bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP187 Doedge-Potter syndrome and papillary thyroid carcinoma: An unusual association
Authors: Gandara Carmen , Puente Guillen , Riestra María , Veiguela Brenda , Felechosa Marta , Gutierrez Gala , Valdes Nuria , Monge Pilar , Diaz Lucia , Diaz Maria Jesus
Published: November 2022

Hypoglycemia can occur in non-diabetic individuals. Doege-Potter is a rare paraneoplastic syndrome presented as a hypoinsulinemic hypoglycemia caused by ectopic secretion of insulin-like growth factor-2 (IGF-2) from a solitary fibrous tumor. There is recent evidence of the involvement of the IGF system in different malignancies as papillary thyroid carcinoma, being exceptional. A 69-year-old female was brought to Emergency after a routine analysis uncovered severe hypoglycemia. She mentioned a history of morning sickness, dizziness, and confusion for the last week that reverted after breakfast, and dry cough for three months. She had a 25-pack-year history of smoking, no history of alcohol use, no other antecedent of interest, no history ofdiabetes mellitus or weight loss surgery, nor chronic treatments. Physical examinations revealed diminished breath sounds in the left middle lung. A thorax radiography showed a submassive left pleural effusion and toracocentesis revealed a hemorrhagic exudate. Laboratory data showed normal GH, and cortisol levels. Despite marked hypoglycemia, insulin level was 0.4 μIU/mL (2,6-24,9), C-peptide 0.11ng/ml (1,1-4,4) and hydroxy butyrate <0.1 mg/dl. The serum IGF-2 level was 428μg/dL (350-1000), and the IGF-1 level was 55.4 μg/L(161-384). Anti-insulin antibodies and sulfonylureas concentration were negative. CT showed a solid mass concerning parietal pleura with areas of necrosis and calcifications, measuring 14.6×15.4×20cm. Low blood glucose with suppressed insulin, C-peptide and IGF-1 levels, elevated IGF-2/IGF-1 ratio (7,7, normal<3) and CT findings suggested the possibility of non-islet cell tumor hypoglycemia (NICTH). Corticoid treatment was initiated to manage the hypoglycemia. Biopsy of the mass showed a malignant solitary fibrous tumor, positive for CD34 and BCL2. After surgery, glucose and IGF-2 levels returned to normal, the patient didn't experience further episodes of hypoglycemia, and corticoid treatment was gradually suspended. A FDG-PET scan, part of extension study, found a PET-positive thyroid nodule. A thyroid ultrasound confirmed a solid, taller than wide thyroid nodule, measuring 6.7×6.4×9,5mm and fine-needle aspiration biopsy was suggestive of papillary thyroid carcinoma. Hemithyroidectomy was performed. The patient is with no evidence of disease. Doege-Potter syndrome is a rare cause of hypoglycemia, resulting from a tumor producing elevated levels of IGF-2. Diagnosis is suggested by low insulin, C-peptide and IGF-1 levels, normal or elevated IGF-2, and elevated IGF2/IGF1 ratio. High levels of ''big-IGF-2'' are associated with high risk papillary thyroid carcinoma, suggesting the relation between the IGF-system and tumor growth, nevertheless there are few cases reported describing this association. Surgical resection of the tumor is the treatment of choice.

Presentation: No date and time listed
ODP189 Effects of Exercise Initiation and Smoking Cessation after New-Onset Type 2 Diabetes Mellitus on Risk of Mortality and Cardiovascular Outcomes
Authors: Yoo Soon Jib , Kwon Prof Hyuk-Sang , Kim Mee Kyoung , Han Kyungdo
Published: November 2022

Lifestyle changes after a diagnosis of type 2 diabetes mellitus (T2DM) can affect vascular health outcomes. The objective of this study was to investigate the effects of changes in smoking and exercise on the risk of cardiovascular disease (CVD) and mortality in patients with newly diagnosed T2DM. Data were analyzed for 181,591 people with newly diagnosed T2DM who underwent 2 serial health examinations within 2 years before and after diagnosis of diabetes. The study population was followed from the baseline to the date of death or cardiovascular events, or until December 31, 2018 and median follow-up was 6. 07 years. Based on the change in status from before to after the diagnosis of T2DM, participants were grouped into smoking groups (continuous smokers, quitters, new smokers, and nonsmokers) and exercise groups (constant exercisers, new exercisers, exercise dropouts, and non-exercisers). Compared with the non-exercisers, those who initiated exercise after their diagnosis had a lower risk of myocardial infarction (MI), stroke, and all-cause mortality: the hazard ratio (HR; 95% confidence interval [CI]) was 0.85 (0.76–0.94) for MI, 0.86 (0.78–0.94) for stroke, and 0.84 (0.89–0.90) for all-cause mortality. Quitters had a higher risk of MI, stroke, and all-cause mortality than nonsmokers, but their risk level was much lower than that in continuous smokers. Whenthe group ofcontinuous smokers and non-exercisers was considered as the reference group,participants who quit smoking and remained non-exercisers had a 21% lower risk of CVD (HR 0.79; 95% CI 0.70–0.90). Those who quit smoking and started exercising had a 46% reduced risk of CVD (HR 0.54; 95% CI 0.41–0.71) and a 22% reduced risk in all-cause mortality (HR 0.78; 95% CI 0.63–0.96). Smoking cessation and exercise initiation after a diagnosis of new-onset T2DM was associated with a reduced risk of CVD and all-cause mortality.

