bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Breaking Triglycerides
Authors: Dauterive Ellen , Wright Virginia
Published: May 2021

A 40 yo African American female with pmhx of T2DM, DLD was admitted for worsening leg and arm pain that started a year prior but had worsened in the last 6 months. Pain started in the right arm and progressed to include the right leg and left leg. She had presented to the ER 3 times in the last 3 weeks with no diagnosis and prescribed anti-inflammatories. On ROS she had unintended weight loss of 50 lbs. Pain was not relieved with anti-inflammatories or narcotics. She was diagnosed with diabetes in the previous 5 years and had not been compliant with her medications. Plain x-rays showed OA of the hip. An osseus survey showed multiple expansile, bubbly, and lucent intramedullary lesions consistent with polyostotic fibrous dysplasia versus multiple myeloma. CT showed a radiolucent lesion of the left femur with absence of normal bone trabeculae. Her labs showed normal calcium, phosphorous, renal function, PTH and no evidence of monoclonal gammopathy. Vitamin D was low at 8.2 ng/ml (6.6–49 ng/ml). CT CAP showed no concern for malignancy in other organs. A lipid profile was done and showed elevated fasting triglycerides of 2617 mg/dL (<150 mg/dl) and LDL direct 54 mg/dl (<100 mg/dl). A1c was 11.2% on admission. She denied any use of alcohol, estrogens, SSRI’s. No history of pancreatitis. On physical exam she did not have tendinous xanthomas, eruptive xanthomas, palmar xanthomas, or lipemia retinalis. Family history not significant for lipid disorders. Patient was fasted for 24 hours and then started on intensive insulin regimen as well as fenofibrate for hypertriglyceridemia. Triglycerides came down to less than 500 over 7 days. She was evaluated by ortho for her bone lesions and underwent bone lesion biopsy as well as prophylactic IMN of her bilateral femurs for prevention of impending fragility fractures. Bone biopsy was significant for xanthoma of the bone. Following discharge, she remained on fenofibrate and fish oil as well as a basal/bolus insulin regimen. Triglycerides remained controlled. She has not followed up outpatient for further workup. This case highlights an atypical presentation of triglyceride deposition in the setting of hypertriglyceridemia. It shows that hypertriglyceridemia should be included in the differential for lytic lesions when preliminary workup is negative. It also highlights that complications other than pancreatitis and cardiovascular disease can significantly alter a patient’s life if triglycerides go untreated.
Challenges in Managing Metabolic Complications in a Patient With Familial Partial Lipodystrophy Type 3
Authors: Shah Kajal , Charitou Marina
Published: May 2021

Familial partial lipodystrophy (FPL) is a rare group of autosomal dominant genetic disorders which causes variable loss of subcutaneous fat from abdomen, thorax or extremities in addition to the numerous metabolic complications like insulin resistance, diabetes mellitus and dyslipidemia1. FPL type 3 was first characterized by Agarwal et al. in 20021, in which peroxisome proliferator-activated receptor-γ (PPARγ) gene was the molecular basis of this disorder. It is extremely rare and so far only 30 patients or so have been recognized with this mutation2. FPL3 is unique because it generally spares the loss of fat from trunk, face and neck region and also presents with more severe metabolic derangements. We report a case of a young female with PPARγ mutation leading to numerous metabolic complications. A 19 year old female with FPL3 was seen by adult endocrinology as a transition from pediatric endocrinology. She was found to have hypertriglyceridemia on routine labs done at the age of 11. Patient reported loss of subcutaneous fat from her extremities and eruptive xanthoma on flexor surfaces at the time of diagnosis along with a positive family history of hypertriglyceridemia induced pancreatitis and Myocardial infarction at the age of 40 in her father. Her triglyceride level has varied between 600 and 3000 (normal 20–149 mg/dl) over the years. FPL3 was diagnosed based on genetic testing. She was prescribed fenofibrate and fish oil, and statin was added thereafter. She developed type 2 diabetes and was started on metformin and pioglitazone. She was noted to have hypertension and was treated with amlodipine and lisinopril. She also was found to have Polycystic Ovarian Syndrome (PCOS) based on menstrual irregularities, hirsutism and ultrasound showing multiple ovarian cysts, and was treated with spironolactone. Her most recent labs show triglyceride level of 2400 mg/dl and HbA1c of 8.3. PPARγ gene mutation in FPL3 leads to insulin resistance and hence patients often develop hypertriglyceridemia, type 2 diabetes, PCOS and hypertension. In terms of treatment options, we are still limited to pioglitazone, metformin, statins and fish oil. Often these are not sufficient in addressing the complexity of metabolic derangements in these patients who have an increased risk of cardiovascular events at a young age. Further research about agents targeting this gene in particular would be beneficial. 1. Agarwal et al. A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familial partial lipodystrophy. J Clin Endocrinol Metab. 2002 Jan; 87(1):408–411. 2. Garg A. Lipodystrophies: Genetic and Acquired Body Fat Disorders. J Clin Endocrinol Metab. 2011;96(11): 3313–3325.
Familial Partial Lipodystrophy: A Case Study and Review of Recent Literature
Authors: Tipu Ali , Hasan Farhad , Grimes Michael
Published: May 2021

