bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium Glucose Co-Transporter2 (SGLT2) Inhibition for Refractory Hypomagnesemia in Monogenic Diabetes Type 5 (MODY 5)
Authors: Paul Anju A , Korytkowski Mary T 
Published: May 2021

Abstract
Background: MODY 5 is an infrequently reported form of monogenic diabetes attributed to deletions of chromosome 17q12 with impaired expression of HNF1β (Hepatocyte Nuclear Factor 1 Beta). We report a patient who presented with hyperglycemia and hypomagnesemia with an eventual diagnosis of MODY5 that responded to treatment with the SGLT2 inhibitor (SGLT2i), canagliflozin.
Clinical case: A 64-year-old male diagnosed with diabetes at age 60 and treated with glimepiride and metformin (HbA1c 6.1–6.2% without hypoglycemia) presented to establish care. He had a prior history of hypermagnesuric hypomagnesemia (serum Magnesium (Mg) 1.4 ± 0.3 mg/dl with Fractional Excretion of Mg (FEMg) 32 ± 3% [values &gt;3–4% in the setting of normal renal function and hypomagnesemia indicates renal Mg loss]) that developed while taking Triamterene- HCTZ for hypertension, prompting discontinuation. Treatment with oral and intravenous (IV) Magnesium along with Amiloride failed to normalize serum Mg levels. Genetic evaluation revealed 17q12 deletion consistent with a diagnosis of MODY 5. Referral to nephrology resulted in discontinuation of glimepiride and addition of canagliflozin 100 mg titrated to 300 mg daily. Mg levels normalized (serum Mg level 1.9 ± 0.1 mg/dL) within 8 weeks of canagliflozin therapy, allowing discontinuation of IV Mg and patient reported improvement in physical stamina and quality of life. At his 1 year follow up visit, his serum Mg remains stable at 1.8mg/dl with a FEMg of 22 ± 2.5%. His current therapy includes Metformin 2 gm, Canagliflozin 300 mg, Amiloride 10 mg tid, and oral Mg.
Discussion: Prior to introduction of the SGLT2i, MODY 5 patients required oral and IV Mg repletion in combination with amiloride to achieve near normal Mg levels. Several clinical trials with SGLT2i demonstrated dose and agent dependent improvement in Mg levels in patients with type 2 diabetes. Proposed explanations include reductions in eGFR, changes in intraluminal electrical potential, and activation of renin angiotensin aldosterone system. Mg replacement results not only in symptomatic improvement, but has also been demonstrated to reduce risk of stroke and all-cause mortality.
In summary, SGLT2 inhibitors in patients with MODY 5 can be effective in restoring normal Mg levels, improving quality of life, and reducing all cause mortality.
Unfortunate Case of Hypoglycemia Induced Seizures Resulting in Anoxic Encephalopathy
Authors: Nallamothu Kavya , Douedi Steven , Hu Katherine , Ong Raquel , Cheng Jennifer 
Published: May 2021

Abstract
Background: Severe hypoglycemia in patient with diabetes mellitus can manifest as seizures and coma, most commonly occurring after excessive insulin administration.
Clinical Case: A 35-year-old woman with uncontrolled type 1 diabetes mellitus on basal-bolus insulin, complicated by gastroparesis, hypoglycemia unawareness, and frequent hypoglycemic episodes due to a tendency to give more than the recommended amount of insulin, who presented with seizures and diffuse brain edema as severe manifestations of profound hypoglycemia. Hemoglobin A1c was 7.3% but patient had wide variation in blood glucose (40- 300 mmol/L) on her glucometer. Patient had initially self-treated overnight hypoglycemic symptoms by drinking soda and then fell asleep without re-checking her blood sugar. She was then unresponsive in the morning. Patient’s husband reported that there was no glucagon at home since he used the last one and did not refill. On EMS arrival, patient had a blood glucose of 25, for which she received dextrose and glucagon with improvement of blood glucose but no change in mentation. En route to the hospital, patient developed tonic-clonic seizures and decerebrate posturing. She received Ativan and was intubated for airway protection. On exam, she had bilateral dilated sluggishly reactive pupils, eyes opened spontaneously but did not track, and limbs moved spontaneously but there was no purposeful movement. Initial CT head without contrast showed significant diffuse brain edema. Repeat MRI brain with and without contrast showed bilateral basal ganglia diffusion restriction with associated T2 and FLAIR hyperintense signal, suggestive of toxic-metabolic etiology including hypoglycemia. Video EEG showed findings consistent with anoxic encephalopathy. Patient received IV mannitol and IV dexamethasone for cerebral edema and Keppra for seizure prophylaxis, but was unable to be weaned from the ventilator and had to undergo tracheostomy and PEG tube placement, and was eventually discharged to inpatient rehabilitation. Conclusion: This case highlights the dangers of accidental overcorrection of high blood sugar with short-acting insulin and not appropriately treating hypoglycemia, which can lead to irreversible brain injury due to prolonged hypoglycemia. This unfortunate case highlights the importance of educating patients with diabetes mellitus on insulin how to appropriately manage low sugars to avoid such outcomes.
Current Utilization Trends of SGLT-2 Inhibitors in Type 2 Diabetics With Heart Failure
Authors: Dhillon Puneet , Grover Harshwant , Haq Shujaul , Patel Tirth , Sadiq Usama , Tariq Shafaq , Abideen Zain Ul , Rosenberg Daniel , Mallavarapu Vamshi 
Published: May 2021

