bluuebunny/crossref_metadata_2025 huggingface dataset:
LBODP034 Metformin Associated Lactic Acidosis, Rare But Real
Authors: Khalifa Maram , Kantorovitch Vitaly
Published: November 2022

Background

Metformin has been widely used as a first-line agent to treat type 2 diabetes mellitus. Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e. g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA).

Case description

We present a case of a severe metformin-induced lactic acidosis in a patient with type 2 DM admitted to the emergency department with a history of dehydration due to diarrhea and complicated by acute renal failure Our patient is a 57-year-old female with a medical history of DM on metformin 1000 mg twice daily, hypertension, hyperlipidemia, and hypothyroidism who presented to the hospital with a concern of altered mental status. Upon presentation, the patient could not provide much history, but her daughter confirmed that she was in her normal state of health until 2 weeks ago when she started complaining of knee pain and stated that she was taking ibuprofen 600 mg every 8 hours for pain with good response. Later, 2 days prior to her presentation she started having severe nausea, vomiting, weakness and was noted to be confused so she was brought to the emergency department. Upon arrival the patient's blood pressure was noted to be 104/50, GCS 15, rest of the vitals were within normal. Potassium was 5.5(3.4 - 5.3 mmol/L), bicarbonate 5(22 - 33 mmol/L), creatinine 10.2(0.4 - 1.1 mg/dL) compared to normal creatinine 6 months ago, GFR<5(>59 ml/min/1.73 sq meters, anion gap 41(4-16), PH 6.7(7.33 - 7.43), After resuscitation, her severe acidemia persisted despite aggressive intervention with volume resuscitation and vasopressors, leading to the initiation of renal replacement therapy. After multiple dialysis treatments, her severe acidemia resolved and creatinine improved back to baseline after which she was discharged home in stable condition.

Conclusion

The reported incidence of lactic acidosis in clinical practice has proved to be very low (<10 cases per 100,000 patient-years). This literature-based review provides an update on the impact of renal function and other conditions (cirrhosis, sepsis, or hypoperfusion) on metformin plasma levels and the risk of MALA in patients with type 2 diabetes. As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment to minimize the potential for toxic metformin levels and MALA.

Presentation: No date and time listed
PSUN248 Mitochondrial diabetes - a rare but important cause of diabetes
Authors: Botros Mina , Ohri Anupam
Published: November 2022

Background

Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder which presents with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. Mitochondrial diabetes is the cause in 1% of all diabetic patients. Here we present a case of a patient with insulin dependent diabetes mellitus (DM) who experienced sensorineural deafness and was diagnosed with MELAS.

Case

33-year-old female presented with stroke like symptoms in December 2018. Medical history was significant for Diabetes Mellitus (DM), bilateral deafness and end stage renal disease requiring peritoneal dialysis with subsequent kidney transplant. On presentation, she had left sided weakness, lab work revealed lactic acidosis. MRI brain showed large areas of restricted diffusion in right hemisphere and cerebral edema. CSF analysis was positive for lactate and pyruvate. Left lower extremity muscle biopsy and mitochondrial genome analysis were positive for m.3243A>G in the MT-TL1 with 80% heteroplasmy, confirming the diagnosis of MELAS. Patient was started on Arginine, CoQ10, Levetiracetam, phenytoin, IVIG and her symptoms improved. DM was diagnosed in 2013 when patient was on peritoneal dialysis. Family history significant for type 2 DM in maternal uncle.

Discussion

Mitochondrial diseases are rare, maternally inherited, heterogeneous conditions caused by mutations in mitochondrial DNA and present with a variety of clinical symptoms. Mitochondrial diabetes results from the 3243 A>G gene mutation, responsible for both MELAS and Mitochondrial inherited diabetes and deafness (MIDD). MELAS presents with encephalopathy, stroke like symptoms and lactic acidosis (1). MIDD presents with nerve deafness, which usually occurs at an early age (2). In our patient, she presented with neurological symptoms suggesting MELAS and bilateral deafness suggesting MIDD. Her presentation is unusual and constitutes an overlap between both disorders.

Conclusion

Early recognition and diagnosis of mitochondrial diabetes is important. The diagnosis has important genetic implications for other family members. This case report highlights the presentation of MELAS and MIDD and importance of genetic studies in the confirmation of diagnosis

1) D. M. Sproule and P. Kaufmann, "Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome," Annals of the New York Academy of Sciences, vol. 1142, pp. 133–158, 20082) Murphy R, Turnbull DM, Walker M, Hattersley AT. Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation. Diabetic Medicine 2008. Apr;25(4): 383-99. doi: 10.1111/j.1464-5491.2008.02359.x.Epub 2008 Feb 18. PMID: 18294221.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN249 Starvation Ketoacidosis as the Presenting Finding of Glycogen Storage Disorder Type III
Authors: Fiacco Nicholas , Caraccio Donald
Published: November 2022

