bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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<0.0001), hemoglobin A1c (9.5±3.0, 6.5±1.6, 6.5±1.9% at baseline, 1y, & 3-5y, P<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<0.001). Only HOMA-IR improved in PLD (P<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<0.01), LV mass (140.7±45.9, 128.7±37.9, 110.9±29.1 at baseline, 1y, & 3-5y, P<0.01), and LV mass index (88.6±22.0, 81.6±16.9, 81.6±16.9 at baseline, 1y, & 3-5y, P<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<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

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<0.0001) and Zn (P<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<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

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

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

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 >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

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 >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

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<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<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<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.
Characterization of Patients With Type 2 Diabetes Mellitus and COVID-19
Authors: Videa Elvin Omar , Murillo Nancy Gabriela Rodríguez , Alvarenga Pamela Carolina , Ochoa Vania Lizeth Barahona
Published: May 2021

The coronavirus is a pathogen that mainly attacks the human respiratory system Previous coronavirus outbreaks (CoV) include severe acute respiratory syndrome (SARS), the clinical spectrum of COVID19 is very broad ranging from mild symptoms to ARDS to multiple organ failure and death. A history of DM2, advanced age and other comorbidities are considered predictors of higher morbidity and mortality, it is also known that blood glucose and DM levels are independent predictors of morbidity and mortality in patients with SARS. It should be remembered that patients with DM2 suffer from a chronic low grade inflammation that could facilitate the cytokine storm which in turn would be the cause of severe cases of COVID 19 pneumonia and the eventual death of many patients. Glucocorticoids have a stimulating and inhibitory effect on the immune response according to the moment in which it is administered and its circulating levels insulin therapy has been shown to decrease inflammation. For the control of glycemia the objectives must be individualized. Glycemic and individualized targets for non critical hospitalized patients have been established by different scientific societies such as ADA and AACE and Endocrine Society. In Honduras the protocol for the clinical management of adult patients with COVID 19 was developed to establish and standardize timely treatment in patients with suspected or confirmed COVID 19 which consists of the MAIZ scheme and the MAIZ scheme AAA. A retrospective longitudinal descriptive study was carried out with a review of the data obtained from 32 patients diagnosed with DM2 and COVID19 during the months of June through September 2020 at the CAMI Comprehensive Medical Care Clinic located in the city of Tegucigalpa Honduras collecting epidemiological and clinical data. The results of the research show that of the 32 patients with DM2 and COVID 19, 59% (19) belong to the male gender and 41% (13) to the female gender, with an average age of 60 years. In the COVID19 severity classification the evaluated patients presented in the following condition mild 25% (8), moderate 69% (22) and severe 6% (2). The diagnostic method used was detection of anti SARS CoV2 antibodies 56% (17) and TR-PCR 43% (14). 75% (24) received steroids, 8.69% (2) of the patients who used steroids in their management had hyperglycemia and required management with regular insulin. 100% (32) of the patients who were treated recovered without registering any death. Conclusions: are that the pathophysiological factors of DM2 in relation to the immune system of patients can be a determining factor to present a degree of severity greater than that presented by the general population that falls ill with COVID19. Adequate glycemic control can determine a better prognosis in the evolution of the disease despite its degree of severity.
Covid Lockdown Impact on Type 1 Diabetes Health and Well-Being
Authors: Calma Jamie , Sangha Sabrina , Basina Marina
Published: May 2021

