bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP224 Metformin Associated Lactic Acidosis in a Nondiabetic Young Female
Authors: Saberi Elnaz , Izkhakov Neriy , Radpour Omid , Vernetti Nicholas , Nakhle Sameer
Published: November 2022

Background

Metformin is the first line of treatment for patients with Diabetes Mellitus type 2. Despite multiple benefits, metformin is contraindicated in stage 4 renal disease due to an increased risk of metformin associated lactic acidosis (MALA). MALA is estimated to have a high mortality rate of 30-50%. The presentation of MALA can mimic sepsis and organ failure.

Clinical Case

We report a case of a 32 year old female who presented with generalized weakness and shortness of breath. She was found to have severe metabolic acidosis (PH 7. 04, PCO2 40 mmHg, Bicarb 15 mmol/L, anion gap 14 mmol/L, lactic acid 8.7 mmol/L), hypotension (82/46 mmHg), pancytopenia, moderate transaminitis, severe acute kidney injury (creatinine 3.2 mg/dL, GFR 17 mL/min/1.73 m2), and profound hypoglycemia (serum glucose 42 mg/dL). Endocrinology was consulted due to hypoglycemia and suspected adrenal insufficiency. During the encounter the patient was alert and oriented, but reported severe nausea and appeared in significant distress. On review of medications, she reported taking phentermine and metformin for weight loss, hydrochlorothiazide for hypertension, and fluoxetine for depression. She denied taking other supplements. She denied any history of diabetes mellitus or prediabetes. Computed tomography (CT) of the chest and abdomen were unremarkable. The patient's potassium was normal. Lactic acidosis continued to increase (16.1 mmol/L) despite intravenous fluids, empiric broad spectrum antibiotics, and stress dose steroids. Approximately 19 hours after the arrival, she underwent dialysis due to suspected MALA. Her lactic acid improved after dialysis transiently (6.1 mmol/L), but later worsened again (11.3 mmol/L). Urine and blood cultures returned positive for Klebsiella Pneumoniae (pan-sensitive). She was treated appropriately for sepsis since presentation to the emergency room, but her clinical condition (and lactic acid) continued to deteriorate. On the second day of admission, the patient developed respiratory failure requiring intubation and mechanical ventilation. Her hypotension persisted and she required multiple pressors. Sustained low-efficiency dialysis was restarted due to worsening of metabolic acidosis. Patient then became unresponsive on hospital day 4. Sedation was stopped and CT of the brain revealed significant edema and mild bilateral subarachnoid hemorrhage. Patient was confirmed brain dead by perfusion study.

Conclusion

This case illustrated a constellation of factors that led to a poor outcome. Off label use of metformin for weight loss, late diagnosis of acute severe renal failure, and delayed diagnosis of MALA all contributed to the poor outcome in this patient. Even though MALA has a relatively low estimated incidence rate, this case emphasizes the importance of medication reconciliation and the need for recognition that MALA can present as sepsis.

Presentation: No date and time listed
ODP225 Mixed Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome with recent diagnosis of Diabetes Mellitus.
Authors: Adyanthaya Sindhoora , Anila Fnu , Jackson Bethany
Published: November 2022

Background

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia syndrome (HHS) are often discussed as two distinct clinical entities but can present in the same patient. Combined DKA and HHS is associated with higher mortality than either DKA or HHS alone. Clinical case: A 68 years old female diagnosed with type 2 diabetes 3 months prior to hospitalization was brought into the hospital with severe hyperglycemia and altered mental status. On exam she was unresponsive with grimace only to sternal rub. Pulse was elevated at 113, RR 31, temperature 100.3, and blood pressure 130/80. Initial labs showed severe hyperglycemia with glucose of 1454 (74-106 mg/dL), elevated beta-hydroxybutyrate of 8.6 (0. 02-0.27 mmol/L), sodium 138 (135-145 mmol/L), potassium 5.3 (3.6-5.2 mmol/L), serum bicarbonate 16 (21-32 mmol/L), anion gap 31 (6-18), plasma osmolality 353 (273-304 osm/kg), pH 7.33 (7.35-7.45) and lactic acid 4 (0.7-1.9 mmol/L). DKA protocol with normal saline, intravenous insulin infusion, and potassium replacement initiated and patient was transferred to ICU for further management. Sequential labs revealed development of hypernatremia with calculated free water deficit of 8.8 liters. Fluids changed to ½ normal saline. On Day 2 of hospitalization, she became responsive. She had resolution of acidosis but continued to have severe hypernatremia with peak sodium level of 163 on day 3. Urine studies showed urine osmolality of 700 mOsm/kg ruling out diabetes insipidus; urine sodium level was 5 mmol/L. Fluids were again changed to ¼ Normal saline with careful monitoring of serum sodium and glucose at 2 hour intervals. Hypernatremia resolved with aggressive fluid resuscitation. Her A1c prior to discharge was found to have increased to 13.3% from 6.5% (< 5.6%), 3 months prior. Prior to discharge she had measurable C-peptide, insulin autoantibodies and negative GAD antibodies making autoimmune diabetes unlikely.

