bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case of Euglycemic DKA With SGLT 2 Inhibitor Use- A Diagnostic and Therapeutic Dilemma
Authors: Nallu Ravali , Azmath Misbah , Aftab Hassaan , Kantorovich Vitaly
Published: May 2021

Background: The increasing use of SGLT-2 inhibitors driven by the apparent renal and cardiovascular benefits has been associated with increased incidence of euglycemic diabetic ketoacidosis (DKA), we present a case of euglycemic DKA following bariatric surgery in a patient on SGLT-2 inhibitors.

Case: 32 year old female with history of diabetes mellitus, obesity, hypertension, and triglyceride induced pancreatitis was admitted for an elective gastric sleeve procedure. She was diagnosed with type 2 diabetes after birth of her first child. Prior to the surgery she was treated with metformin 1000 mg twice daily, Empagliflozin 25 mg once daily, Tresiba 46 units and Humalog 12–15 units with each meal. She was placed on a strict calorie restricted diet leading up to the surgery. Empagliflozin and metformin were held 1 day prior to the surgery, insulin was decreased. Patient’s laparoscopic surgery was complicated by bleeding and hypotension and had to be converted to open surgery. Post operatively labs showed metabolic acidosis with bicarbonate level of 13 mmol/l (22–33), anion gap of 22 (7–17) and arterial pH of 7.29. Serum glucose of 223 mg/dl (65- 99), AST 541 u/l (10–50) ALT 580 u/l (10–50), beta hydroxy butyrate 5.89 mmol/l (< 0.28), serum osmolality 305. Urinalysis showed a glucose of 500 mg /dl with the presence of large ketones. She was started on an insulin infusion and transferred to the ICU for close monitoring and management of euglycemic DKA. She was eventually transitioned to a basal bolus regimen of insulin at discharge with discontinuation of SGLT - 2 inhibitor therapy. Later, it was revealed that the patient had history of EDKA while on SGLT2 inhibitors, which was not reported to her new endocrinologist and hence she was re-initiated on them a year ago.

Discussion: Euglycemic DKA [EDKA] in the setting of SGLT- 2 inhibitor use has been associated with Type I diabetes with an incidence of 9.4 % whereas in type II at a rate of 0.2 %. In type 2 diabetics, it is more common in patients with beta cell insufficiency and may predict risk of developing type 1 diabetics which is likely the case in our patient. SGLT2 inhibitors act by promoting glucosuria, which in turn promotes sodium and ketone body reabsorption and increased ketone body production because of increased glucagon to insulin ratio. (1) Most patients with DKA while on SGLT 2 inhibitor have a precipitating event like dehydration, infection, surgery or change in insulin dose. We propose that strict carbohydrate diet and continuation of SGLT2 inhibitors before bariatric surgery resulted in EDKA. It led to complications peri-operatively. In conclusion, despite the increasing benefits of SGLT2 inhibitors in type 2 diabetics, one must be cognizant of its limitations and in particular association with EDKA. This especially holds true for patients suspected to have beta cell dysfunction or ketosis prone diabetes and patients on strict/low carbohydrate diets.
A Case of Immune Checkpoint Inhibitor Induced Autoimmune Diabetes
Authors: Thambuluru Sirisha Reddy
Published: May 2021

