bluuebunny/crossref_metadata_2025 huggingface dataset:
7456 Artifactual Hypoglycemia Leading To the Diagnosis of Monoclonal Gammopathy
Authors: Ha L T , Maximous M , LaValley C K , Lado J
Published: October 2024

Disclosure: L.T. Ha: None. M. Maximous: None. C.K. LaValley: None. J. Lado: None.

Background: Low glucose readings in the absence of classic hypoglycemic symptoms are not unusual, especially among diabetic patients with unaware hypoglycemia. Discrepant measurements between capillary and venous blood are well-described, mostly due to poor reagent quality or circulatory deficits causing interference with the former. Less commonly, monoclonal gammopathies have been observed to cause true or artifactual hypoglycemia in venous blood sampling related to the presence of insulin antibodies or interference with chemistry assays, respectively. Because this interference is rare and occurs unpredictably with different testing modalities, detection is challenging and often preceded by extensive workup for underlying causes of true hypoglycemia. Clinical Case: A 69-year-old man with Parkinson’s disease, hypertension, dyslipidemia, chronic kidney disease stage 3, and obesity was referred to us for evaluation of hypoglycemia. His fasting venous glucose was consistently measured as undetectable (<10 mg/dl) on serial routine bloodwork (using the hexokinase method on Beckman-Coulter AU 5800 analyzer). He remained asymptomatic, with normal home and in-office fasting fingerstick levels. A thorough medication review did not reveal a clear etiology for this recurrent hypoglycemia. Initial workup by his primary care physician was notable for elevated total protein of 9.0 g/dl (n 6.1-8.1 g/dl), elevated globulin of 4.5 g/dl (n 1.9-3.7 g/dl), and elevated erythrocyte sedimentation rate of 111 mm/h (n<20 mm/h). Hemoglobin A1c, proinsulin, beta-hydroxybutyrate, insulin, and C-peptide were within normal range. On repeat evaluation at our institution (using the hexokinase method on Roche cobas 8000 c702 analyzer), his sample was flagged for a high lipemic index but displayed no evidence of lipemia upon visual inspection, suspicious for paraprotein presence. Protein electrophoresis was performed on the same plasma sample, revealing hypergammaglobulinemia (1.5 g/dl) subsequently characterized by serum immunofixation as a monoclonal IgM kappa. Conclusion: Recurrent “hypoglycemia” in an asymptomatic patient without other metabolic abnormalities should prompt clinicians to consider etiologies of falsely measured low glucose, including hyperleukocytosis, prolonged specimen delivery time, and paraproteinemia. In the appropriate clinical context, such as an elevated serum or plasma lipemic index, these cases should be further investigated with protein electrophoresis to rule out an underlying gammopathy. As the hexokinase method relies on optical parameters susceptible to interference by paraprotein-induced turbidity, an alternative sampling device utilizing amperometry (point-of-care glucometer or blood gas analyzers) may be employed to differentiate between true hypoglycemia as a rare complication of monoclonal gammopathy versus laboratory artifact.

Presentation: 6/1/2024
9232 Assessing the Risk of Recurrence in Acute Pancreatitis Among Patients with Type 2 Diabetes Initiating GLP-1 Receptor Agonists Therapy
Authors: Nassar Mahmoud , Abosheaishaa Hazem , Dandona Paresh , Ghanim Husam , Chaudhuri Ajay
Published: October 2024

Disclosure: M. Nassar: None. H. Abosheaishaa: None. P. Dandona: None. H. Ghanim: None. A. Chaudhuri: None.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recognized therapeutic agents for patients with type 2 diabetes mellitus and obesity. However, due to concerns about pancreatitis, clinicians do not recommend these agents for patients with a history of pancreatitis. Existing research presents conflicting evidence about this association. Our primary aim was to evaluate the risk of recurrence of acute pancreatitis (AP) associated with initiating GLP-1 RAs in patients with a history of AP. Methods: Our retrospective cohort study deployed the TriNetX platform, leveraging a large dataset from 106 healthcare organizations and approximately 127 million patients across 15 countries. We obtained data specific to our research on September 21, 2023. Using the ICD-10-CM code, we identified groups of adults with AP. We investigated the effect of GLP-1 RA vs. SGLT2i, DPP4i, and no medication (GLP-1 RA, SGLT2i, and DPP4i) on the recurrence of AP within 5 years of starting treatment. We ensured comparability between cohorts by employing propensity score matching, which focused on critical variables such as age, gender, body mass index (BMI), cholelithiasis, tobacco use, serum triglyceride, and HbA1c levels. Results: We matched the GLP-1 and SGLT2i cohorts, which initially had 4,680 and 7,212 patients, respectively, down to 3,926 in each group. Similarly, the GLP-1 vs. DPP4i comparison matched both cohorts to 3,324 patients from initial counts of 4,680 and 5,723 patients. In the matched cohorts, the GLP-1 group showed a lower AP recurrence risk (15.2%) than the SGLT2i group (24%). This difference was significant (-8.9%, 95% CI: -0.106, -0.071), with a notable risk ratio of 0.630 and an odds ratio of 0.564. For the GLP-1 vs. DPP4i comparison, the GLP-1 group's AP recurrence risk was 14.4%, lower than the 23.3% in the DPP4i group. This difference (-8.9%, 95% CI: -0.108 to -0.071) was also significant, with a risk ratio of 0.616 and an odds ratio of 0.552. For the GLP-1 vs. no medication (GLP-1RA, DPP4i, and SGLT2i) comparison, the GLP-1 group's AP recurrence risk was 14.5%, lower than the 51.6% in the comparison group. This difference (-37.1%, 95% CI: -0.388 to -0.353) was also significant, with a risk ratio of 0.282 and an odds ratio of 0.16. Conclusion: Our research showed that starting GLP-1 RA therapy in people who have had a history of AP does not increase and may potentially lower the risk of recurrence of AP than starting SGLT2i or DPP4i therapy and no medication group. These findings highlight the potential of GLP-1 RA therapy as a safer therapeutic option in this patient population, which requires further investigation.