A 30-year woman with a history of heart transplantation and a history of post-transplant diabetes mellitus presents with severe euglycemic ketoacidosis. Initial concern was for diabetes related ketoacidosis given history of diabetes however blood glucose was within goal range in the absence of pregnancy and use of sodium glucose transporter type 2 inhibitor use. Initial laboratory evaluation showed a serum glucose of 177 mg/dL, a serum beta hydroxybutyrate of greater than 12.66 mmol/L, serum lactate of 0.6 mmol/L, with a calculated anion gap of greater than 30 mmol/L. C-peptide levels were repeatedly normal and appropriate for blood glucose level ranging between 2.8 ng/mL and 7.5 ng/mL ruling out insulin deficiency as causative. It was discovered that the patient had intentionally fasted for greater than 18 hours and thus had not used the premixed insulin regimen prescribed. Metabolic disturbance corrected with a dextrose and insulin infusion. Evaluation for inborn error of metabolism showed: acylcarnitine panel returned normal making an inborn error of fatty acid metabolism unlikely. The mitochondrial DNA mutation panel was negative for point mutations or deletions. Further testing for urinary organic acids did not reveal elevation of 3-hydroxybutyric acid suggesting SCOT enzyme levels were sufficient in our patient. Review of pathology records for heart transplantation completed for idiopathic cardiomyopathy 20 years prior to this presentation showed high levels of glycogen deposition prompting evaluation for glycogen storage disorders. Results revealed a heterozygous abnormality at exon 9 of the AGL gene; AGL gene c.1139A>G (p.Glu380Gly). This is not a reported pathologic mutation, and given the heterozygosity of the mutation in this autosomal recessive condition, it is felt that either environmental factors or the presence of other unrecognized genetic mutations allowed for the phenotypic expression of GSDIII with euglycemic starvation ketoacidosis. The patient was treated with dietary counseling regarding ketone suppression with basal insulin during periods of fasting and preference to avoid periods of prolonged fasting with frequent carbohydrate-containing meals.

Conclusion

This case represents a novel, potentially pathologic defect in the AGL gene. This finding should prompt further investigations into genetic variabilities that may lead to this phenotypic expression.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN253 Cocaine Use Resulting in Inadvertent Sulfonylurea Overdose
Authors: Gothong Chikara , Whitlatch Hilary B
Published: November 2022

Introduction

Most street cocaine is cut with other substances to increase drug volume. Often, cutting agents are used that change or intensify the effects of the drug. We present a case in which sulfonylurea-laced cocaine resulted in life-threatening hypoglycemia.

Clinical Case

A 61-year-old male with a history of heart failure with reduced ejection fraction, moderate aortic stenosis, and substance abuse was found unconscious with a fingerstick of 25 mg/dL. He had no personal history of diabetes. No one in his household had diabetes, and he denied any use of insulin or oral anti-diabetic medications. In the emergency department, he had recurrent hypoglycemia despite D10 boluses, glucagon, oral glucose tablets, and a full meal. He required initiation of a continuous intravenous D10 drip, which was titrated to 250 mL/hr to maintain normoglycemia. The endocrinology service was consulted for further evaluation and treatment. The patient recalled smoking a new supply of cocaine prior to his current admission. He had been admitted to two other hospitals within the month prior with similar episodes of severe hypoglycemia. Biochemical evaluation during a prior hospitalization suggested hyperinsulinemic hypoglycemia and a CT abdomen did not visualize an insulinoma. However, diagnostic evaluation was not completed at that time as the patient left against medical advice.Tests during this hospitalization included a low serum glucose 42 mg/dL, high insulin 107 uIU/mL (normal <3), high proinsulin 42.8 pmol/L (normal <5 pmol/L), high c peptide 13 ng/mL (normal <0.6) and low beta-hydroxybutyrate 1.2 mg/dL (normal >2.7mg/dL), consistent with hyperinsulinemic hypoglycemia. Other results included negative insulin antibody, normal TSH, and appropriately elevated cortisol levels. Given desire to rapidly wean D10 drip to avoid volume overload, octreotide therapy was initiated. He received octreotide 50mcg subcutaneously three times over a span of 24 hours, and the D10 drip was discontinued. His sulfonylurea screen subsequently resulted positive for glipizide. Considering the timing of cocaine use preceding the onset of hypoglycemia, it was postulated that the hyperinsulinemic hypoglycemic event was due to use of cocaine that was intermixed with sulfonylurea.

Conclusion

In cases of hypoglycemia with a known history of illicit substance abuse, clinicians should consider the presence of contributing cutting agents, such as sulfonylureas.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN257 Acute Onset Diabetes and GAD Antibody Positivity After COVID-19
Authors: Wilson Jessica
Published: November 2022

Background

Viral infections can trigger the development of auto-antibodies including against the pancreas (1). The Sars-CoV2 virus can infect the pancreas (2). Limited data exist linking COVID-19 infection and the development of islet related auto-antibodies and diabetes in adults.

Case

A 46-year-old healthy man (BMI 24.7kg/m2) developed upper respiratory symptoms in mid-July 2021. He did not have a family or personal history of autoimmune diseases. His mother has mild type 2 diabetes mellitus. He underwent Sars-CoV-2 testing in July which was positive. In August, upper respiratory symptoms resolved, however, he developed acute onset polyuria, polydipsia, fatigue, and weight loss. He lost 12.7kg within one month. On his own, he noticed that he felt worse after eating carbohydrates and modified his eating (limiting to 20g of carbohydrates per meal), which reduced his polyuria, polydipsia, and weight loss. In September, he presented to his primary care physician who diagnosed him with hyperglycemia and diabetes. Fasting blood glucose was 331mg/dL (18.4mmol/L) and hemoglobin A1C was 11.3%. He presented to endocrinology clinic in October for evaluation and was started on insulin therapy for diabetes. Laboratory studies included: glucose 194mg/dL (10.8mmol/L), repeat hemoglobin A1C 10.1%. Autoantibody testing was positive for GAD65 (glutamic acid decarboxylase 65 antibody 34.4nmol/L, reference <0.02nmol/L). Other type 1 diabetes related autoantibodies were negative. Blood glucose normalized on insulin therapy (average 115mg/dL (6.4mmol/L) on continuous glucose monitor).

