bluuebunny/crossref_metadata_2025 huggingface dataset:
THU310 A Presentation Of Diabetic Ketoacidosis In Gestational Diabetes
Authors: Yim Carly , Laura Liu Selina , Spaic Tamara
Published: October 2023

Disclosure: C. Yim: None. S.L. Liu: None. T. Spaic: None.

Diabetic ketoacidosis (DKA) is a diabetic emergency characterized by wide anion gap acidosis, presence of ketones (in serum and/or urine) and, frequently, uncontrolled hyperglycemia. In pregnancy, DKA more commonly occurs in women with pre-existing diabetes, usually type 1 diabetes, and is exceptionally rare in women with gestational diabetes mellitus (GDM). We report a case of a 37-year-old woman in her second pregnancy who presented to hospital with DKA at 29+3 weeks gestation shortly after diagnosis of GDM 4 days earlier.

In her first pregnancy, she was diagnosed with GDM at 28 weeks, required treatment with metformin at 35 weeks, which she stopped postpartum. She conceived her second pregnancy 3 months postpartum so was not screened for diabetes postpartum. In her second pregnancy, there was no evidence of diabetes on early antenatal labwork at 7 weeks: Hemoglobin A1c (HbA1c) 5.6%, random glucose 3.6 mmol/L. Early GDM screening at 21+1 weeks with 75 gram oral glucose tolerance test (OGTT) was normal: fasting glucose 4.4 mmol/L 1-hour glucose 9.0 mmol/L, 2-hour glucose 6.5 mmol/L.

She presented to hospital at 29+3 weeks gestation with a 2-day history of polyuria, polydipsia, dizziness, and decreased oral intake without nausea or vomiting. Four days prior to presentation, she was diagnosed with GDM on a 75g OGTT (fasting glucose 6.2 mmol/L, 1-hour glucose 15.1 mmol/L, 2-hour glucose 11.9mmol/L). Admission labwork showed serum glucose 34.8 mmol/L, anion gap 18, pH 7.29, bicarbonate 17 and beta-hydroxybutyrate 2.97. She was treated with IV fluids and insulin and initiated on multiple daily injections of insulin. Other than pregnancy, no clear precipitating factor was found. HbA1C was 6.4%, serum insulin and C-peptide levels were inappropriately low at 22 pmol/L and 296 pmol/L respectively. Her anti-glutamic acid decarboxylase and anti-islet cell antibodies were negative. Lipase was mildly elevated at 226U/L but improved to 144U/L with treatment. Abdominal ultrasound did not demonstrate any findings suggestive of acute pancreatitis. Her 24-hour urinary free cortisol was 366 nmol and 442 nmol, both within normal trimester-specific range. Her salivary cortisol was in the normal range (10.5nmol and 10.9nmol). Following discharge, she remained significantly insulin resistant with suboptimal glycemic control (total daily insulin requirements ∼3.5 units/kg/day, HbA1C 7.9% at 35+6 weeks).

Due to increased insulin resistance in pregnancy, DKA can progress more rapidly compared to nonpregnancy. Given increased rates of perinatal morbidity and mortality associated with DKA, treatment and monitoring should be promptly initiated. A high index of suspicion is especially important given that DKA is a rare presentation in GDM. Other precipitating factors of newly decompensated diabetes should also be ruled out.

Presentation: Thursday, June 15, 2023
THU328 Appropriate Initial Insulin Dosage For Management Of Steroid-induced Hyperglycemia In Hospitalized COVID-19 Patients
Authors: Ketaroonrut Nuttavadee , Kiertiburanakul Sasisopin , Sriphrapradang Chutintorn
Published: October 2023

Disclosure: N. Ketaroonrut: None. S. Kiertiburanakul: None. C. Sriphrapradang: None.

Introduction: Steroid was recommended for the treatment of severe COVID-19 infection. There are limited studies on the management of steroid-associated hyperglycemia in hospitalized COVID-19 patients. We aimed to determine the appropriate initial insulin dosage to control hyperglycemia in hospitalized COVID-19 patients who received steroid therapy. Methods: We conducted a retrospective single-center analysis of electronic medical records of COVID-19 patients with steroid-induced hyperglycemia who had been treated with insulin. We divided the patients into 4 groups according to the total daily dose (TDD) of subcutaneous insulin therapy at the initiation of dexamethasone ≥6 mg/day or an equivalent dose of glucocorticoid. Glycemic outcomes were compared between groups. Results: A total of 156 patients [age 64±14 years; 50% men; body mass index 26.9±6.9 kg/m2; initial TDD of insulin (units/kg/day): group A, <0.29 (n=79); group B, 0.3-0.49 (n=33); group C, 0.5-0.69 (n=27); group D, >0.7 (n=17)] were included. Most patients (62%) had pre-existing type 2 diabetes. Mean admission blood glucose (BG) and HbA1c were 233±112 mg/dL and 7.8±2.3%, respectively. HbA1c was lowest in group A (6.7±1.2%) and highest in group D (9.8±2.5%). The average daily dexamethasone dosage or equivalent was 49.49±45.4 mg and there were no significant differences between the groups in the dexamethasone dose. The proportion of treatment failure (mean BG >280 mg/dL after the first day of insulin therapy or BG >400 mg/dL for at least 1 time/day) was lowest in group A. Among patients who received TDD >0.3 units/kg/day, group D had the lowest in both the percentage of treatment failure (B (52%) vs C (37%) vs D (29.4%), p=0.006) and mean BG during the 3 days of insulin therapy (B (246.0± 56.7 mg/dL) vs C (246.9±59.0 mg/dL) vs D (228.5±64.4 mg/dL), p=0.21). Three patients had severe hypoglycemia (BG <54 mg/dL) in this study (A: n=1 vs B: n=1 vs C: n=0 vs D: n=1, p=0.51). Conclusions: In the patients who require TDD >0.3 units/kg/day, the treatment failure of hyperglycemia was lowest in the patients who received TDD >0.7 units/kg/day without increasing severe hypoglycemia. This initial insulin dosage may guide physicians to achieve better glycemic control among hospitalized COVID-19 patients who received steroid therapy.

