bluuebunny/crossref_metadata_2025 huggingface dataset:
Abducens Nerve Palsy as the First Manifestation of Type Two Diabetes Mellitus
Authors: Ibrahim Amira , Loseva Victoria
Published: May 2021

Introduction: Diabetes mellitus has varied presentations at different times from onset. One of the uncommon presentations is cranial nerve palsy secondary to microvascular ischemia. Approximately 20% of isolated abducens nerve palsies are secondary to vascular microangiopathy. Clinical Case: A 53-year-old female with no significant past medical history presented to the emergency department with concerns of double vision. The patient first noticed her symptoms five days prior to presentation. The patient endorsed blurry vision and stated that she has double vision in certain gazes that resolves with shutting either eye. Furthermore, she has also developed headaches during that period, described as a pressure-like sensation in her forehead and behind her eyes. She otherwise denied any tearing, redness, or pain. On review of systems, she denied numbness, tingling, changes in hearing, changes in speech, or extremity weakness. Due to the persistence of symptoms the patient presented to the emergency department. On exam, the patient’s vitals were normal. Pupils were equal and briskly reactive to light with no relative afferent pupillary defect. External examination was unremarkable without scalp tenderness, proptosis, or ptosis. Color vision was intact. Ocular motility testing revealed limited abduction of the left eye causing double vision on lateral gaze. Confrontation visual fields were full in each eye. Bilateral lower extremity exam revealed decreased sensation in the sole of the foot. The rest of the physical exam was unremarkable. Laboratory work revealed blood glucose level of 305 mg/dl (Reference range 70–99 mg/dl). HBA1C was 12.3% (Reference range 3.8–5.6%). CT head and CTA of the neck was performed and were unremarkable. Given the normal imaging and findings on examinations, her ocular motor findings were attributed to diabetes mellitus. The patient was started on insulin, aspirin, and received diabetic education for lifestyle modification, and was scheduled for outpatient follow up. The patient’s acute isolated left sixth cranial nerve palsy was most likely owing to microvascular ischemia from previously undiagnosed diabetes mellitus. A study of 59 patients with an isolated sixth cranial nerve palsy showed a 6-fold increase in the odds of having diabetes compared with controls.(1) Conclusion: Given the infrequent presentation of Diabetes with Abducens nerve palsy, diagnosis is usually delayed with the expense of ordering costly investigations that put a financial and psychological burden on patients. Thus, we urge clinicians’ awareness when encountering cases of isolated cranial nerve palsies. References: 1) Sanders SK, Kawasaki A, Purvin VA. Long-term prognosis in patients with vasculopathic sixth nerve palsy. Am J Ophthalmol. 2002;134(1):81–84.
Acute Sensorineural Hearing Loss - an Unusual Presentation of Uncontrolled DM
Authors: Arudkumaran Dharscika , Chang Albert , Umadat Deviani , Eschler Deirdre Cocks
Published: May 2021

Background: Diabetes mellitus (DM) is a systemic metabolic disorder that possesses macro- and microangiopathic consequences. Studies have demonstrated that a relationship exists between sensorineural hearing loss (SNHL) and DM, particularly in patients of older age, longer disease duration, and uncontrolled DM. The pathophysiology of DM related hearing loss is poorly understood, however proposed mechanisms include ischemia, fibrosis, demyelination, and atrophy of the eighth cranial nerve. We however, present a case of acute, transient sensorineural hearing loss in the setting of diabetic ketoacidosis that resolved with blood glucose control.

Clinical Case: A 34-year-old male with type 2 diabetes mellitus (A1c 6.5% -diagnosed 6 months prior), hypertension, hyperlipidemia, and morbid obesity presented with shortness of breath and acute hearing loss without tinnitus, after being treated for pneumonia and otitis media with a course of levofloxacin for 7 days. On presentation, patient was tachypneic and tachycardic. Physical examination was significant for mild erythema of the right tympanic membrane without bulging, fluid level, mastoid tenderness, or discharge. Laboratory values were significant for hyperglycemia with blood glucose of 628 mg/dL(n 70–99 mg/dL), A1c 15.9% (n 4.8–5.6%), bicarbonate 8 mmol/L (21–31 mmol/L), anion gap 37 mmol/L (9–16 mmol/L), beta-hydroxybutyrate 11.7 mmol/L (0.02–0.27 mmol/L). Venous gas was suggestive of metabolic acidosis, urinalysis was positive for moderate ketones and glucose >500 mg/dL. The patient was diagnosed with diabetic ketoacidosis and was started on an insulin drip. An audiogram revealed profound bilateral sensorineural hearing loss. A Computerized tomography (CT) scan of the bilateral temporal bones was negative for abnormalities, and a magnetic resonance imaging (MRI) of the brain was negative for morphologic abnormalities of 7th and 8th cranial nerves. Infectious and rheumatologic etiologies were excluded with normal syphilis FTA-ABs, Lyme PCR, Rheumatoid factor, ANCA, and ANA. The patient received one dose of empiric prednisone. His hearing improved after 2 days with normalization of blood glucose to a range of 100–200 mg/dL. A repeat audiogram and auditory brainstem response showed significant improvement with normal bilateral hearing.

Discussion: SNHL in DM typically presents in a gradual progression with bilateral involvement, affecting higher frequencies. In patients with DM, studies show that chronicity (greater than 10 years) is strongly associated with SNHL. Other variables include older age and HbA1c greater than 8%. This is the first case to demonstrate acute bilateral SNHL, associated with uncontrolled type 2 diabetes mellitus, which resolved after blood glucose control. In the appropriate context, clinicians should consider significant hyperglycemia as a possible etiology of acute hearing loss.
Alpelisib-Induced Diabetic Ketoacidosis
Authors: Espinosa Luis Borges , Vendrame Francesco
Published: May 2021

Introduction: Alpelisib is a alpha-specific phosphoinositide 3-kinase inhibitor (PI3K) recently approved for patients with advanced or metastatic breast cancer with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and activating mutations in the PIK3CA gene. PI3K is involved in the insulin receptor signaling pathway that leads to glucose uptake. Hyperglycemia is a frequent adverse effect of Alpisilib but diabetic ketoacidosis (DKA) is considered a rare occurrence.

