bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Sclerostin Is Associated With Central Fat Distribution in Patients With Type 2 Diabetes and Peripheral Neuropathy
Authors: Costi Bruna , Correia Carolina , Medeiros Karoline , Filho Paulo Barros , Bandeira Francisco
Published: May 2021

Background: Peripheral neuropathy (PN) is the most common chronic diabetic complication occurring in both type 1 and type 2 (T2DM) patients as well as in prediabetes states. Metabolic syndrome seems to be as important as glycemic control in determining the onset and course of DPN, but the mechanisms underlying this association is far from conclusive. Sclerostin (SCL) is a glycoprotein secreted by osteocytes that has an antagonistic effect on the Wnt/beta-catenin pathway which is related to bone formation as well as to increased ectopic fat including marrow fat. Besides to its well-documented role in bone metabolism, the relationship between SCL and adiposity and metabolic syndrome is poorly understood. Objective: To determine SCL levels in patients with T2DM and DPN and evaluate their relationship with metabolic and body composition parameters. Design: Cross-sectional study including 56 patients with T2DM and DPN. Serum SCL levels, glycemic and lipid profile, anthropometric measurements, and percent body fat (PBF) were determined. Results: Mean age was 61.80 ± 10.67 years, duration of T2DM 13.30 ± 8.13 years, 57.1% men, 78.6% hypertensive, body mass index 28.74 ± 5.04 kg/m2, abdominal circumference 99.86 ± 13.37 cm, waist-to-hip ratio (WHR) 0.97 ± 0.08, fasting plasma glucose 169.73 ± 83.13 mg/dL, HbA1c 8.88 ± 2.09%, Triglycerides (TG) 163.54 ± 75.93 mg/dL, SCL 207.41 ± 215.13 pg/mL, and PBF 34.45 ± 8.42%. There were significant correlations between SCL and TG (r=0.407, p=0.003) and significant differences in TG according to quartiles (< p25 vs >p75) of SCL: 125.15 ± 47.45 mg/dL vs 223.50 ± 88.77 mg/dL, p = 0.002; and in WHR: 0.97 ± 0.07 vs 1.01 ± 0.07, p = 0.027. Conclusion: We found that increased levels of SCL were associated with WHR and TG in T2DM patients with DPN.
Yy1 Depletion in Pancreatic Beta Cells Leads to Energy Source Switch From Glycolysis to Oxidative Phosphorylation
Authors: Perez-Garcia Eliana M , Liu Ruya , Yechoor Vijay K
Published: May 2021

Background: Gene expression is determined by structural interactions in between transcription factors, cofactors and enhancer elements, as well as enhancer-promoter interactions (1). Both YY1 and CTCF are essential, zinc finger proteins that bind hypo-methylated DNA sequences, form homodimers, and thus facilitate DNA loop formation (1). ​However, YY1 preferentially occupies interacting enhancers and promoters, whereas CTCF preferentially occupies sites distal from these regulatory elements, forming larger loops and participating in insulation (1). A sequencing study of spontaneous functional insulinomas in a Chinese cohort identified a somatic a hotspot mutation in YY1 (c.C1115G/p.T372R) in 30% of the cases, associated with increased YY1 activity (2). YY1 is a critical transcription factor involved in the regulation of proliferation and metabolism (2).

Hypothesis: YY1 loss-of-function alters energy source preference in pancreatic β-cells.

Methods: YY1 stable loss-of-function in mouse insulinoma cell lines was achieved by shRNA lentiviral transduction. Mitochondrial membrane potential (MMP) was measured via flow cytometry of aggregated mitochondria to monomeric mitochondria ratio. Mitostress and complex-substrate controlled respiration were measured by Seahorse analyzer. Mitochondrial copy number was assessed by mitochondrial to nuclear DNA ratio. Quantitative qPCR and Western blotting were used to assess mitochondrial gene and protein expression.

Results: Our data indicated that YY1 deficient β-cells showed increased MMP and maximal respiration. No significant differences were found in basal respiration, ATP production, proton leak, non-mitochondrial oxygen consumption or coupling efficiency. We also found that YY1 deficient β-cells exhibited reduced glycolytic capacity and decreased ETC complex IV activity, with concurrent increased complex I and II activity. In addition, YY1 deficient β-cells exhibited elevated mitochondrial copy number​ and increased quantitative mRNA of mitochondrial gene expression, which could be correlated with increased PGC1-α expression.