Op de Beeck, Anne and Decio L. Eizirik, Nature Reviews, May 2016.Muller, J, et al. Nature Metabolism, Feb 2021.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN259 A Severe Case of Fournier's Gangrene Associated With Dapagliflozin
Authors: Syed Shumail , Sindi Ghassan , Zena Mohsen
Published: November 2022

Background

SGLT2 inhibitors have gained popularity in treatment of Type 2 Diabetes, and recently in lowering the risk of major adverse cardiovascular events (MACE). Genitourinary infections are well known side effects of SGLT2 inhibitors. Fournier's gangrene is a necrotizing fasciitis of the perineum which can be rarely associated with SGLT2 inhibitors. Between 2013 to 2018, the FDA received 12 case reports of Fournier's gangrene in patients taking SGLT2 inhibitors. Glucosuria from the medication creates a milieu which increases the chances of developing Fournier's gangrene. The annual incidence of Fournier's gangrene in the general population is 1.6/100,000 males in the US. Here, we present a case of Fournier's gangrene within few months of starting Dapagliflozin.

Clinical case

A 62-year-old male with history of poorly controlled Type 2 DM was brought to the ED after being found down at his residence covered in feces. He reportedly had nausea, vomiting and diarrhea for 3 days prior to his presentation. His diabetes home regimen consisted of metformin 1000 mg BID, oral semaglutide 14 mg daily, glimepiride 8 mg daily, pioglitazone 45 mg daily and dapagliflozin 10 mg daily. Of note, dapagliflozin was started 3.5 months prior to presentation. Workup revealed WBC count 14.2 k/ul with left shift, sodium 132 mmol/L, HCO3 15 mmol/L, anion gap 26 mmol/L, glucose 432 mg/dL, Cr 3.27 mg/dL (Baseline 1.18 mg/dL), Lactic acid 2.7 mmol/L, AST 131 u/l, CK 905 u/l and A1c 9.2%. CT abdomen and pelvis with contrast showed necrotizing infection of the scrotum and perineum, consistent with Fournier's gangrene. Gas was seen tracking into the mesorectal fascia layer in the extraperitoneal spaces of the pelvis. He was given IV antibiotics and IV fluids per sepsis protocol. Urology and General Surgery consultations were obtained with the patient taken emergently to the operating room and underwent exploration of groin with debridement of genitals, right gluteal and perianal debridement, and bilateral orchiectomy. The patient had an extensive hospital stay with gradual improvement in clinical status. He later underwent extensive reconstructive plastic surgery. All oral diabetes medications were discontinued, and he was ultimately discharged on an insulin regimen consisting of insulin glargine 20 units BID, insulin lispro 5 units before meals and insulin lispro correction scale.

Conclusion

SGLT2 inhibitors remain valuable drugs in treating Type 2 Diabetes. Fournier's gangrene is a rare but serious possible adverse effect of SGLT2 inhibitors that requires a high index of suspicion to recognize. Time to onset of Fournier's gangrene after initiation of SGLT2 inhibitor therapy can be variable. Patients on SGLT2 inhibitors should be alerted to seek medical attention if they develop fever associated with pain, redness, or swelling in the genital or perineal area.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN272 Opportunity for Inpatient Use of Continuous Glucose Monitoring: A Case Report of Acute Pancreatitis Secondary to Hypertriglyceridemia
Authors: Romo Karina G , Regennitter Nicholas S , Martinez-Vargas Valerie , Karam Susan
Published: November 2022

Background

Continuous glucose monitoring (CGM) is a convenient method of estimating blood glucose (BG) levels through a minimally invasive subcutaneous electrode that senses interstitial fluid glucose readings. With recent advancements, this technology has the potential to transmit interstitial fluid glucose readings to electronic health records (EHR) in real-time. While some benefits of CGM have been studied in outpatient settings, current CGM research is beginning to explore the use and benefits of CGM in inpatient settings. The following case of acute pancreatitis (AP) secondary to hypertriglyceridemia (HTG) presents a novel opportunity for inpatient use of CGM.

Clinical Case

A 33-year-old-man with anxiety, alcohol use disorder, and without insulin resistance, presents as a transfer to a tertiary-care-center for consideration of plasmapheresis in the setting of AP secondary to HTG. He initially presented to outside hospital with acute onset diffuse abdominal pain. Family history of father with controlled HTG and hyperlipidemia on statins. Hemodynamically stable. Examination revealed diffuse abdominal tenderness. Labs revealed triglyceride (TG) level 3550 mg/dL (n<150 mg/dL), lipase 1423 U/L (n 0-160 U/L), TSH normal, A1c 5.2% (n<5.7%). CT abdomen pelvis with contrast revealed moderate acute interstitial edematous pancreatitis without necrosis, pseudocyst, or mass. He was volume resuscitated with intravenous (IV) fluids, then started on a non-titratable regular insulin infusion (N-TII) at 2 U/hr and continuous IV fluids with dextrose. Upon arrival, his BG was 101 mg/dL. The N-TII rate was decreased to 1 U/hr and managed with hourly finger-stick BG checks and continuous IV fluids with dextrose plus KCl. Arrival TG was 954 mg/dL. The case was discussed with Transfusion Medicine—given the down-trending TG level, plasmapheresis was not initiated. The next morning, repeat TG level was <500 mg/dL, thus, the N-TII was discontinued. During admission, BG ranged from 86-179 mg/dL and IV fluids with dextrose required titration of rate and concentration to avoid hypoglycemia while severe HTG resolved.

