation of branched-chain keto acids (BCKAs) inhibits glucose production in hepatocytes. BCKAs suppress liver mitochondrial pyruvate carrier (MPC) activity and pyruvate-supported respiration. Pyruvate-supported gluconeogenesis is selectively suppressed in Ppm1k-deficient mice and can be restored with pharmacological activation of BCKA catabolism by BT2. Finally, hepatocytes lack branched-chain aminotransferase that alleviates BCKA accumulation via reversible conversion between BCAAs and BCKAs. This renders liver MPC most susceptible to circulating BCKA levels hence a sensor of BCAA catabolism.

Neurons require large amounts of energy, but whether they can perform glycolysis or require glycolysis to maintain energy remains unclear. Using metabolomics, we show that human neurons do metabolize glucose through glycolysis and can rely on glycolysis to supply tricarboxylic acid (TCA) cycle metabolites. To investigate the requirement for glycolysis, we generated mice with postnatal deletion of either the dominant neuronal glucose transporter (GLUT3cKO) or the neuronal-enriched pyruvate kinase isoform (PKM1cKO) in CA1 and other hippocampal neurons. GLUT3cKO and PKM1cKO mice show age-dependent learning and memory deficits. Hyperpolarized magnetic resonance spectroscopic (MRS) imaging shows that female PKM1cKO mice have increased pyruvate-to-lactate conversion, whereas female GLUT3cKO mice have decreased conversion, body weight, and brain volume. GLUT3KO neurons also have decreased cytosolic glucose and ATP at nerve terminals, with spatial genomics and metabolomics revealing compensatory changes in mitochondrial bioenergetics and galactose metabolism. Therefore, neurons metabolize glucose through glycolysis in vivo and require glycolysis for normal function.

Pseudomonas putida have emerged as promising biocatalysts for the conversion of sugars and aromatic compounds obtained from lignocellulosic biomass. Understanding the role of carbon catabolite repression (CCR) in these strains is critical to optimize biomass conversion to fuels and chemicals. The CCR functioning in P. putida M2, a strain capable of consuming both hexose and pentose sugars as well as aromatic compounds, was investigated by cultivation experiments, proteomics, and CRISPRi-based gene repression. Strain M2 co-utilized sugars and aromatic compounds simultaneously; however, during cultivation with glucose and aromatic compounds (p-coumarate and ferulate) mixture, intermediates (4-hydroxybenzoate and vanillate) accumulated, and substrate consumption was incomplete. In contrast, xylose-aromatic consumption resulted in transient intermediate accumulation and complete aromatic consumption, while xylose was incompletely consumed. Proteomics analysis revealed that glucose exerted stronger repression than xylose on the aromatic catabolic proteins. Key glucose (Eda) and xylose (XylX) catabolic proteins were also identified at lower abundance during cultivation with aromatic compounds implying simultaneous catabolite repression by sugars and aromatic compounds. Reduction of crc expression via CRISPRi led to faster growth and glucose and p-coumarate uptake in the CRISPRi strains compared to the control, while no difference was observed on xylose+p-coumarate. The increased abundances of Eda and amino acid biosynthesis proteins in the CRISPRi strain further supported these observations. Lastly, small RNAs (sRNAs) sequencing results showed that CrcY and CrcZ homologues levels in M2, previously identified in P. putida strains, were lower under strong CCR (glucose+p-coumarate) condition compared to when repression was absent (p-coumarate or glucose only).IMPORTANCEA newly isolated Pseudomonas putida strain, P. putida M2, can utilize both hexose and pentose sugars as wel

Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms generated by the concerted activity of these clocks is associated with metabolic disease. Here we tested the interactions between clocks in two critical components of organismal metabolism, liver and skeletal muscle, by rescuing clock function either in each organ separately or in both organs simultaneously in otherwise clock-less mice. Experiments showed that individual clocks are partially sufficient for tissue glucose metabolism, yet the connections between both tissue clocks coupled to daily feeding rhythms support systemic glucose tolerance. This synergy relies in part on local transcriptional control of the glucose machinery, feeding-responsive signals such as insulin, and metabolic cycles that connect the muscle and liver. We posit that spatiotemporal mechanisms of muscle and liver play an essential role in the maintenance of systemic glucose homeostasis and that disrupting this diurnal coordination can contribute to metabolic disease.

Conventional whole-body static 18F-FDG PET imaging provides a semiquantitative evaluation of overall glucose metabolism without insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric 18F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19). Methods: The study included 13 healthy subjects and 12 recovering COVID-19 subjects within 8 wk of confirmed diagnosis. Each subject had a 1-h dynamic 18F-FDG scan on the uEXPLORER total-body PET/CT system. Semiquantitative SUV and the SUV ratio relative to blood (SUVR) were calculated for different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify the microparametric blood-to-tissue 18F-FDG delivery rate [Formula: see text] and the phosphorylation rate k 3, as well as the macroparametric 18F-FDG net influx rate ([Formula: see text]). Statistical tests were performed to examine differences between healthy subjects and recovering COVID-19 subjects. The effect of COVID-19 vaccination was also investigated. Results: We detected no significant difference in lung SUV but significantly higher lung SUVR and [Formula: see text] in COVID-19 recovery, indicating improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate k 3 but not with [Formula: see text], which suggests that glucose phosphorylation, rather than glucose delivery, drives the observed difference of glucose metabolism. Meanwhile, there was no or little difference in bone marrow 18F-FDG metabolism measured with SUV, SUVR, and [Formula: see text] but a significantly higher bone marrow [Formula: see text] in the COVID-19 group, suggesting a difference

Methyl jasmonate (MeJA) is a known elicitor of plant specialized metabolism, including triterpenoid saponins. Saponaria vaccaria is an annual herb used in traditional Chinese medicine, containing large quantities of oleanane-type triterpenoid saponins with anticancer properties and structural similarities to the vaccine adjuvant QS-21. Leveraging the MeJA-elicited saponin biosynthesis, we identify multiple enzymes catalyzing the oxidation and glycosylation of triterpenoids in S. vaccaria. This exploration is aided by Pacbio full-length transcriptome sequencing and gene expression analysis. A cellulose synthase-like enzyme can not only glucuronidate triterpenoid aglycones but also alter the product profile of a cytochrome P450 monooxygenase via preference for the aldehyde intermediate. Furthermore, the discovery of a UDP-glucose 4,6-dehydratase and a UDP-4-keto-6-deoxy-glucose reductase reveals the biosynthetic pathway for the rare nucleotide sugar UDP-D-fucose, a likely sugar donor for fucosylation of plant natural products. Our work enables the production and optimization of high-value saponins in microorganisms and plants through synthetic biology approaches.

Methyl jasmonate (MeJA) is a known elicitor of plant specialized metabolism, including triterpenoid saponins. Saponaria vaccaria is an annual herb used in traditional Chinese medicine, containing large quantities of oleanane-type triterpenoid saponins with anticancer properties and structural similarities to the vaccine adjuvant QS-21. Leveraging the MeJA-elicited saponin biosynthesis, we identify multiple enzymes catalyzing the oxidation and glycosylation of triterpenoids in S. vaccaria. This exploration is aided by Pacbio full-length transcriptome sequencing and gene expression analysis. A cellulose synthase-like enzyme can not only glucuronidate triterpenoid aglycones but also alter the product profile of a cytochrome P450 monooxygenase via preference for the aldehyde intermediate. Furthermore, the discovery of a UDP-glucose 4,6-dehydratase and a UDP-4-keto-6-deoxy-glucose reductase reveals the biosynthetic pathway for the rare nucleotide sugar UDP-D-fucose, a likely sugar donor for fucosylation of plant natural products. Our work enables the production and optimization of high-value saponins in microorganisms and plants through synthetic biology approaches.

