bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Diabetes Type 3 After SARS-COV-2 Pancreatic B Cell Injury
Authors: Zayas Francisco Jose , Hernandez-Negron Marianne , Garcia Michelle Marie Mangual 
Published: May 2021

Abstract
SARS-COV-2 has caused millions of deaths in less than one year, yet little is known about the long-term consequences survivors may suffer. The novel coronavirus uses the ACE2 receptor to infect human cells, allowing it to target organ systems with such receptors including the respiratory, cardiovascular, gastrointestinal and endocrine system. The purpose of this case report is to describe the long-term implications COVID-19 may cause in the endocrine system. A 46-year-old woman was referred to our clinic due to abrupt uncontrolled blood glucose levels ranging from 200-550mg/dL after being infected with COVID-19 for approximately 10 weeks. She has a past medical history of Diabetes Mellitus Type 2 which was diagnosed 3 years ago and was well controlled with diet. Present history reveals polyuria, polydipsia, tiredness and a decreased appetite. Laboratory values show HbA1C 12, negative islet cell antibodies/GAD antibodies, low C-peptide, high TSH, normal FT4 and positive anti-TPO antibodies/thyroglobulin antibodies. The sudden loss of blood glucose control along with low c peptide levels without evidence of autoimmunity support the diagnosis of Pancreatic Diabetes. SARS-COV-2 infection may cause Diabetes Type 3, rendering a patient dependent on insulin use for life. Covid-19 survivors, with or without a previous history of endocrinopathy, should be evaluated for possible long-term sequels of infection as the virus targets tissues throughout the body.
Diabetic Ketoacidosis With Alpelisib
Authors: Jeun Rebecca , Lavis Victor Ralph , Thosani Sonali 
Published: May 2021

Abstract
Background: Hyperglycemia is a frequently reported adverse effect of alpelisib, an isoform specific phosphoinositide 3 kinase inhibitor, which is recently approved for use in hormone receptor positive advanced or metastatic breast cancer. Though two patients in clinical trials with alpelisib developed diabetic ketoacidosis (DKA), there have been no case reports to date characterizing this complication after drug approval. We present the first case of DKA in patients on alpelisib therapy.
Clinical Case: A 55-year-old woman with a history of hormone-receptor positive metastatic breast cancer was started on treatment with fulvestrant and alpelisib. The patient did not have any previous history of diabetes nor gestational diabetes, though she had evidence of prediabetes prior to starting treatment. Patient was non-obese and had a family history of type 2 diabetes. Baseline hemoglobin A1c was 5.6% (n &lt;5.7%) with impaired fasting glucose of 108 mg/dl (n&lt;105 mg/dL) immediately prior to starting therapy. One week after starting alpelisib, she presented to the emergency center in diabetic ketoacidosis. Initial laboratory evaluation showed serum glucose 690 mg/dl, anion gap metabolic acidosis, with undetectable serum bicarbonate and ketonuria. C-peptide on hospital day 1 was found to be 2.8 ng/ml (n 0.5 - 3.4 ng/ml) with a concurrent glucose of 479 mg/dl. GAD65 and Islet Antigen 2 antibodies were negative. Diabetic ketoacidosis quickly resolved with continuous insulin infusion and stopping alpelisib. The patient was able to come off all insulin therapy prior to discharge and was discharged on metformin with adequate glycemic control.
Conclusions: Current manufacturer guidelines for alpelisib recommend screening for diabetes mellitus at baseline and monitoring blood glucose and/or fasting plasma glucose weekly for the first two weeks of treatment and monthly thereafter. However, patients with no pre-existing history of diabetes mellitus may be at risk for life-threatening hyperglycemic crises which may develop within a week of initiation of alpelisib and more frequent monitoring may be indicated. The hyperglycemic effect of alpelisib appears to be reversible upon stopping the drug.