Presentation: 6/1/2024
7201 Association of Chronotype and Glycemic Control Among Patients with Diabetes Mellitus: A Single Center Study
Authors: Nunez Noemi Angela D , Dampil Oliver Allan C , Ong Lopez Albert Macaire C
Published: October 2024

Disclosure: N.D. Nunez: None. O.C. Dampil: None. A.C. Ong Lopez: None.

Chronotype preference is an emerging risk factor to the development of diabetes mellitus and poor glycemic outcomes. This study aims to determine the association of chronotype based on the Munich Chronotype questionnaire among patients with diabetes mellitus and their level of glycemic control. This is a cross sectional analytical research study conducted at the outpatient department at St. Luke’s Medical Center Quezon City from June 1 to October 31, 2023. Inclusion criteria were adults above 18 years of age who were diagnosed with diabetes, and on oral hypoglycemic medication and/or insulin therapy for at least 6 months. Excluded were those with diagnosed sleep wake disorders, obstructive sleep apnea, pregnant or lactating women, night-shift workers, and those on medications that affect sleep patterns. Among the 290 participants evaluated, majority had early chronotypes (n=250) compared to late chronotypes (n=40). There was no statistical difference between the two groups in terms of the demographic, clinical and laboratory data. Chi-square was done to compare the groups in terms of HBA1c level, and the result was not significant (p=0.3124), indicating that the early and late chronotype groups have the same likelihood of having controlled or uncontrolled HBA1c. The Breslow-day test for homogeneity of odds ratio was done to compare the groups in terms of HBA1c level and use of two or more oral medications and insulin, and the result was not significant (p=0.9281), indicating that the relationship between Hba1c level and use of two or more oral medications and insulin is relatively the same for both chronotypes. In conclusion, there appears to be no influence of chronotype on glycemic control among diabetes mellitus treated Filipino patients.

Presentation: 6/3/2024
8152 Benefits of Inpatient Diabetes Management by a Specialized Diabetes Team
Authors: Bojarian M , Ohri A , Buettner C
Published: October 2024

Disclosure: M. Bojarian: None. A. Ohri: None. C. Buettner: None.

Background: Inpatient dysglycemia is associated with poor clinical outcomes such as prolonged length of stay (LOS), increased risk of ICU admission, and in-hospital mortality. The benefits of managing diabetic patients in the hospital with a dedicated diabetes team, as opposed to standard care on episodes of hypoglycemia or hyperglycemia, reduction in LOS, and 30-day readmission rates, remain uncertain. A potential confounder is the likelihood that patients receiving a diabetes consult may be sicker than those without a consult. Given the growing evidence supporting the role of specialized diabetes teams in improving care for diabetes patients, we sought to examine these benefits at our hospital. We plan to address confounding variables through propensity score matching. Objective: To assess whether diabetes patients experience reduced LOS, hypoglycemia, hyperglycemia, and 30-day readmission rates when managed by a specialized diabetes team compared to inpatients managed by a hospitalist team. Material and Methods: This quality improvement study compared LOS, hypoglycemia (glucose <70 mg/dL), hyperglycemia (glucose >180 mg/dL), and 30-day readmission rates in diabetes patients managed by a specialized diabetes team versus a hospitalist team at our hospital between June 2022 and December 2022. Results: 5676 patients with diabetes were admitted between June and December 2022 at our hospital, and a specialized diabetes team managed 417 patients (7.34%). In a preliminary analysis in which no propensity matching was performed yet, the 30-day readmission rate was significantly lower (87,16.6%) in patients who received a diabetes consult compared to patients who did not receive a diabetes consult (320,17.9%). The rate of hypoglycemia was higher (24.4%) in the specialized diabetes consult group than in the non-diabetes consults group (19.9%). Additionally, LOS was longer in patients with a specialized diabetes consult (7.1 vs. 3.1 days), and hyperglycemia (glucose >180 mg/dL) was more prevalent in the specialized diabetes consult group (78.9%) compared to the non-diabetes consult group (39.2%). Conclusion: In this retrospective analysis, patients managed by a specialized diabetes team showed lower readmission rates despite longer hospitalization and increased dysglycemic episodes. This could be attributed to sicker patients receiving diabetes consults, influencing dysglycemia rates. To account for such confounders, ongoing propensity score matching aims to provide a clearer understanding. Reduced readmission rates suggest improved care transitions, potentially resulting in significant cost savings for the healthcare system.

Presentation: 6/1/2024
7481 Beyond the Operation Room: A Retrospective Study on Diabetes and Post-Operative Hyperglycemia Outcomes
Authors: Aron Polina , Zaihra Rizvi Tasneem , Hodge Mary Beth , Jean Karen St , Upadhyay Jagriti
Published: October 2024

Disclosure: P. Aron: None. T. Zaihra Rizvi: None. M. Hodge: None. J. Upadhyay: None.