Presentation: No date and time listed
ODP190 Efficacy of Esaxerenone on Hypertensive Patients with Type 2 Diabetes or Those with Impaired Glucose Tolerance
Authors: Kuwabara Saki , Kameda Hiraku , Miya Aika , Nomoto Hiroshi , Yong Cho Kyu , Nakamura Akinobu , Koyanagawa Naohide , Takeuchi Jun , Nagai So , Miyoshi Arina , Wada Norio , Taneda Shinji , Kurihara Yoshio , Miyoshi Hideaki , Atsumi Tatsuya
Published: November 2022

Patients with diabetes may develop mineralocorticoid receptor (MR) related hypertension due to abnormal activation of MR, thusMR blocker (MRB) is used for the treatment of hypertensionin patients with diabetes. Although theselective MRB esaxerenone (Esax)approved for hypertension, the effectiveness of Esax in daily clinical practice has not provenin hypertensive patients with type 2 diabetes (T2D) or those withimpaired glucose tolerance (IGT). The aim of this study is to clarifythe efficacy of Esax in these patients. In this retrospective study, patientswho initiated Esax from May 2019 to February 2020 and thosewho initiated amlodipine (Amlo) were screened. After excluding patients with a history of hypersensitivity to these drugs, K > 5. 0 mEq/L at the baseline and severe renal dysfunction (eGFR < 30 mL/min/1.73m 2), and patients receiving potassium preparations, 35 and 70 patients were enrolled in the Esax and Amlo group, respectively. After propensity score matching with the parameters including gender, age, body mass index (BMI), concomitant use of angiotensin receptor blocker, systolic blood pressure (SBP), diastolic blood pressure (DBP), K, AST, ALT, TG and eGFR, finally each 24 cases were analyzed. Primary endpoints were changes (Δ) in SBP and DBP from the baseline to 6 months after the initiation of the drugs. Secondary endpoints comprised changes in liver enzymes and those in lipid metabolism markers. Unpaired t-test was used for statistical analysis. The dose of Esax and Amlo were 2.2±0.5 mg and 4.1±1.2 mg at the baseline, and 3.4±1.3 mg and 5.3±1.2 mg at 6 months, respectively. SBP was more decreased in the Esax group compared with the Amlo group (ΔSBP: -27± 20 mmHg vs -11± 14 mmHg, p<0. 05). DBP was not significantly different between the two groups (ΔDBP: -11± 10 mmHg vs -9± 14 mmHg). In the Esax group, ALT and TG were significantly decreased (ΔAST: -7.3 ± 11.5 U/L vs +0.9 ± 9.5 U/L, p<0. 05,ΔTG: -14.3 ± 51. 0 mg/dL vs +33.5 ± 59.4 mg/dL, p<0. 05), and HDL-C significantlyincreased (ΔHDL: +1.8 ± 6.1 mg/dL vs -3.8 ± 4.8 mg/dL, p<0. 05). Severeadverse events were not observed in any subjects. These results suggest the efficacy of Esax for controlling blood pressure as well as the plausible benefit in liver disease and lipid metabolism in hypertensive patients with T2D or IGT.

Presentation: No date and time listed
ODP192 Empagliflozin associated Euglycemic Diabetic Ketoacidosis and the Terrible Triad
Authors: Nievera Karl Homer , Uy Melissa Claire
Published: November 2022

Background

Among diabetic patients, newer drug classes such as SGLT2i have been reported to present with Euglycemic Diabetic Ketoacidosis (eDKA), wherein these patients are without signs of elevated glucose levels. However, this condition can coexist with acute pancreatitis (AP) and hypertriglyceridemia (HTG), which is also known as the terrible triad.

Clinical Case

We were presented with a 31-year old diabetic male maintained on empagliflozin 25mg OD and metformin 500mg OD, discontinued his medication four months ago, and recently started retaking empagliflozin one week ago. He presented with drowsiness, severe abdominal pain rated as 9/10, and vomiting. An NGT was inserted and on further workup, acidosis was present on ABG with an anion gap of 28 mEq/L. AP was noted on abdominal ultrasound with an amylase of 768 U/L. CBG was 167mg/dL, Hba1c of 7.4%, Creatinine of 1. 05mg/dL, with ketonuria on urinalysis. Hydration was started with referral to endocrinology service. Insulin drip was started, and CBGs ranged from 145-229mg/dL while on drip. Hydration was increased accordingly, considering the patient's intake and output. Further workup was done, and lipid profile revealed severe hypertriglyceridemia at 1724.78mg/dL and elevated VLDL at 342mg/dL. Statin was prescribed, and eventually, insulin drip was titrated down with resolution of acidosis. Insulin was then shifted to subcutaneous regimen. Diet was also transitioned to clear liquids and eventually into diabetic diet. The patient was sent home and was uneventful after. eDKA develops due to increased glucagon secretion and decreased insulin production, promoting glucose to fat metabolism and ultimately stimulating ketogenesis. These agents decrease the blood glucose level by increasing urinary glucose excretion leading to a reduction in insulin secretion from the pancreatic β-cells. The terrible or enigmatic triad consisting of AP, HTG, and DKA/eDKA has been well reported but has a complex process. HTG results as a product of the reduced lipoprotein lipase activity in peripheral tissues, which decreases the removal of VLDL from the plasma. In AP cases, HTG only accounts for a minority (2-7%) of cases, but the risk was increased with levels above 1000mg/dL, such as in our patient. In the study by Simons-Linares et al., having the said triad had higher odds of having SIRS, shock, sepsis, and parenteral nutrition when compared to AP patients alone. eDKA patients can present with non-specific signs and symptoms such as nausea, vomiting, and abdominal pain, which can delay the diagnosis in patients. Fortunately, it was recognized early on, and there was a quick response in managing the case.

Conclusion

To date, there is scarcity among reports of the terrible triad, especially with empagliflozin use. Therefore, we can stress the importance of keen assessments and history taking in detecting the triad for an early aggressive approach to prevent adverse outcomes.