Diabetic Myonecrosis: A Rare Complication of Uncontrolled Diabetes Mellitus
Authors: Tumyan Gayane , Oubre Aaron , Feldman Mark 
Published: May 2021

Abstract
Background: Diabetic myonecrosis is a rare complication of long-standing, poorly controlled diabetes mellitus, and is more common in patients with microvascular complications. The diagnosis is frequently missed due to symptoms mimicking other conditions associated with diabetes mellitus.
Clinical Case: A 31-year-old woman with a past medical history of long-standing type I diabetes mellitus, end-stage renal disease, diabetic retinopathy, and cataracts presented to our hospital with a chief complaint of right thigh pain and swelling for a week. She did not have any other relevant symptoms and denied a history of trauma. On admission, physical examination revealed right thigh edema, induration, tenderness on palpation, more pronounced in the medial aspect of the thigh, and decreased range of motion of the right hip. Laboratory analysis showed leukocytosis of 13.29 k/uL (normal = 4.23 - 9.71 k/uL) with neutrophilic predominance of 91.4 %, elevated inflammatory markers (ESR &gt; 130 mm/h (normal = 0 - 30 mm/h), CRP 33.84 mg/dL (normal &lt;= 0.49 mg/dL)) and elevated CK levels of 1675 U/L (normal = 29 - 168 U/L). Additionally, the patient was anemic with a hemoglobin level of 8.4 g/dL (normal = 11.0 - 15.0 g/dL) and had a creatinine level of 2.67 mg/dL (normal = 0.55 - 1.11 mg/dL). Hemoglobin A1C level was 10.8 % (normal = 4.0 - 6.0 %). Blood cultures were drawn and did not grow any organisms. A doppler ultrasound of the right leg was negative for a deep venous thrombosis. CT angiogram of right lower extremity revealed diffuse calcifications in the walls of small and medium vessels and edematous changes in thigh musculature associated with subcutaneous edema. Noncontrast MRI revealed localized edema within the vastus medialis, sartorius, and right thigh adductor muscles. The patient improved with analgesics, rest, and gentle physical therapy. She was counseled on compliance with insulin and advised for a close follow up with her endocrinologist.
Conclusion: This case reinforces the importance of including diabetic myonecrosis in the differential diagnosis of acute to subacute nontraumatic muscular pain in diabetic patients, particularly in patients with poor glycemic control and known complications. While muscle biopsy can be performed for histological confirmation, the typical imaging findings and clinical presentation can lead to the diagnosis, making further invasive testing unnecessary. In most described cases, the course of this condition is self-limiting.
Hemi Chorea and Hemi Balllismus: A Rare Presentation of Prolonged Uncontrolled Hyperglycemia
Authors: Karam Jocelyne Georges , Eze-Raphael Chinenye Uchenna , Calliste Chrystel 
Published: May 2021

Abstract
Background: Hemi chorea and hemiballismus interestingly, are rare presentations of severe chronic persistent hyperglycemia which resolves with correction of hyperglycemia in most cases.
