bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Perfect Storm: Rapid Progression of Diabetic Ketoacidosis in Pediatric Diabetes in the Setting of COVID-19
Authors: Modarelli Rachel , Hendrix Grace , DeRusso Michelle , Ozment Caroline , Balikcioglu Pinar Gumus 
Published: May 2021

Abstract
Introduction: The COVID-19 pandemic has introduced countless challenges to the medical field and has brought increased attention to pediatric patients with pre-existing diagnoses such as diabetes. While pediatric patients have lower rates of COVID-19 mortality, the presence of pre-existing conditions can heighten the severity of their clinical presentation. Here we discuss how COVID-19 may contribute to the pathophysiology of DKA.
Case Presentation: Our patient is a 6-year old female with known type 1 diabetes for 6 months, with positive GAD 0.25 nmol/L, c-peptide 0.3 ng/ml, blood glucose 555 mg/dl, HbA1c 10.9, beta hydroxybutyrate (βOHB) 3.21mmol/l, pH 7.35, HCO3 21 mEq/L at her initial presentation, and insulin requirement &lt;0.5 IU/kg/day (in honeymoon). She presented to an outside hospital due to acute onset of abnormal breathing and altered mental status. The day prior, she had one episode of emesis, diarrhea, and abdominal pain, but no fever. She was reported to be agonal breathing with a GCS of 8 and unresponsive to physical or verbal stimuli. She was intubated shortly after arrival and given mannitol. Initial labs included a glucose 486 mg/dL, pH 6.88, bicarbonate 4 mEq/L, lactate 5.8 mmol/L, βOHB 11.9 mmol/L, and anion gap 29 mEq/L, all consistent with severe DKA. With a known family member with COVID-19, she was tested and found to be COVID-19 positive. She was transferred via flight to a higher level of care. Remarkably, she was appropriate for extubation the following day with return to her baseline mental status with improved acidosis. On day three of hospitalization, she developed further COVID-19 symptoms which included sore throat, productive cough, fatigue, headache, and high fever. These symptoms persisted four more days until she was afebrile and discharged home in good condition.
Conclusion: Our patient’s rapid progression and severity of illness, including the need for intubation, requires the discussion of how COVID-19 might affect diabetes and suggests opportunities for improvement in clinical practice in children with preexisting diabetes. 1) COVID-19 might change the underlying pathophysiology and cause severe metabolic complications. Possible mechanisms might include a) binding to angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in key metabolic organs and tissues, including pancreatic beta cells, leading to insulin resistance and islet cell destruction b) enabling a proinflammatory “cytokine storm” in the setting of higher basal proinflammatory state from diabetes. Additionally, ketoacidosis and altered mental status have been discovered in patients with COVID-19 without diabetes, which could potentiate the symptoms of DKA. 2) Prompt recognition and treatment of DKA is warranted as caregivers may attribute the symptoms to COVID-19 rather than DKA and recognition could be too late if symptoms are as acute as described in this case report.
Climate Changes’ Effect on Blood Pressure in Diabetic Patients
Authors: Madrigal-Campos David Alberto 
Published: May 2021

Abstract
There has been noted a correlation between atmospheric temperature and some chemical, hematological and homeostatic variables on blood presure. Blood pressures’ variation was determined in diabetic patients with no high blood pressure issues living in a region with hot summers of 90–100º F (BP Hot) and cold winters with snow (BP cold). Chihuahua city has such weather conditions. 221 patients were included, 44 were women (20%) and 177 men (80%). The timeline was from May 2016 to January 2019 were all the cardiovascular events were noted. Group I had 89 patients (40.2%), having Diabetes Mellitus for more than 20 years. Average age of the group is 70 years old (60 - 84 years old). The increase in systolic blood pressure (BP) was of 27.5 mmHg (15–30 mmHg) and of the diastolic BP of 10 mmHg. As extra data it was noted that pulse increased 10 beats per minute (bpm). As a clinical presentation, 35 patients (39.3%) patients were found to be in NYHA class I, 27 (30.3%) in class II, and 27 (30.3%) in class III. Dyslipidemia was present in 70 (78.6%) of them, hypertensive cardiomyopathy (per ECG or Echocardiogram) in 37 (41.5%). From this group, 27 (30.3%) were admitted in the ER for uncontrolled blood presure with no symptoms, 45 (50.5%) admitted for high BP with symptoms (headaches, dizzines, epistaxis or conjuctival hemorrhage), 9 (10.1%) were admitted due to heart insuficiency and 4 (4.4%) sudden cardiac death. Group II included 132 patients (59.8%) with less than 20 years with DM and an average age of 64 years old (53–71 years of age). The increase in systolic BP was of 8.5 mmHg (less than 10 mmHg) and diastolic BP of 5.8 mmHg. Heart rate varied by 3.3 bpm (less than 5). Clinical presentacion of NYHA class I were 89 (67.4%) patients, 30 (22.7%) in class II, and 13 (9.8%) in class III. 92 (69.6%) patients presented dyslipidemia, and 30 (22.7%) hypertensive cardiomyopathy. Out of this group, 30 (22.7%) patients were admitted due to high BP without symptoms and 17 (12.8%) were admitted with high BP and symptoms. It is concluded that patients that have been diabetic for a longer time, with greater cardiovascular problems and older in age have a diminished reaction to the body’s control mechanisms and react more to the cold weather.
Evaluation of Small Fiber Peripheral Neuropathy With Infrared Thermographic Camera in Prediabetes
Authors: Vasconcellos Larissa Frazao , Mágero Felipe Rodrigues Lima , de Farias Maria Elba Bandeira , Bandeira Francisco Farias 
Published: May 2021