Cellulose hydrolysis to glucose using a heterogeneous catalyst is a necessary step in producing bio-based chemicals and polymers. The requirement for energy-intensive pretreatments, such as ball milling, to increase the reactivity of cellulose is one of the major issues in this area. Here, we show that by using solvent-assisted adsorption as a pretreatment step, cellulose can be adsorbed on the surface of a carbon catalyst. For adsorption pretreatment, phosphoric acid (H3PO4) performed better than other solvents such as sulfuric acid (H2SO4), tetrabutylammonium fluoride/dimethyl sulfoxide (TBAF/DMSO) and 1-butyl-3-methylimidazolium chloride ([BMMI]Cl). Hydrolysis after the adsorption of cellulose and the removal of H3PO4 produced a 73% yield of glucose. Partial hydrolysis of cellulose in H3PO4 before adsorption increased the final glucose yield. The glucose yield was proportional to the number of weakly acidic functional groups on the carbon catalyst, indicating the reaction was heterogeneously catalyzed. In a preliminary lab-scale life-cycle analysis (LCA), greenhouse gas (GHG) emissions per kg of glucose produced through the hydrolysis of cellulose were calculated. The H3PO4-assisted adsorption notably reduces GHG emissions compared to the previously reported ball milling pretreatment.

Cephalic-phase insulin release (CPIR) occurs before blood glucose increases after a meal. Although glucose is the most plausible cue to induce CPIR, peripheral sensory systems involved are not fully elucidated. We therefore examined roles of sweet sensing by a T1R3-dependent taste receptor and sugar sensing by oral glucose transporters in the oropharyngeal region in inducing CPIR. Spontaneous oral ingestion of glucose significantly increased plasma insulin 5 min later in wild-type (C57BL/6) and T1R3-knockout mice, but intragastric infusion did not. Oral treatment of glucose transporter inhibitors phlorizin and phloretin significantly reduced CPIR after spontaneous oral ingestion. In addition, a rapid increase in plasma insulin was significantly smaller in WT mice with spontaneous oral ingestion of nonmetabolizable glucose analog than in WT mice with spontaneous oral ingestion of glucose. Taken together, the T1R3-dependent receptor is not required for CPIR, but oral glucose transporters greatly contribute to induction of CPIR by sugars.

Diabetes is a chronic metabolic disease characterized by high blood glucose levels, when the pancreas does not produce enough insulin or when the body cannot metabolize it efficiently, it usually occurs with various comorbidities that deteriorate the health of patients. Community-acquired pneumonia is an infection at the lung level, which together with other factors can cause complications and lead the patient to death. Objective: To determine the morbidity and mortality of community pneumonia in type 2 diabetics with mechanical ventilation, admitted to the intensive care unit of the Luis Vernaza Hospital, through the review of medical records, providing information to promote its prevention and reduce its incidence. Methodo-logy: It is a non-experimental, descriptive and correlational investigation of a retrospective, cross-sectional nature, with an observational, quantitative approach, in addition to the bibliographic review that provides theoretical support for the study. The technique and the APACHE II assessment score, the instrument was an observation sheet for the medical records of 86 patients admitted to intensive care at the Luis Vernaza Hospital, from March 2020 to March 2021. Results. The APACHE II assessment score revealed; high mortality rate and the presence of comorbidities was 100%. The patients were between 60 and 79 years old and had a stay of 1 to 7 days in intensive care, 79.3% had a glucose level greater than 126 mg/dl. Con-clusions: Hospital institutions should generate prevention strategies, with the support of specialists, raising awareness in diabetic patients about good glycemic control, improving their lifestyle, promoting immunization, especially in older adults to prevent pneumonia, avoiding admissions, complications and deaths in the intensive care unit., La diabetes es una enfermedad metabólica crónica caracterizada por niveles elevados de glucosa en sangre, cuando el páncreas no produce suficiente insulina o cuando el organismo no puede metabolizarla eficientemente, suele cursar con diversas comorbilidades que deterioran la salud de lo pacientes. La Neumonía adquirida en la comunidad, es una infección a nivel pulmonar, que junto a otros factores pueden causar complicaciones y llevar al paciente a la muerte. Objetivo: Determinar la morbimortalidad de la Neumonía comunitaria en diabéticos tipo 2 con ventilación mecánica, ingresados en la unidad de cuidados intensivos del Hospital Luis Vernaza, a través de la revisión de las historias clínicas brindando información para promover su prevención y reducir su incidencia. Metodología: Es una investigación no experimental, descriptiva y correlacional de carácter retrospectivo transversal, con enfoque observacional, cuantitativo, además de la revisión bibliográfica que proporciona sustento teórico del estudio. La técnica y el puntaje de valoración APACHE II, el instrumento fue una ficha de observación para las historias clínicas de 86 pacientes ingresados a cuidados intensivos en el Hospital Luis Vernaza, periodo de marzo 2020 a marzo 2021. Resultados: El puntaje de valoración APACHE II reveló; elevado índice de mortalidad y la presencia de comorbilidades fue del 100%. Los pacientes tenían entre los 60 y 79 años y tuvieron una estadía de 1 a 7 días en cuidados intensivos, el 79.3% tenía un nivel de glucosa mayor a 126 mg/dl. Conclusiones: Las instituciones hospitalarias deben generar estrategias de prevención, con apoyo de especialistas, formando conciencia en pacientes diabéticos, sobre un buen control de la glucemia, mejorando su estilo de vida, promoviendo la inmunización, especialmente en los adultos mayores para prevenir neumonía, evitando ingresos, complicaciones y falle-cimientos en la sala de cuidados intensivos

Thanks to a general multidisciplinary and interdisciplinary approach, during the last few decades there have been huge advances in the diagnostic field. In particular, the miniaturization and automation of several assays have led to the development of the so-called point-of-care tests (PoCT), which are devices capable to provide accurate and specific detection of analytes such as glucose, other clinically-relevant biomarkers, pathogens, and drugs. The detection with these devices typically takes place in a few minutes and without the need of specialized personnel. Here we discuss the key technologies and applications of PoCTs, as well as the major challenges in the clinical environment.

Diabetes is a chronic metabolic disease characterized by high blood glucose levels, when the pancreas does not produce enough insulin or when the body cannot metabolize it efficiently, it usually occurs with various comorbidities that deteriorate the health of patients. Community-acquired pneumonia is an infection at the lung level, which together with other factors can cause complications and lead the patient to death. Objective: To determine the morbidity and mortality of community pneumonia in type 2 diabetics with mechanical ventilation, admitted to the intensive care unit of the Luis Vernaza Hospital, through the review of medical records, providing information to promote its prevention and reduce its incidence. Methodo-logy: It is a non-experimental, descriptive and correlational investigation of a retrospective, cross-sectional nature, with an observational, quantitative approach, in addition to the bibliographic review that provides theoretical support for the study. The technique and the APACHE II assessment score, the instrument was an observation sheet for the medical records of 86 patients admitted to intensive care at the Luis Vernaza Hospital, from March 2020 to March 2021. Results. The APACHE II assessment score revealed; high mortality rate and the presence of comorbidities was 100%. The patients were between 60 and 79 years old and had a stay of 1 to 7 days in intensive care, 79.3% had a glucose level greater than 126 mg/dl. Con-clusions: Hospital institutions should generate prevention strategies, with the support of specialists, raising awareness in diabetic patients about good glycemic control, improving their lifestyle, promoting immunization, especially in older adults to prevent pneumonia, avoiding admissions, complications and deaths in the intensive care unit., La diabetes es una enfermedad metabólica crónica caracterizada por niveles elevados de glucosa en sangre, cuando el páncreas no produce suficiente insulina o cuando el organismo no puede metabolizarla eficientemente, suele cursar con diversas comorbilidades que deterioran la salud de lo pacientes. La Neumonía adquirida en la comunidad, es una infección a nivel pulmonar, que junto a otros factores pueden causar complicaciones y llevar al paciente a la muerte. Objetivo: Determinar la morbimortalidad de la Neumonía comunitaria en diabéticos tipo 2 con ventilación mecánica, ingresados en la unidad de cuidados intensivos del Hospital Luis Vernaza, a través de la revisión de las historias clínicas brindando información para promover su prevención y reducir su incidencia. Metodología: Es una investigación no experimental, descriptiva y correlacional de carácter retrospectivo transversal, con enfoque observacional, cuantitativo, además de la revisión bibliográfica que proporciona sustento teórico del estudio. La técnica y el puntaje de valoración APACHE II, el instrumento fue una ficha de observación para las historias clínicas de 86 pacientes ingresados a cuidados intensivos en el Hospital Luis Vernaza, periodo de marzo 2020 a marzo 2021. Resultados: El puntaje de valoración APACHE II reveló; elevado índice de mortalidad y la presencia de comorbilidades fue del 100%. Los pacientes tenían entre los 60 y 79 años y tuvieron una estadía de 1 a 7 días en cuidados intensivos, el 79.3% tenía un nivel de glucosa mayor a 126 mg/dl. Conclusiones: Las instituciones hospitalarias deben generar estrategias de prevención, con apoyo de especialistas, formando conciencia en pacientes diabéticos, sobre un buen control de la glucemia, mejorando su estilo de vida, promoviendo la inmunización, especialmente en los adultos mayores para prevenir neumonía, evitando ingresos, complicaciones y falle-cimientos en la sala de cuidados intensivos