Case ReportA 53 year-old woman with metastatic breast cancer presented with 5 days of worsening polydipsia, fatigue, nausea, vomiting, slurred speech and altered mental status. She was started on Alpelisib 300 mg daily two weeks prior to admission and instructed to check glucose twice weekly but did not follow directions. Family history was significant for type 2 diabetes. On physical exam blood pressure was 150/90, heart rate 120 beats/minute, respiratory rate 120 breaths/minute; BMI was 27 Kg/m2. The neurological exam was significant for a lethargic state with the patient arousable to verbal stimuli. The skin exam was negative for acanthosis nigricans or skin tags. Laboratory tests showed glucose at 1425 mg/dl, bicarbonate 11 mEq/l (19–34), anion gap 39 (6–22), sodium 138 mmol/l (135–146), potassium 5.0 mmol/l (3.5–5.5), serum osmolality 378 mosm/kg (275–295), Cr 3.99 mg/dl (0.4–1.1), lactic acid 3.5 mmol/l (0.5–2.0), ketonuria and glucosuria. No arterial blood gas was performed. HbA1c was 5.9% before starting Alpelisib. Results were consistent with DKA and hyperosmolar hyperglycemic state. Additional tests showed HbA1c 10.5 %, c-peptide 1.2 ng/ml (1.1–4.4) with glucose 183 mg/dl; type 1 diabetes autoantibodies were negative. Alpesilib was held and the patient managed with insulin drip and then insulin basal/bolus regimen. Patient was discharged on basal insulin and metformin with the plan to resume alpelisib at a lower dose and monitor.

ConclusionIn the SOLAR-1 trial hyperglycemia was reported in 63% of patients taking alpesilib and two cases of DKA were observed. A case of a patient who developed DKA with Alpesilib was also recently reported. The mechanism underlying DKA in these patients is unclear. PI3K inhibitors may prevent the transcription of the insulin gene in response to high concentrations of glucose and the combination of impaired peripheral glucose uptake with impaired insulin secretion trigger DKA. Further studies are needed to identify which patients on Alpelisib are at increased risk of developing DKA. Clinicians should be aware of this life threatening complication.

References: F André, et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med 2019; 380.SJ. Farah, et al. Diabetic ketoacidosis associated with alpelisib treatment of metastatic breast cancer. AACE Clinical Case Reports 2020; Vol. 6, No. 6.
An Atypical Presentation of Hyperosmolar Hyperglycemic State Induced by SARS CoV 2
Authors: Rivera Nazario Ivan Augusto , Ortiz Arnaldo Nieves , Rivera Jose Ayala , Moya Kyomara Hernandez , Rojas Arnaldo , Lopez Zahira Marie Lugo , Torres Marina Torres , Cintron-Colon Hector R , Fonseca Vanessa , Bisono Nicolas Cabrera , Miranda Maria De Lourdes
Published: May 2021

Hyperglycemic emergencies such as Diabetic Ketoacidosis (DKA) or Hyperosmolar Hyperglycemic State (HHS) are commonly precipitated by infectious processes. Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) is a novel infectious process prompting hyperglycemic crisis. SARS-CoV-2 at the level of the lungs affects ACE2 functioning which in turns decrease the B cells proliferation at the pancreas and hinders insulin secretion. Advanced age and comorbidities such as hypertension, cardiovascular disease and diabetes mellitus are considered to be a risk factors for severe illness and mortality between patients with SARS-CoV-2.

We present the case of a 39-year-old woman with medical history of uterine fibroma, who presented with complains of general malaise, polyuria and polydipsia of one week evolution, associated with sore throat, subjective fever, dry cough, abdominal pain, nausea and vomiting. Physical examination remarkable for dry oral mucosa, decreased skin turgor, and prolonged capillary refills. Vital signs significant for hypertension, tachycardia, and tachypnea. Laboratory work up remarkable for glucose of 1321 mg/dL, HCO3- of 16 mEq/L, serum osmolality of 333 mOsm/kg, serum ketones positive and HbA1C of 15%. ABG’s showed pH of 7.33, PCO2 of 29.8 and a PAO2 of 158.5 mmHg for a high anion gap metabolic acidosis (AG of 15.3 mEq/L), non-anion gap metabolic acidosis with respiratory alkalosis. Chest X-ray revealed bilateral perihilar, peribronchial cuffing. SARS-CoV-2 PCR testing was positive. Clinical and laboratory workup met criteria for diagnosis of HHS and Diabetes Mellitus de Novo most likely secondary to SARS-CoV-2 infection. Patient was treated with aggressive IV hydration and insulin infusion with resolution of hyperglycemia, ketonemia and symptoms.

SARS-CoV-2 infection can precipitate acute metabolic complications in patients with diabetes or unknown diagnosis of diabetes. The effect of the virus could be direct effect on β-cell function. To our knowledge, there are only a few cases reported of HHS precipitated by SARS-CoV-2 infection therefore medical awareness is important for early diagnosis of possible triggering factors such as COVID-19 and early management of patients presenting with new onset hyperglycemic emergencies.
An Unusual Case of Latent Autoimmune Diabetes in Adult and Pancreatic Neuroendocrine Tumor in a Patient Presenting With Diabetes
Authors: Baral Neelam , Gubbi Sriram , Al-Naqeeb Ghadah , Verbalis Joseph G
Published: May 2021

Introduction: Latent autoimmune diabetes in adults (LADA) and pancreatic neuroendocrine tumors (PNETs) are rare causes of adult-onset diabetes mellitus (DM). The existence of both LADA and a PNET in a single patient has not been previously reported.