Introduction: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block checkpoints such as CTLA-4, PD-1, PDL-1 resulting in an antitumor immune response. ICIs can cause immune-related adverse events such as autoimmune diabetes. Clinical Case: 64 yr old male with history of non-small cell lung cancer (NSCLC) undergoing therapy with carboplatin, taxol, and pembrolizumab (monoclonal PD-1 receptor inhibitor) presented to the ED with weakness and dizziness. Patient reported a 1 week history of polyuria, fatigue, polydipsia, and weakness. He started his cancer treatment 2 months prior to presentation and received a total of 3 cycles with the last cycle being 3 weeks prior to presentation. Patient had no personal or family history of diabetes. On presentation to the ED vitals were: HR 130, RR 40, BP 166/100. Labs were significant for Na 122(135–145 mmol/L), bicarb 5(22–30 mmol/L), creatinine 1.76(0.70–1.30 mg/dl), glucose 1,147(70–179 mg/dl), beta hydroxybutyrate 10(0.02–0.27 mmol/L), anion gap 38(7–15 mmol/L), hemoglobin A1c 7.8%(4.8–5.6%), islet cell ab 0 (<=0.02 nmol/L), GAD65 Ab 0.36 (<=0.02 nmol/L). CT abdomen showed no pancreatic abnormalities. Patient was diagnosed with DKA from autoimmune diabetes induced by pembrolizumab. He was given fluids, started on an insulin drip and admitted to the ICU. He was transitioned off the insulin drip onto basal/basal insulin on discharge. One month post discharge the patient continues to require insulin. Learning points: Although the incidence of autoimmune diabetes mellitus associated with ICIs is only 0.2–0.9%, most of these patients present with severe DKA making this a dangerous adverse event that clinicians should be aware of1. The patient in this case had symptoms of new onset severe fatigue, polyuria, polydipsia 1 week prior to his presentation to the ED. This case teaches us that patients undergoing therapy with ICIs should be educated about the signs and symptoms of hyperglycemia and DKA, with directions to inform a health care provider should they occur. Potential interventions that will allow us to identify these patients prior to presentation with dangerous DKA include patient self-monitoring of symptoms and blood glucose checks with a glucometer. Reference: Akturk, H. K., Kahramangil, D., Sarwal, A., Hoffecker, L., Murad, M. H., & Michels, A. W. (2019). Immune checkpoint inhibitor-induced Type 1 diabetes: a systematic review and meta-analysis. Diabetic medicine: a journal of the British Diabetic Association, 36(9), 1075–1081. https://doi.org/10.1111/dme.14050
A Rare Cause of Diabetes: COVID-19
Authors: Rida Rima , Rios Paola , Manzano Alex
Published: May 2021

A Rare Cause of Diabetes: COVID-19

Introduction: Environmental factors like viruses have been described in the mechanism of pancreatic beta cell destruction. Various viruses can trigger autoimmunity in individuals genetically predisposed to diabetes. Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has been shown to bind to angiotensin-converting enzyme 2 (ACE 2) which is expressed throughout the body, including pancreatic cells, leading to direct injury of the endocrine pancreas. We report a case of coronavirus infection disease 2019 (COVID-19) causing a new onset of diabetes mellitus presentation with hyperglycemia, polyuria, polydipsia and weight loss.

Case Presentation: A 53 year-old, previously healthy, male presented with five days of fever, fatigue, dry cough, dyspnea and diarrhea. On admission he was hypoxic, with a body mass index of 25 kg/m2 and no evidence of insulin resistance on physical exam. He was diagnosed with SARS CoV-2 and admitted for high requirements of oxygen without the need of the intensive care unit. He was treated with tocilizumab, atazanavir, hydroxychloroquine, full dose anticoagulation and azithromycin. Dexamethasone 4 mg every 8 hours was given for three days. During this admission, his fasting glucose was 75–108 mg/dL. Once started on steroids his fasting and prandial glucose was 85–96 mg/dL and 140 mg/dL on one occasion. He was eventually discharged with 2 liters of nasal cannula which he required for one week. One and a half months after, he presented to the emergency department due to a 6 kg weight loss, polyuria, polydipsia, malaise and fatigue. On arrival his glucose was 549 mg/dL, without anion gap or ketones. He had no evidence of new infection and SARS CoV-2 test was negative. He was started on insulin glargine at night and insulin Humalog before each meal with corrections. Hemoglobin A1c was 13.4% with a C-peptide 0.36 ng/mL and glucose of 195 mg/dL at the time of C-peptide test. His antibodies, anti-islet cell antibody, zinc transporter 8 and glutamic acid decarboxylase-65, were negative. He was discharged with basal/bolus regimen and followed up outpatient with Endocrinology. During follow-up, his c-peptide normalized and he was tapered off insulin.

