bluuebunny/crossref_metadata_2025 huggingface dataset:
Schmidt’s Syndrome Presenting as Diabetic Ketoacidosis and Adrenal Crisis: A Case Report and Review of Literature
Authors: Faya Marines , Abdelmasih Randa , Tuna Kubra Melek , Gatt Adrianna , Bapatla Amruth
Published: May 2021

Introduction: Schmidt’s Syndrome, is a rare endocrine disorder defined by the combined occurrence of Addison disease, autoimmune thyroid disease, and type 1 diabetes mellitus. The rarity of the condition and the presentation of adrenal insufficiency and hypothyroidism often lead to misdiagnosis with life-threatening consequences for the patients. We report a case presenting with adrenal insufficiency and diabetic ketoacidosis who was diagnosed with Schmidt’s Syndrome. Case Description: We describe the case of a 38-year-old male with a past medical history of hypothyroidism, who was admitted for worsening abdominal pain, nausea, vomiting, fevers, and chills. Physical exam revealed underweight male with marked dehydration, diaphoresis, in moderate abdominal pain. Initial vital signs and laboratory panel raised suspicion for adrenal insufficiency and diabetic ketoacidosis. Blood pressure 82/42mmHg, HR of 121, sodium 128mmol/L, potassium 6.8mmol/L, chloride 104mmol/L, bicarbonate 5mmol/L, BUN 20mg/dl, Creatinine 1.5mg/dl, Glucose 402mg/dl, TSH 60, and serum osmolality 319mosm/kg. The electrolyte derangements and vital signs improved after the initiation of the high-dose steroids and insulin. The patient was transitioned to a regimen of hydrocortisone/ fludrocortisone, levothyroxine, and insulin basal/bolus and was discharged in clinically stable conditions to follow up with an endocrinologist. Discussion: The prevalence of Schmidt’s syndrome is 1:20,000 in the general population and a 3:1 ratio of females to males. Autoimmune thyroid disease is present in 70–75%, T1DM in 40–60%, and Addison’s disease in 40–50%. This syndrome can be associated with other non-endocrine autoimmune disorders, such as vitiligo, myasthenia gravis, Sjogren’s syndrome, rheumatoid arthritis, and primary antiphospholipid syndrome. The initial step in diagnosis should be checking serum morning cortisol levels to identify adrenal insufficiency. Autoimmune antibodies play an important role to confirm the diagnosis including 21-hydroxylase, 17-hydroxylase, thyroid peroxidase, glutamic acid decarboxylase, islet cells, anti-tissue transglutaminase antibodies, parietal cell, and anti-intrinsic factor antibodies. Currently, treatment is limited to hormone replacement in patients with organ failure. But it is crucial to replace corticosteroids before starting thyroid replacement in patients with adrenal insufficiency. Conclusion: A high level of diagnostic suspicion is required for the diagnosis of Schmidt’s syndrome when encountering a patient with autoimmune disease. The diagnosis of this syndrome is often delayed, causing adverse events. With this case presentation, we add to the data pool of Schmidt’s syndrome with the ability to significantly improve patients outcomes with early diagnosis and hormone replacement.
An Open-Access Platform for Translating Diabetes and Cardiometabolic Disease Genetics Into Accessible Knowledge
Authors: Costanzo Maria , Bruskiewicz Kenneth , Caulkins Lizz , Duby Marc , Gilbert Clint , Hoang Quy , Jang Dong-Keun , Kluge Alexandria , Koesterer Ryan , Massung Jeffrey , Ruebenacker Oliver , Singh Preeti , von Grotthuss Marcin , Flannick Jason , Burtt Noel
Published: May 2021

Most associations from genome-wide association studies (GWAS) result from as-yet-unknown alterations of molecular or cellular function; the causal variants and effector genes responsible for them, and the tissues and pathways through which they act, remain largely unknown. Thousands of associated loci have now been identified for each common disease and its related traits. In order to translate GWAS data into biological knowledge, they must be integrated with functional genomic annotations reflecting tissue-specific regulation and with the results of bioinformatic methods that predict the functional effects of associations. However, these data types are typically spread across disparate resources, and working with them requires bioinformatic expertise.

To make these results accessible and understandable to the broader diabetes and cardiometabolic disease research communities, we have developed the open-access Common Metabolic Diseases Knowledge Portal (CMDKP; cmdkp.org), which brings together a robust software and data storage platform with a streamlined and intuitive user interface for four disease areas: diabetes (both types 1 and 2); cardiovascular disease; cerebrovascular disease; and sleep and circadian disorders.

The CMDKP enables researchers to access and explore a comprehensive matrix of genetic, genomic, and computational results. It includes 3 classes of genomic data: 1) GWAS summary statistics from the most current and authoritative datasets available, as identified by disease-area experts; 2) functional genomic annotations, such as chromatin accessibility, that reflect the tissue-specific regulatory potential of genomic regions; and 3) the results of bioinformatic methods applied to these aggregated data (for example, overlap-aware meta-analysis to determine “bottom-line” p-values, the GREGOR method for determining tissue-specific enrichment of genetic associations, the MAGMA method for generating gene-level association scores, and more). All of these data types are integrated and accessible via interactive tools that allow researchers to explore and evaluate the data in order to identify candidate disease effector genes for further research. The CMDKP provides researchers with the data and tools necessary to translate genetic associations and functional annotations into knowledge about disease mechanisms and potential therapeutic targets.
Hyperglycemia Regulated Circulating MicroRNAs and Their Effects on Renal Function Decline in Type 2 Diabetes
Authors: Kobayashi Hiroki , Satake Eiichiro , Krolewski Andrezej S
Published: May 2021

