bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tyhroid Storm-Induced Worsening Acute Myocardial Infarction: A Case Report
Authors: Diba Sonya Farah 
Published: May 2021

Abstract
Background: As a true endocrine emergency, thyroid storm is rarely associated with acute myocardial infarction. However Graves’ disease is the most common underlying cause of thyroid storm. Clinical Case: A 47-year women experienced typical chest pain since 30 minutes before visited emergency room. The patient had type two diabetes as a cardiovascular risk factor and regularly took metformin thrice daily. The electrocardiogram showed non-ST segment elevation in leads I, V4-V6. Coronary arteriography showed stenosis in the three and left main vessels (70% stenosis of right coronary, 80% stenosis of left circumflex, 90% stenosis of left anterior descendent, and 90% stenosis of mid distal, in left main stem) then the patient was planned to do bypass surgery. At day 6 of hospitalization, the typical chest pain was worsening, epigastric pain became more painful, had 5 times diarrhea per day, high grade fever (&gt;38.5oC), severe nausea and vomiting, then generalized tonic clonic seizure and respiratory failure was occurred. The patient was intubated in intensive care unit. Through a detail physical examination, a diffuse palpable thyroid enlargement and class I ophthalmopathy were found. Laboratory findings of free T4 was 2.23 ng/dL and Thyroid Stimulating Hormone (TSH) was 0.003 µIU/mL. The patient was assessed as thyroid storm then immediately, treated with three times of 100 mg hydrocortisone, two times of 20 mg of propranolol, and three times of 400 mg propylthiourasil. The patient’s clinical appearance was gradually recovered. After 3 days of treatment, she was extubated from ventilator. Two weeks later, no complaint of chest pain or epigastric pain in observation. Conclusion: Our case highlight the possibility that hyperthyroidism may be involved in the development of acute myocardial infarction.
Genome-Wide Meta-Analysis and Mendelian Randomization Identify Early Biomarkers of Non-Alcoholic Fatty Liver Disease
Authors: Gobeil Emilie , Abner Erik , Ghodsian Nooshin , Taba Nele , St-Amand Alexis , Perrot Nicolas , Couture Christian , Mitchell Patricia , Bossé Yohan , Mathieu Patrick , Vohl Marie-Claude , Thériault Sébastien , Tchernof Andre , Esko Tõnu , Arsenault Benoit J 
Published: May 2021

Abstract
Background: The diagnosis of non-alcoholic fatty liver disease (NAFLD) is often challenging. Blood-based biomarkers which are causally influenced by NAFLD and that are not modulated by secondary non-causal pathways, are promising candidates for the identification of patients with NAFLD. Objectives: To identify blood metabolites and blood proteins that are causally impacted by the presence of NAFLD using Mendelian randomization (MR). Methods: We created a NAFLD genetic instrument through the identification of independent single-nucleotide polymorphisms associated with NAFLD in a meta-analysis of genome-wide association studies (GWAS) (6715 cases and 682,748 controls). Using inverse-variance weighted MR, we investigated the impact of NAFLD on 123 blood metabolites (in 24,925 participants from 10 European cohorts) and 3283 blood proteins (in 3301 participants from the INTERVAL cohort). Results: Our genetic instrument for genetically predicted NAFLD included 12 SNPs at the MTARC1, GCKR, LPL, TRIB1, LMO3, FTO, TM6SF2, APOE and PNPLA3 loci. After correction for false-discovery rate, we found a positive effect of NAFLD on blood tyrosine levels and on blood levels of eight proteins (encoded by the IDUA, ADH4, HMGCS1, GSTA1, ASL, POR, FBP1 and CTSZ genes). These association were robust to outliers and we found to evidence of horizontal pleiotropy. Conclusions: We report the existence of a potentially causal impact of the presence of NAFLD on tyrosine metabolism as well as on eight circulating proteins, which could potentially represent early biomarkers of NAFLD.
Leptin Improves Cardiac Structure and Function in Patients With Generalized Lipodystrophy
Authors: Nguyen My-Le , Sachdev Vandana , Burklow Thomas , Li Wen , Brown Rebecca J 
Published: May 2021