Introduction: Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by loss of subcutaneous adipose tissue, mainly from the extremities and gluteal region. FPLD is associated with a variety of metabolic abnormalities including severe hypertriglyceridemia (HTG), insulin resistance (IR), and hepatic steatosis. We present a case of FPLD and summarize recent literature on the metabolic features and their management in patients with this rare disease. Case: A 44 year old female with medical history of Type 2 DM, hypertension, hypothyroidism and recurrent pancreatitis from severe HTG was referred to our clinic. She was diagnosed with Type 2 DM in her 30s. Over the ensuing years she had significant IR requiring increasing doses of concentrated insulin (up to 250 units/day). She reported progressive loss of subcutaneous fat from extremities in the preceding 2–3 years. She had recurrent pancreatitis, including a recent hospitalization with TG>8000 mg/dL. On examination, she had typical features of FPLD including loss of subcutaneous adipose tissue from upper and lower extremities including gluteal region, visible skeletal muscles and veins in the extremities, and neck and truncal obesity (Fig. 1). Family history was significant for similar physical and metabolic manifestations in her father and brother. For HTG, she is treated with fibrates and high intensity statin. We avoided the use of fish oil in the patient, because she did not feel well when she was previously on this. Results of the genetic testing are pending. Discussion: FPLD is rare, predominantly autosomal dominant, disorder characterized phenotypically by variable loss of subcutaneous fat and metabolically by severe HTG and insulin resistance. The severity of metabolic derangements is proportional to the degree of the lipodystrophy. The proposed mechanism is limited capacity of adipose tissue to store fat leading to ectopic fat deposition, lipotoxicity and vascular inflammation. Diagnosis is often clinical, especially the loss of subcutaneous fat in the extremities and signs of IR, and is confirmed by genetic testing. Dunnigan syndrome is the most common type of FPLD, which occurs from an autosomal dominant missense mutation in lamin A/C (LMNA). Gene mutations encoding for PPAR-gamma, Akt2, CIDEC, perilipin and the ZMPSTE 24 enzyme are much less common. Treatment of FPLD is challenging, and mostly focuses on managing the metabolic abnormalities. Recent evidence suggests that fish oil may in fact worsen HTG when the main defect driving increased TG is impaired chylomicron clearance, which our patient had on lipid NMR profile. Metreleptin, a human leptin analog, has recently been approved for the management of FPLD with evidence of improved metabolic abnormalities. Recent data also suggests that GLP1 agonists and SGLT2 inhibitors improved glycemic control and reduced daily insulin requirements.
Severe Hypercholesterolemia in Very-Low-Carbohydrate Diet
Authors: Modarressi Taher
Published: May 2021

There is growing popularity and interest in very-low-carbohydrate (VLC) diets for a variety of established and perceived health benefits. While some impacts have been seen in cardiometabolic diseases such as diabetes, hypertension and short-term weight loss (particularly when paired with caloric restriction), other effects such as in energy levels, mood and sense of well-being are variable. In the extreme, these diets suggest restriction of dietary carbohydrates (CHO) to less than 20 grams daily and often encourage a compensatory increase in dietary fat to promote ketogenesis. There has been concern about the long-term effects of these changes, as well as unintended consequences of increased saturated fat intake. A minority of patients, such as in the case below, may experience exaggerated lipid changes, thought to be influenced by underlying metabolic and genetic factors. Meta-analyses have shown conflicting results of the effects of VLC diets on low density lipoprotein cholesterol (LDL-C) levels.

A 63-year-old woman presented for outpatient consultation for markedly elevated LDL-C 524 mg/dL. The rest of her lipid panel was as follows: total cholesterol 637 mg/dL, triglycerides 152 mg/dL, HDL-C 83 mg/dL. She was asymptomatic. Record review of annual laboratory testing from her primary care physician revealed baseline LDL-C 114–134 mg/dL between 2012 and 2017. Her lipid panel in 2017 was as follows: total cholesterol 216 mg/dL, triglycerides 82 mg/dL, HDL-C 68 mg/dL, LDL-C 132 mg/dL. She described that in late 2017 she began a VLC diet for perceived metabolic benefits, and in the past year intensified CHO restriction to less than 15 grams daily. In 2018–2019, her LDL-C level increased to 303–316 mg/dL, and in 2020 to 524 mg/dL.

She had no history of diabetes, liver or kidney disease, nephrotic syndrome, hypothyroidism or alcohol use. She took no prescribed medications. She reported over-the-counter use of magnesium and potassium. She denied use of any other supplements or herbal remedies. Her past medical history included osteoarthritis. Her family history included hyperlipidemia in her mother, and coronary artery disease in both parents with age of onset in their 70s. She was a lifelong non-smoker and did not drink alcohol. Her BMI was 21.5. On examination, she was normotensive, euthyroid-appearing, and had no stigmata of familial hypercholesterolemia. Other labs were grossly normal, including blood counts, comprehensive metabolic panel, thyroid function tests, hemoglobin A1c and urinalysis. She was counseled extensively regarding her laboratory results and concerns about her cardiovascular safety.

This case demonstrates an exaggerated lipid response to a VLC diet, and supports the National Lipid Association scientific statement Class IIa recommendation to obtain baseline and follow-up lipid profiles in patients who follow such diets due to variation in lipid response.
Antidiabetic Effects of NRDT50, the Enzyme Composition for Regulating Sugar Metabolism, in Db/db Mice
Authors: Kim Daham , Ku Cheol Ryong , Kim Jung Seung , Hwang Jihwan , Cho Yoon Hee , Lee Eun Jig
Published: May 2021

