bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Performance of Glycated Hemoglobin Versus Oral Glucose Tolerance Test in the Diagnosis of Glycemic Disorders Among Women With Polycystic Ovary Syndrome in Southern Iraq
Authors: Altemimi Mahmood Thamer , Musa Alaa Khattar , Mansour Abbas Ali 
Published: May 2021

Abstract
Background: Obese women with PCOS are at high risk for developing diabetes mellitus (T2DM). A baseline oral glucose tolerance test (2hrs-OGTT) annually is an important to screen for dysglycemia in women with PCOS particularly those with at least one risk factor. Due to its advantages by fasting is not required and less day-to-day variability during periods of stress or illness, glycated hemoglobin (HbA1c) might consider a convenient screening tool. This study aimed to evaluate the performance of HbA1c versus 2hrs-OGTT in the diagnosis of glycemic disorders in women with PCOS and to evaluate the correlation between glycemic disorders, insulin resistance (IR), and anthropometric measures. Patients and methods: One hundred and thirty women of a mean age 26.3 ± 6.85 year were diagnosed with PCOS according to Rotterdam 2003 criteria in Basrah, Southern Iraq. All women were examined for weight, BMI and waist circumference then they were sent for fasting plasma glucose (FPG), 2hrs-OGTT, HbA1c, and fasting insulin to assess IR. Results: By 2hrs-OGTT, impaired glucose tolerance and T2DM were diagnosed in 16.1% and 2.4% of women with PCOS respectively and 6.7% of lean women were prediabetes. HbA1c was underestimate the diagnosis of T2DM (0.8%) and overestimate prediabetes (20%) (p=0.011) and at HbA1c= 5.55%, the specificity was (74.3%) and sensitivity (56.5%) to discriminate normal from abnormal glucose status in women with PCOS (AUC: 0.645; 95% C.I.: 0.503–0.77; p = 0.03). One hundred women (76.9%) were either overweight or obese and most of them had IR (78%). Conclusion: screening of glycemic disorders is a crucial for PCOS by using 2hrs-OGTT regardless risk factor and HbA1c seems to be unsatisfactory screening tool to predict glycemic disorders in women with PCOS.
Effects of Exercise, Metformin, Pioglitazone and Exenatide Treatment on Inflammation Induced Insulin Resistance and Ubiquitin Proteasome System in Diabetes and Obesity
Authors: Akarsu Ersin , Demirel Can , Balci Sibel Oguzkan , Sayiner Zeynel A , Yilmaz İbrahim , Korkmaz Murat , Eraydin Ayten , Tabur Suzan 
Published: May 2021

Abstract
Purpose: The aim of this study is; To examine the destruction of insulin receptor substrate-1 (IRS-1) molecule, which is one of the mechanisms that cause insulin resistance in diabetes and obesity, and its effect to reduce this destruction. For this purpose, the effects of exercise, metformin, exenatide and pioglitazone treatments on IRS-1 ubiquitination in pancreas, muscle and adipose tissue were investigated in an obese and diabetic animal model.
Method: Obese rat model was used in this study. This model is characterised by obesity, diabetes and insulin resistance. This study investigated the molecular mechanisms of IRS-1 breakdown in diabetes. IRS1, SOCS1, SOC3 expressions were evaluated in the liver, muscle and adipose tissue of this model. At the same time, immunohistochemical analyses were performed in terms of IRS1, SOCS1 and SOCS3 in the same tissues.
Results: Gene expression and Immunohistochemical analysis results were evaluated, the increase in IRS1 was noticeable in rats treated with exenatide, especially in the liver tissue despite the greater decrease in SOCS1 (P&gt; 0.05). It was determined that other drugs in this study and used in the treatment of diabetes may also affect this mechanism to different degrees.
Conclusion: Our findings showed that some drugs used in the treatment of diabetes may alter the SOCS effect and / or proteasomal degradation of the IRS-1 protein. This effect was particularly pronounced in liver tissue. However, more comprehensive studies are required to show the contribution of ubiquitination in the destruction of IRS-1 and which drugs are effective on this mechanism.
Acknowledgement: This study was supported by the Scientific And Tecnological Research Council Of Turkey (TÜBİTAK) Project No: 217S089
Osteocyte-Specific TGFβ Signaling Mitigates Obesity-Induced Deregulated Energy Metabolism and Compromised Bone Quality
Authors: Dole Neha S , Yee Cristal , Alliston Tamara 
Published: May 2021