Presentation: No date and time listed
ODP201 Fyn regulates sarcopenia via autophagy
Authors: Yamada Eijiro , Uehara Ryota , Bastie Claire C , Horiguchi Kazuhiko , Ishida Emi , Matsumoto Shunichi , Yoshino Satoshi , Osaki Aya , Okada Shuichi , Yamada Masanobu
Published: November 2022

Sarcopenia is an important element that impairs daily activity. Sarcopenia is also linked to insulin resistance, and the number of diabetic patients also presenting sarcopenia is increasing. In recent years, autophagy has been identified as one of the novel mechanisms associated with sarcopenia. We previously reported that Fyn not only participates in the metabolic syndrome but also that autophagy-regulating sarcopenia was decreased in muscle specific Fyn transgenic mice through STAT3 regulation (Cell metabolism 2010, Cell Rep. 2012). More recently, we revealed Fyn-dependent STAT3 phosphorylation by IL6, which is involved in chronic inflammation and metabolic syndrome, using mouse C2C12 myotube cells expressing shRNA for Fyn. Furthermore, using WT mice with both the denervated and the hind limb suspension (HS) that promotes disuse atrophy by suspending the hind limb, not only both Fyn and IL6 gene expressions were increased but the expression and phosphorylation levels of STAT3 were also augmented, while the autophagic activity was decreased. To confirm those regulations are Fyn dependent, we took advantage of Fyn null mice (FynKO) with HS. Compare to WT mice with HS, all the muscles of FynKO were resistant for the loss of muscle mass induced by HS. The expressions of bothatrogin-1 and muRF-1,the key muscle specific E3 ubiquitin ligases as well as the markers for sarcopenia, were not changed in the muscles of FynKO with HS. Moreover, the STAT3 phosphorylation on tyrosine 705 was decreased in the muscle of FynKO compared to WT mice after hind limb suspension, while expression levels of STAT3 were not changed. IL-6mRNA expression levels were increased in the HS muscle of control mice, but were not changed in FynKO HS muscle. Finally, the autophagic activity, examined by both LC3-2 protein levels after intraperitoneal administration of colchicine andSQSTM1/p62 immunofluorescence in muscles, was retained in FynKO after HS. These results strongly suggest that Fyn is involved not only in the metabolic syndrome but also in the pathogenesis of sarcopenia, and may lead to a better understanding of the pathology of sarcopenia-associated obesity and the development of therapeutic methods.

Presentation: No date and time listed
ODP203 Health Questionnaires are a Positive Behavioral Modifier In Patients with Impaired Blood Sugar In the African American Population.
Authors: Patel Krish , Patel Ishan , Patel Sunil
Published: November 2022

Type 2 diabetes and its complications have a higher incidence in African Americans as compared to other racial groups (1). As per the American Diabetes Association, the prevalence of diabetes in non-Hispanic African American patients is 11.7% compared to 7.5% in non-Hispanic white patients. However, few studies have explored what can be done to spark a positive behavioral change leading to lower blood sugar. The purpose of this study is to evaluate if a patient filling out a health questionnaire has any impact on his or her habits by enhancing self-management and awareness to reduce HbA1c.

Methods

In an outpatient urban clinic, a prospective randomized study was conducted with African American patients with prediabetes with HbA1c 5.6 to 6.7. Patients were randomly assigned to either a survey group or a control group who did not take a survey. The survey included demographic information, weight, diabetes mellitus complication awareness, exercise frequency 3-5 days/week, eating habits, and self-perception. The patients in the survey group filled a follow-up survey 3-6 months later.

Results

The survey group had 50 respondents and 46 respondents who took the post-survey compared to the control group for which there were 50 respondents with 47 respondents in the control follow-up. In the survey group, 54% were males with an average age of 57 years. In the survey group, on followup HbA1c decreased (6.1 vs 5.7 p<0. 021), BMI decreased (32 vs 29.1 p<0.562), exercise frequency 3-5 days/week increased (10% to 35% p=0. 041), awareness of diabetic complication improved (15 to 74% p=0. 029), willingness to see a dietician increased (28% to 60% p=0. 038), and probability of reading nutrition labels increased (16% to 38% p=0. 058). In the control group, 58% were males with an average age of 56 years. In the control group, on followup HbA1c increased (6.1 vs 6.2), BMI increased (32 vs 33), exercise frequency 3-5 days/week increased (13% to 19% p=0.820), awareness of diabetic complication improved (12%to 16% p=0.673), willingness to see a dietician increased (29% to 38% p=0.340), and probability of reading nutrition labels increased (14% to 19% p=0.646).

Conclusion

Health questionnaires served as a positive behavioral modifier and helped patients identify and correct their harmful lifestyle habits. Patients in the survey group showed larger amounts of positive change compared to patients in the control group. Reference: (1) Marshall MC Diabetes in African Americans. Postgraduate Medical Journal2005;81: 734-740.

Presentation: No date and time listed
ODP222 Liragluitde Increased IL-1RA Concentrations in Obese Type 2 Diabetes: A Small Randomized Controlled Trial
Authors: Sathavarodom Nattapol , Roongjiraroj Thanasate , Pinphanichakarn Verapon
Published: November 2022

Background

Therapy with exenatide, exendin-4-based glucagon liked peptide-1 receptor agonist (GLP-1 RA) increased plasma interleukin-1 receptor antagonist (IL-1RA), an endogenous anti-inflammatory protein which protected pancreatic ß cells independent of glycemic and weight controlled. We hypothesized that liraglutide, long-acting GLP-1 analogue might contribute to a potential protective effect on ß cells in diabetes.

