bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemichorea Associated With Nonketotic Hyperglycemia: Rare Presentation of Uncontrolled Diabetes Mellitus
Authors: Katkar Rujuta Baban 
Published: May 2021

Abstract
Introduction: Hemichorea is usually associated with a contralateral lesion in the central nervous system and can result from infection, genetic mutation, neoplasms, neurodegeneration, stroke, metabolic disease, drug-exposure, and autoimmune disease. Nonketotic hyperglycemic (NKH) hemichorea is mainly seen in elderly patients, especially females from East Asian origin with poor blood glucose control. The general treatment measures include improving control of blood glucose and the use of neuroleptic drugs. We report a unique case of hemichorea secondary to nonketotic hyperglycemia with negative imaging changes. Case Presentation: A 72-year-old woman with history of COPD, CKD stage III, CAD, diabetes type II for more than 30 years with poor glycemic control presented with sudden onset of uncontrolled involuntary dance like movements of left upper and lower extremities and left side of the face. These activities occurred while awake and disappeared during sleep. Neurological examination found that patient has a clear verbal ability, sanity, present involuntary dance-like movements of limbs, facial, jaw, and tongue. She had normal muscle strength and mild hypotonia. Other physical examination found no abnormalities. A CAT scan of the head showed high density in basal ganglia region and brain MRI(T1-weighted) showed and hyperintensity in the right basal ganglia. Laboratory tests showed that random blood sugar was 572 mg/dL, urine sugar (4+), and negative urine ketone, Hba1c was 14%. The patient’s subsequent thyroid function tests, autoantibodies, liver and kidney function tests, anti-neutrophilic cytoplasmic antibodies, ceruloplasmin, vitamins D and B12, and folic acid found to be normal. She was diagnosed with hemichorea associated with NKH. The treatments included improving blood glucose with IV insulin and symptomatic treatment of chorea with risperidone 2mg and clonazepam 1mg every night. On sixth day of admission patient’s involuntary movements improved. Blood sugar level normalized after a week. After 10 days, her dance-like symptoms disappeared completely. She tapered off risperidone and clonazepam within 3 months and continued to control blood sugar with premixed insulin after discharge. Conclusion: In conclusion, although uncommon, chorea/ballism associated with nonketotic hyperglycemia can be the first presenting sign of unknown diabetes mellitus or can occur after weeks or even months of poor glycemic control in diabetic patients. Timely neuro imaging examination and active blood glucose control can avoid misdiagnosis and delay in treatment.
Necrotizing Pancreatitis Secondary to Dulaglutide Use
Authors: Bhat Salman Zahoor , Goudarzi Atta 
Published: May 2021

Abstract
Introduction/ Background: GLP-1 agonists are an essential component of the anti-diabetes armamentarium. Common side effects include mild gastrointestinal distress and headaches. Uncommon side effects include acute pancreatitis and can limit use. We report a case of acute severe necrotizing pancreatitis most likely attributed to dulaglutide.
Clinical Case: A 69-year-old man presented lethargic with diffuse abdominal pain associated with nausea and vomiting of 1-day duration. His past medical history consisted of type 2 diabetes, hyperlipidemia, hypertension, and hypothyroidism. His diabetes regimen included metformin, glipizide, and empagliflozin. Dulaglutide was added three months prior at 0.75 mg weekly, and the dose was increased to 1.5 mg weekly three days before presentation, the patient having received one such dose. Initial workup showed lipase 2800 units/mL, amylase 1185 units/mL, lactate 12.6 mmol/L, white blood cells 20 x 109/L, glucose 348 mg/dL, AST 30 unit/L, hematocrit 51.5%, blood urea nitrogen 24 mg/dL, and serum creatinine 1.57 mg/dL, calcium 8.1 mg/dL. No stones or CBD dilation were noted on ultrasound. Initial CT showed an enlarged pancreas with peripancreatic stranding and slightly diminished enhancement consistent with early signs of necrotizing pancreatitis. The patient became increasingly hypoxic and hypotensive and required intubation and triple pressor support to maintain adequate perfusion. On the second day of hospitalization, his hematocrit was 35.7%, blood urea nitrogen 37 mg/dL, calcium 6.8 mg/dL, and bicarbonate 21 mmol/L. AST and ALT peaked at 209 and 398 unit/L respectively. Calculated 48 hours Ranson’s score was 7. He completed 7 days of meropenem for necrotizing pancreatitis. He developed cholecystitis secondary to inflammatory damage of the biliary tract and received a cholecystostomy tube. A follow-up CT scan 7 days after the initial scan showed a prominent pancreas with extensive inflammation and without cysts, with several areas of nonenhancement/poor perfusion in the pancreatic head consistent with pancreatic necrosis. The patient made a full recovery and was discharged to a rehabilitation unit. Investigation into other causes of pancreatitis revealed triglycerides 104 mg/dL, a normal distribution of IgG subclasses (IgG4 36 mg/dL), no significant alcohol use, and no family history of pancreatitis.
Conclusion: Pancreatic safety studies of dulaglutide have shown a good safety profile1. However, FDA safety warning exists on GLP-1 agonist prescriptions. Necrotizing pancreatitis with GLP-1a is rarely reported. We present a case of severe necrotizing pancreatitis due to dulaglutide use with the existence of temporality, after ruling out other causes of pancreatitis.
Reference: 1. Nauck MA et al. Assessment of Pancreas Safety in the Development Program of Once-Weekly GLP-1 Receptor Agonist Dulaglutide. Diabetes Care 2017;40:647–54.
Phosphoinositide 3-Kinase Inhibitor-Induced Hyperglycemia
Authors: Shey Susan , Kim Sarah , Kim Julie , Murphy Elizabeth J 
Published: May 2021