Introduction: Optimal, evidence based intraoperative and postoperative glycemic management may reduce poor surgical outcomes. Research design: This is a retrospective study from a single center to estimate quality gaps in perioperative glycemic management in patients with diabetes undergoing major surgery requiring general anesthesia between Oct 2022 and Dec 2022. Study Cohort: Patients > 18 years old, who underwent major surgery (>3 hrs) under general anesthesia, had diabetes mellitus based on Hba1c > 6.5% within last 1 year or as listed diagnosisThis is an ongoing study. We have currently looked at 79 patients of which 61 were in the hyperglycemic group (glucose > 180 mg/dL) and 18 in normoglycemic group (glucose < 180mg/dL) post-operatively. Methods: Baseline characteristics, perioperative outcomes, and operative details between the hyperglycemic and normoglycemic groups were compared using Kruskal-Wallis's rank sum test for continuous variables and χ2 or Fisher's exact tests using categorical variables. Results: Patients who were found to have hyperglycemia in the first 24 hours after surgery had a higher preop A1c of 7.4% vs 6.7% in the normoglycemia group (p-value = 0.047). They also had a higher BMI of 32 as compared to 30 respectively and a reduced GFR of 60 vs 73 in the normoglycemic group (P=0.069). 24 hours leading into surgery, the hyperglycemia group had a high average glucose of 196 mg/dL as compared to 135 mg/dL (p-value = 0.001). During the intraoperative period which lasted on average of 350 minutes (5.5 hours) there was an average glucose check of 3.2 times averaging 221 mg/dL for the hyperglycemia group compared to 2.2times averaging 174 mg/dL (P = 0.017). 62% of patients with intraoperative hyperglycemia DIDNOT receive IV insulin treatment in the hyperglycemic group. Steroid use was equal in both groups. 24 hours after surgery, patients in the hyperglycemia group had an average glucose reading of 252 mg/dL compared to 145 mg/dL in the normoglycemia group (P < 0.001).Endocrinology was not consulted in 87% of patients with hyperglycemia. Looking at our endpoints, readmission rate was 23% in the hyperglycemia group as opposed to 11% in normoglycemia. There were 4 patients who had a 90-day mortality from the hyperglycemia group compared to no patients in normoglycemia. 37% of patients had post-op complications in the hyperglycemia vs 22% in the euglycemia group (P 0.269). The hospital stay was the same for both groups averaging 8 days. Conclusions: Intraoperative hyperglycemia leads to poor outcomes. Formulating policy around insulin administration, frequency and monitoring of blood sugars during major surgeries and endocrine consultation in patients with Type 2 DM can achieve better glycemic management and postoperative outcomes.

Presentation: 6/2/2024
5099 Capturing the Patient Voice for Diabetes Eye Exams
Authors: Du S , Lambrechts S , Freeby M , Han M
Published: October 2024

Disclosure: S. Du: None. S. Lambrechts: None. M. Freeby: None. M. Han: None.

Background: Diabetic retinopathy (DR) is a leading cause of blindness among adults 20-74 years old. Ophthalmic exams are recommended every 1-2 years for type 2 diabetes patients with minimal to no DR. The 50th percentile Integrated Healthcare Association benchmark for DR screening is 49%, but at our academic medical center, the completion rate is 30%. Potential barriers to screening noted in the literature include lower levels of education, lack of knowledge about DR, and financial barriers. Objective: To understand motivating factors and barriers to DR screening among patients in our health system. Methods: We utilized the Patient Voice qualitative research method to uncover themes and identify interventions to improve care delivery. The literature was synthesized to develop a structured interview guide. From our urban academic health system, 15 patients were randomly selected for interview, six of whom had completed the “Diabetes Eye Exam” care gap and nine that had not. Interviews were transcribed and coded for thematic analysis. Results: Six opportunity areas were identified. 1) There are currently only six retinal cameras located across primary and specialty care clinics serving more than 38,000 diabetes patients. 67% of patients felt the current clinic locations were inconvenient, with distant locations and long travel times. 2) 20% of patients expressed that they would like increased flexibility of appointments offered, such as evening, weekend, and same day appointments. 3) Patients were motivated by automated diabetes eye exam specific reminder messages and appreciated the ability to self-schedule within the patient portal. 47% of patients wanted yearly reminder messages, while 40% had no preference. 4) 53% of patients expressed that they did not fully understand DR or were confused about the difference between an optometrist exam and diabetes eye exam. 5) 40% of patients completed their eye exam with their local optometrist and found this to be a more convenient option. One patient expressed that she wished her doctor had informed her that she could complete her diabetes eye exam at a local optometry clinic. 6) If patients do choose to complete their exam with their local optometrist, they would like reminders to send their records to their primary care physician or endocrinologist. A more streamlined processes to upload outside records through the patient portal would decrease this barrier. Conclusion: It is important to engage patient stakeholders and understand their needs to improve overall experience and close care gaps. Through the Patient Voice, we learned that factors such as driving distance, traffic, scheduling, and issues with uploading records are major barriers to care gap completion. Convenient clinic locations, education, and reminder messages are motivating factors. Future work will focus on developing and implementing solutions in each opportunity area.

Presentation: 6/1/2024
9250 carRNA m6A methylation regulates transcription state and chromatin accessibility in human islets in normal physiology and type 2 diabetes
Authors: Shukla Namrata , Ju Cheng-Wei , Li Han , He Chuan , Kulkarni Rohit
Published: October 2024

Disclosure: N. Shukla: None. C. Ju: None. H. Li: None. C. He: None. R. Kulkarni: Advisory Board Member; Self; Novo Nordisk, Biomea Fusion Inc, REDD Pharma. Grant Recipient; Self; Inversago.