Up to 25% of patients with long COVID experience persistent night sweats. However, in most cases they remain untreated until they disappear on their own. Since SARS-CoV-2 is known to disrupt glucose homeostasis, we hypothesized that impaired mitochondria would result in faster glycogen depletion at night due to reduced ATP production yield, inducing adrenaline production ultimately leading to the onset of persistent night sweats. To test our hypothesis we investigated whether incorporating carbohydrates into the diet of three non-diabetic patients with long COVID before bedtime would have any effect decreasing their night sweats. Remarkably, after one week with the dietary intervention, the patients reported that their night sweats had completely disappeared. Therefore, we propose carbohydrate supplementation as an affordable solution for night sweats in long COVID patients.

by Valentin Leonard Schwartz, BSc, Masterarbeit Universität Innsbruck 2023

[Resumen] Durante los últimos años, el desarrollo de sensores de concentración de glucosa a través de resonadores planares de microondas ha llamado la atención de una considerable parte de la comunidad científica. Tras mostrar algunos resultados prometedores, los sensores experimentales actuales se enfrentan a ciertos desafíos primordiales. Entre ellos, el más crítico parece ser la selectividad a la concentración de glucosa frente a las variaciones de las concentraciones de otros componentes o parámetros. En este artículo estudiamos la selectividad experimental de sensores basados en resonadores de microondas al medir disoluciones multicomponente. Evaluamos minuciosamente el funcionamiento de estos sensores al medir disoluciones de agua pura, NaCl, albúmina y glucosa, analizando el impacto de las variaciones simultáneas de las concentraciones de glucosa y albúmina. Los resultados muestran una clara influencia de la concentración de albúmina en las medidas de la concentración de glucosa, lo que apunta a una falta de selectividad para estos los sensores. Hemos modelado esta influencia, y a partir de ella proponemos estrategias para afrontar el desafío de la selectividad con este tipo de sensores., [Abstract] During the last years, the development of glucose concentration sensors with microwave planar resonators has raised the attention of a notable part of the academic community. After showing some promising results, the current experimental sensors are facing certain key challenges. Particularly, the selectivity to the glucose concentration against the changes in the concentrations of other solutes or variables is one of the most worrying ones. In this paper we perform a close scrutiny of the experimental selectivity found in microwave resonant sensors when making measurements with multicomponent solutions. We painstakingly evaluate the performance of these sensors while measuring solutions of pure water, NaCl, albumin and glucose, and we analyze the influence of the simultaneous variations of the glucose and albumin concentrations. The results reveal an evident influence of the albumin concentration on the identification of the glucose concentration, therefore indicating a weak selectivity. We have modelled this effect, and we thereby propose strategies for dealing with this selectivity issue.

Electrocatalytic glucose oxidation can produce high value chemicals, but selectivity needs to be improved. Here we elucidate the role of the Pt oxidation state on the activity and selectivity of electrocatalytic oxidation of glucose with a new analytical approach, using high-pressure liquid chromatography and high-pressure anion exchange chromatography. It was found that the type of oxidation, i.e. dehydrogenation of primary and secondary alcohol groups or oxygen transfer to aldehyde groups, strongly depends on the Pt oxidation state. Pt0 has a 7-fold higher activity for dehydrogenation reactions than for oxidation reactions, while PtOx is equally active for both reactions. Thus, Pt0 promotes glucose dialdehyde formation, while PtOx favors gluconate formation. The successive dehydrogenation of gluconate is achieved selectively at the primary alcohol group by Pt0, while PtOx also promotes the dehydrogenation of secondary alcohol groups, resulting in more complex reaction mixtures.

Background: It has been shown under experimental conditions that cognitive performance, especially working memory, is impaired in patients with type I and type II diabetes mellitus during hyperglycemic and hypoglycemic conditions, perhaps due to altered cerebral glucose metabolism. It is not known if patients with neurodegenerative diseases, who also exhibit pathological cerebral glucose metabolism, are affected in a similar manner by their plasma glucose levels. Objective: We aimed to test if performance on two cognitive screening tests was associated with plasma glucose levels in a memory clinic cohort. Methods: We included patients from the Copenhagen Memory Clinic Cohort with an available Mini Mental-State Examination (MMSE) test score and a plasma glucose measurement performed in conjunction with cognitive testing. We built linear regression models with MMSE and Addenbrooke's Cognitive Examination (ACE) test scores as the outcome and plasma glucose as the explaining variable and adjusted models for age, sex, and diabetes (plasma glucose measurement >11.1 mmol/L). We explored non-linear relationships by adding quadratic terms and by fitting a cubic spline regression model. Results: In total, 2714 patients had an available MMSE score and a plasma glucose measurement. MMSE and ACE total scores were not associated with plasma glucose in a linear or non-linear fashion when we adjusted for age, sex, and diabetes. Conclusion: Plasma glucose levels, predominantly within normal ranges, were not associated with performance on routinely applied cognitive tests and do not need to be taken into consideration when interpreting test results from memory clinic patients.