Abstract
Background: Phosphoinositide 3-kinase inhibitors (PI3Ki) are a new class of medications used to treat HR positive, HER2 negative, PIK3CA mutated advanced or metastatic breast cancer. Inhibition of PI3K, a key enzyme in the insulin signaling pathway, leads to disruption of glucose metabolism and frequently hyperglycemia. Here we present a case of difficult to treat PI3Ki-induced hyperglycemia from alpelisib.
Case: 78 yo woman with metastatic breast cancer and NASH cirrhosis was referred for new hyperglycemia after starting alpelisib. Baseline HbA1c was 6%. She was initially started on metformin and glipizide without any blood glucose (BG) improvement. After 6 days, alpelisib was held with BG recovery. Alpelisib was restarted 1 month later, again resulting in hyperglycemia. Dapagliflozin treatment quickly improved BG to &lt;200 mg/dL, but she developed candida intertrigo so it was discontinued and insulin was started. She also began a ketogenic diet. After 2 weeks of insulin titration, she had stable BG &lt;200 on 47u of insulin a day.
Within days, she was admitted with encephalopathy and a UTI which improved with antibiotics and lactulose. Alpelisib, initially held, was restarted on day 2 resulting in worsening hyperglycemia. Inpatient BG ranges on alpelisib were: fasting 191–358, pre-lunch 260–383, pre-dinner 308–404, and bedtime 330–355, despite a rapid increase of basal-bolus insulin and initiation of metformin, pioglitazone, and a ketogenic diet. Total daily insulin needs went from 18u, to 124u by day 5 of alpelisib. Imaging revealed new bone and hepatic metastases. With difficult to control hyperglycemia and cancer progression, alpelisib was discontinued with rapid improvement of hyperglycemia.
Discussion: Hyperglycemia is a common adverse and on target effect of PI3Ki use. PI3K inhibition leads to acute hyperglycemia within hours. The pancreas responds by increasing insulin release. Transient hyperglycemia can occur in all patients, but may become persistent with underlying insulin resistance, as seen in our patient. T2DM (with HbA1c &gt;6.5%) and all T1DM patients were excluded in alpelisib trials yet diabetes is not a formal contraindication. Providers should be vigilant for this complication in patients with diabetes and prediabetes. It has been suggested that exogenous insulin and medications that increase endogenous insulin secretion may be counterproductive because they overcome PI3Ki-induced insulin signaling disruption and compromise anti-tumor effectiveness of PI3Ki. Thus, the preferred and most effective treatment may be an SGLT2i as was the case in our patient. Insulin sensitizers and a ketogenic diet can potentially also be effective. Increasing insulin may have limited efficacy as seen with our patient. Future studies are needed to determine the best way to manage PI3Ki-induced hyperglycemia and the effect of potential treatments on anti-tumor efficacy.
Pseudohypoglycemia: A Simple Approach to Complex Phenomenon
Authors: Alkaissi Hussam R , Chillumuntala Seeta , Kubbar Alaa , Banerji MaryAnn 
Published: May 2021