Background: It has been reported that microRNAs (miRNAs) play an important role in the pathogenesis of diabetic complications. We aimed to search for circulating miRNA that were associated with hyperglycemia in type 2 diabetes and examine their effects on renal function decline. Methods: Using the next-generation sequencing-based HTG EdgeSeq miRNA platform, a total of 2,083 miRNAswere measured in baseline plasma specimens obtained from73 subjects with type 2 diabetes (T2D) and normal renal function (discovery panel) and 136 subjects with T2D and impaired renal function (replication panel). Subjects in both panels were followed for 6–12 years to determine eGFR decline. Results: We identified 11 candidate miRNAsthat were strongly associated with elevated levels of glycated hemoglobin (HbA1c) in both screening and replication panels. Using bioinformatics analyses, we found that the candidate miRNAs targeted proteins of 6 pathways (the Ras signaling pathway, Signaling pathways regulating pluripotency of stem cells, the MAPK pathway, Glutamatergic synapse, the Rap 1 signaling pathway, and the AMPK signaling pathway). Importantly, 4 of these 11 miRNAs were significantly associated with risk of renal function decline. Conclusion: There were few previous reports about the association between circulating miRNAs, hyperglycemia, and diabetic kidney disease in T2D. The present study comprehensively examined and identified hyperglycemia-regulated miRNAs in human samples. Our finding are novel in that circulatingmiRNAsregulated by hyperglycemia are associated with risk of eGFR decline in T2D.
Management of Late Dumping Syndrome Induced Hypoglycemia With GLP-1R Agonist
Authors: Shaghouli Amna Ali , Ballani Razan , Mesbah Naglaa
Published: May 2021

Background: Late dumping syndrome is a prominent post-bariatric surgery side effect. Glucose-dependenthyperinsulinemia, induced by elevated gastric inhibitory polypeptide (GIP) and glucagon-likepeptide-1 (GLP-1) levels, leading to 2–3 hours post-prandial hypoglycemia. In literature, several managements are available: dietary changes, glucosidase inhibitor, andsomatostatin analogues. In case of failure of those strategies, partial or total pancreatectomy isindicated. Recently, management using GLP-1R agonists showed promising effect inmanagement of late dumping syndrome induced post-prandial hypoglycemia. (1)AimThe aim of this study was to investigate the effect of using GLP-1R agonists w/o low glycemicindex diet for treating dumping syndromes induced post-prandial hypoglycemia in post bariatricsurgery patients. Methods: A sample of 27 cases (25 females, 2 males) mean age 44.64, SD 10.2 of post-bariatric surgerywere managed using GLP-1R w/o low-glycemic index diet after being diagnosed with the latedumping syndrome induced post-prandial hypoglycemia for duration 1–3 years post-surgery. The27 were sent a survey of 13 questions related to their experience pre-and post-management plan. Results: Out of the 27 patients, 15 responded to the survey. The results showed 100% of the participantsdeveloped episodes of severe symptomatic late dumping syndrome with hypoglycemiasymptoms diagnosed after one and half years of their symptoms. 87% of them experiencedhypoglycemia post meals 2–3 hours.70 % of the participants got hypoglycemia more than 5episodes per week (less than 4.0 mmol/l) which was confirmed by blood glucose monitoring. After starting treatment with GLP-1R agonists with or without low-glycemic index diet, 87% ofthe participants reported that the hypoglycemia episodes were reduced. Out of those 87%participants 46% did not get any hypoglycemia episode and 54% of them experienced 1–2 timeshypoglycemia episodes. Conclusion: The results of the survey showed the successful reduction or prevention of late dumpinghypoglycemia episodes frequency post-bariatric surgery by GLP 1R agonist with or without lowglycemicindex diet. References: Non, A.N.H.W.H. and Black, H., 2012. Scope of the Problem. Am J Prev Med, 42, pp.563–70.Chiappetta, S. and Stier, C., 2017. A case report: Liraglutide as a novel treatment option in late dumping syndrome. Medicine, 96(12).
Presentation and Management of Liraglutide-Related Pancreatitis: Systematic Review of Case Reports
Authors: Singh Som P , Qureshi Fahad
Published: May 2021

Background: Liraglutide is a glucagon-like peptide-1 (GLP-1 agonist) aimed towards promoting glucose-dependent insulin secretions. This medication is an emerging treatment option for the management of obesity through promoting satiety. However, there are a growing number of cases noting adverse effects of liraglutide. Of note, liraglutide has been seen to elevate serum amylase and lipase levels among users, and therefore promoting acute pancreatitis. Moreover, the overall presentation of liraglutide-related acute pancreatitis can be variable. The aim of this study is to determine qualitative patterns of presentation and meta-analysis of lab changes among acute pancreatitis patients on liraglutide. Methodology: Systematic review of the literature was performed on MEDLINE, Google Scholar, and the Cochrane Database of Systematic Reviews for liraglutide-related acute pancreatitis case studies, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklist. Meta-Analysis performed using Stata. Results: Twenty-one patient cases were identified then contingently evaluated for acute pancreatitis based on presentation, labs, and treatment outcomes. Within the pancreatitis cases, the average age of onset was 59 ± 16.5 (male = 58 ± 24.5; female = 56 ± 24.6). Upon qualitative review, 14.3% of patients were asymptomatic but showed elevated serum amylase and lipase levels following liraglutide administration (p < 0.05). Among the symptomatic group, there was variation in the duration of liraglutide administration and reported compliance. There was no significant difference among treatment regimes between symptomatic and asymptomatic groups. Conclusion: Longer duration of liraglutide treatment without dose adjustment was notable to show elevated rises in both serum amylase and lipase. However, the variation of patient symptoms cannot be determined through the duration of treatment. Patient demographics do not seem to play a role in acute pancreatitis episodes. Future studies ought to focus on larger patient samples to further develop an understanding of treatment duration, presentation, and management of acute pancreatitis management after liraglutide administration.
Prevalence and Predictors of Hepatic Steatosis Among Adult Population With Prediabetes: Data From NHANES 2017–2018
Authors: Shaheen Magda , Pan Deyu , Friedman Theodore C
Published: May 2021

