bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the Need for Basal-Bolus Insulin in Hospitalized Patients With Hyperglycemia: Is Sliding Scale Sometimes the Answer?
Authors: Jankovic Ivana , Nguyen Minh , Kalesinskas Laurynas , Chen Jonathan H 
Published: May 2021

Abstract
Uncontrolled blood glucose (BG) is associated with increased risk of infection, complications, and mortality in hospitalized patients. American Diabetes Association guidelines currently recommend basal insulin for all hospitalized, non-critically ill patients requiring insulin and state that “use of only a sliding scale insulin regimen in the inpatient hospital setting is strongly discouraged”. In practice, however, sliding scale only is used not infrequently. Here, we challenge the recommendation for universal basal insulin use and leverage machine learning to predict which inpatients would indeed benefit from basal insulin at time of admission.
Querying inpatient electronic health record data for hospitalizations between 2008–2020, we identified a cohort of 16,868 unique patients who achieved a day of “good control”, defined as ≥ 3 BGs that were within 100–180 mg/dL without any values outside that range. Inclusion criteria were adult inpatients receiving subcutaneous insulin with BG of 100-180mg/dL on one calendar day. If patients had more than one “good day”, the first day of their most recent hospitalization was chosen. We excluded patients ordered for insulin pumps, insulin infusion, any insulin type that is rarely used (ordered &lt; 25 times), TPN or PPN, or tube feeds. We also excluded patients with missing weights.
We aimed to predict which patients would require &gt; 6 units of insulin. We chose this threshold clinically, as patients with a total daily dose (TDD) of insulin &lt; 6 units could reasonably be managed on sliding scale insulin alone. Using the threshold of 6 units, we used an ensemble machine learning method, called SuperLearner, to model a binary classification for high vs. low insulin users. Features included in the algorithm were collected prior to prediction time, including weight, height, age, sex, race, insurance status, A1c categories (normal, high, panic high, and missing), creatinine, diet, steroid use in prior 48 hours, admission BG, summary statistics of BG, numerous counts of relevant lab values in quantiles, history of basal insulin use, and counts of major diagnosis code groups. Prior insulin doses were not considered to better simulate admission insulin dosing.
Compared to using only weight in the model, with an area under the receiver operating curve (AUROC) of 0.59, our machine learning algorithm showed excellent predictive ability, with an AUROC of 0.85 (95% CI: 0.84 - 0.87) and area under the precision recall curve (AUPRC) of .65 (95% CI: 0.64 - 0.68) vs 0.29 with the weight-only model. Although it will need to be validated prospectively, our algorithm could be used to emphasize basal-bolus insulin on admission in patients predicted to require more insulin, whereas those predicted to require less could be started on sliding scale insulin or considered for oral anti-hyperglycemics.
Insulin Resistance and Gender Define a Cell Autonomous Supernetworkof Protein Phosphorylation
Authors: Haider Nida , Lebastchi Jasmin , Jayavelu Ashok K , Batista Thiago M , Pan Hui , Dreyfuss Jonathan M , Carcamo-Orive Ivan , Knowles Joshua W , Mann Matthias , Kahn Carl Ronald 
Published: May 2021

Abstract
Many hormones and growth factors, including insulin, act through networks of protein phosphorylation. Insulin resistance is an important factor in the pathophysiology of many metabolic disorders. The aim of this study was to uncover the cell autonomous determinants of insulin action and protein phosphorylation using induced pluripotent stem cell (iPSC)-derived myoblasts (iMyos) in vitro. Here, we show that iMyos from non-diabetic individuals in the highest quintile of insulin resistance show impaired insulin signaling, defective insulin-stimulated glucose uptake and decreased glycogen synthase activity compared to iMyos from the insulin sensitive individuals, indicating these cells mirror in vitro the alterations seen in vivo. Global phosphoproteomic analysis uncovered a large network of proteins whose phosphorylation was altered in association with insulin resistance, most outside the canonical insulin-signaling cascade. More surprisingly, we also observed striking differences in the phosphoproteomic signature of iMyos derived from male versus female subjects, involving multiple pathways regulating diverse cellular functions, including DNA and RNA processing, GTPase signaling, and SUMOylation/ubiquitination. These findings provide new insights into the cell autonomous mechanisms underlying insulin resistance in the non-diabetic population and provide evidence of a major, previously unrecognized, supernetwork of cell signaling differences in males and females that must be considered in understanding the molecular basis of sex-based differences in normal physiology and disease.
Dipeptidyl Peptidase-4 (DPP-4) Inhibitor Therapy in the Management of Latent Autoimmune Diabetes in Adults (LADA): A Systematic Review and Meta Analysis
Authors: Alanes Escueta Luz Margaret , Jasul Gabriel Villaflor , Dampil Oliver Allan Castillo , Laforteza Alexis Roberto Yamane 
Published: May 2021