Methods

Twenty-four obese patients with type 2 diabetes receiving oral hypoglycemic agents with insulin therapy, except pioglitazone or incretin-based therapy, were randomly assigned to receive either maximum tolerate dose of liraglutide (n=12) or standard therapy (n=12) for twelve weeks.

Results

Among 24 participants who completed over 12 weeks of this study, median change was +258.7% (78.7, 656.6) and +101. 0% (-3.3, 189.4) of IL-1RA; P<0. 04, and -1.2% (-1.7, -0.8) and -0.4% (-1. 0, 0.3) of A1c; P<0. 03 in liraglutide and standard group, respectively. Percent changes of fasting plasma glucose, body weight, neck circumference and body mass index were all not statistically significant, when comparing between group. Pearson correlation between percent change of IL-1RA and percent change of A1c response to therapy were also not statistically significant.

Conclusion

Liraglutide might have anti-inflammatory effect independent of the glycemic control during initial short-term duration. Keywords: Liraglutide, Interleukin-1 receptor antagonist, obese type 2 diabetes.

Presentation: No date and time listed
ODP226 MONITORING THE INCIDENCES OF ALLERGIC CONTACT DERMATITIS AND OTHER SKIN REACTIONS ASSOCIATED WITH CONTINUOUS GLUCOSE MONITORING SYSTEMS
Authors: Lightstone Hodaya , Murphy Margaret
Published: November 2022

The CDC reports 1 in 10 Americans have Diabetes and that number only continues to rise each year. Diabetes is a lifestyle altering condition that requires those diagnosed to monitor their blood sugar daily. Traditionally finger prick blood draws were the only method to do this and it put many at increased risk for infection and reduced digit sensation, until Continuous Glucose Monitoring (CGM) was later developed. CGM's are unique because they can attach to any part of the body and upload data to smart devices. Unfortunately, CGM's brought about new issues for diabetics. As CGM use increased, as did incidences of allergic and irritant contact dermatitis (ACD & ICD), preventing many from continuing its use. The purpose of this Literature Review is to assess current articles focused on ACD, ICD, and other skin conditions related to CGM use and consider how diabetics can prevent and treat these side effects to safely resume CGM use.

Presentation: No date and time listed
ODP235 Quality Improvement Survey to Identify Barriers to Oral Glucose Tolerance Test in Patients with Cystic Fibrosis
Authors: Trevino Alexandra , Afshariyamchlou Sonia , Khare Swapnil
Published: November 2022

Background

Cystic Fibrosis (CF) is the most common autosomal recessive disorder in Caucasians and can involve multiple organ systems. Cystic Fibrosis Related Diabetes (CFRD) is the most common complication which affects at least 40-50% of the adult patients with CF. Untreated CFRD adversely affects pulmonary function, nutritional status, and is associated with overall poor outcomes. Early diagnosis and treatment with insulin improve nutritional status, pulmonary function and is associated with reduced mortality. An annual two-hour Oral Glucose Tolerance Test (OGTT) is recommended for all patients with CF beginning at 10 years of age. Unfortunately, OGTT screening rates remain very low in patients with CF. The aim of this study was to identify patient barriers to OGTT screening and list them in order of relative importance from patient perspective.

Methods

A survey was designed to identify patient barriers associated with completing the screening OGTT in the CF population. Data collection included patient demographics and pertinent clinical information. All patients >18 years of age and who receive care at the Cystic Fibrosis center at our institute received a survey. Survey was sent through email, postal mail, or during CF center visits. Patients who did not initially complete survey received a reminder email, phone call, and hand survey during CF appointment. Participants were excluded if they had a diagnosis of CFRD or were currently pregnant. There was no intervention planned during this study.

Results

49 patients without CFRD and 19 patients with CFRD responded to survey. Only 12.2% patients were appropriately screened by OGTT in last 1 year. The survey demonstrated that the top 3 barriers to obtaining OGTT in descending order were "I don't think I have diabetes, I don't need this"; "I don't like the taste of glucola"; and "I don't think OGTT is important for assessing my health".

Conclusions

The prevalence of CFRD continues to increase as the median life expectancy increases in patients with CF and is associated with worse outcomes. Early diagnosis and treatment with insulin are crucial. Unfortunately, screening for CFRD remains low in this population. Our study highlights the patient perceived barriers for screening OGTT. The top 3 barriers noted in study show the importance of patient education and awareness about CFRD. Further research is needed to identify specific interventions that will improve CFRD screening and lead to earlier diagnosis and treatment.

Presentation: No date and time listed
ODP251 Thioredoxin-Interacting Protein (Txnip) And Cellular Senescence: Potential Adverse Effects of Txnip Deficiency.
Authors: Abubaker Mohammed , Fantus George I
Published: November 2022

Thioredoxin-interacting protein (TXNIP) is a ubiquitously expressed protein that belongs to the α-arrestin family of proteins but is unique in that it interacts with and inhibits the function of the endogenous antioxidant, Thioredoxin (Trx). TXNIP is strongly upregulated by hyperglycemia and is associated with increased oxidative stress and promotes pancreatic beta cell apoptosis accelerating the progression of diabetes. Age-dependent dysregulation of the Trx/TXNIP redox system has been implicated in cellular senescence and aging. However, the mechanisms are not fully understood. While Trx overexpression has been reported to protect against aging and age-related diseases, and we found that TXNIP-/- (KO) mice were protected from Diabetic kidney disease, paradoxically, others reported TXNIP KO mice had reduced survival in response to paraquat mediated oxidative stress. To investigate the potential effects of TXNIP in cellular senescence we used primary mouse renal glomerular mesangial cells (MC) from WT and TXNIP KO mice. Passaging of cells leads to replicative senescence. In WT MC this was associated with a significant reduction in TXNIP expression in late passage (LP-passage 25) compared to early passage (EP-passage 5-7) (p<0. 05), and this was accompanied by appearance of the senescence phenotype determined by significant increases in expression of the cellular senescence markers, p53, p16, p21, phosphorylation of histone H2AX (p<0. 05) and senescence associated beta-galactosidase staining (13-fold increase) (p<0. 01). To determine whether TXNIP downregulation played a causal role, primary MC from TXNIP KO were compared to WT at EP 5. TXNIP KO showed significantly higher expression of senescence markers P53 and P16 (p<0. 05), and beta-galactosidase staining (15-fold). AKT activation has been implicated in replicative senescence. Here, increased phosphorylation of AKT and its substrate FOXO were found in LP versus EP WT, and EP KO versus WT MC (p<0. 05). These studies indicate that TXNIP downregulation is a mediator of replicative senescence associated with increased AKT signaling. Thus, while beneficial for diabetes, targeting TXNIP may have long term untoward effects on aging.