Objective: The enzyme composition (NRDT50) which includes glucosyl transferase, fructosyl transferase, amylase, glucose oxidase, and catalase can regulate the absorption of glucose into the body by converting the carbohydrates in food to a form of sugar that is not absorbed in the stomach before being decomposed in the small intestine into glucose. The aim of this study was to evaluate the antidiabetic effects of repeated oral administration of NRDT50 in db/db mice. Methods: The 7-week-old db/db mice were divided into 3 groups; control, NRDT50 (300mg/kg/day), and voglibose (0.3mg/kg/day). Mice received a standard diet containing drugs for 1 month. Fasting and postprandial glucose level was measured every week. Mixed meal test, biochemical assays, and fecal microbiota analysis were performed. Results: There were no significant differences in body weight or food intake between the three groups. However, NRDT50 treatment led to a significant reduction in fasting and postprandial blood glucose levels compared to control after 3, 4 weeks. The blood glucose levels during the mixed meal test were significantly lower in NRDT50 group compared to control group. NRDT50 treatment reduced triglyceride level, tend to reduce LDL level, and increased relative Bacteroidetes-Firmicutes ratio. NRDT50 treatment did not demonstrate any negative side effects on biochemical and histopathological examination. Conclusion: NRDT50 is expected to be useful for people who are at risk of hyperglycemia or diabetes and thus need to regulate blood sugar with safe. It may also improve the gut microbiota profile by inducing the production of oligosaccharides in the alimentary tract.
Comparison Between Linagliptin and Canagliflozin Effect on Inflammatory Markers, CD34+ Cell Gene Expression and Urine Exosomes in Type 2 Diabetes Subjects
Authors: Nandula Seshagiri R , Janapala Rajesh , Sen Sabyasachi
Published: May 2021

Introduction: Peripheral blood derived CD34 +ve Endothelial progenitor cells (EPCs) has been shown to help vascular regeneration and are dysfunctional in subjects with type 2 diabetes mellitus (T2DM) leading to poor endothelial cell function (ECF). We conducted two separate clinical trials using Canagliflozin, an SGLT2 inhibitor and Linagliptin, a DPP4 inhibitor where these medications or matched placebo was added to other oral antidiabetic medication such Metformin and Insulin. Our goal was to do a comparative analysis based on the effect of the medications on CD34+ve hematopoetic progenitor cell function such as migration, colony formation and podocyte specific urine exosome analysis. Methods: Approximately 30 subjects were enrolled in the two studies 29 subjects were enrolled in this 12–16 weeks, double-blind, two-arm, randomized placebo matched trial, with 100 mg Canagliflozin (Cana, low dose) compared to placebo AND Linagliptin (Lina 5mg), compared to placebo. T2DM (30–70 years old), HbA1c of 7–10%, were included. Peripheral blood derived CD34+ cell number, migratory function, mRNA gene expression along with cardiometabolic parameters such as arterial stiffness, biochemistry, resting energy expenditure, and body composition were measured. Data were collected at weeks 0 (baseline), 6 or 8 (mid-point), and 12 or 16 (final). A mixed model regression analysis was done with a p-value <0.05 considered significant. Results: We found a statistically significant reduction in systolic (p=0.008) and diastolic (p=0.038) blood pressure in cana group. There was a statistically significant increase in adiponectin (p=0.0062) and trend level reduction in IL6 (p=0.16), indicating an anti-inflammatory effect of canagliflozin on endothelium, not seen in Lina group. There was an increase in mRNA expression of genes associated with endothelial function in CD34+ cells such as VEGFA, PECAM-1, a mature endothelial marker and NOS3 (or eNOS) with both Cana and Lina. There was improvement in CD34+ numbers by direct counting (not statistically significant) with both medications. Data on urine podocyte specific exosomal protein indicates an advantage with Cana compared to Lina, though it did not reach stat significance. Conclusions: Our study indicates that Canagliflozin improves several components of vascular function by improving adiponectin, reducing inflammatory cytokines, and by increasing expression of endothelium specific genes in CD34+ progenitor cells compared to Linagliptin.
Medicsen Smartpatch: A New Approach to Diabetes Management
Authors: Ruiz Alejandro , García Rafael Danilo , Jorgensen Carlos , Jorgensen Eduardo
Published: May 2021

Introduction: Diabetes is a metabolic disorder characterized by a dysregulation of the glucose levels. With insulin being the main drug to be administrated for glucose levels modulation, it needs to be injected subcutaneously with daily injections, which can lead to poor patient compliance, apart from several side-effects. Although other administration methodologies have been investigated (oral or inhaled insulin), they show enough drawbacks to not to be consider as feasible alternatives for diabetes therapy. That′s why Medicsen has developed a Smartpatch that integrates a wide range of technologies, with the purpose of ensuring the correct insulin delivery from the skin′s surface to the bloodstream using a non-invasive and painless drug delivery method through a phenomenon induced by sonophoresis. Materials and Methods: Several in vitro and in vivo tests have been performed to prove the efficacy and safety of the technology, allowing us to collect experimental evidence through different methodologies that demonstrate the therapeutic potential of the device. Among these methodologies, permeability studies using Franz diffusion Cell and swine models (that prove efficacy of the technology) as well as safety studies, for both the insulin and the skin are highlighted. Results: In voltage experiments, the mean time for the disappearance of the membrane potential between the compartments separated by skin was: 334.7 (SD+/-103.6) seconds. Regarding the slope of the voltage line, as an approximation to the transfer speed, an arithmetic mean of (μ)= 0.0164 Mvolts/sec (+/- SD(σ): 0.006) was obtained. No significant differences were found between the circular dichroism spectra of samples (minimum peak at 219nm (sd+/-8.31) and that of the standard, which suggests that the molecular structure of insulin maintains stability. In the same way, HPLC studies shows no variability between the standard and all groups tested. Regardin skin safety, SEM images shows no significant damage to the skin, and ELISA test for TNF α and IL-2, as well as other biochemical tests, show no differences between control and samples. On In vivo experiments with our technology, glucose changes are comparable to those evoked through direct drug injection using conventional syringes. Lastly, the technology proved to be effective in the delivery of insulin through the skin in a non-invasive way, as observed in a Franz Diffusion Cell system and in the in vivo model of blood glucose reduction. Conclusions: Results observed during in vitro and in vivo studies indicate that the technology developed by Medicsen is effective and safe for the patient and the insulin. Following steps, including human trials, will be critical to fully demonstrate its potential in the treatment of diabetes.
Covid-19 and New Onset Diabetes: A Case Series
Authors: Saleem Marwa , Zahra Tasneem , Menon Vidya , Vargas-Jerez Julia , Sarwal Amara
Published: May 2021