Abstract
Background: Sodium glucose cotransporter-2 inhibitors (SGLT2 inhibitors) are a recent addition to the armamentarium for treating type 2 diabetes. Over the last couple of years, these agents have been studied in patients with cardiovascular disease, particularly heart failure. Results of the EMPA-REG (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), CANVAS (Canagliflozin Cardiovascular Assessment Study) and DECLARE-TIMI (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction) have clearly shown SGLT2 inhibitors to be beneficial for patients with heart failure. FDA has approved Canagliflozin and Dapagliflozin for reduction of risk of adverse cardiovascular events in patients with Type 2 Diabetes with established Cardiovascular disease. This study was conducted to determine the current utilization trends of SGLT2 inhibitors in Type 2 Diabetics admitted with congestive heart failure exacerbation at Abington Memorial Hospital. Methods: The study was an observational retrospective chart review of 287 patients who were admitted to the telemetry floor with an admitting diagnosis of Congestive Heart Failure with a concomitant diagnosis of Type 2 Diabetes from 06/01/2019 to 11/30/2019. 186 patients met the inclusion criteria. Results: Mean age of the patient population was 69 years. Mean ejection fraction was 39%. Mean A1C was 7.7. Out of 186 patients who met the inclusion criteria, 2 patients were on SGLT2 inhibitor on admission and were discharged on it. 1 patient was started on a SGLT2 inhibitor during hospitalization and was discharged on it. Out of our patient population, only 1.6% of the patients were discharged on SGLT2 inhibitor. Conclusion: Even after FDA approval of SGLT-2 inhibitors in reducing heart failure hospitalizations in patients with known history of Type 2 diabetes and heart failure, the utilization of these drugs is very minimal. No other drug has been proven to improve mortality in patients of heart failure with preserved ejection fraction. Based on the results of this study, we propose that initiation of SGLT2 inhibitor should be one of the core measures during discharge of Type 2 Diabetics after a hospitalization with Heart Failure.
Predicting Major Adverse Cardiovascular Events in Asian Type 2 Diabetes Patients With Lasso-Cox Regression
Authors: Rui Lam Amanda Yun , Chan Min Min , Carmody David , Teh Ming Ming , Bee Yong Mong , Hsu Wynne , Lee Mong Li , Ng See Kiong , Ong Marcus Eng Hock 
Published: May 2021