Chromatin-associated regulatory RNAs (carRNA), which include promoter- and enhancer-associated RNAs as well as several non-coding repeat elements have been established in the literature as important regulators of global gene transcription. However, the regulation of carRNAs themselves has been an enigma. Recent publications from the He Lab at UChicago have shown the role of RNA N6-methyladenosine (m6A) in regulating carRNA stability and function. m6A is among the most abundant mRNA modifications in mammals. Seminal work from our lab has reported that the “writers” of m6A (e.g. methyltransferase-like [METTL3] and METTL14) are significantly downregulated in islets of humans with type 2 diabetes (T2D). Consequently, the global m6A landscape in the islets segregates the T2D from the control group significantly better than the transcriptome (n=7 for Control and n=8 for T2D islets). Hypomethylation of key transcripts in the insulin/IGF-1-AKT-PDX1 pathway led to impaired insulin secretion and decreased β-cell proliferation. We now show this decreased m6A on RNA is not limited to the mRNA but also affects chromatin-associated regulatory RNAs (carRNA). Intriguingly, downregulation of METTL3 and METTL14 in human β-cell line EndoC-βH1 differentially regulates these regulatory versus protein-coding transcripts. We observe that while METTL14 KD causes global downregulation of transcripts belonging to pathways important for β-cell identity and function (including calcium signaling, PI3K-AKT/MAPK signaling pathway, pancreatic secretion etc.), it leads to an upregulation of pathways involved in RNA processing and global gene transcription (Transcription by RNA Pol II, metabolism and splicing of mRNA, chromatin organization and modification etc.) {false discovery rate (FDR) < 0.05}. Considering carRNAs have been previously reported to regulate global chromatin accessibility and transcription, our observations on their ability to get differentially regulated m6A writer proteins provide novel insights into the epigenetic regulation of human islet cells. These findings provide opportunities to develop therapeutic approaches to regulate β-cell identity and/or insulin secretion in T2D.

Presentation: 6/3/2024
7241 Catamenial Diabetic Ketoacidosis
Authors: Javed Laraib , Rehan Aiman , Hashim Laila , Lim Jonea
Published: October 2024

Disclosure: L. Javed: None. A. Rehan: None. L. Hashim: None. J. Lim: None.

Introduction: Diabetic ketoacidosis (DKA) is a common cause of hospitalization and readmission in patients with diabetes mellitus. Etiologies are generally due to medication non-adherence, trauma, infection, or other precipitating illness. In approximately 10% of DKA cases, no discernible precipitating cause can be determined. The word catamenial is derived from a Greek word meaning monthly. It is used to describe the monthly occurrence of menstruation. Catamenial hyperglycemia is a phenomenon in which blood glucose levels change with the different phases in the menstrual cycle. This can precipitate recurrent, unexplained episodes of DKA. Here, we present a similar case. Case description:A 19-year-old woman with type 1 diabetes, gastroparesis, hypertension, dysmenorrhea and cyclical vomiting disorder presented with unrelenting nausea and vomiting for one day. Other symptoms included abdominal & chest pain that the patient attributed to premenstrual symptoms. She is afebrile, doesn’t have any other symptoms of infection and no recent sick contacts. She is compliant with her home insulin regimen of Insulin detemir 20 units BID and pre meal 8 units insulin aspart. Further interrogation reveals she has regular menstrual cycles and has been hospitalized three times in the last three months due to DKA coinciding with premenstrual symptoms, specifically severe abdominal pain and vomiting, typically starting five days before the onset of her menstrual cycle. She is hemodynamically stable and physical exam is significant for mid epigastric tenderness. Significant labs: WBC 16.52 (N<11 K/mm3), glucose 457 mg/dl, anion gap 23, K 4.1 (mmol/L), bicarbonate 18 (≥19 mmol/L), lactate 3.2 (N ≤ 1.9 mmol/L), beta hydroxybutyarate 4.0 (N ≤ 0.27 mmol/L), trop T 6 (N<10 ng/L), BHCG negative . Hba1c a month ago was 9.6%. Infectious work up was negative. EKG showed no signs of ischemia. She was treated per DKA protocol which results in resolution of symptoms and normalization of labs. Since no other precipitating factors for DKA are identified, and her symptoms corresponded with her menstrual periods, she is given a diagnosis of Catamenial DKA and scheduled for regular follow up in endocrinology clinic. Conclusion: This case highlights the importance of considering the association betweenmenstrual cycle phases and blood sugar levels as a possible trigger, underscoring the role of a thorough menstrual history in patients presenting with DKA. The impact of menstrual cycle fluctuations on glycemic control varies among patients however glucose profiles seem to be consistent across cycles for each individual woman. This highlights the need for personalized management strategies including patient education and adjustment of insulin during these periods. Addressing this adequately will improve overall glycemic control, reduce hospitalizations, and help improve the quality of life.

Presentation: 6/1/2024
8083 Challenging Management of Diazoxide as a Double-Edged Sword in an Adult Patient with Recurrent Hypoglycemia
Authors: Fredrick J R , Qu J , Endo M
Published: October 2024

Disclosure: J.R. Fredrick: None. J. Qu: None. M. Endo: None.

Introduction: An insulinoma is a rare neuro-endocrine tumor that leads to fasting hypoglycemia with adrenergic, cholinergic, and neuroglycopenic symptoms. Diagnosis can be challenging, especially when imaging is negative for neuroendocrine tumor. To prevent recurrent hypoglycemic episodes, treatment can include dextrose and octreotide or diazoxide. We present a case of a patient who responded well to diazoxide but at higher doses, developed life-threatening side effects. Clinical Case 74-year-old female with history of osteoporosis presented with recurrent hypoglycemia with associated symptoms of dizziness, palpitations, and headaches, improved with food. TSH 1.0ulU/mL (0.4-4.7ulU/mL). Morning cortisol 14ug/dL (n>14ug/dL). Patient underwent a 72-hour fasting test, which showed a point-of-care blood sugar of 47mg/dL. Labs included serum glucose 56mg/dL (70-140mg/dL), c-peptide 5.7ng/mL (0.78-5.19ng/mL), insulin 43.6ulU/mL (3-30ulU/mL), and beta-hydroxybutyrate 0.13mmol/L (0-0.5mmol/L). Screening was negative for insulin antibodies and presence of hypoglycemic agents. She became dependent on a dextrose infusion to maintain blood sugars. Magnetic resonance imaging of abdomen was negative for any lesion. Octreotide did not resolve the hypoglycemia. Diazoxide was started, with dose titrated up to 175mg three times daily with decreasing dextrose infusion requirements. However, she developed hypoxic respiratory failure, which was felt due to atelectasis or fluid overload, treated with mild diuresis and incentive spirometry. In the coming days, this escalated to requiring high-flow nasal cannula. Diazoxide was discontinued, and she returned to a dextrose infusion to prevent hypoglycemia. Dotatate scan was completed, revealing a focal intense dotatate tracer uptake within the pancreatic tail. This was followed by magnetic resonance cholangiopancreatography, which confirmed an arterially enhancing diffusion restriction lesion in the pancreatic tail and found several small hyper-vascular liver lesions, primarily hemangiomas, with two lesions indeterminate. The patient was weaned off oxygen and underwent distal pancreatectomy. Pathology confirmed a neuroendocrine tumor. She remained without a dextrose infusion after surgery with no recurrence in hypoglycemia and was discharged 3 days later. Conclusion: Diazoxide is known to improve recurrent hypoglycemia for patients evaluated for hyperinsulinemia. However, caution should be made due to life threatening side effects, including pulmonary edema and severe hypoxic respiratory failure. More expansive literature evaluating these risks would be beneficial(1). Reference 1. Chen, X., Feng, L., Yao, H., et al. Efficacy and safety of diazoxide in treating hyperinsulinemic hypoglycemia: A systemic review and meta-analysis. PLoS One. 2021 Feb 11;16(2):e0246463.