Presentation: Thursday, June 15, 2023
THU340 Efficacy And Safety Of Low-dose Spironolactone On Chronic Kidney Disease In Adults With Type 2 Diabetes: A Multicenter, Randomized Clinical Trial
Authors: Oiwa Ako , Hiwatashi Dai , Takeda Teiji , Miyamoto Takahide , Kawata Iori , Koinuma Masayoshi , Kubota Satoshi , Takayama Shyouhei , Yamazaki Masanori , Komatsu Mitsuhisa
Published: October 2023

Disclosure: A. Oiwa: None. D. Hiwatashi: None. T. Takeda: None. T. Miyamoto: None. I. Kawata: None. M. Koinuma: None. S. Kubota: None. S. Takayama: None. M. Yamazaki: None. M. Komatsu: None.

Objective: To evaluate the albuminuria-lowering effect and safety regarding hyperkalemia of adding low-dose spironolactone (12.5 mg/day) to the renin-angiotensin system (RAS) blockers in adults with chronic kidney disease and type 2 diabetes. Research Design and Methods: This was a multicenter, open-label, randomized controlled trial. We enrolled 130 Japanese individuals aged ≥20 years with type 2 diabetes and albuminuria (≥30 mg/gCre), estimated glomerular filtration ≥30 mL/min/1.73 m2, and serum potassium level <5.0 mEq/L. They were randomly assigned to the spironolactone-administered and control groups. The main outcomes were changes in urine albumin-to-creatinine ratio (UACR), serum potassium levels and renal function from baseline to the 24-week interventional period. Results: The spironolactone-administered group showed a significant reduction in UACR by a mean of 103.47 ± 340.80 mg/gCre from baseline compared with the control group that showed increased UACR by a mean of 63.93 ± 310.14 mg/gCre (p = 0.0007, Wilcoxon rank-sum test and T-test). As for serum potassium levels, although there was a statistically significant increase (p = 0.0026), none of the participants had a potassium level ≥5.5 mEq/L at 24 weeks. Further, there was a tendency that the higher the initial potassium level, the smaller the increase in serum potassium level (estimate −0.37, analysis of covariance). Conclusions: This study first demonstrated that low-dose spironolactone administration reliably reduced albuminuria and was safe against hyperkalemia. The administration of spironolactone, which is the oldest known and most cost-effective of all the other mineralocorticoid receptor antagonists, should be re-evaluated with consideration of lower doses.

Presentation: Thursday, June 15, 2023
THU344 Pandemic Effect On National Hospitalizations For Acute Hyperglycemic Complications In Adults With Diabetes
Authors: Krishnaraju Ellil , Israel Ilelaboye Ayodeji , Kanemo Philip , Vardar Ufuk , Bess Olva , Baskaran Naveen , Shaka Hafeez
Published: October 2023

Disclosure: E. Krishnaraju: None. A.I. Ilelaboye: None. P. Kanemo: None. U. Vardar: None. O. Bess: None. N. Baskaran: None. H. Shaka: None.

Introduction: In 2020, The SARS-CoV-2 outbreak (COVID-19) was quickly classified as a pandemic, prompting a nationwide lockdown. Numerous studies have implicated patients with diabetes to have a higher susceptibility to the COVID-19 virus and more deleterious hospital outcomes. This study aims to describe the effect of the COVID-19 pandemic on epidemiologic trends, and disparities in outcomes among hospitalizations with acute hyperglycemic complications (AHC). Methods: This was a retrospective study of the National Inpatient Sample (NIS) database from 2016 to 2020. The NIS was searched for hospitalization of adults with AHCs. We defined AHC as hospitalizations with diabetic ketoacidosis (DKA) in T1D and DKA and hyperglycemic hyperosmolar state (HHS) in T2D. The admission rate for each calendar year was obtained as admissions per 100,000 adults hospitalized. We obtained the AHC admission rates per 100,000 adult hospitalizations during each calendar year in adults with T1D and T2D. We then compared the admission rate and in-hospital mortality rate in 2019 and 2020 to estimate the pandemic effect. This study also highlights disparities in outcomes of hospitalizations for AHC stratified by sex, race, income quartile, and hospital regions. Results: Pre-pandemic, there was a gradual increase in the number of hospitalizations for AHC in T1D. During the pandemic, there was a decrease in the AHC hospitalization rate per 100,000 admissions for T1D (577 vs 600). However, there was an increase in T2D (117 vs 125). There was no statistically significant difference observed in mortality in T1D (0.20 vs 0.23 p=0.419) and T2D (1.1 vs 0.8 p=0.098). There was also no difference in mortality after stratifying into gender, race, median household income, and hospital region. During the pandemic, COVID-19 was the principal diagnosis in 5.5% of those with AHC in T1D and 9.1% in those with AHC in T2D. However, COVID-19 was a comorbidity in about one in five and one in six mortalities associated with AHC in T1D and T2D respectively. Conclusion: We found that the pandemic had a reciprocal impact on the hospitalization rate for AHC in both T1D and T2D. This brings to light the sheer impact that the COVID pandemic has had and the complex variables that may affect glycemic control. It will be helpful to further stratify the variables that influence AHC hospitalizations to tailor treatment, improve glycemic control and minimize hospitalizations in the future.