This was an exploratory, prospective, longitudinal, cohort study that aimed to establish “healthy” reference levels related to growth parameters and glucose metabolites in preterm infants. This was conducted to further investigate growth and metabolic disturbances potentially related to neonatal illness. The study sample consisted of 108 preterm infants born before 32 weeks in 2018–2019 in the Capital Region of Denmark. Repetitive blood samples were acquired at the neonatal wards, while clinical data were obtained from the regional hospital medical record system. Thirty-four “healthy” preterm infants (31%) were identified. The “ill” infants were divided into four subgroups dependent on gestational age and small for gestational age. Reference levels for the growth parameters and metabolic biomarkers glucose, albumin, and adiponectin, and two glucose control indicators, glycated albumin and fructosamine, were determined for the “healthy” and “ill” subgroups. The “ill” extremely preterm infants had increased glucose levels (mean difference 0.71 mmol/L, 95% CI 0.23; 1.18 mmol/L) and glycated albumin (corrected; %) (mean difference 0.92 mmol/L, 95% CI 0.38 mmol/L;1.47 mmol/L) compared to the “healthy” infants. In “ill” extremely preterm infants and “ill” very preterm infants born small for gestational age, levels of biomarkers containing proteins were decreased. In the “Ill” extremely preterm infants and infants born small for gestational age, postnatal growth was continuously decreased throughout the postconceptional period. The short-term glucose-control indicator, glycated albumin (corrected; %), reflected well the high glucose levels due to its correction for the depleted plasma-protein pool. Keywords: preterm infants; blood biomarkers; glucose; metabolism; plasma-protein depletion; healthy reference levels, This was an exploratory, prospective, longitudinal, cohort study that aimed to establish “healthy” reference levels related to growth parameters and glucose metabolites in preterm infants. This was conducted to further investigate growth and metabolic disturbances potentially related to neonatal illness. The study sample consisted of 108 preterm infants born before 32 weeks in 2018–2019 in the Capital Region of Denmark. Repetitive blood samples were acquired at the neonatal wards, while clinical data were obtained from the regional hospital medical record system. Thirty-four “healthy” preterm infants (31%) were identified. The “ill” infants were divided into four subgroups dependent on gestational age and small for gestational age. Reference levels for the growth parameters and metabolic biomarkers glucose, albumin, and adiponectin, and two glucose control indicators, glycated albumin and fructosamine, were determined for the “healthy” and “ill” subgroups. The “ill” extremely preterm infants had increased glucose levels (mean difference 0.71 mmol/L, 95% CI 0.23; 1.18 mmol/L) and glycated albumin (corrected; %) (mean difference 0.92 mmol/L, 95% CI 0.38 mmol/L;1.47 mmol/L) compared to the “healthy” infants. In “ill” extremely preterm infants and “ill” very preterm infants born small for gestational age, levels of biomarkers containing proteins were decreased. In the “Ill” extremely preterm infants and infants born small for gestational age, postnatal growth was continuously decreased throughout the postconceptional period. The short-term glucose-control indicator, glycated albumin (corrected; %), reflected well the high glucose levels due to its correction for the depleted plasma-protein pool.

Sodium-dependent glucose transporters (SGLTs) couple a downhill Na+ ion gradient to actively transport sugars. Here, we investigate the impact of the membrane potential on vSGLT structure and function using sugar uptake assays, double electron-electron resonance (DEER), electrostatic calculations, and kinetic modeling. Negative membrane potentials, as present in all cell types, shift the conformational equilibrium of vSGLT towards an outward-facing conformation, leading to increased sugar transport rates. Electrostatic calculations identify gating charge residues responsible for this conformational shift that when mutated reduce galactose transport and eliminate the response of vSGLT to potential. Based on these findings, we propose a comprehensive framework for sugar transport via vSGLT, where the cellular membrane potential facilitates resetting of the transporter after cargo release. This framework holds significance not only for SGLTs but also for other transporters and channels.

Diabetes is a chronic metabolic disease characterized by high blood glucose levels, when the pancreas does not produce enough insulin or when the body cannot metabolize it efficiently, it usually occurs with various comorbidities that deteriorate the health of patients. Community-acquired pneumonia is an infection at the lung level, which together with other factors can cause complications and lead the patient to death. Objective: To determine the morbidity and mortality of community pneumonia in type 2 diabetics with mechanical ventilation, admitted to the intensive care unit of the Luis Vernaza Hospital, through the review of medical records, providing information to promote its prevention and reduce its incidence. Methodo-logy: It is a non-experimental, descriptive and correlational investigation of a retrospective, cross-sectional nature, with an observational, quantitative approach, in addition to the bibliographic review that provides theoretical support for the study. The technique and the APACHE II assessment score, the instrument was an observation sheet for the medical records of 86 patients admitted to intensive care at the Luis Vernaza Hospital, from March 2020 to March 2021. Results. The APACHE II assessment score revealed; high mortality rate and the presence of comorbidities was 100%. The patients were between 60 and 79 years old and had a stay of 1 to 7 days in intensive care, 79.3% had a glucose level greater than 126 mg/dl. Con-clusions: Hospital institutions should generate prevention strategies, with the support of specialists, raising awareness in diabetic patients about good glycemic control, improving their lifestyle, promoting immunization, especially in older adults to prevent pneumonia, avoiding admissions, complications and deaths in the intensive care unit., La diabetes es una enfermedad metabólica crónica caracterizada por niveles elevados de glucosa en sangre, cuando el páncreas no produce suficiente insulina o cuando el organismo no puede metabolizarla eficientemente, suele cursar con diversas comorbilidades que deterioran la salud de lo pacientes. La Neumonía adquirida en la comunidad, es una infección a nivel pulmonar, que junto a otros factores pueden causar complicaciones y llevar al paciente a la muerte. Objetivo: Determinar la morbimortalidad de la Neumonía comunitaria en diabéticos tipo 2 con ventilación mecánica, ingresados en la unidad de cuidados intensivos del Hospital Luis Vernaza, a través de la revisión de las historias clínicas brindando información para promover su prevención y reducir su incidencia. Metodología: Es una investigación no experimental, descriptiva y correlacional de carácter retrospectivo transversal, con enfoque observacional, cuantitativo, además de la revisión bibliográfica que proporciona sustento teórico del estudio. La técnica y el puntaje de valoración APACHE II, el instrumento fue una ficha de observación para las historias clínicas de 86 pacientes ingresados a cuidados intensivos en el Hospital Luis Vernaza, periodo de marzo 2020 a marzo 2021. Resultados: El puntaje de valoración APACHE II reveló; elevado índice de mortalidad y la presencia de comorbilidades fue del 100%. Los pacientes tenían entre los 60 y 79 años y tuvieron una estadía de 1 a 7 días en cuidados intensivos, el 79.3% tenía un nivel de glucosa mayor a 126 mg/dl. Conclusiones: Las instituciones hospitalarias deben generar estrategias de prevención, con apoyo de especialistas, formando conciencia en pacientes diabéticos, sobre un buen control de la glucemia, mejorando su estilo de vida, promoviendo la inmunización, especialmente en los adultos mayores para prevenir neumonía, evitando ingresos, complicaciones y falle-cimientos en la sala de cuidados intensivos

Diabetes is a chronic metabolic disease characterized by high blood glucose levels, when the pancreas does not produce enough insulin or when the body cannot metabolize it efficiently, it usually occurs with various comorbidities that deteriorate the health of patients. Community-acquired pneumonia is an infection at the lung level, which together with other factors can cause complications and lead the patient to death. Objective: To determine the morbidity and mortality of community pneumonia in type 2 diabetics with mechanical ventilation, admitted to the intensive care unit of the Luis Vernaza Hospital, through the review of medical records, providing information to promote its prevention and reduce its incidence. Methodo-logy: It is a non-experimental, descriptive and correlational investigation of a retrospective, cross-sectional nature, with an observational, quantitative approach, in addition to the bibliographic review that provides theoretical support for the study. The technique and the APACHE II assessment score, the instrument was an observation sheet for the medical records of 86 patients admitted to intensive care at the Luis Vernaza Hospital, from March 2020 to March 2021. Results. The APACHE II assessment score revealed; high mortality rate and the presence of comorbidities was 100%. The patients were between 60 and 79 years old and had a stay of 1 to 7 days in intensive care, 79.3% had a glucose level greater than 126 mg/dl. Con-clusions: Hospital institutions should generate prevention strategies, with the support of specialists, raising awareness in diabetic patients about good glycemic control, improving their lifestyle, promoting immunization, especially in older adults to prevent pneumonia, avoiding admissions, complications and deaths in the intensive care unit., La diabetes es una enfermedad metabólica crónica caracterizada por niveles elevados de glucosa en sangre, cuando el páncreas no produce suficiente insulina o cuando el organismo no puede metabolizarla eficientemente, suele cursar con diversas comorbilidades que deterioran la salud de lo pacientes. La Neumonía adquirida en la comunidad, es una infección a nivel pulmonar, que junto a otros factores pueden causar complicaciones y llevar al paciente a la muerte. Objetivo: Determinar la morbimortalidad de la Neumonía comunitaria en diabéticos tipo 2 con ventilación mecánica, ingresados en la unidad de cuidados intensivos del Hospital Luis Vernaza, a través de la revisión de las historias clínicas brindando información para promover su prevención y reducir su incidencia. Metodología: Es una investigación no experimental, descriptiva y correlacional de carácter retrospectivo transversal, con enfoque observacional, cuantitativo, además de la revisión bibliográfica que proporciona sustento teórico del estudio. La técnica y el puntaje de valoración APACHE II, el instrumento fue una ficha de observación para las historias clínicas de 86 pacientes ingresados a cuidados intensivos en el Hospital Luis Vernaza, periodo de marzo 2020 a marzo 2021. Resultados: El puntaje de valoración APACHE II reveló; elevado índice de mortalidad y la presencia de comorbilidades fue del 100%. Los pacientes tenían entre los 60 y 79 años y tuvieron una estadía de 1 a 7 días en cuidados intensivos, el 79.3% tenía un nivel de glucosa mayor a 126 mg/dl. Conclusiones: Las instituciones hospitalarias deben generar estrategias de prevención, con apoyo de especialistas, formando conciencia en pacientes diabéticos, sobre un buen control de la glucemia, mejorando su estilo de vida, promoviendo la inmunización, especialmente en los adultos mayores para prevenir neumonía, evitando ingresos, complicaciones y falle-cimientos en la sala de cuidados intensivos