Conclusion

Individuals with concomitant DKA and HHS may have normal sodium or even hyponatremia at presentation due to the pseudo-hyponatremia induced by severe hyperglycemia. However, actual sodium concentration may be markedly elevated due to the osmotic diuresis induced by severe hyperglycemia. Aggressive fluid resuscitation is required to treat the profound dehydration found in HHS but the serum sodium concentration must be monitored carefully. A switch from normal saline to hypotonic fluids may be necessary to treat hypernatremia in HHS but overly rapid correction of serum sodium must be avoided for volume overload especially in elderly, owing to heart failure and due to higher mortality. The incidence of hypernatremia is noted in 14% of children and 27% of adults, however degree of hypernatremia is variable from mild to moderate and in rare instances is severe.

Presentation: No date and time listed
ODP233 Predicting Hospital Readmission for Patients with Diabetes: A Comparison of Models
Authors: Rubin Daniel , Hai Ameen Abdel , Obradovic Zoran , Brown Jeremiah , Paranjape Anuradha , Livshits Alice , Weiner Mark
Published: November 2022

In patients with diabetes, current models for predicting the risk of readmission within 30 days of hospital discharge vary in performance. We previously published the Diabetes Early Readmission Risk Indicator (DERRI TM), a logistic regression (LR) model based on 10 simple features with modest predictive performance (C-statistic 0.69). The current study aims to develop a more accurate model using deep learning on electronic health record (EHR) data. We electronically abstracted data from 36,563 patients with diabetes and at least 1 hospitalization at an urban, academic medical center between 7/1/2010 and 12/31/2020. One hospitalization per patient (index hospitalization) was randomly selected for analysis. A deep learning long short-term memory Recurrent Neural Network (RNN) was developed and compared to traditional linear and non-linear models: LR, AdaBoost, and Random Forest (RF). Models to predict unplanned, all-cause readmission were developed using demographics, vital signs, diagnostic and procedure codes, medications, laboratory tests, and administrative data as defined by the National Patient-Centered Clinical Research Network (PCORnet) Common Data Model. Unplanned readmissions were identified according to the Centers for Medicare and Medicaid (CMS) definition. A look-back time of 1 year before the index hospitalization and up to 60 previous ambulatory and hospital visits were used for learning and inference. Data dimensionality was reduced to 3,000 features by Singular Value Decomposition. The RNN model C-statistic is significantly greater than those of the traditional models (RNN 0.78, AdaBoost 0.71, RF 0.73, and LR 0.71, p<0. 0001). Likewise, the F1-score is numerically greater for the RNN model (RNN 0.76, AdaBoost 0.75, RF 0.75, LR 0.72). Direct comparison to the DERRI TM is limited by lack of EHR data on two of the component variables (employment status and zip code). The deep learning RNN model outperforms the DERRI TM and is based on more generalizable EHR data. This new model may provide the basis for a more useful readmission risk prediction tool for patients with diabetes. Deep learning models may outperform traditional models at predicting readmission risk in this population.

Presentation: No date and time listed
ODP238 RELATIONSHIP BETWEEN BODY COMPOSITION, POST PRANDIAL GLUCOSE AND INSULIN FOR EARLY PREDICTION OF TYPE 2 DIABETES AND CARDIOVASCULAR RISK.
Authors: Moya Elena Amoroso , Nicollade Marcelo , Cellery Herbarth Torres
Published: November 2022

Different studies report that visceral fat percentage, visceral adiposity index (VAI) and body mass index (BMI) are considered markers of dysfunction and adipose tissue distribution, which are considered early detection tools and indirect expression of cardio metabolic risk; however it is also reported that post prandial glucose and insulin are abnormalities that detect early type 2 diabetes and cardiovascular risk, due to their toxic effect on the vascular endothelium. The objective of the research was to evaluate the association of body composition, glucose and insulin postprandial for early prediction of diabetes and cardiovascular risk. It is a non-experimental study of cross-sectional design, in a total population of 271 adults between the ages 19 and 65 years, without diabetes, in a non-random sample calculated with 95% confidence level of patients attending outpatient clinics of private and IESS hospitals of Riobamba. Descriptive statistics were performed for all variables. With the variables related to cardio metabolic risk such as age, sex, abdominal circumference, mean arterial pressure, BMI, visceral fat and biochemical measures of HbA1c, fasting glucose, postprandial glucose and insulin, HOMA-IR index, and HDLC, triglycerides, cardio vascular risk index given by the ratio triglycerides/HDLc cholesterol over 3.5. These variables were grouped by a multivariate cluster analysis, kmeans, and two homogeneous groups were obtained, different from each other and different from the others, and then the average cardiovascular risk in each group was calculated. A 9: 1 ratio of women/men was found, for cluster 1 the average age was 49, and in cluster 2 it was 48 years, TAM: 87.5 mmHg, BMI: 27.12, PAB: 109 cm, visceral fat 12.79 and cardiovascular risk 4.78. In group 2 with predominance in cluster 2 the average values of the variables studied were significantly higher with a statistically significant p value for the differences between groups of postprandial glucose and insulin (p less than 0. 05).