Presentation: Thursday, June 15, 2023
THU349 Association Of Non-alcoholic Fatty Liver Disease And Type 2 Diabetes Mellitus - A Cross-Sectional Study
Authors: Amaan Parvez Mohammad , Patel Urvish K
Published: October 2023

Disclosure: M. Parvez: None. U.K. Patel: None.

Introduction: Nonalcoholic fatty liver disease (NAFLD) and Type 2 diabetes mellitus (T2DM) commonly exist together and have been regarded as a manifestation of metabolic syndrome. But there are limited studies showing prevalence and association of NAFLD with T2DM patients in US populations. Aims and Objective: Primary outcome of the study was to identify the prevalence and association of NAFLD amongst patients with T2DM amongst the US populations. Methods: A cross-sectional study was performed using the National Health and Nutrition Examination Survey database from 2015 to 2018. Adults with diagnosis of NAFLD and non-NAFLD were identified. We ran univariate analysis using Mann Whitney U test and chi-square test. Multivariable survey logistic regression analysis was performed to find out the association between NAFLD and T2DM. Results: Out of a total 275,968 people, 0.26% had NAFLD. Older population (median: 62 years), male, Mexican American, and people with median household income >$100,000 had a higher prevalence of NAFLD. The diagnosis of NAFLD (40.31% vs 14.23%; p<0.0001) was more prevalent amongst patients with T2DM in comparison to those without NAFLD. In regression analysis, T2DM patients had significantly higher odds of having NAFLD (aOR: 10.40, 95%CI: 10.37- 10.42, p<.0001, c=0.736). Conclusion: Long term follow-up, early identification, and prompt treatment may mitigate the burden of NAFLD in T2DM patients.

Presentation: Thursday, June 15, 2023
THU356 Muscle Pain In A Diabetic: Think Outside The Box
Authors: Ellangovan Rithikaa , Rizk Michelle-Ashley , Singh Vinita , Sherpa Chheki
Published: October 2023

Disclosure: R. Ellangovan: None. M. Rizk: None. V. Singh MD: None. C. Sherpa: None.

Introduction: Stiff person syndrome (SPS) is a rare immunological disorder associated with GAD antibody-spectrum disorders and characterized by rigidity and painful muscle spasms. SPS has a prevalence of 1-2 cases per million and affects females more than men. We present a case of SPS who was admitted for progressive muscle pain and rigidity causing impaired ambulation. Case Presentation: A 60-year-old female with a two-year history of type 2 diabetes, Graves' disease was diagnosed with acral lentiginous melanoma of the left foot. One month after Nivolumab immunotherapy, she converted to type 1 diabetes with low C-peptide and positive GAD antibody. She was admitted with severe muscle pain and spasms in her lower extremities and trunk, debilitating enough to make her bedbound. Her muscle strength and sensory function were intact. MRI of thigh was concerning for myositis versus diabetic myonecrosis. She was initiated on NSAIDs with no improvement. Core muscle biopsy revealed necrosis and granulation tissue with no evidence of malignancy. Extensive work up including myositis panel and myasthenia gravis panel were negative. The presence of GAD antibodies and no improvement to NSAIDs, prompted suspicion for SPS. The patient declined lumbar puncture (LP) for further evaluation. Diazepam showed mild improvement. Due to persistent severe symptoms, she was treated with IVIG for 5 days that resulted in marked improvement. Discussion: There is no gold standard test for definitive diagnosis of SPS. Classic features of SPS include muscle spasms, pain, and rigidity typically involving the trunk and lower extremities. There are GAD antibodies in serum and CSF and glycine receptor or amphiphysin antibodies. EMG study will show continuous motor unit activity in affected muscles. A robust response to muscle relaxants like GABA agonists and exclusion of alternative neurological disorder favors SPS. LP or EMG was not performed on this patient, yet she met other criteria including the presence of other GAD disorders like type 1 diabetes. Current recommended therapy for symptomatic relief includes GABA agonists or baclofen. If no improvement is noted, IVIG can be considered. Plasmapheresis and rituximab have been used with variable efficacy. Prognosis is variable and many patients experience disability despite combining multiple therapies. Hence it is crucial to have a high index of suspicion in GAD spectrum disorders for early recognition and prompt treatment.

Presentation: Thursday, June 15, 2023
THU357 A Case Of Recurrent Insulin-induced Edema In A Pediatric Adolescent Patient
Authors: Mora Calderon Guido Jesus , Aguirre Roxana L , Preston Debara
Published: October 2023

Disclosure: G.J. Mora Calderon: None. R.L. Aguirre: None. D. Preston: None.

Introduction: Insulin induced edema is a very rare complication seen after initiation of insulin therapy or after escalation of previous insulin regimen in patients with diabetes. The exact incidence of this condition is unknown. Insulin induced edema seems to have a female predominance and is associated primarily with patients who are underweight. The severity of insulin induced edema can range from mild localized peripheral edema to more severe and generalized complications, including cardiac failure and serosal effusions. There is a higher risk for severe complications in older patients with pre-existing cardiac, hepatic, or renal conditions. Usually, the course is benign and self-resolved without any intervention. Severe and prolonged cases have been reported to need adjuvant therapy (e.g diuretics or sympathomimetic agents) or sodium-restricted dietary regimens. Increasing blood glucose target with a decreased insulin regimen has been proposed as a possible option to prevent insulin induced edema. We present a 14 year-old-male patient with history of poor controlled type 1 diabetes mellitus and recurrent insulin-induced edema after strengthening of his insulin therapy. Case Presentation: A 14-year-old male with poorly controlled type 1 diabetes mellitus presented to the emergency with pitting edema of his face and hands that started a week after intensification of his insulin regimen. His weight increased from 73 kg to 84 kg in about 10 days. His vital signs at presentation were stable and besides the pitting edema, the rest of the physical examination was unremarkable. His mother reported a previous episode of edema that occurred approximately a year before this presentation and about a month after he was first diagnosed with diabetes mellitus. His most recent HbA1c was 14.4%. Patient was admitted for evaluation. Electrocardiogram, transthoracic echocardiogram, chest x-ray, and multiple laboratories (including a comprehensive metabolic panel, complete blood count, B-type natriuretic peptide, urine microalbumin, and thyroid function test ) came back all normal. The edema slowly improved and was eventually discharged. No adjuvant therapy was needed during his hospitalization. Conclusion: The diagnosis of insulin induced edema is primarily based on the exclusion of other etiologies. Most cases reported only one episode after initiation of insulin therapy or after escalation of previous insulin regimen, but it can happen multiple times as noted in our patient.