Abstract
Objective: Latent autoimmune diabetes in adults (LADA) has been shown in recent studies to have heterogeneous pathophysiology and phenotype. Although insulin is considered as the therapeutic choice for these patients, other antidiabetic drugs have been studied in terms of glycemic control and beta cell function preservation. In particular, dipeptidyl peptidase-4 (DPP-4) inhibitors have shown immunomodulatory effects in animal models since it was demonstrated a higher DPP-4 activity in patients with LADA compared to patients with Type 1 and Type 2 diabetes suggesting a possible effect on autoimmunity found in LADA. This study aims to review the outcomes of the included studies and evaluate the efficacy of DPP-4 inhibitors in the treatment of LADA. Methods: We searched Medline, Embase, PubMed and Cochrane Library Databases and ClinicalTrials.gov for studies concerning the use of DPP4 inhibitors in patients with latent autoimmune diabetes in adults (LADA). Results: Preclinical studies demonstrated drug’s immunomodulatory effects in terms of suppression of inflammatory processes and oxidative stress providing endothelial protection leading to improved metabolic control and prevention of vasculopathy. From this meta-analysis, pooled data from 8 randomized controlled trials revealed that the use of DPP-4 inhibitors in LADA patients resulted in an improved glycemic control, decreased insulin requirement and increased beta cell function as assessed by a decrease in GADA titers, increased C peptide levels and HOMA B. Conclusion: Beneficial effects of DPP4 inhibitors are shown by the included studies indicating that they are promising therapeutic agents for patients with LADA. However, caution should still be exercised since there is still much to learn about the disease itself and larger scale prospective randomized trials are needed to assess the efficacy and safety of DPP4 inhibitors for these patients.
Prolonged Honeymoon Period in a Thai Patient With Adult-Onset Type 1 Diabetes Mellitus - Metabolic Flexibility in Autoimmune Diabetes?
Authors: Thewjitcharoen Yotsapon , Wanothayaroj Ekgaluck , Chatchomchuan Waralee , Jaita Haruethai , Nakasatien Soontaree , Butadej Siriwan , Krittiyawong Sirinate , Himathongkam Thep 
Published: May 2021

Abstract
Background: ‘Honeymoon’ period among people with type 1 diabetes mellitus (T1DM) refers to the period of time (mostly less than 1 year) which beta-cell is still able to produce insulin to maintain good glycemic control shortly following the development of diabetes. This phenomenon remained incompletely understood but previous studies showed that absence of diabetic ketoacidosis (DKA) at initial presentation, short duration of symptoms, older age at presentation, and strenuous exercise could be potential factors. Herein, we report a 24-year old Thai patient with T1DM who has been in sustained complete remission for more than 5 years while he is maintaining low carbohydrate intake and regular exercise.
Clinical Case: A 24-year-old male presented with a 6-month history of polyuria, polydipsia and weight loss of 15 kilograms (baseline BMI at 27.8 kg/m2). His initial laboratory data showed plasma glucose 398 mg/dL and A1C 9.3%. No ketonemia was found. He was diagnosed with stage 3 of Type 1 DM based on clinical presentation and positive pancreatic auto-antibodies (anti-GAD and anti-IA2). Euthyroid Hashimoto’s thyroiditis was also diagnosed based on his enlarged thyroid gland and positive thyroid auto-antibodies. He was started on basal-bolus insulin regimen for only 2 month and then A1C reversed to 5.9% within 2 months. Insulin was gradually withdrawn and completely stopped. Mixed meal stimulation test (MMST) was firstly evaluated at the second year of his diagnosis. The result revealed stimulated C-peptide at 5.5 ng/dL. Next-generation sequencing panel for monogenic diabetes revealed negative results. The patient maintains healthy lifestyle habit with low carbohydrate intake and regular exercise 5–6 times per week. His body weight was maintained at 60–63 kilograms during the past 4 years. His A1C was maintained between 5.0 to 6.0% without any anti-diabetic medication for more than 5 years. Repeated MMST in every 6–12 months still revealed preserved beta-cell functions and normal stimulated plasma glucose. Interestingly, repeated pancreatic auto-antibodies at 3 years after diagnosis showed negative anti-GAD and anti-IA2, but positive anti-ZnT8. The patient was advised to maintain his bodyweight and healthy behavior together with closely regular OPD follow-up.
Conclusion: Restored beta-cell function with completely insulin withdrawal in new-onset T1DM has been reported in very few cases which have some common factors as in our patient (low carbohydrate intake with regular exercise). Delaying autoimmune activity by reducing metabolic load in newly diagnosed T1DM might play a role in maintaining a honeymoon period and could lead to an innovative therapeutic option in new-onset T1DM.
Type 1 Diabetes Mellitus and Familial Hypokalemic Periodic Paralysis: A Management Dilemma
Authors: Khine Aye H , Hernandez Joel , Sohal Aalam , Yin Ngwe 
Published: May 2021