Previous studies have examined the prevalence of hepatic steatosis in patients with diabetes but few studies examined the relationship between hepatic steatosis and prediabetes. The purpose of this study was to examine the relationship between hepatic steatosis and prediabetes in a representative sample of the U.S. adult 20 years and older. Data from 5,492 participants in the National Health and Nutrition Examination Survey (NHANES) 2017–2018 were analyzed. Participants were considered normal if they have hemoglobin A1c (HbA1c) <5.7%, have prediabetes if their HbA1c was 5.7% to 6.4% and had diabetes if their HbA1c was > 6.5. Hepatic steatosis was diagnosed using fibroscan. We analyzed the data using descriptive, bivariate Chi square, and multiple logistic regression to determine the association between diabetes status, prediabetes status and hepatic steatosis, adjusting for confounding variables and considering the design and sample weights. Of the 5,492 participants, 8.5% had diabetes and 22.6% had prediabetes. The prevalence of hepatic steatosis was 70% among population with diabetes, 46% among the prediabetes group, and 21% in the normal group (p<0.05). In the adjusted logistic regression model, relative to the normal group, patients with diabetes were four times more likely to have hepatic steatosis relative to normal group (adjusted odds ratio [AOR]=4.0, 95% confidence level [CI]=2.4–6.8, p<0.05). Population with prediabetes were two times more likely to have hepatic steatosis relative to the normal group (AOR=2.1, 95% CI=1.6–2.6, p<0.05). Among the population with prediabetes, the predictors of hepatic steatosis were age 50–65 years old relative to 20–34 years old (AOR=1.9, 95% CI=1.1–3.2, p<0.05), overweight (AOR=5.4, 95% CI=2.5–11.8, p<0.05), obese (AOR=16.6, 95% CI=7.2–38.0, p<0.05) relative to normal body mass index, and high triglyceride level (>=200 mg/dL) (AOR=4.2, 95% CI=2.6–6.6, p<0.05) versus normal (<=150 mg/dL). Blacks with prediabetes were 40% less likely to have hepatic steatosis relative to Whites (AOR=0.6, 95% CI=0.4–0.9, p<0.05). Our study indicates that the prevalence of hepatic steatosis is higher in diabetic and prediabetes groups compared to normal group. In addition, those with prediabetes had more than two times higher chance of having hepatic steatosis relative to the normal group. Further longitudinal studies are needed to explore the causal relation between prediabetes and hepatic steatosis among the adult population. Grant numbers: R01MD012579, R24DA017298, U54MD007598, S21MD000103, UL1TR001881
To Evaluate the Relationship of Risk Factor Between Diabetes Mellitus and Thyroid Dysfunction (Thyrobetes)
Authors: Varma Madhumati
Published: May 2021

Introduction: Type 2 diabetes and thyroid dysfunction are common endocrine disorder and shown mutually influence each other. As per the GOQii is a smart-tech enabled, integrated preventive healthcare platform headquartered in California, diabetes has increased from 7.1 to 12% this year. “The incidence of diabetes is highest among older adults at 23.81 per cent and seniors at 36.82 per cent.” As per the report, 13.5% of Indians have cholesterol issues. This past year, thyroid issues have increased from 6.8% to 10.7%. The thyrobetes illustrates relationship the between thyroid diseases and diabetes mellitus.

Objective of the Study: This study’s objectives are as follows:To define the interrelation of factors responsible for the link between diabetes and thyroid disease development;To estimate thyroid hormone TSH, free T3, free T4, lipid profile, blood glucose fasting and PP, HbA1c, S. Insulin, ant-TPO antibodies, and USG neck for some thyroid patients;To describe each factor correlation between developing diabetes and thyroid diseases; andTo explain preventive measures for diabetes and thyroid diseases. Research problem of the studyThere are an increasing number of patients who experience diabetes mellitus, hypothyroidism and other types of thyroid dysfunction, but it is difficult to say which disease occurs first. This study seeks to identify the overlapping risk factor for diabetes and thyroid dysfunction. Review of literatureType 2 diabetes mellitus and thyroid dysfunction (TD) are two major public health endocrine problems. The status of iodine and thyroid with diabetic patients less studied. Materials and Methods: The study included 300 patients of diabetes and thyroid dysfunction. The questionnaires were used to record the findings on thyroid hormone TSH, free T3, free T4, lipid profile, blood glucose fasting and PP, and USG neck for some thyroid patients. Inclusion criteria:Sample size -300 patientsNo limit to the age groupNew or follow up cases of diabetic mellitus and thyroid diseaseExclusion criteria:Patients who had an acute illness that affects thyroid gland activityPatients who consumed drugs that could influence the thyroid hormone statusPatients who had feverData collection and tools for statistical analysisInstruments used for analyzing the samples that are availability at JNU hospital.