Presentation: Thursday, June 15, 2023
THU360 Hyperglycemic DKA In Patient On Monotherapy With SGLT-2 Inhibitor
Authors: Ahmed Samihah , Medina Mora Luis , Sanchez Ruiz Angelica , Poretsky Leonid
Published: October 2023

Disclosure: S. Ahmed: None. L. Medina Mora: None. A. Sanchez Ruiz: None. L. Poretsky: None.

Background: SGLT2 inhibitors have a rare but increasingly reported risk of euglycemic diabetic ketoacidosis. Hyperglycemic diabetic ketoacidosis is not an expected risk of SGLT-2 inhibitors. Clinical Case: 52-year-old male with history of type 2 Diabetes presented with progressive weakness, shortness of breath, nausea and vomiting worsening over 48 hours. He reported increased polydipsia and polyuria. Patient was found to have a blood glucose of 685 mg/dL associated with an anion gap of 28 mm/L and bicarbonate level of 6 mm/L. Beta hydroxybutyrate level was >8.0 mmoL/L. He was diagnosed with hyperglycemic diabetic ketoacidosis, given intravenous isotonic fluid and started on an insulin drip. The anion gap closed and he was successfully transitioned off the insulin drip to a basal bolus regimen of insulin. The patient improved quickly without any complication. The patient was never on insulin therapy prior to admission. No obvious source of infection was discovered to precipitate the event. The patient had a 7-year history of diabetes and was only managed on oral medications at home. He was previously on Janumet 50-1000mg twice a day and changed to only dapagliflozin 10mg 9 months prior to the current episode. He never experienced ketoacidosis or hyperosmolar hyperglycemic state. Hemoglobin A1c was found to be 8.0%. He reported that his A1c levels were always less than 8%. Autoimmune workup for type 1 Diabetes was done. C-peptide level was found to be 1.5ng/mL. Patient appeared to have an adequate insulin level despite the recent event of diabetic ketoacidosis. Patient was discharged on 10 units of Glargine® at bedtime and 3 units of Lispro® before meals. He was given glucometer teaching with an appointment for endocrine follow up. During follow up Glutamic Acid decarboxylase, Islet cell, Insulin and Zinc 8 transporter antibodies have come back negative. Patient is being planned for transition to oral antihyperglycemic agents which will not include an SGLT2 inhibitor. A MODY panel is pending results for further evaluation. Conclusion: Monotherapy of SGLT-2 inhibitors appears to not only have a risk of euglycemic diabetic ketoacidosis but also a risk of hyperglycemic diabetic ketoacidosis in type 2 diabetics. In this case we presented a case of hyperglycemic diabetic ketoacidosis in a type 2 diabetic on therapy with dapagliflozin.

Presentation: Thursday, June 15, 2023
THU363 Misdiagnosing Latent Autoimmune Diabetes Mellitus In Adults: A Case Report
Authors: Rafat Ummara , Akhter Wajeeha , Alshantti Raeda , Gilden Janice L
Published: October 2023

Disclosure: U. Rafat: None. W. Akhter: None. R. Alshantti: None. J.L. Gilden: None.

Background: Latent Autoimmune Diabetes Mellitus (DM) in Adults (LADA) is often misdiagnosed as Type 2 DM. This can lead to increased risk of complications. Therefore, knowledge and awareness of LADA is essential. LADA is diagnosed based on three features, age greater than 35 years, presence of antibodies to pancreatic islet cell antigens (Glutamic Acid Decarboxylase GAD, Insulinoma antigen-2 IA-2A, Zinc Transporter 8 ZnT8A) and lack of insulin requirement for at least 6 months after diagnosis. It is important to diagnose LADA early, so that patients can be started on insulin earlier, thereby achieving better glycemic control and preserving residual beta cell function. Case Presentation: We present the case of a 44-year-old female of mixed African American and Greek ethnicity with a history of DM complicated by nephropathy, hypertension, obesity, acne and uterine fibroids. She was diagnosed with Type 2 DM at age 36 from routine screening with a HbA1c of 6.9% and started on Metformin by primary care provider. Family history was significant for transient postpartum hypothyroidism in her mother, and DM in both maternal and paternal grandparents. She was unable to tolerate Metformin due to gastrointestinal side effects and was switched to Insulin Detemir therapy one year later. She first presented to the endocrine clinic for evaluation and management of abnormal thyroid function tests with symptoms of weight loss, excessive hair fall, anxiety, and palpitations. Vital signs: Blood pressure 146/65 mmHg, Heart rate 89 bpm, Respiration 14 breaths/min, BMI 31 kg/m2. Physical examination was significant for marked edema of eyelids, but no thyromegaly or tremors, and marked acanthosis nigricans. Laboratory tests were consistent with Grave’s disease with TSH less than 0.005 uIU/mL (n= 0.358-3.74), free T3 22.93 pg/mL (n=2.18-3.98), free T4 4.63 ng/dL (n=0.76-1.46) and positive TSI of 291%. (n<140). The patient was started with methimazole therapy. GAD 65 was found to be positive >250 IU/mL (n<5) and islet cell antibodies were negative. A revised diagnosis of LADA was made. The co-existence of Grave’s disease enabled reclassifying the type of her DM. Conclusion: Type 1 diabetes mellitus or autoimmune diabetes mellitus should always be ruled out if the clinical picture does not match with type 2 Diabetes Mellitus or in a relatively young patient. Our case aims to increase awareness of Autoimmune Polyendocrine syndrome, which occurs as a result of loss of immune tolerance, leading to impairment of multiple endocrine glands.

