bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Metformin Use Associated With a Decreased Mortality for COVID-19 Diabetic Patients? A Meta-Analysis
Authors: Sun Chenyu , Cheng Ce , Kim Keun Young , Ahmed Mubashir Ayaz , Manem Reveena 
Published: May 2021

Abstract
Introduction: Coronavirus disease 2019 (COVID-19) has been spreading globally for more than half a year. Previous studies remain controversial regarding whether metformin is associated with reduced risk for COVID-19 diabetic patients. Thus, this meta-analysis is performed. Method: A comprehensive literature search on PubMed and Web of Science was conducted to identify all relevant studies published prior to October 2020 according to the established inclusion criteria. This meta-analysis was reported in conformity to the Preferred Reporting Project declared by the Systematic Review and Meta-Analysis (PRISMA). The quality assessment was performed by the Newcastle-Ottawa Scale (NOS). The pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated to estimate the association between metformin use and mortality for COVID-19 patients. A random-effect or fixed-effect model was used based on heterogeneity significance. Subgroup analysis was performed based on in-hospital-use or home-use, and different sample sizes. Sensitivity analysis and publication bias detection were also performed. All statistical analyses were performed using RevMan software (version 5.3; Cochrane library) and STATA 12.0 statistical software (Stata Corp., College Station, TX), and all P values were two-tailed, the test level was 0.05. Result: 97 articles were obtained from the database search, and 5 articles obtained from other sources. 8 articles involving 11,169 participants were included. Most studies were considered moderate quality. A statistically significant association between metformin use and decreased mortality of COVID-19 patients was found (OR 0.53, 95%CI: 0.34, 0.83, P=0.005, I2=77%). In the subgroup analyses, home-use of metformin was also associated with a reduced risk of mortality (OR 0.54, 95%CI: 0.35, 0.84, P=0.006, I2=66%), and one study reporting in-hospital use did not find reduced mortality among COVID-19 patients taking metformin (OR 1.65, 95%CI: 0.71, 3.86, P=0.247). For sample size &gt;1,000, no statistically significant reduced risk of mortality (OR 0.84, 95%CI: 0.57, 1.26, P=0.41, I2=73%) was found, however, for sample ≤1,000, a statistically significant reduced risk of mortality (OR 0.29, 95%CI: 0.19, 0.44 P&lt;0.00001, I2=0%) was found. Sensitivity analysis by change fixed-effect models to random-effect models and by omitting each study at a time confirmed the relative stability of the result. Begg’s test (z=0.37, P=0.711) and Egger’s test (t=-1.98, P=0.096) did not detect a significant risk of publication bias. Conclusion: The current meta-analysis demonstrates that metformin use is associated with decreased mortality for COVID-19 diabetic patients. However, only one study investigating the in-hospital use of metformin. More high-quality original studies are needed to further explore the association between metformin use and mortality risk of COVID-19.
Proportion of Patients With HbA1c Corresponding to Prediabetes and Diabetes Ranges Without Previous Diagnosis in a Covid-19 Unit in Mexico City
Authors: Aguilar-Soto Mercedes , Cuenca Dalia , Mercado Moises 
Published: May 2021

Abstract
Mexico has been one of the most affected countries by COVID-19, with case rate of 1195.32 per 100,000 patients and one of the highest mortality rates worldwide. Diabetes has been found a major risk factor for severe COVID-19. Mexico has a high prevalence of diabetes, estimated around 10.3%. On top of this, recent estimates suggest that 4.1% of the population has diabetes but does not have a proper diagnosis. We conducted a retrospective study in patients hospitalized for COVID-19 in tertiary private hospital in Mexico City from March 15th to July 10th, 2020. We classified patients as having diabetes or prediabetes if it was registered in the electronical medical record. Patients were classified as newly diagnosed diabetes if they had an HbA1c on admission greater or equal than 6.5%. A total of 144 measurements of HbA1c were done on non-diabetic patients. Eighteen patients (12.5%) had a level of HbA1c equal or higher than 6.5%, while 70 (48.6%) patients had a level between 5.7% and 6.5%. Of the patients with HbA1c levels suggesting prior diabetes, 9 (50%) of them did not have hyperglycemia (&gt;140 mg/dl) on admission. Our findings suggest that Mexican patients with COVID-19 might need HbA1c measurements regardless of glucose levels on admission since unknown diabetes is frequent and might modify in-hospital glucose management and discharge follow up and treatment.