Conclusions

postprandial glucose and insulin are early predictors of cardiovascular risk and diabetes. Key words: postprandial glucose, postprandial insulin, cardiovascular risk, body composition.

Presentation: No date and time listed
ODP240 Routine Glucose-lowering Therapies and Risk of Adverse Outcomes in COVID-19 Patients with Diabetes: a Network Meta-analysis
Authors: Zhu Zheng , Chen Gang
Published: November 2022

Background

We aimed to evaluate the mortality of eight glucose-lowering therapies for COVID-19 patients with diabetes prior to diagnosis of COVID-19.

Methods

We searched PubMed, Embase, Cochrane Central Register, Web of Science, and ClinicalTrials.gov through June 2021. COVID-19 patients with diabetes while receiving glucose-lowering therapies for at least 14 days prior to COVID-19 confirmed were included. The Newcastle Ottawa scale (NOS) was used to assess the risk of bias in nonrandomized studies. Bayesian network meta-analyses were performed.

Results

Eleven distinct observational studies (3,631,682 COVID-19 patients with diabetes mellitus) were included. Compared with insulin, DPP4i, secretagogues, glucosidase inhibitors, and thiazolidinediones, the incidence of adverse outcomes in diabetics who took SGLT2i was relatively lower: OR 0.30 (95% CrI 0.17-0.55); 0.42 (0.24-0.83); 0.43 (0.24-0.83); 0.32 (0.16-0.70); 0.47 (0.23-0.95). The SUCRA value of SGLT2i was the lowest (1.8%), followed by GLPIRA (22.1%) and biguanides (33.3%).

Conclusion

SGLT2I may be an optimal choice for diabetics before COVID-19 infection. GLP1RA and guanidine can also be a good choice for the protection of diabetics during COVID-19 pandemic times.

Presentation: No date and time listed
ODP242 Safety of SGLT2-Inhibitors in Patients with Multiple Myeloma and Diabetes
Authors: Shyu Margaret , Rosa Tracey , Mazori Alon , Gallagher Emily
Published: November 2022

Background

An estimated 10-20% of patients with multiple myeloma (MM) have type 2 diabetes (T2DM). About half of patients with MM will experience renal insufficiency,the risk of which increases in the setting of T2DM. While sodium-glucose cotransporter 2 inhibitors (SGLT2i) are beneficial in patients with chronic kidney disease (CKD) due to diabetic or hypertensive nephropathy, the role of SGLT2i in MM-related CKD is unknown. Moreover, as MM therapies target the immune system, concurrent use with SGLT2i may increase the risk of adverse events such as infections. The current work is the first to examine the potential benefit and safety of SGLT2i in patients with MM and T2DM.

Methods

This study was approved by the Institutional Review Board. A retrospective cohort study was performed on patients aged 18 years or older with MM who received SGLT2i therapy between March 2013 and December 2020 at a quaternary academic medical center. Electronic medical records were reviewed for the following data: demographics, comorbidities, MM parameters, medication and medical history, SGLT2i usage and duration, and hemoglobin A1c(HbA1c) and serum creatinine pre- and post-SGLT2i initiation. Data are presented as mean ± standard deviation or counts and percentages, and was analyzed using SPSS software (version 25. 0, IBM Corp).

Results

In total, 50 patients were identified. Patients who were diagnosed with MM after initiation of SGLT2i (n= 12), did not have any MM data available (n=1), or for whom SGLT2i usage could not be verified (n= 4) were excluded. Thirty-three patients were included in the final analysis. The mean age was 63 (±7.8) years, 63.6% were male, and 87.9% had active MM or MM in remission. Most had received stem-cell transplantation (55. 0%) and multiple lines of chemotherapy (63.6%) prior to SGLT2i initiation. The average HbA1c was 7.4% (±1.2%) and 20% of patients had CKD prior to SGLT2i initiation. The overall SGLT2i discontinuation rate was 42.4%, and the mean duration of therapy was 2.2(±1.5) years. Notably, 21.4% of discontinuation events were due to an increase in creatinine; however, for the entire cohort, there were no statistically significant changes in serum creatinine, total body weight, HbA1c, or 24-hour urine protein at 15 months’ follow-up. Other reasons for SLGT2i discontinuation included loss to follow-up, change of health insurance coverage for SGLT2i, and unrelated hospital admission. Genitourinary infection was not cited as a reason for any SGLT2i discontinuation.