Conclusion

This case presents a novel scenario in which there is an opportunity for inpatient use of CGM. In addition to point-of-care finger-stick BG checks, the implementation of inpatient CGM may be beneficial in tracking glucose trends when N-TII are required for management of severe HTG, but risk iatrogenic hypoglycemia. Not only does this highlight an area in need of further research and technological developments that link CGM data to EHR in real-time, but also, by continuing to identify new opportunities for inpatient CGM use, we can better understand its nuances and implications, thus, thoughtfully advocate for policies and protocols that optimize benefits and justify cost of inpatient CGM.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN276 GLP1RAs use for treating NALFD in a multidisciplinary clinic in low socioeconomic community
Authors: West Brittany , Mon Sann , Myint Alex , Lees Heather
Published: November 2022

GLP1RAs have been proven beneficial for weight loss in patients with NAFLD with or without Diabetes. However, such use is limited due to cost and limited insurance coverage in those without diabetes.

Method: Retrospective chart review of patients with NAFLD seen at Multidisciplinary NAFLD clinic in Low SES community

Result: A total of 11 patients (55% Female, mean age 49.2±13.8 yrs, BMI 39.3±7.8 kg/m2) diagnosed with NAFLD were seen by hepatologist, endocrinologist and dietician and instructed and counseled for lifestyle modification aiming for at least 5% weight loss within 6 months. Five had diabetes with A1C 6.7% to 8.3%, and the remaining had Pre-Diabetes. Semaglutide 1 mg weekly SC was used in 8 patients (72.3%), liraglutide 3 mg qd in 1 patient, metformin in 1 patient, generic phentermine topiramate in 1 patient. Initial data of SBP(mean 129±9.0 mmHg), LDL (mean 97.8±31.6 mmol/L), TAGs (mean 193.6±109.6 mg/dl), AST (mean 43.5±21.8 U/L), and ALT (mean 50.8±25.9 U/L) were collected and followed at 6 and 12 months. Among 8 patients with complete 1 year data, all except one (87.5%) achieved weight loss goal at least 5% at 6 and 12 months. Among Five patients with greatest weight lost 14-20% at 1 year with significant improvement in metabolic panels, 80% of them were on GLP1RA. At 6 months and 12 months mean SBP was 125.3±5.8 and 123.9±10.3 mmHg, mean LDL was 75.5±16.4 and 71.4±21.2 mmol/L, mean TAGs was 161.2±114.5 and 158.7±90.9 mg/dl, mean AST was 19.4±4.0 and 19.4±4.5 U/l, and mean ALT was 26.7±8.3 and 33±16.1 U/L respectively.

Conclusion

In this case series from our multidisciplinary NAFLD clinic, we observed the achievement of weight loss goal and improved clinical parameters by 12 months. The clinic can be beneficial in low SES community.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN277 Symptomatic Hypoglycemia Associated with Over The Counter Supplement
Authors: Izkhakov Neriy , Zweibach Eugenia , Vernetti Nicholas , Nakhle Samer
Published: November 2022

Background

Insulin autoimmune syndrome (IAS), first described in 1970 in Japan, is characterized by spontaneous fasting or postprandial hypoglycemia with evidence of elevated serum insulin levels and anti-insulin antibodies in individuals with no prior exposure to exogenous insulin. IAS has been mostly reported in Asia. Genetically susceptible individuals, with HLA-DR4, are reported to have higher incidence of IAS. Possible triggers include Sulfyhdryl group containing compounds.

Clinical Case

We report a case of a 25-year-old female of asian descent (133lbs, BMI 22.3 kg/m2) with no significant medical or surgical history, who was referred for an evaluation of hypoglycemia. She did not have diabetes mellitus and never administered insulin or sulfonylureas. Patient started a glutathione supplement for skin care and six months later she switched to glutathione-blend supplement (total daily intake Glutamic Acid 360 mg, Glycine 400mg, L-Cysteine 240mg, NAC 200 mg, Vitamin C 200mg, Alpha Lipoic Acid 100mg, Grapeseed Extract 50mg). Patient reported being asymptomatic for the initial 3 months of taking the new glutathione blend supplement. At that time she developed symptoms of dizziness, diaphoresis, palpitations, muscle weakness, headaches and sugar craving. She reported that these symptoms resolved with administration of glucose and recurred every 2-3 hours after meals and overnight. Baseline continuous glucose monitor (CGM) data showed average glucose of 74 mg/dL, 60% in target range (70-180mg/dL), 38% Low glucose levels (54-69 mg/dL), and 2% very low (<54 mg/dL) Her baseline labs while on glutathione blend supplement showed serum glucose 71 mg/dL, insulin 815 uIU/mL (UNL 25 uIU/mL), proinsulin 18.6 pmol/L (UNL 10 pmol/L), c-peptide 4.2 ng/mL (UNL 4.4 ng/mL), insulin antibodies > 625 uU/mL (<5 uU/mL negative). A week after supplement discontinuation, patient's symptoms have improved with reduction in frequency of hypoglycemia. Serum markers were repeated on 3 separate occasions (at 2 weeks, 3 months, and 5 months off supplement). All markers of insulin production were progressively decreasing. Insulin antibodies remained above the upper limit of the detection. By five months off supplement, she was able to fast for 6 hours without episodes of hypoglycemia. At that time her labs showed serum fasting glucose 83 mg/dL, insulin 286 uIU/mL, proinsulin 6.7 pmol/L, c-peptide 3.3 ng/mL, insulin antibodies > 625 uU/mL. CGM data at five months off supplement showed average glucose of 95 mg/dL, 100% in target range.