Abstract
Bone fragility associated with obesity is well recognized and is attributed to a cumulative decline in bone quality despite high BMD. Moreover, novel insights into skeletal physiology have revealed that bone-derived factors are key regulators of systemic energy balance. Despite the revelation that bone is both a target and a driver of energy metabolism, it is not entirely clear how obesity compromises the metabolic function of bone and whether deregulated energetics in bone play a causal role in declining bone quality.
Transforming growth factor-beta (TGFβ), a key mediator of bone homeostasis, was recently shown by us to play a positive role in osteocytes, where its ablation (TβRIIocy-/-) compromised bone quality. TGFβ signaling has been previously implicated in etiologies of obesity and type 2 diabetes. Also, our unpublished unbiased transcriptomic analysis in TβRIIocy-/- mouse bones (osteocyte-enriched RNA) has shown that osteocytic ablation of TGFβ signaling causes profound changes in the expression of genes implicated in glucose and fatty metabolism. Together these observations led us to hypothesize that osteocytic TGFβ plays an integral role in regulating obesity impacted bone architecture and function in metabolism.
Using hyperglycemia to model the metabolic milieu of obesity in vitro, we found that hyperglycemia upregulated TGFβ signaling in osteocytes. We also found that TGFβ acts similarly to hyperglycemia in reprogramming osteocyte cellular metabolism to promote glycolysis at the expense of oxidative phosphorylation. Thus, TGFβ may be a crucial mediator of hyperglycemia-induced metabolic reprogramming in osteocytes.
In TβRIIocy-/- mice, inhibition of osteocyte-intrinsic TGFβ signaling reduced age-dependent weight gain and improved glycemic control relative to littermate controls. When subjected to a high-fat diet (HFD, 18 weeks), TβRIIocy-/- mice continued to be leaner, with lower food intake, and higher levels of activity and fatty acid metabolism in the liver compared to HFD fed littermate controls. This implicates osteocyte-intrinsic TGFβ signaling as a crucial regulator of systemic energy metabolism. TβRIIocy-/- mice on HFD also showed increased trabecular and cortical bone mass, increased bone mineral density, and protection against reduced bone strength compared to littermate controls on a similar diet.
Overall, our study identifies a novel role for osteocytic TGFβ signaling in regulating energy metabolism and bone health in obesity.
The Role of TGFβ Ligands and Signalling on Insulin Resistance in Skeletal Muscle in Women With PCOS
Authors: Moreno-Asso Alba , McIlvenna Luke C , Patten Rhiannon K , McAinch Andrew J , Rodgers Raymond J , Stepto Nigel K 
Published: May 2021

Abstract
Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy affecting metabolic and reproductive health of 8–13% of reproductive-age women. Insulin resistance (IR) appears to underpin the pathophysiology of PCOS and is present in approximately 38–95% of women with PCOS. This underlying IR has been identified as unique from, but synergistic with, obesity-induced IR (1). Skeletal muscle accounts for up to 85% of whole-body insulin-stimulated glucose uptake; however, in PCOS this is reduced by about 27% when assessed by a euglycaemic-hyperinsulinaemic clamp (2). Interestingly, this reduced insulin-stimulated glucose uptake observed in skeletal muscle tissue is not retained in cultured myotubes (3), suggesting that in vivo environmental factors may play a role in this PCOS-specific IR. Yet, the molecular mechanisms regulating IR remain unclear (4). A potential environmental mechanism contributing to the development of peripheral IR may be the extracellular matrix remodelling and aberrant transforming growth factor beta (TGFβ) signalling. Previous work demonstrated that TGFβ superfamily ligands are involved in the increased collagen deposition and fibrotic tissue in the ovaries, and suggested that these ligands may be involved in the metabolic morbidity associated with PCOS (5). In this study, we investigated the effects of TGFβ1 (1, 5 ng/ml), and the Anti-Müllerian hormone (AMH; 5, 10, 30 ng/ml), a TGFβ superfamily ligand elevated in women with PCOS, as causal factors of IR in cultured myotubes from women with PCOS (n=5) and healthy controls (n=5). TGFβ1 did not have a significant effect on insulin signalling but induced expression of some ECM related genes and proteins, and increased glucose uptake via Smad2/3 signalling in myotubes from both groups. Conversely, AMH did not appear to activate the TGFβ/Smad signalling pathway and had no significant impact on insulin signalling or glucose uptake in any of the groups. In conclusion, these findings suggest that TGFβ1, but not AMH, may play a role in skeletal muscle ECM remodelling/fibrosis and glucose metabolism in PCOS but does not have a direct effect on insulin signalling pathway. Further research is required to elucidate its contribution to the development of in vivo skeletal muscle IR and broader impact in this syndrome. References: (1) Stepto et al., Hum Reprod 2013 Mar;28(3):777–784. (2) Cassar et al., Hum Reprod 2016 Nov;31(11):2619–2631. (3) Corbould et al., Am J Physiol-Endoc 2005 May;88(5):E1047-54. (4) Stepto et al., J Clin Endocrinol Metab, 2019 Nov 1;104(11):5372–5381. (5) Raja-Khan et al., Reprod Sci 2014 Jan;21(1):20–31.
Use of Intranasal Insulin as Neuroprotection From Hyperglycemia in Rat Model of Extremely Preterm Infants
Authors: Yauch Lauren McClure , Ennis Kathleen , Tkac Ivan , Rao Raghavendra 
Published: May 2021