Conclusions: YY1 is critical in the metabolic regulation of β-cells, particularly in the facilitation of glycolytic metabolism. YY1 activating mutations in functional spontaneous insulinoma cells can lead to a proliferation dysregulation accompanied by a metabolic switch that favors glycolysis, while the opposite occurs in YY1 deficient β-cells.

References: (1) Weintraub AS et al, Cell 2017 Dec 14; 171:1573–1588 (2) Cao Y et al, Nat Commun 2013 Dec 10; 4:2810
Clinical Effectiveness of a Protocol to Manage Deamthasone-Induced Hyperglycemia Among Hospitalized Patients With COVID-19
Authors: Asiri Alanood Ahmed , AlGuwaihes Abdullah , Jammah Anwar Ali , Alfadda Assim Abdulaziz , Al-Sofiani Mohammed E
Published: May 2021

Importance: Well-controlled glucose levels during hospitalization (i.e. 70–180 mg/dl) have been associated with lower mortality in patients with COVID-19. The recent addition of dexamethasone to COVID-19 treatment protocols has raised concerns about the negative metabolic consequences of dexamethasone including hyperglycemia. We developed a simplified, yet comprehensive, protocol to guide the management of dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19.

Objectives: To present our protocol for the management of dexamethasone-induced hyperglycemia and examine its clinical effectiveness in the real world.

Methods: An algorithm-based protocol that outlines all aspects of the inpatient management of dexamethasone-induced hyperglycemia in COVID-19 patients, from time of admission to discharge including guidance on insulin titration, was disseminated to the COVID-19 teams in our hospital. Medical records of 163 patients admitted between June and September, 2020 who tested positive for COVID-19 and developed dexamethasone-induced hyperglycemia were reviewed. Fasting, pre-lunch, pre-dinner and bedtime glucose levels during the first five days of admission and day of discharge were compared between the 47 patients who were managed “Pre-Protocol” implementation and the 116 patients who were managed “Post-Protocol” implementation.

Results: On admission, there were no significant differences in age, proportion of women, BMI, prevalence of diabetes, and Charlson score between the “Pre-Protocol” and “Post-Protocol” groups (56 vs 56 years old, 30 vs 32% women, 28 vs 29 kg/m2, 45 vs 35% with diabetes, and 2 vs 2 median Charlson scores; respectively, all p>0.05). The “Post-Protocol” group had higher proportions of patients with well-controlled glucose (i.e. 70–180 mg/dL) compared to the “Pre-Protocol” group, across all pre-meals and bedtime glucose readings throughout the hospital stay. The differences between the “Post-Protocol” and “Pre-Protocol” groups were statistically significant (p<0.05) for fasting glucose on day 4, 5, and discharge day; pre-lunch glucose on discharge day; pre-dinner glucose on day 3, 5, and discharge day; and bedtime glucose on day 1. In regression analyses adjusted for age, sex, nationality, BMI, Charlson score, and diabetes status, the odds ratios of having well-controlled glucose were significantly higher in the “Post-Protocol” group versus the “Pre-Protocol” group for fasting glucose on day 4, 5, and on discharge; pre-lunch glucose on day 5 and on discharge day; pre-dinner glucose on day 3 and 5; and bedtime glucose on day 1.

Conclusion: The implementation of a simplified protocol for the management of dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19 results in more patients achieving well-controlled glucose levels that have been previously associated with lower mortality of COVID-19.
Complications and Outcomes in Patients With Diabetic Ketoacidosis and COVID19
Authors: Hwang Patricia , Vellanki Priyathama , Galindo Rodolfo Javier , Brechtelsbauer Erika , Van Prooyen Amanda , Ashraf Shanza
Published: May 2021