Conclusion

This is a rare case of supplement induced insulin autoimmune syndrome due to which the patient developed profound hypoglycemia. This case illustrates that once the supplement (alpha lipoic acid and glutathione) is discontinued there is an improvement in clinical and laboratory markers of hypoglycemia.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN281 Safety and Efficacy of Virtual Insulin Pump Initiation in Adults with Diabetes
Authors: Everett Estelle , Freeby Matthew , Gaffny Kailee , Educator Certified Diabetes
Published: November 2022

Background

Insulin pump therapy is an integral part of diabetes management. The COVID-19 pandemic posed challenges to the usual insulin pump initiation process, prompting an increased reliance on virtual training, but the effectiveness and safety of this approach is unclear.

Methods

In an academic urban diabetes clinic, we examined insulin pump initiations in 30 sequential patients who underwent virtual training between May 2020 and February 2021 and in 15 patients who received in-person training between October 2018 and April 2020. Patients met with a diabetes educator for 4 sessions either remotely in the virtual group, or in-person in the routine care group. All patients used a continuous glucose monitor (CGM) prior to insulin pump training. We compared glycemic control using the following CGM metrics at baseline and 6 months: percentage time in range (70-180mg/dL), hypoglycemia (BG <70), and hyperglycemia (BG >180). We calculated the time interval between decision to start and the day of insulin pump initiation (lead time). We used descriptive statistics to report baseline characteristics of patients. We plotted each measure and used Shapiro-Wilk Test to determine the distribution of each outcome. As these measures were non-normally distributed, we used medians and interquartile ranges to describe glycemic outcomes and Wilcoxon signed rank test to assess statistical differences between the groups.

Results

Overall both patient groups were predominantly white (77.8%), non-Hispanic (86.6%), male (60.0%), and with type 1 diabetes (80%); the average age was 43 years. Baseline time in range was 61.0% (IQR 34.0%, 78.4%) and 65.8% (IQR 35.0%, 78.0%) in the virtual and routine groups, and 70.9% (IQR 52.2%, 83.0%) and 65.0% (IQR 48.8%, 88.9%) at 6 months. Baseline time in hypoglycemia was 0.4% (IQR 0%, 1.6%) and 0.5% (IQR 0.1%, 2.0%) in virtual and routine groups, and 0.8% (IQR 0.2%, 1.75%) and 0.3% (IQR 0%, 1.0%) at 6 months. Baseline time in hyperglycemia was 40.0% (IQR 20.3%, 66.0%) and 34.1% (IQR 13.0%, 65.0%) in the virtual and routine groups, and 25.0% (IQR 16.9%, 43.0%) and 35.0% (IQR 11.1%, 50.9%) at 6 months. There was no statistically significant difference in glycemic outcomes between the groups at baseline or at 6 months. One case of diabetic ketoacidosis occurred in both groups after pump initiation; there were no hospitalizations in either group. The lead time for virtual group training was 45 days (IQR 35, 60), significantly shorter than routine care at 80 days (IQR 50, 123; p=0.026).

Conclusion

Our study demonstrates timely initiation of pump therapy via virtual training without increased rates of hypo- or hyperglycemia. The data suggest virtual insulin pump training can be effective, efficient, and safe. Larger studies are needed to confirm these findings.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN30 Circulating EVs from patients with SDHB mutations increase HIF signaling in hPheo1 cells
Authors: Ghayee Hans , Bala Niharika , Liu Lauren , Xu Yiling , Cusi Kenneth , Pacak Karel , Alli Abdel
Published: November 2022

Extracellular vesicles (EVs) are nanosized vesicles that carry bioactive cargo from one cell to another and play an important role in intracellular signaling, cell differentiation, and intercellular communication. We investigated and found that packaged cargo of circulating EVs from SDHB mutated pheochromocytoma/paraganglioma patients increase hypoxia-inducible factor (HIF) signaling in a cell model system compared to EVs from control subjects. Keywords: Adrenal Tumors, Endocrine Neoplasia, Neuroendocrinology, succinate dehydrogenase

Presentation: Saturday, June 11, 2022 1:00 p.m. - 2:00 p.m.
RF04 | PSUN295 Evolution of Monomeric Multi-Agonists of GLP-1 and NPY Receptors
Authors: Chichura Kylie , Elfers Clinton , Salameh Therese , Sweet Ian , Roth Christian , Doyle Prof Robert
Published: November 2022

Current treatments for type 2 diabetes (T2D) and obesity do not reliably achieve long-term weight-loss and up to 50% of patients experience nausea and vomiting. Thus, there is a critical need for obesity medications that provide glycemic control with enhanced hypophagic response without nausea/emesis. Based on rational design and in silico modelling of the glucagon-like peptide 1-receptor agonist (GLP1RA) exendin-4 (Ex4) and the neuropeptide Y2 receptor (Y2R) agonist peptide YY (PYY) 3-36, we have developed and screeened several new monomeric chimeric peptides that display dual agonism of the anorectic Y2R and the glucoregulatory GLP1R. In addition, we explored a third agonistic behavior at the neuropeptide Y1 receptor (Y1R), which potentially relates to pancreatic beta-cell protection. Our current lead, GEP44, binds the Y2R, Y1R, and GLP1R. We tested effects of daily injections of these chimeric peptides in adult Sprague-Dawley rats on food intake (FI), body weight (BW) changes, blood glucose levels and an indicator of nausea (kaolin intake). GEP44 produced profound reduction in FI (2-d average GEP44 at 20 nmol/kg FI -71%; Ex-4 20 nmol/kg FI -40%). Anorectic doses of GEP44 did not trigger a pica response assessed by kaolin consumption in treated rats, while in Ex-4 treated rats, kaolin consumption accounted for 28% of total daily solid intake, indicating a clear nausea response. In addition, we assayed for emetic response in the musk shrew, with little to no such emesis displayed (n=8) for GEP44 (1/8), but emesis noted across all animals tested for Ex4. During 11 d of treatment with GEP44, FI was consistently reduced resulting in a significantly stronger reduction of BW compared to Ex4 at the end of treatment (GEP44 -7.6%, Ex4 -3.7%, p<0.05). Furthermore, 5-day injections of GEP44 showed greater reduction of glucose levels than for Ex4 in diet induced obese rats receiving ip glucose. In conclusion, simultaneously targeting serial anorectic pathways with single molecule chimeric peptides can address multiple coexisting conditions to more efficaciously reduce FI, BW and blood glucose levels, devoid of side-effects to improve patient patient and quality of life.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF16 | PSUN335 Clinical Effects of Sodium Glucose Transporter Type 2 Inhibitors in Patients with Severe Insulin Resistance
Authors: Bansal Rashika , Brown Rebecca , Cochran Elaine , Startzell Megan
Published: November 2022