Introduction: Data on the impact of the COVID-19 lockdown on glycemic control and psychological well-being in individuals with Type 1 Diabetes Mellitus (T1DM) showed mixed results. Some studies showed improvement in glycemic control attributed to more time for self-care and a more regular lifestyle schedule during the lockdown. However, most published data reflects a short duration of 3–5 months. The impact of long-term social isolation and transition to telemedicine on the health of T1DM patients remains unknown. Our study analyzes patient perception surrounding the impact of an 11-month lockdown on glycemic control, well-being, and self-reported depression symptoms. Methods: PHQ-9 was integrated into a 55-question survey created using RedCap, a secure portal for managing surveys. The survey was sent to 160 T1DM patients over the age of 18 to gauge their current diabetes management and overall well-being prior to, and during the pandemic. The survey also inquired about patients’ perceived effectiveness of telemedicine visits. PHQ9 scores were collected and analyzed along with survey responses. Results: Data collection is still ongoing. From the 47 responders, the PHQ9 screening showed 51% were in the minimal depression score, 34% in the range of mild depression, 11% in moderate depression, and 4% scored in moderate to severe depression. No patients scored within severe depression. In a regular week during the pandemic, 40% of patients experienced difficulty with their motivation and diabetes management and 60% reported no concern, as compared to 36% and 64% respectively before the pandemic. Among the 47 of patient respondents, 30 reported both A1c levels prior and during the pandemic of which 46% showed an improved A1c amid the pandemic, 10% had no change, and 44% reported a worsened A1c level. For the telehealth part of the survey, 90% of patients reported feeling “comfortable with the level of care” they receive via telemedicine, whereas the other 10% were not. Whilst 54% of patients preferred in-person visits and 46% indicated a preference for telehealth visits. Conclusion: T1DM management is challenging. The pandemic adds to the complexity and burden to both self-management and healthcare delivery. Staying locked down for a prolonged period of time imposes economical, psychological, and medical constraints to diabetes care, as nearly half of the patients reported worsening of glycemic control. Our comprehensive survey reports the longest duration reported up to date of how the COVID-19 lockdown impacts patient’s perceived changes in their mental health and diabetes management. It helps clinicians understand the connection between mental and physical health during the pandemic and improve time-restricted telehealth visits by understanding patient concerns. Additional larger scale studies are imperative to expand the knowledge in this field.
COVID19 Induced Diabetes; New Type of Diabetes Mellitus? Viral Genetic Material a Step Towards Cure of Diabetes?
Authors: Phatale Hemant Nagnath , Nikalje Anand , Phatale Priti Hemant
Published: May 2021

The worldwide pandemic of coronavirus disease 2019 (COVID-19), seen in multiple races, ethnicities, age groups, with various co-morbidities. The bidirectional relationship between COVID-19 and diabetes (DM) is already established. The associations of DM with a variety of virus infections have been reported previously. COVID-19 infection could be causally linked to new-onset of DM. We report 13 cases of new type of COVID-19 induced DM. While working in noncovid endocrine clinic we could notice 5 patients presented with fever and URI or osmotic symptoms or post URI cramps in legs. All 5 cases was having hyperglycemia with ketonuria and HbA1c more than 11% with fasting or premeal C peptide levels more than 10 ng/ml. All five patients have new onset DM and they are neither obese nor having family history of DM. Presentation includes fever with cough and/OR osmotic symptoms with hyperglycemia, weight loss in weeks. Out of five, in four patients either RT PCR OR Rapid Antigen Test was positive. One patient presented with cramps in legs with past history of URI without fever. In her COVID 19 IgG antibody was positive. All patients initially treated with insulin but on follow up they are controlled with metformin plus gliptin. All patients have HbA1c less than 6.7 on follow up at 3 months. We have retrospectively analysed data at COVID hospital. We have used inclusion criteria as1Not known diabetes 2Either RT PCR + ve OR COVID-19 Ag +ve OR HR CT SCAN show atypical pneumonia or COVID-19 Ab positive 3Presented as hyperglycemia RBG > 200 mg% 4HbA1c > 7 with Urine Ketones + Exclusion Criteria Received steroids in recent past <2 wk. Total 30 patients presented with hyperglycemia at admission in last one month (September). Out of these, 8 patients who are neither obese nor having family history of DM, nor received steroids in last 2 weeks. All 13 patients (5 + 8) are of new onset DM with BMI around 24, presented with ketonuria, with no family history of DM and who did not received steroids. Hence we propose COVID-19 can cause switch in metabolism to form new type of DM. There are case reports are published about COVID-19 induced DM with ketoacidosis. In another retrospective analysis of 658 COVID-19 patients, 42 presented with ketosis.(Am J Emerg Med 2020:S0735-6757(20)30488-5) Out of these 27 were newly diagnosed DM. But other features like BMI, family history of DM, C peptide levels, use of steroid are missing. We coined new type of DM which cause metabolic switch in metabolism leading to ketosis with HbA1c more than 11 & high normal C peptide requiring insulin initially but later controlled with metformin and gliptin with HbA1c less than 6.7!We further propose that genetic material of virus can cause switch in metabolism, then why should not we use other viral genetic material to reswitch leading towards cure of DM. Further research is needed in this direction.
Do GLP-1 Receptor Agonists Increase the Risk of Breast Cancer? A Systematic Review and Meta-Analysis
Authors: Piccoli Giovana Fagundes , Mesquita Leonardo A , Stein Cinara , Aziz Marina M , Zoldan Maira , Degobi Nathalia A H , Spiazzi Bernardo Frison , Junior Gilberto L Lopes , Colpani Veronica , Gerchman Fernando
Published: May 2021