Introduction: COVID-19 infection caused by the novel coronavirus SARS-CoV-2 has been associated with new-onset diabetes and diabetic ketoacidosis. There are currently limited reports observing the effect of COVID-19 infection on outcomes in patients hospitalized with diabetic ketoacidosis (DKA). Methods: This retrospective study used electronic medical records, between March 1, 2020 to September 14, 2020, and included patients aged ≥ 18 years with DKA. Clinical characteristics, hospital course, and complications (ICD-10 codes) were compared between patients admitted with DKA and confirmed COVID-19 infection (COVID+) to those with DKA without COVID-19 infection (COVID-). The American Diabetes Association criteria was used to define DKA. Results: Among 757 patients with DKA, 80 COVID+ patients with and 677 COVID- patients were included (mean age 49.1 years, female 52.7%, African-American 70.4%). Baseline characteristics were similar between groups. The COVID+ group had a lower admission glucose (mean glucose 413.1 ± 218.7 mg/dL vs 441.1 ± 222.6 mg/dL, p-value 0.05), and higher serum bicarbonate levels (18.2 mmol/L vs 16.6 mmol/L, p-value <0.05) compared to the COVID- group. Compared to the COVID- group, COVID+ required a longer time to achieve blood glucose < 250 mg/dl from admission (8.8 hours vs 7.1 hours, p-value <0.01), and had higher rates of acute respiratory failure (48.8% vs 9.5%, p-value <0.001), mechanical ventilation (32.5% vs 10.9%, p-value <0.001), sepsis (37.5% vs 15.7%, p-value <0.001), acute thrombotic events (11.3% vs 2.7%, p-value <0.05), and pneumonia (70% vs 10.3%, p-value <0.001). COVID+ had higher mortality (16.3% vs 3.1%, p-value < 0.001), ICU length of stay (median 5.5 days or 2–58 days vs median 2 days or 2–123 days, p-value <0.001), and total LOS (median 7.5 or 1–47 days vs median 5 days or 1–98 days, p-value <0.001). Both groups required similar total insulin doses throughout the entire hospitalization (mean 143 +/- (SD) vs 142 +/- SD units, p-value 0.088). Conclusion: Our data shows that COVID-19 infection is associated with increased mortality, worse clinical outcomes, and longer LOS among patients hospitalized with DKA, while presenting with less severe hyperglycemia and acidemia compared to those without COVID-19 infection.
Endocrine Elective Primer for Medical Students
Authors: Bassin Sandhya , Lubitz Sara E
Published: May 2021

Background: Endocrine modules available online have shown improvement in student learning and increased student satisfaction with self-guided learning (Kirk, 2016). However, most available modules are geared towards preclinical medical students rather than clinical students. Therefore, we developed an endocrine primer, defined as a set of introductory preparatory material, in the form of a PowerPoint. The primer reviews commonly seen endocrine disorders in adults, including their presentation, diagnosis, and management, in order to offer students access to self-paced learning and help bridge the gap between the basic science curriculum and clinical experience.

Methods: Third and fourth year medical students enrolled in the endocrine elective from Feb 2020-Oct 2020 completed a 15 question pre-and post-knowledge assessment, as well as an endocrine primer satisfaction survey. The knowledge assessments evaluated students’ knowledge of topics surrounding type 1 and 2 diabetes, hyper- and hypothyroidism, thyroid nodules, adrenal and pituitary disease, hyperparathyroidism, and osteoporosis. The pre-knowledge assessment was completed prior to starting the endocrine elective and viewing the endocrine primer. The post-knowledge assessment was completed at the end of the two or four week endocrine elective.

Results: A paired-T test was used to compare the pre- and post-knowledge survey results. A total of 7 third- and fourth-year medical students completed the knowledge assessment and satisfaction survey. Knowledge results showed a nonsignificant mean improvement of 1.4 points, p=0.09, from the start of the elective to completion, with a decreased variability between student scores. Student satisfaction was high, with 100% of students who completed the primer agreeing it made them more prepared for the endocrine elective and all students recommending other electives create similar primers as well.

Conclusion: The endocrine primer standardized students’ endocrinology knowledge and enhanced satisfaction with the endocrinology elective. This self-paced learning opportunity was well received by medical students and should be included in other clinical electives. This pilot study will be expanded to a larger sample size and incorporate internal medicine residents on the endocrinology elective. We also plan to review faculty satisfaction before and after the primer was initiated.
Endocrinology in the Time of Coronavirus: A Virtual Endocrinology Elective for Medical Students
Authors: Moxley Meaghan C , Lamos Elizabeth , Malek Rana
Published: May 2021

Introduction: During the COVID-19 pandemic, the Association of American Medical Colleges recommended that medical students halt in-person learning. Our institution created a competency based virtual endocrinology elective to provide continued clinical experience with a focus on type 2 diabetes (T2DM) and health equity in diabetes care.