Discussion: In 2003, atypical pneumonia caused by SARS CoV-2 was reported to be associated with hyperglycemia in patients without prior history of diabetes. At 3 year follow-up, the patients no longer had diabetes. Moreover, patients with mild SARS CoV-2 during the first day of hospitalization had a higher fasting plasma glucose than patients admitted for other causes of pneumonia. It is known that SARS CoV-2 binds to ACE 2 which downregulates the receptor, leading to impairment of insulin secretion and hyperglycemia. SARS CoV-2 also produces a direct injury in beta pancreatic cells. It is imperative to monitor patients post COVID-19 to evaluate for new onset diabetes and likely resolution.
Approach to Diagnosis and Management Latent Autoimmune Diabetes in Adults: A Case Report
Authors: Gemiana Dita , Alfian Andi , Tahapary Dicky Levenus , Rachman Andhika
Published: May 2021

Introduction:. Latent Autoimmune Diabetes in Adults (LADA) is used to describe a form of autoimmune diabetesthat has a later onset and a slower progression toward an absolute insulin requirement. The presence of pancreaticauto antibodies especially to Glutamic acid decarboxylase (GAD65) is the best single marker required to diagnoseLADA. Case Illustration. A 35-year-old male came to emergency room with complaints of shortness of breath since twodays before admission. Tightness was not affected by activities or changes in position. The patient also hadcomplaints of vomiting since 3 days before admission. There was a weight loss of 10 kg in the last 1 month andcomplaint urinated frequently. There is no family history of diabetes and autoimmunity. The patient’s blood sugarlevel was 422 mg/dL, blood ketone was 5.6 mmol/L, and the blood gas analysis showed metabolic acidosis. The c-peptide level was 0.35 ng/mL (1.1 - 4.4 ng/mL). Patients was positive for glutamic acid decarboxylase (GAD)autoantibodies. Patients was diagnose with LADA and treated with basal insulin 1x36 unit and prandial insulin 3x20unit. Discussion: C-peptide is mostly undetectable in classical T1DM and normal or high in patients with newlydiagnosed T2DM, whereas individuals with LADA tend to have low but still detectable C-peptide values at the timeof diagnosis. Thus, islet autoantibodies screening, especially GADA, should be required as a second step for patientswith adult-onset diabetes showing low serum C-peptide. To date, evidence shows that patients with LADA shouldbe treated with insulin at an earlier stage. Conclusion: Routine GADA screening should be considered. However, since testing for islet-cell autoantibodiesmay not always be indicated because of high costs, C-peptide measurement may be a useful tool to rule outdiagnosis of LADA in case of low clinical suspicion.
Can Anti-Hypertensives Cause Hypoglycaemia? - A Rare Presentation of Recurrent Hypoglycaemia Secondary to an ACE-Inhibitor
Authors: Kapoor Ashutosh , Banerjee Moulinath , Thant Aye Aye , Sankar Adhithya
Published: May 2021

Introduction: Angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed Anti-hypertensives which are first line treatments in patients with Diabetes. We report a rare but significant side-effect of ACE inhibitor treatment, relevant to Diabetic and non-diabetic patients alike. Case Details: We report the case of a 79 year male, with a background of Hypertension (HTN), established on Ramipril and Bendroflumethiazide, who was admitted following an episode of unresponsiveness secondary to Hypoglycaemia, which was initially presumed secondary to Alcohol, the intake of which was minimal. He did not have a history of Diabetes Mellitus. 7 weeks later, he had a similar presentation and as found to be profoundly Hypoglycaemic. On arrival, his observations were unremarkable except for CBG 1.9 and GCS of 14/15, which responded well to IM glucagon, and IV Dextrose. Relevant investigations revealed significantly impaired renal functions and normal CT imaging. There was no history of alcohol intake or intoxication.