Background: Risk of cancer is a major concern in the development of drugs for the treatment of obesity and diabetes. In randomized controlled trials (RCTs) of the liraglutide development program, a glucagon-like peptide-1 receptor agonist (GLP-1RA), subjects treated with the active drug had a higher absolute number of breast cancer events. Aim: To assess whether patients treated with GLP-1RAs had a higher risk of breast neoplasms. Methods: We searched MEDLINE, Embase, Web of Science, and CENTRAL from inception to February 8, 2020. Three pairs of reviewers examined and retrieved abstractsand full-text articles for RCTs of GLP-1RAs versus non-GLP-1RA controls(active or placebo) in adults with overweight, obesity, prediabetes, or diabetes,with a minimum follow-up period of 24 weeks and which reported at least oneevent of breast cancer or benign breast neoplasm. Divergences were dealt withby consensus. Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with GRADE. This study follows PRISMA reporting guidelines. Results: We included 52 trials, of which 50 reported breast cancer events and 11 reported benign breast neoplasms. Overall methodological quality was high. Among 48267 subjects treated with GLP-1RAs, 130 developed breast cancer compared to 107 of 40755 controls (relative risk [RR], 0.98; 95% confidence interval [CI], 0.76 to 1.26). Subset analyses according to follow-up, participant/investigator blinding, and type of GLP-1RA did not reveal any differences. The risk of benign breast neoplasms also did not differ between groups (RR, 0.99; 95% CI, 0.48 to 2.01). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. Conclusion: Treatment with GLP-1RAs for obesity and diabetes does not increase the risk of breast neoplasms. Register: This systematic review was preregistered in PROSPERO (CRD42019132704).
Anaphylactic Reaction to Dulaglutide: A Glucagon Like Peptide- 1 Receptor Agonist
Authors: Quadri Hamza , Ataallah Basma , Haggerty Gregory
Published: May 2021

Introduction: The development of Glucagon like peptide-1 (GLP-1) receptors agonists represents an important advancement in the management of type 2 diabetes. The long-acting GLP-1 receptor agonists improve glycemic control, promote weight loss. Anaphylaxis to GLP-1 receptor agonists and mainly Dulaglutide is a rare but serious side effect. We report a patient with Type 2 DM who was recently started on Dulaglutide and started to experience systemic hypersensitivity reactions that required discontinuing the medication and inpatient hospitalization. Case: A 53-Year-old Caucasian female with past medical history of type 2 DM on Metformin presented to the ED with sudden onset of sporadic itchy rash on the lip and chin associated with lip swelling within one hour of her first injection of Dulaglutide. She denied difficulty breathing, rash or pruritus on any other part of the body. She denied any food allergies. The patient used two tablets of Oral Diphenhydramine 25 mg with minimal improvement in her symptoms which warrant her to come to the ED. On arrival, she was Afebrile with a HR 97 beats/minute, a BP of 105/58 mm of Hg and a RR of 17 breaths/minute. The rash was blotchy, non- tender, more evident on the upper lip as compared to the lower lip. Lab results showed WBC count of 11 k/uL with basophils of 2% and HbA1c 8.6%. She was treated for her allergic reaction with Intramuscular injection of Epinephrine 0.3mg, Intravenous Dexamethasone 6mg and Intravenous Diphenhydramine 25mg. She was then transferred to the observation unit for monitoring. Her home metformin 500mg two times a day was continued. After 48 hours, the patient’s symptoms were improved and she was discharged home. She was advised to follow up with her PCP and endocrinologist and stop Dulaglutide. Discussion: GLP-1 receptor agonists are commonly used currently in the management of DM due to their beneficial effect in controlling blood glucose as compared to other diabetic medications. Rarely, a potentially life-threatening reaction, such as anaphylactic reactions have been documented with GLP-1 receptor agonist. Systemic allergic reaction to GLP-1 Agonist Exenatide has been reported in the literature. Our patient had anaphylactic reaction after using Dulaglutide. The mechanism of action of anaphylaxis in GLP-1 receptor agonists is thought to be related to IgE mediated and the immune response was demonstrated by basophil activation.
Continuous Subcutaneous Insulin Infusion Therapy Resulting in Improved Glycemic Control in Patient With Low Health Literacy
Authors: Mandal Shobha , Fnu Manas , Baniya Srijana , Singh Sneha , MolsKowalczewski Barbara
Published: May 2021