Abstract
Lipodystrophy (LD) syndromes are rare disorders of deficient adipose tissue and severe metabolic disease, including insulin resistance, diabetes, and hypertriglyceridemia. LD may affect all adipose depots (generalized LD, GLD) or only some depots (partial LD, PLD). Low adipose mass leads to very low leptin in GLD, and variable leptin in PL. Treatment with exogenous leptin (metreleptin) improves metabolic disease in LD, particularly GLD. Left ventricular (LV) hypertrophy is frequent in LD, especially GLD. The mechanism for hypertrophy in LD is not known and may relate to glucose or lipotoxicity. We hypothesized that metreleptin would improve cardiac abnormalities in LD, and that this would be mediated by improvements in glucose and triglycerides (TG). We analyzed echocardiograms (echo), blood pressure (BP), heart rate (HR), and metabolic parameters in 38 subjects with LD (18 GLD, 20 PLD) who were treated with metreleptin in open-label clinical studies at the National Institutes of Health. 27 had repeat echo after 1y of metreleptin (mean 1.0 ± 0.2y), and 23 after 3 to 5y (mean 3.7±0.6y). In GLD, metreleptin significantly improved metabolic disease, including reduced TG (median(IQR) 740(403–1239), 138(88–196), 211(136–558) mg/dL at baseline, 1y, & 3-5y, P&lt;0.0001), hemoglobin A1c (9.5±3.0, 6.5±1.6, 6.5±1.9% at baseline, 1y, & 3-5y, P&lt;0.001), and insulin resistance by HOMA-IR (34.1 (15.2–43.5), 8.7 (2.4–16.0), 8.9 (2.1–16.4), P&lt;0.001). Only HOMA-IR improved in PLD (P&lt;0.01). Systolic BP and HR decreased after metreleptin in GLD (BP 120±11, 117±10, 109±16 mmHg, P=0.046; HR 89±9, 82±12, 80±16 bpm, P=0.018; at baseline, 1y, 3-5y, respectively) but not PLD. Metreleptin improved cardiac parameters in patients with GLD, including reduced posterior wall thickness (9.8±1.7, 9.1±1.3, 8.3±1.7 at baseline, 1y, & 3-5y, P&lt;0.01), LV mass (140.7±45.9, 128.7±37.9, 110.9±29.1 at baseline, 1y, & 3-5y, P&lt;0.01), and LV mass index (88.6±22.0, 81.6±16.9, 81.6±16.9 at baseline, 1y, & 3-5y, P&lt;0.01). Metreleptin also improved septal e’ velocity, a measure of early diastolic cardiac function, in GLD (8.6±1.7, 10.0±2.1, 10.7±2.4 at baseline, 1y, & 3-5y, P&lt;0.01). All changes remained significant after adjustment for BP. In GLD, multivariate variable selection models suggested that changes in posterior wall thickness and LV mass index related to metreleptin-induced reductions in TG, and changes in septal e’ velocity related to metreleptin-induced reductions in hemoglobin A1c. No changes in echo parameters were seen in PLD. These findings suggest that metreleptin improves cardiac hypertrophy and diastolic function in patients with GLD, and these improvements may be mediated by reduced lipotoxicity and glucose toxicity. The applicability of these findings to a broader, leptin-sufficient population with LV hypertrophy and/or diabetic cardiomyopathy remains to be determined.
Comparison of Serum Copper, Selenium and Zinc Concentrations Among the States of Glucose Tolerance
Authors: Pattan Vishwanath , Villacreses Maria Chang , Karnchanasorn Rudruidee , Feng Wei , Samoa Raynald , Chiu Ken C 
Published: May 2021

Abstract
Trace element is essential for the proper growth, development, and physiology of the organism and the primary source of trace element is dietary intake. Among trace elements, the role of copper (Cu), selenium (Se), and zinc (Zn) in the pathogenesis of diabetes have been widely recognized. However, there is little information available about these 3 trace elements across the different states of glucose tolerance.
We examined associations between serum levels of trace elements - Cu, Zn, and Se with various stages of glucose tolerance in a representative, cross-sectional sample of US adults. Our sample included 5,087 adults (≥20 years) with available serum concentrations of Cu, Zn and Se as well as states of glucose tolerance, defined by history, HbA1c, fasting, and 2-hour plasma glucose concentrations. Serum concentrations of trace elements were compared with glucose tolerance status with the consideration of covariates. Regression analyses was used to examine the relationship of trace elements with HOMA-IR, HOMA-B, and BMI in non-diabetic subjects with the consideration of appropriate covariates.
Serum Se (P&lt;0.0001) and Zn (P&lt;0.0001) concentrations differed significantly among 3 groups based on the states of glucose tolerance, while no difference was noted in serum Cu concentration. In non-diabetic subjects, serum Cu concentration was positively correlated with BMI (P&lt;0.0001) with a possible compensatory increased beta cell function (P=0.018). Serum Se concentration was negatively correlated with insulin resistance (P=0.016) but not with beta cell function or BMI. Serum Zn concertation was negatively correlated with beta cell function (P=0.0023) and BMI (P=0.018), but not with insulin resistance.
We found that a higher serum concentration of trace elements was associated with negative glucose and fuel homeostasis in a non-deficiency population possibly through different mechanisms. Although the casual relationship remains to be elucidated, we recommend against trace element supplementation in a non-deficiency population.
Cornus Officinalis Induction of Pancreatic β-cell Autophagy as Revealed by Increased LC3 Expression and P62 Phosphorylation
Authors: Fletcher Justin D , Sharp-Tawfik Arielle E , Burkhardt Brant Roger 
Published: May 2021