Usefulness of the Continuous Glucose Monitoring (Freestyle Device) to Assess Glycemic Control of Diabetic Patients With and Without COVID 19 in a Hospital of Bogotá Colombia
Authors: Medina Adriana , Veronesi Luz Amaya 
Published: May 2021

Abstract
In the context of the COVID19 pandemic, diabetes mellitus constitutes a main risk factor that increases overall mortality (1). The continuous glucose monitoring system (CGM) is an alternative that allows strict glucose monitoring and reduces the contact of the healthcare providers with the patients in the pandemic era. We conducted a study using CGM in COVID vs non-COVID patients hospitalized at the San José Hospital in Bogotá Colombia. Methods: Single center, prospective study of glucose monitoring in patients with and without COVID19 using the Freestyle system. We included patients of 18 years and older, hospitalized at Hospital San José de Bogotá, with diagnosis of diabetes and treated with insulin. We used the T student distribution to analize the data. Primary outcomes were the usefulness of the device in inpatients, and the clinical outcomes according to glucometric measures in patients with and without COVID19 infection. Results: CGM devices were placed on 30 patients: 10 with, and 20 without COVID. The system was feasible with good nurse acceptance. The age of the patients was between 18 and 90 years. Of the COVID positive patients, 30% required ICU and 10% died, the mean HBA1C was 9.5% (CI 95% 7.5–10.09%) with a general variability of 35.6%, only 3 patients archieved goals of time in range. The general glycemic index was 7.04% (CI 0.66-0.100)Of the non COVID patients, 10% required ICU and 10% died, the average variability was 30.9% and hypoglycemic episodes predominated in 3 patients. The general glycemic index was 6.6% (CI 0.61–0.71)The patients who required ICU had an average HBA1C of 10.4%, 80% received corticosteroid management during the hospital stay. No patient had skin or soft tissue infection at the sensor insertion site. Conclusions:
During the COVID-19 pandemic, CGM is a useful method for glucometric control that reduces the contact of healthcare providers and allows early interventions to improve metabolic control. Worse outcomes are seen in patients with higher variability and with COVID infection. References: 1. Apicella M. Campopiano MC. Mantuano M. Mazoni L. Coppelli A. Del Prato S. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol.2020: 8; 782–92.
The Risks of Polycystic Ovary Syndrome and Diabetes Vary by Ethnic Subgroup Among Young Asian Women
Authors: Guo Lynn , Gordon Nancy P , Chandra Malini , Dayo Olumayowa M , Lo Joan Chia-Mei 
Published: May 2021

Abstract
Background: Previous studies demonstrate that aggregation of Asian ethnic subgroups masks variation in the prevalence of diabetes (DM) across these groups. Population data also suggest that Asian ethnic differences exist in the prevalence of diagnosed polycystic ovary syndrome (PCOS), but few studies have compared the risk of PCOS and DM in the same Asian subgroups, accounting for differences in BMI. We previously found that the prevalence of PCOS based on ≥1 diagnosis ranged from 1.6–1.9% in White, Hispanic, and Black women and 1.2%, 1.7%, and 3.5% for Chinese, Filipina, and South Asian women age 21–44 years. In this study, we further examined and compared the risk of clinical PCOS and clinical DM by weight status in these Asian subgroups. METHODS: Using data from women receiving care in a large integrated healthcare system, we conducted a cross-sectional, retrospective study of 19,848 Chinese, 23,890 Filipina, and 19,905 South Asian women aged 21–44 years who had ≥1 clinic visit in 2016. Ethnicity was based on data from the electronic health record (EHR), and those identified in the EHR as Asian with unspecified ethnicity were assigned as Chinese, Filipina, and South Asian based on algorithms that included primary language and surname. BMI was calculated from non-gestational height and weight and classified as healthy, overweight (23 to &lt;27.5), or obese (≥27.5 kg/m2) using Asian BMI thresholds. Clinical PCOS was defined by ≥2 ambulatory PCOS diagnoses (ICD-9 256.4, ICD-10 E28.2) in 2015–2016 and clinical DM by ≥2 ambulatory DM diagnoses (ICD-9 250, ICD-10 E10-11,13) in 2015–2016 and history of DM pharmacotherapy. Multivariable logistic regression was used to produce adjusted odds ratios (aOR) for PCOS and DM comparing Filipina and South Asian to Chinese women after adjusting for age and weight status. Results: Among Chinese, Filipina, and South Asian women, respectively, prevalence of PCOS was 1.0%, 1.5%, and 3.2%, prevalence of DM was 1.2%, 4.2%, and 2.5%, and prevalence of obesity was 15.6%, 38.5%, and 30.1%. The prevalence of obesity was high in women with PCOS (58.9%) and women with diabetes (70.0%). South Asian women had a 2.5-fold higher adjusted odds of PCOS than Chinese women (95% CI 2.1–3.0), with no difference for Filipina versus Chinese women (aOR 1.0, 95% CI 0.8–1.2). In contrast, South Asian (aOR 1.5, 95% CI 1.3–1.8) and Filipina women (aOR 2.2, 95% CI 1.9–2.6) had higher adjusted odds of DM than Chinese women. Conclusion: Despite the known metabolic association of PCOS and insulin resistance, we found that the risk profiles of PCOS and DM differed by Asian ethnicity, with risk of PCOS highest in South Asian women and risk of DM highest in Filipina women. While our analyses were limited to women with BMI assessed at a clinical visit and not a screened population, the differential risk of PCOS and DM in Asian subgroups and higher burden of PCOS in South Asian women, independent of BMI, warrant further study.