References: Standards of Care in Diabetes—2023 Diabetes Care 2023;46(Suppl. 1):S5-S9 Volume 46 Issue Supplement_1 | Diabetes Care | American Diabetes Association (diabetesjournals.org)

Presentation: Thursday, June 15, 2023
THU364 A Rare Case Of Concurrent Diabetic Ketoacidosis And Grave’s Thyrotoxicosis
Authors: Quadros Teixeira Aline De , Ukponmwan Esosa , Kachhadia Palak , Aldasouqi Saleh , Abu Limon Ahmad
Published: October 2023

Disclosure: A.D. Teixeira: None. E. Ukponmwan: None. P. Kachhadia: None. S. Aldasouqi: None. A. Abu Limon: None.

Introduction: Type 1 Diabetes Mellitus (T1DM) is marked by deranged glycemic control due to the autoimmune destruction of insulin producing β cells in the pancreas. It affects 1.5 million adults in the United States. Approximately one-third of these patients may develop autoimmune polyglandular syndrome (APS). Autoimmune Thyroid Disease (AITD) is the most commonly associated autoimmune disease, with Hashimoto’s Thyroiditis more commonly observed than Graves Disease (GD). Patients with AITD and T1DM meet criteria for APS type 3A. Here, we present a case of a patient hospitalized for T1DM with diabetic ketoacidosis (DKA) who was also found to have concurrent GD. Case Presentation: Our patient was a 50 year old male who presented to the hospital with complaints of nausea and vomiting for a two day duration. He had symptoms of unintentional weight loss, polyuria and polydipsia for about two months prior to presentation. He was found to have blood sugar level of 438 mg/dL, with pH of 7.05 (7.35-7.45), anion gap of 30, bicarbonate level of 7.0 mmol/L (20-30 mmol/L), Beta-hydroxybutyrate level of 82mg/dL (n<4.10 mg/dL). Hemoglobin A1C was 15.1% . EKG revealed atrial fibrillation with RVR, and therefore thyroid function tests (TFTs) were ordered and showed a thyroid stimulating hormone (TSH) level of 0.01uIU/mL (0.35-4 uIU/mL), free thyroxine (FT4) of 1.29 ng/dL (0.61-1.37 ng/dL) and free triiodothyronine (FT3) levels of 4.4 pg/mL (2.8-4.4 pg/mL). Endocrinology evaluation of the patient’s Thyroid US showed some mild vascularity. Cardiac evaluation of patient’s atrial fibrillation did not reveal any other causes of arrythmia. Further labs showed TSI of 2.6 (n<1.3 TSI index) with normal TRAb and TPO levels. T1DM antibody testing revealed GAD-65 antibody (Ab) level of 51.3 nmol/L (n <0.02 nmol/L), Zinc Transporter 8 Ab level of >500 U/mL (n<15 U/mL). He was started on methimazole with good tolerance and was discharged upon resolution of his DKA with multiple daily injections of insulin. Discussion: AITD is the most prevalent autoimmune disease associated with T1DM, with GD being a less common association compared to Hashimoto’s thyroiditis. Many patients diagnosed with T1DM may develop other autoimmune conditions. On rare occasions these diseases can present concurrently, as it did with our patient. Recognition and awareness of APS types helps physicians recognize and screen for other autoimmune conditions that have previously been seen together. Literature search shows very few cases with both diseases presenting at the same time on hospitalization. However, with the recent COVID-19 pandemic, 5 cases were reported of simultaneous disease following vaccination. Our patient had no known exposure to COVID-19 virus or vaccine when he developed symptoms.

Presentation: Thursday, June 15, 2023
THU367 Hyperosmolar Hyperglycemic State In A Middle-old Male With Primary Hyperparathyroidism
Authors: Mandocdoc Dimayuga Diana Colleen , Capuli Isidro Maria Jocelyn
Published: October 2023

Disclosure: D.M. Dimayuga: None. M.C. Isidro: None.