Abstract
Background: Familial hypokalemic periodic paralysis (FHPP) is a rare condition characterized by episodes of painless muscle weakness associated with hypokalemia. It can be precipitated by heavy exercise and high carbohydrate meals. There have been cases illustrating treatment options to decrease the frequency of episodic weakness. However, insulin use in patients with FHPP has not been well studied or documented in literature.
Clinical Case: A 21-year-old male with known FHPP (heterozygous positive CACNA1S R1239H mutation) presented with nausea, vomiting, abdominal pain, and profound weakness. He had 1/5 strength in his upper and lower extremities bilaterally on examination. He was found to be in diabetic ketoacidosis (DKA). Insulin drip was initiated per DKA protocol and eventually converted to subcutaneous insulin. He continued to be weak and persistently hypokalemic, requiring potassium replacement (200 mEq/day). He had been on acetazolamide as preventive treatment for FHPP. It was switched to spironolactone in efforts to better control his potassium levels. His strength improved gradually, and he recovered 5/5 strength in his upper and lower extremities bilaterally by day 3 of admission. His weakness did not acutely worsen after receiving subcutaneous insulin. Further testing revealed elevated glutamic acid decarboxylase (GAD) antibodies consistent with type 1 diabetes mellitus (T1DM). His serum potassium on discharge was 4.4 mEq/L. He was discharged with subcutaneous insulin, potassium chloride 40 mEq three times daily, and spironolactone 100 mg daily. After discharge, serum potassium levels remained stable and potassium requirement decreased significantly to 40 mEq once daily.
Conclusion: This case illustrates the management dilemma between an unusual combination of diseases. The balance of potassium levels between insulin use in T1DM and FHPP creates significant challenges. Fortunately, the use of subcutaneous insulin in this patient did not appear to trigger episodic weakness. Further studies of hypokalemic periodic paralysis are critical to the institution of appropriate therapy and prevention of symptoms in patients with these conditions. Careful replacement and monitoring of potassium is recommended as patients require high doses of potassium during acute episodes of flaccid paralysis, and requirement significantly decreases after an acute episode.
Irisin Precursor FNDC5 and Glycemic Control in Patients With Type 2 Diabetes
Authors: Lima Mágero Felipe Rodrigues , Vasconcellos Larissa Frazao , Frazão Larissa , Bandeira Francisco 
Published: May 2021