Methods: A 4-week virtual endocrinology elective alternated between different mini-rotations to maximize exposure to inpatient and outpatient endocrine care, as well as self-directed and faculty/fellow directed educational experiences. Post-elective surveys assessed student satisfaction with elective components and change in comfort levels with T2DM management and social determinants of health (SDH) on diabetes care.

Results: Overall, 87% (n=13) of students were “extremely satisfied” with the elective. Increased comfort was seen with management of type 2 DM and the impact of SDH on DM care (DM 88% neutral/uncomfortable to 94% comfortable, SDH 50% neutral/uncomfortable to 94% comfortable). Students were satisfied with the quality of patient care and requested opportunities for more direct involvement.

Conclusions: This virtual endocrine elective shows that curricula can be creatively designed to educate students in endocrinology, assess students across core competencies, and demonstrate impacts of telehealth and social determinants of health on endocrine and patient care.
Glycaemic Control in Children and Adolescents With Type 1 Diabetes Following a Single Telehealth Visit:What Have We Learned From the COVID-19 Lockdown?
Authors: Rachmiel Marianna , Lebenthal Yael , Mazor-Aronovitch Kineret , Brener Avivit , Levek Noah , Levran Neria , Chorna Efrat , Dekel Michal , Barash Galia , Landau Zohar , Pinhas-Hamiel Orit
Published: May 2021

Aims: Children with chronic diseases were unable to receive their usual care during COVID-19 lockdown. We assessed the feasibility and impact of telehealth visits on the time-in-range (TIR) of pediatric individuals with type 1 diabetes (T1D). Methods: An observational multicenter real-life study. Patients scheduled for an in-clinic visit during the lockdown were offered to participate in a telehealth visit. Sociodemographic, clinical, continuous glucose monitor and pump data were recorded 2 weeks prior and 2 weeks after telehealth visit. The primary endpoint was change in relative-TIR, i.e change in TIR divided by the percent of possible change (∆TIR/(100-TIRbefore)*100). Results: The study group comprised 195 individuals with T1D (47.7% males), mean±SD age 14.6±5.3 years, diabetes duration 6.0±4.6 years. Telehealth was accomplished with 121 patients and their parents (62.0%); 74 (38.0%) did not transfer complete data. Mean TIR was significantly higher for the two-week period after the telehealth visit than for the two-week period prior the visit (62.9±16.0, p<0.001 vs. 59.0±17.2); the improvement in relative-TIR was 5.7±26.1%. Initial higher mean glucose level, lower TIR, less time spent at <54 mg/dl range, longer time spent at 180–250 mg/dl range, higher daily insulin dose and single parent household were associated with improved relative-TIR. Multiple regression logistic analysis demonstrated only initial lower TIR and single-parent household were significant, odds ratio: -0.506, (95%CI -0.99,-0.023), p=0.04 and 13.82, (95%CI 0.621, 27.016), p=0.04, respectively.

Conclusions: Pediatric patients with T1D benefited from a telehealth visit during COVID-19. This modality and its benefit should be employed, and used in the future as well. However, this modality is not yet suitable for a considerable proportion of patients.
High Prevalence of Diabetes in Hospitalized Patients With COVID-19 and Its Association With Greater Severity of COVID-19 in Delhi, India
Authors: Mithal Ambrish , Jevalikar Ganesh , Sharma Rutuja , Singh Anshu , Farooqui Khalid J , Dewan Arun , Budhiraja Sandeep
Published: May 2021