Abstract
Type 1 diabetes (T1D) is an autoimmune disease that results in the destruction of pancreatic beta cells, diminishing the body’s ability to produce insulin. Currently, over 1.2 million people are affected by this disease in the United States with the only treatment being exogenous insulin. The ideal preventative treatment of diabetes would be to target the interventional window during the critical pre-diabetic stage to inhibit the complete loss of pancreatic β-cells. Cornus officinalis (CO) is considered a source of novel therapeutics for this purpose due to prior reports and work from our laboratory (Mol. and Cell. Endo.2019:494:110491) demonstrating that CO may protect β-cells from autoimmune mediated cytotoxicity and enhance function. To elucidate the molecular mechanism of how CO may be biologically impacting a human pancreatic β-cell line (1.1B4), we previously performed a global and phosphorylation mass spectrometry analysis revealing an increased phosphorylation of p62, which is an important regulator of autophagy. To validate the mass spectrometry results and determine if CO is truly capable of inducing pancreatic β-cell autophagy, we examined LC3 expression which serves as a typical marker for autophagic membranes. 1.1B4 cells were treated with CO for 6 and 12 hours with at concentrations of 500 and 1000 µg/ml, respectively. Cells were fixed with formaldehyde and permeabilized with Triton X-100 followed by fluorescent detection with an LC3 antibody along with DAPI nuclear staining. The cells and nuclei were then imaged using a florescent microscope and it was discovered that upon treatment of CO, an increase in cytoplasmic LC3 puncta was markedly observed as compared to untreated controls. Western analysis also demonstrated increased expression of intracellular LC3 upon CO induction. We then went on to confirm the autophagic process by immunoblotting of p62, which is a cargo receptor for autophagy. Immunoblotting demonstrated increased expression of phosphorylated p62 in a concentration and time dependent manner after treatment with CO. Altogether, CO appears to increase expression in the critical markers of autophagy and suggests that CO may have potential as a T1D interventional therapy by promoting protective autophagy in the pancreatic β-cells.
Hyperglycemia-Induced Metabolic Reprogramming Mediates a Proatherogenic Phenotype in Healthy Human Monocytes
Authors: Castro-Grattoni Anabel Lourdes , Oh Jisu , Zhang Rong Mei , Dusso Adriana , Riek Amy Elizabeth , Bauerle Kevin Thomas , Bambouskova Monika , Stone Pamela , Arbelaez Ana Maria , Bernal-Mizrachi Carlos 
Published: May 2021