Statistical Analysis: Statistical analysis will be performed by using SPSS software, student ‘t’ tests, and Pearson’s correlation; if the P* value < 0.005, then it will considered to be statistically significant. Conclusion: Thyroid disease and diabetes are two intertwined conditions. If you have a thyroid condition, you’re at an increased risk for developing diabetes, and if you have diabetes, you’re at an increased risk for thyroid disease.
Virtual Patient Simulation in DKD: Successful Strategy for Improving Recognition and Management
Authors: Larkin Amy , LaCouture Michael
Published: May 2021

Intro: we sought to determine if virtual patient simulation (VPS)-based continuing medical education (CME) intervention could improve performance of diabetologists/endocrinologists related to recognition and management of diabetes kidney disease (DKD). Methods: The intervention comprised a patient presenting at two different time points in a VPS platform that allows learners to order lab tests, make diagnoses, and prescribe treatments in a manner matching the scope and depth of actual practice. Tailored clinical guidance (CG), based on current evidence and expert recommendation, was provided following each decision, followed by the opportunity for the learner to modify to their decisions. Decisions were collected post-CG and compared with each user’s baseline (pre-CG) decisions using a McNemar’s test to determine P values. The activity posted August 30, 2019; initial data was collected through November 7, 2019. Results: 270 diabetologists/endocrinologists completed the activity (all decisions within at least 1 case) and were included. Significant improvements were observed after CG: 1st Patient: • Diagnose CKD stage 3b: 29% absolute improvement (5% pre-CG vs 34% post-CG; P<.01) • Initiate SGLT2 inhibitor: 50% improvement (24% pre-CG vs 74% post-CG; P<.01) • Order patient education: 19% improvement (52% pre-CG vs 71% post-CG; P<.01) • Order follow-up appointment: 18% improvement (53% pre-CG vs 71% post-CG; P<.01) 2nd Patient: • Diagnose CKD stage 3a: 49% absolute improvement (10% pre-CG vs 59% post-CG; P<.01) • Initiate SGLT2 inhibitor: 36% improvement (51% pre-CG vs 87% post-CG; P<.01) • Initiate ACE inhibitor: 11% improvement (85% pre-CG vs 96% post-CG; P<.01) • Order patient education: 12% improvement (66% pre-CG vs 78% post-CG; P<.01). Conclusion: VPS that immerses and engages specialists in an authentic and practical learning experience can improve evidence-based clinical decisions related to patient identification and management of DKD.
Effect of Chronic Kidney Disease on Outcomes of Adult Patients Admitted With Hyperosmolar Hyperglycemic State: Analysis of National Inpatient Sample
Authors: Shaka Hafeez , Velazquez Genaro , Velagapudi Sujitha , Edigin Ehizogie , Murthi Mukunthan , Marcos-Abdala Hernan Gerardo , Asemota Iriagbonse , Akuna Emmanuel
Published: May 2021

Background: Treatment guidelines have been well established in patients with HHS and a normal renal function. The mainstay of treatment for patients with HHS includes intravenous volume replacement, potassium replacement, and blood glucose correction by administering insulin. However, this treatment protocol cannot be directly applied to a patient with decreased GFR as it increases the risk of hypoglycemic episodes due to decreased insulin clearance along with increasing the risk of hyperkalemia and volume overload. Hence titrating insulin, maintaining euvolemia and normokalemia becomes further challenging in a patient with HHS in the setting of CKD. Although the above-mentioned complications are well described in multiple studies, there is not enough evidence demonstrating the association between the inpatient mortality and secondary outcomes in patients with HHS with and without CKD.

Objective: To compare the inpatient mortality and secondary outcomes in patients admitted with HHS with CKD vs without CKD.

Methods: A retrospective cohort study was conducted using the Nationwide Inpatient Sample from 2016 and 2017. About 42 740 hospitalizations who had HHS as primary diagnosis were enrolled and further stratified based on the presence or absence of CKD as a secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality and secondary outcomes included length of hospital stay, total Hospital charges, Sepsis, Septic Shock, Acute Kidney Injury (AKI), and Acute Respiratory Failure (ARF). Multivariate regression analysis was done to adjust for confounders.

Results: Out of the 42 740 hospitalizations with HHS, about 9 545 had CKD. The in-hospital mortality for patients with HHS was 305 overall, out of which 105 patients had Atrial Fibrillation as a secondary diagnosis. Compared with patients without CKD, patients with CKD had similar in-hospital mortality (aOR 0.93, 95% CI 0.48–1.8, p=0.83) when adjusted for patient and hospital characteristics. Patients with HHS and CKD had similar length of hospital stay, total hospital charges, rate of Sepsis, Septic Shock, and ARF in comparison to patients without CKD; however, patients with CKD had higher odds of developing AKI thorough out hospitalization.

Conclusion: This study found that patients admitted with HHS and CKD have similar in-hospital mortality when compared to patients without CKD. However, the study group with CKD has higher odds of developing AKI when compared to the group without CKD. Although AKI is common and correctable in HHS, the above-mentioned association is possible due to the judicious IV fluid replacement in an HHS patient with CKD as a concern for volume overload. Further studies are needed to identify contributing risk factors and establishing fluid replacement guidelines in a patient with HHS and CKD.
Impact of Atrial Fibrillation on In-Hospital Outcomes in Patients With Hyperosmolar Hyperglycemic State: Analysis of National Inpatient Sample
Authors: Velazquez Genaro , Shaka Hafeez , Murthi Mukunthan , Marcos-Abdala Hernan , Velagapudi Sujitha , Akuna Emmanuel , Asemota Iriagbonse , Edigin Ehizogie , Williams Dimeji
Published: May 2021

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia and its negative prognostic impact on the morbidity and mortality of hospitalized patients has been well described. In patients with Hyperosmolar hyperglycemic state (HHS), mortality rates can reach up to 20% and poor outcomes have been reported in people with older age, presence of comorbid conditions and concurrent infections. However, the impact of atrial fibrillation on the hospital outcomes of patients admitted with HHS has not been well documented.

Objective: We wanted to compare the outcomes for HHS hospitalizations for patients with and without Atrial fibrillation.