Presentation: No date and time listed
ODP252 Urosepsis and Sodium-Glucose Co-Transporter-2 Inhibitors: A Systematic Review and Meta-Analysis
Authors: Prasongdee Klaorat , Toloza Freddy J , Fernandes Talmas P , Poloju Alekya , Lopez-Saldana Rigoberto , Lock John P
Published: November 2022

Objective

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are very effective in reducing hemoglobin A1c. They also have benefits in reducing cardiovascular events, heart failure hospitalization, and progression of renal disease in patients with and without T2DM. However, FDA issued a warning for a possible severe UTI. Conversely, the evidence from randomized clinical trials and observational studies is limited and controversial. Therefore, we aimed to investigate the association of urosepsis and SGLT-2 inhibitors using the method of systematic review and meta-analysis.

Methods

Potentially eligible studies were identified from MEDLINE, Scopus, EMBASE, Ovid, and the Cochrane Library from inception to September 2020 with the help of an experienced librarian aiming to identify studies reporting the number of adults users of any SGLT2 inhibitor (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, remogliflozin, and tofogliflozin) who developed urosepsis, compared to those who never used SGLT2 inhibitors. The following exclusion criteria were used: only abstracts or pilot data, studies reporting rates of urosepsis only in SGLT2 inhibitors users without comparison, or studies with a comparison group in which SGLT2 was not the only differential treatment.

Results

In total, 1203 papers were identified with our search strategies, of which 169 were evaluated as full text, and 6 studies were finally selected for the meta-analysis after two rounds of the independent review by five investigators. The overall risk of bias of the included studies was low-to-moderate. We found no difference in the risk of urosepsis in users of SGLT2 inhibitors (OR= 1.34; 95% CI, 0.79 to 2.28; P=0.28; I2=48%) compared to the comparison group. In a subgroup analysis by the type of SGLT2 inhibitor evaluated we found no differences between dapagliflozin (OR= 0.92; 95% CI, 0.51 to 1.67; P=0.82; I2=0%) or canagliflozin (OR= 0.32; 95% CI, 0. 03 to 3.63; P=0.27; I2=17%) users in the risk of urosepsis. Publication bias was assessed by performing funnel plots which showed visual asymmetry suggestion potential publication bias.

Discussion/Conclusion

In this systematic review and meta-analysis, including 6 publications and 456301 participants, we found that individuals treated with SGLT2 inhibitors do not have a significantly higher risk of urosepsis than individuals of the comparison group. Additionally, no differences were found in the risk of urosepsis when each SLGT2 inhibitor agent was assessed separately.

Presentation: No date and time listed
ODP259 Evaluating the Efficacy and Safety of Long-Acting GLP-1 Receptor Agonist in T1DM Patients
Authors: Mohandas Deene , Gao Catherine , Calma Jamie , Basina Marina
Published: November 2022

Introduction

GLP-1 receptor agonist is a medication class that mimics the endogenous incretin hormone GLP-1. Short-acting GLP-1 agents were studied as adjunct therapies in type 1 diabetes (T1DM) but not approved due to concern of increased diabetic ketoacidosis (DKA) risk. Long-acting GLP-1 medications are still commonly prescribed for T1DM patients. One study has assessed the impact of a long-acting GLP-1 in 11 T1DM patients. No hospitalizations were observed, and time in range was not reported. [1] Our study aims to evaluate the efficacy and safety of long-acting GLP-1 medications in a larger cohort of T1DM patients.

Methodology

We conducted a retrospective chart review of T1DM patients taking a long-acting GLP-1 for at least three months. ICD-10 code E10. Type 1 diabetes mellitus was used to search our institution's Electronic Health Record system (EPIC). Primary parameters collected included A1C and glycemic trends. Data analysis was done by averaging values over a two-year period before and after starting the medication.

Results

We identified 27 participants with T1DM (mean age 42yrs, mean T1DM duration 18.1yrs) on a long-acting GLP-1 (semaglutide 70.4%, dulaglutide 33.3%, long-acting exenatide 3.7%, albiglutide 3.7%). Mean therapy duration was 24.28±19. 01mo. A1C values decreased significantly from7.61±1. 08% to 7.16±0.73% (p=0. 015, N=25). Per CGM data, average time in range (TIR) increased significantly from48.82±22.35% to64.70±16.58% (p=0. 0002, N=15), average time in hyperglycemia decreased from42.39±23.32% to 31.58±16.65% (p=0. 019, N=14) and 14-day blood mean glucose decreased from 190.40±38.42 mg/dl to 167. 06±25.86 mg/dl (p=0. 001, N=17). There were no statistically significant differences in time in hypoglycemia and incidence of DKA. Hyperglycemic and hypoglycemic episodes were defined per patients’ individualized CGM settings (most commonly Blood Glucose levels>180 and <70 respectively). Patients’ weight decreased non-significantly from182. 00±50.92 lbs to 170.88±51.37 lbs (p=0.128, N=8). There were no ER visits or hospitalizations for DKA while on GLP-1 therapy.

