History Of T2DM Research Articles

12315 Unveiling A Paraganglioma: Catecholamine-Induced Hyperglycemia Masquerading As Type 2 Diabetes Mellitus

Abstract Disclosure: S. Salman: None. M. Hussine: None. J. Tibaldi: None. Background: Excessive catecholamines have been demonstrated to exert adverse effects on insulin homeostasis and carbohydrate metabolism, potentially resulting in the onset of secondary DM. We present a case of a patient who had been previously misdiagnosed with T2DM for an extended period. Clinical Case: A 34-year-old woman with history of T2DM, HTN, and chronic tachycardia on beta blockers, presented with complaints of palpitations, headaches, and abdominal pain for two weeks. Upon admission, she was found to be in DKA, necessitating transient administration of insulin drip. Furthermore, she exhibited persistent tachycardia and intermittent episodes of hypertensive urgency. Notably, thyroid levels revealed euthyroidism. Although DKA resolved, her fasting blood sugar levels remained elevated and refractory to escalating insulin therapy. CT abdomen with contrast revealed a large enhancing mass in the RUQ. MRI abdomen confirmed an 8.1 cm heterogeneously enhancing T2 hyperintense mass located in the RUQ, abutting the right hepatic lobe, right adrenal gland, extrahepatic biliary ducts, and adjacent vessels. Given suspicions of a neuroendocrine tumor, she was transferred to the surgical service for tumor excision. Hormonal analysis revealed elevations in plasma metanephrines (620 pg/mL, n 0-88 pg/mL), plasma normetanephrines (9954 pg/mL, n 0-210.1 pg/mL), 24-hr urine normetanephrines (10,952 μg/24hr, n 110-720 μg/24hr) and 24-hr urine metanephrines (1406 μg/24hr, n 35-278 μg/24hr). Additionally, she exhibited elevated 24-hr urine epinephrine fraction (218 μg/g Cr, 0-20 μg/g Cr) and 24-hr urine norepinephrine fraction (2775 μg/g Cr, 0-45 μg/g Cr). Preoperatively, appropriate alpha and beta blockade were administered, followed by successful retroperitoneal tumor resection. Postoperatively, her glucose levels normalized without the need for further insulin therapy, and no episodes of hypoglycemia were reported. Histopathological examination of the excised mass revealed an 11 cm sympathetic paraganglioma with retention of SDHB staining. Genetic testing for SDHB, SDHD, VHL, and RET mutations is pending. Conclusion: This case underscores the potential oversight of pheochromocytomas and paragangliomas due to their nonspecific symptomatology, often mimicking more prevalent conditions, thereby presenting diagnostic challenges. The catecholamines secreted by these tumors can lead to both impaired insulin secretion and increased insulin resistance, resulting in clinically significant manifestations. The exact mechanism underlying the glycemic dysregulation remains controversial, necessitating further investigation through large-scale multicenter prospective studies to enhance understanding and inform diagnostic and therapeutic strategies for these tumors, which can manifest with severe and potentially fatal glycemic disturbances. Presentation: 6/1/2024

6660 Euglycemic DKA Induced by SGLT-2 Inhibitor Following Administration ofTirzepatide

Abstract Disclosure: K. Gurel: None. S. Mathew: None. M. Zeidan: None. S. Al Barznji: None. F. Alkhankan: None. Introduction Tirzepatide has side effects of diarrhea, nausea, vomiting, and loss of appetite(2). SGLT-2 inhibitors may cause Euglycemic Diabetic ketoacidosis(EDKA) by inducing carbohydrate starvation and volume depletion(1). Clinical Case A 72-year-old male with a past medical history of T2DM(Hg A1c 8.4[≤ 6%]) on empagliflozin, metformin, hyperlipidemia, obesity on tirzepatide who presents with complaining of nausea, vomiting, and abdominal pain. The patient noted that he started experiencing symptoms two days before admission following receiving tirzepatide dose. He takes Tirzepatide every 10 days and he was started on empagliflozin 1 month ago. The patient started to have a loss of appetite, nausea, and vomiting on the day he received his tirzepatide injection. Over the next two days, the patient’s nausea and vomiting worsened and the patient was not able to tolerate food. On admission, ABG demonstrated pure metabolic acidosis (pH of 7.24[7.30-7.40], bicarb of 11.8 [21 - 28 mmol/L] PCO2 of 27.4[ 41 - 51 mmHg]). BMP showed anion gap of 20(3-15 mmol/L) with glucose level of 145(74-106 mg/dl) . Beta-Hydroxybutyrate level was 6.3(0.0 -0.27 mmol/L). UA was only significant for glucose level of >1000(negative) and ketone level of 40(negative). Lipase level was 539(73-393 U/L). CT abdomen ruled out acute pancreatitis. No infection source was identified. Upon admission to the ICU unit, the patient was started on D5 with KCL 20 mEq and Insulin drip. The patient was followed up with a glucose check every hour and BMP every 4 hours. On day 2 of admission, the Anion gap was normalized and the insulin regimen was transitioned to subcutaneous insulin. The patient was placed on carbohydrate consistent diet. On discharge, the patient was advised to avoid taking SGLT-2 inhibitors including empagliflozin. Conclusion Tirzepatide's potential side effects, including diarrhea, vomiting, and appetite loss, may contribute to volume depletion and carbohydrate starvation(2). Individuals using both SGLT-2 inhibitors and Tirzepatide should be closely monitored for these symptoms. Reference 1-)Baggio LL, Drucker DJ. Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease. Mol Metab. 2021 Apr;46:101090. doi: 10.1016/j.molmet.2020.101090. Epub 2020 Sep 25. PMID: 32987188; PMCID: PMC8085566. 2-)Plewa MC, Bryant M, King-Thiele R. Euglycemic Diabetic Ketoacidosis. [Updated 2023 Jan 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554570/ Presentation: 6/2/2024