A 79-year-old male was brought to our hospital for drowsiness. He had low-grade fever with associated cough and anorexia 1 week prior. He had a previous history of hypertension and primary hyperparathyroidism (PHPT) maintained on cinacalcet. He did not have a history of diabetes and a family history of diabetes, and his HbA1c was 5.4% three months before. On admission, the results of his physical examination and vital signs were as follows: height, 152cm; weight, 56.0 kg; BMI, 24.2 kg/m2; temperature, 36.5C; heart rate, 85 beats/min; SpO2, 98% (on room air); respiratory rate, 22 breaths/min; and blood pressure, 115/60 mm Hg. His blood glucose level was 966 mg/dL, HbA1c 13.4%, and serum osmolality 324 mOsm/kg. Serum ketones were 15 mg/dL and blood gas analysis was normal. He was diagnosed with hyperglycemic hyperosmolar state (HHS) and infusion of insulin and saline was subsequently initiated. With clinical suspicion of chronic pancreatitis given the patient’s history of PHPT, serum lipase was checked, 105 U/L (NV: 12-53 U/L). Ionized calcium was 1.36 mmol/L. On CT scan of abdomen, there was no evidence of duct dilatation and calcification, and instead, “features of diffuse fatty atrophy of the pancreas” were seen. His endogenous insulin secretory capacity was sufficient (serum C-peptide: 2.76 ng/mL, NV: 0.78-5.19 ng/mL). Eventually, the patient’s level of consciousness improved and glycemic control was achieved. Soon after, insulin was shifted to basal-bolus regimen. On the 7th day of hospitalization, patient was discharged with minimal insulin requirements. Two weeks later, on follow up, his blood glucose levels were found to be stable. It was not clear whether our patient had new-onset autoimmune or type 2 diabetes. Although autoimmune diabetes generally occurs when about 90% of the pancreatic beta cells have been destroyed, the patient could have been in the honeymoon period wherein beta cell activity was transiently regained after commencement of insulin therapy. Our plan is to monitor his C-peptide titers and test his insulin antibodies. Evidence suggests that PHPT may cause insulin resistance and glucose intolerance. The rise in free intracellular calcium may reduce glucose transport in insulin-stimulated glucose transporters, increasing the need for insulin. This could be the case in our patient hence we diagnosed him with type 2 diabetes. To the best of our knowledge, this is the first case demonstrating the co-occurrence of HHS and PHPT.

Presentation: Thursday, June 15, 2023
THU371 Empagliflozin Associated Pancreatitis: A Case Report
Authors: Poloju Alekya , Majety Priyanka , Groysman Anna Y
Published: October 2023

Disclosure: A. Poloju: None. P. Majety: None. A.Y. Groysman: None.

Background/Objective: Sodium glucose cotransporter 2 (SGLT2) inhibitors are increasingly being used in the treatment of type 2diabetes mellitus (T2DM). With the recent FDA approval of these medications for treatment of heart failure, their use is expected to increase further. Common adverse events associated with SGLT2 inhibitors are genitourinary infections, hypotension, acute kidney injury and euglycemic diabetic ketoacidosis. Recently, SGLT2 inhibitors are increasingly associated with drug induced acute pancreatitis (DIAP). We present a case of empagliflozin associated DIAP, with the intent to add to the limited data on this possible adverse effect. Clinical Case: A 57-year-old woman with a history of T2DM presented to the hospital with severe abdominal pain. She had no recent alcohol use or prior episodes of pancreatitis. There was no history of trauma. Home medications include metformin, glipizide, empagliflozin, and lisinopril. Exam showed epigastric tenderness to palpation without guarding or rebound tenderness. Labs were notable for elevated white blood cell count, normal lipase, calcium, triglycerides, and liver function tests. CT abdomen showed induration of the peri-pancreatic fat, suggestive of pancreatitis. After ruling out common causes of pancreatitis, DIAP and idiopathic pancreatitis were considered possible etiologies. Obtaining further history revealed that patient was started on empagliflozin two weeks prior to this presentation. The only other medication that is known to cause pancreatitis is lisinopril but our patient was on this medication for several years. The Naranjo probability scale for empagliflozin showed a possible association between the drug and side effect. Empagliflozin was discontinued and the patient was discharged on metformin and glipizide. Conclusions: Pancreatitis is a common diagnosis requiring hospital admission and is associated with significant costs to the healthcare system. Although pancreatitis is a known side-effect with other medications used in treatment of T2DM, such as GLP1RAs and DPP-4inhibitors, it has not been well described with SGLT2 inhibitors. The prevalence of DIAP is difficult to assess since most of the existing data comes from individual case reports. Our patient had no known risk factors for pancreatitis. It is yet to be studied if genetic predisposition has a role in the development of pancreatitis with SGLT-2 inhibitors. With the increasing use of these medications in the treatment of type 2diabetes mellitus and heart failure, more cases of DIAP are being reported. It is important for physicians to consider SGLT2 inhibitors as a cause of pancreatitis after excluding other common etiologies. This may reduce episodes of recurrent pancreatitis and the burden of extensive workup for idiopathic pancreatitis.

Presentation: Thursday, June 15, 2023
THU377 Arterio-enteric Fistula, A Rare Complication After Pancreatic Transplant
Authors: Herrera Chancay Azucena M , Calderon Andres , Manavalan Anjali
Published: October 2023

Disclosure: A.M. Herrera Chancay: None. A. Calderon: None. A. Manavalan: None.

Introduction: Areterio-enteric (AE) fistula is a rare but life-threatening complication of a failed pancreas transplant and most often presents with a gastrointestinal (GI) herald bleed. This case illustrates the importance of the prompt recognition and appropriate evaluation of GI bleeding in patients with a failed pancreas transplant and highlights the challenges associated with the management of an AE fistula. Case Description: A 53-year-old man with history of T1D complicated by retinopathy, neuropathy, nephropathy, end-stage renal disease (ESRD) and failed combined pancreas-renal transplant, presented to our hospital with diabetic ketoacidosis secondary to insulin pump malfunction. His course was complicated by a GI bleed. He was initiated on proton pump inhibitors but endoscopy was deferred due to resolution of bleeding. The patient was discharged from the hospital with plans for outpatient endoscopy however, he returned to the emergency room with hematemesis, malena and hemorrhagic shock complicated by cardiac arrest. Emergent endoscopy was performed but the source of bleeding could not be visualized due to large clots and fresh blood. A CT angiogram revealed brisk bleeding from the right common iliac pancreatic transplant graft. Coil embolization was attempted but unsuccessful and the patient was ultimately treated with two stents to the right iliac artery with subsequent resolution of bleeding. The patient was ultimately discharged home in stable condition. Conclusion: During pancreas transplant, the donor pancreas and duodenum are connected by a Roux en Y anastomosis to the small bowel of the recipient. The donor pancreas is placed in the right iliac fossa followed by anastomosis of the recipient right common iliac artery with the donor Y graft (Consisting of the iliac artery, its bifurcation, and the splenic and superior mesenteric arteries). AE fistula is an extremely rare complication of pancreatic transplant with only about 30 reported cases. This occurs in the setting of transplant failure, possibly due to the increased local inflammation. Endoscopy is often unsuccessful in locating the bleeding source. Angiography and stenting of the bleeding vessel seem to offer the most success and should be considered in patients with failed pancreas transplant presenting with GI bleeding.