Clinical Case: A 65-year-old female with history of type 2 DM diagnosed 15 months ago, on metformin 500mg twice a day presented with fatigue, dry mouth, polyuria, and blurry vision for one week and weight loss of 12 pounds over 3 months. Plasma glucose was 599 (nl 65–144 mg/dL) with an elevated anion gap (17; nl 5–15 mmol/L), low bicarbonate (19; nl 21–32 mmol/L) and elevated beta hydroxybutyrate (4.79; nl 0.02–0.27 mmol/L). Diabetic ketoacidosis was diagnosed, and intravenous fluids and insulin were administered. Work up revealed HbA1C of 14% (nl 4.2%-5.6%) which had increased from 7% noted three months ago. glutamic acid decarboxylase antibodies (GAD65 Ab) was >250 (0.0–0.5 IU/mL) and C peptide was 0.42 (0.81–3.85 ng/mL). A computed tomogram of the abdomen performed to evaluate the acute worsening of her HbA1C revealed a 1.4 x 1.3 cm poorly defined hypoenhancing pancreatic head lesion, which on magnetic resonance imaging was 1.6 x 1.2 cm. Further evaluation showed normal levels of glucagon (127; nl <=208 ng/L), somatostatin (26; nl <=30ppg/mL) and vasoactive intestinal peptide (<13; nl 0–60 pg/mL), and an elevated chromogranin A (155; nl 0-95ng/mL). An endoscopic ultrasound guided fine needle aspiration of pancreatic head mass revealed a well differentiated NET with Ki-67 proliferation index of <1%. She underwent pylorus preserving pancreaticoduodenectomy and histopathology showed a 2 cm grade one NET on pancreatic head with no involvement of the 23 tested lymph nodes. Immunohistochemistry was positive for chromogranin and synaptophysin and negative for insulin, somatostatin and gastrin, confirming diagnosis of well-differentiated pancreatic NET Stage Ib (T2N0M0). Whole body PET CT scan done 2 months following surgery did not reveal any focal radiotracer uptake to suggest metastasis. Given the presence of GAD65 Ab, age of onset of DM, and an initial non-requirement of insulin, the patient was diagnosed with LADA and insulin therapy was initiated.

Conclusion: We report a unique case of a patient with LADA who was incidentally found to have a non-functioning pancreatic NET. Although functional PNETs such as glucagonoma and somatostatinoma cause hyperglycemia, DM associated with non-functioning NETs is rare, but has been reported with gastrointestinal NETs (1). Our patient likely developed uncontrolled hyperglycemia from LADA but was incidentally found to have a PNET which may have contributed to the worsening of hyperglycemia. This highlights the importance of thorough evaluation for the causes for acute worsening of hyperglycemia.
Application of the S (AD) SAD System as a Prognostic and Evaluation Tool for the Multidisciplinary Treatment of a Diabetic Foot Ulcer
Authors: de Oliveira Izabela , Baldissera Vilmar , Souza Gabriella S
Published: May 2021

Introduction: Foot ulcers combined with infection is one of the main complications of type 2 diabetes mellitus (DM2), and when not diagnosed and treated, amputation is the most frequent outcome. Thus, patients with DM2 are ten times more likely to be hospitalized for infections when compared to normal ones. For this reason, it is indisputable that diabetic foot ulcers have a major impact on health and the early approach can reduce the chances of amputations. Case Report: A 48-year-old woman, admitted with an ulcer on her right foot for 30 days, reports worsening and pain for 7 days. Previous history of DM2 diagnosed 2 years ago, using metformin irregularly. On physical examination, he had edema, flushing, impaired tibial pulses and ulcer in the calcaneus with exudate in the right lower limb. In addition, he had a BMI of 32.5, showing overweight. Having considered the hypothesis of a diabetic foot associated with hyperglycemia, the S (AD) SAD system (SEPSIS, ARTERIOPATY, DENERVATION) was applied, in order to assess the prognosis of foot ulcer (healing), setting a score of 10 due to the presence of an affected area greater than 3 cm², affected depth up to the joint capsule, presence of osteomyelitis, reduced pulses, and reduced sensitivity at the site. In this sense, the system suggested an expectation for cure in a period greater than 6 months and with a high risk for limb amputation. The exams were consistent with the hypothesis of hyperglycemia, revealing decompensated diabetes mellitus. Thus, he presented elevated glycated hemoglobin (11.8%), estimated mean glycemia (292 ml / dL), and elevated basal glucose (191 mg / dL). Treatment with antibiotic therapy was initiated for 30 days and the patient was asked to go to the health service three times a week to perform debridement with SF 0.9% and apply the ionic silver dressing to treat the ulcer. In addition, the patient received guidance related to dietary reeducation, and started treatment with empagliflozin to control DM2. The patient progressed with progressive ulcer healing and weight reduction. After 3 months of treatment, after monitoring and multidisciplinary intervention, the patient had an adequate glycated hemoglobin rate (6.9%) and the patient achieved total healing of the ulcer, with improved sensitivity and peripheral circulation of the affected limb. Conclusion: Although ulcers are a frequent problem, there are difficulties not only in choosing the most appropriate approach, but also in a system that provides a prognosis and that makes it possible to assess the risk of amputation. Therefore, the S (AD) SAD system, a reproducible tool that favored decision making, provided a prognosis for slow healing and a high risk for amputation. Thus, the multidisciplinary team was able to measure the severity of the condition, choose a treatment, and evaluate the success of the approach adopted, which configured the total healing in 3 months.
Diabetes and Tuberculosis: Challenge of Modern Medicine
Authors: Kostitska Iryna Oleksandrivna , Ostrovskyi Mykola Mykolayovych , Makoida Iryna Yaremivna , Molodovets Olga Bogdanivna , Babliuk Lyudmyla Antonivna , Maniv Lesya Yaroslavivna
Published: May 2021