Abstract
Introduction: The typical microvascular complications of diabetes may ocasionaly occur in patients with prediabetes (PD). Diabetic peripheral neuropathy (DPN) is associated with poor glycemic control as well as with the metabolic syndrome components independently of HbA1c levels. Small fiber DPN is one of the most chalenging diagnosis due to the usualy normal physical examination as well as electrophysiological nerve evaluation. The thermographic camera has emerged as a novel tool for the detection of small nerve fiber dysfunction. The aim of the present study was to evaluate thermography of the plantar foot in individuals with PD. Methods: This was a cross-sectional study with a sample of 51 patients aged 27 to 71 years. Patients were divided into the following three groups: control (n = 18), diabetic (n = 17), and prediabetic (n = 16). The diagnosis of PD was made according to ADA standards. Thermographic analysis of the plantar region was performed using a FLIR C2 camera. Results: Overall, 510 foot regions were analyzed. There were significant diferences in plantar temperatures between prediabetes vs controls as follows: hallux (L: 25.24 ± 2.02 vs 23.6 ± 1.79 ºC; p=0.009/ R: 25.44 ± 2.05 vs 23.89 ± 1.73 ºC; p=0.01); fifth metatarsal (L: 26.31 ± 1.72 vs 24.88 ± 1.38 °C; p=0.006 /R: 26.12 ± 1.60 vs 24.74 ± 1.41 °C; p= 0.006); and calcaneus (L: 26.46 ± 1.71 vs 24.93 ± 1.41 °C; p=0.005 / R: 26.58 ± 1.85 vs 25.07 ± 1.18 °C; p=0.004). There were no similar results for temperatures in individuals with diabetes comparing with prediabetes: hallux (L:25.24 ± 2.02 vs 25.76 ± 2.30 °C; p=0.24 /R: 25.44 ± 2.05 vs 25.64 ± 1.92 °C; p=0.38); fifth metatarsal (L: 26.31 ± 1.72 vs 26.03 ± 1.27 °C; p=0.3 / R: 26.12 ± 1.60 vs 26.21 ± 1.57 °C; p=0.43); and calcaneus (L26.46 ± 1.71 vs 26.82 ± 1.41 °C; p=0.23 / R: 26.58 ± 1.85 vs 26.99 ± 1.42 °C; p=0.24). Conclusion: We found siginificant abnormalities in temperature of various sites of the plantar region in PD feets suggesting that small fiber damage may occur before the onset of type 2 diabetes.
Evaluation of the Prognostic Significance of Adipose Tissue Hormones in the Development of Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus
Authors: Kyryliuk Mykhailo L , Mogilevskyy Sergiy Yu , Serdiuk Valeriy M 
Published: May 2021