Abstract
Introduction: Poor glycemic control is considered an important contributor to cardiovascular disease in patients with diabetes. Episodic hyperglycemia as a surrogate for glycemic variability promotes monocyte adhesion and increases the prevalence of proinflammatory monocytes within atherosclerotic plaques of patients with diabetes. We previously found that acute hyperglycemia-induced a pro-inflammatory phenotype and promoted the development of foamy monocytes by increasing total cholesterol deposition, cholesterol ester, and free cholesterol content by enhancing oxidized LDL uptake. However, the mechanism by which acute hyperglycemia induces monocyte cholesterol deposition and inflammation remains unknown. Methods: Monocytes isolated from healthy individuals (age range 20–40; n=5) were cultured in low (5mM) or high (16.7mM) glucose conditions with or without a glycolysis inhibitor (2-deoxyglucose, 2DG, 5 mM) or an endoplasmic reticulum stress inhibitor (4-phenylbutyric acid, PBA; 20mM) for 6 hrs. After treatment, cytokine release, oxidized LDL uptake, and metabolic assays using Seahorse Technology were performed. Results: Healthy human monocytes exposed under high glucose conditions showed a pro-atherosclerotic phenotype with higher levels of the pro-inflammatory cytokines, TNFα(median of differences 6.34 pg/ml, p=0.002) and IL1β(12.04 pg/ml, p=0.003), and increased oxidized LDL uptake (5062ug Dil-Ox LDL/mg, p=0.001). Furthermore, hyperglycemia resulted in higher levels of glycolysis (basal glycolysis 12.94 pmol/min, p=0.01; basal proton efflux rate 15.5 pmol/min, p=0.03) and mitochondrial respiration (percentage of respiratory capacity 16pmol/min p=0.04), suggesting a significant alteration in the metabolic programming of these monocytes. Treatment with 2-DG or PBA attenuated the pro-atherosclerotic phenotype induced by hyperglycemia, promoting a reduction of cytokine release, a reduction of oxidized LDL uptake, and near normalization of the glycolic rate and mitochondrial respiration, stabilizing cellular bioenergetics. Conclusions: Altogether, our results suggest that monocyte ER stress in response to acute hyperglycemia promotes a hypermetabolic state characterized by a proinflammatory and proatherogenic monocyte phenotype. Therefore, acute hyperglycemia is a potential mechanism promoting atherosclerosis in patients with type 2 diabetes.
Accuracy and Reliability of Tempo Pen and Tempo Smart ButtonTM
Authors: Ringenberger Kimberly , Kaufman Benjamin , Rosilio Myriam , Turakhiya Ankit , Liao Birong 
Published: May 2021

Abstract
Background: Understanding the extent and causes of suboptimal insulin dosing is key for the coordinated diabetes management. Integrating the benefits of monitoring, education, and clinical support can facilitate self-care among people with diabetes mellitus. Methods: This study presents the technical aspects and performance tests on Tempo Pen, a new connection-enabled insulin pen available for Humalog (insulin lispro), Basaglar/Abasaglar (insulin glargine), and Lyumjev (ultra-rapid lispro) U100 formulations. Tempo Pen, as part of the connected care system, work with the Tempo Smart ButtonTM (pending CE mark), which captures insulin dosing information and transmits it to mobile applications to display. The Tempo device (Tempo Pen + Tempo Smart ButtonTM) can track the date, time of day, insulin dose, and type of insulin accurately. Results: The pen met the ISO 11608-1:2014 requirements for dose accuracy at all doses and conditions tested, and all results were within the ISO specification limits. Tempo Smart ButtonTM has been found to be compatible with Tempo Pen, and met the acceptance criteria and target k-values for glide force, dose accuracy, and attachment/detachment force testing. It demonstrated &gt;95% dose recording accuracy with 95% confidence, and also met requirements for data transfer after every injection. Battery life of Tempo Smart ButtonTM was found to be at least one year. Conclusions: Tempo device is the first connected system with a smart disposable pen. It accurately captures real-time insulin dosing information which can help patients and healthcare professionals address suboptimal insulin management to reach the desired glycemic goal.
Effect of Long-Term Metreleptin Treatment on Glycemic Control in Rabson-Mendenhall Syndrome
Authors: Okawa Marinna , Cochran Elaine , Brown Rebecca J 
Published: May 2021