The world medical community is strongly concentrated on the fight COVD-19, HIV/AIDS, tuberculosis. The combination of two or more concurrent nosologies is a major problem in patient management. Thus considering the abovementioned facts, we would like to focus your attention on such comorbidities as diabetes and tuberculosis. Patient M., 49 y.o., type 2 diabetes during 10 years. In July 2018, she consulted her physician and complained of non-productive mild cough, low-grade fever, fatigue, reduced workability. After the follow-up examination which involved chest X-ray and complete blood cell count, she was diagnosed with an abscess forming pneumonia in the right lower lobe and prescribed treatment with the use of broad-spectrum antibiotics according to the protocol. After the treatment, the patient’s condition has slightly improved, though the labile diabetes with frequent episodes of hypoglycemia and hyperglycemia, and cough still persisted. The level of HbA1C was 7.8%. At the patient’s request, she continued to receive: glimepiride 6 mg/day, metformin 1000 mg/day. Considering the patient’s general condition as gradual recovery the doctor has discharged the patient. In January 2019, the patient consulted a tuberculotherapist, because the cough persisted, the body temperature markers sometimes attained feverish indices, the general weakness increased. After the follow-up examination: complete blood cell count, chest X-ray, sputum smear microscopy, genetic-molecular study with GeneXpert-test and culture test on the BACTEC system, the patient was diagnosed with disseminated tuberculosis with bacterial excretion, susceptible. The patient received treatment according to the 2HRZE 4HR scheme. Results: the treatment was completed, whereas the cavern was preserved, the patient refused to undergo surgical treatment. After 7 months, the previous symptoms reappeared, after additional examination the patient was diagnosed with multi-drug resistant tuberculosis and was prescribed treatment with second-line agents for 20 months, and the patient was given insulin degludec/aspart at a daily dose of 64 IU. The therapy resulted in patient’s recovery, the cavern was closed, and compensation of diabetes was achieved: no episodes of hypoglycemia were recorded; the HbA1C - 6.5%. Analyzing the previous data it is necessary to note the mistakes that were made. The mismatch of clinical symptoms with the established diagnosis, the absence of a sputum smear for acid-resistant bacteria, apical localization of tuberculosis which is typical for patients with diabetes was not characteristic in this case, all these factors have led to an incorrect diagnosis at the primary level. At the beginning of tuberculosis treatment, the patient should be transferred to the correction of blood glucose levels with insulin and, if the cavern preserves, the patient should be prepared for its surgical removal.
Diabetic Ketoacidosis Presenting in Major Thalassemia With Pancreatic Hemosiderosis: A Case Report
Authors: Mulyadi Calvin Kurnia , Effendi Bonita , Pratomo Robby , Kesuma Pratiwi , Tahapary Dicky Levenus
Published: May 2021

Introduction: Iron overload is a common complication of thalassemia, responsible for multiple organ damage, including pancreas. The prevalence of diabetes in thalassemia was 9.7–29%,1 while the incidence of diabetic ketoacidosis (DKA) is only 0,3%.2

Case Illustration: A 26 year-old male with thalassemia major (TM) admitted due to dyspnea, which later revealed as first episode of DKA. No prior history of hyperglycemia, but the patient has unexplained weight loss. He receives combination of chelators (deferiprone, desferroxamine, deferriprox) with ferritin level 8,387 μg/mL. Serum glucose was remarkably high (690 mg/dL), with ketosis (4.2 μg/dL) and metabolic acidosis (pH 7.2; bicarbonate 5.6 mEq/L). No single insult was identified, but recurrent ventricular tachycardia was documented. T2* MRI demonstrates severe cardiac and mild pancreatic hemosiderosis. Echocardiography shows reduced ejection fraction (25.6%), atrioventricular dilatation, and hypokinetism.

Discussion: Impaired glucose metabolism in TM is initially mediated by insulin resistance, but later, the interplay between defect in insulin secretion and resistance determines the various clinical picture of diabetes in TM.3 Several mechanisms have been linked: oxidative stress, induction of autoimmunity, and zinc deficiency; yet, current evidence remains inadequate.4 The T2* MRI provides the most reliable tool to predict the development of glycemic dysregulation, whereas relying solely on ferritin could lead to imprecise measurement of iron deposits.5 The presence of cardiac abnormality might responsible for the DKA and suggests the need of rescue chelation for this patient.

Conclusion: DKA is a rare endocrine complications which can be prevented by routine T2* MRI screening and has wide spectrum of clinical characteristics.
Diabetic Myonecrosis: A Case Study
Authors: Reisner Timothy , Burks James K
Published: May 2021

Background: Diabetic myonecrosis is a rare complication of diabetes mellitus with less than 200 cases reported in the literature since initial description in 19651. Diabetic myonecrosis most commonly affects the thigh and usually presents with acute muscle pain, edema, and erythema in the absence of trauma or fever1. The pathogenesis has yet to be elucidated—atherosclerosis, microangiopathy, vasculitis, and ischemia-reperfusion injury have been theorized. Laboratory findings are relatively nonspecific—of the findings reported in a systematic review, CRP was elevated in 90%, ESR elevated in 83.3%, WBC elevated in 42.5%, and CK elevated in 31.6%1. Definitive diagnosis can be made by muscle biopsy which demonstrates muscle necrosis and edema; however, it is not routinely recommended due to procedural complications. MRI is the diagnostic modality of choice for diabetic myonecrosis which is both sensitive and specific for the diagnosis2.