Clinical Case: Here we report a case of a 67 YO woman with a PMH of prolonged uncontrolled DM evidenced by average baseline HbA1c of 14.6% (n&lt;5.7%) presenting with dance-like movements of the left arm and mouth deviation. Initially the patient presented as a stroke code. Vital signs were unremarkable. On Physical exam, there was mild L face weakness and obvious abnormal hand movement. Other neurological exams were unremarkable for stroke. MRI showed the typical decreased T2/flair signal within the right frontal lobe, white matter, right caudate head, and bilateral lenticular nucleus with mild increased T1 signal of the right caudate and lenticular nucleus compatible with hyperglycemic nonketotic hemichorea hemiballismus. Her significant admission lab values of random blood glucose of 306mg/dl (n 74-200mg/dl), HbA1c of 18.7% (n&lt;5.7%), urine sugar &gt;1000 (n neg mg/dl), absence of ketonuria and acidosis also support the diagnosis. With improvement in her blood sugar control, there was a significant decrease in her abnormal hand movements. However, sugar control was not enough as there was the need for additional medications to improve the chorea such as risperidone and tetrabenazine. Eventually over the course of many months of tight glucose control, there was significant symptomatic improvement. While the exact etiology is unclear, the hyperintensity usually seen on head CT scan and the pathognomonic T1 hyperintensity of the basal ganglia on MRI is postulated to be related to metabolic abnormalities caused by hyper viscosity of the blood in the end arteries supplying the basal ganglia. Many case reports associated movement disorders to chronic persistent hyperglycemia but there are many other cases that described hemiballismus in acute cases of hyperglycemia or persisting despite adequate glycemic correction. Most of the patients described had an underlying markedly elevated HbA1c as a common factor which suggests that a prolonged period of uncontrolled hyperglycemia may be necessary to produce hemiballismus. When thinking of complications of diabetes, we often think of CAD, ESRD, CVD, DKA and HHS. We aim to create an awareness of this rare association and to recognize hemiballismus as one of the varying presentations of severe hyperglycemia in order to ensure early diagnosis and treatment of this condition.
Conclusion: Hemichorea and hemiballismus are increasingly becoming popular as one of the many complications of severe chronic or acute hyperglycemia. This warrants recognition in literature.
Hyperglycemia With Use of Vagal Nerve Stimulator
Authors: Castellanos-Diaz Jessica , Amole Morolake , Surabhi Swapna , Kadiyala Sushma 
Published: May 2021

Abstract
Introduction: In patient with diabetes and refractory epilepsy requiring vagal nerve stimulator (VNS), glycemic management can be challenging. Clinical experience is limited in this scenario. Case Report: A 67-year-old male, BMI 30 kg/m2, with history of type 2 diabetes and hemispheric hemangioma complicated by seizure disorder is referred to our diabetes clinic for evaluation of persistent hyperglycemia. The patient reports 25-year history of seizures that have been difficult to control with antiepileptic drugs alone and eventually requiring VNS placement. Patient has normal kidney (eGFR &gt; 60mL/min) and liver function. His antiepileptic drug regimen consisted of gabapentin and as needed lorazepam. He was never on glucocorticoids. Glycated hemoglobin (HgA1c) at our initial evaluation was 10.1%. His anti-glycemic regimen consisted of glipizide monotherapy. Fasting and pre-prandial blood glucose were in the 200-400mg/dL range with occasional values higher than 500mg/dL. This was confirmed with 14-day continuous glucose monitoring that showed average blood glucose of 287mg/dL with 100 percent above target (higher than 180 mg/dL). We optimized therapy by adding once daily glargine, pioglitazone and continued glipizide. At follow up visit, HgA1c still remained high at 10.5%, despite medication adherence. Patient emphasized that hyperglycemia was related to VNS use and given documented hyperglycemia with blood glucose range 500–600 mg/dL when on higher output current of 2 milliamps, his neurologist approved a trial off VNS for 4 weeks. His glucose improved to average less than 200 mg/dL and HgA1c decreased to 9.1% on the same anti-glycemic regimen. Device was re-started due to recurrence of seizures, however the output current and “on time” were reduced to minimal effective range for optimizing seizure therapy while avoiding hyperglycemia. Subsequent HgA1C improved to 8.7%. Discussion: VNS is a FDA approved device for epilepsy and depression. It works by intermittent stimulation or “on/off” periods. In animal studies, elevation of blood glucose was noted with afferent stimulation. Conversely, efferent activation lowers blood glucose. There are limited human studies on the effects of vagal nerve stimulation on glycemic control. The few available, showed variation in blood glucose based on output current and length of on/off period. This should be factored in during glycemic evaluation and management and close collaboration with neurology is essential. Reference: (1) Strauss H, et al. Cervical Vagal Nerve Stimulation Impairs Glucose Tolerance and Suppresses Insulin Release in Conscious Rats. Physiological Reports 2018; 6(24): 1–9 (2) Strauss H, et al. Effect of Vagus Nerve Stimulation on Blood Glucose Concentration in Epilepsy Patients - Importance of Stimulation Parameters. Physiological Reports 2019; 7(14): 1–10
Is Hypoglycemia Caused by G6PD Deficiency?