Background

Severe insulin resistance syndromes including lipodystrophy and pathogenic variants in the insulin receptor (INSR) lead to diabetes that is challenging to control. Oral antidiabetic agents have been used to control hyperglycemia, however the efficacy of these treatments has not been studied systematically. This study explores safety and efficacy of sodium glucose cotransporter 2 inhibitors (SGLT2i) in these patients.

Methods

This was a retrospective chart-review assessing safety (N=31) and efficacy (N=18) of SGLT2i use in patients with clinically or genetically confirmed diagnosis of lipodystrophy or INSR pathogenic variants at our institute. Efficacy outcomes included HbA1c, insulin dose, C-peptide, fasting insulin and 24-hour urine glucose at 12 months and throughout follow-up from 2 to 24 months. Glycemic parameters were analyzed as change from baseline (prior to SGLT2i) adjusted for baseline values after 12 months of SGLT2i and across all timepoints using linear mixed models with post-hoc Dunnett-adjusted comparison of each time point compared to baseline. For HbA1c, additional models were conducted including change in insulin dose as a covariate.

Results

HbA1c did not significantly change after 1 year of SGLT2i (baseline 9.5±2.5 [80.3±27.7]; 12 months 8.8±2.3% [72.6±25.3 mmol/mol]; p=0.093), or across all time points (p=0.11). However, most patients (83%) were taking insulin, and SGLT2i treatment led to 35% reduction in total daily dose of insulin after 12 months (baseline 186 [100,1010]; 12 months 120 [75,260] units/day; p=0.07) and across all visits (p=0.035), which may have mitigated the reduction in HbA1c. Reduction in HbA1c was significant after adjustment for changes in insulin dose over time (p=0.0498). No significant change was noted in C-peptide, however fasting insulin decreased after 12 months (p=0.021) and across all visits (p=0.005). Urinary glucose excretion increased greater than 5-fold after 12 months of SGLT2i, to over 80 grams per day after 1 year (p=0.04). Adverse effects occurring in >1 subject included hypoglycemia, fungal infections, and extremity pain.

Conclusions

SGLT2i reduced insulin dose, insulinemia, and insulin dose-adjusted HbA1c in patients with severe insulin resistance, with a similar safety profile compared to type 2 diabetes. SGLT2i use may lead to overall better glycemic control and should be considered as part of the treatment armamentarium for these rare forms of diabetes, but larger trials are needed to confirm these findings.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m.
RF28 | PSUN184 New American Diabetes Association Definition of Diabetes Remission Does not Correlate with Time in Remission in Ketosis-Prone Diabetes
Authors: Oladejo Omolade , Rashied Ammar , Umpierrez Guillermo , Vellanki Priyathama
Published: November 2022

Introduction

Approximately 50% of obese Black patients presenting with diabetic ketoacidosis (DKA) at new-onset of diabetes have immunologic and metabolic features of type 2 diabetes, also called ketosis-prone diabetes (KPDM). With intensive insulin treatment, ∼70% have improvements in beta-cell function and insulin sensitivity and achieve diabetes remission. The definition of remission in KPDM has been heterogeneous with our group defining remission as HbA1c < 7%, fasting blood glucose (BG) < 130 mg/dl and random BG < 180 mg/dl while off insulin injections for at least 1 week. In 2021, the American Diabetes Association (ADA) consensus recommended that the definition of diabetes remission as HbA1c < 6.5% or a fasting BG < 126 mg/dl while off medications for > 3 months. We hypothesized that patients who achieved the more intensive ADA definition of remission (HbA1c < 6.5%) will have longer time in remission compared to our previous non-intensive definition of remission (HbA1c 6.5-7%).

Methods

Forty obese Black patients (BMI ≥ 28 kg/m2) with newly diagnosed diabetes and unprovoked DKA had intensive insulin therapy until HbA1c < 7% without insulin therapy for at least one week. Patients were followed until hyperglycemia relapse (HbA1c > 6.5% or fasting BG > 126 mg/dl and/or requiring antidiabetic medications). Baseline characteristics and clinical time to hyperglycemia relapse-free survival were compared between patients with HbA1c < 6.5 (n= 24) and HbA1c 6.5-7% (n=16).

Results

Age, sex, family history of type 2 diabetes, BMI, HbA1C, weight change and insulin doses received between the two groups (HbA1c < 6.5 vs 6.5-7%) did not differ significantly. Median follow-up overall was 404 days with a range of 7-1099 days. In patients that experienced a hyperglycemia relapse, bivariate analysis shows that median days to hyperglycemia relapse was longer in HbA1c < 6.5% (411 days, range (17-804) vs HbA1c 6.5-7% (126 days, range (7-391), p= 0.05) but without a statistical difference. Survival analysis showed that time in remission did not statistically differ between the two groups (log rank, p=0.6853).