P055 ELECTROCARDIOGRAPHIC ABNORMALITIES AND ASSOCIATED FACTORS IN NORMOTENSIVE TYPE II DIABETIC PATIENTS

Background/Objective: Type II diabetes mellitus (T2DM) is a coronary heart disease (CHD) equivalent in the presence of target organ damage or at least three cardiovascular disease (CVD) risk factors. Resting electrocardiography (ECG) is recommended in T2DM patients only in the presence of hypertension or on suspicion of CVD. ECG abnormalities occur early in T2DM, are associated with future cardiovascular events/mortality after adjustment for traditional CVD risk factors. Early screening and detection may improve long term survival in T2DM patients hence, aim of study- to assess the patterns and factors associated with ECG abnormalities in T2DM patients without co-existing hypertension. Methods: One hundred normotensive (BP<130/80mmHg, not on any antihypertensive agent) T2DM patients were recruited consecutively, from the Endocrinology and Diabetes clinics of the Medical Outpatient Clinic and Family Medicine department of the University of Nigeria Teaching Hospital. Consents were obtained, before interviewers, administered questionnaire to get the biodata, T2DM history, complications and treatment. Anthropometric and blood pressure readings were taken using standard methods. A 12-hour overnight fasting blood sample was taken for biochemical assessment of blood glucose, glycated haemoglobin, lipids, urea and creatinine. A 12 lead ECG was performed and interpreted by one cardiologist using the Minnesota ECG code criteria. Descriptive statistics was used for patterns of ECG abnormalities while association between categorical variables were cross tabulated and tested using chi square. Results: Participants were majorly females 68(68.0%), overweight/obese 52(52.0%) with a mean age of 55.56±9.89 years. Duration of T2DM illness post diagnosis was 6.57±6.26years. T2DM was poorly controlled in 92(92.0%) while 93(93.0%) had dyslipidaemia. ECG was abnormal in 56(56.0%) with multiple abnormality in 12(21.4)%. Left atrial abnormality was the commonest 14(25.0%) ECG abnormality. No factor was associated with ECG abnormality. Conclusions: ECG abnormalities are common in T2DM, occurring early in the absence of co-existing hypertension. ECG should be done at diagnosis of T2DM irrespective of CVD risk factors, with frequent monitoring than recommended by guidelines. Table. Pattern of electrocardiographic abnormalities in normotensive type II diabetic patients.

The Impact of Genetic History on the Risk of Developing Type II Diabetes

Type II Diabetes Mellitus (T2DM) is a global health issue with a growing prevalence due to both environmental and genetic factors. Genetic predisposition is a critical determinant of risk, with heritability studies revealing that 40-80% of T2DM risk can be attributed to genetic factors. Key genetic variants, such as those in TCF7L2, PPARG, KCNJ11, and FTO, have been associated with increased risk, impacting pathways related to insulin secretion and resistance. Monogenic forms of diabetes like Maturity-Onset Diabetes of the Young (MODY) highlight the role of single-gene mutations in early-onset diabetes. Familial aggregation studies highlight the significant role of genetic predisposition, with individuals having a family history of T2DM at a markedly higher risk. Epigenetic mechanisms further complicate this risk by introducing heritable changes in gene expression influenced by environmental factors. Genetic testing, including Polygenic Risk Scores (PRS), aids in identifying individuals at increased risk, but their predictive power is limited by the polygenic nature of T2DM. Personalized prevention and management strategies are crucial, utilizing genetic information to tailor interventions and pharmacogenomics to optimize treatment. Culturally sensitive support and education are also essential for managing T2DM. Future research directions include leveraging advanced genomic technologies to further elucidate T2DM’s genetic basis and improve personalized medicine approaches. Keywords: Genetic History, Risk, Type II Diabetes Mellitus.

The Association of Dietary Inflammatory Index with the Risk of Type 2 Diabetes: A Case-Control Study

Background: The prevalence rate of type 2 diabetes (T2DM) is increasing worldwide, and the role of diet in its etiology has been established. The Dietary inflammatory index (DII) has attracted significant attention in evaluating associations between diet and diseases due to the role of chronic inflammation as an underlying cause of numerous disease processes. Therefore, the relationship between DII score and the risk of T2DM is evaluated in the Iranian population for the first time. Methods: 113 newly diagnosed T2DM patients and 226 apparently disease-free control cases aged 23-59 participated in this case-control study. A valid semi-quantitative food frequency questionnaire was used to assess dietary intake. Then, energy-adjusted DII (E-DII) scores were computed and categorized into quartiles based on values in the population study. A logistic regression model was used to estimate the association between DII and the risk of T2DM after controlling for important potential confounders and effect modifiers. Results: A significant association was observed between E-DII score and T2DM in the crude model (P-trend<0.001), model I (adjusted for physical activity, gender, education level, and family history of T2DM, P-trend<0.001), model II (adjusted for model I + body mass index, P-trend=0.005) (ORquartile4vs1 =2.98 (95% CI: 1.18, 9.12; P= 0.005). Conclusions: A direct association was observed between DII score and the risk of T2D, implying that consuming a more anti-inflammatory diet would help to prevent T2DM. Future longitudinal studies should be conducted to further explore this association.