Diabetes is a chronic metabolic disease characterized by high blood glucose levels, when the pancreas does not produce enough insulin or when the body cannot metabolize it efficiently, it usually occurs with various comorbidities that deteriorate the health of patients. Community-acquired pneumonia is an infection at the lung level, which together with other factors can cause complications and lead the patient to death. Objective: To determine the morbidity and mortality of community pneumonia in type 2 diabetics with mechanical ventilation, admitted to the intensive care unit of the Luis Vernaza Hospital, through the review of medical records, providing information to promote its prevention and reduce its incidence. Methodo-logy: It is a non-experimental, descriptive and correlational investigation of a retrospective, cross-sectional nature, with an observational, quantitative approach, in addition to the bibliographic review that provides theoretical support for the study. The technique and the APACHE II assessment score, the instrument was an observation sheet for the medical records of 86 patients admitted to intensive care at the Luis Vernaza Hospital, from March 2020 to March 2021. Results. The APACHE II assessment score revealed; high mortality rate and the presence of comorbidities was 100%. The patients were between 60 and 79 years old and had a stay of 1 to 7 days in intensive care, 79.3% had a glucose level greater than 126 mg/dl. Con-clusions: Hospital institutions should generate prevention strategies, with the support of specialists, raising awareness in diabetic patients about good glycemic control, improving their lifestyle, promoting immunization, especially in older adults to prevent pneumonia, avoiding admissions, complications and deaths in the intensive care unit., La diabetes es una enfermedad metabólica crónica caracterizada por niveles elevados de glucosa en sangre, cuando el páncreas no produce suficiente insulina o cuando el organismo no puede metabolizarla eficientemente, suele cursar con diversas comorbilidades que deterioran la salud de lo pacientes. La Neumonía adquirida en la comunidad, es una infección a nivel pulmonar, que junto a otros factores pueden causar complicaciones y llevar al paciente a la muerte. Objetivo: Determinar la morbimortalidad de la Neumonía comunitaria en diabéticos tipo 2 con ventilación mecánica, ingresados en la unidad de cuidados intensivos del Hospital Luis Vernaza, a través de la revisión de las historias clínicas brindando información para promover su prevención y reducir su incidencia. Metodología: Es una investigación no experimental, descriptiva y correlacional de carácter retrospectivo transversal, con enfoque observacional, cuantitativo, además de la revisión bibliográfica que proporciona sustento teórico del estudio. La técnica y el puntaje de valoración APACHE II, el instrumento fue una ficha de observación para las historias clínicas de 86 pacientes ingresados a cuidados intensivos en el Hospital Luis Vernaza, periodo de marzo 2020 a marzo 2021. Resultados: El puntaje de valoración APACHE II reveló; elevado índice de mortalidad y la presencia de comorbilidades fue del 100%. Los pacientes tenían entre los 60 y 79 años y tuvieron una estadía de 1 a 7 días en cuidados intensivos, el 79.3% tenía un nivel de glucosa mayor a 126 mg/dl. Conclusiones: Las instituciones hospitalarias deben generar estrategias de prevención, con apoyo de especialistas, formando conciencia en pacientes diabéticos, sobre un buen control de la glucemia, mejorando su estilo de vida, promoviendo la inmunización, especialmente en los adultos mayores para prevenir neumonía, evitando ingresos, complicaciones y falle-cimientos en la sala de cuidados intensivos

Diabetes is a chronic metabolic disease characterized by high blood glucose levels, when the pancreas does not produce enough insulin or when the body cannot metabolize it efficiently, it usually occurs with various comorbidities that deteriorate the health of patients. Community-acquired pneumonia is an infection at the lung level, which together with other factors can cause complications and lead the patient to death. Objective: To determine the morbidity and mortality of community pneumonia in type 2 diabetics with mechanical ventilation, admitted to the intensive care unit of the Luis Vernaza Hospital, through the review of medical records, providing information to promote its prevention and reduce its incidence. Methodo-logy: It is a non-experimental, descriptive and correlational investigation of a retrospective, cross-sectional nature, with an observational, quantitative approach, in addition to the bibliographic review that provides theoretical support for the study. The technique and the APACHE II assessment score, the instrument was an observation sheet for the medical records of 86 patients admitted to intensive care at the Luis Vernaza Hospital, from March 2020 to March 2021. Results. The APACHE II assessment score revealed; high mortality rate and the presence of comorbidities was 100%. The patients were between 60 and 79 years old and had a stay of 1 to 7 days in intensive care, 79.3% had a glucose level greater than 126 mg/dl. Con-clusions: Hospital institutions should generate prevention strategies, with the support of specialists, raising awareness in diabetic patients about good glycemic control, improving their lifestyle, promoting immunization, especially in older adults to prevent pneumonia, avoiding admissions, complications and deaths in the intensive care unit., La diabetes es una enfermedad metabólica crónica caracterizada por niveles elevados de glucosa en sangre, cuando el páncreas no produce suficiente insulina o cuando el organismo no puede metabolizarla eficientemente, suele cursar con diversas comorbilidades que deterioran la salud de lo pacientes. La Neumonía adquirida en la comunidad, es una infección a nivel pulmonar, que junto a otros factores pueden causar complicaciones y llevar al paciente a la muerte. Objetivo: Determinar la morbimortalidad de la Neumonía comunitaria en diabéticos tipo 2 con ventilación mecánica, ingresados en la unidad de cuidados intensivos del Hospital Luis Vernaza, a través de la revisión de las historias clínicas brindando información para promover su prevención y reducir su incidencia. Metodología: Es una investigación no experimental, descriptiva y correlacional de carácter retrospectivo transversal, con enfoque observacional, cuantitativo, además de la revisión bibliográfica que proporciona sustento teórico del estudio. La técnica y el puntaje de valoración APACHE II, el instrumento fue una ficha de observación para las historias clínicas de 86 pacientes ingresados a cuidados intensivos en el Hospital Luis Vernaza, periodo de marzo 2020 a marzo 2021. Resultados: El puntaje de valoración APACHE II reveló; elevado índice de mortalidad y la presencia de comorbilidades fue del 100%. Los pacientes tenían entre los 60 y 79 años y tuvieron una estadía de 1 a 7 días en cuidados intensivos, el 79.3% tenía un nivel de glucosa mayor a 126 mg/dl. Conclusiones: Las instituciones hospitalarias deben generar estrategias de prevención, con apoyo de especialistas, formando conciencia en pacientes diabéticos, sobre un buen control de la glucemia, mejorando su estilo de vida, promoviendo la inmunización, especialmente en los adultos mayores para prevenir neumonía, evitando ingresos, complicaciones y falle-cimientos en la sala de cuidados intensivos

Support effects in supported metal catalysts are well studied for thermocatalytic reactions, but less studied for electrocatalytic reactions. Here, we prepared a series of Pt supported on carbon nanofiber catalysts which vary in their Pt particle size and the content of oxygen groups on the surface of the CNF. We show that the activity of these catalysts for electrocatalytic glucose oxidation relates linearly with the content of support oxygen groups. Since the electronic state of Pt (XAS) and Pt surface structure (CO-stripping) were indistinguishable for all materials, we conclude that sorption effects of glucose play a crucial role in catalytic activity. This was further confirmed by establishing a relation between the annulus of the Pt particles and the activity.