Management: Following acute management and stabilisation, he was admitted under the Endocrine and Diabetes team, who suspended his regular medications, including his ACE-I. As an inpatient, he underwent extensive biochemical investigations which were unremarkable followed by a prolonged 72 hours fasting test and an Oral Glucose Tolerance Test, wherein no significant drop in Blood Glucose was noted in both. Subsequently, there were no further episodes of hypoglycaemia and he remained asymptomatic whilst off his ACE-I and he was safely discharged. He was followed up in our Endocrine clinic and was found to have no episodes of Hypoglycaemia since discharge and remained asymptomatic. Discussion: We report the rare presentation of recurrent hypoglycaemia in a non- diabetic secondary to ACE-I. Hypoglycaemia may be defined by the Whipple’s triad, a classical triad of hypoglycaemic symptoms, low Blood Glucose levels and relief of symptoms following ingestion of glucose. The mechanism by which ACE-I treatment leads to hypoglycaemia remains unclear. It has been postulated that ACE-I related alterations in the Kininogen-Kinin system, are associated with hypoglycaemia. This mechanism may lead to an increase in Insulin sensitivity, mediated by increased muscle tissue uptake and diminished hepatic glucose production. Another proposed mechanism is the suppressive effect that ACE-inhibitors exhibit on the peripheral sympathomimetic overactivity, thus causing Hypoglycaemia. Exacerbating factors comprise of concurrent renal impairment, as in this case. The first case of ACE-I induced Hypoglycaemia was reported in 1985, with the usage of Captopril. To the best of our knowledge, this is one of the rare peculiar cases wherein an ACE-I has been implicated as the underlying aetiology causing Hypoglycaemia in a Non-Diabetic.
Capecitabine-Induced Hyperosmolar Hyperglycemic State
Authors: Yim Carly , Arnason Terra G , Hussein Nassrein
Published: May 2021

Capecitabine is an orally administered prodrug of 5-fluorouracil (5-FU) which is often used for treatment of solid tumour cancers such as breast cancer and gastrointestinal tumours. Common adverse effects include nausea, diarrhea, anorexia and erythrodysthesia (hand-foot syndrome). However, there have been case reports of metabolic disturbances linked to capecitabine including hyperlipidemia, and less commonly, hyperglycemia.

We report a case of a new diagnosis of persistent diabetes mellitus following an acute presentation of hyperosmolar hyperglycemic syndrome (HHS) subsequent to treatment with the chemotherapy agent, capecitabine. A 72 year old female with a history of metastatic breast cancer was admitted to hospital for management of hyperglycemic hyperosmolar state (HHS) after bloodwork from her family doctor revealed an elevated random blood glucose (40.2 mmol/L). Leading up to her presentation, the patient had completed 7 cycles of capecitabine treatment for her breast cancer. Prior to her capecitabine treatment, the patient did not have a history of diabetes mellitus. However, on admission, her hemoglobin A1C (HbA1C) was found to elevated into the diabetic range. Offending medications were considered and given the temporal dysglycemia following the patient’s chemotherapy regimen, capecitabine was thought to be a probable offending agent. The patient was acutely treated for HHS, and eventually transitioned to a basal-bolus insulin regimen at discharge. Her capecitabine was held pending review with her oncology team and she was closely followed up by her family doctor. The patient’s insulin regimen was ultimately titrated down to basal insulin only.

Given the increasing use of capecitabine therapy in breast cancer, it is important to recognize the risk of hyperglycemia and hyperglycemic emergencies as a potential adverse effect of this treatment. It highlights the need to ensure that blood glucose is monitored throughout treatment to prevent hyperglycemic emergencies.
Diabetic Myonecrosis: A Rare Condition That Present With Pain
Authors: Bicchi Amelia Guzman , Lubrano Heinsen Antonio E , Gomez-Daspet Joaquin , Tourtelot John
Published: May 2021

Diabetic myonecrosis is the term used for spontaneous ischemic necrosis of skeletal muscle, unrelated to atheroembolism or occlusion of major arteries. This is an uncommon manifestation of long-standing and poorly controlled diabetes mellitus.