Presentation: Thursday, June 15, 2023
FRI637 Missed MODY With Complex Mutation
Authors: Bulchandani Sheetal , Chandra Majety Sarat , Kundra Priya
Published: October 2023

Disclosure: S. Bulchandani: None. S. Majety: None. P. Kundra: None.

Introduction: The prevalence range of Maturity-Onset Diabetes of the Young (MODY) is 1-5% among all patients diagnosed with diabetes. Strong family history of diabetes is suggestive of autosomal dominant inheritance. The symptoms of MODY range from mild asymptomatic hyperglycemia to overt insulinopenia requiring insulin therapy. Clinical Case: 33-year-old male presented to the endocrinology clinic for evaluation. He was diagnosed with type 2 diabetes mellitus at the age of 13 years and was initially treated with insulin which was subsequently transitioned to repaglinide and metformin. Reported history of hypoglycemia at birth in self and recently born daughter. Family History was significant for diabetes mellitus diagnosed in biological father at the age of 16 years. Genetic testing for monogenic diabetes revealed pathogenic variant in hepatocyte nuclear factor 4 alpha (HNF4a) and variant of unknown significance in Paired Box Gene 4 (PAX4). Therapy was switched to glipizide 2.5 mg orally which resulted in adequate glycemic control. Genetic testing was recommended for his daughter. Conclusion: MODY is a rare condition and because of its wide clinical presentation, it is common for it to be missed. There are about 14 subtypes of MODY with different genetic mutations, each affecting the beta cell function in a different way. Our case is unique given that our patient had two genetic mutations. Amongst all forms of MODY, HNF4a with a prevalence of 5% to 10% is the third most common mutation of MODY. PAX4 is a transcription factor that is critical for the formation of beta cells, and is important as a regulator in commitment of progenitor cells to mature islet cells. Mutations in PAX gene associated with monogenic diabetes were first identified in two patients of Thai origin, who did not present with mutations in the other known MODY genes. There should be high vigilance and low threshold for genetic testing for MODY in patients who have high likelihood of possessing a form of MODY, particularly as the treatment can be tailored to the clinical presentation of the patient. References: 1. Abreu GM, Soares CAPD, Tarantino RM, da Fonseca ACP, de Souza RB, Pereira MFC, Cabello PH, Rodacki M, Zajdenverg L, Zembrzuski VM, Campos Junior M. Identification of the First PAX4-MODY Family Reported in Brazil. Diabetes Metab Syndr Obes. 2020 Jul 24; 13:2623-2631. doi: 10.2147/DMSO.S256858. PMID: 32801813; PMCID: PMC7399458. 2. Antal Z. Maturity-Onset Diabetes of the Young (MODY): Genetic Causes, Clinical Characteristics, Considerations for Testing, and Treatment Options. Endocrines. 2021; 2(4):485-501. https://doi.org/10.3390/endocrines2040043

Presentation: Friday, June 16, 2023
SAT053 Development Of A Novel Peptide-based Insulin Sensitizer Through Disruption Of Inositol Polyphosphate 5-Phosphatase K (SKIP) - p21-activated Kinase 1 (Pak1) Interactions
Authors: Kimbrough Alyssa M , Dev Gaddameedi Jitender , Lipchik Andrew M
Published: October 2023

Disclosure: A.M. Kimbrough: None. J. Dev Gaddameedi: None. A.M. Lipchik: None.

Type 2 diabetes (T2D) is a prominent, chronic metabolic disease that affects approximately 462 million people worldwide. The driving force behind T2D is insulin resistance (IR), defined as an impaired biological response to insulin, and leads to a multitude of more severe conditions including heart disease, stroke, and neuropathy. Most therapies fail to improve insulin sensitivity, and instead drive physiological compensation. It is imperative to develop new therapies to correct the underlying pathology by targeting mechanisms of IR. Inositol polyphosphate 5-phosphatase K (INPP5K/SKIP) is a potential target to treat IR. SKIP resides in the endoplasmic reticulum (ER) in resting cells, and translocates to the plasma membrane (PM) following growth factor stimulation. SKIP is recruited to the PM through binding to p21 activated kinase 1 (Pak1) and inhibits growth factor signaling through dephosphorylation of phosphoinositol-(3,4,5)-triphosphate. In obesity and IR, SKIP is overexpressed leading to PM localization and suppression of insulin signaling. Here, we developed a novel insulin sensitizer utilizing a peptide derived from Pak1 to inhibit SKIP-Pak1 interactions and prevent PM localization. We found that the Pak1 derived peptide displayed alpha helical properties and thermostabilized SKIP. In controlled in vitro assays, the Pak1 peptide was successfully taken up in target tissues. Additionally, treatment with the Pak1 peptides was sufficient to restore insulin sensitivity in skeletal muscle, adipose, and liver models of IR. Together these results demonstrate the use of a peptide-based insulin sensitizer as a novel therapeutic for T2D that requires further investigation.

Presentation: Saturday, June 17, 2023
SAT066 Leukotriene B4 Receptor 2 Mediates Macrophage Migration To Injured β Cells
Authors: Ermis Ebru , Nargis Titli , Kulkarni Abhishek , May Sarah , Tersey Sarah A , Mirmira Raghavendra G , Anderson Ryan M
Published: October 2023

Disclosure: E. Ermis: None. T. Nargis: None. A. Kulkarni: None. S. May: None. S.A. Tersey: None. R.G. Mirmira: None. R.M. Anderson: None.