Abstract
Background: Hyperglycemia is common in extremely preterm infants (EPI) and is a risk factor for increased mortality and morbidity, including abnormal neurodevelopment. Hippocampus-mediated cognitive deficits are common in this population. In a rat model of insulinopenic hyperglycemia, abnormal neurochemistry in the hippocampus was found, with lactate, glutamate (Glu):glutamine (Gln) ratio lower and Phosphorylated Creatinine (PCr):Creatinine (Cr) higher. Intranasal insulin has been shown to improve cognitive function in animal models of Alzheimer’s disease and type 2 diabetes mellitus, as well as in adult human studies of Alzheimer’s disease. No study has previous investigated the use of intranasal insulin on preventing the long-term effects of hyperglycemia in the EPI population. Objective: To determine whether administration of intranasal insulin during early postnatal days would negate the effects of hyperglycemia on the developing hippocampus in neonatal rat model of streptozotocin (STZ)-induced hyperglycemia. Design/Methods: STZ (80mg/kg IP) was injected on postnatal day (P) 2, and littermates in the control group were injected with an equivalent volume of citrate buffer. STZ pups were randomized to intranasal insulin, 3U twice daily from P3-P6 (STZ + INS) or left untreated (STZ). Neurochemical profile (consisting of 20 metabolites, PCr:Cr and Glu:Gln ratios) of the hippocampus was evaluated using ultra-high-field (9.4 T) magnetic resonance spectroscopy (MRS) on P7 (acute effects) and P56 (long-term effects) compared with the control group (CON)(N=6/group). Results: Mean glucose values from P3-P6 were higher in STZ groups (STZ = 279.0 +/- 132.2 mg/dL, STZ+INS = 274.4 +/- 89.5 mg/dL, CONT = 128.4 +/- 15.1 mg/dL). The neurochemical profile was different at both P7 and P56. On P7, compared with the control, the taurine (Tau) was higher in the STZ groups (p = 0.007. At P56, PCr:Cr was higher in the STZ group compared to CONT and STZ+INS groups (p = 0.04). No difference noted between the STZ+INS and CONT groups. No other metabolites were altered. Conclusion: Neonatal hyperglycemia alters the acute and long-term neurochemical profile in the hippocampus of developing rats. The increase in PCr:Cr ratio in the STZ group indicates lower demand for ATP and PCr, secondary to decreased neuronal activity, which has been demonstrated in previous studies. PCr:Cr ratio of the STZ+INS group was no different than control, indicating that intranasal insulin reverses the negative effect on neuronal activity caused by neonatal hyperglycemia.
Hyperglycemia Requiring Insulin Among Pediatric Patients Diagnosed With Hemophagocytic Lymphohistiocytosis
Authors: Schweisberger Cintya , Palaniappan Nila , Wood Nicole , Amos Lauren , Halpin Kelsee 
Published: May 2021