Abstract
Relevance: There are evidences of the participation of adipose tissue hormones (ATH) in the development of diabetic microangiopathy and retinal neovascularization. The disign of methods for the mathematical evaluation of the prognosis of the development of diabetic retinopathy (DR) with the participation of ATH is an actual problem in modern diabetology. Goal: Elaboration of a mathematical model for assessing the prognostic significance of ATH to study the likelihood of developing and progressing DR in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: An open observational single-center one-stage selective study was conducted. The study was approved by the Local Ethics Committee. 59 patients (187 eyes) with T2DM and DR (men and women; mean age - 58.20±0.18 years; mean T2DM duration - 9.19±0.46 years; mean HbA1C - 9.10±0.17 %), were assigned to 3 groups, based on the stage of DR (according to fundus instrumental examination), and underwent the study. The diagnostic predictive value was assessed by discriminant analysis. Models with linear combinations of the serum leptin, adiponectin and resistin, triglyceride (TG), also HbA1C, type of antidiabetic therapy (ADT) were developed, and, subsequently, formulas for classification-relevant discriminant functions were derived. ADT included metformin, either alone (type 1 ADT), or in combination with oral anti-hyperglycemic medication (type 2 ADT) or insulin therapy (type 3 ADT). The classification functions (CF) computed based on the variables found from the above developed models provided the basis for predicting the development of DR. Results: The formulas for CF from model are as follows: CF1 = 0.29 * TG + 1.55 * HbA1 + 1.81 * ADT_Type + 0.04 * Leptin + 0,34* Adiponectin + 0,91* Resistin – 13,82; CF2 = 0.05*TG + 1.36 * HbA1 + 3.01 * ADT_Type + 0.08 * Leptin + 0,35* Adiponectin + 1,01 * Resistin – 15.95. A step-by-step approach to diagnostic decision making should be used. First, blood samples are tested for serum leptin, adiponectin and resistin, TG, blood HbA1, and the patient is assigned a code for ADT_Type (1, 2 or 3). Second, CF1 and CF2 values are calculated. Finally, the two values are compared to determine which is greater. The predictive decision is made by selecting the classification function with the greater value. Thus, if CF1&gt;CF2, the process can be stabilized at this stage given an adequate glycemic control (through compensation of carbohydrate metabolism) and body-mass control as well as patient compliance. If CF1&lt;CF2, the pathological process may progress to the next stage or even within stage 3, and there is an urgent need to reduce BMI, and to correct the ADT and the blood lipid profile. Conclusion: Informativeness and statistical significance of model is 71.4 % and p=0.040, respectively.
Extracellular Vesicle Influence on Wound Healing
Authors: Visentin Erica C , Pogue Robert E , Rosa Thiago , Marra Brenda 
Published: May 2021

Abstract
Diabetes is a highly prevalent disease in the world and it is involved in several chronic complications, such retinopathy, nephropathy, neuropathy, cardiovascular disease and the diabetic foot. Up to 28% of diabetic foot ulcers result in some form of amputation that lead to reduced productive activity and quality of life, as well as increased social costs. Advance in the understanding of the healing process changes in diabetic individuals is fundamental to improve diabetic foot care. Extracellular vesicles are intercellular communication agents that influence physiological and pathological processes. The objective of this research was to examine the influence of extracellular vesicles collected of diabetic individuals on cell proliferation, viability and migration in wounds. The procedures included in vitro assay of migration, senescence, cellular viability and oxide nitric production. Extracellular vesicles have been shown to stimulate the cell migration process and this function was not poorly influenced by metabolic control. References: 1. International Diabetes Federation. Diabetes Atlas, 2019. www.diabetesatlas.org. 2. Than UTT, Guanzon D, Leavesley D, Parker T. Association of Extracellular Membrane Vesicles with Cutaneous Wound Healing. Int J Mol Sci. 2017;18(5):956. 3. Van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–228.
4. Lampugnani MG. Cell migration into a wounded area in vitro. Methods Mol Biol. 1999;96:177–182.5. Sociedade Brasileira de Diabetes. Diretrizes da Sociedade de Diabetes 2017–2018. ISBN: 978-85-93746-02-4. São Paulo: Editora Clannad, 2017.6. Sociedade Brasileira de Cardiologia. Atualização da Diretrizes da Sociedade de Dislipidemia e Prevenção da Aterosclerose - 2017. ISBN: 0066-783X, vol 109, nº2, supl 1, agosto, 2017.7. Leroyer AS, Tedgui A, Boulanger CM. Microparticles and type 2 diabetes. Diabetes Metab. 2008;34 Suppl 1:S27-S32.8. International Society for Extracellular Vesicles. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. Journal of Extracellular Vesicles, 7:1, 2018.9. Deng F, Wang S, Zhang L. Endothelial Microparticles Act as Novel Diagnostic and Therapeutic Biomarkers of Diabetes and Its Complications: A Literature Review. Biomed Res Int. 2016;2016:9802026.
Mild Cognitive Impairment Screening in Older Adults With Type 2 DM
Authors: Pirela Daniela Victoria , Cevallos Victor , Ruiz Jorge G 
Published: May 2021