Background: During the SARS CoV1 pandemic in 2003, there was much literature published about newly diagnosed diabetes mellitus (DM) in the patient population infected. This phenomenon has not been well established during this SARS CoV2 pandemic. In this case series, we aim to evaluate patients admitted to our facility with new onset DM who had a history of COVID-19 infection.

Method: This was a single center case series that included adult patients who presented to our facility with new onset DM during June-October 2020 who had a history of SARS CoV2 positive PCR and/or positive IgG antibody to SARS CoV2. Pregnant patients were excluded. Data was collected from the hospital electronic medical records. Diagnosis of diabetes was determined in these patients via hemoglobin A1C (HbA1C) level greater than 6.5%.

Results: Six patients fulfilled our diagnostic criteria. All patients were male with a median age of 54 years. The median BMI is 33.9, with 5 patients considered to be obese and 1 overweight. Other than the increased BMI, 2 patients with pre-DM and 3 patients who had a family history of DM, no other identifiable risk factors for DM were noted in this cohort.

Five patients required hospitalization for HHS or DKA and 1 patient was managed as an outpatient. Median random serum glucose on presentation was 761.5 mg/dl and median HbA1C on presentation was 11.5%. Significant dosages of parenteral insulin (0.45 U/Kg) was required for hospitalized patients during their inpatient stay along with immediately after discharge to control their hyperglycemia. Glutamic Acid Decarboxylase and Islet Cell antibodies were done for 2 of the patients and were negative.

Three of the patients who had follow up in 2 months showed improvement in their HbA1C (median of 7.1% [5.4–10.7]) and considerably diminished subcutaneous insulin requirement (0.2U/Kg). Two of these patients continued to follow up, and at 4 months from onset of DM, median HbA1C was 5.85% with insulin ceased. Of note, the patient who was lost to follow up was found to have an HbA1C improvement from 11.4% to 5.4% at the 2 month mark.

Discussion: Both SARS CoV1 and SARS CoV2 activates the RAAS, causing insulin resistance by altering insulin signaling and increasing oxidative stress leading to dysfunction of pancreatic beta calls. The inflammatory cytokine storm response seen in COVID-19 can also decrease skeletal muscle sensitivity to insulin and decrease peripheral glucose uptake. These mechanisms may be leading to the new-onset DM noticed in our COVID-19 patients. In addition, there may be a possible immune-mediated mechanism given the matched time line between the COVID-19 antibody life span and the duration of DM.

It is unknown whether this effect is permanent or temporary, although our results do support the latter. More studies that utilize a larger cohort and longer follow up are needed in order to get a better understanding of the mechanism of DM in COVID-19 infection.
Type ll Diabetic Patients’ Attitudes Toward Influenza and Covid-19 Vaccination
Authors: Gilfix Reisa , Elstein Jack , Elstein Eleanor
Published: May 2021

Influenza vaccination (fluv) is free and easily accessible to diabetics in Quebec. The importance of vaccination (v) during the Covid19 (CV19) pandemic has been widely discussed in the media. To ascertain the receptiveness of type 2 diabetics (T2D) to fluv during the CV19 pandemic and their acceptance of an eventual CV19 vaccine (CVv) we carried out telephone interviews with 34 unselected T2D pts in Montreal, Quebec post the 1st wave of CV19 in that region. Pts were asked if they planned taking the fluv and/or an eventual CVv, reasons for reticence to v, and attitudes toward and compliance with public health (PH) directives. They were also asked their primary source of health related information. Recent HbA1c and insulin use were recorded. Thirty four T2Ds were surveyed, 22 M 50–87 yrs (mean 69.2) and 12 F 49–84 yrs (mean 68.8). Eleven M and 5 F were on insulin. HbA1c ranged from 5.9–13.0 (mean 7.3). None of the pts had recently discussed v with a healthcare provider (HCP). One pt received his health related information from Facebook, the others from mainstream media. None had contraindications to v. None had been diagnosed with CV19. Past influenza history was unknown. Forty one percent (14/34) of pts, 11 M 50–86 yrs (mean 66.0) and 3 F 49–66 yrs (mean 59.0) did not plan to take the fluv. They explained their decisions as never having taken fluv (12 pts) or having been ill despite having taken it (2 pts). Neither accessibility nor cost were issues. Two F, 62 and 66 yrs, who refused fluv also refused CVv. Six M aged 60–86 yrs (mean 70.5) and 1 F aged 73 yrs were planning to wait to access real life safety (6pts) or efficacy (1pt) data before accepting CVv. All pts claimed to be following PH guidelines including social distancing, hand washing, and mask recommendations; 91.2% (31/34) fully agreed with PH policies, 2 were in moderate agreement and 1 thought PH policy was not strict enough. Of the latter 3 pts none planned on taking the fluv. One planned taking the CVv, 1 planned not to, and the 3rd planned to wait before deciding. Despite a long history of use, recommendations by experts, and free and easy accessibility, T2D pts questioned after the 1st wave of CV19 are not convinced of the fluv’s importance. Despite high case numbers and being themselves at high risk, not all T2Ds are willing to unequivocally accept a potential Health Canada sanctioned CVv. This study underlines the important work HCPs have ahead in educating and reassuring pts with regard to vaccination.
A Case of Euglycemic Diabetic Ketoacidosis Following Canagliflozin Therapy
Authors: Tuna Kubra M , Abdelmasih Randa , Abdelmaseih Ramy , Alsamman Mrhaf , Robbins Joseph
Published: May 2021