Conclusion

There is an urgent need for strategies to improve glycemic control and reduce morbidity and mortality in T1DM. Long-acting GLP-1s are a promising adjunct to insulin. Our study is the first to demonstrate significant A1C reduction and TIR increase without increased hypoglycemia and DKA risk in 27 T1DM patients on long-acting GLP-1s. Longer prospective studies are warranted.

Presentation: No date and time listed
ODP623 Life Threatening Diabetic Ketoacidosis as First Presentation of Tacrolimus-Induced Diabetes Mellitus.
Authors: Bulchandani Sheetal , Goyal Rachna M
Published: November 2022

Background

New-onset diabetes after transplantation (NODAT) is a serious complication after a solid organ transplant. NODAT occurs in 2% to 53% of all solid organ transplant recipients.1 Tacrolimus is an immunosuppressive agent associated with diabetogenic potential which predominantly is a result of suppression of insulin secretion from pancreatic beta cells. Diabetic ketoacidosis as the first presentation of new onset tacrolimus induced diabetes is rare. We report a case of diabetic ketoacidosis (DKA) in a patient without prior history of diabetes mellitus and receiving tacrolimus as part of immunosuppressive regime post-renal transplant.

Clinical Case

A 62-year-old female with past medical history of autosomal polycystic kidney disease status-post deceased donor renal transplant and hypertension presented with weakness and fatigue. She had undergone transplant 8 months prior to this presentation and her immunosuppressive regime consisted of mycophenolate mofetil and tacrolimus. The patient was encephalopathic on arrival with normal vitals. Laboratory evaluation was significant for blood glucose of 673, bicarbonate of <10, anion gap of 24, Beta-hydroxybutyrate >8 and a pH of 7.19 on arterial blood gas analysis thus confirming diagnosis of diabetic ketoacidosis (DKA). Tacrolimus level was elevated at 35.7. Intravenous fluids and insulin were initiated with resolution of symptoms and DKA. She was transitioned to a basal-bolus insulin regimen. Further labs revealed Hemoglobin A1C of 11.6% (no previous value), negative insulin antibodies and glutamic acid decarboxylase antibody, and a low C-peptide level at 0.47 (when blood glucose was 150mg/dl). Her tacrolimus dose was adjusted, and she was discharged on a basal-bolus insulin regimen. On follow up, the patient had lower insulin requirements with improvement in C-peptide level to 1.8, thus, indicating beta cell dysfunction in setting of supratherapeutic tacrolimus levels.

Conclusion

Tacrolimus remains the preferred immunosuppressive agent after kidney transplantation given lower incidence of acute rejections and better tolerance. However, due to its toxic effects on pancreatic beta cells it is imperative blood sugar levels should be routinely monitored in patients on tacrolimus. Appropriate monitoring can lead to timely diagnosis and successful outcomes. Further studies are required to investigate risks factors associated with tacrolimus induced DKA. References 1. Pham PT, Pham PM, Pham SV, Pham PT, Pham P. New onset diabetes after transplantation (NODAT): an overview. Diabetes Metab Syndr Obes. 2011;4: 175-186, https://doi.org/10.2147/DMSO.S19027

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
ODP628 Quality Improvement Project (QIP) On Management Of Diabetic Ketoacidosis (DKA) In Adults In A District General Hospital.
Authors: Haddad Aiman , Yanagisawa Yuuki , Khan Mustafa
Published: November 2022

Aim

A Quality Improvement Project was conducted to assess if Bedford Hospital NHS Foundation Trust was meeting current Trust guidelines for the diagnosis and management of diabetic ketoacidosis (DKA) in adult patients. Method Retrospective data was collected from adult patients admitted with a diagnosis of DKA from January 2020 to December 2020. Data was collected for five key standards based on Trust guidelines: (1) Correct diagnosis of DKA, (2) Correct prescription of Intravenous (IV) fluids and potassium chloride (KCL) replacement, (3) Switching from Fixed Rate Intravenous Insulin Infusion (FRIII) to Variable Rate Intravenous Insulin Infusion (VRIII) following resolution of DKA, (4) The prescription of long-acting insulin during FRIII/VRIII and (5) Appropriate biochemical monitoring via regular venous blood gases (VBGs). Following data analysis, an intervention phase (with distribution of 'DKA diagnosis and management' posters, DKA teaching sessions and email updates on DKA management for medical doctors) was implemented. The cycle was repeated a further two times, with the most recent cycle based on patients admitted between August to November 2021.

Results

The first cycle consisted of 25 patients. Results showed a 72% adherence to Standard 1, a 64% adherence to Standard 3 and a 76% adherence to Standard 5. There was a notably low adherence to Trust guidelines for Standards 2 and 5, which were 32% and 12% respectively. After the intervention phases described earlier, results from the final cycle of 20 patients admitted between August to November 2021 showed significant improvement in standards 1,3 and 4 with 90%, 100% and 100% adherence to Trust guidelines respectively. Although there was a slight improvement in biochemical monitoring of patients with regular VBGs (20% adherence in the final cycle versus 12% in the first cycle), the correct prescription of IV fluids and KCL replacement remained low (17% adherence in the final cycle versus 32%).