Abstract
Introduction: Older adults (O-A), more than 65 years old, are a heterogeneous group of patients in terms of functionality, social support and health status that implies a wide range of co-morbidities including mild cognitive impairment (MCI) and unidentified dementia. De-intensification of treatment is recommended for O-A with T2DM, tight glycemic control and high risk of hypoglycemia. Assessment of all geriatric domains (medical, functional, social and psychological including screening for MCI) is encouraged to support a complete clinical picture that leads to appropriate targets and adequate therapeutic approach. The literature suggests that de-intensification of treatment in this population is uncommon, which calls for the development of new strategies to prevent potential harm, however we also question if previously established tools are being used. Methods: We performed a retrospective chart review of a community-dwelling Veterans with at least two office visits in the Geriatric Clinic between January 1st 2018 to December 31st 2019. 210 patients with 65 years of age or older with T2DM and A1C &lt; 7.5 were found. 64 (30%) of the patients where on hypoglycemic medication including sulfonylureas or insulin. From this subgroup, only 9 (14%) patients where recommended to de-intensify therapy. 189 (90%) of all the patients were screened for memory disorders. Interestingly 20 patients (31%) of those using sulfonylureas or insulin as part of their diabetes treatment were not screened, which was a higher percentage compared to 48 (25%) patients not on hypoglycemic medications also not screened for memory disorders. Conclusion: similar to previous studies de-intensification is uncommon not only among endocrinologist but in other sub-specialties involved in the care of the Geriatric population. This data emphasizes the importance of using previously developed treatment tools specially in those with at higher risk of overtreatment side effects such as older adults with tight glycemic control and hypoglycemic medication
Screening for Diabetic Retinopathy in Endocrinology Clinics by Using Handheld Cameras and Applying Artificial Intelligence Algorithms
Authors: Dvey-Aharon Zack , Huhtinen Petri 
Published: May 2021

Abstract
According to estimations of the World Health Organization (WHO), there are almost 500M people in the world that suffer from diabetes. Projections suggest this number will surpass 700M by 2045 with global prevalence surpassing 7%. This huge population, alongside people with pre-diabetics, is prone to develop diabetic retinopathy, the leading cause of vision loss in the working age. While early screening can help prevent most cases of vision loss caused by diabetic retinopathy, the vast majority of patients are not being screened periodically as the guidelines instruct. The challenge is to find a reliable and convenient method to screen patients so that efficacy in detection of referral diabetic retinopathy is sufficient while integration with the flow of care is smooth, easy, simple, and cost-efficient. In this research, we described a screening process for more-than-mild retinopathy through the application of artificial intelligence (AI) algorithms on images obtained by a portable, handheld fundus camera.
156 patients were screened for mtmDR indication. Four images were taken per patient, two macula centered and two optic disc centered. The 624 images were taken using the Optomed Aurora fundus camera and were uploaded using Optomed Direct-Upload. Fully blinded and independently, a certified, experienced ophthalmologist (contracted by Optomed and based in Finland) reviewed each patient to determine ground truth. Indications that are different than mtmDR were also documented by the ophthalmologist to meet exclusion criteria. Data was obtained from anonymized images uploaded to the cloud-based AEYE-DS system and analysis results from the AI algorithm were promptly returned to the users.
Of the 156 patients, a certified ophthalmologist determined 100% reached sufficient quality of images for grading, and 36 had existing retinal diseases that fall under exclusion criteria, thus, 77% of the participants met the participation criteria. Of the remaining 120 patients, the AEYE-DS system determined that 2 patients had at least one insufficient quality image. AEYE-DS provided readings for each of the 118 remaining patients (98.3% of all patients). These were statistically compared to the output of the ground truth arm. The patient ground truth was defined as the most severe diagnosis from the four patient images; the ophthalmologist diagnosed 54 patients as mtmDR+ (45% prevalence). Of the 54 patients with referable DR, 50 were diagnosed and of the 64 mtmDR- patients, 61 were correctly diagnosed by the AI. In summary, the results of the study in terms of sensitivity and specificity were 92.6% and 95.3%, respectively.
The results indicated accurate classification of diabetic patients that required referral to the ophthalmologist and those who did not. The results also demonstrated the potential of efficient screening and easy workflow integration into points of care such as endocrinology clinics.
Efficient Restoration of Beta Cell Dedifferentiation by Calorie Restriction With High Fat/Low Carbohydrate Diet in Obese Diabetes Model and the Possible Role of GLP-1
Authors: Ishida Emi , Lei Xiao , Horiguchi Kazuhiko , Matsumoto Shunichi , Yoshino Satoshi , Nakajima Yasuyo , Yamada Eijiro , Yamada Masanobu 
Published: May 2021