Clinical Case: 76-year-old male with T2DM presented to regional hospital with severe right lower leg pain in the absence of fever, tachycardia, hypotension, or recent trauma. Physical exam demonstrated discrete erythema of distal 2/3 of posterior right lower leg extending to the ankle distally. Labs demonstrated normal CK, elevated ESR, HgbA1c 8.2%, and negative blood cultures. MRI of the right lower extremity demonstrated abnormal prolongation of T2 relaxation time involving posterior muscle compartment including soleus and gastrocnemius with associated perifacial and subcutaneous edema. These findings were consistent with diabetic myonecrosis without evidence of osteomyelitis or abscess. Rest, optimal glycemic control, and aspirin were recommended and patient improved gradually with complete clinical resolution on outpatient follow-up.

Conclusions: Diabetic myonecrosis is a rare complication of diabetes and should be considered in patients presenting with acute muscle pain. Among cases described in literature, 5.7% have affected the soleus and 5% have affected the gastrocnemius respectively1. The diagnostic modality of choice is contrast enhanced MRI with typical findings including hyperintense signal on T2 weighted images with associated muscular, perifascial, and/or subcutaneous edema3. The optimal treatment is yet unknown, but reasonable strategies based on case series include rest, glycemic control, and NSAID therapy1.

References: 1. Horton WB, Taylor JS, Ragland TJ, Subauste AR. Diabetic muscle infarction: a systematic review. BMJ Open Diabetes Res Care. 2015;3(1):e000082. doi:10.1136/bmjdrc-2015-000082

2. Morcuende JA, Dobbs MB, Crawford H, Buckwalter JA. Diabetic muscle infarction. Iowa Orthop J. 2000;20:65–74.

3. Goswami P, Baruah MP. The Role of MRI in Diagnosis of Diabetic Muscle Infarction : an Underdiagnosed Entity. Int J Endocrinol Metab. 2012;9(2):353–355. doi:10.5812/kowsar.1726913X.1886
Glucose-6-phosphate Dehydrogenase Deficiency Induced Haemolysis in Male With Newly Diagnosed Diabetes During Diabetic Ketoacidosis Treatment: A Case Report
Authors: Albasri Eman Ebrahim
Published: May 2021

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency could be a risk factor for diabetes, as suggested by various epidemiological data, but still a matter of debate. The occurrence of haemolysis during diabetes crises was reported in patients with G6PD deficiency, furthermore the fall in glucose level during the treatment of hyperglycemia is suggested as a possible cause for hemolysis in G6PD deficiency. We reviewed the mechanisms that may link the two diseases. Clinical Case: A 19-year-old male, with G6PD deficiency, presented to the emergency department in our institution with history of generalised weakness, epigastric pain, nausea, and vomiting. He gave history of polyuria, polydepsia and weight loss over a period of two weeks. Diagnosis of DM was confirmed by laboratory tests that showed a mild DKA: arterial pH 7.28, HCO3 18 mmol/l, plasma glucose 21 mmol/l, urinary ketones ++, and hemoglobin 16.1 g/dl (12.0–15.0 g/dl). DKA was treated according to DKA guidelines. Ketoacidosis remission was achieved two days after rehydration and treatment with continuous intravenous insulin infusion (0.05–0.1 IU/kg). The patient then started on subcutaneous intensive insulin injection therapy, three times daily before meals and once before bedtime. Fasting and post-prandial blood glucose levels decreased to 7-8mmol/L, and 10 –13 mmol/l respectively. On day 4, the patient developed dizziness while he was taking a bath, On examination he was pale and had icterus, however, the vital signs and systemic examination were normal, blood tests revealed a hemolytic anemia as follows: (normal values): Hemoglobin 9 g/dl (12.0–15.0 g/dl), reticulocytes 8.5% (0.5–1.5%), total bilirubin 82 umol/l (0–20 umol/l), unconjugated bilirubin 58 umol/l (3–15 umol/l), By the 7th day, hemoglobin levels had fallen to the lowest value of 8.3, then gradually raised to 10.2 g/dl, 2 weeks later, hemoglobin electrophoresis was normal, Coombs test was negative. G6PD activity was below 300 U/L (reduced activit<600) with two separate measurements. The patient had no bacterial infections and had not ingested haemolytic drugs. Hemolysis ceased spontaneously and hemoglobin increased gradually. Conclusion: G6PD deficiency and diabetes mellitus could aggravate each other, and In patients at risk of G6PD deficiency screening of the enzyme activity should be considered following diabetes decompensation, and in case of G6PD deficiency, it is advisable to correct plasma glucose level gradually to avoid the rapid drop in glucose availability, which may cause hemolysis in these patients.
Intravenous Insulin Resistance in a Critically Ill Patient Secondary to Decreased Peripheral Perfusion
Authors: Umadat Deviani , Arudkumaran Dharscika , Eschler Deirdre Cocks
Published: May 2021

Introduction: Intravenous (IV) insulin infusion is the preferred treatment modality for hyperglycemia in the intensive care unit (ICU) due to its short duration of action and easy titratability. However, administration of IV insulin has challenges. These include frequent monitoring, site infiltration, and high insulin dose requirements with other ICU medications such as epinephrine. There are, however, limited reports demonstrating an elevated insulin requirement due to poor peripheral perfusion. Below illustrates such a case, necessitating a change from peripheral to central IV insulin administration.