Abstract
Background: South-East Asia has seen a dramatic increase in type 2 diabetes (T2D). Risk prediction models for Major adverse cardiovascular events (MACE) identify patients who may benefit most from intensive prevention strategies. Existing risk prediction models for T2D were developed mainly in Caucasian populations, limiting their generalizability to Asian populations. We developed a Lasso-Cox regression model to predict the 5-year risk of incident MACE in Asian patients with T2DM using data from the largest diabetes registry in Singapore. Methodology: The diabetes registry contained public healthcare data from 9 primary healthcare centers, 4 hospitals and 3 national specialty centers. Data from 120,131 T2D subjects without MACE at baseline, from 2008 to 2018, were used for model development and validation. Patients with less than 5 years of follow-up data were excluded. Lasso-Cox, a semi-parametric variant of the Cox Proportional Hazard Model with l1-regularization, was used to predict individual survival distribution of incident MACE. A total of 69 features within electronic health records, including demographic data, vital signs, laboratory tests, and prescriptions for blood pressure, lipid and glucose-lowering medication were supplied to the model. Regression shrinkage and selection via the lasso method was used to identify variables associated with incident MACE. Identified variables were used to generate individual survival probability curves. Incident MACE was defined as the first occurrence of nonfatal myocardial infarction, nonfatal stroke, and CV disease-related death. Results: A total of 12,535 (10.4%) subjects developed MACE between 2008 and 2018. Model performance was evaluated by time-dependent concordance index and Brier score at 1, 2 and 5 years. The results of 5-fold cross validation shows that the model displayed good discrimination, achieving time-dependent C-statistics of 0.746±0.005, 0.742±0.003 and 0.738±0.002 at 1, 2 and 5 years respectively. The model demonstrated low Brier scores of 0.0355±0.0004, 0.0601±0.0011, 0.104±0.004 at 1, 2 and 5 years respectively, indicating good calibration. Factors most predictive of MACE were age and a history of hypertension and hyperlipidemia. Conclusions: We have developed a risk prediction model for MACE in Asian T2D using a large Singaporean T2D cohort, which can be used to support clinical decision-making. The individual survival probability estimates achieve an average C-statistics of 0.742 and are well-calibrated at 1, 2 and 5 years.
Libre in Inpatient Covid Units
Authors: Pandya Reeni K , Sukkari Mohamad Anas , Olson Darin E 
Published: May 2021

Abstract
Continuous glucose monitors (CGM) have demonstrated accuracy in outpatients and were accurate with pilot data using blinded systems in inpatients. Libre CGMs were approved and donated to hospitalsfor use during the COVID-19 to minimize exposure and PPE use. We made a prospective plan to assess accuracy of the Libre on inpatients admitted to COVID units during an initial “validation phase”. Fingerstick blood glucose (FSBG) was checked for the first three days after placing the sensor and compared to Libre values within the next 1–15 minutes. Patients were instructed to scan the sensor after each FSBG, and at other times as clinically warranted. FSBG values were recorded from the medical record (CPRS) and compared to Libre values downloaded to LibreView. The mean absolute relative difference (MARD) between FSBG and Libre was calculated for each patient for one to three days. The average MARD across all patients was calculated. Accuracy was further assessed using the Bland-Altman Plot and error grid analysis using web-based tool. Of the 21 patients assessed in the validation phase, 19 had at least one day of data and 11 had at least three days. The mean MARD was 11.2% after one day, and 12.5% after three days. Four patients after one day and three patients after three days had a MARD of 15–20% where use of the Libre was continued with confirmatory FSBG. In 15/19 (78%) patients with one day of data and 8/11 (73%) of patients with 3 days of data had a MARD &lt;15% and continued using the Libre without further FSBG. One patient had a MARD &gt;20% that did not improve with changing the sensor, and Libre was discontinued. In 16 of 19 patients, the Libre values were lower than FSBG. No adverse events relating to Libre use were identified. Error grid analysis showed that most patients had no values outside the A and B ranges, and very few values outside of the clinically accurate range, occurring in 2 of the 19 patients (9% of values in the “slight risk” zone in 9% in one and 6% in the other). The Libre was well-accepted by patient and nursing staff, but did not have measurable effect on glycemic control, hypoglycemic events, or hospitalization measures. The libre was deemed a useful intervention in inpatients, but it can be inaccurate or only moderately accurate compared to FSBG in enough patients to require checking accuracy for at least 1–3 days. Inaccurate Libre values were mostly lower than FSBG requiring confirmatory measures of low Libre values with FSBG in our experience.
Publication Model, Ownership and Impact of the Top Endocrinology Journals
Authors: Shamsudeen Isabel , Jain Mehr , Ding Jeffrey , Khosa Faisal 
Published: May 2021