A 65-year-old Hispanic female presented to the Hospital with one-week history of worsening right thigh pain. She denied associated fever, trauma, history of blood clots, past surgery, recent travel, ect. Patient has history of uncontrolled diabetes type 2, diabetic neuropathy and End-Stage Kidney Disease on hemodialysis for the last 3 years. Home medications include gabapentin 300 mg daily and insulin 70/30 20 units twice a day. On physical exam, vital signs appeared within normal limits. There was right medial and anterior thigh fullness, warmth and tenderness without erythema or fluctuance. Laboratory studies are pertinent for HbA1C 8.8% (n <6.5%), C-reactive protein (CRP) 12.97 (n <0.5 mg/dL), Erythrocyte sedimentary rate (ESR) >130 (n 0–30 mm/hr), Creatinine: 6.2 (n 0.57–1.11 mg/dL), BUN 77 (n 6–20 mg/dL), CO2 19 (n 22–29 mEq/L) and albumin 2.7(n 3.5–5.0 gm/dL). Other labs including CPK, glucose, ANA panel and CBC are within normal limits. Patient was admitted with initial diagnosis of cellulitis without improvement in clinical status after 3 days of antibiotics. MRI of the right thigh showed proximal thigh muscle, cutaneous and subcutaneous edema. Right thigh muscle biopsy showed marked myonecrosis with surrounding endomysial edema, foci of histiocytes, fibroblasts, and regenerating muscle fibers. Histologic features, together with localized muscle pain, normal CPK, negative microbiologic studies and uncontrolled diabetes are consistent with diabetic myonecrosis. Insulin was adjusted for tight glucose control and patient was started on low dose aspirin with outpatient follow-up.

Diabetic myonecrosis presents with acute onset of painful swelling that evolves over days or weeks. The most common affected areas are the front and back of the thigh and calf. The pathophysiology is not well understood but appears related to thromboembolic events secondary to microvascular endothelial damage leading to tissue ischemia, which triggers an inflammatory cascade causing local tissue damage and ischemic necrosis. Common laboratory findings include elevated ESR, CRP and HbA1C level. Treatment involves symptomatic management, rest, glycemic control, analgesia and low-dose aspirin. The optimal approach is uncertain and current treatment is based upon published case reports and case series; there have been no randomized trials to compare approaches or specific agents. Close patient follow-up and tight glycemic control are key elements to prevent progression of this condition.
Do COVID-19 Apps Address Diabetes Mellitus and Health Equity Issues
Authors: Nguyen Brian , Lau Chap-Kay Kendra , Wu Gloria , Lubrin Dwight , Siu Vincent
Published: May 2021

Purpose: To evaluate if COVID-19 apps address risk factors such as diabetes, hypertension, race, gender, sexual orientation, language. Background: In 2019, there were 204 Billion app downloads and 3.7 billion downloads of ehealth apps. COVID-19 affects ethnic minority patients with diabetes, hypertension, and other risk factors. Spanish is the second most commonly used language after English in the U.S.. African Americans, Hispanic Americans, and Asian Americans are at an increased risk of COVID-19. LGBTQ+ communities are also at higher risk for COVID due to historically poor access to healthcare. Methods: The search term, “COVID,” in Google Play store and Apple App store was used to find the most popular COVID-19 apps. App inclusion criteria: 1) Contains COVID-19 information and/or COVID symptom tracker, 2) Marketed and designed for the general public, 3) Free, 4) Android (DROID): 100,000+ Downloads; Apple (iOS): highest star ratings. Apple does not provide a number of downloads. App features: COVID-19 information, COVID-19 symptom questionnaire (QN), Diabetes, Hypertension, Cardiovascular disease, Languages (Spanish, Chinese), Race, Gender, and Sexual Orientation. Results: The top 10 DROID apps in descending order are: 1) GuideSafe, 2) CO Exposure Notifications, 3) Care19 Diary, 4) Care19 Alert, 5) Crush COVID RI, 6) MI COVID Alert, 7) DC CAN, 8) CombatCOVID MDC, 9) CombatCOVID PBC, 10) Stronger than C19. The top 10 iOS apps in descending order are: 1) SlowCOVIDNC, 2) COVIDWISE, 3) COVID Alert Pennsylvania, 4) COVID Alert DE, 5) COVID Alert NY, 6) Covid Watch Arizona, 7) Apple COVID-19, 8) COVID Alert NJ, 9) COVID Trace Nevada, 10) CDC. Of the 20 apps: COVID 19 information: 20/20; COVID-19 symptom QN: 8/20; DM: 2/20; HTN: 1/20; CardioVasc: 2/20; Spanish: 11/20 (2/11 of the Spanish apps have Chinese as well). Race: 5/20. Gender: 8/20; Sexual Orientation: 3/20; Age: 10/20. Conclusion: 1) Most apps do not ask about important risk factors such as DM, HTN, and Race. 2) Smartphone apps are not uniform in their health education features. 3) Healthcare providers should continue to play an important role in public education despite the ubiquity of mobile apps.
Endoscopic Ethanol Ablation as Definitive Therapy for Suspected Insulinoma
Authors: Taneja Charit , Groff Andrew J , Lam Milay Luis
Published: May 2021