The single point insulin sensitivity estimator (SPISE) is associated with bone health in Arab adults

BackgroundThe Single Point Insulin Sensitivity Estimator (SPISE) index is a surrogate marker for insulin sensitivity. Given the emerging role of bone as an active endocrine organ, its associations with non-invasive measures of extra-skeletal functions such as insulin sensitivity warrant investigation.AimsThis study aimed to explore the relationship between the SPISE index and Bone Mineral Density (BMD) in an adult population.MethodsData from a total of 1270 Arab adults (84% females, mean age 56.7 ± 8.1 years) from the Osteoporosis Registry Database of the Chair for Biomarkers of Chronic Diseases in King Saud University, Riyadh, Saudi Arabia was used in this study. T-scores and SPISE were calculated. Regression models were used to determine associations between SPISE and bone health indices.ResultsThe low BMD group (N = 853; T-score <-1.0) had significantly higher SPISE values than those with normal BMD (N = 417; T-score − 1.0 and above) (4.6 ± 1.3 vs. 4.3 ± 1.2, p < 0.001). Multivariate linear regression, adjusted for covariates, confirmed a significant inverse association between SPISE and BMD for all participants (β=-0.22, p < 0.001), as well as both groups [normal BMD (β = -0.10, p = 0.02) and low BMD groups (β = -0.15, p < 0.001)]. SPISE, family history of T2DM, and history of fractures collectively account for 17% of the variances perceived in T-score for all participants (p < 0.001).ConclusionsA significant inverse association between the SPISE index and BMD was observed in adults, suggesting a link between BMD and extra-skeletal health. Underlying mechanisms need to be investigated prospectively using BMD as secondary outcomes in lifestyle modification programs.

Analysis of risk factors and clinical implications for diabetes in first-degree relatives in the northeastern region of China.

The prevalence of diabetes has risen fast with a considerable weighted prevalence of undiagnosed diabetes or uncontrolled diabetes. Then it becomes more necessary to timely screen out and monitor high-risk populations who are likely to be ignored during the COVID-19 pandemic. To classify and find the common risks of undiagnosed diabetes and uncontrolled diabetes, it's beneficial to put specific risk control measures into effect for comprehensive primary care. Especially, there is a need for accurate yet accessible prediction models. Based on a cross-sectional study and secondary analysis on the health examination held in Changchun City (2016), we aimed to evaluate the factors associated with hyperglycemia, analyze the management status of T2DM, and determine the best cutoff value of incidence of diabetes in the first-degree relatives to suggest the necessity of early diagnosis of diabetes after first screening. A total of 5658 volunteers were analyzed. Prevalence of T2DM and impaired fasting glucose were 8.4% (n=477) and 11.5% (n=648), respectively. There were 925 participants (16.3%) with a family history of T2DM in their first-degree relatives. Multivariable analysis demonstrated that family history was associated with hyperglycemia. Among the 477 patients with T2DM, 40.9% had not been previously diagnosed. The predictive equation was calculated with the following logistic regression parameters with 0.71 (95% CI: 0.67-0.76) of the area under the ROC curve, 64.0% of sensitivity and 29% of specificity (P < 0.001): P = \frac{1}{1 + e^{-z}}, where z = -3.08 + [0.89 (Family history-group) + 0.69 (age-group)+ 0.25 (BMI-group)]. Positive family history was associated with the diagnosis of T2DM, but not glucose level in the diagnosed patients. The best cutoff value of incidence of diabetes in the first-degree relatives was 9.55% (P < 0.001). Family history of diabetes was independently associated with glucose dysfunction. Classification by the first-degree relatives with diabetes is prominent for targeting high-risk population. Meanwhile, positive family history of diabetes was associated with diabetes being diagnosed rather than the glycemic control in patients who had been diagnosed. It's necessary to emphasize the linkage between early diagnosis and positive family history for high proportions of undiagnosed T2DM.

Vericiguat and Cardiovascular Outcomes in Heart Failure by Baseline Diabetes Status: Insights From the VICTORIA Trial

BackgroundType 2 diabetes mellitus (T2DM) significantly worsens heart failure (HF) prognosis. ObjectivesThis study sought to investigate the impact of T2DM on outcomes in patients enrolled in VICTORIA and assess the efficacy of vericiguat in patients with and without T2DM. MethodsPatients with HF with reduced ejection fraction were randomized to receive vericiguat or placebo in addition to standard therapy. The primary outcome was a composite of cardiovascular death or first heart failure hospitalization (HFH). A Cox proportional hazards model was used to calculate HRs and 95% CIs to assess if the effect of vericiguat differed by history of T2DM. ResultsOf 5,050 patients enrolled, 3,683 (72.9%) had glycosylated hemoglobin (HbA1c) measured at baseline. Of these, 2,270 (61.6%) had T2DM, 741 (20.1%) had pre-T2DM, 449 (12.2%) did not have T2DM, and 178 (4.8%) had undiagnosed T2DM. The risks of the primary outcome, HFH, and all-cause and cardiovascular mortality were high across all categories. The efficacy of vericiguat on the primary outcome did not differ in patients stratified by T2DM by history (HR: 0.92; 95% CI: 0.81-1.04), T2DM measured by HbA1c (HR: 0.77; 95% CI: 0.49-1.20), and pre-T2DM measured by HbA1c (HR: 0.88; 95% CI: 0.68-1.13) and in those with normoglycemia (HR: 1.02: 95% CI: 0.75-1.39; P for interaction = 0.752). No significant differences were observed in subgroups with respect to the efficacy of vericiguat on HFH and all-cause or cardiovascular death. ConclusionsIn this post hoc analysis of VICTORIA, vericiguat compared with placebo significantly reduced the risk of cardiovascular death or HFH in patients with worsening HF with reduced ejection fraction regardless of T2DM status. (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction [HFrEF] [Mk-1242-001] [VICTORIA]; NCT02861534)