BACKGROUND: To compare risk of diabetic retinopathy (DR) between patients taking sodium-glucose cotransporter-2 inhibitors (SGLT2is) and those taking glucagon-like peptide-1 receptor agonists (GLP1-RAs) in routine care. METHODS: This retrospective cohort study emulating a target trial included patient data from the multi-institutional Chang Gung Research Database in Taiwan. Totally, 33,021 patients with type 2 diabetes mellitus using SGLT2is and GLP1-RAs between 2016 and 2019 were identified. 3,249 patients were excluded due to missing demographics, age <40 >years, prior use of any study drug, a diagnosis of retinal disorders, a history of receiving vitreoretinal procedure, no baseline glycosylated hemoglobin, or no follow-up data. Baseline characteristics were balanced using inverse probability of treatment weighting with propensity scores. DR diagnoses and vitreoretinal interventions served as the primary outcomes. Occurrence of proliferative DR and DR receiving vitreoretinal interventions were regarded as vision-threatening DR. RESULTS: There were 21,491 SGLT2i and 1,887 GLP1-RA users included for the analysis. Patients receiving SGLT2is and GLP-1 RAs exhibited comparable rate of any DR (subdistribution hazard ratio [SHR], 0.90; 95% confidence interval [CI], 0.79 to 1.03), whereas the rate of proliferative DR (SHR, 0.53; 95% CI, 0.42 to 0.68) was significantly lower in the SGLT2i group. Also, SGLT2i users showed significantly reduced risk of composite surgical outcome (SHR, 0.58; 95% CI, 0.48 to 0.70). CONCLUSION: Compared to those taking GLP1-RAs, patients receiving SGLT2is had a lower risk of proliferative DR and vitreoretinal interventions, although the rate of any DR was comparable between the SGLT2i and GLP1-RA groups. Thus, SGLT2is may be associated with a lower risk of vision-threatening DR but not DR development.

Background: Previous studies have shown an increased risk for atrial fibrillation and atrial flutter (AF) in people with type 2 diabetes and prediabetes. It is unclear whether this increase in AF risk is independent of other risk factors for AF. Objective: To investigate the association between diabetes and different prediabetic states, as independent risk factors for the onset of AF. Methods: We performed a population-based cohort study in Northern Sweden, including data on fasting plasma glucose, oral glucose tolerance test, major cardiovascular risk factors, medical history, and lifestyle factors. Participants were divided into six groups depending on glycemic status and followed through national registers for AF diagnosis. Cox proportional hazard model was used to assess the association between glycemic status and AF, using normoglycemia as reference. Results: The cohort consisted of 88,889 participants who underwent a total of 139,661 health examinations. In the model adjusted for age and sex, there was a significant association between glycemic status and development of AF in all groups except the impaired glucose tolerance group, with the strongest association for the group with known diabetes (p-value <0.001). In a model adjusted for sex, age, systolic blood pressure, body mass index, antihypertensive drugs, cholesterol, alcohol, smoking, education level, marital status, and physical activity, there was no significant association between glycemic status and AF. Conclusions/interpretation: The association between glycemic status and AF disappears upon adjustment for potential confounders. Diabetes and prediabetes do not appear to be independent risk factors for AF.

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BackgroundContinuous glucose monitoring (CGM) is approved for insulin dosing decisions in the ambulatory setting, but not currently for inpatients. CGM has the capacity to reduce patient-provider contact in inpatients with coronavirus disease 2019 (COVID-19), thus potentially reducing in hospital virus transmission. However, there are sparse data on the accuracy and efficacy of CGM to titrate insulin doses in inpatients.MethodsUnder an emergency use protocol, CGM (Dexcom G6) was used alongside standard point-of-care (POC) glucose measurements in patients critically ill from complications of COVID-19 requiring intravenous (IV) insulin. Glycemic control during IV insulin therapy was retrospectively assessed comparing periods with and without adjunctive CGM use. Accuracy metrics were computed and Clarke Error Grid analysis performed comparing CGM glucose values with POC measurements.ResultsTwenty-four critically ill patients who met criteria for emergency use of CGM resulted in 47 333 CGM and 5677 POC glucose values. During IV insulin therapy, individuals' glycemic control improved when CGM was used (mean difference -30.7 mg/dL). Among 2194 matched CGM: POC glucose pairs, a high degree of concordance was observed with a mean absolute relative difference of 14.8% and 99.5% of CGM: POC pairs falling in Zones A and B of the Clarke Error Grid.ConclusionsContinuous glucose monitoring use in critically ill COVID-19 patients improved glycemic control during IV insulin therapy. Continuous glucose monitoring glucose data were highly concordant with POC glucose during IV insulin therapy in critically ill patients suggesting that CGM could substitute for POC measurements in inpatients thus reducing patient-provider contact and mitigating infection transmission.

ObjectivesInvestigating empirical relationships among laboratory measures in children with diabetic ketoacidosis (DKA) can provide insights into physiological alterations occurring during DKA. We determined whether alterations in laboratory measures during DKA conform to theoretical predictions.MethodsWe used Pearson correlation statistics and linear regression to investigate correlations between blood glucose, electrolytes, pH and PCO2 at emergency department presentation in 1,681 pediatric DKA episodes. Among children with repeat DKA episodes, we also assessed correlations between laboratory measures at the first vs. second episode.ResultspH and bicarbonate levels were strongly correlated (r=0.64), however, pH and PCO2 were only loosely correlated (r=0.17). Glucose levels were correlated with indicators of dehydration and kidney function (blood urea nitrogen (BUN), r=0.44; creatinine, r=0.42; glucose-corrected sodium, r=0.32). Among children with repeat DKA episodes, PCO2 levels tended to be similar at the first vs. second episode (r=0.34), although pH levels were only loosely correlated (r=0.19).ConclusionsElevated glucose levels at DKA presentation largely reflect alterations in glomerular filtration rate. pH and PCO2 are weakly correlated suggesting that respiratory responses to acidosis vary among individuals and may be influenced by pulmonary and central nervous system effects of DKA.

Insulin resistance (IR) is a well-established risk factor for breast cancer (BC) development in African American (AA) postmenopausal women. While obesity and IR are more prevalent in AA than in white women, they are under-represented in genome-wide studies for systemic regulation of IR. By examining 780 genome-wide IR single-nucleotide polymorphisms (SNPs) available in our data, we tested 4689 AA women in a Random Survival Forest framework. With 37 BC-associated lifestyle factors, we conducted a gene-environment interaction analysis to estimate risk prediction for BC with the most influential genetic and behavioral factors and evaluated their combined and joint effects on BC risk. By accounting for variations of individual SNPs in BC in the prediction model, we detected four fasting glucose-associated SNPs in PCSK1, SPC25, ADCY5, and MTNR1B and three lifestyle factors (smoking, oral contraceptive use, and age at menopause) as the most predictive markers for BC risk. Our joint analysis of risk genotypes and lifestyle with smoking revealed a synergistic effect on the increased risk of BC, particularly estrogen/progesterone positive (ER/PR+) BC, in a gene-lifestyle dose-dependent manner. The joint effect of smoking was more substantial in women with prolonged exposure to cigarette smoking and female hormones. The top genome-wide association-SNPs associated with metabolic biomarkers in combination with lifestyles synergistically increase the predictability of invasive ER/PR+ BC risk among AA women. Our findings highlight generically targeted preventive interventions for women who carry particular risk genotypes and lifestyles.