Introduction: Hypoglycemia is defined as plasma glucose <70mg/dL, with autonomic and/or neuroglycopenic symptoms often occurring at levels less than 55mg/dL. Diagnostic workup of hypoglycemia unrelated to use of hypoglycemic agents is crucial as it is linked to increased mortality. After ruling out common culprits such as drugs (insulin, sulfonylureas), ethanol and malnutrition, further testing should be pursued for patients who meet the Whipple’s Triad: symptoms of hypoglycemia, documented low plasma glucose and relief of symptoms upon raising plasma glucose. We present the case of an 85-year old male with a suspected insulinoma who underwent endoscopic alcohol ablation as definitive therapy.

Case: An 85-year-old male with a history of metastatic prostate cancer was found to have recurrent episodes of asymptomatic hypoglycemia with fasting plasma glucose levels as low as 50-60s during an unrelated inpatient admission. He had no history of diabetes mellitus or insulin use. On further investigation, he was noted to have recurrent falls, though these symptoms could not be temporally linked to documented hypoglycemia as the patient was not monitoring blood sugars at home. Further workup revealed fasting plasma glucose of 58mg/dL and negative sulfonylurea screen. Plasma C-peptide and fasting plasma insulin levels during an episode of hypoglycemia were elevated at 6.42ng/mL and 38uIU/mL respectively. IGF-II and insulin autoantibody testing was negative. Abdominal imaging revealed a 1.3cm hypervascular pancreatic head lesion consistent with a neuroendocrine tumor, concerning for an insulinoma in view of his lab findings. Surgical removal of this lesion was not within the patient’s goals of care. Attempts at medical management included escalating doses of prednisone and subcutaneous octreotide; however, he continued to have hypoglycemic episodes despite therapy. His cardiac history precluded the use of other medical therapies. After careful evaluation, he underwent ultrasound-guided ethanol ablation of his neuroendocrine tumor as potential definitive therapy, with successful resolution of hypoglycemic episodes noted during his post-procedural hospital stay.

Discussion: Traditionally, insulinomas are primarily managed surgically. Poor surgical candidates can benefit from medical management including diazoxide, somatostatin analogs and verapamil among others. Ultrasound-guided ethanol ablation is a newer modality aimed achieving cure in selected patients, thus avoiding need for surgery. Our case highlights the challenges in management of insulinomas, especially in complicated patients like ours who are not surgical candidates and who may be resistant to medical therapy. Though there are not many studies on the long-term efficacy and outcomes with ethanol ablation of insulinomas, it appears to be a promising option and certainly deserves further study.
Euglycemic Diabetic Ketoacidosis Secondary to SGLT2-inhibitor Use in Combination With a Ketogenic Diet
Authors: Hester Joi C , Zimmerman Stacy , Nimmo Teresa Allison , Cunningham Wesley , Liu Joshua , Sukpraprut-Braaten Suporn , Pasquel Francisco J
Published: May 2021

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are cardiorenal protective agents increasingly used in patients with diabetes. Cases of euglycemic diabetic ketoacidosis (euDKA) have been reported particularly among patients with type 1 diabetes. Our case is an example that highlights the role SGLT-2 inhibitors play in the development of euDKA in a patient with type 2 diabetes with confounding factors of strict adherence to a ketogenic diet and ankle fracture.