Impact of anticoagulants, antiplatelet agents, and oral antidiabetic drugs on the risk of stroke in patients with diabetes and nonvalvular atrial fibrillation: A case-referent study

BackgroundType 2 diabetes mellitus (T2DM) and atrial fibrillation are risk factors for stroke. The potential preventive effects of cardiovascular and antidiabetic treatments on stroke risk in patients with these diseases remain insufficiently documented. Sulfonylureas have also been reported to be associated with stroke. This study aimed to assess the risk of stroke according to the use of drugs (anticoagulants, antiplatelet agents, and oral antidiabetic drugs [OADs]) in patients with T2DM and nonvalvular atrial fibrillation (NVAF). MethodsPatients with a history of T2DM and NVAF were identified from two systematic registries: a registry of patients with stroke and a registry of patients with atrial fibrillation. Patients with stroke were randomly matched to patients without prior stroke events based on age, sex, body mass index, and index date. All treatments administered 12 months before the index date were documented. The associations between anticoagulants, antiplatelet agents, and OADs and stroke were assessed using multivariate conditional logistic models that yielded adjusted odds ratios (aORs) and 95 % confidence intervals, controlling for risk factors identified in the univariate comparison of cases and matched referents. ResultsThree-hundred and fifteen patients with stroke with both diabetes and NVAF were matched to 523 referents with both diabetes and NVAF but no history of stroke. The aORs for the use of drugs and stroke were 0.24 [0.15–0.40] for direct oral anticoagulants (DOACs), 0.42 [0.27–0.67] for vitamin K agonists (VKA), 0.80 [0.52–1.24] for antiplatelet agents, and 0.68 [0.45–1.02] for OADs. No significant associations were found between individual OAD use and stroke risk. Similar results were obtained for ischemic stroke. Only VKAs were significantly associated with hemorrhagic stroke (odds ratio = 4.25 [1.16–15.64]). ConclusionsAnticoagulant use was associated with a protective effect against the risk of stroke in patients with diabetes and NVAF, with no increase in the risk of hemorrhagic stroke for DOAC. No increased risk of stroke was observed because of any OAD, including sulfonylureas.

Screening of Type 2 Diabetes Patients of Khyber Pakhtunkhwa for CDKAL1 Variant (rs10946398)

Diabetes Mellitus Type 2 (T2DM) is a metabolic disorder influenced by environmental and genetic factors, with varied genetic predispositions across populations. Research on T2DM's genetic risk factors in the Pakistani community is limited. Objective: To explore the association between the CDKAL1 gene variant (rs10946398) and T2DM in the Khyber Pakhtunkhwa population in Pakistan. Methods: The study involved 100 T2DM patients and 100 controls, matched by age and gender, following specific inclusion and exclusion criteria. Sociodemographic data were collected alongside 3ml of whole blood for DNA extraction. The CDKAL1 gene was analyzed using PCR-based Sequence Restriction Fragment Length Polymorphism (RFLP), and the data were processed with SPSS version 26.0s. Results: Findings showed that 47% of cases were aged 39 to 59, with 94% having a family history of T2DM and 85% leading a sedentary lifestyle. A significant association was observed between the CDKAL1 rs10946398 variant and T2DM. The GC variant was linked to a fourfold increase in risk (OR: 4.833, CI: 1.197-19.509, P=0.027), and the CC variant had a twofold association (OR: 2.788, CI: 1.545-5.033, P=0.001). These associations persisted after adjusting for family history, age, socioeconomic factors, exercise, and diet. Conclusions: The study identified a significant correlation between the CDKAL1 rs10946398 variants and T2DM susceptibility in the Khyber Pakhtunkhwa population, emphasizing the role of genetic factors in the disease's prevalence within this community.

Haplotype-based association study of TCF7L2 gene variants with the development of diabetic retinopathy in an Iranian population

ABSTRACT Background Diabetic retinopathy (DR) is recognized as one of the most prevalent complications of diabetes and a major cause of morbidity. Transcription factor 7-like 2 (TCF7L2), a pivotal component in the Wnt-signaling pathway, plays a significant role in β-cell development, blood-glucose homeostasis, cell survival, cell migration, and cell proliferation. Thus, this study aimed to assess the association between TCF7L2 variants (rs7903146, rs11196205, and rs12255372) with DR in a population-based association study. Materials and Methods DNA was extracted from whole blood of all subjects by salting-out procedure. Total 524 T2DM patients including 234 T2DM individuals without DR and 290 T2DM individuals with DR were genotyped by TaqMan assay technology. Clinical characteristics of subjects were conducted to evaluate the plausible association between TCF7L2 variants and DR with univariate linear regression analysis. Results Demographic analysis between case and control groups revealed significant differences in FBS, HbA1c, lipidemia, heart disease, and family history of T2DM (p < 0.05). No significant difference was observed in either genotypes distribution or allele frequency (p > 0.05) between T2DM individuals with and without DR in any models of inheritance. Genotype-phenotype association showed no significant association. Result of analysis indicated that HbAlc with adjusted OR of 1.8 (p < 0.0001) and first-degree relatives of family history with adjusted OR of 3.04 (p < 0.0001) were significantly associated with DR. Finally, haplotype analysis showed no noticeable association. Conclusion In conclusion, there was no significant genetic association between rs7903146, rs11196205, and rs12255372 with DR among T2DM Iranians; however, these variants may play unknown roles in other populations.