Abstract
Introduction: Irisin is a newly discovered myokine whose expression is induced by exercise and PGC1α. Studies have reported its action on adipose tissue cells, leading to their “browning,” and consequent increase in energy expenditure and thermogenesis. In the first description of this hormone, which is a product of cleavage of its precursor (protein 5 containing fibronectin type III domain), elevated irisin levels were associated with improved insulin sensitivity, weight reduction, and better glucose tolerance in animal models. Hence, studies have tried to characterize the role of irisin in glucose regulation, with controversial results. Muscle mass has been a good predictor of irisin circulation in humans and, because it is predominantly synthesized and secreted by skeletal muscle, its use as a potential biomarker of sarcopenia has been investigated. Methods: The aim of this study was to evaluate serum FNDC5 levels according to clinical and metabolic parameters as well as muscle mass from patients with type 2 diabetes (T2DM). Body composition was evaluated by Dual X-ray absortptiometry (DXA) and multifrequency Bioelectric Impedance (BIA) and FNDC5 was measured using an ELISA kit. Results: We evaluated 44 women with type-2 diabetes, mean age of 61.95±8.52 years, mean diabetes duration of 10.25±7.06 years, mean HbA1c of 7.66±1.37, mean fasting plasma glucose of 149.11±38.26 mg/dL, mean BMI of 29.20±5.15 kg/m2, and mean abdominal circumference of 95.02±12.80 cm. Mean FNDC5/irisin was 18.69±3.67 ng/mL. Although there were no differences in DXA and BIA analyses according to first and top quartiles of serum FNDC5, we identified a negative correlation of serum FNDC5 with fasting plasma glucose (−0.479; P=0.001) and a positive correlation with age (0.422; P=0.004). Conclusion: our data demonstrated that increased serum FNDC5 is related to increased age and poor glycemic control in T2DM.
Reference: (1) Perakakis N et al., Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol. 2017 (2) Hyun HP et al., The novel myokine irisin:clinical implications and potential role as a biomarker for sarcopenia in postmenopausal women. Endocrine. 2018.
Online CME Successful at Improving Awareness, Understanding, and Clinical Use of T2D Treatments
Authors: Larkin Amy , Le Anne 
Published: May 2021

Abstract
We sought to determine if an online continuing medical education (CME) curriculum could improve the clinical knowledge and competence of endocrinologists and primary care physicians (PCPs) related to knowledge and clinical use of GLP-1 RAs. The online CME curriculum consisted of 3 text- or video-based activities focused on practical tips for utilizing GLP-1 RAs in practice, benefits of GLP-1 RAs over therapeutic classes, and knowledge of oral GLP-1 RAs. The educational effects were assessed using a repeated pre-assessment/post-assessment study design. For all questions combined, a chi-squared test assessed whether the mean post-assessment score differed from the mean pre-assessment score (absolute changes reported). P values &lt;.05 are statistically significant. The activities launched between June-August, 2019 and outcomes data were collected through November 2019. After being online and accredited for 1 year, the 3 activities have reached over 15,000 clinicians, over 9,500 of which were physicians. Improved knowledge and competence was demonstrated among the target audiences: • 13% increase in endocrinologists (P&lt;.001) and PCPs (P&lt;.001) who effectively utilized a GLP-1 RA in a practical scenario (competence) • 24% increase in endocrinologists (P&lt;.001) and 21% increase in PCPs (P&lt;.001) who identified the impact of GLP-RA therapy on cardiovascular outcomes (knowledge) • 17% increase in endocrinologists (P&lt;.001) and 14% increase in PCPs (P&lt;.001) who correctly identified cardiovascular impact of an emerging GLP-1 RA (knowledge) Persistent knowledge/competence gaps remain: • 9% of endocrinologists and 38% of PCPs need additional education to improve competence related to clinical use of GLP-1s in practice • 64% of endocrinologists and 62% of PCPs need additional education to improve knowledge on the impact of GLP-1 RAs on cardiovascular outcomes • 64% of endocrinologists and 74% of PCPs need additional education to improve knowledge on the cardiovascular impact of emerging GLP-1 RAs This study demonstrates the success of an online curriculum at improving knowledge and competence of endocrinologists and PCPs related to knowledge and clinical use of GLP-1 RAs. Persistent gaps were identified for future educational targets.
Trends in Medication Utilization and Glycemic Control Among Type 2 Diabetes Using a Common Data Model Based on Electronic Health Records From 2000 to 2019
Authors: Lee Kyung Ae , Jin Heung Yong , Jeong Seung Han , Kim Jang Hyeon , Kim Yuji , Park Tae Sun 
Published: May 2021