Presentation: 6/3/2024
12596 Characterizing Glycemic Variability In Novel Subphenotypes Of Individuals At Elevated Risk For Type 2 Diabetes Using Continuous Glucose Monitoring
Authors: Kretowski Adam Jacek , Konopka Paulina , Janucik Adrian , Citko Anna , Paszko Adam , Klak Mateusz , Golonko Aleksandra , Szklaruk Agata , Szczerbinski Lukasz
Published: October 2024

Disclosure: A.J. Kretowski: None. P. Konopka: None. A. Janucik: None. A. Citko: None. A. Paszko: None. M. Klak: None. A. Golonko: None. A. Szklaruk: None. L. Szczerbinski: None.

Background: The heterogeneity among individuals at elevated risk for Type 2 Diabetes (T2D) recently has led to the identification of six subphenotypes, each with distinct risks for developing T2D, its complications, and mortality. Our study leveraged Continuous Glucose Monitoring (CGM) to offer a detailed characterization of these subphenotypes, aiming to uncover differences in glycemic variability and control. Methods: CGM data from 616 individuals without diabetes, from the Polish Registry of Diabetes (PolReD) study, classified into six clusters, were analyzed. The PolReD used Freestyle Libre 2 (Abbott) as the CGM device. CGM-derived measures of glucose control and glucose variability were calculated using the iglu R package. We utilized Analysis of Variance (ANOVA) and Analysis of Covariance (ANCOVA), adjusting for age and sex, to identify significant differences in CGM parameters across the clusters. Results: Our analysis identified significant differences in several CGM-derived parameters among the clusters, notably in the Glycemic Risk Assessment Diabetes Equation (GRADE), Standard Deviation of weekly glucose values (SDw), Mean Amplitude of Glycemic Excursions (MAGE), Maximum glucose value, Glucose range, and Mean Absolute Glucose (MAG). Clusters 3 and 5, characterized by beta-cell dysfunction and high insulin resistance respectively, and associated with the highest risk of T2D, exhibited the greatest glucose variability, with elevated risk for glycemic excursions. In contrast, Cluster 4, indicative of a metabolically healthy obesity profile with a low risk of T2D, demonstrated the most stable glycemic control and the lowest variability among the clusters. Conclusions: This study shows that subtypes of patients at elevated risk for T2D exhibit distinct patterns in CGM-derived parameters, indicating variations in glucose control and stability that extend beyond traditional fasting and post-challenge glucose assessments. Notably, we found that subtypes facing the highest T2D risk display increased glycemic variability, despite their differing underlying mechanisms of dysglycemia. These findings highlight the utility of CGM as a tool for identifying individuals at an increased risk of T2D, reducing the need for extensive phenotyping typically required for cluster assignment.

Presentation: 6/1/2024
8177 Clinical Characteristics of Ketosis Prone Diabetes: Evaluating Diagnosis and Management Practices in a Real-Life Setting
Authors: Tariq Z , Sinha A , Shokry G , Moors K , Kodukula S S , Saeed Z I
Published: October 2024

Disclosure: Z. Tariq: None. A. Sinha: None. G. Shokry: None. K. Moors: None. S.S. Kodukula: None. Z.I. Saeed: None.

Aims: While evidence supports the Aß (Auto-antibody status, Beta-cell function) classification of Ketosis Prone Diabetes (KPD), its implementation by healthcare providers (HCPs) remains unclear. We examined practices in managing KPD in a tertiary-care center and compared features between Aß subgroups. Methods: A retrospective longitudinal cohort study was conducted consisting of individuals aged 18 and above with diabetes who experienced diabetic ketoacidosis (DKA) between 2016 and 2021. Demographics, causes of DKA, auto-antibody status, beta-cell function, clinical characteristics, and follow-up care were assessed. Data were analyzed using descriptive and inferential statistics. Results: Among 1557 individuals with KPD, 11.6% underwent A testing, 20.2% underwent ß testing, and only 9.8% underwent both A and ß testing. HCPs were more likely to assess Aß status among those who were young, Black, and had new-onset diabetes (p<0.001). A-ß+ was the most common (53.9%), and A+ß+ was least common (5.9%) KPD. Clinical characteristics differed among subgroups, with ß- having a leaner BMI and more insulin dependence. Infection was the leading cause of DKA (37.9%), followed by unprovoked DKA (22.6%). Conclusion: Our study further validates and highlights the underutilization of Aß classification in KPD management and emphasizes the need for increased education among HCPs to improve care for people with KPD.