BackgroundInsulin resistance (IR) is a well-established factor for breast cancer (BC) risk in postmenopausal women, but the interrelated molecular pathways on the methylome are not explicitly described. We conducted a population-level epigenome-wide association (EWA) study for DNA methylation (DNAm) probes that are associated with IR and prospectively correlated with BC development, both overall and in BC subtypes among postmenopausal women.MethodsWe used data from Women's Health Initiative (WHI) ancillary studies for our EWA analyses and evaluated the associations of site-specific DNAm across the genome with IR phenotypes by multiple regressions adjusting for age and leukocyte heterogeneities. For our analysis of the top 20 IR-CpGs with BC risk, we used the WHI and the Cancer Genomic Atlas (TCGA), using multiple Cox proportional hazards and logit regressions, respectively, accounting for age, diabetes, obesity, leukocyte heterogeneities, and tumor purity (for TCGA). We further conducted a Gene Set Enrichment Analysis.ResultsWe detected several EWA-CpGs in TXNIP, CPT1A, PHGDH, and ABCG1. In particular, cg19693031 in TXNIP was replicated in all IR phenotypes, measured by fasting levels of glucose, insulin, and homeostatic model assessment-IR. Of those replicated IR-genes, 3 genes (CPT1A, PHGDH, and ABCG1) were further correlated with BC risk; and 1 individual CpG (cg01676795 in POR) was commonly detected across the 2 cohorts.ConclusionsOur study contributes to better understanding of the interconnected molecular pathways on the methylome between IR and BC carcinogenesis and suggests potential use of DNAm markers in the peripheral blood cells as preventive targets to detect an at-risk group for IR and BC in postmenopausal women.

Timing of nutrient intake for athletes may affect exercise performance and cardiometabolic factors. Our objective was to examine the effect of time-restricted eating (TRE) on cardiometabolic health. Using a cross-over study design, 15 endurance-trained male runners were randomized to either a normal dietary pattern (ND) first (12 h eating/fasting times) followed by time-restricted eating (TRE) pattern (16 h fast; 8 h eating) or the reverse, with a 4-week washout period between interventions. Body composition, resting energy expenditure, blood pressure and serum insulin, glucose and lipids were measured using standard laboratory methods. Exercise training and dietary intake (calories and macronutrients) were similar across interventions. No significant differences were observed in resting energy expenditure, markers of insulin resistance, serum lipids or blood pressure. Body composition did change significantly (p < 0.05) with whole body fat mass (-0.8 ± 1.3 kg with TRE vs. +0.1 ± 4.3 kg with ND), leg fat mass (-0.3 ± 0.5 kg with TRE vs. +0.1 ± 0.4 kg with ND), and percent body fat (-1.0 ± 1.5% with TRE vs. +0.1 ± 1.3% with ND) declining more in the TRE intervention, with no change in fat-free mass. This study is one of a few to investigate the effects of an isocaloric 16/8 TRE eating pattern in trained endurance athletes and confirms no change in cardiometabolic risk factors. In conclusion, TRE is not detrimental to cardiometabolic health in endurance-trained male runners but could be beneficial on exercise performance by reducing fat mass.

Adipose tissue plays a crucial role in maintaining metabolic homeostasis by storing lipids and glucose from circulation as intracellular fat. As peripheral tissues like adipose tissue become insulin resistant, decompensation of blood glucose levels occurs causing type 2 diabetes (T2D). Currently, modulating the glycocalyx, a layer of cell-surface glycans, is an underexplored pharmacological treatment strategy to improve glucose homeostasis in T2D patients. Here, we show a novel role for cell-surface heparan sulfate (HS) in establishing glucose uptake capacity and metabolic utilization in differentiated adipocytes. Using a combination of chemical and genetic interventions, we identified that HS modulates this metabolic phenotype by attenuating levels of Wnt signaling during adipogenesis. By engineering, the glycocalyx of pre-adipocytes with exogenous synthetic HS mimetics, we were able to enhance glucose clearance capacity after differentiation through modulation of Wnt ligand availability. These findings establish the cellular glycocalyx as a possible new target for therapeutic intervention in T2D patients by enhancing glucose clearance capacity independent of insulin secretion.

Mitochondria are critical to the governance of metabolism and bioenergetics in cancer cells1. The mitochondria form highly organized networks, in which their outer and inner membrane structures define their bioenergetic capacity2,3. However, in vivo studies delineating the relationship between the structural organization of mitochondrial networks and their bioenergetic activity have been limited. Here we present an in vivo structural and functional analysis of mitochondrial networks and bioenergetic phenotypes in non-small cell lung cancer (NSCLC) using an integrated platform consisting of positron emission tomography imaging, respirometry and three-dimensional scanning block-face electron microscopy. The diverse bioenergetic phenotypes and metabolic dependencies we identified in NSCLC tumours align with distinct structural organization of mitochondrial networks present. Further, we discovered that mitochondrial networks are organized into distinct compartments within tumour cells. In tumours with high rates of oxidative phosphorylation (OXPHOSHI) and fatty acid oxidation, we identified peri-droplet mitochondrial networks wherein mitochondria contact and surround lipid droplets. By contrast, we discovered that in tumours with low rates of OXPHOS (OXPHOSLO), high glucose flux regulated perinuclear localization of mitochondria, structural remodelling of cristae and mitochondrial respiratory capacity. Our findings suggest that in NSCLC, mitochondrial networks are compartmentalized into distinct subpopulations that govern the bioenergetic capacity of tumours.

IntroductionAfrican Americans are at increased risk for type 2 diabetes.ObjectivesThis work aimed to examine metabolomic signature of glucose homeostasis in African Americans.MethodsWe used an untargeted liquid chromatography-mass spectrometry metabolomic approach to comprehensively profile 727 plasma metabolites among 571 African Americans from the Insulin Resistance Atherosclerosis Family Study (IRAS-FS) and investigate the associations between these metabolites and both the dynamic (SI, insulin sensitivity; AIR, acute insulin response; DI, disposition index; and SG, glucose effectiveness) and basal (HOMA-IR and HOMA-B) measures of glucose homeostasis using univariate and regularized regression models. We also compared the results with our previous findings in the IRAS-FS Mexican Americans.ResultsWe confirmed increased plasma metabolite levels of branched-chain amino acids and their metabolic derivatives, 2-aminoadipate, 2-hydroxybutyrate, glutamate, arginine and its metabolic derivatives, carbohydrate metabolites, and medium- and long-chain fatty acids were associated with insulin resistance, while increased plasma metabolite levels in the glycine, serine and threonine metabolic pathway were associated with insulin sensitivity. We also observed a differential ancestral effect of glutamate on glucose homeostasis with significantly stronger effects observed in African Americans than those previously observed in Mexican Americans.ConclusionWe extended the observations that metabolites are useful biomarkers in the identification of prediabetes in individuals at risk of type 2 diabetes in African Americans. We revealed, for the first time, differential ancestral effect of certain metabolites (i.e., glutamate) on glucose homeostasis traits. Our study highlights the need for additional comprehensive metabolomic studies in well-characterized multiethnic cohorts.