Abstract: India is home to 77 million people with diabetes and has a large number of COVID 19 cases, albeit with a low fatality (<1.5%). Little Indian data is available about the prevalence of diabetes in COVID 19 and its impact on outcomes. This observational prospective study (approved by the Institutional Ethics Committee) was carried out in a designated COVID facility, largely catering to middle and upper socioeconomic classes. A total of 401 (125 F, mean age 54 y, range 19–92 y) consecutive adults hospitalized with COVID-19 infection as proven by positive nasal swab for SARS-CoV2 by RT-PCR were included. Diabetes mellitus was diagnosed either by known history or HbA1c≥6.5%. Severity was assessed using the WHO ordinal scale1. Clinical outcomes and markers of inflammation were compared between diabetes and non-diabetes groups. Out of 401 patients, 210 (52.4%) had either diabetes (189,47.1%) or hyperglycemia requiring insulin treatment (21, 5.2%). 152 (37.9%) reported known diabetes, and 37 (9.2%) had preexisting but undiagnosed diabetes (HbA1c≥ 6.5%). People with diabetes were significantly older (mean age 59.9 vs 47.7 y), and had a higher proportion of men (74.6 vs 63.7 %), hypertension (58.7 vs 25%), CAD (13.8 vs 4.2%), and CKD (5.3 vs 0.9%) and a higher mean baseline severity score (3.4±0.7 vs. 3.2±0.5, p-0.000). The diabetes group had a higher number of severe cases (WHO scale≥5) (20.1% vs 9%, p-0.002) and higher mortality (6.3 vs 1.4%, p-0.015). A higher proportion of the diabetes group required ICU admissions (24.3 vs 12.3%, p-0.002), glucocorticoid therapy (78.3 vs 54.2%, p-0.000), oxygen administration (53.4 vs 28.3%, p-0.000), inotropic support (7.4 vs 2.4%, p-0.019), and renal replacement therapy (3.7% vs 0,p-0.005). The mean duration of hospital stay was higher for the diabetes group (10.4 vs 9.1 days, p-0.016). Of those who died, 12/15 (80%) had diabetes. Baseline Hba1c (n=331) showed a significant correlation with outcome severity scores (r 0.136, p-0.013). Markers of inflammatory response, CRP (41.0±4.4 vs. 19.4±3.8, p-0.000), ferritin (404.8±41.6 vs. 258.8±40.2, p-0.012), IL6 (65.5±11.6 vs. 26.9±4.4, p-0.002), LDH (321.8±10.1 vs. 286.8±8.4, p-0.008) were significantly higher in the diabetes group. Procalcitonin and D Dimer did not differ significantly. In conclusion, we report the highest prevalence of diabetes in a hospitalized COVID-19 population so far. The diabetes group had more severe disease and greater mortality. Baseline HbA1c correlated with poor outcomes. The comorbidities could have contributed to these poorer outcomes in the diabetes group. Strategies to improve outcomes in this pandemic it is imperative to include screening for and better control of diabetes.

Reference: 1 https://www.who.int/blueprint/priority-diseases/key-action/COVID-19_Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf
Impact of COVID 19 National Lockdown on Glycaemic Control in Children and Adolescents With Type 1 Diabetes (T1DM): A Retrospective Review at a Large UK Teaching Hospital
Authors: Lawrence Neil Richard , Natarajan Anuja , Petkar Razia , Joseph Lovlin
Published: May 2021

Introduction: The coronavirus disease global pandemic led to national lockdown in the United Kingdom on 23rd March 2020. We compared the glycaemic control of children and adolescents with Type 1 diabetes (T1DM) at Doncaster & Bassetlaw Teaching Hospitals in the 12 weeks prior to the lockdown, to the 12 weeks following lockdown. Methods: HbA1c result 3 months following lockdown was compared to the last HbA1C prior to lockdown. Data from Continuous Glucose Monitors (CGMs), Flash Glucose Systems (FGS) and those performing Self-Monitoring of Blood Glucose (SMBG) were compared alongside changes to patient contact that occurred. Results: In 264 patients under 20 years of age across both hospitals in the Trust, face-to-face consultations decreased (245 vs 151, 39%), and remote consultations increased (1751 vs 2269, 30%) (χ 2 p<0.001). Excluding those within a year of diagnosis, 122 had paired HbA1c results, and 80 had more than 70% of glucose monitoring data available. HbA1c levels decreased (67.4 mmol/mol vs 61.3 mmol/mol, p<0.001) and glucose monitoring data showed lower mean glucose after lockdown (9.7mmol/L vs 9.5mmol/L, p=0.034) with lower standard deviation (4.4mmol/L vs 4.2mmol/L, p<0.001). Proportion of time in range (3.9mmol/L to 10mmol/L) increased (n=47, 55.2% vs 58.0%, p=0.017), with no change to time below range (4.8% vs 5.0%, p=0.495). Conclusion: Glycaemic control improved in the 12 weeks following national lockdown. This demonstrates the difficulties faced by patients and carers managing T1DM around school pressures, meals away from home, social life and peer pressure. Increased remote contact with patients with T1DM has not been detrimental to glycaemic control.
In-Hospital Glycemic Dysregulation Associated With Worse Outcomes in COVID-19
Authors: Rodriguez Lisette Patricia , Farhangi Vida , Braham Julaine , Smith Robert A , Wiese-Rometsch Wilhelmine
Published: May 2021