Analysis of risk factors for post-operative recurrence after percutaneous endoscopic lumbar discectomy in patients with lumbar disc herniation: a meta-analysis

BackgroundThis study aimed to systematically evaluate risk factors for post-operative recurrence after percutaneous endoscopic lumbar discectomy (PELD) in patients with lumbar disc herniation (LDH).MethodsThe eligible studies were retrieved from PubMed, Embase, and Web of Science databases. Quality assessment was performed. The effects of binary variables (sex, Modic change (MC), type 2 diabetes (T2DM), and smoking) on post-operative recurrence were evaluated as odds ratio (OR) and 95% confidence interval (CI). The effects of continuous variables (sagittal range of motion (SROM), body mass index (BMI), and age) were assessed as weighted mean difference (WMD) and 95% CI. Sensitivity analysis and publication bias were conducted to evaluate the reliability of pooled results.ResultsEight studies were included, and their methodological quality was medium. MC (OR (95% CI) = 3.88 (2.24–6.74), P < 0.001), smoking (OR (95% CI) = 1.87 (1.45, 2.42), P < 0.001), T2DM (OR (95% CI) = 1.61 (1.12, 2.31), P = 0.010), SROM (WMD (95% CI) = 2.33 (0.95, 3.70), P = 0.001), BMI (WMD (95% CI) = 1.68 (1.37, 1.99) kg/m2, P < 0.001), and age (WMD (95% CI) = 9.95 (5.05, 14.86) years, P < 0.001) were significantly related to post-operative recurrence in patients with LDH after PELD. Significant publication bias was not observed among studies in all outcome indicators.ConclusionOur findings reveal that high levels of age, BMI, and SROM, history of T2DM or smoking, or more MC may be correlated with post-operative recurrence after PELD.

Abstract 116: Reversal of Acute Ocular Ischemic Syndrome Following Rescue Carotid Revascularization: A Case Report

Introduction Ocular ischemic syndrome (OIS) is a rare, vision‐threatening condition resulting from severe carotid artery disease secondary to severe atherosclerosis or arteritis. Common clinical features include acute/subacute to gradual vision loss, ocular pain, amaurosis fugax, photophobia and diplopia. We are presenting a case of acute ocular ischemic syndrome secondary to acute re‐occlusion of the right internal carotid artery (RICA) post Carotid Endarterectomy (CEA), that reversed with carotid revascularization. Methods Case Summary: 59‐year‐old male with history of T2DM, hyperlipidemia, tobacco use presented to an outside hospital with complaints of dizziness, blurry vision, left upper extremity weakness and multiple falls with head trauma. Exam revealed left lower quadrantanopia, mild left arm weakness and left hemineglect. Computed Tomography (CT) Head showed scattered right middle cerebral artery (MCA) territory infarcts. CT Angiography (CTA) revealed ulcerated plaque with a small focus of thrombus intraluminally in the RICA. Subsequently, the patient was initiated on heparin infusion and underwent CEA. On postoperative day (POD) 2, the patient experienced severe stabbing right eye pain with reduced visual acuity and worsening of left arm weakness. Imaging revealed complete occlusion of the right common carotid artery (RCCA). Perfusion imaging did not reveal a core or a penumbra. Given acute loss of vision likely secondary to ocular ischemic syndrome, decision was taken to proceed with rescue stenting. Using a transfemoral approach, an 8‐French balloon guide catheter was advanced into the proximal RCCA. A primary suction thrombectomy was performed under proximal flow arrest. After achieving a complete recanalization in one pass, we started the patient on cangrelor 30 mcg/kg intravenous bolus followed by 4 mcg/kg/min infusion. Post bolus, we placed a tandem closed‐cell carotid stent measuring 8x36mm &amp; 10x37mm. The patient reported immediate relief of ocular pain, vision and weakness following the procedure. He transitioned from cangrelor infusion to ticagrelor 90 mg twice daily and aspirin 81 mg daily. On post‐stenting day 7, the patient experienced acute onset headache, and imaging revealed re‐occlusion of the entire carotid artery sparing only the ophthalmic segment of the RICA which now filled retrograde via anterior communicating artery (AcoA) from the contralateral carotid artery. However, his visual acuity remained unchanged and reported no ocular pain. At one month follow‐up the patient remains symptom‐free. Results Discussion: Incidence of OIS is estimated to be 7.5 cases per million every year. Carotid artery atherosclerosis is the most common etiology. Majority of OIS (∼90%) present with gradual vision loss and approximately 40% present with ocular pain. Gradual vision loss is predominantly related to chronic ocular hypoperfusion and resultant iris neovascularization and glaucoma. In this case, patient suffered acute vision loss secondary to acute ICA occlusion following CEA. Emergent carotid revascularization resulted in restoration of vision and resolution of ocular pain. Conclusion Our main goal is to emphasize the importance of rescue stenting to address symptoms of aOIS. Immediately post‐stenting, there was remarkable improvement in ocular pain and visual acuity. Although, the carotid re‐occluded within seven days post‐stenting, we hypothesize that gradual re‐occlusion while on DAPT provided enough time recruit and preserve collaterals into the right ophthalmic artery via retrograde flow into the ophthalmic segment of RICA from the contralateral carotid artery via the AcoA which was subsequently confirmed on imaging.