Abstract
Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder marked by massive cytokine release due to macrophage and T-cell activation. Hallmarks of the diagnosis include fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogemia, and elevations in ferritin and soluble IL-2 receptor. Given HLH is associated with critical illness, elevation in inflammatory markers, and treated with glucocorticoids, the development of hyperglycemia during its course is not unexpected. However, detailed descriptions of the severity of hyperglycemia and strategies in insulin management among HLH patients are lacking. We describe 10 years’ experience at a single tertiary pediatric health center with HLH patients who developed insulin dependent hyperglycemia.
Objectives: To describe the demographics, clinical and laboratory findings, treatment regimens, and outcomes for children with HLH treated with insulin due to hyperglycemia.
Study Design: Retrospective chart review from 2010 through 2019 of youth 0 to 21 years of age who required insulin therapy during or shortly after a hospitalization where they were diagnosed with HLH using established criteria. Descriptive statistics were used to characterize the population of interest.
Results: Of 30 patients diagnosed with HLH, 33% (n=10) required insulin therapy. Half (n=5) were female and half (n=5) male. The mean age was 8.4 years (7.8 months - 17 years). The majority (80%) were non-Hispanic white. Mean BMI at admission was 53rd percentile (5th - 87th percentile). Max serum glucose ranged from 267 to 725 mg/dL (mean 421 mg/dL). Marked inflammation was present (max CRP 2.6 - 44.9 mg/dL, max ferritin 1,091 - 90,219 ng/mL). All were treated with dexamethasone, doses ranging from 5 to 11 mg/m2/day and duration from 2 to 70 days. Most (90%) received parenteral nutrition (PN) with a mean max GIR of 8 mg/kg/min (SD=2.7). Intravenous infusions of regular insulin were used in 80% of patients, though 2 patients were later transitioned to long and short acting subcutaneous insulin. Mean duration of IV insulin therapy was 9.5 days (2–24 days); however, 2 patients died while on IV insulin therapy. The majority (70%) needed insulin within 5 days of starting steroids. Two patients (20%) were treated with subcutaneous insulin only (no IV). Only 1 patient was discharged home on insulin therapy. Mean hospital stay was 60 days (10–202 days). Mortality was 50% (n=5).
Conclusions: One-third of pediatric HLH patients required insulin during their hospitalization for severe hyperglycemia likely secondary to multiple factors including glucocorticoid use, parenteral nutrition, inflammation, and severe illness. Insulin is typically started within 5 days of initiating steroid therapy, limited to IV infusions, and often is not needed by the time of discharge. Risk of mortality is very high.
An Unusual Form of Type 1 Diabetes With an Elevated Proinsulin Level
Authors: Havranova Jana , Gallagher Thomas , Arastu Mohammad Ishaq 
Published: May 2021

Abstract
Introduction: Diabetes is one of the most prevalent diseases in the world. We recognize the three most common types of diabetes: type1, type2 and gestational diabetes. It is estimated that around 425 million of people worldwide have diabetes and about 90% of those represent type 2 diabetes. The most common types of diabetes are polygenic -- they are caused by a defect in multiple genes. Monogenic diabetes is caused by a mutation in a single gene. We currently have over 10 different types of monogenic diabetes called MODY (Maturity Onset Diabetes of the Young). Sun et al. states that over the past few years, 30 different insulin gene mutations were reported to cause a new syndrome called MIDY (Mutant INS-gene-induced Diabetes of Youth). Most of these mutations lead to proinsulin misfolding in the endoplasmic reticulum. We present a rare case of a young obese female with an elevated proinsulin level and low C-peptide level diagnosed with type 1 diabetes requiring therapy with insulin. Case Description: A 21 year old female with past medical history of chronic diarrhea initially presented with a complaint of dry mouth, dizziness, excessive urination, and thirst. She was found to have hyperglycemia of 203 mg/dL, A1C 8.3, and negative ketones. Patient had a strong family history of diabetes. She had a family history of: father with type 1 diabetes; mother with a past medical history of gestational diabetes who became diabetic postpartum; and three of the patient’s grandparents with a history of diabetes. Patient was started on the oral hypoglycemic agents metformin and glipizide, but she only had partial response to these medications. Because of her strong family history and incomplete response to oral hypoglycemic agents, additional testing was performed. Patient was found to have a low C-peptide level (1.6 ng/mL), elevated proinsulin (72.9 pmol/L), positive GAD antibody (10.3 units/mL) and negative islet cell autoantibody. Patient had a very good response to insulin and subsequently became insulin dependent. She is currently on an insulin pump. Conclusion: Sun et al. reports that proinsulin misfolding causes beta cell failure. Increased misfolding occurs under certain pathological conditions that are currently unknown. We think that there might be some increased proinsulin misfolding abnormality that might be occurring in this patient. There are most likely many epigenetic modifiers that would trigger certain individuals to be more prone to this phenomena of misfolded proinsulin. Future research in diabetes may one day yield antibodies that would specifically recognize misfolded proinsulin in the plasma. Further research is required to elucidate how defective proinsulin folding may lead to beta cell dysfunction and subsequent evolution of diabetes mellitus.
Chronic Kidney Disease Prevalence and Glomerular Filtration Rate Trends in Children With Type 1 Diabetes
Authors: Favel Kristen , Mammen Cherry , Panagiotopoulos Constadina 
Published: May 2021