Introduction: Evidence establishes that COVID-19 patients with DM2 are at increased risk for severe disease and worse outcomes. Peer reviewed data is sparse comparing glycemic control and clinical outcomes among COVID-19 patients with vs. without DM2, and thus we sought to address this gap. Methods: We selected patients at least 18 years old who expired or were discharged between March 16, 2020 through September 15, 2020. Principal analysis compared glycemic patterns among patients with DM2 vs. non-DM2. Median, coefficient of variation (CV), maximum and minimum glucose parameters were computed to characterize longitudinal glycemic patterns. Logistic regression modeling identified significant (p<.05) associations between composite outcome vs. glycemic parameters and putative risks for progression to severe COVID-19. Receiver operating characteristic (ROC) curve identified cut points for glycemic parameters. Cox regression models were employed to control for significant confounders. Continuous data summarized as median was compared using Kruskal-Wallis test. Discrete data were compared with Pearson’s chi-square test. Two-tailed p<.05 was significant. Results: Among 494 patients, 157 (32%) had DM2 with no intergroup differences in age (68 [56–79]), sex (52% male, 48% female), or race (68% Caucasian, 19% Other, 13% African American). Insulin was administered to DM2 (93%) and non-DM2 (54%) patients (p<.0001). Comorbidities were more prevalent in DM2, including cardiovascular (68% vs. 54%, p=.003), renal (72% vs. 52%, p<.0001) and obesity (51% vs. 38%, p<.0001). Markers including D-dimer (0.98 [0.61–1.95] mg/L), lactate dehydrogenase (308 [230–392] U/L), ferritin (436 [174–856] ng/mL), and triglycerides (172 [109–239] mg/dL), were not different in DM2 vs. non-DM2 (p>.05). CRP was greater in patients with (8.6 [3.6–14.6]) vs. without (6.1 [2.0–12.6]) DM2 (p=.005). Baseline glucose in DM2 (163 [121–253] mg/dL) vs. non-DM2 (107 [96–124] mg/dL) was significantly greater, with former an independent predictor of composite outcome (p=.0005). Cox modeling of other glucose parameters in DM2 vs. non-DM2 demonstrated various impact regarding risk for composite outcome including median (155 [128–209], p=.46) vs. (103 [94–118], p=.09); coefficient of variation (28 [19–38], p=.08) vs. (15 [9–20], p=.002); maximum (252 [187–362], p=.0005) vs. (129 [110–156], p=.002); and minimum (99 [79–128], p=.95) vs. (89 [81–98], p=.02). The unified baseline glucose cut point for composite outcome risk controlled for significant covariates was 138 gm/dL (p<.0001), which included respectively 20% and 10% of patients with and without DM2. Conclusion: Glycemic dysregulation in COVID-19 patients is independently associated with ICU admission and/or hospital mortality. Presence of DM2 amplifies glycemic dysregulation, but risk stratification appears warranted in all COVID-19 patients.
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

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 >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<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

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 (>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

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

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 <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

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 <1.6 pmol/L (<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

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

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 < 12) and elevated HbA1c (7.9%; n < 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 (<5 [IU]/mL; n 0–5 [IU]/mL) and IA-2 (<5.4 U/mL; n <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

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 >=80 mg/dl, Protein 30 mg/dl, urine glucose >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.