“The Unusual Suspect” - Insulin Autoimmune Syndrome, an Extremely Rare Cause of Hypoglycemia
Authors: Aftab Hassaan B , Malchoff Carl D 
Published: May 2021

Abstract
Background: Insulin autoimmune syndrome (IAS), also called Hirata syndrome, is a rare diagnosis which is characterized by hypoglycemia, normal or elevated fasting insulin level, and elevated anti-insulin antibody titers. Clinical Case: 45-year-old nondiabetic Caucasian female presented to the emergency department (ED) with chief complaint of near-syncope. She reported difficulty concentrating and feeling faint roughly 1 hour after consuming breakfast. Upon ED arrival, fingerstick glucose (FSG) was 47 mg/dL. Her symptoms resolved with ingestion of orange juice and repeat blood glucose (BG) 15 minutes later was 120 mg/dL. She reported similar symptoms in the last 5 years happening “every few months” without a predictable pattern; twice with witnessed loss of consciousness. Workup for syncope in the past included normal neurologic, cardiac, and tilt-table testing. She had no prior low FSG/BG recorded, no personal history of bariatric surgery or family history of diabetes mellitus and no access to antihyperglycemic medications. Past medical history included ulcerative colitis and medications included sulfasalazine and multivitamins. Pertinent review of systems was negative for weight loss, nausea, and diarrhea. Vital signs were within normal limits. Physical exam was unremarkable. Height was 165 cm, weight 67.8 kg and body mass index 24.9 kg/m2. Blood draw after overnight fast revealed BG of 78 mg/dL, C-peptide 0.7 ng/mL (ref range 0.8–3.5), insulin 10 µIU/mL (3–19), proinsulin &lt;1.6 pmol/L (&lt;8.0), insulin-like growth factor-2 (IGF-2) 339 ng/mL (180–580) and insulin antibody level 10.0 U/mL (0.0–0.4). She was managed conservatively with frequent small meals and patient has continued to do well without recurrence of symptoms. Conclusion: IAS is an exceedingly rare disease entity with about 460 cases described in literature, mostly in patients of Asian descent. Workup for hypoglycemia in non-diabetic patients should include insulin antibody titers to rule out IAS. There appears to be a genetic predisposition to developing IAS in patients with major histocompatibility complex (MHC) genes HLA-DQA1, HLA-DQB1 and HLA-DRB1. It is now being more frequently described in patients of non-Asian descent, particularly those with other autoimmune or plasma cell dyscrasias. It is also associated with drugs containing sulfhydryl groups and viral infections. Treatment should be tailored to severity of disease. Most drug induced IAS resolves after cessation of culprit drug. Conservative management is usually the first step with frequent, low carbohydrate meals with diazoxide or octreotide as adjunctive options. Immunosuppression (high-dose prednisolone or rituximab) and plasma exchanged are reserved severe or refractory cases.