Children and Adolescents With Hybrid Diabetes: A Management Conundrum

ObjectiveHybrid diabetes (HD); ie, insulin resistance with positive diabetes-associated autoantibodies (DAAs) is increasing in children. We aimed to compare the characteristics of children with HD with those with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) at diagnosis and after 2 years. MethodsA retrospective review of patients aged 0 to 19 years, with C-peptide and 4 DAA measurements available, who were diangosed with new-onset diabetes from 2016 to 2020 were included in the analysis. ResultsOverall, 102 subjects were included, 32 with T1DM, 21 with HD, and 49 with T2DM. Amongst the groups (T1DM vs HD vs T2DM), there were differences in the proportion of non-Hispanic Whites (81.3% vs 47.6% vs 16.4%, P < .001), frequency of family history of T2DM (37.5% vs 100% vs 85.4%, P < .001), acanthosis nigricans (0% vs 42.9% vs 93.9%, P <.001), median body mass index z-score (−0.55 vs 1.8 vs 2.4, P <.001), and median C-peptide (0.4 ng/mL vs 0.9 ng/mL vs 2.4 ng/mL, P <.001). At 2 years, differences were seen in median body mass index z-scores (0.3 vs 1.9 vs 2.3, P <.001), mean HDL-cholesterol (58.0 mg/dL vs 48.2 mg/dL vs 39.5 mg/dL, P <.001), and the use of basal insulin (100% vs 100% vs 74.4%, P <.001). ConclusionPhenotypic and metabolic differences were seen in youth with T1DM, HD, and T2DM at diagnosis and follow-up. At 2 years, all subjects with HD remained insulin dependent whereas some with T2DM were not, indicating the need for targeted interventions to address the etiopathogenesis.

FRI657 Case Series On GLP-1 Receptor Agonist Related Acute Pancreatitis

Abstract Disclosure: A.U. Kulkarni: None. V. Mehta: None. M. Renzu: None. K. Pereira: None. M.A. Rather: None. Introduction: Acute pancreatitis (AP) has now become one of the leading causes of GI related hospital admissions in the United States. With increasing use of GLP-1 Receptor Agonists (GLP-1 RA) in T2DM and obesity, they are now being identified as one such class of drugs which can cause AP. We present this case series to discuss these adverse effects. Case 1: A 50 yo AA male with a history of T2DM and hypertension presented with acute severe epigastric pain, nausea and vomiting for 5 days. Vitals were stable. On physical exam, tenderness in the RUQ was noted. Labs revealed lipase of 313 U/l (11-82 U/l), BG of 213 mg/dL, HbA1c 11.3, normal LFT and lipid panel. Blood EtOH was negative. He denied tobacco, alcohol, and illicit drug use. CT abdomen showed acute interstitial edematous pancreatitis without cholelithiasis or choledocholithiasis. Liver ultrasound showed hepatic steatosis. He noted recent initiation of Semaglutide 6 months ago which was stopped 3 weeks prior to this visit due to abdominal discomfort. Previous Dulaglutide therapy was also discontinued due to GI intolerance. Home medication for DM otherwise included metformin and basal insulin. Case 2: A 68 yo AA woman with a history of T2DM, hypothyroidism presented after a week of severe epigastric pain, radiating to her back, with nausea and vomiting. Labs showed lipase 593 U/l (11-82 U/l), BG of 427 mg/dl, HbA1c of 10. Social history was non-contributory. CT Abdomen showed AP and no gallstones or bile duct dilatation. LFTs and lipid panel were unremarkable. Chart review noted prior admission for AP a month ago. Her home medications were basal Insulin and Dulaglutide (4 yrs). Drug induced AP from Dulaglutide was suspected. Lack of clinical improvement after 3 days of management prompted RUQ ultrasound, which was prematurely terminated due to pain during the scan. Subsequent CCK-HIDA was negative for acute cholecystitis but noted low gallbladder EF. Thus dulaglutide was identified as a potential trigger along with gallbladder dysmotility as a possible etiology for her recurrent AP. Both patients were managed with IV fluids, NPO diet and morphine. They were instructed to stop GLP-1 RA and discharged with PCP follow-up. Discussion: GLP-1 RA are now being widely used due to low risk of hypoglycemia and weight loss. Clinical trials with GLP-1 RA have shown mild, asymptomatic increase in lipase, amylase levels as well as rare incidences of AP. This has been attributed to the stimulation of pancreatic beta cells and exocrine duct cells leading to acinar cell hypertrophy, proinflammatory cytokine induction, causing pancreatic injury. Though drug-induced AP is uncommon and is a diagnosis of exclusion, detailed history taking, medication review and investigating for all other causes is of utmost importance. A good understanding of the drugs associated with AP should alert the physician to identify these agents and promptly discontinue them to prevent further complications. Presentation: Friday, June 16, 2023

THU255 Tirzepatide-induced Weight Loss In A Type 2 Diabetic Taking Oral Contraceptives