Conclusion

In obese Black patients with KPDM, HbA1c < 6.5% at time of insulin discontinuation does not prolong diabetes compared to patients that achieved HbA1c 6.5-7%, suggesting that predictors of prolonged remission may differ among diverse populations with diabetes.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:44 p.m. - 12:49 p.m.
RF28 | PSUN301 Sex Differences in the Indolepropionic Acid Alterations in Response to Obesity Surgery
Authors: Silva Thaís R , Mara Spritzer Poli , Tuomainen Marjo , Sehgal Ratika , Pihlajamäki Jussi , de Mello Vanessa D
Published: November 2022

Introduction

Obesity surgeries improve type 2 diabetes (T2D) in most cases, with effects frequently evident before substantial weight reduction. Therefore, this study hypothesizes that the increase in indolepropionic acid (IPA), a gut-derived tryptophan metabolite considered to be a potential biomarker for the development of T2D, might contribute to the metabolic benefits occurring after obesity surgery. Since sex impacts the pathogenesis of numerous diseases, including T2D, our objective was to investigate sex-specific effects on the changes in IPA in response to obesity surgery.

Methods

One-hundred and twenty-one obese individuals (36 males and 85 females; age 48.4 ± 9.4 years; BMI 42.9 ± 5.3kg/m2) participants from the ongoing Kuopio OBesity Surgery (KOBS) Study, who were accepted for Roux-en-Y gastric bypass (RYGB) were included. Serum samples drawn after 12h fasting were available from both baseline and 1-year follow-up visits for measuring IPA by LC-QQQ-MS. Impaired fasting glucose (IFG) was defined as a fasting glucose level ≥5.6nmol/L.

Results

Male and female participants had similar ages, BMI and IPA [93.2 (44.3–137.8) vs 67.0 (44.6–113.8) ng/dL, P=0.444, males and females respectively) at baseline. Weight loss after 1 year of RYGB was lower in males in comparison with females (19.8 vs 23.5%, P=0.014). A significant interaction between time and sex on IPA changes was found during the first year of RYGB (P=0.028). We observed an increase in IPA in females but not in males, especially in the youngest female group (median age <48.7 years). Fasting insulin interacted significantly with sex on the changes in IPA (P<0.001), but not fasting glucose (P=0.962). In addition, females had lower prevalence of IFG at 1-year (25 vs 57%, P=0.042, female and male participants respectively), which was associated with changes in IPA independently of weight loss.

Conclusion

Our results suggest that changes in IPA concentrations may be associated with beneficial changes in glucose metabolism observed after obesity surgery in females. A comprehensive understanding of the sex-specific effects of the IPA could contribute to future non-surgical treatments for T2D.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.
PMON13 The Effects of Perfluorooctanesulfonic Acid (PFOS) on the Expression of Estrogen Receptor Alpha (ERα) and Tumor Suppressor Gene BRCA1 in Breast Cancer Cells
Authors: Hallman Erin , Farrar Katelyn , Whittaker Kaylin , Pfiffner Samantha , Zanib Aisha , Dinda Sumi
Published: November 2022

Perfluoroctanesulfonic Acid (PFOS) is a perfluorinated chemical (PFC) and endocrine-disrupting compound (EDC) found in fire-extinguishing foams, food packing, and commonly used household products such as nonstick cookware and cleaning products. PFOS is also an environmental toxicant that has polluted air, soil, and water in past years. Few studies have suggested PFOS may cause endocrine-disrupting effects, therefore it is critical to explore the effects of PFOS on breast cancer cells. This study examined the estrogenic-like effects of PFOS, alone and in combination with hormones and antihormones, on the expression of ERα and BRCA1 in T-47D and MCF-7 breast cancer cell lines by utilizing western blot analyses, cellular viability assays, confocal microscopy, apoptosis assay and RT-qPCR analyses. The cells were cultured with 5% charcoal-stripped fetal bovine serum (FBS) for six days to deplete endogenous steroids or growth factors. In the concentration-dependency study, cells were treated with various concentrations of PFOS (300µM-800µM) for 24 hours. Western blot analysis revealed alterations in the expression of ERα and BRCA1 related with these varying concentrations of PFOS (300 µM-800µM). In comparison to the control, a concentration-dependent decrease of ERα expression levels were seen in both cell lines. A concentration-dependent increase of BRCA1 was seen in both cells. Western blot analysis revealed the optimal concentration of PFOS to be 700 µM in cells, which exhibited the maximal estrogenic-like effect. To further examine the effects of PFOS on breast cancer cells, the optimal concentration (700 µM PFOS) was then used alone and in combination with hormones and anti-hormones in T-47D cells. Treatment with PFOS, E2and the combination of PFOS and E2 for 24 hours showed a significant down-regulation of ERα in T-47D cells when compared to the control. Treatment of PFOS with antiestrogen ICI revealed a significant down-regulation of ERα (approximately 50%) in T-47D cells. Image cytometric analysis with propidium iodide staining was utilized to examine the effects of PFOS on cellular viability in T-47D cells. PFOS alone and in combination with E2 revealed an increase in cellular proliferation compared to the control in T-47D cells and these effects were sensitive to the presence of antiestrogens. RT-qPCR studies revealed a transcriptional expression of ESR1 and BRCA-1 mRNA levels that correlate with the translational data obtained via western blot analyses. Cytolocalization experiments and effects of PFOS with hormones and antihormones on MCF-7 cells studies are in progress. Our studies provide exciting leads to clearly delineate the molecular mechanisms of PFOS as an EDC on the steroid receptors and tumor suppressor gene in breast cancer cells.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP610 Assessing ABO and Rh Blood Group as a COVID-19 Risk Factor
Authors: Heard Madeleine , Kim Luna , Comite Florence
Published: November 2022