A Case of Concomitant COVID-19 Infection-Induced Acute Respiratory Distress Syndrome and Diabetic Ketoacidosis: Another Challenge in Fluid Management
Authors: Panjawatanan Panadeekarn , Jha Samir , Hughes Joseph , Riesenfeld Erik 
Published: May 2021

Abstract
Background: Coronavirus Disease 2019 (COVID-19) has been announced as a pandemic worldwide. The respiratory tract is a target organ-system which can result in serious complications like acute respiratory distress syndrome (ARDS). Management of this condition is more challenging in diabetes who developed diabetic ketoacidosis (DKA).
Clinical Case: We report a case of a 59-year-old male who presented with 4 days of productive cough with blood-tinged sputum, shortness of breath, and chills. Patient had decreased oral intake and had not been compliant with his medication. He had underlying disease significant for type 2 diabetes, essential hypertension, obesity (BMI 32 kg/m2), history of pancreatitis and diabetic ketoacidosis. His diabetes medications included insulin degludec 126 units with insulin lispro sliding scale, dulaglutide, metformin, and sitagliptin. On examination, the patient was lethargic. Initial vital signs included a temperature of 36.8°C, respiratory rate 24/min, heart rate 65 bpm, BP 140/67 mmHg, and oxygen saturation 91% on room air. Lung auscultation revealed bilateral widespread crackles. Laboratory was significant for glucose 387 mg/dL (70–139), pH 7.25 (7.35-7.28), anion gap 15.8 mEq/L (6–14) and concurrent normal gap acidosis, urine ketones 15 mg/dL (negative), and LDH 325 U/L (140–171). An initial chest x-ray showed bilateral peripheral pulmonary infiltrates. Workup was negative for influenza, pneumococcus, and legionella. The patient was subsequently intubated on the first day for worsening hypoxia due to severe ARDS (PaO2/FiO2 ratio of 71). He was concomitantly treated for DKA and hypotension with intravenous insulin, initially started at 12 units/hour with subsequent titration down to average of 5 units/hour, fluid resuscitation (approximate 34 ml/kg actual body weight) and, potassium repletion on the first day. On the same day, his hypoxia worsened with an increase in pulmonary infiltrates, so we stopped intravenous fluids and initiated norepinephrine for 24 hours. His mechanical ventilation settings followed ARDS guidelines. Positive COVID-19 was detected from real-time RT-PCR. After maintaining a negative fluid balance, we were able to extubate in 72 hours. Intravenous insulin was continued for 46 hours then was switched to subcutaneous basal-bolus regimen. He was discharged with insulin degludec 100 units with insulin lispro sliding scale, metformin, and sitagliptin. Dulaglutide was held.
Conclusion: Type 2 diabetes are rarely affected by DKA but can be found in up to 27% of the cases. There are reports of ARDS as a serious complication in severe DKA in adults and children, yet no data for concomitant DKA and ARDS has been published. We propose that the management of DKA in COVID-19 patients with ARDS may be similar to the paradigm utilized for other volume restriction in patients with congestive heart failure and end-stage renal failure.
A Case of Possible SARS-COV-2 Induced Beta-Cell Failure
Authors: Perlman Jordan E , Echouffo-Tcheugui Justin B 
Published: May 2021

Abstract
Background: There are several known viral triggers of ketosis-prone diabetes, including SARS-1 and HHV-81,2. SARS-COV-2 can bind ACE-2 receptors on the beta-cell causing destruction and acute impairment of insulin secretion3. There is accruing evidence to suggest that COVID-19 infection can worsen preexisting diabetes or induce new disease4.
Clinical Case: A 40-year-old Hispanic male presented to the ER complaining of fatigue, polyuria, and polydipsia. A screening COVID-19 PCR was positive but he denied URI symptoms. His admission labs were notable for hyperglycemia (434 mg/dL; n 71–99), metabolic acidosis (pH 7.1 [n 7.35–7.45]; HCO3 3 mmoL/L [n 21–32]), increased anion gap (27 mmoL/L; n &lt; 12) and elevated HbA1c (7.9%; n &lt; 5.7%). The patient’s fructosamine was also high (464 umol/L; n 200–285) and discordant from his HbA1c. There was no evidence of pancreatitis, lactic acidosis, renal impairment or hepatic dysfunction. The patient had no known medical problems, did not drink alcohol to excess, and reported good access to nutrition. He had a strong family history of T2DM, but his BMI (23.3 kg/m2) and lipid panel were normal. The DKA was managed in the medical ICU using fluids and IV insulin per protocol. The patient required 180 units of IV insulin/24-hours (2.5 units/kg/day) to maintain blood glucose 180–250 mg/dL. After 48-hours of IV insulin, he was transitioned to subcutaneous insulin and prescribed multiple daily injections at discharge. There were concerns about possible T1DM and/or glucose toxicity leading to further diagnostics. His GAD-65 (&lt;5 [IU]/mL; n 0–5 [IU]/mL) and IA-2 (&lt;5.4 U/mL; n &lt;5.4 U/mL) antibodies were negative but his c-peptide was suppressed (0.64 ng/mL; n 0.8–3.85). The patient was reevaluated at three months post-discharge. His glycemic control and insulin requirements had improved but repeat c-peptide level was undetectable. He was thought to have beta-cell failure and referred to a diabetologist.