Authors: Agarwal Shubham , Unjom Zubina , Gilden Janice L , Singh Aditi , Shaik Shayaan 
Published: May 2021

Abstract
Background: Individuals with G6PD deficiency are mostly asymptomatic but develop hemolytic anemia with the use of certain medications, chemicals, or food. Hemolytic anemia episodes in patients with G6PD deficiency have been observed to occur following hypoglycemia. Case: An 18-year-old, vigorously exercising African American male was referred to the endocrine clinic for post-prandial hypoglycemia (Blood glucose (BG) of 47 mg/dl) accompanied by palpitations, lightheadedness, dyspnea, diaphoresis, and tremulousness. He admitted to having short symptomatic episodes, almost daily over four years. His mother has sickle cell trait, and due to the need for blood typing, a qualitative direct fluoroscopic screening test was positive for G6PD deficiency. Physical examination revealed a height of 5’2” with a weight of 126 lbs. (BMI: 22.7 kg/m2), blood pressure of 97/55 mmHg, and heart rate of 62/minute. The patient was a normal male with low set ears, and no other abnormalities, except for questionable non-genetic short stature. Fingerstick BG was 62 mg/dl. Lab tests showed a fasting BG of 90 mg with concomitant proinsulin of 8.2 pmol/l (≤ 18.8 pmol/l), fasting insulin of 8.98 mIU/l (≤ 25 mIU/l), 2-hour post-prandial insulin of 33.4 µIU/ml (5.0–55.0 µIU/ml), and a c-peptide 1.24 ng/ml (0.81–3.85 ng/ml). Uric acid, TSH, Free T4, LH, FSH, Prolactin, IGF-1, PTH, free and total testosterone were all normal. Fasting cortisol level was normal with an elevated ACTH of 72 pg/ml (0–47 pg/ml), low 25-hydroxyvitamin D at 18.5 ng/ml (30–100 ng/ml), and a flat oral glucose tolerance test. A continuous glucose monitor revealed average daily glucose of 85 mg/dl with 34% of the time spent &lt; 80 mg/dl. A high carbohydrate diet with frequent meals improved symptoms with normal fingerstick BG. However, due to the concern that hypoglycemia can be related to G6PD deficiency, hemoglobin electrophoresis, and gene testing for G6PD were done to confirm this diagnosis, and they were both normal. In addition, a bone density scan was done, which revealed osteopenia. He was started on vitamin D supplementation. Conclusion: Case reports exist of G6PD deficient hospitalized patients with type 1 diabetes mellitus and DKA in recovery, who have had new onset hemolytic anemia, proposing that relative hypoglycemia can be responsible for this effect. Multiple screening tests have been developed for the detection of G6PD deficiency, which assay the normal function of the enzyme and reduction of NADP to NADPH. However, confirmatory testing needs to be conducted if the screening test is positive. Although this adds to the burden of testing, screening tests can result in false positives and lead to a misdiagnosis, as in our case. References: Messina MF et al. Hemolytic crisis in a non-ketotic and euglycemic child with glucose-6-phosphate dehydrogenase deficiency and onset of type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2004 Dec;17(12):1671–3
Mitochondrial Diabetes: The Clinical Spectrum of MIDD and MELAS in Association With the A3243G Mutation
Authors: Bukhari Khulood , Pennant Marjorie 
Published: May 2021

Abstract
Introduction: Maternally inherited diabetes and deafness (MIDD) is a multisystem disorder characterized by insulinopenia and sensorineural hearing loss. This rare form of monogenic diabetes is most commonly associated with the A3243G mutation of mitochondrial DNA (mtDNA). The same mutation is seen in 80 percent of patients with MELAS (Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes). MIDD and MELAS have overlapping features suggesting a continuum of expression for the A3243G mutation. Clinical Case: A 41-year-old male was referred for genetic testing and counseling by his ophthalmologist following detection of bilateral punched-out retinal pigment epithelium (RPE) lesions on routine exam. His medical history was significant for type 1 diabetes mellitus (T1DM) diagnosed at the age of 21 and bilateral sensorineural hearing loss diagnosed at the age of 38. The referral was triggered by patient reported family history of MELAS in two of his brothers who were both diagnosed at the age of 10 and died at the ages of 20 and 27. Whether the