Abstract
Background: Subscription-based (SB) is the traditional publication model for peer-reviewed research; however, open-access (OA) models have been rising in popularity in recent years. Journals may be owned by commercial, professional society, university or government publishers. SCImago Journal Rank (SJR) indicator is a measure of the scientific influence of scholarly journals.
Objectives: The purpose of this study is to assess the publication model, ownership and SJR indicator of the top Endocrinology journals. This will help inform researchers’ decisions when selecting a journal to submit their work to.
Methods: The SCImagoJR website was used to obtain a database of active, peer-reviewed Endocrinology journals worldwide. Publishers were grouped by parent company and categorized as commercial, professional society, university or government. Journals were searched on the National Library of Medicine catalogue to determine whether they are indexed on MEDLINE. Data was analyzed using IBM Statistics version 25. Fischer’s exact test was performed to assess the distribution of publication model and indexing status. Kruskal-Wallis H test was used to assess the distribution of SJR.
Results: 207 Endocrinology journals were included; 134 SB (64.73%) and 73 OA (35.27%). 122 journals are indexed in MEDLINE. The top three publishers of Endocrinology journals are Elsevier, Springer Nature and Wiley, all of which are commercial entities. They collectively own 91/207 (43.96%) Endocrinology journals and 70/122 (57.38%) MEDLINE-indexed journals. The top three publishers own more SB than OA journals, though this difference was not statistically significant (p = 0.080). There was no significant difference in the distribution of indexing status across the top three publishers (p = 0.250) and the four publisher types (p = 0.928). There were significantly more SB than OA journals indexed in MEDLINE (p&lt;0.001). There was no significant difference in the distribution of SJR indicator across the top three publishers (p = 0.283) and publisher types (p = 0.873) (see Table 1). SB journals had significantly higher SJR indicators compared to OA journals (all journals, p = 0.002; indexed journals only, p = 0.013).
CONCLUSIONS: Endocrinology journals are largely controlled by a few commercial entities and are primarily SB. Compared to OA, SB journals have significantly higher SJR indicators, meaning they are more influential. This is an important consideration for researchers when considering where to submit their work.
Identification of Sortilin Alternatively Spliced Variants in 3T3L1 Adipocytes
Authors: Lui Ashley , Patel Rekha , Patel Niketa A 
Published: May 2021

Abstract
Type 2 diabetes mellitus (T2DM) is a chronic and progressive metabolic disease with no cure. Adipocytes play a crucial role in glycemic regulation and take up circulating glucose in response to insulin signaling. In T2DM, translocation of major glucose transporter 4 (Glut4) from cytoplasmic locations to the plasma membrane is impaired. Sortilin is an important constituent of Glut4 storage vesicles and interacts with guiding proteins to determine location of Glut4 in the trans-Golgi network. Sortilin levels are shown to affect adipocyte function. Using mouse 3T3L1 adipocytes, we demonstrate that alternative splicing of sortilin pre-mRNA results in an inclusion of an exon (17b) between exons 17 and 18 in the 10CC motif of the VPS10p domain crucial for ligand interaction. Sort17b expression correlates to insulin resistance and over-expression of Sort17b decreases glucose uptake in adipocytes. Using co-immunoprecipitation assays, we demonstrate that Sort17b is a strong binding partner of Glut4. Using bioinformatic analysis, we show that this insertion results in a novel intrinsically disordered region and has potential sites of proteolytic cleavage. Our study is the first to describe sortilin’s alternatively spliced variants in adipocytes and their effects on glucose uptake. As a broader approach, the research demonstrates the impact of a post-transcriptional event on the metabolic fate of adipocytes in conditions of insulin resistance.
Young Adult LEW.1WR1 Rats Develop Dysregulated Islet Function and Impaired Liver Insulin Responses
Authors: Wilkerson-Vidal Quiana C , Collins Genoah L , Fowler Evann , Wimalarathne Madushika M , Mercado Luis D , Gibson Helen , Martin Sidney C , Love-Rutledge Sharifa Tahirah 
Published: May 2021