Presentation: 6/1/2024
7490 Comparative Clinical Analysis of DPP-4 inhibitors and SGLT2 inhibitors; Switch Study in Real-World Setting
Authors: Choe Hun Jee , Kwak Mi Kyung , Lee Ji Woo , Choi Yun Mi , Hong Eun-Gyoung
Published: October 2024

Disclosure: H. Choe: None. M. Kwak: None. J. Lee: None. Y. Choi: None. E. Hong: None.

Objective: Dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) represent two distinct pharmacological pathways in the management of type 2 diabetes, both aiming to improve glycemic control without risk of hypoglycemia. Metabolic implications and glycemic control associated with the interchange between SGLT2i and DPP-4i are scarce. This study aimed to evaluate the effect of switching between SGLT2i and DPP4i on various clinical parameters in Korean patients with type 2 diabetes. Methods: We conducted a retrospective cohort study at Hallym University Dongtan Sacred Heart Hospital, using clinical data warehouse. Baseline measurements and follow-up data at 3 months were collected for parameters including hemoglobin A1c (HbA1c), blood pressure, lipid profile, liver enzymes, renal function, and other metabolic markers. Results: Between 2015 and 2023, 104 participants switched from SGLT2 inhibitors to DPP4 inhibitors, while 321 switched in the opposite direction. Initially, those who switched from SGLT2 inhibitors to DPP4 inhibitors presented with lower baseline HbA1c levels (7.22 ± 0.73% versus 7.42 ± 0.76%, P = 0.017) and higher estimated glomerular filtration rates (eGFR) (95.2 ± 23.1 versus 85.9 ± 23.7 mL/min/1.73m², P = 0.001) compared to those who switched from DPP4 inhibitors to SGLT2 inhibitors. At three months of follow-up, the SGLT2 inhibitors to DPP4 inhibitors group exhibited a more significant reduction in HbA1c (adjusted β 0.22, 95% CI 0.03 to 0.40, P = 0.023), especially in patients with reduced eGFR (<60 mL/min/1.73 m²) (β 1.2, 95% CI 0.30 to 2.11, P = 0.013; P for interaction = 0.005). On the other hand, the DPP4 inhibitors to SGLT2 inhibitors group showed a greater decrease in fasting glucose levels (β -9.73, 95% CI -17.6 to -1.86, P = 0.016), along with more pronounced reductions in liver enzymes AST (β -4.15, 95% CI -6.49 to -1.81, P < 0.001) and ALT (β -6.42, 95% CI -9.58 to -3.27, P < 0.001), and a significant increase in hematocrit (β 3.31, 95% CI 2.36 to 4.26, P < 0.001) compared to the initial group. Conclusions: The study concludes that in Korean patients with type 2 diabetes, switching from SGLT2 inhibitors to DPP4 inhibitors is associated with a greater reduction in HbA1c, particularly in those with reduced renal function. Conversely, switching from DPP4 inhibitors to SGLT2 inhibitors results in more substantial improvements in fasting glucose and liver enzyme levels, suggesting differential benefits depending on the direction of the medication switch.

Presentation: 6/3/2024
8066 Compensatory Signatures of Islet Cells That Protect Obese Humans From Diabetes
Authors: Kim Hyunki , Li Yan , Zhu Houxiang , Jellas Khadija El , Shukla Namrata , Ren Ziyou , Fukuda Kazuki , Chen Mengjie , Kulkarni Rohit
Published: October 2024

Disclosure: H. Kim: None. Y. Li: None. H. Zhu: None. K. El Jellas: None. N. Shukla: None. Z. Ren: None. K. Fukuda: None. M. Chen: None. R. Kulkarni: Advisory Board Member; Self; Novo Nordisk, Inversago, Biomea, REDD.

The increasing prevalence of obesity and type 2 diabetes (T2D) continues to be a major global socioeconomic burden. Healthy humans adapt to metabolic stress by increasing their functional β-cell mass. Failure of this process, called decompensation, potentially triggers the development of T2D in many but not all obese humans. Furthermore, the molecular mechanism(s) underlying the ability of heterogeneous human β-cells to compensate and protect obese humans from developing T2D remain elusive. Here we report unique gene signatures of β-cell subtypes and their molecular interactions with islet stellate cells during successful compensation in human obesity. Using a single-nucleus multiomics approach, we profiled gene expression and chromatin accessibility of 160,954 islet nuclei from non-diabetic lean, overweight, obese, or T2D human donors. We identified multiple β-cell subtypes and their unique sets of genes, biological pathways, and transcription factors associated with compensation. The genome-wide association studies corroborated the compensatory genes identified in the subsets, showing significant associations with metabolic phenotypes in humans. Unbiased cell-cycle gene and ligand-receptor analyses of islet cell types revealed that activated stellate cells proliferate and interact with the β-cell subtypes that involves the extracellular matrix-integrin protein complex in non-diabetic obesity. These results highlight the physiological roles of islet stellate cells in regulating β-cell compensation and point to therapeutic opportunities in precision medicine to protect obese humans from developing T2D.

Presentation: 6/3/2024
8814 Concordance in Defining Diabetes Remission: A Comparative Analysis of HbA1c, eA1c, and FPG Criteria After One Year of Digital Twin (DT) Intervention
Authors: Shamanna P , Dharmalingam M , Vadavi A , Keshavamurthy A , Bhonsley S , Thajudeen M , Balasubramanian A , Joshi S R
Published: October 2024

Disclosure: P. Shamanna: None. M. Dharmalingam: None. A. Vadavi: None. A. Keshavamurthy: None. S. Bhonsley: None. M. Thajudeen: None. A. Balasubramanian: None. S.R. Joshi: None.