A 72-year-old female with a history of type 2 diabetes presented to the emergency department (ED) with right ankle pain and obvious deformity after a mechanical fall. Radiography of the right lower extremity confirmed distal fracture of the tibia and fibula. After reduction of her fracture in the ED, she was admitted in anticipation of an open reduction internal fixation. Her diabetes was controlled on empagliflozin monotherapy and adhering to a ketogenic diet. She monitored her blood ketones daily at home and reported values in the 3–4 mmol/L range. On admission, her basic metabolic panel (BMP) revealed a blood glucose of 148 mg/dL, bicarbonate of 20 mEq/L, anion gap of 18 mEq/L, Cr of 1.3 mg/dl, and eGFR of 40 mL/min. Her beta-hydroxybutyrate (BHB) was 5.09 mmol/L. The initial assessment was presumed starvation ketosis.

On hospital day three, she complained of continued nausea, polydipsia, and abdominal pain. Chart review revealed nocturia with approximately 3–4 voids per night. Repeat BMP showed a blood glucose of 152 mg/dL, bicarbonate of 16 mEq/L, anion gap still at 18 mEq/L, Cr 1.4 mg/dl, and eGFR of 37 mL/min. Since admission, all of her blood glucose levels ranged between 118–178 mg/dL. She denied dyspnea but exhibited Kussmaul respirations on physical exam. Repeat labs revealed a BHB of 8.92 mmol/L, and arterial blood gas (ABG) showed pH 7.2, pCO2 23, pO2 100, bicarbonate 8.6 mEq/L, consistent with high-anion gap metabolic acidosis, confirming the diagnosis of euDKA. Her empagliflozin had been held since admission, but she had not received any insulin up to this point due to euglycemia. She was immediately started on a weight-based dose of 12 units of insulin glargine with subsequent improvement of her BHB and anion gap.

This patient’s use of an SGLT2-inhibitor in combination with her being on a ketogenic diet, contributed to a nonregulated state of ketone production leading to euDKA in the perioperative period. As SGLT2-inhibitors become more readily available, it is important to educate physicians and patients about the risk of euDKA during fasting, ketogenic diets, and the perioperative period.
Euglycemic DKA in Patients on SGLT2 Inhibitor and Potentially Ketotic State
Authors: Khalifa Maram , Aftab Hassaan , Kantorovich Vitaly
Published: May 2021

Background: With mounting evidence demonstrating improved cardiovascular and renal outcomes with the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors, this class of newest antidiabetic agents is rapidly gaining favor. SGLT2 inhibition lowers the renal threshold for glucose excretion, resulting in renal glycosuria, a shift in substrate utilization from carbohydrate to fat oxidation and hyperglucagonemia and thus poses the risk of developing euglycemic DKA as a rare but serious adverse effect. Clinical Cases: the first case is A 36-year-old female was diagnosed with type 2 DM with an HbA1c of 10% and was started on multi-agent antihyperglycemic therapy including metformin 500 mg BID, extended release exenatide 2 mg once a week and empagliflozin 25 mg once daily which were all initiated simultaneously. 2 days after starting regimen, she complained of nausea, vomiting and was unable to tolerate oral diet and fluids by day 4 which potentially predisposed to starvation ketoacidosis. She presented to the ED with normal vitals, grossly normal physical exam and labs were significant for beta-hydroxybutyrate of over 7 mmol/L (ref range <0.28), bicarbonate of 10 mmol/L (22 - 33), anion gap 25 (7 - 17), arterial pH 7.16 (7.33 - 7.43), serum glucose 111 (7.33 - 7.43). GAD-65 antibody titer was <5 IU/mL (< 5). She was diagnosed with euglycemic DKA, transferred to ICU and started on DKA protocol to which she responded very well. Second patient is A 65 Years old male with past medical history of CAD, HTN, HDL, history of PE/DVT and Type 2 DM was on insulin and jardiance, started ketodiet while continuing taking the jardiance and stopped taking his insulin because his sugars were controlled presented to the ED with abdominal pain, nausea and vomiting, had relatively normal vitals and benign physical exam, labs showed Bicarbonate of 9 mmol/L (22 - 33), anion gap of 31 (7 - 17), venous pH of 7.07 (7.33 - 7.43) glucose was 189 (7.33 - 7.43), beta-hydroxybutyrate of over 7.7 mmol/L (ref range <0.28), patient was admitted to the ICU and started on insulin on DKA protocol Conclusion: SGLT2 inhibitors may be associated with DKA due to their ketogenic effects secondary to enhanced lipolysis and increased glucagon to insulin ratio. although not expected, euglycemic DKA could be much more present in cases where there is predisposition to increase ketones generation w/without appropriate clearance eg. starvation, ketotic diet, AKI, etc. These should be monitored for and the patient needs to be educated about accordingly to prevent both adverse outcomes and potential decrease in drug use if not strongly indicated. also,It would be prudent for prescribing clinicians to advise patients to withhold potentially harming medications temporarily if they cannot maintain adequate oral intake.
Glycogenic Hepatopathy in a Patient with Pancreatogenic Diabetes
Authors: Baggett A Brooke , Jiwani Rahim Ali , Shahid Basma
Published: May 2021