Abstract
Obesity in humans can lead to metabolic problems such as glucose intolerance and insulin resistance, which may result from pancreatic islet dysregulation and reduced insulin sensitivity in the liver. LEW.1WR1 (1WR1) rats became more glucose intolerant than LEW/SsNHsd (SsNHsd) rats after 12 weeks on a moderate sucrose diet.1 We hypothesize that the 1WR1 rats develop decreased insulin sensitivity due to impaired islet function and liver responses to insulin. To test this hypothesis we measured blood hormone levels and islet and liver gene expression. The terminal blood insulin (14988+/- 4024 vs. 22703+/-5101 pg/mL; p=0.0085; n=7,7) and glucagon (127.3+/-73.31 vs. 188.6+/-46.87 pg/mL; p=0.0537; n=7,7) were higher in the the 1WR1 rats. Using qRT-PCR, we determined the islets of 1WR1 rats had 3 fold increased insulin (p&lt;0.0001; n=3,3) and glucagon (p&lt;0.0001; n=3,2) relative gene expression. Yet, the β-cell area (22.05+/-6.408 vs. 2.276 +/-1.284mm2; p=0.0016; n=3,4) was significantly reduced in 1WR1 rats. Islet Plin5 expression was upregulated in 1WR1 rats (5.388+/-0.3806 F.C.; p&lt;0.0001; n=3,3) indicating increased lipid droplet production, while Cyclin D (0.5726+/-0.08797 F.C.; p=0.0035; n=3,2) was downregulated indicating decreased cell cycle proliferation. These results indicate that the islets of the 1WR1 rats were insensitive to insulin signaling, which may have been caused by increased lipid droplets and a decrease in compensatory islet area. We also measured the relative expression of insulin-sensitive genes in the liver tissue to determine if there were alterations in liver insulin signaling. Downregulation of Irs-2 (0.5840+/-0.001045 F.C.; p&lt;0.0001; n=7,7) expression was likely caused by the upregulated fat10 gene in 1WR1 rats.2 Fat10 (2315+/-0.01380 F.C.; p&lt;0.0001; n=4,6) expression in the liver was significantly increased. Foxo1 (2.644+/- 0.001211 F.C.; p&lt;0.0001; n=7,7) expression, which is normally reduced by insulin, was upregulated which indicates reduced insulin sensitivity. Upregulated expression of Fgf21 (2.260+/-0.002376 F.C.; p&lt;0.0001; n=6,7), which improves glucose homeostasis, in the liver is why the fasting blood glucose of 1WR1 rats were not significantly different from the SsNHsd rats.1 In conclusion, 1WR1 rats show increasingly impaired metabolism over time. These rats have increased insulin and glucagon levels coupled with liver fat10 overexpression leading to impaired gene regulation of insulin-responsive genes in the liver. These changes synergistically increase susceptibility to pathological obesity and metabolic disease.
References: (1) Collins et al., Journal of the Endocrine Society. 2019 3(S1). (2) Ge, Q. et al., Frontiers in Physiology. 2018; 9(1051): 1–16.
Clinical Utility of 30-Min Postload Plasma Glucose in Paediatric Obesity
Authors: Poon Sarah Wing-yiu , Tung Joanna Yuet-ling 
Published: May 2021

Abstract
Introduction: Intermediary glucose measurements at other time points in a standard 2-hour oral glucose tolerance test (OGTT) is increasingly being investigated, and a number of studies have demonstated strong predictive value of 1-hour plasma glucose (PG) in identifying subjects with high risk of future diabetes and vascular complications. The association between 30-minute PG and incidence of diabetes is less extensively studied and all the suggested 30-minute PG cutoff values in current literature are derived from adult population. Our study aimed to evaluate the optimal cutoff value of 30-minute PG in predicting abnormal OGTT (prediabetes/diabetes) in a cohort of paediatric subjects with overweight or obesity. Since 30-minute PG could be easily performed even in a busy clinic setting, such cutoff allows clinicians identify high risk subjects who should proceed to a 2-hour OGTT.
Methods: Record of 332 paediatric subjects with overweight/obesity who had OGTT done in a tertiary unit from January 2012 to December 2018 was reviewed. Standard OGTT was performed and blood samples for PG and insulin were obtained at 0 minute, 30 minutes and 120 minutes. Subjects with prediabetic and diabetic response were considered together as a group (abnormal OGTT group) for statistical analysis. 30-min PG and insulinogenic index (IGI) were compared, and 30-min PG cutoff which predicts abnormal OGTT response was derived.
Results: Our cohort consists of 97.3% Chinese with mean age of 15.4 ± 2.3 years and mean BMI z-score of 2.7 ± 0.6. Sixty subjects (18.1%) had abnormal OGTT – out of which 47 (14.2%) and 13 (3.9%) had prediabetes and diabetes range of glycaemic response respectively. 30-minute PG was statistically higher in the abnormal OGTT group compared to the normal OGTT group (9.6 vs 7.9 mmol/L, p=0.001). IGI was statistically lower in the abnormal OGTT group compared to the normal group (262.1 vs 377.2, p=0003). 30-min PG ≥ 9.2 mmol/L predicts abnormal OGTT with best combination of sensitivity and specficity (AUC 0.77, sensitivty 62.1%, specificity 83.7%).
Conclusion: Children with abnormal OGTT reseponse showed impaired first phase insulin secretion suggestive of beta-cell loss. Instead of performing a 2-hour OGTT in every child referred for obesity, 30-min PG, with a cutoff value of 9.2mmol/L, could be used as a stratification tool in identifying high risk subjects who should return for a 2-hour OGTT in another visit.