Methods: A retrospective cohort study was conducted using the Nationwide Inpatient Sample from 2016 and 2017. About 42 740 hospitalizations who had HHS as primary diagnosis were enrolled and further stratified based on the presence or absence of Atrial Fibrillation as secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality and secondary outcomes included length of hospital stay, total Hospital charges, Sepsis, Septic Shock, Acute Kidney Injury (AKI), and Acute Respiratory Failure (ARF). Multivariate regression analysis was done to adjust for confounders.

Results: Out of the 42 740 hospitalizations with HHS, about 3 295 had Atrial Fibrillation. The in-hospital mortality for patients with HHS was 305 overall, out of which 60 patients had Atrial Fibrillation as secondary diagnosis. Compared with patients without Atrial Fibrillation, patients with Atrial Fibrillation had a similar in- hospital mortality (aOR 0.77, 95% CI 0.39–1.52, p=0.45) when adjusted for patient and hospital characteristics. Patients with HHS and Atrial Fibrillation had similar length of hospital stay, total Hospital charges, rate of Sepsis, Septic Shock, AKI, and ARF in comparison to patients without Atrial Fibrillation.

Conclusion: Our study suggests that the presence of atrial fibrillation in hospitalized HHS patients is not associated with increased mortality or longer duration of hospital stay. This data is essential since it helps identify HHS patients with increased risk of complications. As previous reports have suggested that AF, especially of new onset in critically ill patients is a marker of increased disease severity, the lack of such impact in patients with HHS requires further studies.
Inpatient Hypoglycemia in Patients With Chronic Kidney Disease
Authors: Do Justin , Mojazi-Amiri Hoda , Heineke Hyunju S , Ayutyanont Napatkamon , McQueen Chelsea , Moghadam Bahman , Kubomoto Scott
Published: May 2021

Background: Inpatient hypoglycemia has been shown to be associated with increased mortality, more complications, and greater length of stay [1]. Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) are at greater risks for hypoglycemia due to their decreased degradation of insulin, reduced glycogen stores, and decreased renal gluconeogenesis. With the association between inpatient hypoglycemia and increased morbidity and mortality, it is valuable to determine other risks factors that may contribute to hypoglycemia in the hospital setting.

Objective: Determine the rates of hypoglycemia (glucose <70 mg/dl) and severe hypoglycemia (glucose <54 mg/dl) along with risk factors, such as type of insulin used and initial hyperglycemia at admission, for patients with diabetes mellitus (DM) and CKD/ESRD.

Methods: A retrospective cohort analysis was conducted on 74,266 hospitalized patients who had DM and CKD/ESRD or DM alone, within 155 HCA Healthcare hospitals from January 2019 through June 2019.

Results: Among hospitalized patients with DM, hypoglycemia was more common in patients with ESRD (n=5234) compared to patients with CKD without ESRD (n=18659) and patients without CKD/ESRD (n=52373) (34.37% vs. 23.66% vs. 12.91%, respectively, p<0.01). Similarly, severe hypoglycemia was more common in patients with ESRD compared to patients with CKD without ESRD, and patients without CKD/ESRD (18.09% vs. 11.19% vs. 5.28%, respectively, p<0.01).

When evaluating patients with ESRD, a higher point of care (POC) glucose at time of admission was associated with an increased risk of subsequent hypoglycemia. Within the first 24 hours of hospital admission, hypoglycemia was more common if the patient’s initial POC glucose was greater than 300 with an incidence of 13.67% compared to 11.21% (n=955, p=0.033). Among patients with ESRD and an admission glucose > 300, having an order for dialysis within the first 24 hours of admission was associated with increased risk of hypoglycemia (OR= 1.2181, p=0.0014). Diabetics with subsequent hypoglycemia had higher initial glucose levels on admission when compared to diabetics who did not experience hypoglycemia during their hospital stay. Mean = 221.61±82.32 vs 205.54±74.51 (p=0.000002).

Conclusion: In hospitalized patients with DM, CKD and ESRD are associated with increased risk of hypoglycemia. Amongst diabetics, patients with ESRD and CKD account for over 50% of cases of severe hypoglycemia. Severe hypoglycemia occurred in 18% of patients who had both diabetes and ESRD. An elevated glucose at admission is associated with a subsequent hypoglycemia in patients with ESRD. It is important to manage DM in patients with CKD and ESRD carefully as they may be more likely to experience hypoglycemia due to overcorrection and decreased clearance of insulin.

1.Hulkower et al., Diabetes Manag 2014 Mar;4(2):165–176.
Trends of Diabetes-Related Hospital Admission in Emerging Adults in the State of California
Authors: Nip Angel Siu-ying , Lodish Maya Beth
Published: May 2021