Abstract
Rabson-Mendenhall Syndrome is caused by mutations of the insulin receptor, resulting in extreme hyperinsulinemia and poorly controlled diabetes. We examined whether long-term treatment with metreleptin, a recombinant analog of the hormone leptin, improves glycemia in patients with Rabson-Mendenhall Syndrome. We measured HbA1c in 11 patients with Rabson-Mendenhall Syndrome treated with high-dose metreleptin (≥0.15 mg/kg/day) after 6, 12, 18, 24, 36, 48, and 60 months, and at last follow up in patients treated &gt;60 months (mean 90 months). We measured HbA1c over a comparable time frame in 7 untreated patients with Rabson-Mendenhall syndrome. 5 of these patients were also in the treatment group and were studied prior to starting metreleptin treatment or after metreleptin withdrawal. 2 patients in the untreated cohort were never treated with high-dose metreleptin. We calculated change in A1c from baseline at each of these timepoints in both the treated and untreated groups. At baseline the treatment group had similar age (13.8±5.0 vs 11.3±5.3 years, P=0.35) and trended toward higher A1c (10.7%±1.5 vs 8.9%±2.3%, P=0.08). All analyses were therefore adjusted for baseline A1c. In the untreated group, A1c increased non-significantly over time (P=0.2). Least-square mean change in A1c from baseline was 0.2%±1.4%, 0.2%±1.6%, 0.8%±1.5%, 1.0%±1.5%, 1.8%±1.5%, 1.5%±1.5%, 0.9%±1.4%, and 2.4%±1.4%. at 6, 12, 18, 24, 36, 48, and ~90 months of follow-up. During high-dose metreleptin treatment, A1c decreased non-significantly over time (P=0.2). Least square mean change in A1c from baseline was -1.9%±1.7%, -1.4%±1.8%, -1.0%±1.7%, -1.1%±1.7%, -1.1%±1.7%, -1.5%±1.7%, -0.6%±1.7%, and -0.2%±1.7% at 0, 6, 12, 18, 24, 36, 48, and ~90 months of follow-up. Reductions in A1c after metreleptin were statistically significant at months 6 (p=0.009), 12 (p=0.03), and 48 (p=0.04). Over time, A1c was 1.4% higher in the untreated group vs. the metreleptin treated group (P=0.04). These results suggest that treatment with metreleptin may lower A1c over time in patients with Rabson-Mendenhall syndrome. Better glycemic control, as indicated by lower average HbA1c levels, may reduce the risk of diabetic complications over time.
A Single Virtual Consult Reduces Severe Hyperglycemia in Patients Admitted with COVID19 Infection
Authors: Athonvarangkul Diana , Gunawan Felona , Nagel Kathryn , Bak Leigh , Herold Kevan C , Hwang Janice Jin , Jastreboff Ania M , Kibbey Richard , Shulman Gerald I , Vatner Daniel , Alausa Jameel , Subair Labeebah , Inzucchi Silvio E 
Published: May 2021

Abstract
Diabetes and hyperglycemia are risk factors for morbidity and mortality in hospitalized patients with COVID19. Subspecialty consultative resources to help front-line clinicians treat these conditions is often limited. We implemented a “Virtual Hyperglycemia Surveillance Service (VHSS)” to guide glucose management in COVID19 patients admitted to our 1541-bed academic medical center.
From April 22 to June 9, 2020, hospitalized adult patients with COVID19 and 2 or more blood glucose (BG) values greater than 250 mg/dl over 24-h were identified using a daily BG report. The VHSS reviewed BGs and treatment plans, then made recommendations for future glycemic management via a one-time note, visible to all providers. Some patients with re-admission or persistently elevated BG after 1 week received a second VHSS note. We compared BGs from 24-h pre- and 72-h post-intervention starting at 6AM on the day following VHSS review. We also evaluated for hypoglycemia, insulin infusion use and use of formal diabetes consults. A subgroup analysis was performed on patients in the intensive care unit (ICU). At the end of the intervention, we identified a retrospective control cohort admitted to the same hospital from March 21 to April 21, 2020 who met the inclusion criteria for a VHSS assessment.
The VHSS group consisted of 100 patients with 126 individual VHSS encounters, and the control group comprised 50 patients. Baseline characteristics in the VHSS and control groups, respectively, were: mean age 62.5 vs 62.1 years, % male 58 vs 56, mean weight 91.4 vs 93.4 kg, BMI 31.8 vs 33.0 kg/m2, and HbA1c 9.1 vs 8.8 %. There were fewer patients in the ICU in the VHSS than control group (44% vs 66%). In the VHSS group, mean BG pre- vs. post-intervention was 260.3 ±21.7 and 227.4 ±25.3 mg/dl (p&lt;0.001). In the control group, mean BG pre-and post- the day they met assessment criteria was 264.8 ± 6.5 mg/dl and 250.6 ± 8.6 mg/dl (p=0.18). There was no difference in the use of insulin infusions or diabetes consults between the two groups. More hypoglycemia (BG&lt;70 mg/dl) occurred in the VHSS than control group (8.3% vs 0%, p=0.04). Within the VHSS group, the average change in BG was significantly greater in ICU than non-ICU patients (-51.8 ±8.7 vs -19.6 ±5.0 mg/dl, p&lt;0.01) and the reduction in the % of BG over 250 mg/dl was also significantly greater in the ICU (-32.2% vs -16.8%, p=0.02).
Implementation of a single virtual consult for severely hyperglycemic hospitalized COVID19 patients was associated with rapidly reduced BG concentrations, especially in the ICU. The mean reduction in BG with VHSS intervention was more than 2-fold greater than that observed in our control group. Glucose control remained suboptimal, however, suggesting the need for subsequent input from this specialty service.