Conclusion

SGLT2i therapy may be safe in patients with MM and T2DM, but no benefit was found with respect to serum creatinine, HbA1c, or 24-hour urine protein. Prospective research is required to further evaluate the potential benefit and safety of SGLT2i therapy in this population.

Presentation: No date and time listed
ODP253 Utilizing EMR Optimization to Streamline Inpatient Blood Glucose Management and Improve Clinician Efficiency
Authors: Mathews Tony
Published: November 2022

Introduction

Diabetes mellitus is a common disease that is prevalent in over 30.3 million people in the US. The annual cost of diabetes related inpatient care is over $97 billion. Poor glycemic control has been associated with increase hospital length of stay, increased cost and increased mortality. One of the challenges faced by clinicians in managing inpatient blood glucose is the lack of easy access to necessary data. The various pieces of information needed for comprehensive inpatient blood glucose management were in different parts of the EMR and required multiple clicks to access. The glucose flowsheet 2. 0 was created to remedy this problem. The flowsheet aggregated data necessary onto one screen and displayed it in a context specific manner. The flowsheet aimed to decrease the amount of time spent and the number of clicks needed to gather data clinicians need to manage blood glucose in inpatients. Method/Quality Improvement action: Glucose flowsheet 2. 0 aggregates the following information. Blood Glucose, Fingerstick Glucose, A1c, Dextrose infusions, Steroid (name/dosing), Tube feeds (name/rate), Nutritional Supplement (name//frequency), Percentage of Meal eaten, Vasopressors and Creatinine/GFR. After the flowsheet went live inpatient providers and nursing staff were sent an email educating them about the changes to diabetes flowsheet and how to access it. Six Months after the diabetes flowsheet went live a 6-question survey was sent to approximately 300 residents and advanced practitioners taking care of inpatients and received 69 responses.

Results

The survey had a response rate >20% with a confidence interval of 90% and less than 10% margin of error between the survey responders and the population of clinicians involved in adult inpatient management. 90.7% of survey respondents agreed/strongly agreed "flowsheet 2. 0 gives me relevant and up to date information needed manage blood glucose for hospitalized patients." 87.7% of respondents agreed/strongly agreed that "allows me to view more relevant diabetes and blood glucose related data than on one screen compared to glucose flowsheet 1. 0." 80% and 85% of participants agreed/strongly agreed that the flowsheet 2. 0 improved efficiency by reducing time needed and clicks required to gather necessary data for inpatient blood glucose management. 80.6% of respondents agreed/strongly agreed that "Glucose Flowsheet 2. 0 helps me to save time without compromising quality of diabetes care." 80.6% of respondents agreed/strongly agreed that "the changes implemented in the Glucose flowsheet 2. 0 makes it more likely for me to minimize, prevent, identify or correct errors". Clinicians found the optimization of EMR to be a net positive that saves time without compromising quality of care. This quality improvement project shows that data presented in EMR can be optimized in a context specific manner to improve clinicians’ sense of efficiency.

Presentation: No date and time listed
ODP258 CRHR1 gene shows extensive linkage to major depression and type 2 diabetes in Italian families
Authors: Amin Mutaz , del Bosque-Plata Laura , Gonzalez Manuel Gea , Wu Rongling , Postolache Teodor T , Vergate Michael , Gordon Derek , Ott Jurg , Gragnoli Claudia
Published: November 2022

Background

Major Depressive Disorder (MDD) and Type 2 Diabetes (T2D) are heterogeneous polygenic and complex disorders and are often comorbid. This shared comorbidity can be partially explained by several genetic, environmental, and hormonal factors such as hypercortisolism in MDD and a subset of patients with T2D. CRH receptor-1 (CRHR1) dysfunction may explain the MDD- and T2D-hypercortisolism, at least in a subgroup of patients. CRHR1-variants predisposing to impaired CRHR1 dosage and/or function may lead to hypercortisolism (substrate for serotonin dysfunction and MDD), as well as hyperglycemia, insulin resistance, and increased visceral fat, all T2D-traits. We hypothesize that CRHR1-variants may impair the stress and cortisol response, conferringincreased risk for MDD, T2D, and MDD-T2D comorbidity.

Methods

Using 212 Italian families with T2D, enriched T2D-familial history, and MDD, we amplified and tested 158 CRHR1 SNPs by two-point parametric analysis for linkage and linkage-disequilibrium (LD), using the models dominant (D) and recessive (R), with complete (1) and incomplete (2) penetrance (Pseudomarker).