Background: As adolescents with diabetes transition to adulthood, they may demonstrate poorer adherence to treatment regimens and may be vulnerable to complications such as diabetic ketoacidosis (DKA) or severe hypoglycemia. A number of important factors have been identified as risk factors for these poor outcomes, including loss of health insurance coverage, increased risk-taking behaviors, and difficulty coping with added responsibility. National data may inform efforts to improve health outcomes and prevent complications for vulnerable young adults during this challenging transition to independence. Objectives: To estimate the incidence of diabetes-related admissions and to describe the characteristics among youth and young adults with type 1 (T1D) and type 2 diabetes (T2D) in the state of California. Study design and method: This is a retrospective cohort study using the inpatient database from the Office of Statewide Health Planning and Development during the years 2014 to 2018. Individuals aged 13–24 years hospitalized with DKA, or hypoglycemia, were identified by ICD codes. Results: A total 28,754 admission encounters were recorded. Mean ages for T1D and T2D were 17.3±5.6 years and 17.9±4.6 years, respectively. Hospitalization rates increased with age with a significant rise during the transition to adulthood, from 70.3/100,000 population at age 17 to 132.2/100,000 population at age 19 in T1D. Among hospital admissions in T1D and T2D, 16.3% and 18.7% were Black young adults respectively (p <.001). More young adults were on public insurance when compared to youth (64.1% vs 45.1% in T1D; 68.4% vs 50.4% in T2D, p <.001), and approximately 48.8% and 41.6% were from the lowest income quartile in T1D and T2D respectively (p <.001). There was no difference in mean length of hospital stay, but hospital charges were higher among young adults with both types of diabetes when compared to youth ($41,370 vs $36,160 in T1D; $37,218 vs $30,991 in T2D, p <.001). More young adults were admitted for severe cases such as DKA or hypoglycemia with coma in T1D, with rates tripling from 0.3/100,000 population in youth to 1.0/100,000 population in young adults. Conclusion: We demonstrated a significant rise in admission rates during the transition to adulthood in individuals with T1D. Among admissions in both types of diabetes, there were significantly more Black young adults who were on public insurance with lower socioeconomic status. This population group had poorer health outcomes with higher incidence for moderate and severe complications, and they cost more hospital charges than the youth population with both types of diabetes. Our findings suggest that the US healthcare system fails many emerging adults with diabetes, particularly for people of color, and that improving the medical transition is crucial. More resources should be focused on this at-risk population from a healthcare system perspective.
Effects of Extracts of Plathymenia Reticulata Benth and Azadirachta Indica (Neem) in Glycated Hemoglobin in Diabetic Rats
Authors: Neto Ezio De Martino , da Silva Joyce Satil Chaves , Lourenço Eliane Cristina , de Castro Neto Arthur Cesário , Ferreira Isabella Cecilio Resende , Silva Gyovanna de Oliveira , Vendramini Natalia Escoura , Silva Maria Vilaça Omena , Bichuetti Vinícius Pontes , Leão Amanda Vilela , Lopes Isabel Cristina Rezende , Resende Luísa Tassinari , de Menezes Carolina Magalhães Hueb , Marra Danilo Oliveira , Montes Marta Santos Anjo , Ceron Patrícia Ibler Bernardo , Thedei Geraldo , Magalhães Fernanda Oliveira
Published: May 2021

Introduction: The Plathymenia reticulata benth is a herbal medicine that has properties of pancreatic islet hyperplasia and glycemic control in diabetic rats. Neem (Azadirachta indica A. Juss, Meliaceae) is a tree native to India that has several medicinal effects. Goal: To verify the effect of glycated hemoglobin levels in rats with type 1 and non-diabetic diabetes mellitus, in treatment with Plathymenia Reticulata Benth, Neem and the association between them. compared to insulin. Methodology: Diabetes was induced by intraperitoneal streptozotocin (65mg/kg) administration after a 24-hour fast. The diagnosis was made using a blood glucose value above 200mg/dl. The study was conducted in 60 male adult Wistar rats, weighing between 180 and 220 grams, divided into 9 groups, between diabetics (DM) and non-diabetic controls (NdM), and treated with Neem (300 mg/kg), cold aqueous extract of Plathymenia (100 mg/kg), water (negative control) and insulin (3 IU/day) - positive control; and association between plants. The treatment was performed by orogastric gavage for a period of 28 consecutive days, and weekly weight and daily feed intake were performed. Data were analyzed using ANOVA and Tukey-Kramer’s pos-hoc test, with a significance level of 5% using the SPSS25.0 software. The results are expressed on average ± EPM. Results: There was a significant difference in glycated hemoglobin levels in rats submitted to insulin treatment (6.18 ± 0.36) compared to those submitted to treatment with Neem (10.12 ± 1.29, p=0.047), Plathymenia+Neem (12.09 ± 0.38, p=0.006) and water (10.86 ± 1.26, p=0.015). However, no significant difference was observed between the reduction in glycated hemoglobin levels in the groups submitted to insulin treatment compared to the group treated with Plathymenia (7.30 ± 0.68, p=0.911). Conclusion: The results allow us to evaluate a non-inferiority condition in relation to the use of the Plathymenia when compared to treatment with insulin therapy, positive control in the treatment of type 1 diabetes mellitus. The Plathymeniamay present as a herbal option in the treatment of the disease and prevention of complications. Further studies are necessary to evaluate the effect of the extract on other aspects related to the pathology.
Effects of Sodium Glucose Cotransporter 2 Inhibitor on Renal Renin-Angiotensin-Aldsoterone System
Authors: Takeda Yoshiyu , Takeda Yoshimichi , Demura Masashi , Kometani Mitsuhiro , Karashima Shigehiro , Hashimoto Atsushi , Aono Daisuke , Sawamura Toshitaka , Yoneda Takashi
Published: May 2021

Objective: The renoprotective effect of sodium glucose cotransporter 2 inhibitor (SGL2i) has been reported in diabetic patients. Local renin-angiotensin-aldosterone system (RAAS) is activated in diabetes mellitus and hypertension. We examined the effects of SGL2i on the RAAS in the obese diabetic rats fed a high salt diet. Methods: Zucker-diabetic rats (ZDR) and control rats were fed a high or normal salt diet and were treated with canagliflozin for 8 weeks. Blood pressure (BP), blood glucose (BG), PRA, plasma aldosterone (PAC), urinary albumin excretion (UAE), urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG), gene expression of angiotensinogen in the kidney were measured. Results: ZDR febd a high salt diet showed high BP, increased UAE and urinary 8-OHdG and elevated angiotensinogen mRNA levels. Treatment with canagliflozin significantly decreased BP, BG, UAE, urinary 8-OHdG and and renal angiotensinogen mRNA levels compared with control rats (p<0.05). Discussion and Conclusion: The closer mechanism of renoptotection of SGL2i in diabetes mellitus is unclear. We have reported that the repoprotective effects of type 2 angiotensin receptor antagonist or mineralocorticoid receptor blocker were partly due to the decreased RAAS in the kidney. Decreased renal RAAS by the treatment with canagliflozin may contribute to the renoprotection in DZR.
In Utero Maternal Benzene Exposure Predisposes to the Metabolic Imbalance in the Offspring
Authors: Koshko Lisa , Debarba Lucas Kniess , Sacla Mikaela , Lima Juliana , Didyuk Olesya , Fakhoury Patrick , Klueh Ulrike , Sadagurski Marianna
Published: May 2021