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus (DM). In general, DKA characterized by blood sugar over 250 mg/dL, anion-gap metabolic acidosis, and increased plasma or urine ketones. Approximately 2–3% of DKA patients can present with normal blood glucose levels (less than 250 mg/dl) which called euglycemic DKA. Some of the etiologies of euglycemic DKA include recent use of insulin, low caloric intake, alcoholism, chronic liver disease, and pregnancy. Very rarely, SGLT2 inhibitor use may be responsible for euglycemic DKA.

Case Presentation: Here we present a case of 44 years old female with a past medical history of DM type 2 who presented with acute onset of nausea and vomiting. Initial laboratory findings were remarkable for anion gap metabolic acidosis with a blood glucose level of 201 mg/dl. The patient was on long-acting insulin along with Canagliflozin and Metformin therapy over years and reported being compliant with medications. She was treated with intravenous insulin therapy which resolved acidosis as well as symptoms. The patient was discharged with recommendations of discontinuation of Canagliflozin.

Discussion: SGLT2 inhibitors are the novel class of oral antidiabetic drugs which widely used due to their favorable cardiovascular and renal outcomes independent of glycemic control. However, their side effects remain a concern. DKA is a rare but serious side effect of SGLT2 inhibitors with an incidence rate of 9.4% in type 1 DM and less than 0.2% in type 2 DM. Patients typically present with euglycemia or low-grade hyperglycemia which results in a diagnostic challenge for treating physicians. SGLT2 inhibitors increase urinary glucose excretion with a subsequent decrease in circulating insulin and an increase in glucagon, rendering a metabolic shift from glucose to fatty acid utilization. During times of intercurrent illness (decreased oral intake, sepsis) or metabolic stress (surgery), decreased carbohydrate intake coupled with the aforementioned changes will result in decreased insulin secretion and increased counter-regulatory hormones including adrenaline and cortisol, promoting lipolysis, fatty acid oxidation, and ketone production by the liver which ultimately leading to euglycemic DKA.

Conclusion: SGLT2 inhibitors induced euglycemic DKA treatment is identical to classic DKA with consideration of the lack of hyperglycemia. Appropriate patient counseling to ensure safe SGLT2 inhibitor therapy is crucial, including appropriate holding parameters during concomitant volume-depleting illnesses and decreased oral intake. Timely diagnosis of euglycemic DKA, and recognitions of other rare but lethal side effects to decrease overall morbidity and mortality.
Alpelisib Induced Hyperglycemic Ketoacidosis; Broadening the Adverse Effect Profile of an Emerging Cancer Therapy
Authors: Prasad Apurwa , Ali Faisal S , Thapa Pratikshya , Tuason John P W , Kim Keun Young
Published: May 2021

Introduction:

Alpelisib (PIQRAY) is a Phosphatidylinositol 3-Kinase Inhibitor (PIP-3K) recently approved by the united states food and drug administration (FDA) for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated, advanced, or metastatic breast cancer in post-menopausal women or men with an adjuvant to Fulvestrant. Hyperglycemia is a well-known side effect of Alpelisib. However, hyperglycemic ketoacidosis is a rare and life-threatening side effect.

Case Presentation:

A 63-year-old Caucasian woman with ER/PR+, HER2- metastatic breast cancer presented to the emergency room (ER) with polydipsia, polyuria, dryness of the mouth and skin, along with a 12-pound weight loss over a period of three weeks. Alpelisib was initiated three months prior to her presentation with Hba1c: 6.4% and random BG: 89 mg/dl at the time. Her initial lab work in the ER revealed blood glucose of 474 mg/dl, sodium 129 mmol/L, potassium 5.1 mmol/L, and an anion gap of 15 with a Co2 of 19 mmol/L, HCO3 of 20 mmol/L, and a blood ketones level of 2.6. Her urinalysis revealed glucosuria and ketonuria. She was admitted to the general medical floor and Alpelisib was held. In light of her insulin naivety and no history of diabetes mellitus, it was decided to treat her with subcutaneous insulin with hourly titration based on monitoring of serum glucose and electrolytes with IV hydration. She required a total of 31 units of regular insulin along with 15 units of long-acting insulin. Her ketosis resolved within 12 hours of admission. Endocrinology was consulted and she was discharged on long-acting insulin 15. On follow-up, Alpelisib was resumed, metformin added along with long-acting insulin. Despite anti-diabetic therapy, due to persistent hyperglycemia (fasting blood glucose >300 mg/dl), Alpelisib was discontinued 3 weeks after presentation.