Results

We detected linkage to and/or LD with MDD: for 93 SNPs (D1), 57 SNPs (D2), 91 SNPs (R1), and 14 (R2); and T2D for 15 SNPs (D1), 18 SNPs (D2), twelve SNPs (R1) and ten SNPs (R2), for a total of 122 SNPs. Specific LD-blocks’ underlined each disorder without overlap. Of note, three independent SNPs were comorbid forMDD and T2D. All risk SNPs are intronic, except for one synonymous, one splice site, one missense, and one 3'UTR. In-silicoanalysis detected functional gene and tridimensional protein changes in a risk-SNP.

Conclusion

We are the first to report CRHR1 in linkage and LD with MDD and T2D in T2D-families. CRHR1contribution to MDD appears stronger thanthe contribution to T2D and may thus antecede its onset . Genetically impaired stress and cortisol response may lead to comorbid MDD-T2D, likely a molecular-clinical entity in a subset of families. Our findings should be replicated in families from other ethnic groups.

Presentation: No date and time listed
ODP632 Preadmission Use Of Antidiabetic Medications And Mortality Among Patients With Covid-19 Having Type 2 Diabetes: A Meta-analysis
Authors: Nguyen Nam Nhat , Ho Dung S , Nguyen Hung Song , Dang Ngan Ho Khanh , Li Hung-Yuan , Lin Chia-Yuan , Chiu Hsiao-Yean , Chen Yang-Ching
Published: November 2022

Introduction

Diabetes is an independent predictor of poor outcomes in patients with COVID-19. We compared the effects of the preadmission use of antidiabetic medications on the in-hospital mortality of patients with COVID-19 having type 2 diabetes.

Methods

A systematic search was performed until November 30, 2021. We used a random-effects meta-analysis to calculate the pooled OR (95% CI).

Results

We included 61 studies (3,061,584 individuals). We found some medications protective against COVID-related death, including metformin, GLP-1RA and SGLT-2i. DPP-4i and insulin users were more likely to die during hospitalization. SU, TZD, and AGI were mortality neutral. Metformin use was associated with better outcome in a dose-response manner.

Conclusions

Metformin, GLP-1RA, and SGLT-2i were associated with lower mortality rate in patients with COVID-19 having type 2 diabetes. DPP-4i and insulin were linked to increased mortality. SU, TZD and AGI were mortality neutral.

Presentation: No date and time listed
ODP633 Impact of Undiagnosed Diabetes on Cardiovascular Events and Clinical outcomes in Patients Hospitalized with COVID-19 Pneumonia
Authors: Krishnasamy Sathya , Sheikh Daniya , Ali T’Shura , Arnold Forest , Ramirez Julio , Furmanek Stephen , Clemons Victoria , Abdelhaleem Ahmed , Salunkhe Vidyulata , Akbar Usman Ali , Chlebowy Diane
Published: November 2022

Type 2 diabetes has emerged as an important risk factor for poor prognosis in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hyperglycemia can independently predispose the patients with SARS-CoV-2 to adverse outcomes, irrespective of the diagnosis of diabetes 1. Despite the accentuated risk, there is limited evidence about the complex interplay of undiagnosed diabetes and SARS-CoV-2 pneumonia on the clinical outcomes. We propose to investigate the cardiovascular events and clinical outcomes in patients with undiagnosed and type 2 diabetes hospitalized with SARS-CoV-2 pneumonia.

Methods

This retrospective study included patients hospitalized with SARS-CoV-2 pneumonia between March 7, 2020, through March 30, 2021. The diagnosis of SARS-CoV-2 pneumonia required a positive reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2, presence of new or worsening pulmonary infiltrates on computed tomography scan or chest X-ray, and at least one of the following: new or increased cough, a temperature of >37.8 °C or dyspnea. The diagnosis of undiagnosed diabetes was determined in patients with no previous history of diabetes and glycated hemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol) or an admission serum glucose ≥ 200 mg/dL (≥ 11.1 mmol/mol). The outcomes included in-hospital cardiovascular events, intensive care unit (ICU) admissions and in-hospital mortality. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for association of undiagnosed diabetes and type 2 diabetes for individual outcomes. Results Among the 1,645 adults hospitalized with SARS-CoV-2 pneumonia, 107 (10.8%) patients were identified with undiagnosed diabetes and 634 (39%) had established diagnosis of type 2 diabetes. Patients with undiagnosed diabetes had increased odds of developing cardiovascular events (OR: 1.73, 95% CI 1. 07, 2.80), ICU admissions (OR: 1.61, 95% CI 1.10, 2.34), and mortality (OR: 1.77, 95% CI 1. 02, 3. 07), compared to patients type 2 diabetes and no diabetes. A prior history of type 2 diabetes was not significantly associated with primary study outcomes.