Environmental chemicals play a significant role in the development of metabolic disorders, especially when exposure occurs early in life. We have recently demonstrated that benzene exposure, at concentrations relevant to a cigarette smoke, induces a severe metabolic imbalance in a sex-specific manner affecting male but not female mice. However, the roles of benzene in the development of aberrant metabolic outcomes following gestational exposure, remain largely unexplored. In this study, we exposed pregnant C57BL/6JB dams to benzene at 50 ppm or filtered air for 5 days/week (6h/day from gestational day 1 to birth) and studied male and female offspring metabolic phenotypes in their adult life. While no changes in body weight or body composition were observed between groups, 4-month-old male and female offspring exhibited reduced parameters of energy homeostasis (VO2, VCO2, and heat production). However, only male offspring from benzene-exposed dams were glucose intolerant and insulin resistant at this age. By six months of age, both male and female offspring displayed glucose and insulin intolerance, associated with elevated expression of hepatic gluconeogenesis and inflammatory genes. Additionally, this effect was accompanied by elevated insulin secretion and increased beta-cell mass only in male offspring. Thus, gestational benzene exposure can reprogram offspring for increased susceptibility to metabolic imbalance in adulthood with differential sensitivity between sexes.
Preclinical Characterization of Once Weekly Basal Insulin Fc (BIF)
Authors: Moyers Julie S , Hansen Ryan J , Day Jonathan W , Dickinson Craig D , Zhang Chen , Kahl Steven D , Ruan Xiaoping , Ding Liyun , Brown Robin M , Baker Hana E , Beals John M
Published: May 2021

Weekly basal insulin injections may increase treatment adherence in subjects with diabetes and an appropriately engineered weekly basal insulin may reduce daily pharmacokinetic (PK)/pharmacodynamic (PD) fluctuations compared to currently available daily basal insulins. Therefore, a weekly insulin has the potential to not only ease the burden of insulin therapy, but also improve outcomes for subjects with diabetes in a real-world setting. Basal insulin Fc (BIF, LY3209590) is an insulin Fc-fusion protein in clinical testing as a once weekly treatment for type 1 and type 2 diabetes mellitus (T1DM, T2DM). BIF is comprised of a human single-chain insulin fused to a human IgG2 Fc domain through a peptide linker. The in vitro evaluation determined that BIF exhibited reduced insulin receptor (IR) potency with full agonism, selectivity against human insulin-like growth factor-1 receptor (hIGF-1R), and functional properties similar to native human insulin. The binding affinity of BIF for hIR isoform A, Ki = 25 nM (SEM = 4, n=10), and hIR isoform B, Ki = 26 nM (SEM = 4, n=10), was more than two orders of magnitude weaker than human insulin. BIF stimulated IR phosphorylation in cells with reduced potency, but full agonism, and showed a significantly faster hIR dephosphorylation profile than either human insulin or AspB10 insulin. BIF stimulated de novo lipogenesis in 3T3-L1 adipocytes and cell proliferation in SAOS-2 and H4IIE cells with at least a 70-fold reduction in potency compared to human insulin. BIF possessed markedly reduced binding and activation of hIGF-1R making definitive mitogenic measurements unattainable. In preclinical in vivo pharmacology studies using streptozotocin (STZ)-treated diabetic rats, a statistically significant decrease in blood glucose compared to vehicle-treated animals was seen 24 hours post-injection and persisted through 336 hours post-injection following a single subcutaneous administration (30 nmol/kg) of BIF. In STZ-treated rats, BIF reached a Tmax at 48 hours, possessed an apparent clearance rate of ~0.85 mL/hr/kg, and t1/2 of ~120 hrs. Collectively, these results demonstrate that BIF possesses selective IR agonism with a pharmacological profile similar to native insulin, however with a significantly reduced potency, and a significantly extended time action profile in preclinical animal models supporting once weekly testing in the clinic.
The IgG Antibody Paradox in Insulin Resistance: Pathogenic and Therapeutic
Authors: Lipchik Andrew , Lee Sooyeon , Annes Justin P , Snyder Michael P
Published: May 2021