Case Presentation: A 50 year old male with well controlled type 2 diabetes and previous aortic valve replacement presented to our facility for prosthetic valve endocarditis complicated by aortic root abscess. He was admitted to the ICU, treated with IV antibiotics, abscess washout and aortic valve replacement. Preoperatively, he was started on IV regular insulin via continuous infusion through a central line. During the pre and intraoperative periods, his hourly IV insulin requirement ranged from 2.4 to 5 units/ hour (hr). His blood glucose (BG) ranged from 107-251mg/dL (n 70-99mg/dL). The patient became hypotensive intraoperatively requiring vasopressor support. Dobutamine and norepinephrine infusions were started via central access and were continued postoperatively at steady rates. Vasopressin was added through central access as the patient failed to meet hemodynamic targets. Postoperatively, the propofol infusion was discontinued and the IV regular insulin infusion was moved to the peripheral line where the propofol had previously been administered. BG increased steadily to a maximum of 402 mg/dL despite an increase in the peripheral IV insulin rate to 152.4 units/hr. The site of the IV insulin drip was changed to another solitary peripheral access without success in decreasing the IV insulin infusion rate. The elevated requirements were deemed secondary to the patient’s lack of peripheral perfusion and should decrease with transition to a central line. A preemptive decrease in insulin drip rate to 10% of the peripheral dose was used to avoid hypoglycemia. The insulin drip was changed to a central access with a rate of 15units/ hr. BG values declined to a range of 140 -180 mg/dL. The patient remained on the multiple vasopressors for hemodynamic support, however, the insulin drip was able to be decreased and ultimately, discontinued.

Conclusion: This case illustrates a unique challenge in the treatment of hyperglycemia with multifactorial shock and our approach to management. Elevated IV insulin requirements persisted despite stability in vasopressor dose, change to a solitary peripheral IV site, and lack of interfering medications in the treatment regimen. This is the first case to demonstrate a relationship between high IV insulin requirements and poor peripheral perfusion.
Role of Octreotide in Sulfonylurea-Induced Hypoglycemia
Authors: Zafar Sheema , Mahali Lakshmi Priyanka , Ahsan Hamza
Published: May 2021

Introduction: The most common adverse effect associated with sulfonylurea ingestion is hypoglycemia. Sulfonylureas have very narrow therapeutic indices with a prolonged half-life in End-Stage renal Disease (ESRD). As per literature review, insulin and oral sulfonylureas are responsible for 13.9% and 10.7% of emergency hospitalizations respectively. It is, however, not surprising that intentional or unintentional overdose with these agents can lead to prolonged hypoglycemia which can prove to be fatal.

Case Report:76-year-old female presented to the Emergency Department (ED) with complaints of generalized weakness since the past three days. Her past medical history was significant for ESRD, Hypertension and Non-Insulin Dependent Diabetes Mellitus type II (home regimen of glipizide 10 mg daily). On physical exam, she was tachypneic and appeared lethargic. Her neurological exam was intact, and she was oriented to time, place and person. Her labs were significant for BUN of 77 mg/dL (5–20 mg/dL), Creatinine of 9.94 mg/dL (<1.3mg/dL) and blood glucose of 89 mg/dL (70-140mg/dL). Liver and thyroid function tests were normal. Computed Tomography scan of the head was unremarkable. In the ED, she received 5 mg of glipizide after which she became more confused and lethargic. Her blood glucose level was 21mg/dL thus she received seven pushes of intravenous (IV) dextrose (25g each), two doses of intramuscular glucagon (1mg each) and was started on a continuous infusion of dextrose (D10) at 75cc/hour. Her blood glucose levels continued to remain low with a repeat value of 34 mg/dL and her mental status continued to worsen. Labs checked at that time were significant for a C-Peptide level of 22.13ng/ml (1.00–4.00ng/ml) and an insulin level of 43.7uU/ml (<20uU/ml) suggesting it to be sulfonylurea toxicity. Sulfonylurea level could not be checked due to laboratory limitations. She was started on subcutaneous octreotide 30 mcgs every 6 hours as per endocrinology recommendations. Her blood glucose started to improve, and her mental status returned to baseline. Per oral food intake was resumed, she remained euglycemic and octreotide was discontinued.

Conclusion: Octreotide is a synthetic octapeptide analogue of somatostatin which can effectively suppress insulin secretion. Glucose, on the other hand, would stimulate insulin release and cause rebound hypoglycemia. Boyle et al, showed that octreotide was superior to diazoxide and glucose in preventing sulfonylurea-induced hypoglycemia. Therefore, we as clinicians should be able to quickly recognize sulfonylurea toxicity as the cause of hypoglycemia and attempt to administer octreotide as soon as possible. This in turn would help decrease length of hospital stay and avoid the detrimental effects of hypoglycemia like seizures, coma and death especially in older individuals.
SARS-CoV-2 Infection Related Diabetes Mellitus
Authors: Beliard Kara A , Yau Mabel , Wilkes Meredith , Romero Christopher Joseph , Wallach Elizabeth , Rapaport Robert
Published: May 2021

Introduction: SARS-Cov-2 (severe acute respiratory distress syndrome- coronavirus 2) viral infection has a predilection for pancreatic beta cells causing insulin deficiency. Studies from the SARS-CoV outbreak in 2003 highlighted the relationship between SARS-CoV and ACE-2 (angiotensin-converting enzyme 2) receptors in pancreatic islet cells. We describe a pediatric patient who developed Diabetes Mellitus after exposure to the Sars-CoV-2 virus.

Case Report: A previously healthy 13-year-old female of Mexican descent was found to be hyperglycemic at her annual visit. The patient endorsed polyuria and polydipsia for 3 weeks, and weight loss for 3months. 3 months prior to presentation, her mother became ill and tested positive for SARS-CoV-2 by PCR analysis. The patient had no SARS-CoV-2 associated symptoms.