Abstract Disclosure: A. Arunachalam: None. A. Nguyen: None. N.L. Shah: None. Obesity is a global health challenge which can lead to type 2 diabetes, hypertension, cardiovascular disease, and decreased life expectancy. In addition to lifestyle intervention, pharmacotherapy to sustain weight loss has remained limited due to effectiveness, cost, and adverse effects. Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like-peptide-1 receptor agonist currently approved for type 2 diabetes treatment. Tirzepatide-induced weight loss may provide new options for treatment of obesity. We report a 32-year-old female with a history of T2DM and PCOS originally on metformin who was started on semaglutide 0.25 mg, which was uptitrated to 0.5mg weekly for 6 months. She lost 25 lbs with no side effects. Semaglutide and OCPs were discontinued due to fertility with her weight and hemoglobin A1C rebounding off medication. She was started on tirzepatide 2.5mg weekly. At that time, she weighed 223 lbs with a hemoglobin A1C 8.2%. She was counseled to resume OCPs and improve glucose control and weight reduction prior to attempting to conceive. Once increased tirzepatide dosing to 5mg weekly, she endorsed severe nausea and intermittent epigastric abdominal pain on day of injection. She attempted to increase dose to 7.5mg weekly, but dose was reduced due to complaints of constipation and worsened abdominal pain requiring bowel regimen. She remained on tirzepatide for a total of 4 months prior to becoming pregnant while on oral contraceptives. Her weight decreased from 223 to 212 lbs with reduction in hemoglobin A1C from 8.2% to 6.1%. While initially studied for use in type 2 diabetes, tirzepatide was found to induce clinically significant weight reduction. The recent SURMOUNT-1 trial, which studied the effects of tirzepatide in non-diabetics, demonstrated that once-weekly tirzepatide at three different doses demonstrated substantial and sustained weight reduction in patients with obesity. In trials involving patients with once-weekly injectable semaglutide, the mean reduction in hemoglobin A1C was 1.8 percentage points and reduction in mean body weight was 6.5 kg. In the SURPASS-2 trial, reductions in body weight were greater with tirzepatide when compared to semaglutide with mean estimated treatment difference −1.9kg, -3.6kg, and -5.5 kg respectively based on dosing of 5mg, 10mg, and 15mg. The adverse events most commonly reported in patients on tirzepatide include nausea, vomiting, and diarrhea, which occurred most commonly during dose-escalation. Mounjaro is known to reduce the efficacy of oral contraceptive pills due to delayed gastric emptying. This delay is largest after the first dose so recommended to switch from oral to non-oral contraceptives for the first four weeks when tirzepatide is initiated. It is important to counsel patients on the decreased efficacy of oral contraceptives while on tirzepatide. &amp;lt;!--EndFragment--&amp;gt; Presentation: Thursday, June 15, 2023

FRI652 Type 2 Diabetes Management: More GLP1 Agonists And Less Metformin?

Abstract Disclosure: F.J. Lopez Maldonado: None. R.A. Cota: None. Case presentation: A 41-year-old male patient with family history of T2DM in both parents and brother, personal history of mild alcohol consumption and a sedentary job (public accountant), and obesity since age 30 presented to the endocrinology clinic due to failure to lose weight after 1 year of treatment with a nutritionist. During his first visit, the was asymptomatic and had acanthosis nigricans, his blood pressure was measured at 142/92 mmHg, weight was 100.8 kg, waist circumference was 128 cm, and serum glucose was at 280 mg/dL with an HbA1c of 11.9%. Further laboratory tests showed elevated levels of triglycerides (310 mg/dL), LDL (139 mg/dL), AST (96 U/L), and ALT (65 U/L). Two days later, glucose and HbA1c were repeated with similar results. A liver ultrasound was ordered which revealed diffuse hyperechogenicity of the liver and severe fatty liver disease. The ASCVD risk score was 5.4%. The patient was diagnosed with T2DM, obesity, mixed dyslipidemia, and fatty liver disease. The patient received education, nutrition support, exercise, and pharmacotherapy management with stepped-dose oral semaglutide without metformin. The dose was increased monthly starting at 3 mg and reaching the target dose of 14 mg QD. After three months, the patient demonstrated significant improvements in various parameters such as blood pressure (−10/−8 mmHg), weight (−9.8 kg), waist circumference (−25 cm), serum glucose (−179 mg/dL), HbA1C (−5.7%), triglycerides (−154 mg/dL), LDL (−18 mg/dL), AST (−60 U/L), and ALT (−38 U/L), along with an increase in HDL (+6 mg/dL). After approximately 4 months on the target dose the patient showed further improvements in several parameters including ASCVD risk score (2.1%), blood pressure (−20/12 mmHg), weight (−14.8 kg), waist circumference (−30 cm), serum glucose (−183 mg/dL), HbA1C (−6%), LDL (−25 mg/dL), AST (−63 U/L), and ALT (−40 U/L), and HDL (+10 mg/dL), except for triglyceride levels (−130 mg/dL). Follow-up liver ultrasound showed significant improvement in fatty liver disease. Real-world experiences with newly introduced drugs should be reported, as they may have beneficial effects beyond the ones studied. Oral semaglutide, the first oral GLP-1 analog, has been shown to be non-inferior to other subcutaneous GLP-1 analogs. In this case, improvements were observed in glycemic control, weight loss, lipid levels, and a reduction in cardiovascular risk, as well as an improvement in fatty liver disease. Presentation: Friday, June 16, 2023