Abstract
In type 2 diabetes, pancreatic beta cells are gradually ‘exhausted’ and fall into beta cell dysfunction, which proceeds more severe insulin dependence. Among the proposed mechanisms of beta cell dysfunction such as endoplasmic reticulum stress and oxidative stress, the beta cell heterogeneity has attracted the researcher’s interest recently. In 2012, Talchai et al. revealed that the beta cells were dedifferentiated in diabetic mice model, and nowadays it is considered as one form of the beta cell heterogeneity and is observed broadly among diabetic animal models and human patients. Previously we showed that food restriction had the best effect to restore beta cell gene expression in obese diabetic model mice, among the known diabetic treatments which we tested. In the current study, we aimed to unveil the molecular basis in the improvement of beta cell dedifferentiation during the calorie restriction. First, we utilized the high-fat/low carbohydrate diet (HF) or low-fat/high carbohydrate (HC) diet, to determine whether fat restriction or sugar restriction reduces the beta cell dedifferentiation in obese mice. When calorie intake was restricted evenly, both HF diet and HC diet decreased the body weight and hyperglycemia in db/db mice equally. Albeit the same metabolic profile, db/db group fed with HC diet had more enlarged islets and more dedifferentiated beta cell features than db/dbs fed with HF diet, which indicated the compensatory beta cell response in HC diet group. Moreover, HC diet group showed more severe fatty liver than HF diet group, along with the elevated synthesis and accumulation of triglycerides and cholesterol in liver. It is speculated that the insulin resistance in liver might impact on the beta cell dedifferentiation. Next, we analyzed the effect of glucagon-like peptide 1 (GLP-1) on beta cell dedifferentiation, since GLP-1 is secreted more from intestine by protein and fat intake, rather than by sugar intake. Also, increasing number of reports have suggested the improving effect of GLP-1 on beta cell dysfunction and fatty liver. Indeed, GLP-1 administration altered the reduced beta cell/alpha cell ratio in db/db mice, which indicated the restoration of beta cell heterogeneity. We are now investigating if GLP-1 administration reimburse the beta cell dedifferentiation in db/db mice fed with HC diet, to illuminate the role of incretins in beta cell dedifferentiation induced by unbalanced nutrition during diet. Also, we will present the RNA sequencing data of the liver in db/db mice fed with HF and HC diet, to elucidate the key molecules and genes which connect the beta cell function and metabolic state in liver.
Insertion of a Synthetic Switch Into Insulin Provides Metabolite-Dependent Regulation of Hormone-Receptor Activation
Authors: Chen Yen-Shan , Gleaton Jeremy , Yang Yanwu , Dhayalan Balamurugan , Phillips Nelson B , Liu Yule , Broadwater Laurie , Jarosinski Mark , Chatterjee Deepak , Lawrence Michael C , Hattier Thomas , Michael Dodson M , Weiss Michael Aaron 
Published: May 2021

Abstract
Insulin signaling requires conformational change: whereas the free hormone and its receptor each adopt autoinhibited conformations, their binding leads to large-scale structural reorganization. To test the coupling between insulin’s “opening” and receptor activation, we inserted an artificial ligand-dependent switch into insulin. Ligand binding disrupts an internal tether designed to stabilize the hormone’s native closed and inactive conformation, thereby enabling productive receptor engagement. This scheme exploited a diol sensor (meta-fluoro-phenylboronic acid at GlyA1) and internal diol (3,4-dihydroxybenzoate at LysB28). The sensor recognizes monosaccharides (fructose &gt; glucose). Studies of insulin signaling in human hepatoma-derived cells (HepG2) demonstrated fructose-dependent receptor autophosphorylation leading to appropriate downstream signaling events, including a specific kinase cascade and metabolic gene regulation (gluconeogenesis and lipogenesis). Addition of glucose (an isomeric ligand with negligible sensor affinity) did not activate the receptor. Similarly, metabolite-regulated signaling was not observed in control studies of (i) an unmodified insulin analog or (ii) an analog containing a diol sensor in the absence of internal tethering. Although as expected CD-detected secondary structure was unaffected by ligand binding, heteronuclear NMR studies revealed subtle local and nonlocal monosaccharide-dependent changes in structure. Insertion of a synthetic switch into insulin has thus demonstrated coupling between hinge-opening and holoreceptor signaling. In addition to this basic finding, our results provide proof of principle for a mechanism-based metabolite-responsive insulin. In particular, replacement of the present fructose sensor by an analogous glucose sensor may enable translational development of a “smart” insulin analog designed to mitigate risk of hypoglycemia in the treatment of diabetes mellitus.