Her exam was notable for a BMI was in the 78%ile for age with no acanthosis nigricans. She had no family history of diabetes or autoimmune disease.

Initial blood glucose was 729 mg/dL, with bicarbonate of 20.6 mEq/L, pH 7.45, and anion gap of 14 mEq/L. Large ketones were present in the urine. Her concomitant C-peptide level of 1.0 ng/ml was low in the setting of hyperglycemia. Her HbA1c was 14.3%. Diabetes-related autoantibodies, celiac, and thyroid antibodies were negative. Her Sars-CoV-2 antibody titer was positive with a negative PCR.

The patient was treated with a basal-bolus regimen of subcutaneous insulin at a maximal total daily dose of 0.7 u/kg/day. 5 weeks later, her insulin requirement and HbA1C were both lower; at 0.5 u/kg/day and 9.3% respectively.

Discussion: This patient’s symptoms of hyperglycemia started shortly after her exposure to the SARS-CoV-2 virus. She had no features consistent with Type 2 DM. She similarly had no serological evidence of DM related autoimmunity, thus being different from reports of new-onset Type 1 DM with confirmed autoimmunity presenting during the Sars-CoV-2 pandemic. Although Type 1B DM without evidence of humoral islet autoimmunity and monogenic DM could not be fully excluded, we postulate that the patient developed SARS-CoV-2 associated DM given her time course and documented exposure to SARS –CoV-2 with the presence of SARS-CoV antibodies. One similar case has previously been reported By Holstein et al. 1 While we share the lack of direct evidence of causation, we postulate that more patients with similar presentations will be reported during the current pandemic.

Reference: 1.Hollstein, T et al. Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report [published online ahead of print, 2020 Sep 2]. Nat Metab. 2020;10.1038/s42255-020-00281-8. doi:10.1038/s42255-020-00281-8
Selecting Patients at Risk of Developing DKA on Gliflozins
Authors: Maletkovic Jelena
Published: May 2021

Background: Since the introduction of gliflozins less than a decade ago we have witnessed how these medications are changing our approach to treating patients with type 2 diabetes mellitus. While recognizing tremendous benefits from these medication we are aware of potentially fatal risks. We present three cases of diabetic keto-acidosis in patients with type 2 diabetes mellitus and no prior history of diabetic emergencies while on SGLT2 inhibitors. Cases: A 58 year old woman with history of type 2 diabetes mellitus for 8 years and history of bulimia was treated with an SGLT2 Inhibitor for 12 months with stable control of diabetes mellitus. After an episode of very low calorie diet for 30 hours the patient was admitted to ICU with findings of diabetic ketoacidosis. She was critically ill but responded to treatment and needed only oral medication for future diabetic control. The second patient was a 49 year old man with type 2 diabetes mellitus and obesity who has been treated with oral antidiabetics for 7 years prior to requiring MDI insulin regimen in the past 3 years. The patient was well controlled in the past one year since introduction of SGLT2 inhibitors to his therapy. After a 2 day episode of eating carb heavy diet and using about 20% of prescribed insulin the patient developed DKA and was admitted to ICU where he needed to be intubated but improved and stabilized over the next few days. The third patient was a 52 year old man with history of type 2 DM for 13 years, well controlled in the past 3 years since SGLT2Is were added to his oral antidiabetic therapy. After one night of binge drinking alcohol with poor calorie intake the patient was diagnosed with DKA. After successful treatment this patient remains on oral antidiabetic medications. Conclusion: SGLT2Is have been prescribed in our clinic with great success since the first introduction of these medications. These are the only three patients who developed DKA on SGLT2 inhibitors in the past 6 years to our knowledge. All three patient had risk factors that were recognized but likely not enough emphasized. The first patient developed DKA during a “starvation phase” of eating disorder, the second one during a short episode of non-compliance with insulin while on a high carb diet and the third one after one episode of binging on alcoholic drinks. When prescribing SGLT2 inhibitors we are turning some patients with classical type 2 DM into ketosis prone diabetics. Eating disorders, extremely low or heavy carbohydrate intake, alcohol consumption and non-compliance with other antidiabetic medications should be subjects that we discuss when starting gliflozins in order to avoid significant risks. While using impressive benefits of these medications we should be aware of their side effects and recognize those that are at risk of serious side effects.
Sudden Onset Diplopia Associated With Better Diabetes Control - Too Fast Is Not Too Good
Authors: Vemparala Pranathi , Bekele Yididiya , Krishnamurthy Mahesh
Published: May 2021

Introduction: Treatment-induced neuropathy of diabetes (TIND) presenting as a new-onset peripheral neuropathy usually associated with autonomic dysfunction has been documented in literature. It can occur when there is a drop of more than 2% in HbA1C in a three month period. Worsening of existing peripheral neuropathy and retinopathy has also been observed suggesting a common pathophysiological mechanism. However, the onset of a cranial neuropathy temporally linked to intensified glycemic control has not been well reported.

Case Report: A 32-year-old male patient presented to the emergency department with double vision, preceded by headache, and increased burning in his feet. No other neurologic symptoms were reported. Past medical history was significant for poorly controlled, labile type 1 diabetes mellitus. His home medications included gabapentin for peripheral neuropathy, long-acting and short-acting meal time insulin regimen. Physical examination was unremarkable except for a neurological exam which showed pupil-sparing third cranial nerve palsy. CT angiography of the head and neck revealed no acute ischemia, hemodynamically significant stenosis, aneurysm or dissection. MRI of the brain also showed no abnormality. Review of his prior HbA1c values showed a decrease of 3.6 % (14% to 10.4%) over 3 months. The patient was diagnosed with TIND presenting with simultaneous worsening of peripheral neuropathy and new onset right oculomotor nerve palsy. He was discharged on reduced doses of insulin, targeting a gradual decline in HbA1c after initial stabilization. The patient was also asked to liberalize his diet and was given an eye patch. While his peripheral neuropathy improved, there was not much improvement in his diplopia at a two week follow-up visit.