Conclusions

Patients with undiagnosed diabetes hospitalized with SARS-CoV-2 pneumonia have an increased risk of developing cardiovascular complications and overall poor clinical outcomes compared to patients with type 2 diabetes and no diabetes. Implementation of healthcare-wide strategies for screening and early intervention of prediabetes and diabetes are needed to improve the disease outcomes in the current pandemic and future public health threats. References Khunti, K., et al., COVID-19, Hyperglycemia, and New-Onset Diabetes. Diabetes Care, 2021. 44(12): p. 2645-2655.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
OR03-1 Achievement of HbA1c <6.5% without weight gain and hypoglycemia in people with type 2 diabetes treated with tirzepatide across the phase 3 SURPASS program
Authors: Allen Sheryl Elaine , Cheng Alice , Choudhary Pratik , Levine Joshua A , Ranta Kari , Thieu Vivian Thuyanh , Valderas Elisa Gomez , Lingvay Ildiko
Published: November 2022

Introduction

Tirzepatide, the novel dual GIP/GLP-1 receptor agonist for the treatment of type 2 diabetes, has been shown to reduce HbA1c and weight, with more patients achieving HbA1c ≤6.5%, compared to placebo and active comparators in the phase 3 SURPASS 1-5 studies. This analysis compared the percentage of patients treated with tirzepatide achieving a composite endpoint of HbA1c <6.5% without weight gain and hypoglycemia in these studies.

Methods

We compared the proportion of participants achieving the composite endpoint between the tirzepatide (5, 10, or 15 mg) and respective comparator groups while patients were on treatment and without rescue medication. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. End of treatment HbA1c and weight were evaluated at week 40 (SURPASS-1, 2, 5) and week 52 (SURPASS-3, 4). Weight gain was defined as a change from baseline in weight <0.1 kg. Hypoglycemia included blood glucose level <54 mg/dL with symptoms of hypoglycemia or severe hypoglycemia.

Results

In SURPASS-1, 2, 3, 4, and 5 significantly more patients treated with tirzepatide achieved the composite endpoint compared to placebo or comparator (P≤0.002). As a monotherapy in SURPASS-1, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than placebo (75%, 78%, 83%, and 5%, respectively; all P<0.001). As add-on to metformin in SURPASS-2, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than semaglutide (67%, 77%, 83%, and 59%, respectively; P=0.002, P<0.001, P<0.001, respectively). When compared to basal insulin in SURPASS-3, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than insulin degludec (63%, 76%, 82%, and 13%, respectively; all P<0.001). When added to 1-3 oral antihyperglycemics in SURPASS-4, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than insulin glargine (56%, 68%, 75%, and 10%, respectively; all P<0.001). As an add-on to basal insulin in SURPASS-5, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than placebo (63%, 70%, 76%, and 8% respectively; all P<0.001).

Conclusions

Significantly more patients treated with tirzepatide achieved a composite endpoint of HbA1c <6.5% without weight gain or hypoglycemia than those treated with placebo, semaglutide, insulin degludec, or insulin glargine in the phase 3 SURPASS program.

Presentation: Saturday, June 11, 2022 11:30 a.m. - 11:45 a.m.
OR03-2 Phase 1, Randomized, Controlled Trial of GFB-024, a Once-Monthly CB1 Inverse Agonist, in Healthy Overweight and Obese Participants and in Participants with Type 2 Diabetes Mellitus
Authors: Bilic Sanela , Dagon Yossi , Gustafson Thomas , Johnson Leslie , Lawler John , Rudolph-Own Lori , Gaich Gregory , Tucker Edwin
Published: November 2022

Evidence from nonclinical studies suggests a role of cannabinoid-1 receptor (CB1) in the development of diabetic nephropathy (DN). Kidney CB1 expression is upregulated in podocytes and tubular cells in murine models of obesity and diabetes mellitus (DM). Inhibition by CB1 inverse agonists has been shown to ameliorate diabetes-induced albuminuria, inhibit kidney fibrosis and inflammation, and prevent podocyte dysfunction. Mouse models of DM have shown that genetic deletion of CB1 in podocytes or proximal tubular cells protects against glomerular and tubular dysfunction.

GFB-024 is a recombinant humanized monoclonal antibody functioning as a CB1-specific inverse agonist. Pharmacodynamic studies demonstrated that GFB-024 protects human podocytes in vitro. Targeting the CB1 pathway with GFB-024 is a potentially novel approach to protecting podocytes from injury in patients with CB1-associated DN.