Introduction: This study investigates the concordance among HbA1c, estimated A1c (eA1c), and fasting plasma glucose (FPG) remission criteria following one year of Digital Twin (DT) intervention. Understanding the agreement of these criteria in a cohort of 209 patients is critical for evaluating diabetes treatment efficacy. Methods: Diabetes remission was assessed in 209 patients after one year of DT intervention, using HbA1c, eA1c, and FPG criteria. Kappa values, along with sensitivity, specificity, and p-values, were calculated for concordance. Mean, standard deviation, and p-values for age, duration of diabetes, HbA1c, fasting plasma glucose, and eA1c were also computed. Results: The study revealed substantial agreement between HbA1c and eA1c criteria (Kappa: 0.751, indicating 'substantial' agreement), HbA1c and FPG criteria (Kappa: 0.703, indicating 'substantial' agreement), and eA1c and FPG criteria (Kappa: 0.719, indicating 'substantial' agreement), post one year of DT intervention. The average age of participants was 43.89 years (±8.72), with a diabetes duration of 3.65 years (±2.66). The initial HbA1c was 9.02% (±1.90), reducing to 6.00% (±0.67) at the end of the study. Initial and final fasting plasma glucose levels averaged 170.75 mg/dL (±61.11) and 109.33 mg/dL (±30.60), respectively. Remission rates were 72.73% for HbA1c, 75.60% for eA1c, and 71.29% for FPG. Conclusion: Our findings suggest that remission using either eA1c or FPG criteria can be reliably compared to the gold standard HbA1c criteria, with all showing 'substantial' agreement post one year of DT intervention. This high concordance, reflected in the statistically significant kappa values, highlights the effectiveness of eA1c and FPG criteria as robust tools in assessing diabetes remission alongside the HbA1c criteria. These insights are crucial for clinical practice and diabetes research, offering flexibility in evaluating patient outcomes.

Presentation: 6/1/2024
8088 Connecting the Dots: Semaglutide, Constipation, and Diverticulitis - A case report
Authors: Tiwari K , Sajid F , Karam J G
Published: October 2024

Disclosure: K. Tiwari: None. F. Sajid: None. J.G. Karam: None.

Introduction: Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used for the treatment of type 2 diabetes mellitus and weight management. Common side effects, primarily gastrointestinal (>10%), include nausea, vomiting, diarrhea, and constipation. Here, we present a case of acute sigmoid diverticulitis with an adjacent abscess in a patient who was recently initiated on GLP-1 receptor agonist therapy. Case presentation: A 76-year-old female with a medical history of type 2 diabetes mellitus on metformin and empagliflozin, hypertension, chronic kidney disease stage 3A, obesity (BMI: 43), and no known history of diverticulosis was started on semaglutide for additional glycemic, renal, and weight loss benefits, given suboptimal control of her obstructive sleep apnea, blood pressure, and knee arthritis. She received semaglutide subcutaneously at a dose of 0.25 mg weekly for 4 weeks, followed by an increased dosage of 0.5 mg for one week. However, she experienced a slight worsening of underlying constipation as a side effect. On the sixth week of therapy, she started having progressive lower abdominal pain with nausea, chills, and diarrhea, for which she presented to the Emergency Department. She was found to have leukocytosis, and a Computed Tomography (CT) of the abdomen/pelvis revealed peri-colonic fat stranding in the mid-ascending colon, wall thickening in the distal sigmoid colon, and a low-density fluid collection abutting the sigmoid/descending colonic wall, indicative of diverticulitis with a small abscess. She was admitted to the hospital for six days and was treated conservatively with Intravenous (IV) antibiotics, and her diet was slowly advanced as tolerated. Semaglutide was discontinued, and the patient was discharged home with outpatient endocrinology and gastrointestinal follow-up. A post-discharge colonoscopy showed diffuse diverticulosis. Conclusion: Constipation and old age are common risk factors for diverticulitis. While GLP1-1 receptor analogs have proven significant and multiple benefits, more knowledge about associated gastrointestinal complications resulting from slower food transit in the gastrointestinal tract is emerging. Older patients with underlying constipation and/or diverticulosis should particularly be monitored and treated for worsening constipation to avoid complications such as acute diverticulitis. Vigilance and awareness in recognizing and managing this potential complication are crucial with the wider indications and use of GLP-1 receptor analogs.

Presentation: 6/3/2024
6521 Continuation of Continuous Glucose Monitors in Hospitalized Diabetic Patients Decreased the Incidence of Hypoglycemia
Authors: DeClue Cory E , Bao Shichun
Published: October 2024

Disclosure: C.E. DeClue: None. S. Bao: None.

Objective: Glycemic control improves patient outcomes in hospitalized patients, and this is generally achieved by monitoring point-of-care (POC) capillary glucose levels. In the outpatient setting, continuous glucose monitoring (CGM) devices have shown improved glycemic control in diabetic patients, but their evidence in hospitalized patients is lacking. Methods: To evaluate CGM accuracy and safety of use in the inpatient setting, 567 consults were analyzed in a single-center inpatient diabetes service between November 2022 and January 2023. Patients were included if managed with multiple daily injections or insulin pump therapy and separated into four groups based on CGM continuation and type of diabetes. POC glucose and incidence of hypoglycemia were recorded over 72 hours from the time of consultation. Results: Forty-six Type-1 (T1DM) and 72 Type-2 (T2DM) diabetic patients were included in this study, with average hemoglobin A1c of 8.6% and 9.0%, respectively. Both diabetic groups showed an average POC glucose that was not statistically different based on CGM continuation (185 mg/dL for T1DM and 187 mg/dL for T2DM continued on CGM versus 183 mg/dL for T1DM and 188 mg/dL for T2DM not using CGM). However, only 2 of the 18 T1DM patients continued on CGM experienced hypoglycemia, whereas 17 of the 28 T1DM patients not using CGM experienced at least 1 hypoglycemic event. Similarly, only 2 of the 20 T2DM patients continued on CGM experienced hypoglycemia, whereas 13 of the 52 patients not using CGM experienced at least 1 hypoglycemic event. Additionally, less glucose variability was observed in both T1DM and T2DM patients continued on CGM (average standard deviation of 64 mg/dL and 55 mg/dL, respectively) compared to those not using CGM (average standard deviation of 84 mg/dL and 62 mg/dL, respectively). Conclusion: CGM has great potential to improve patient care and nursing workload in the hospital, but the safety and accuracy are not yet well-established. In this study, there seemed to be a statistically insignificant trend to less glycemic variability for CGM users despite no glycemic difference on average POC testing. Importantly, significantly fewer hypoglycemic events were observed in patients continued on CGM devices regardless of type of diabetes or baseline glycemic control. This study adds further evidence to the growing body of work supporting improved safety of CGM utilization in hospitalized diabetic patients.