Conclusion

Awareness and diagnosis of DKA remains high at Bedford Hospital, however there are issues regarding the ongoing management of DKA patients. In particular, the correct prescription of IV fluids with KCL replacement, and regular biochemical monitoring. There is still a lack of awareness as to the appropriate rate of IV fluid resuscitation, and the correct monitoring and replacement of potassium, as well as pH. Recommended changes to improve DKA management are to expand teaching sessions to include Emergency Department (ED) doctors, as well as ED and medical nursing staff, to improve awareness of the correct management and diagnosis of DKA. Further emphasis will be placed on keeping a paper copy of the Trust Adult DKA management protocol in the patients’ notes.

Presentation: No date and time listed
OR03-6 Further Clinical Evaluation of Stem Cell-Derived Islet Replacement Therapy (VC-02) Demonstrates Production of C-Peptide with Improvements in Glycemic Control Parameters in Multiple Patients with Type 1 Diabetes and Hypoglycemia Unawareness
Authors: Bellin Melena , Daniels Mark , Foyt Howard , Keymeulen Bart , Kieffer Timothy , Kroon Evert , Pipeleers Daniel , Thompson David , Wang Richard , Jaiman Manasi
Published: November 2022

VC-02 combination product (PEC-Direct) is a clinical-stage regenerative medicine therapy being developed for patients with type 1 diabetes and hypoglycemia unawareness intended to restore homeostatic glycemic control. It is comprised of stem cell-derived pancreatic progenitors (PEC-01) loaded into a macroencapsulation device that facilitates the in-growth of blood vessels into the device lumen, supporting the maturation and differentiation of the graft into hormone-positive islet cells comprising glucose-responsive beta cells. Initial data from one patient (2021, Keymeulen) demonstrated clinically-relevant levels of stimulated C-peptide and corresponding improvements in glycemic control within six months after subcutaneous implantation. These improvements now include a time-in-range consistently >90% and a persistent HbA1C <7%.Enrollment of additional patients with negligible C-peptide levels in the ongoing VC02-101 study implanted with the same device configuration has now resulted in multiple patients demonstrating C-peptide levels ≥0.3 ng/mL. All patients are challenged with a mixed-meal tolerance test at baseline and post-implantation to detect and monitor increases in plasma C-peptide levels. In some cases, the increased C-peptide levels are observed to occur as soon as two months post-implant with subsequent increases resulting as the patients progress further into the treatment period as high as 0.4 ng/mL by five months with additional time points at longer periods of exposure pending. This progressive rise in beta cell function is consistent with preclinical findings showing time-dependent differentiation of the pancreatic progenitors into beta cells and subsequent increases in beta cell mass.The increases in plasma C-peptide levels also correlate with trends toward improved glycemic control parameters. Relative to baseline levels, improvements are observed in time-in-range data captured from continuous glucose monitoring, as well as substantial decreases in HbA1C by as much as 1.5%. These positive trends also correlate with decreases in the amount of exogenous insulin required by as much as 70%. Importantly, these data and observations have been obtained at separate clinical sites involving different surgeons, indicating that the achievement of functional engraftment of PEC-Direct is reproducible with proper product handling, surgical training, and patient compliance with an adjunctive immunosuppression regimen. These data provide further proof-of-concept that continued optimization of PEC-Direct can result in a functional cure for T1D.

Presentation: Saturday, June 11, 2022 12:45 p.m. - 1:00 p.m.
PMON31 IL-4 Serum Levels Correlate with Triglycerides and VLDL in African American males
Authors: Johnson Abraham , Glover Jordan , Greene Natasha , Kimbro Sean
Published: November 2022

Background

Cytokines can play dual roles in diseases, while they signal the activation of the immune system, their mechanism of action results in inflammation. Low grade inflammation is often associated with metabolic diseases and a network of serum cytokines. IL-4 has been found to play a pro-inflammatory role in many conditions surrounding inflammation such as: atopic dermatitis and asthma. As it pertains to lipid metabolism IL4 has been shown to play a protective role in mice. A previous study has shown that IL4 regulates glucose and lipid metabolism by increasing sensitivity to insulin, inhibiting adipogenesis, and increasing glucose tolerance. Dysfunction in lipid metabolism can lead to other metabolic diseases such as cardiovascular disease, diabetes, and obesity. The molecular characterization of IL4's effect in metabolic diseases has yet to be completed. IL4 has been shown to correlate with serum triglyceride and cholesterol, VLDL levels. However, further studies must be carried out to illuminate the molecular cause of these relationships as well as other relationships among metabolic diseases.

Methods

A total of 68 serum samples were collected from 34 obese, normal HbA1c and 34 obese, elevated HbA1c African American men. Clinical metabolic parameters were determined using standard commercial kits administered by Laboratory Corporation of America. Thirty chemokines/cytokines were measured using a multiplexing assay Luminex X-MAP® technology. Descriptive statistics were computed for each variable for participants with normal and elevated HbA1c. Data are expressed as mean ± SEM. A series of unpaired t-test were computed to determine if there were significant differences between participants with and without elevated HbA1c. Pairwise Pearson Correlation (r) test was computed for each variable.

Results

In participants with normal HbA1c levels, IL-4 is positively correlated with VLDL (R= 0.6175, P=0.0014). There was no significant correlation in participants with elevated HbA1c in this study (R=0.08168, P=0.1758). Total cholesterol did not have any significant correlation with IL4 in this study; however, there was a positive correlation with IL-4 (R=0.6269, P=0.0013) and triglycerides in participants with normal HbA1c, no correlation seen in this study in participants with high HbA1c.

