bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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 &lt;.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 &lt;.001), and approximately 48.8% and 41.6% were from the lowest income quartile in T1D and T2D respectively (p &lt;.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 &lt;.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

Abstract
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

Abstract
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&lt0.05). 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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 &lt;70 mg/dL and &gt;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 &lt;70 mg/dL and &gt;120 mg/dL were 9.1% and 4.8%, respectively. Using the Dexcom G6, the mean percent of time that participant glucose values measured &lt;70 mg/dL and &gt;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.
Novel Perspectives of Super-High Dose Glybenclamide in an Infant With DEND Syndrome
Authors: Barash Galia , Bassan Haim , Ayelet Livne , Benyamini Lilach , Heyman Eli , Bowman Pamela , Barash Galia 
Published: May 2021

Abstract
Mutations in KCNJ11 gene cause a variety of persistent neonatal diabetes mellitus syndromes (PNDM), with and without developmental delay and epilepsy presentations (developmental delay, epilepsy, and neonatal diabetes - DEND Syndrome). We report a heterozygous mutation for pathogenic KCNJ11 missense variant: c.190G&gt;A, p. (Val64Met), reported once so far, associated with severe epilepsy and neurological deterioration phenotype, responsive to a combination of super high doses of Glibenclamide (Sulfonylurea) and oral steroids. We had the patient attached to continuous glucose monitoring, performed electroencephalogramic tracings, magnetic resonance imaging and whole exome sequencing on parents and patient DNA and Sanger sequencing (SS) on candidate gene mutations. His phenotypic description and management during 18 months, demonstrates this mutation is responsive to super-high doses of SU combined with high dose 6 weeks steroids protocol. In conclusion, we have identified a de novo heterozygous missense mutation as the etiology for severe DEND syndrome in a one day old neonate, presenting with asymptomatic hyperglycemia, responsive to a novel management combination.
The Impact of Multi-Disciplinary Input on Glycaemic Control Over Time in Children on Intensive Insulin Therapy Using Real World Prospectively Collected Data
Authors: Foran Jason , O’Connell Susan M , Cody Declan , Somers Eric 
Published: May 2021

Abstract
Aims: To investigate the factors impacting on glycaemic control over time including treatment type, educational input and patient demographics within an Irish tertiary paediatric diabetes centre. Methods: Using a prospectively maintained database of clinical encounters, data was analysed in age matched pairs from 2007 to 2019. Pairs were matched by insulin treatment type (pump v multiple daily injection (MDI)). Matching was performed on the basis of gender, current age, age at diagnosis and HbA1c at pump commencement. Panel data regression was performed on the entire sample and analysed for the impact of differing insulin regimens by gender, age and duration of diagnosis. This model was then used to assess the impact of intensive re-education sessions on HbA1c. Results: From 999 patients there were 104 matched pairs. Compared to MDI, matched pump patients had a lower HbA1c 6 months after commencement [Difference in HbA1c = 0.60% p &lt;0.01], this effect persisted to 8 years [0.57% p=0.01]. Panel data analysis showed CSII therapy reduces HbA1c by 0.57% relative to MDI therapy (p&lt;0.001). Patients who required intensive re-education showed a HbA1c 0.91% greater than otherwise identical patients prior to re-education, after these sessions HbA1c drops by a statistically significant 0.79% (p&lt;0.001). Conclusions: Compared to matched peers on MDI treatment regimens, patients on pump therapy showed significant improvements in HbA1c which was an effect sustained up to 8 years. Panel data regression confirms these findings and in addition shows that intensive re-education is associated with a significant drop in previously elevated HbA1c levels.