Introduction: According to White et al., health literacy is defined as ‘the degree to which individuals can obtain, process, understand, and communicate about health-related information needed to make informed health decisions. Nearly 36 percent of adults in the United State have low health literacy. Low health literacy not only affects the individual and the communities but also puts a lot of burden on healthcare resulting in high healthcare costs. It has adversely influenced diabetes care due to lack of use of preventive services, poor physician-patient communication, poor comprehension of medical instructions, and errors in medication dosing, and timing. Continuous subcutaneous insulin infusion (CSII), also known as insulin pump therapy, and continuous glucose monitors (CGM) are commonly indicated in patients with inadequate glycemic control, high glucose variability, unpredictable hypoglycemia, patients with an erratic schedule or varied work shifts. We present a case of uncontrolled diabetes mellitus in a patient with low health literacy, with significant improvement in glycemic control after starting CSII with CGM.

Case: A 59-year-old female with a 13-year history of Latent Autoimmune Diabetes in Adults, on Insulin and Semaglutide, presented for evaluation in the clinic. She was struggling with insulin dosing and blood glucose control with multiple hospital admissions for hypo- and hyperglycemia. Her home blood glucose levels ranged from 92 to 536 mg/dl. Her HbA1C was between 12 and 18% in the past years. She had developed microvascular complications like diabetic nephropathy, neuropathy, and had a cerebrovascular accident in the past. Her current insulin dose was Glargine 50 units daily at nighttime and Lispro 25 units with each meal. Her most recent HbA1c was 14.5. She was not compliant with diet and has difficulty exercising due to residual weakness from CVA. The patient was struggling with insulin injection with errors in the dosing and timing of insulin due to difficulty in understanding medical instructions. Considering all the struggles and uncontrolled diabetes, CSII with CGM was initiated, with a simple protocol for her, one-click, or two clicks depending on the meal size. Within two months there was a significant improvement in her glycemic control. Her recent HbA1C was 9.5%.

Conclusion: CSII can be considered as a viable treatment option in patients with low health literacy with uncontrolled diabetes mellitus like in our patient.
Diabetes and Tuberculosis: Is There a Relationship?
Authors: Webster John , Vinales Karyne Lima , Correa Ricardo Rafael
Published: May 2021

Background: There is growing evidence that Diabetes Mellitus (DM) is an important risk factor for Tuberculosis (TB) and might affect disease presentation and treatment response. Risk factors for TB include HIV/AIDS, immune suppression (i.e. steroids), silicosis, malnutrition, smoke from domestic stoves and cigarettes, and DM. In recent decades, TB incidence has declined in high-income countries, but incidence remains high in countries that have high rates of HIV infection, malnutrition, and crowded living conditions. Furthermore, DM prevalence is increasing globally, fueled by obesity. Several case–control studies have shown that the odd ratios of developing TB in diabetic patients ranges from 2.44 to 8.33 compared with non-diabetic patients. Several large-scale longitudinal cohort studies have shown similar findings.

Case: A 63-year-old male with poorly controlled type 2 DM (HbA1C of 15%), HTN, COPD and history of pulmonary TB who had previously received 2 courses of treatment, was admitted with sudden dyspnea with non-productive cough. In the ED, he was hypoxic, had bilateral pleural effusions, lower extremity edema and newly diagnosed acute systolic CHF. Sputum smear analysis was AFB positive and Mycobacterium tuberculosis was confirmed via PCR. The smear microbes were resistant to rifampin, poor sample limited further sensitivities, and the patient was started on empiric treatment for multi drug resistant TB with RIPE, Capreomycin, Linezolid, and Moxifloxacin. Endocrinology was consulted to assist in control of hyperglycemia. The patient was managed with high doses of insulin. At the time of discharge his blood glucose where in the range of 120–180 mg/dl during the entire day and the importance of having good BG control was reinforced. He continues his treatment for TB.

Discussion: Diabetes leads to increased susceptibility to Mycobacterium tuberculosis infection and disease via multiple mechanisms, including those directly related to hyperglycemia, as well as indirectly via the effect on macrophage and lymphocyte function, leading to diminished ability to contain the organism. It is possible the refractory course of this patient’s TB and subsequent development of MDR disease was in part due to his poorly controlled diabetes due to poor compliance to prior regimens.