Conclusion

This data suggests that IL4-JAK-STAT pathway may play a role in the regulation of IL4, triglycerides, and VLDL in males. The correlations between IL-4 and both serum triglyceride and serum cholesterol, VLDL levels prompt the need to further study possible molecular relationships with other inflammatory biomarkers for metabolic diseases.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PSAT277 Glucocorticoid Therapy for Management of Hypoglycemia in the context of Non-Islet Cell Tumor-Induced Hypoglycemia
Authors: Agarwal Rahul , Rodriguez Ortega Susel , Vasquez Mendez Juan
Published: November 2022

Background

Non-islet cell tumor-induced hypoglycemia (NICTH) is a rare paraneoplastic syndrome which can cause recurrent hypoglycemia. There is no clear standard of care for management of hypoglycemia. Often, these patients have high morbidity and therefore surgical tumor resection is not always possible. Clinical case: This is the case of a 69 year-old male presenting with altered mental status in the context of hypoglycemia without clear etiology with an initial serum glucose level of 32 mg/dL (normal range 60-100 mg/dL) which quickly corrected after administration of intravenous glucose. He was found to have a large bowel obstruction with CT abdomen revealing an underlying neoplasm. Biopsy of suspected lesion on colonoscopy revealed colorectal adenocarcinoma. Repeated episodes of hypoglycemia complicated by seizures required inpatient management. Workup included serum insulin level which resulted in suppressed level (<1. 0 uU/mL, normal range 1.9-23. 0 uU/mL), low c-peptide level (0.1 ng/mL, normal range 1.1-4.4 ng/mL), low beta hydroxybutyrate level (0. 07 mmol/L, normal level <0.3 mmol/L), cortisol level of 43.7 mcg/dL, undetectable insulin like growth factor-1 (IGF-1) level (<10 ng/mL, normal range 59-230 ng/mL) and low insulin like growth factor-2 (IGF-2) level (66 ng/mL, normal range 333 - 967 ng/mL). IGF2: IGF1 ratio was 66 (ratio >10 is indicative for diagnosis of non-islet cell tumor hypoglycemia). Due to extremely poor oral intake and recurrent episodes of hypoglycemia despite continuous dextrose infusion, the patient was started on 20 mg prednisone daily. Eventually, 40 mg of intravenous methylprednisolone in addition to dextrose infusion was needed as maintenance therapy effectively preventing hypoglycemia. Given his poor functional status, the surgical and oncology team decided he was no longer a surgical or chemotherapy candidate. Eventually, palliative medicine was consulted and the patient was transitioned to comfort care with a plan for outpatient hospice.

Conclusion

NICTH should be suspected in any patient with hypoglycemia without clear etiology, especially if there are suggestions to NICTH such as known malignancy or newly diagnosed mass. Once NICTH is identified and a primary tumor is found, complete tumor resection represents ideal management, however, not always attainable. In such cases, dextrose infusion might be insufficient to prevent hypoglycemia and is not always the preferred option given the required long-term venous access. In these circumstances, early high dose glucocorticoids are safe and appear to successfully prevent hypoglycemic events.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSUN134 Loss of Glp-1r Signaling in the β-Cell Impairs Adaptive Proliferation and Insulin Secretion
Authors: Olvera Angela , Saghafi Samuel , de Souza Arnaldo , Tang Jaiyin , Yadev Amanjot , Meyer Riley , Davis Dawn B
Published: November 2022

Type 2 diabetes mellitus is characterized by insulin resistance and loss of pancreatic b-cell mass. b-cells are located in the pancreatic islets and secrete insulin. Though many therapies exist that address insulin resistance and to augment b-cell insulin secretion, there is a critical need to find therapies to preserve b-cell mass in order to decrease the incidence and severity of diabetes. In non-diabetic obesity, an early adaptive response to insulin resistance is increased b-cell proliferation. This compensatory mechanism leads to increased b-cell mass and increased insulin secretion from b-cells. This increase in b-cell mass is seen in as little as 4 days of high fat diet (HFD) feeding in murine models.

A promising therapeutic for the preservation of b-cell mass is glucagon-like peptide-1 receptor (Glp-1r) agonists. The ability of GLP-1 to stimulate b-cell proliferation and inhibit apoptosis is largely based on studies using pharmacologic treatment, but the importance of GLP-1 in b-cell mass regulation in normal physiology or pathophysiology has not been well studied. Notably, GLP-1 is secreted from alpha cells in the local islet environment and this paracrine signaling pathway is important for islet function. The goal of this work is to investigate the contribution of b-cell Glp-1r signaling to b-cell mass regulation in the metabolic stress condition of a one-week HFD. We hypothesize that b-cell Glp-1r signaling is necessary for the compensatory mechanisms needed to maintain glucose homeostasis during metabolic stress conditions and that lack of b-cell Glp-1r will lead to decreased proliferation of b-cells. Understanding the role of β-cell Glp-1r signaling in adaptive b-cell mass expansion will allow for development of new strategies to augment β-cell mass in type 2 diabetes.

We used a newly generated murine model with a b-cell specific knockout of Glp-1r, where the Ins1-Cre knock-in transgene drives recombination in b-cells. Glp-1r fl/fl mice (WT) and Glp-1r fl/fl – Ins1Cre mice (KO) were fed a HFD for one week. There was a trend toward elevated fasting (171+/-29 mg/dl vs 205+/-36 mg/dl, p=0.0475, n=9) and non-fasting blood glucose (195+/-24 mg/dl vs 216+/-40 mg/dl, p=0.0537, n=18) and impaired glucose tolerance in the KO mice. Notably, we found that insulin secretion in response to intraperitoneal glucose is impaired in KO mice. KO mice have a blunted proliferation response to a 1-week HFD stress, as measured by Ki67 mRNA levels (1.5-fold induction of Ki67 in WT vs. 0.6-fold induction in KO, p=0.0167, n=8-10). b-cell proliferation will also be measured by immunofluorescent image analysis of whole pancreas sections. These data suggest there is a critical role for b-cell Glp-1r signaling in the early proliferative response of b-cells in response to metabolic stress.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.