patient was previously tested during early childhood remains unclear. His medical history was negative for stroke-like episodes or seizures. Neurologic evaluation revealed mild fluent aphasia with paraphasic errors and some comprehension difficulties. MRI of the brain without contrast showed no focus of restricted diffusion. Mitochondrial DNA sequence analysis was performed. A pathogenic variant (m.3243 A&gt;G) was detected in the MT-TL1 gene at approximately 25% heteroplasmy. The patient was advised to avoid metformin given increased risk for lactic acidosis. He was also instructed against use of statins. At the age of 45, the patient presented to the emergency department (ED) with a complaint of headache, vertigo and incoordination. Physical examination revealed left homonymous hemianopsia, right horizontal nystagmus and bilateral upper extremity dysmetria. MRI of the brain without contrast showed a large area of predominantly cortical restricted diffusion involving the right temporal and occipital region with associated T2/FLAIR hyper-intensity. Cross over between the PCA and MCA territories was suggestive of a stroke-like episode related to MELAS. The patient received a bolus of IV arginine at 0.5 g/kg followed by an IV infusion of 0.5 g/kg/day for 3 days. He was later transitioned to oral arginine 5g three times daily and was discharged to a rehab facility. Clinical Lesson: This case demonstrates the evolution of MIDD to MELAS, supporting the concept that both syndromes represent a spectrum of the same disease. A few case reports describe the progression of MIDD to MELAS. Why some patients develop MELAS and others develop MIDD is unclear but may be related to heteroplasmy. Early identification of MIDD and MELAS is crucial given associated comorbidities and unique management issues.
Severe Fasting Hypoglycemia Mimicking Insulinoma in Three Patients With Insulin Autoimmune Syndrome
Authors: Rossini Alessandro , Cassibba Sara , Scaranna Cristiana , Corsi Anna , Bellante Rosalia , Trevisan Roberto 
Published: May 2021

Abstract
Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by the presence of insulin autoantibodies (IAA) in patients without prior exposure to exogenous insulin. Differential diagnosis with other causes of hypoglycemia may be complex. We report three IAS cases with severe fasting hypoglycemia, referred to our Unit for the diagnostic workup of insulinoma. All three patients (two women and a man, age 66, 44, and 50 years) had history of severe fasting hypoglycemia leading to loss of consciousness along with weight gain. Both insulin and C-peptide were high, but their levels varied greatly among patients, ranging from 24 to 1500 μU/ml (n.v. &lt;16.3) and from 11 to 27 ng/mL (n.v. &lt; 4,2), respectively. Imaging studies for insulinoma were negative. In all patients, evidence of elevated IAA (ranging from 310 to 660 UA, n.v. &lt; 5) allowed diagnosis of IAS. Two patients were taking alpha lipoic acid, a sulphydryl compound consistently associated to IAS, while in the other the HLA-DRB1*0403 haplotype, conferring susceptibility to IAS, was detected. Continuous monitoring glucose (CGM) (iPro2; Medtronic Diabetes, CA, USA) showed in all patients the presence of prolonged hypoglycemia (with time spent with blood glucose below 54 mg/dL ranging from 9 to 20% of total monitoring time), and in one case the coexistence of high glucose levels after meals. One patient responded well to diazoxide treatment, while the others required both chronic steroid therapy and the use of plasmaphereses. Conclusion: Clinical manifestations of IAS vary widely among patients, without a direct correlation between symptoms severity and levels of both insulin and IAA; prandial hyperglycemia may also be present, leading to increases in glycated hemoglobin. Our patients displayed severe fasting hypoglycemic attacks that initially posed the suspicion of insulinoma. The assessment of IAA is thus mandatory in cases of fasting hypoglycemia, before proceeding to more expensive and probably unnecessary diagnostic and therapeutic procedures. CGM is a useful tool in evaluation and management of IAS, allowing the assessment of hypoglycemia duration and the detection of the wide glycemic variability secondary to the complex mechanism of insulin binding to IAA.