Conclusion:

Alpelisib-induced hyperglycemic ketoacidosis is an uncommonly reported adverse event with only 3 reported cases to the best of our knowledge. While there are guidelines available to manage Alpelisib induced hyperglycemia, there are no specific recommendations for patients presenting with hyperglycemia and ketoacidosis in terms of admission to intensive care unit (ICU) or general medical floor (GMF), use of the type, route, and dosage of insulin and continuation of insulin for the persistent elevation of FBG despite interruption of Alpelisib. Alternative approaches for the treatment of breast cancer should be considered with continual hyperglycemia despite appropriate management. Multidisciplinary discussion involving the oncologist as well as an endocrinologist can be useful for the management of persistent elevation of FPG even after substantial Alpelisib free days.
Alpelisib-Induced Diabetic Ketoacidosis- A Case Report
Authors: Rodriguez Lisette Patricia , Wiese-Rometsch Wilhelmine , Lorenzo Christian
Published: May 2021

Background: Alpelisib, in combination with Fulvestrant, was approved in 2019 by the Food and Drug Administration for treatment of HR+, HER2- advanced or metastatic breast cancer in patients with PIK3CA mutation. a This combination is currently on phase III of study. One of the most common side effects is hyperglycemia. Rarely, this can be severe enough to induce diabetes ketoacidosis, which is an indication for interrupting Alpelisib treatment.

Clinical Case: A 78 year old female presented to our emergency department with altered mentation. Her past medical history is significant for metastatic breast cancer, with known PIK3CA mutation, started on alpelisib three months prior. Concomitantly, despite not carrying a diagnosis of diabetes mellitus, the patient was started on metformin, due to the known side effect of hyperglycemia. Upon admission, the patient was found to be tachycardic and otherwise hemodynamically stable. Pertinent laboratory studies revealed an initial serum glucose of 600 (nl 70–100) mg/dL, potassium of 5.4 (nl 3.5–5.1) mmol/L, serum carbon dioxide of 8 (nl 21–32) mmol/L, calculated anion gap of 25 (nl <12) mEq/L, and a serum beta-hydroxybutyrate > 4.50(nl 0.02–0.27) mmol/l. ABG revealed a pH of 7.11, PaO2 of 102, pCO2 of 11, and a lactate of 4.0 mmol/L. Glycated hemoglobin was 10.7% (nl <6.5%). EKG revealed sinus tachycardia with PACs, abnormal anterolateral T wave inversion, and a QTc of 519 msec. Initial troponin was elevated at 0.15 with a max troponin at 1.40 ng/mL. Urinalysis revealed glucosuria. Chest x-ray showed no acute cardiopulmonary process. Blood cultures were negative to completion. Patient was admitted for diabetic ketoacidosis and was started on DKA protocol which included aggressive hydration with sodium chloride and insulin drip. Alpelisib was discontinued immediately. Upon resolution of the anion gap metabolic acidosis, the patient’s encephalopathy significantly improved. She was transitioned to subcutaneous insulin. During the same hospitalization, the patient’s serum glucose rapidly normalized and she did not require insulin at the time of discharge.

Conclusion: Diabetic ketoacidosis is an unusual but life-threatening side effect of Alpelisib, even in patients without an underlying diagnosis of diabetes mellitus. This case suggests that such patients should have a close monitoring of glycemic control and intensification of their anti-diabetic medications if required, to prevent hyperglycemic crises.
Clozapine Induced Insulin Dependence
Authors: McCalmon Sean , Weide Lamont G
Published: May 2021

Background: Antipsychotic medications come with an array of potential side effects in a difficult-to-treat population, particularly if management of other comorbidities is required. A review of the literature shows some studies have discussed the possibility of antipsychotic medication inducing hyperglycemia by blocking pancreatic M3 receptors. Other studies have shown dramatic worsening of metabolic parameters in patients who already have Type 2 Diabetes Mellitus after starting Clozapine. Clinical Case: A 23 year old African American Male with a past history of treatment resistant Schizophrenia presented to the ED with hyperglycemia and altered mental status. Blood sugar 489 mg/dL, anion gap 28 mmol/L, bicarb 13 mmol/L, white Blood Cell count 9.0 x10^3/cmm. Urine positive for Ketones. Chest Xray and EKG were normal, there were no obvious signs of infection. This was the sixth admission for Diabetic Ketoacidosis (DKA) in the past 10 months. Antibodies obtained showed negative Glutamic Acid Decarboxylase Autoantibodies (<5 IU/mL), Islet Cell Antibody IgG, Zinc Transporter 8 Antibody (<10 U/mL), IA-2 (<5.4 U/mL). C-peptide levels were in the low normal range (1.12 ng/mL) with a blood sugar 204 mg/dL. Prior to 10 months ago, the patient did not have a diagnosis of diabetes, with labs showing expected normal fasting blood sugar levels (90s mg/dL) and triglyceride levels of 150 - 200 mg/dL. One month after starting Clozapine for treatment resistant Schizophrenia, A1c doubled to 12.3%, Triglycerides increased to 1,378 mg/dL. The patient had been insulin dependent since the time of starting Clozapine. On this admission, Clozapine was held, DKA resolved with intravenous fluid, potassium replacement, and insulin drip. Repeat testing of c-peptide with blood glucose levels analyzed with the Homeostasis Model Assessment (HOMA) showed increasing HOMA%S (from 93% to 174%) and decreasing HOMA-IR with stopping Clozapine. Psychiatry recommended Clozapine as required treatment of his Schizophrenia, therefore the patient required chronic insulin. Conclusion: This case study shows Clozapine as the only major change in medications or lifestyle in this patient’s case. He demonstrated severe hyperglycemia and development of Diabetes Mellitus within a 4-week period of medication initiation as evidenced by multiple admissions for DKA, with low/normal C-peptide levels and insulin resistance. He has since been managed as a patient with Type 1 Diabetes. Clinicians should take a multidisciplinary approach to clinical surveillance during changes in schizophrenia treatment, particularly with second generation antipsychotics such as Clozapine, with attention to metabolic derangements including DKA.
Diabetes Induced Osmotic Demyelination of the Pons in a Patient on Peritoneal Dialysis
Authors: Mandava Sri , Pfeifer Lucas , D’Souza Gretel , Wilson Mark
Published: May 2021

Introduction: Osmotic demyelination of the pons as a result of uncontrolled diabetes is a rare event. Here we present a unique case of central pontine myelinolysis in a patient with poorly controlled type 2 diabetes mellitus in the setting of peritoneal dialysis.