SAT673 Novel Mutation Of TBX3 Associated With Morbid Obesity In Human

Abstract Disclosure: H.R. Alkaissi: None. B. Ji: None. S. McFarlane: None. Background: TBX3 is a transcription involved in the development of the heart conduction system, apocrine and mammary glands, limbs, and lung development and maturation, with variable oncogenic roles. Recently, the role of TBX3 and body weight control has been demonstrated in animal models, showing an essential role for TBX3 in hypothalamic arcuate neuronal maturation, function, and identity [1]. Case: 26-year-old woman referred for the management of morbid obesity and menstrual irregularities. The patient weighed 330 lbs, with a BMI of 55 kg/m2, with hypertension T2DM. The patient had a normal development until age five, after which she experienced regression in milestones and lost the ability to communicate, and was diagnosed with autism. She had a history of food-seeking behavior, leading to progressive weight gain, which was managed by blocking access to food, such as locking the fridge. The patient's weight fluctuated from 290 lbs to 330 lbs. Family history of T2DM in her maternal relatives. She was diagnosed with T2DM at the age of 18, with HbA1c level of 9.4%. Autoantibody testing was negative for glutamic acid decarboxylase (GAD), islet cell antibody (ICA), and zinc transporter 8 (ZnT8). The fasting C-peptide level was detectable at 1.87 ng/mL. T2DM was well controlled with an HbA1C range of 6.0-6.7% with the use of short and long-acting insulin regimen. However, with improved glycemic control, short-acting insulin was stopped and she was started on liraglutide. Syndromic obesity was suspected due to early-onset of the disease and the developmental regression. Testing for Prader-Willi syndrome was negative, based on a normal chromosome 15 methylation study. Leptin levels were elevated at 66 ng/mL, prompting further testing for obesity-related genetic mutations. Next-generation sequencing and targeted Sanger sequencing for 79 genes associated with obesity in human and animal models was performed. A novel mutation was identified in TBX3 activation domain, c. C1513T (p.P505S). UniProt peptide sequence alignment analyzed for sequence conservation. ClinVar, HGMD and GWAS Catalogue databases screened for similar variants. Discussion: We present the first case in human, where novel TBX3 mutation results in hypothalamic dysfunction, leptin resistance manifesting as morbid obesity, hyperphagia, and menstrual irregularities. The reported mutation in the activation domain (A) of TBX3. In silico analysis showed high evolutionary conservation of the mutated domain (across vertebrate species), indicating the mutation is likely pathogenic.

FRI463 A Case Of Post COVID-19 Subacute Thyroiditis: A Thyroid Equivalent Of Long COVID?

Abstract Disclosure: N. Shiraliyeva: None. A. Rios Chen: None. E. Azimi-Nekoo: None. P. Kishore: None. Background: The thyroid can be affected by COVID-19 either directly through viral infection or indirectly through abnormal immune regulation (1). We report a case of subacute thyroiditis (SAT) induced by COVID-19 in which thyroid function (TFT) abnormalities lasted for over a year. Case Presentation: A 36 year old woman with a history of T2DM presented to the clinic with tachycardia, chills, tremors, and subjective fever. On exam, she had mild diffuse non-tender thyromegaly. History was significant for COVID-19 infection one month prior and she denied taking any supplement, including biotin. Laboratory data revealed TSH of 0.064 (0.270-4.2 uIU/mL), prior 0.3 in 2017, FT4 of 1.24 (0.75 – 2.0 ng/dL), TT3 129 (60 - 181.0 ng/dL ), negative TSI, TRAb, and TPO antibodies. Thyroid ultrasound demonstrated normal vascularity and no evidence of thyroid enlargement or nodules. Nuclear medicine uptake scan exhibited low thyroid uptake of 5.9 %. A diagnosis of COVID-19-related SAT (COVID-SAT) was made and she was treated with propranolol. She continued to have palpitations and TSH remained low for 15 months. TSH normalized at 17 months and repeat thyroid uptake scan demonstrated a normal uptake at 15.5%. Conclusion: SAT is a self-limited inflammatory thyroid disorder usually preceded by a viral upper respiratory tract infection. COVID-SAT has been described in multiple patients. Like typical SAT, COVID-SAT can present with neck pain, asthenia, fever and palpitations (1). COVID-19 infection can cause SAT either directly through ACE-2 mediated viral invasion of cells or indirectly through abnormal immune regulation leading to cytokine storm (1). Our literature search found 20 patients with COVID-SAT. The vast majority were middle-aged females with no history of thyroid issues. In most cases of COVID-SAT, TFT abnormalities lasted 4 to 8 weeks (1). Our patient is unique in that her TFT abnormalities lasted for over a year, which is different from the usual course of SAT or COVID-SAT. Prospective studies on patients with long COVID without associated thyroid disorders demonstrated that TFT and anti-thyroid antibodies did not play a significant role in long COVID (2). We speculate that the suppression of TSH and low thyroid uptake for &amp;gt;1 year, may represent a form of long COVID of the thyroid. More studies are needed to elucidate the mechanism of long term effects of COVID infection on the thyroid and thyroid function.

The Prediction of Macrovascular Complications in Individuals with Type 2 diabetes mellitus with Different Risk Factors in ThiQar

Background:Diabetes mellitus (T2DM) is a major health issue globally, posing a significant financial and social burden on individuals, families, and communities.The objectives of the present study were to evaluate the risk factors of T2DM and its relationship with macrovascular complications. Methods:A cross-sectional observational study was conducted on 1189 individuals with T2DM attending Thi-Qar Specialized Diabetes Endocrine and Metabolism Center (TDEMC) in Nasiriya City, Thi-Qar, Southern Iraq. All patients