Conclusion: DM is associated with increased risk of contracting TB, the possible delay in sputum culture conversion, increased mortality, and increased risk of recurrent and refractory disease. Adequate screening and treatment of DM may be essential to help prevent patients with diabetes from contacting the disease especially in countries with high prevalence of TB. Also, it is important to ensure adequate treatment response and prevent the development of multidrug resistant disease in diabetics who have already contracted TB.
Diabetes Apps: Information about COVID-19 and Risk Factors?
Authors: Wu Gloria , Lau Chap-Kay Kendra , Nguyen Brian
Published: May 2021

Background: Annually, there are 3.7 billion downloads of mobile health apps. There are 275.6 million smartphones in the US. Diabetes affects 34.2 million people and 88 million have prediabetes. Diabetes is a risk factor for COVID-19 and affects longterm health of the survivors. Other risk factors for COVID-19, include race and gender. There are also linguistic barriers to care in Diabetes and COVID-19. Both diabetes and COVID-19 have higher risks associated with race and ethnicity. With the pandemic, the US government, Google and Facebook, in March 2020, provided emergency grants for COVID-19 and dissemination of public education. Did the Diabetes apps meet this moment of public health crisis?. Purpose: Do Diabetes Apps provide information about COVID-19 and its risk factors? Methods: Using the search term “diabetes,” the top ten most downloaded android and iOS apps were assessed in the Google Play Store/Apple App Store, respectively. Inclusion criteria: 1) Android: Downloads > 100,000; iOS: Reviews > 300, star rating >4. Apple App store does not provide download information. 2) Free; 3) Ability to track health data: HbA1C, FBS; 4) Language Accessibility via in-app language settings. Results: In the Google Play Store(DROID), the top ten apps in descending order were: 1) mySugr, 2) Onetouch Reveal, 3) OneDrop Diabetes Management, 4) Diabetes: M, 5) Health2Sync - Diabetes Care, 6) Diabetes, 7) Ontrack Diabetes, 8) Blood Glucose Tracker, 9) Glucose Buddy Diabetes Tracker, and 10) Diabetes Connect. In the Apple App Store(iOS), the top ten apps in descending order were: 1) OneTouch Reveal, 2) Glucose Buddy Diabetes, 3) One Drop for Diabetes, 4) Glucose - Blood Sugar Tracker, 5) Blood Sugar Monitor by Dario, 6) mySugr, 7) Sugarmate, 8) DiabetesPal, 9) Diabetes:M, 10) Center Health - The Diabetes App. Of the 10 DROID apps: 0/10 had COVID symptom information in the app; 3/10 had a COVID statement; In-app language settings: 2/10 had Spanish and 1/10 had Chinese. Gender: 7/10 Droid apps. Race/Ethnicity: 0/10. Of the ten iOS apps: 0/10 had COVID symptom information in the app; 4/10 had a COVID statement (Only mySugr has CDC link for COVID information); In-app language settings: 1/10 had Spanish and 0/10 had Chinese settings. Gender: 9/10 Droid apps; 7/10 iOS apps, Race/Ethnicty:1/10. Conclusion: Of the top 20 diabetes apps, none had information about COVID-19 and its symptoms within the app. Also, the overall language accessibility is limited. Despite popularity of ehealth, physicians can continue to play an important role in public education about Diabetes and COVID-19 during this important time of the pandemic.
Hyperglycemia, Hypertriglyceridemia and Acute Pancreatitis in COVID-19 Infection
Authors: Torres Marina Torres , Rodriguez Kimberly Padilla , Vergne-Santiago Norma , Diez Andrea del Toro , Bossolo Alex N Gonzalez , Garcia Michelle Marie Mangual , Torres Gabriela Torres
Published: May 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affects the respiratory tract, but gastrointestinal (GI) symptoms may obscure a secondary diagnosis. GI symptoms similar to the ones presented in acute pancreatitis (AP) have been reported. SARS-CoV-2 binds to angiotensin-converting enzyme 2 receptors, which have been identified in the lungs and pancreas. It has been discussed that systemic response to the infection prompts dysregulation in the affected organs. Hyperglycemia is an independent risk factor for increased mortality and thus a detailed assessment must be performed.