Chronic low-grade inflammation and mitochondrial dysfunction are hallmarks of insulin resistance. However, the mechanisms by which the immune system can propagate systemic insulin resistance remains poorly understood. IgG antibodies are a critical component of immunity and display paradoxical properties. IgG can propagate inflammation by crosslinking Fc receptors activating innate immune cells, and conversely, when given intravenously at high doses (1–2 g/kg intravenous immunoglobulin), actively suppress inflammation. Here, we demonstrate that IgG can exert similar paradoxical properties on glucose metabolism. IgG can elicit insulin resistance, and conversely, when given at high doses, promote insulin sensitivity in a diabetic mouse model. IgG, through its Fc-mediated interactions, suppresses insulin-induced mitochondrial function as well as insulin signaling. Modulation of insulin-dependent mitochondrial respiration by serum or purified IgG highly correlates (R2 = 0.70) with the quantitative measurement of insulin sensitivity accessed by the modified insulin suppression test. Our studies indicate that IgG antibody glycosylation is critically important to these conflicting actions. In mice and humans, the progression of insulin resistance is associated with reduced IgG Fc region sialylation, and administration of asialylated IgG is sufficient to cause insulin resistance in IgG null mice. On the other hand, a single administration of high-dose IgG significantly improved insulin and glucose tolerance as well as plasma glucose levels lasting over 72 days post-administration. These results demonstrate new insights into the systemic nature of insulin resistance, a novel mechanism of the disease, and an innovative therapeutic strategy for treating type 2 diabetes.
Liver-Specific Expression of Constitutively Active Gsα Leads to Hyperglycemia With Impaired Insulin Secretion
Authors: Sun Hui , Chen Min , Zhang Aileen B , Zhang Jianhua , Taira Akiko , Sunahara Satoshi , Jahnke Marshal T , Lee Ji Eun , Ge Kai , Weinstein Lee Scott
Published: May 2021

Liver-specific Expression of Constitutively Active Gsα Leads to Hyperglycemia With Impaired Insulin Secretion

The ubiquitously-expressed G protein Gsα couples hormone receptors to the stimulation of intracellular cAMP generation. We previously showed that mice with liver-specific Gsα deficiency (LGsKO) have improved glucose tolerance and enlarged pancreatic islets1. In the present study, we have generated mice with liver-specific expression of a constitutively activated Gsα (LGsR201C) by breeding mice containing a Lox-STOP-Lox-GsαR201C transgene within the Hipp11 locus with albumin-Cre mice. Male LGsR201C mice had normal survival but reduced body weight and increased liver weight. Compared to control littermates, LGsR201C mice had significantly increased hepatic cAMP levels and enhanced hyperglycemic response to glucagon, confirming the activation of liver Gsα/cAMP signaling in LGsR201C mice. As a consequence, LGsR201C mice showed elevated blood glucose levels during both fed and fasting states, as well as enhanced hepatic gluconeogenesis evidenced by pyruvate tolerance test. Serum levels of insulin, glucagon, free fatty acids and triglycerides were comparable between control and LGsR201C mice in the fed state. Results of glucose and insulin tolerance tests showed that LGsR201C mice had severe glucose intolerance with normal insulin sensitivity. Unlike control mice, when given a high dose of glucose (3mg/g ip.), LGsR201C mice had completely blunted first- and second-phase insulin secretory responses to glucose. Since LGsR201C mice exhibited normal pancreatic islet size and insulin content examined with immunohistochemistry, the impaired glucose tolerance in LGsR201C mice probably resulted from an impaired insulin secretion. Results of RNA-seq analysis revealed that an array of genes was oppositely regulated in the liver of LGsKO mice vs. LGsR201C mice. Thus, our data indicate possible organ-to-organ communication between liver and pancreatic β-cells that is regulated by liver Gsα signaling. 1.Chen M., et al., JCI 115:3217, 2005
Abbott FreeStyle Libre Versus Dexcom G6: Detecting Disorders of Carbohydrate Metabolism in a Youthful Non-Diabetic Cohort Pilot Study
Authors: Comite Florence , Heard Madeleine , Izhar Aalin
Published: May 2021

Objective: Disorders of aging develop decades prior to emerging according to evidence in the literature. Early detection and actionable intervention have tremendous potential to prevent, delay, or even reverse the onset of disease. Individual carbohydrate metabolism data inform interventions to address the progression of underlying disorders of carbohydrate metabolism. Continuous glucose monitoring (CGM) devices can be harnessed to reveal suboptimal glycemic control. In the present study, two CGM devices were used to screen for carbohydrate metabolic dysfunction in 14 individuals without a history of type 2 diabetes. Methods: The two CGM devices used in this prospective cohort study were the Abbott FreeStyle Libre and Dexcom G6. Participants concurrently wore both devices for 30 days and were instructed to maintain their usual dietary habits for the duration of the study. The optimal glucose range was defined as 70–120 mg/dL. Glucose data were compiled and analyzed to screen for metabolic abnormalities. Results: 14 non-diabetic individuals were enrolled in this study. The cohort was 50% female with ages ranging from 22–46 years (mean=31.4 years). Out of the 14 participants, 100% showed glycemic abnormalities, including hypoglycemia and hyperglycemia. Across the cohort, the Abbott FreeStyle Libre and Dexcom G6 detected fasting and postprandial values between 40–237 mg/dL and 40–279 mg/dL, respectively. Both CGM devices detected glucose values <70 mg/dL and >120 mg/dL in all 14 participants. The amount of time each participant spent outside the optimal glucose range was variable. Using the Abbott FreeStyle Libre, the mean percent of time that participant glucose values measured <70 mg/dL and >120 mg/dL were 9.1% and 4.8%, respectively. Using the Dexcom G6, the mean percent of time that participant glucose values measured <70 mg/dL and >120 mg/dL were 1.4% and 19.2%, respectively. Discussion: Using CGM devices, we discovered that these 14 non-diabetic individuals exhibit suboptimal glycemic control, as demonstrated by blood glucose measurements falling outside 70–120 mg/dL for all participants. In addition, the Abbott FreeStyle Libre detected fasting hypoglycemia and reactive hypoglycemic responses more often than the Dexcom G6, while the Dexcom G6 detected more postprandial hyperglycemia than the Abbott FreeStyle Libre. It is plausible that the recommended device placement contributed to these differences, with the Abbott FreeStyle Libre on the tricep and Dexcom G6 on the abdomen. These findings support the utility of CGM devices as screening tools to detect and predict disorders of carbohydrate metabolism and warrant further investigation into the variation between CGM device measurements.