Glycogenic hepatopathy is characterized by acute liver injury secondary to reversible accumulation of excess glycogen in hepatocytes. This phenomenon has been described in type 1 diabetes, with few cases reported in patients with type 2 diabetes. Glycogenic hepatopathy in the setting of pancreatogenic (type 3c) diabetes has yet to be reported.

A 57-year-old female with a history of insulin-requiring pancreatogenic diabetes mellitus secondary to alcohol-induced chronic pancreatitis status post distal pancreatectomy presented with recurrent admissions for abdominal pain, hyperglycemia, hyperosmolar hyperglycemic state (HHS), and unexplained elevation of liver transaminase levels. Glycemic control remained poor over many years with consistently elevated HbA1c in the setting of labile blood sugars, medication noncompliance, and lifestyle non-adherence.

The patient was admitted to the hospital with altered mental status and markedly elevated blood glucose (1,182 mg/dL) concerning for HHS. On admission, her liver function tests (LFTs) revealed elevated alkaline phosphatase (1,011 U/L, n <150 U/L), AST (583 U/L, n <34 U/L), and ALT (517 U/L, n <55 U/L). Direct and total bilirubin were within normal limits. The patient underwent extensive workup including drug and toxin levels, autoimmune evaluation, serology for infectious causes, abdominal computed tomography scanning, right upper quadrant ultrasound, and magnetic resonance cholangiopancreatography (MRCP). All laboratory workup was negative, ultrasound was unremarkable, and MRCP showed no evidence of biliary or common bile duct dilatation. Throughout her hospitalization, LFTs gradually improved with optimization of blood glucose.

Less than one week later, the patient returned with blood glucose of 673 mg/dL and LFTs notable for alkaline phosphatase 789 U/L, AST 1,068 U/L, and ALT 299 U/L. Again, all testing was negative for causes of rapid increase in liver enzymes. Similar to previous admissions, her LFTs improved with resolution of hyperglycemia. Review of electronic medical record revealed a similar trend during previous admissions. The patient did not undergo liver biopsy; however, the parallel relationship of LFTs and hyperglycemia, in the absence of radiologic or laboratory evidence of alternate liver pathology, supports the diagnosis of glycogenic hepatopathy.

This is the first case of glycogenic hepatopathy reported in a patient with pancreatogenic diabetes. Due to the rarity of this condition and minimal literature of its occurrence in adult non-type-1 diabetics, glycogenic hepatopathy is likely infrequently considered when evaluating patients with recurrent hyperglycemia and elevated LFTs. This case accentuates the need for further research of this condition in non-type 1 diabetics as the prognosis and management differ from other forms of acute liver injury.
Hemichorea Associated With Nonketotic Hyperglycemia: Rare Presentation of Uncontrolled Diabetes Mellitus
Authors: Katkar Rujuta Baban
Published: May 2021

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

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

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 <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 <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 >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

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 > 5 seconds, pitting pedal edema, elevated JVP, and crackles on chest auscultation. Labs showed BNP levels of 1130 pg/mL (n < 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 < 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

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<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.