A 47 year-old man with dyslipidemia arrived at the ER due to a severe constant epigastric pain of 1 day of evolution with back radiation associated with nauseas, emesis, and hyporexia. Upon examination he was tachycardic and in distress due to pain. Laboratories revealed normocytosis, normal hemoglobin, mild thrombocytopenia, hyperglycemia (150 mg/dL), corrected hyponatremia (130 mmol/L), and corrected hypocalcemia (7.4 mg/dL). Amylase (2,332 U/L) and lipase (2,990 U/L) were elevated. Triglycerides were 6,256 mg/dL and glycated hemoglobin was 6.1%. Abdominal CT scan revealed pancreatitis. He was admitted to the ICU due to severe AP due to hypertriglyceridemia with IV hydration and IV insulin infusion. During the first day of admission, he developed respiratory distress requiring intubation, marked abdominal distension, hemodynamic instability, and oliguria. Intra-abdominal pressure yielded 24 mmHg leading to the diagnosis of abdominal compartment syndrome. He underwent emergent abdominal decompressive laparotomy with Bogota Bag placement. COVID-19 PCR test was performed and reported positive. 72 hours later, triglycerides improved and IV insulin was discontinued, but hyperglycemic state prompted subcutaneous basal and correction boluses. Insulin requirement progressively decreased and was discontinued after 14 days. He continued to show clinical improvement and by day 40, the patient was successfully extubated and discharged after physical rehabilitation.

SARS-CoV-2 infection has shown a complex multisystem involvement leading to variable presentations which can be fatal if not identified and addressed properly. Albeit, AP is a rare manifestation of COVID-19, clinicians should be aware and pay attention to the related complications. Proposed mechanisms for hyperglycemia and AP include β-cell damage. The pathogenetic role of COVID-19 in hypertriglyceridemia is unclear. Little attention has been paid to the extent of pancreatic injury caused by this virus. To our knowledge this is the second case presenting with hyperglycemia, hypertriglyceridemia, and AP in COVID-19 infection. As the global pandemic is still growing, elucidation of key pathways and mechanisms underlying these associations would aid in the treatment of patients with COVID-19 worldwide.
Maturity Onset Diabetes of the Young Masquerading as New Onset Diabetes Mellitus Type 1
Authors: Miller Assia , Bargman Renee
Published: May 2021

Introduction:/background: Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic disorders with autosomal dominant mode of inheritance. Mutation in hepatocyte nuclear factor-1β (HNF-1β) gene results in an error of embryonic development of pancreas and nephron, leading to MODY type 5. MODY 5 accounts for 1% of maturity-onset diabetes of the young. It has peak incidence in adolescence/early adulthood, and is associated with renal pathology. Clinical Case: A 15-year boy with history of hypertension and Hashimoto thyroiditis with normal thyroid function was referred for Hb A1C of 6.7% (< 6.4%). Physical exam was remarkable for normal weight at 64%, normal BMI at 83%, absence of thyromegaly or acanthosis nigricans. Diabetes was confirmed by 2 hour Oral Glucose Tolerance Test study (baseline glucose 154 mg/dL (<126 mg/dL), 2 hour glucose 384 mg/dL (<140 mg/dL)). Small doses of insulin (total daily dose 0.1 units/kg/day) resulted in good glucose control. Further labs were significant for weakly positive TTG and GAD antibodies (tTG Ab IgA 55.5 U/mL (<4.0 U/mL), GAD-65 Ab 0.05 nmol/L (< 0.02 nmol/L)), positive TPO (0.0 - 34.9 IU/mL) and detectable ATA antibodies 45.8 IU/mL (0.0 - 40.0 IU/mL), C-peptide 2.9 ng/mL (0.9–7.1 ng/mL). Islet cell, Insulin and Zinc transporter 8 antibodies were negative. Over the next few months he was weaned off insulin and subsequently he had a high insulin of 29.43 uU/mL (3.0 - 17.0 uU/mL) with glucose level of 169 mg/dL. Renal US was performed as part of the work up for hypertension and revealed a small right calculus with no hydronephrosis and a small 8-mm cortical cyst in the right kidney. Urinalysis showed microalbuminuria. Upper GI endoscopy and colonoscopy with biopsy ruled out celiac disease. Presumptive diagnosis of MODY was entertained despite positive TPO, ATA, TTG and GAD antibodies suggesting autoimmune endocrinopathies. His Hb A1C levels were in the range of 5.7 to 6 % during the 15 months of follow up. Genetic testing for MODY resulted in heterozygous deletion of exons 1–9 of the HNF1B gene consistent with MODY5. Conclusion: This is a case of MODY 5 with weakly positive GAD 65 antibodies that was initially misdiagnosed as type 1 diabetes. The presence of weakly positive antibodies should not preclude a work up for MODY in a patient who does not have the clinical features of classic type 1 DM.