Abstract
Background and Objectives: Children with type 1 diabetes (T1D) are at risk for acute kidney injury (AKI) secondary to diabetic ketoacidosis, as well as chronic kidney disease (CKD) from diabetic nephropathy. The primary objective of this study was to assess the prevalence of abnormalities in estimated glomerular filtration rate (eGFR) in children with T1D. As a secondary objective, we sought to explore the relationship between clinical characteristics and trends in eGFR. Design, Setting, Participants, and Measurements: This ambispective cohort study involved children aged 18 years or younger with T1D (n = 420), followed in the diabetes clinic at British Columbia Children’s Hospital (BCCH), the tertiary pediatric hospital in Vancouver, British Columbia, Canada. Data was collected from the BCCH paper and electronic health records. CKD was defined as eGFR less than 60 mL/min/1.73 m2. Being at risk of CKD was defined as having a mildly decreased eGFR (60-&lt;90 mL/min/1.73 m2) and/or hyperfiltration (eGFR ≥140 mL/min/1.73 m2). eGFR was calculated using the modified Schwartz formula (36.5 x height in cm / serum creatinine in μmol/L). Linear regression analysis was used to describe the relationship between eGFR and duration of T1D. Covariates included in the analysis included sex, history of DKA, A1c, and BMI. Results: Of the 420 participants, 225 (54%) were male, with a median age at T1D diagnosis of 6.1 years and T1D duration of 4.8 years (range &lt;1.0–15.0 years). One-hundred and eighty-six (44%) children were hospitalized for DKA, of which 89 (48%) developed AKI. No participants had an eGFR &lt; 60 ml/min/1.73m2, and 317 (76%) had normal renal function. Fifty-one participants (12%) had an eGFR &lt; 90 ml/min/1.73 m2, and 52 (12%) demonstrated hyperfiltration. When analyzed as a cohort cross-sectionally based on duration of T1D, there was a significant linear decline in eGFR of 1.4 ml/min/1.73 m2 per year (95% CI -1.95, -0.87 ml/min/1.73 m2). Conclusion: In a large group of pediatric patients with type 1 diabetes, 24% were at risk for chronic kidney disease based on a mildly decreased GFR and/or hyperfiltration. The pattern of eGFR decline over time is concerning and relevant, as this cohort is at risk for CKD secondary to diabetic kidney disease. Strategies are needed to improve the follow-up and management of early CKD in children with type 1 diabetes to maintain their renal function into adulthood, and more studies are needed to quantify further change in eGFR in the young adult population.
Effects of Treatment With Continuous Subcutaneous Insulin Infusion on Arterial Stiffness and Endothelial Glycocalyx Compared to MDI Intensification in Patients With Type 1 Diabetes: Improvement After a Six-Month Pump Treatment
Authors: Kountouri Aikaterini , Thymis John , Kousathana Foteini , Balampanis Konstantinos , Pliouta Loukia , Prentza Vasiliki , Katogiannis Konstantinos , Kostelli Gavriela , Barmpagianni Aikaterini , Liatis Stavros , Lambadiari Vaia , Ikonomidis Ignatios 
Published: May 2021

Abstract
Patients with type 1 diabetes mellitus (T1DM) present signs of atherosclerosis and endothelial dysfunction earlier compared to healthy individuals. The evidence regarding the efficacy of continuous subcutaneous insulin infusion (CSII) in vascular function in T1DM are scarce. The aim of this study is to determine whether insulin intensification with CSII improves arterial stiffness and endothelial function in T1DM compared to multiple daily insulin (MDI) injections. Thirty patients with T1DM were included in our study. Fifteen patients with poor glycemic control were transitioned from MDI to CSII and were reviewed immediately prior (baseline) and six months after the initiation of CSII. Fifteen patients, matched for sex, age and glycemic control, remained on intensified treatment with MDI (control group). In all patients at each visit we measure a) Carotid-femoral PWV b) central systolic blood pressure (cSBP) c) perfused boundary region (PBR) of the sublingual arterial microvessels. Both groups had similar cardiovascular markers and HbA1c at baseline (p&gt;0.05). After a six month treatment period, patients on CSII improved HbA1c (7.9±1.5% vs 7.35±0.7%, p&lt;0.05), PBR (2.1±0.2 vs. 2±0.2 μm, p&lt;0.05), PWV (7.5±0.3 vs. 7.4±1.1m/s, p&lt;0,05) and cSBP (114.6±12.5 vs. 112±5.4 mmHg, p&lt;0.05). There were no statistically significant differences in PBR (2±0.3 vs. 2±0.3 μm, p&gt;0.05), PWV (8±2.3 vs. 8±1.9m/s, p&gt;0.05) and cSBP (115±15.2 vs. 115.7±15.4 mmHg, p&gt;0.05) in patients who remained on MDI, despite improvement of HbA1c (8±1.1% vs 7.36±0.8%, p&lt;0.05). The use of CSII improves the thickness of endothelial glycocalyx and decreases arterial stiffness after six months treatment in patients with T1DM.