In a phase 1, randomized, double-blind, placebo-controlled single ascending dose (SAD) trial, we evaluated the safety, tolerability, pharmacokinetics (PK), and immunogenicity of GFB-024 in up to 56 healthy overweight and obese (BMI 25–40 kg/m2) participants.

A total of 38 subjects have completed 5 cohorts in the SAD, receiving single doses of 5 mg to 300 mg administered subcutaneously. GFB-024 was well tolerated, and there were no dose-limiting adverse effects.

PK exposures achieved in the trial exceeded the estimated efficacious exposure, based on four different in vitro activity assays. Absorption was prolonged with flat exposure over the first 7 days, with a Tmax ranging from approximately 4-7 days. Elimination half-life was approximately 12-13 days, with exposures remaining in the estimated efficacious range at 28 days for all but the lowest dose tested.

In summary, GFB-024 was safe and well tolerated following single doses of up to 300 mg. PK analysis demonstrated potentially efficacious exposure, a prolonged absorption phase, and elimination half-life compatible with once-monthly dosing.

Presentation: Saturday, June 11, 2022 11:45 a.m. - 12:00 p.m.
OR24-3 GPR31 Mediates the Proinflammatory Reponses in the Setting of Diabetic Inflammation
Authors: Anderson Ryan , Avadhanam Sriya , Kulkarni Abhishek , Mirmira Raghavendra , Nelson Jennifer , Tersey Sarah
Published: November 2022

The pathogenesis of type 1 diabetes (T1D) involves the interaction of the immune system with pancreatic islets, featured by inflammation in both macrophages and β cells. The enzyme 12-lipoxygenase (12-LOX) is expressed in macrophages and β-cells, produces the eicosanoid 12(S)-HETE and promotes inflammation. GPR31 has recently been identified as a 12(S)-HETE receptor. GPR31 protein levels increase in human islets after cytokine-induced inflammation. To elucidate the role of GPR31 in the 12-LOX pathway and during diabetic inflammation, we generated Gpr31b-/- mice on the C57BL/6J background. Gpr31-/- mice are viable, with normal body weight, glucose tolerance, and β-cell mass. Upon low dose streptozotocin treatment to induce β-cell inflammation, Gpr31b-/- mice remained normoglycemic unlike wildtype littermates and maintained near normal β-cell mass. To examine GPR31 in islet inflammation, RNA sequencing was performed on isolated mouse islets treated with a cytokine cocktail (IL-1β, IFN-γ, TNF-α). Both wildtype and Gpr31b-/- islets showed expected increases in Nos2 and Il1b after cytokine treatment. By contrast, Gpr31b-/- islets, showed changes in Gene Ontology pathways related to ER stress, oxidative stress, protein targeting, and MAPK activity compared to wildtype islets after cytokine treatment. To test a role for GPR31 in macrophage function, we first interrogated its role in the generation of proinflammatory macrophages upon polarization in vitro to the M1-like state using LPS and IFN-γ; under these conditions, we found no differences between Gpr31b-/- and wildtype macrophages, as assessed by flow cytometric analysis, suggesting that GPR31 does not play a role in macrophage polarization. Next, we tested if GPR31 is required for the ability of macrophages to migrate. To do this, bone marrow derived macrophages were isolated from Gpr31b-/- and wildtype littermates and in vitro migration assays were performed using Transwell chambers. We observed a significant decrease in migration of the Gpr31b-/- macrophages compared to wildtype macrophages. Taken together, our data support the concept that GPR31 promotes proinflammatory responses in both macrophages and pancreatic islets.

Presentation: Monday, June 13, 2022 11:30 a.m. - 11:45 a.m.
OR24-4 Targeting Hyperglucagonemia Reverses Glucagon Resistance
Authors: Bernal-Mizrachi Ernesto , Kramer Nadejda Bozadjieva , Gittes George , Lubaczeuski Camila
Published: November 2022