Abstract
Background: Pseudohypoglycemia is a condition where the measured glucose level is falsely lower than the actual level. It can be due to impaired circulation or in vitro glycolysis. Clinical Case: Patient 1: A 58-year-old male with a past medical history of sickle cell trait was admitted for alcohol intoxication. Low blood glucose levels were found on finger stick point-of-care testing (POCT). Fasting and postprandial glucose levels were between 17 and 60 mg/dL. The patient was asymptomatic, alert with no tremor, palpitation, or sweating. Glucose POCT was repeated from the earlobe each time a low finger stick level was found, showing normal glucose levels ranging between 85 to 115 mg/dL, confirmed with venous blood glucose measurement. On examination, the patient had mild skin thickening of the hands, with no acrocyanosis, calcinosis, or finger ulceration—normal peripheral pulses with no signs of heart failure. Lab results showed macrocytic anemia, otherwise normal metabolic panel. ANA, anti-Scl-70, and anticentromere antibodies were negative. Patient 2: A 91-year-old female admitted for decompensated heart failure was incidentally found to have fasting glucose levels on finger stick POCT ranging between 30–50 mg/dL. Postprandial glucose on finger stick POCT was ranging between 55–120 mg/dL. Venous glucose levels were ranging between 90 and 180 mg/dL. The patient was alert and asymptomatic. Examination showed bilateral acrocyanosis, poor peripheral circulation with capillary refill &gt; 5 seconds, pitting pedal edema, elevated JVP, and crackles on chest auscultation. Labs showed BNP levels of 1130 pg/mL (n &lt; 100 pg/mL), with ejection fraction of about 35% on echocardiography. Heart failure management was optimized, and warming of the hands with blankets improved peripheral circulation, with capillary refill &lt; 2 seconds, and resolution of cyanosis coinciding with matching of finger stick POCT glucose levels to that of venous blood. Both patients were asymptomatic at the time of low POCT glucose and thus did not fulfill Whipple’s triad (measured hypoglycemia, symptomatic, a reversal of symptoms on glucose administration). Furthermore, they had no history of diabetes or the use of any hypoglycemic agents. Thus, normal venous blood glucose levels documented at the time of low POCT glucose lead to a diagnosis of pseudohypoglycemia. The etiology in patient 1 was likely due to peripheral vascular disease. In patient 2, the cause was likely due to congestive heart failure, with poor peripheral perfusion.
Clinical Lesson: Low glucose levels are frequently encountered in clinical practice. It is essential to check if the non-diabetic patient is symptomatic or not. It is worth checking glucose levels from other sites in asymptomatic patients who do not fulfill Whipple’s triad before preceding into an elaborate hypoglycemia work-up.
SARS-CoV-2 Trigger in Severe Insulin Resistance With Acute Haemolytic Crisis in Diabetes and Glucose-6-phosphate Dehydrogenase Deficiency
Authors: Joshi Hareesh , Earle Kenneth 
Published: May 2021

Abstract
Background: We report a case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as trigger for increased insulin resistance and severe haemolytic crisis in a male with type 2 diabetes mellitus and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Clinical Case: A 64-year-old man (BMI 25kg/m2, weight 75kg) with past medical history of type 2 diabetes mellitus (on metformin and sitagliptin; glycated haemoglobin 51 mmol/mol, n&lt;42mmol/mol), hypertension, G6PD deficiency and gout was admitted to hospital with COVID pneumonitis and type 1 respiratory failure giving 5 days’ history of cough, shortness of breath, fatigue and tiredness. As per hospital guidelines, the patient was treated with amoxicillin/clavulanate 625mg three times daily and doxycycline 100mg once daily. Hydroxycholoroquine was not given in view of G6PD deficiency. There was no evidence of diabetic ketoacidosis and a short-acting insulin sliding scale was initiated at 2U/hr. Continuous positive pressure ventilation was offered for next 72 hours, however the patient failed to improve and required transfer to intensive care unit for intubation and mechanical ventilation. Computer tomography scan of pulmonary artery excluded embolism. The patient was fed via nasogastric tube post intubation. On day 8, the patient experienced a sudden drop in haemoglobin levels from 132 g/dl on day 1 to 68 g/dl, requiring multiple blood transfusions. The blood results demonstrated evidence of haemolysis with a rise in total and direct bilirubin and lactate dehydrogenase levels. The peripheral blood smear showed numerous bite cells with polychromasia suggesting an acute haemolytic crisis in the context of G6PD deficiency. A medication review revealed no evidence of drug-induced haemolysis. Later the patient was started on dexamethasone 6mg once daily (day 11) and on remdesivir 100mg once daily (day 15). During this time, the patient’s insulin infusion requirements had progressively increased from 2U/hr to 8U/hr (equivalent to 192 units/24 hr). On day 22, the patient’s clinical condition deteriorated with septicaemia requiring extended course of antibiotics. At this time, continuous insulin infusion was stopped and intermediate acting insulin (insulatard 36U twice daily; later increased to 48U twice daily) was started. In the next 10 days, the patient made good clinical recovery from sepsis with stable haemoglobin and blood sugar levels. He was extubated and transferred for rehabilitation. The patient was successfully weaned off insulin in the community with optimal diabetes control. Conclusion: This is a case demonstrating the possible role of SARS-CoV-2 in increased insulin resistance and severe haemolytic crisis on background of diabetes and G6PD deficiency.
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

Abstract
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

Abstract
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

Abstract
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.