Clinical Case: A 48-year-old male with a history of insulin-dependent diabetes mellitus, hypertension, non-ischemic cardiomyopathy, and end-stage renal disease, treated with peritoneal dialysis, presented to the hospital for slurred speech, inability to walk, and persistent hyperglycemia for 3 days. Approximately 2 years prior to admission, peritoneal dialysis was initiated for ESRD and poor cardiac function. The patient’s outpatient pharmacologic regimen was 30 units of glargine daily and glimepiride. On physical exam, there was evidence of aphasia, dysarthria, and muscle weakness (2/5 in bilateral upper and lower extremities) without muscle rigidity. Deep tendon reflexes were absent in the lower extremities, but sensation to light touch was intact throughout. On admission, the patient was found to be in a hyperosmolar hyperglycemic state without ketosis. Initial lab tests were significant for serum sodium: 138mmol/L (n=134–145 mmol/L), serum sodium corrected for hyperglycemia: 143 mmol/L, serum glucose: 419mg/dL (n=75–99 mg/dL), beta-hydroxybutyrate 2.1 mg/dL (n<4.4 mg/dL), and serum osmolality: 330mosmol/kg (n=275–305 mosmol/kg). Urinalysis showed glucosuria without ketonuria. The cerebrospinal fluid analysis showed protein 57, glucose 109, and WBC 3. Lab studies for meningitis/encephalitis panel were negative. During his 2 years of dialysis, his HbA1C increased from 7.6% to 14.3% (n<5.6%). CT brain without contrast showed midline hypoattenuation of the inferior pons without edema. Magnetic resonance imaging without contrast of the brain demonstrated a lobulated lesion in the pons measuring 1–2 cm that shows T2 hyperintensity without surrounding edema. He was then diagnosed with central pontine myelinolysis in the setting of chronic glycemic changes.

Conclusion: Osmotic demyelination of the pons is typically associated with rapid correction of hyponatremia. We describe osmotic demyelination of the pons as a result of poorly controlled diabetes with normal sodium. To our knowledge, this is the first report of this event in association with worsening diabetes after the initiation of peritoneal dialysis.
Diabetic Ketoacidosis and Acute Pancreatitis in Covid-19 Setting
Authors: Srinivasan Aswin , Wilson Branden , Pansuriya Tusharkumar , Qasmi Syed Talha , Kesavan Ramesh Babu
Published: May 2021

Introduction: Respiratory, kidney and gastrointestinal are some of the systems affected by COVID-19. Although COVID-19 has been studied as a lung pathogen, endocrine system involvement has rarely been studied. In this case report, we present a case of diabetic ketoacidosis (DKA) and acute pancreatitis in the setting of COVID-19.

Case Description: A 52-year-old female with a PMH of type 1 diabetes mellitus and hypothyroidism, presented to the ED with nausea, vomiting, fatigue and diffuse abdominal pain. She reports cosmetic surgery a few weeks prior and she started feeling these symptoms at the beginning of admission day of admission. On admission, WBC was 34.9, blood glucose was 496, lactic acid of 3.1. Arterial blood gas revealed pH of 6.96, PCO2 of 17 mEq/L, PO2 of 143, HCO3 of 5 and anion gap of 23. DKA protocol was initiated and was upgraded to ICU. She was found to be RT-PCR positive for SARS-CoV-2. She denied other symptoms, including melena, jaundice, hematochezia, hematemesis, cough, SOB or diarrhea. She also denied use of alcohol, tobacco or illicit drugs, prior hospitalizations, or family history of pancreatitis. The physical exam was significant for tenderness to palpation in epigastric region without guarding or rebound. Laboratory studies revealed lipase: > 4000U/L, AST: 64 U/L, ALT: 57 U/L, ALKPHOS: 152 U/L, and total bilirubin: 1.1 mg/dL. Serum triglycerides and calcium levels were within normal limits. CT abdomen showed a severe peripancreatic inflammation and edema, moderate non-organized fluid surrounds pancreas. An abdominal ultrasound showed no calcified gallstone or gallbladder wall thickening. The common bile duct was 3 mm, normal size. Over the course of 24 hours, anion gap was 7, pH was 7.28, blood glucose was 158. For sepsis, lactic acid was 0.7 after initiation of azithromycin. For acute pancreatitis, she was treated conservatively with intravenous fluids, bowel rest and analgesia. Patient denied any upper respiratory symptoms and did not require oxygen so steroids were not started for COVID PNA. Her symptoms improved and she was discharged home. Discussion: Here we report a case of a patient who presented with DKA, found to have severe acute pancreatitis as well as SARS-CoV2 PCR positive. Few case reports have reported an association of DKA and acute pancreatitis. Although the exact mechanism by which SARS-CoV-2 is evolving, it is thought to be mediated by the Angiotensin-Converting Enzyme-2 which is present in intestine, and on islet cells of the pancreas. This injury may be due to cytopathic effect of viral replication or indirectly caused by the inflammatory response induced by the virus. Further studies are needed to better understand the pathophysiology behind AP in the setting of COVID-19.