Presentation: 6/1/2024
12395 Continuous Glucose Monitoring In Pseudohypoparathyroidism Type 1a
Authors: Tamaroff Jaclyn , Lee Andrea E , Shoemaker Ashley Hall
Published: October 2024

Disclosure: J. Tamaroff: None. A.E. Lee: None. A.H. Shoemaker: None.

Background: Pseudohypoparathyroidism type 1A (PHP1A), due to heterozygous mutations in GNAS, is a rare disorder that leads to multi-hormone resistance, cognitive impairment, and early-onset obesity. Individuals with PHP1A have dysglycemia on oral glucose tolerance tests and increased rates of type 2 diabetes (T2DM). Individuals with rare diseases, like PHP1A, may travel significant distances for specialized clinical or research care. Wearable technology may alleviate barriers and provide useful information for clinical care or for use as potential biomarkers. The objective of this study is to evaluate glycemia in individuals with PHP1A and feasibility of utilizing continuous glucose monitors (CGMs) in this population. Methods: Observational study of individuals with PHP1A (3R01DK118407-03S1). CGMs (Dexcom Pro, Dexcom Inc, San Diego, CA) were placed on participants’ abdomens, typically by a family member, over secure-video call with study staff. CGMs collected data every 5 minutes for up to 10 days. Results: Seven participants (all female) with PHP1A without a diagnosis of diabetes had available data. Median age was 17 years (IQR: 14, 19; range: 8-23). Body mass index (BMI) categories (by percent of the 95th percentile for those under 18 years and BMI for adults) spanned from overweight to class 3 obesity. In terms of feasibility, 1 individual had to replace a CGM sensor due to an upcoming MRI and 1 individual had a “sensor failure” of unclear etiology. Both were able to place new CGMs. Individuals participated across 5 states in the United States. Median length of wear was 9.8 days (IQR 8.6, 9.9). Participants had a median average glucose of 104mg/dL (IQR 102, 111) and COV of 16% (15, 21). Percent of glucose > 140mg/dL was 5.0% (IQR: 1.8, 10.9; range:1.2-19.4%). One individual had 3.2% of glucose values ≥ 200mg/dL despite a normal hemoglobin A1c (HbA1c) level (5.5%). This level of hyperglycemia is qualitatively higher than published CGM data in healthy individuals. One study found individuals (6-24 years of age) had median percent of glucose values over 140mg/dL ranging from 1.2 to 2.4% with IQR values ranging from 0.3 to 4.4%, based on age categories.1Conclusions: In females with PHP1A, with overweight or obesity, CGM placement at home is a feasible way to collect real-world data. Participants with rare diseases often must travel for clinical and research care and CGMs may provide insight into glycemia without requiring an in-person visit. This “real-world” data mirrors research data reporting glycemia with normal HbA1c levels. The rate of hyperglycemia is higher than expected in some individuals with PHP1A though more data is needed. Ongoing studies will evaluate matched control participants and assess drivers of glycemia including inactivity and decreased sleep duration, as measured by actigraphy. References: 1. Shah VN et al. J Clin Endocrinol Metab. 2019 PMID: 31127824

Presentation: 6/3/2024
12621 Convergence Of Sglt2 Inhibitors And Glp1 Agonists: Unveiling The Recipe For Euglycemic Diabetic Ketoacidosis
Authors: Syed Usheem , Fretes Oviedo Natalia Elizabeth , Variar Vivek
Published: October 2024

Disclosure: U. Syed: None. N.E. Fretes Oviedo: None. V. Variar: None.

Introduction: Euglycemic diabetic ketoacidosis (DKA) is a known adverse effect associated with the use of SGLT2 inhibitors. The concomitant initiation of GLP1 agonists with SGLT2 inhibitors presents a potential synergistic risk, precipitating metabolic acidosis without significant hyperglycemia. The individual propensity of both medication classes to contribute to metabolic disturbances highlights the necessity for heightened clinical awareness. Clinical Case: We present a case of a 34-year-old female with morbid obesity and Type 2 diabetes mellitus, receiving tirzepatide, metformin, and empagliflozin. The patient was initiated on empagliflozin 4 days prior, and tirzepatide one day prior to presentation. Shortly after commencing tirzepatide, she experienced symptoms of decreased appetite, abdominal pain, and vomiting. Workup was consistent with DKA with blood glucose < 250 mg/dL. Management involved strict adherence to DKA protocols. The patient’s symptoms resolved with resolution of ketoacidosis. Conclusion: Euglycemic DKA poses a diagnostic challenge for patients on SGLT2 inhibitors. Concurrent administration of GLP1 agonists, while not directly implicated, may exacerbate this condition, by their gastrointestinal side effects and resultant metabolic abnormalities. Awareness of potential interactions and associated risk factors is crucial for timely diagnosis and management.

Presentation: 6/3/2024