Discussion: Our patient presented with worsening of peripheral neuropathy and pupil sparing oculomotor palsy. Secondary causes including CVA and aneurysm were excluded with brain imaging. Diabetes related microvascular disease presenting with pupil sparing oculomotor palsy is commonly seen in patients older than 50 years of age with uncontrolled diabetes and other vascular risk factors like hypertension and dyslipidemia. Absence of hypertension and hyperlipidemia, sudden onset of presentation and an intense control of DM as evidenced by rapid decline of A1C make TIND the likely cause for his presentation. The paradoxical worsening of his peripheral neuropathy also supports the diagnosis of TIND. Through this case, we highlight the importance of recognizing this entity as management differs significantly. Quality improvement metrics for practitioners in various institutions often include HbA1c target ranges in diabetic patients. Our case highlights the issues associated with rapid corrections of HbA1c and thus we advocate for a gradual decrease of 2 % every 3 months till target goals are reached.
The Mystery of Acidosis
Authors: Naqvi Syeda , Prasad Apurwa , Syed Sabah
Published: May 2021

We present a case of 30-year-old female with past medical history of Type 2 DM, Thyroid nodule and asymptomatic cholelithiasis who presented to ED with abdominal pain, vomiting and sinus tachycardia of 120’s for past one day. She had generalized abdominal pain, not relieved by pain killers. Her lab test includes normal blood count, glucose 150mg/dl, anion gap of 20, metabolic acidosis. Her ultrasound abdomen showed cholelithiasis with no biliary sludge formation. Given her acidosis and severe abdominal pain she was started on Zosyn and underwent cholecystectomy. Her abdominal pain and sinus tachycardia did not resolve till day 3 of admission. Urine was positive for ketones. On chart review, it was found that she started taking sodium glucose transporter 2 inhibitor (SGLT-2 inhibitor), Canagliflozin. She was given IV fluids and insulin. She improved and her tachycardia resolved. Euglycemic acidosis is a rare phenomenon but frequently misdiagnosed. This case emphasizes on importance of side effects of oral glucose lowering agents. SGLT-2 inhibitors can cause lipolysis and ketosis while maintaining euglycemia. Prompt clinical judgement is needed to prevent misdiagnosis. Also, patients should be educated about aggravating factors like stress, dehydration or other severe illnesses.
The Troublesome Triad: Hypertriglyceridemia-Induced Acute Pancreatitis in Diabetic Ketoacidosis
Authors: Rashid Hytham , Martin Jessie , Truong Alan , Nix Emily , Thoppil Deepu , Sadat Mir Ali
Published: May 2021

Background: Diabeticketoacidosis (DKA) is an acute metabolic derangement that can triggerhypertriglyceridemia-induced acute pancreatitis (HTGAP). While DKA classicallypresents in patients with Type 1 Diabetes Mellitus (DM1), previous literaturedescribes HTGAP in DKA as the initial presentation of Type 2 Diabetes Mellitus(DM2). The following case illustrates the diagnostic complexities of thisenigmatic triangle.

Clinical Case: Apreviously healthy, 28-year-old Hispanic male with a family history of DM2presented to the ED complaining of a sharp epigastric 10/10 pain radiating tothe right flank for one day that evolved into nausea with intractablenonbilious, nonbloody vomiting. He recently immigrated from Mexico City and hasnot seen a physician since childhood. He denied any tobacco, alcohol, norillicit substance use. Oninitial exam, he was afebrile and hemodynamically stable with dry mucosa,epigastric tenderness with voluntary guarding, but no evidence of jaundice,scleral icterus, nor abdominal distention. Pertinent initial labs foundglucosuria and ketonuria with a normal CBC, but his CMP was delayed as hisblood was lipaemic requiring serial dilutions that found hyperglycemia (415mg/dL, n <140), decreased carbon dioxide (17 mmol/L, n:23–29), a high aniongap (18 mmol/L, n<12), elevated ALT (154 u/L, n:4–36). Additional testingfound severely elevated triglycerides (4,427 mg/dL, n<150 mg/dL), elevated lipase(536 u/L, n<160), elevated Beta-hydroxybutyrate (5.30 mg/dL, n<2.81), andan elevated HgA1C (10.1%, n<5.7). These findings confirmed the diagnosis ofDKA with concerns for underlying HTGAP. CT abdomen showed hepatic steatosis andperipancreatic inflammation, confirming the diagnosis. Hewas admitted to the ICU, received aggressive IV fluid resuscitation with 5%dextrose in half normal saline while on an insulin infusion, with morphine andondansetron to control his pain and nausea. His abdominal pain resolved as histriglycerides trended down and anion gap closed. He was transitioned to an oraldiet with subcutaneous insulin prior to discharge on insulin and fenofibrate. At 1 month follow up, he reported medication compliance and denied anyrecurrence.

Conclusion: While DKA rarely triggers HTGAP in <4% of pancreatitis cases, HTGAP willexacerbate DKA as the pancreatic inflammation leads to acute beta celldysfunction causing insulin deficiency, propagating lipolysis. A serumtriglyceride level >1000 mg/dL is required for diagnosis of HTGAP, and thedegree of elevation is associated with the severity of pancreatitis.

Reference: Timilsina, S, et al. (2019). Triad of Diabetic Ketoacidosis,Hypertriglyceridemia, and Acute Pancreatitis: Severity of Acute PancreatitisMay Correlate with the Level of Hypertriglyceridemia. Cureus, 11(6), 4930–4934.