Type 1 diabetes (T1D) is an autoimmune disease, characterized in part by islet inflammation and macrophage infiltration leading to β-cell injury and loss. The inflammatory mediator 12/15-lipoxygenase (12/15-LOX) and its lipid product 12-hydroxyeicosatetraenoic acid (12-HETE) have both been implicated in T1D. 12-HETE activates the low affinity receptor leukotriene B4 receptor 2 (LTB4R2, or simply BLT2), which was reported as a low-affinity receptor for 12-HETE, suggesting that BLT2 may play a proinflammatory role. Here, we used both mouse and zebrafish models to probe the roles of BLT2 in macrophage activation and/or recruitment to pancreatic islets during T1D progression. First, we analyzed Blt2 gene expression in a variety of C57BL/6J mouse tissues. We found Blt2 gene expression in bone marrow derived macrophages and peritoneal macrophages, however we found little to no expression in pancreatic islets. Although Blt2-/- mice showed a significantly reduced expression of Blt2, they exhibited overall normal growth and glucose tolerance. To uncover roles for BLT2 in macrophage function, we first interrogated its involvement in the in vitro polarization of proinflammatory macrophages to the M1-like state using LPS and IFN-γ and the M2-like state using IL-4. Under these conditions, we found no differences between Blt2-/- and wildtype macrophages, as assessed by flow cytometry analysis, suggesting that BLT2 does not play a substantial role in macrophage polarization. Next, to query roles for BLT2 in macrophage migration, we employed the transgenic zebrafish line Tg(mpeg:EGFP) in which macrophages are labeled with green fluorescent protein (GFP). Following zebrafish tailfin injury, we quantified macrophage accumulation at the injury at 6 hours post amputation. Inhibitory treatments of zebrafish larvae with either a chemical BLT2 inhibitor (LY255283) or by knockdown of the blt2a gene using an antisense morpholino, both decreased the number of GFP+ macrophages found at the injury site. Moreover, in the latter approach ectopic expression of blt2a mRNA effectively restored the wild-type phenotype. To determine if BLT2 mediates macrophage migration to injured islets, we employed a transgenic zebrafish model of β-cell injury, Tg(ins:NTR), in which metronidazole treatment rapidly induces β-cell injury. We treated the Tg(mpeg: GFP); Tg(ins: NTR) zebrafish with metronidazole and monitored macrophage migration into injured islets. We observed a significant decrease in macrophage migration towards injured β-cells in blt2a-knockdown zebrafish. Collectively, these results show that BLT2 plays a role in macrophage migration associated with tissue injury, including the islet β cell as seen in T1D.

Presentation: Saturday, June 17, 2023
SAT075 Beta Cells Adapt To Insulin Resistance Via Posttranslational Modification Of The Translation Factor eIF5A
Authors: Anderson Cara , Kulkarni Abhishek , Maier Bernhard , Tersey Sarah A , Anderson Ryan , Mirmira Raghavendra G
Published: October 2023

Disclosure: C. Anderson: None. A. Kulkarni: None. B. Maier: None. S.A. Tersey: None. R. Anderson: None. R.G. Mirmira: None.

Prior to type 2 diabetes onset, β cells adapt to insulin resistance through compensation—a process that maintains insulin secretion and glucose homeostasis. Our lab has previously shown that β cell compensation requires the activity of deoxyhypusine synthase (DHPS), which post-translationally catalyzes the formation of the amino acid hypusine at Lys50 of eukaryotic initiation factor eIF5A. Although hypusinated eIF5A is required for β cell compensation, it is unclear if unhypusinated eIF5A limits this compensatory response. To identify the role of unhypusinated eIF5A, we used the following animal and cell-based models: RNAi knockdown and transgenic zebrafish; inducible, β cell-specific knockout mice fed a high fat diet; and cultured HEK-293 cells. Zebrafish embryos injected with morpholinos to reduce global DHPS (and accumulate unhypusinated eIF5A) showed stunted exocrine pancreas growth at 3 days post-fertilization. Although, those injected with anti-eIF5A morpholinos (to deplete all eIF5A) showed normal pancreas growth. Transgenic overexpression of a mutant eIF5A incapable of hypusination resulted in reduced pancreas size in zebrafish. Although a unique function of unhypusinated eIF5A has not yet been documented, these findings suggest that the presence of unhypusinated eIF5A may be the major driver of altered pancreas phenotypes. Similarly, following 4 weeks of high fat diet feeding and obesity, mice lacking total eIF5A in β cells had improved glucose tolerance compared to mice lacking DHPS in β cells, despite similar weight gain and insulin sensitivity. To clarify the molecular mechanisms behind the damaging role of unhypusinated eIF5A, we performed polyribosome profiling to measure translation in lysates from HEK-293 cells in which either DHPS or total eIF5A were depleted by RNAi. Whereas loss of total eIF5A slightly reduced mRNA translation elongation, loss of DHPS (and accumulation of unhypusinated eIF5A) reduced mRNA translation initiation. Further experiments in HEK-293 cells suggest that unhypusinated eIF5A increases levels of phosphorylated eIF2α (an inhibitor of global mRNA translation) by specifically interacting with the kinase GCN2. Taken together, our data provide evidence that DHPS deficiency and obesity conditions impair β cell function, in part, from the accumulation of the unhypusinated form of eIF5A. Our studies reveal a mechanism in which β cells respond to obesity by regulating mRNA translation through the balance between hypusinated and unhypusinated forms of eIF5A.

Presentation: Saturday, June 17, 2023