Abstract
Analyzing the treatment patterns of type 2 diabetes (T2DM) in real practice helps to understand the flow of diabetes management and establish further management plans. Observational Health Data Sciences and Informatics (OHDSI) is an international collaboration created an international data network (Observational Medical Outcomes Partnership Common Data Model, OMOP-CDM). This study was aim to analyze treatment patterns of T2DM using the OMOP-CDM based on electronic health record (EHR) data and to assess whether CDM analysis was feasible to diabetes research. This is a retrospective, observational study using the EHR data of Jeonbuk National University Hospital (JNUH) transformed into OMOP-CDM. The data consisted of medical records of patients visits from January 2000 to December 2019. ATLAS ver. 2.7.6, an OHDSI’s open-source software is publicly available, was used for analysis. The 20 year old EHR data of a JNUH contain about 1.5 million patients. The proportion of adult patients treated for T2DM increased from 1,867 (1.6%) in 2000 to 9,972 (5.1%) in 2019. Sulfonylurea (SU) was the most prescribed drug (73%) followed by metformin (55%) in 2000. On the other hand, in 2019, metformin was the most prescribed (64%), and DPP-4 inhibitor prescription increased rapidly up to 55%, while the SU prescription rate decreased to 36%. The rate of insulin treatment ranged from 16% to 24%, which is higher than national surveyed based on health insurance data. Over time, monotherapy decreased while dual, triple, and quadruple combinations steadily increased. Dual combination was the most common with metformin and DPP-4 inhibitor, triple combination was the most with metformin, SU, and DPP-4 inhibitor in 2019. In analysis of annual HbA1c trends, the proportion of patients with HbA1c of 7% or lower increased (from 32.8% 2000 to 50.2% in 2019). Proportion of patients with HbA1c of 9% or more decreased from 30% to 12%. However, it was found that about half of T2DM patients still had HbA1c values above the target range. In addition, the number of patients who visited our emergency room for severe hypoglycemia did not decrease. Present study revealed that CDM analysis was feasible for diabetes research. Medication utilization patterns have changed significantly over the past 20 years with a shift towards newer drugs. Despite these changes and clinical efforts, improvement in glycemic control is still a challenge and hypoglycemic is still a problem to overcome.
Efficacy and Safety of TLANDO, A Novel Oral Easy to Prescribe and Use TRT Option
Authors: Papangkorn Kongnara , Vangara Kiran , Bruno Benjamin J , Kim Kilyoung , Chidambaram Nachiappan , DelConte Anthony , Patel Mahesh , Carson III Culley C , Goldstein Irwin , Kaminetsky Jed , Miner Martin , Khera Mohit , Dobs Adrian Sandra 
Published: May 2021

Abstract
Most widely used testosterone replacement therapy (TRT) products can be inconvenient and cumbersome topical and invasive injectable requiring dose adjustments to attain efficacy. In a pivotal study, a recently approved oral TRT only 26% of patients did not require any dose adjustment. Typically, patients start on a sub-therapeutic dose with gradual dose increases to attain efficacy resulting in additional visit(s) to clinic and pharmacy. Physician research data (N=402) suggested it typically takes 3-6 months of titrations to reach an efficacious dose for majority of patients, a significant barrier in effecting a switch without a period of “efficacy gap”. The requirement of additional visit(s) presents significant challenges for new and current patients desiring to start and to switch to a convenient TRT option, especially in the current COVID-19 pandemic. Recent reports suggest increase of disease severity/mortality in men with low testosterone is possibly due to underlying co-morbidities commonly associated with male hypogonadism. There remains a need for an effective, safe, and easy to use and prescribe product that does not require dose titration. TLANDO is a “triglyceride-free” oral single strength TRT with single dose designed to lymphatically deliver effective and safe levels of testosterone regardless of meal fat content. Moreover, dose titration is prone to some inherent titration decision errors and requires understanding of often complex titration rules. The objective is to assess whether TLANDO, an oral TRT without requiring dose titration, safely restores effective testosterone (T) levels in hypogonadal men. An open-label, single-arm, multicenter study (NCT03242590) was performed with TLANDO in hypogonadal males (N=95). Subjects received orally 225 mg twice a day testosterone undecanoate (TU) for 24 days without dose adjustment. Efficacy was evaluated by % of subjects who achieved daily T Cavg within the eugonadal range. Using 450mg daily dose without dose adjustment, 80% of subjects (95% CI of 72% to 88%) achieved a T Cavg in the normal range and safely restored with mean T Cavg of 476±184 ng/dL post steady state. T restoration was comparable to other non-oral TRT products. TLANDO was well tolerated with no deaths, no drug-related severe AEs, and no hepatic AEs. In conclusion, effective T restoration using TLANDO, an easy to use and prescribe oral TRT option, was confirmed. Minimal AEs were reported with no hepatic AEs. Upon approval, TLANDO will be the first convenient TRT option without requiring dose adjustments; therefore, enabling selection of an efficacious dose from the start of therapy. TLANDO is well suited for new or existing TRT patients desiring a convenient oral option.