Conclusion: This is a case of absolute insulin deficiency persisting for at least three months most likely attributable to acute COVID-19 infection.
References: 1. Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010;47(3):193–199.2. Sobngwi E, Choukem SP, Agbalika F, et al. Ketosis-prone type 2 diabetes mellitus and human herpesvirus 8 infection in sub-saharan africans. Jama. 2008;299(23):2770–2776.3. Hamming I, Timens W, Bulthuis M, Lely A, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–637.4. Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020;8(6):546–550.
A Case Report of Euglycemic Diabetic Ketoacidosis in the Setting of Keto Diet and SGLT-2 Inhibitors
Authors: Marenych Nadiia , Gilden Janice L 
Published: May 2021

Abstract
Background: Euglycemic diabetic ketoacidosis is relatively uncommon. Studies of SGLT inhibitors, when added to either insulin pumps or multiple daily injections have shown glycemic benefit in type 1 diabetes mellitus (DM), with reductions of Hba1c, body weight, glucose variability, without increased hypoglycemia, but with increase of DKA. We report a case of euglycemic diabetic ketoacidosis in a patient with type 1 DM, precipitated by keto diet and SGLT-2 inhibitor use. Clinical Case: A 24 year-old female with 17 years of type 1DM, using insulin pump therapy and empagliflozin, started a keto diet, then stopped meal time boluses, and eventually turned off her pump. Urine ketones were high. After 12 hours, she developed fatigue, nausea, abdominal pain, and shortness of breath, and presented to the emergency room. She was afebrile with BP 112/68, HR 123 beats/minute, respiratory rate 18, and oxygen saturation on room air 99%. Physical exam: anxious in mild distress, abdomen was diffusely tender without guarding. Laboratory results: sodium 141 mmol/L, potassium 5.3 mmol/L, chloride 103 mmol/L, CO2 8 mmol/L, Anion gap 30 mmol/L, with blood glucose of 201 mg/dL,and BUN 22 mg/dL, creatinine 1.55 mg/dL, GFR 41 ml/min/1.73m, Hba1c 7.2%, Normal thyroid tests, WBC 23.1 10x3/ul, Hgb 16.6 g/dl, HCT 53.3%, normal differential, Urine: ketones &gt;=80 mg/dl, Protein 30 mg/dl, urine glucose &gt;500 mg/dl. CT abdomen and pelvis with contrast: questionable regional colitis of ascending colon with prominent distended stomach, and possible functional obstruction, such as diabetic gastroparesis, and fatty infiltration of liver. An insulin infusion per DKA protocol was started. Over the next few days, she continued with high anion gap and low CO2; requiring bicarbonate drip. By day 3, laboratory results finally improved. Symptoms completely resolved, and the patient was started on a carbohydrate restricted diet with insulin pump therapy, and discharged home after intensive education by the diabetes team. Discussion: Euglycemic diabetic ketoacidosis is a rare, but serious complication of DM, characterized by glucose values ≤200 mg/L, ketosis and metabolic acidosis. Possible risk factors include decreased caloric intake, keto diet, heavy alcohol consumption, change in insulin regimen, chronic liver disease, pregnancy, and sodium glucose cotransporter 2 (SGLT2) inhibitors. This case highlights the complex interplay between type 1 DM, a keto diet, in combination with SGLT-2 inhibitor therapy, which may result in euglycemic diabetic ketoacidosis, and also demonstrates the importance of patient education regarding risks of ketoacidosis in the setting of SGLT-2 inhibitor therapy, in conjunction with low calorie intake and diets, such as the keto diet. Reference: (1) Julio Rosenstock, et al. Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE Trials. Diabetes Care 2018 Dec; 41(12): 2560–2569.