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy1,2. This is mediated in part by a complex tumour microenvironment3, low vascularity4, and metabolic aberrations5,6. Although altered metabolism drives tumour progression, the spectrum of metabolites used as nutrients by PDA remains largely unknown. Here we identified uridine as a fuel for PDA in glucose-deprived conditions by assessing how more than 175 metabolites impacted metabolic activity in 21 pancreatic cell lines under nutrient restriction. Uridine utilization strongly correlated with the expression of uridine phosphorylase 1 (UPP1), which we demonstrate liberates uridine-derived ribose to fuel central carbon metabolism and thereby support redox balance, survival and proliferation in glucose-restricted PDA cells. In PDA, UPP1 is regulated by KRAS-MAPK signalling and is augmented by nutrient restriction. Consistently, tumours expressed high UPP1 compared with non-tumoural tissues, and UPP1 expression correlated with poor survival in cohorts of patients with PDA. Uridine is available in the tumour microenvironment, and we demonstrated that uridine-derived ribose is actively catabolized in tumours. Finally, UPP1 deletion restricted the ability of PDA cells to use uridine and blunted tumour growth in immunocompetent mouse models. Our data identify uridine utilization as an important compensatory metabolic process in nutrient-deprived PDA cells, suggesting a novel metabolic axis for PDA therapy.

Bariatric surgery remains a potent therapy for nonalcoholic fatty liver disease (NAFLD), but its inherent risk and eligibility requirement limit its adoption. Therefore, understanding how bariatric surgery improves NAFLD is paramount to developing novel therapeutics. Here, we show that the microbiome changes induced by sleeve gastrectomy (SG) reduce glucose-dependent insulinotropic polypeptide (GIP) signaling and confer resistance against diet-induced obesity (DIO) and NAFLD. We examined a cohort of NALFD patients undergoing SG and evaluated their microbiome, serum metabolites, and GI hormones. We observed significant changes in Bacteroides, lipid-related metabolites, and reduction in GIP. To examine if the changes in the microbiome were causally related to NAFLD, we performed fecal microbial transplants in antibiotic-treated mice from patients before and after their surgery who had significant weight loss and improvement of their NAFLD. Mice transplanted with the microbiome of patients after bariatric surgery were more resistant to DIO and NAFLD development compared to mice transplanted with the microbiome of patients before surgery. This resistance to DIO and NAFLD was also associated with a reduction in GIP levels in mice with post-bariatric microbiome. We further show that the reduction in GIP was related to higher levels of Akkermansia and differing levels of indolepropionate, bacteria-derived tryptophan-related metabolite. Overall, this is one of the few studies showing that GIP signaling is altered by the gut microbiome, and it supports that the positive effect of bariatric surgery on NAFLD is in part due to microbiome changes.

The discovery of the lactate shuttle (LS) mechanism may have two opposite perceptions, It may mean very little, because the body normally and inexorably uses the LS mechanism. On the contrary, one may support the viewpoint that understanding the LS mechanism offers immense opportunities for understanding nutrition and metabolism in general, as well as in a sports nutrition supplementation setting. In fact, regardless of the specific form of the carbohydrate (CHO) nutrient taken, the bodily CHO energy flux is from a hexose sugar glucose or glucose polymer (glycogen and starches) to lactate with subsequent somatic tissue oxidation or storage as liver glycogen. In fact, because oxygen and lactate flow together through the circulation to sites of utilization, the bodily carbon energy flow is essentially the lactate disposal rate. Consequently, one can consume glucose or glucose polymers in various forms (glycogen, maltodextrin, potato, corn starch, and fructose or high-fructose corn syrup), and the intestinal wall, liver, integument, and active and inactive muscles make lactate which is the chief energy fuel for red skeletal muscle, heart, brain, erythrocytes, and kidneys. Therefore, if one wants to hasten the delivery of CHO energy delivery, instead of providing CHO foods, supplementation with lactate nutrient compounds can augment body energy flow.

The endocannabinoid system (ECS) participates in regulating whole body energy balance. Overactivation of the ECS has been associated with the negative consequence of obesity and type 2 diabetes. Since activators of the ECS rely on lipid-derived ligands, an investigation was conducted to determine whether dietary PUFA could influence the ECS to affect glucose clearance by measuring metabolites of macronutrient metabolism. C57/blk6 mice were fed a control or DHA-enriched semi-purified diet for a period of 112 d. Plasma, skeletal muscle, and liver were collected after 56 d and 112 d of feeding the diets for metabolomics analysis. Key findings characterized a shift in glucose metabolism and greater catabolism of fatty acids in mice fed the DHA diet. Glucose use and promotion of fatty acids as substrate were found based on levels of metabolic pathway intermediates and altered metabolic changes related to pathway flux with DHA feeding. Greater levels of DHA-derived glycerol lipids were found subsequently leading to the decrease of arachidonate-derived endocannabinoids (eCB). Levels of 1- and 2-arachidonylglcerol eCB in muscle and liver were lower in the DHA diet group compared to controls. These findings demonstrate that DHA feeding in mice alters macronutrient metabolism and may restore ECS tone by lowering arachidonic acid derived eCB.

Objetivo: To determine the correlation between salivary glucose levels with fasting blood glucose, HbA1c, and C-peptide in patients with type 2 diabetes mellitus (T2DM). Materials and methods: This is a cross-sectional study performed at the Centro de Investigación en Diabetes, Obesidad y Nutrición (CIDON) in Lima, Peru, during 2021. Patients were categorized as those with good metabolic control (HbA1c<7 %), and poor metabolic control (HbA1c≥7 %). Baseline fasting blood glucose, as well as blood HbA1c and C-peptide values were measured. Salivary glucose was measured using the glucose oxidase method. Spearman’s correlation was used for determining an association between salivary glucose levels and fasting blood glucose, HbA1c, and C-peptide. Results: One-hundred and forty-two subjects with T2DM participated in the study. Salivary glucose was significantly higher in T2DM subjects with poor metabolic control (p<0.01). A weak positive correlation between salivary glucose and fasting blood glucose (r= 0.23, p= 0.04) and HbA1c (r= 0.26, p= 0.02) was observed in subjects with T2DM and poor metabolic control, and also a non-significant negative correlation (r=-0.08; p= 0.47) with C-peptide. Conclusions: Salivary glucose levels show significant and positive association with fasting blood glucose and HbA1c, but not with C-peptide in persons with T2DM and poor metabolic control. However, there are many factors that should be considered and analyzed in detail aiming to determine its potential use., Objetivo: Determinar la correlación entre la glucosa salival con la glucosa en ayunas, HbA1c y el péptido C en personas con Diabetes Mellitus tipo 2 (DM2). Materiales y métodos: Estudio transversal llevado a cabo en el Centro de Investigación en Diabetes, Obesidad y Nutrición (CIDON) en Lima, Perú durante el año 2021. Se categorizó en buen control metabólico (HbA1c<7 %) y mal control metabólico (HbA1c≥7 %). Se midió la glucosa basal, HbA1c y el péptido C en sangre. La glucosa salival se midió con el método glucosa oxidasa. La correlación de Spearman fue usada para determinar la asociación entre la glucosa salival con la glucosa en ayunas, HbA1c y el péptido- C. Resultados: Participaron un total de 142 personas con DM2. La concentración de glucosa salival fue significativamente más elevada en DM2 con mal control metabólico (p<0.01). Se observó una correlación positiva débil significativa entre la glucosa salival y la glucosa basal (r=0.23, p=0.04) y HbA1c (r=0.26, p=0.02) en DM2 con mal control metabólico y una correlación negativa insignificante (r=-0.08; p=0.47) con el péptido C. Conclusiones: La glucosa salival presenta una asociación significativa y positiva con la glucosa en sangre y la HbA1c, pero no con el péptido C en personas con DM2 con mal control metabólico. Sin embargo, hay muchos factores que deben ser considerados y analizados más a fondo para determinar su posible uso