Conclusion: This case highlights DKA and AP as a possible initiating presenting manifestation of COVID-19 infection
DKA in Diet-Controlled Patient With Type 2 Diabetes and ESRD Precipitated by Acute COVID-19
Authors: Shafique Anum , Hamal Savyata , Huq Sabrina
Published: May 2021

Type 2 diabetes mellitus (T2DM) is the main factor for the global rise in end stage renal disease (ESRD), accounting for about 45% of the dialysis patient population in United States. Although T2DM is a common cause for ESRD, it is uncommon for well controlled T2DM patients on dialysis to develop DKA. The COVID-19 pandemic has highlighted infections as a precipitating cause of diabetic ketoacidosis (DKA) and stresses the importance of optimal glycemic control. We report a case of a previously diet controlled patient with T2DM and ESRD admitted with DKA and acute COVID-19. 46-year-old male with diet controlled T2DM, HIV (human immunodeficiency virus) on HAART (highly active antiretroviral therapy), ESRD secondary to HIV associated nephropathy was admitted from an outpatient dialysis unit with vomiting, chills and body aches. He was on metformin monotherapy prior to dialysis initiation. Regular self-monitored blood glucoses ranged 80-130mg/dl with HbA1C of 6% one month prior. Lab tests on admit revealed serum glucose 499mg/dl, elevated anion gap 21mmol/L, potassium 3.5mmol/L (3.5–5.0), HbA1C: 14.7%, elevated beta-hydroxybutyrate 5.6mmol/L(normal:<=0.4), CD4 count 500 (489–1457/µL) with an undetectable HIV viral load however COVID-19 polymerase chain reaction was detectable. He was managed with cautious fluid resuscitation requiring a total of one-liter normal saline, higher potassium dialysate (3K+), and continuous insulin infusion with resolution of abdominal symptoms and DKA. No other infections or precipitating factors were found and acute COVID-19 infection was managed symptomatically. He was discharged on basal bolus insulin regimen on day seven of admit. Up to a third of patients with diabetes on dialysis do not require anti-hyperglycemic therapy, such as our case. Potential factors leading to reduced insulin requirements include reduced renal insulin clearance,reduced renal gluconeogenesis, protein-energy wasting, reduced body weight and accumulation of uremic toxins (guanidino compounds postulated to act as biguanide agents). Our case highlights that acute COVID-19 can precipitate DKA in previously well controlled T2DM patients on hemodialysis while being aware of the need for cautious fluid and potassium administration due to lack of osmotic diuresis in anuric dialysis patients. Close self-monitoring of blood glucose should be emphasized in patients withT2DM with ESRD, including diet controlled T2DM patients, in order to reduce hyperglycemic emergencies and inpatient admissions especially during COVID-19 pandemic.
Does a Supplement Cocktail a Day Keep the Doctor Away? An Unusual Case of Alcohol Induced Diabetes Mellitus: A Case Report and Review of Literature
Authors: Breault Kaley N , Arakaki Brittney H , Cabandugama Peminda K , Rowe Jordan M
Published: May 2021

Background: Currently there are no evidence-based medical recommendations to support the use of supplements in type 1 diabetes mellitus (DM), although there is some data that supports glucose lowering in type 2 DM with supplements such as cinnamon. Additionally, there is no evidence regarding the use of supplements in insulin-dependent DM secondary to pancreatic dysfunction from alcohol use disorder. Despite lack of clear evidence, it is estimated that more than 65% of Americans with DM use at least one dietary supplement for perceived health benefits. (1)Clinical Case: A 58-year old male presented with insulin-dependent DM secondary to pancreatic dysfunction from alcohol use disorder. Initial labs were significant for a low C-peptide of 0.13 ng/mL (0.80–3.85 ng/mL), A1c -9.4%, and blood glucoses ranging from 160–300 mg/dL. Patient’s DM regimen consisted of glargine 40 units nightly and aspart 12 units three times a day with meals. On a subsequent visit two months later, the patient stated that he had begun taking numerous supplements in hopes that these would improve his overall medical status. Supplements included Blood Boost Formula, Ultra K2 with MK-7, Chromium Picolinate, Male Enhancement, Super C Immune Complex, Nugenix Total-T, Niacinamide, Omega Q Plus Max, Cortisol Hormone Balancer, and Vitamin D3. Simultaneously, the patient self-discontinued all his maintenance medications except for his aforementioned insulin regimen due to the fear of negatively impacting his pancreas. Unexpectedly, his blood glucoses improved to a range of 90–150 mg/dL after being on these supplements without increasing his insulin dose. Upon literature review, three ingredients showed the most evidence for the possible explanation for his improvement in glucose control: L-arginine, nettle extract, and biotin with chromium. Conclusion: Literature review of in vivo and randomized, placebo-controlled studies demonstrated mechanisms of action for L-arginine, nettle extract, and biotin with chromium that indicate their potential role in lowering blood glucoses and increasing C-peptide levels in insulin-dependent DM secondary to pancreatic dysfunction from alcohol use disorder. Further investigations include exploring long-term impact on pancreatic function, glucose control, and insulin resistance. Reference: (1) Garrow, D., Egede, L. Association Between Complementary and Alternative Medicine Use, Preventive Care Practices, and Use of Conventional Medical Services Among Adults with Diabetes. Diabetes Care 2006 Jan; 29(1): 15–19.