Severe, New-Onset Diabetes Mellitus Triggered by COVID-19 Infection Followed by Euglycemia Upon Recovery: A Case Report
Authors: Yu Ian , Sutherland Anne , Diaz Monica C Abreu , Cespedes Lissette Maria 
Published: May 2021

Abstract
Background: New-onset diabetes mellitus (DM) and severe metabolic complications in association with COVID-19 has been reported in the literature. Studies indicate a bidirectional relationship between COVID-19 and DM. Not only does severe DM lead to an increased risk for COVID-19 complications, but COVID-19 infection itself may precipitate new-onset DM. Clinical Case: A 45-year-old male with no known past medical history and normal body mass index presented after being found unresponsive at home. One week prior to admission, he tested positive for SARS-CoV-2 virus. On admission, laboratory evaluation showed: serum glucose 1090 mg/dl [70–109 mg/dL], anion gap 31 [&lt;12], serum sodium 159 meq/L [133–145 meq/L], serum bicarbonate 18 meq/L [23–30 meq/L], creatinine 2.9 mg/dL [0.7–1.2 mg/dL], serum osmolality 438 mosm/k [280–295 mosm/k], venous pH 7.29 [7.32–7.42], venous bicarbonate 20 mmol/L [24–28 mmol/L], lactic acid 5.0 mmol/L [0.5–2.2 mmol/L], serum acetone positive 1+, urine ketone 20, hemoglobin 16.1 g/dL [14–18.0 g/dL] and HbA1c 13.5% [4.8–5.9%]. A diagnosis of diabetes with hyperosmolarity was made and he was admitted to the medical intensive care unit for treatment. Rapid resolution of hyperglycemia and hyperosmolarity was achieved with insulin infusion and intravenous fluids. He was transitioned to subcutaneous insulin on hospital day 2 and glycemic control was maintained using a basal/bolus insulin regimen. However, he experienced a prolonged two-month hospitalization due to complications including acute respiratory distress syndrome requiring mechanical ventilation and tracheostomy placement, pleural effusions with need for chest tube placement, and acute renal failure requiring short-term hemodialysis support. He was discharged to a rehabilitation facility on insulin glargine 15 units daily. Two-months after discharge, no weight changes were noted. Insulin was discontinued due to fasting serum glucose around 100 mg/dL and HbA1c 5.9%. Six-weeks later, a random serum glucose was 135 mg/dL and HbA1c 6.6%. He remains off glucose-lowering medications to date. Conclusion: We report an interesting case of new-onset diabetes with hyperosmolarity associated with COVID-19 infection with rapid achievement of euglycemia upon resolution of viral infection. Our case adds to growing evidence demonstrating a possible diabetogenic effect due to COVID-19 infection. There is also a complex interplay between SARS-CoV-2 virus and DM leading to a higher risk for complications. Questions remain regarding the long-term effects of COVID-19 on glucose metabolism. Patients with similar clinical presentations warrant close follow-up since it may be possible to de-escalate or discontinue hypoglycemic agents.