Objective

Precision medicine harnesses the N-of-1 approach to detect, predict, reverse, and stop progression of disorders of aging through longitudinal observation of biomarkers with respect to genetic makeup. ABO and Rh blood group are two genetic markers that inform risk for dysglycemia, hypercortisolemia, and hypothyroidism, among others. Early in the pandemic, scientists sought to understand whether ABO and Rh blood group was also a risk factor for COVID-19 susceptibility. If proven true, the presence of mutual disease mechanisms between COVID-19 and diseases of the endocrine system may also exist. In the present study, ABO and Rh blood group was examined as a risk factor for COVID-19 susceptibility.

Methods

Inclusion criteria for this retrospective observational study were an active patient status in December 2019 and a record of ABO and Rh blood group on Quest Laboratory's online portal. ABO and Rh blood groups were compiled and analyzed using chi-square test, odds ratio (OR), and 95% confidence interval (CI) for association to COVID-19 susceptibility.

Results

136 adult patients met inclusion criteria for this study, 44 of whom tested positive for COVID-19. The cohort was 30% female, ranging in age from 20-78 years (mean=54 years). In the COVID-19 patients, the respective frequencies of A, B, O, and AB phenotypes were 27.27%, 25. 00%, 38.64%, and 9. 09%. Of these patients, 88.64% were Rh positive. Blood group A (OR = 0.70; CI, 0.32-1.5; p > . 05), group B (OR = 1.58; CI, 0.66-3.78; p > . 05), group O (OR = 0.78; CI, 0.38-1.63, p > . 05), and group AB (OR = 2.97; CI, 0.63-13.9; p > . 05) were not significantly associated with COVID-19 susceptibility. Rh factor was also found to be an insignificant variable (OR = 2. 03; CI, 0.70-5.85; p > . 05).

Discussion

These findings support the growing body of literature dissociating ABO and Rh blood group from COVID-19 susceptibility. As such, it could be advised that ABO and Rh blood group is not factored into risk stratification for COVID-19 susceptibility in contrast to particular endocrine disorders. A significant limitation of this analysis is that ABO genotypes were unknown. A recent genome-wide association study confirmed a potential involvement of ABO blood group in COVID-19 clinical presentation1. Therefore, deeper analysis may also reveal the mechanistic influence of ABO genotypes on COVID-19 susceptibility, such as the type and quantity of ABO-antibodies in circulation. Further investigation is warranted to determine whether biomarkers known to inform risk of endocrine disorders also influence COVID-19 susceptibility. Understanding what governs this relationship would allow endocrinologists to develop targeted interventions to optimize an individual's health trajectory. References: 1. The Severe Covid-19 GWAS Group. Genomewide Association Study of Severe Covid-19 with Respiratory Failure. NEJM 2020;383: 1522-1534.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
OR08-2 Functional Association of the Stem Cell Protein Musashi With LSM14B in Control of mRNA Translation
Authors: Banik Jewel , Bronson Katherine , Childs Gwen , Hardy Linda , Lim Juchan , MacNicol Melanie , MacNicol Angus
Published: November 2022

The Musashi RNA-binding protein functions as a gatekeeper of cell maturation and maintains stem cell plasticity by regulating the translation of target mRNAs. The adult anterior pituitary tissue expresses a high level of Musashi and also demonstatres a high level of cell plasticity, indicating a Musashi-dependent function in maintaining endocrine homeostasis in the anterior pituitary. Towards understanding the mechanism(s) by which Musashi functions to control cell plasticity, we have identified co-associated proteins necessary for Musashi function. The two Musashi isoforms (Musashi1 and Musashi2) are conserved across species and are structurally characterized by two N-terminal RNA-recognition motifs (RRMs, that associate with specific sequences in the 3' untranslated region of mRNAs targets) and a disordered C-terminus. Musashi uses these domains to selectively repress, or to activate, mRNA translation in a manner specific to target mRNA and cell context. Both Musashi isoforms contain two C-terminal regulatory serine residues that require phosphorylation to enable mRNA translational activation. However, the Musashi proteins do not have inherent mRNA translation function and utilize co-associated protein complexes to mediate mRNA translation. We have previously identified Musashi1 binding protein partners through mass spectrometry. Here, we have identified the protein interactions that are required for Musashi1-dependent translational activation. Knockdown of target protein levels in Xenopus laevis oocytes indicated that the PABP4, CELF2, LSM14A/B, ELAVL1, ELAVL2, ELAVL4, and PUM1 proteins are required for Musashi target mRNA translational activation. We further determined that the effect of LSM14A/B dual knockdown was in fact specific to LSM14B alone. LSM14B is an RNA-binding protein that is required for RNA granule formation, RNA transcript metabolism, and mRNA translation. Studies in mouse oocytes have shown that LSM14B is required to maintain transcript levels of the Musashi1 target Cyclin B1 (Ccnb1) mRNA prior to mRNA translation. In the adult murine pituitary, LSM14B is ubiquitously expressed in both hormone-producing cells and in stem cells as indicated through single cell RNA sequencing. These findings indicate that LSM14B and Musashi1 may function cooperatively to regulate pituitary hormone production and cell differentiation in response to changes in physiological demand.

Presentation: Saturday, June 11, 2022 11:45 a.m. - 12:00 p.m.