Elevation of glucagon levels and increase in alpha-cell mass are associated with states of hyperglycemia in diabetes. A better understanding of the molecular mechanisms governing glucagon secretion could have major implications in understanding abnormal responses to hypoglycemia in diabetic patients and provide novel avenues for diabetes management. Stimulation of glucagon secretion in hypoglycemia, or by amino acids, induces hepatic glucose production via cellular mechanisms including suppression of glycogenesis and glycolysis and stimulation of glycogenolysis and gluconeogenesis. The close link between amino acids and the alpha-cell is highlighted by the liver–alpha-cell axis. This axis was identified by the major increase in alpha-cell hyperplasia and hyperglucagonemia in models of reduced glucagon action in hepatocytes genetically or pharmacologically by treatment with glucagon receptor antagonists, which was subsequently attributed to the dramatic rise in amino acids. Induction of mTORC1 by constitutive genetic deletion of TSC2 in alpha-cells (aTSC2KO) recapitulated the effects of chronic hyperaminoacidemia with increases in alpha-cell mass and chronic hyperglucagonemia indicating that mTORC1 mediates amino acids signals in alpha-cells. However, the effects of acute versus chronic induction of alpha-cell mTORC1 signaling on these outcomes have not been explored. Using mice with doxycycline induction of Rheb (activator of mTORC1 signaling) (aRhebTg) and inducible Cre-mediated deletion of the mTORC1 inhibitor, TSC2, in alpha-cells (iaTSC2KO), we showed that induction of hyperglucagonemia is associated with two phases: Acute phase characterized by impaired glucose tolerance because of increased gluconeogenesis and glucose output by the liver. And a chronic phase, characterized by normalization of glucose tolerance due to downregulation of the hepatic glucagon receptor (Gcgr), Pepck, and some genes involved in amino acid metabolism and urea production. Importantly, the consequences of chronic hyperglucagonemia were reversible after normalization of glucagon levels by turning off alpha-cell Rheb expression. These studies uncovered the acute versus chronic effects of hyperglucagonemia on glucose homeostasis and further demonstrate that glucagon resistance is a reversible process. These observations provide insight into the impact of glucagon in the pathogenesis of hyperglycemia and the physiological effects of administration of dual GLP1/Glucagon receptor agonists.

Presentation: Monday, June 13, 2022 11:45 a.m. - 12:00 p.m.
OR28-1 Racial and Ethnic Disparities in Diabetes Technology Use amongst Persons with Type 1 Diabetes
Authors: Alzedaneen Yazan , Bukhari Khulood , Munir Kashif , Sagar Prem Raj , Park Jeayoung
Published: November 2022

Objective

Despite recent advances in diabetes technology, the distribution of healthcare resources is often unequal among racial and socio-economic groups. A recent multicenter study looking at technology use amongst young adults with T1D demonstrated that socioeconomic status (SES) was not the sole driver of racial/ethnic disparities and that adjustment for income, insurance level, and health literacy did not significantly attenuate disparities. Here we present a retrospective cohort study looking at racial/ethnic disparities in insulin pump and CGM use in adults with T1D at an urban university hospital system.

Methods

We reviewed the charts of all adults aged 18 to 89 with T1D who attended the University of Maryland Center for Diabetes and Endocrinology (UMCDE) between 1/2019 and 12/2019. Age, gender, race/ethnicity, type of insurance, ZIP code, BMI, A1c, method of insulin delivery, and type of glucose monitoring device were obtained from each chart. We utilized the 2019 US Census data to determine the median income for each ZIP code. Patient charts were re-accessed in 2021 to check for changes in diabetes technology use from 1/2020 until 12/2021. Logistic regression modeling was done in PRISM to control for age, gender, race, insurance type, ZIP code, last known provider, BMI, and A1c. Hosmer-Lemeshow test was done to evaluate goodness of fit. Stratified analysis was done for potential confounders such as insurance type and income. The Breslow-Day test and Likelihood Ratio test for nested models were used to evaluate their degree and significance.

Result

A total of 532 adults were included in the study; 277 identified as non-Hispanic (NH) White, 204 identified as NH Black, 7 identified as Hispanic, and 44 identified as other racial/ethnic groups. NH White adults had a significantly higher insulin pump use when compared to NH Black (adjusted ratio 54.0% vs. 18.4%, OR 2.43 after regression, 95%CI [1.41-4.22]). Similarly, NH White adults had significantly higher CGM use when compared to NH Black (66.5% vs. 35.2%, OR 2.00 after regression, 95%CI [1.24-3.22]). Disparities between NH White and NH Black patients did not resolve throughout 2020-2021. Insurance type was a potential effect modifier for CGM prescriptions between NH White and NH Blacks (Crude OR 4.04, Commercial Strata OR 2.68, Medicaid 1.79, Medicare 2.79, Other/Self-pay 25.7, p=0.039 on Breslow-Day test). There was large heterogeneity in the rate of Pump or CGM prescriptions between providers.

Conclusion

NH White adults with T1D were significantly more likely to have been prescribed diabetes-related technologies when compared to other racial/ethnic groups, and this difference did not resolve over 2 years of follow-up. Future directions include a comprehensive survey of our population regarding patient-derived and patient-perceived factors driving disparities beyond socioeconomic status.

Presentation: Tuesday, June 14, 2022 9:45 a.m. - 10:00 a.m.
OR28-6 Combating Therapeutic Inertia: Project ECHO for Diabetes Improves Primary Care Providers’ Comfort and Use of Diabetes Medication and Technology
Authors: Ajabnoor Yasser , Aldous Annette , Bouchonville Matt , Cuttriss Nicolas , Ehrhardt Nicole , Hood Nancy , Peek Monica , Thomas Celeste , Zou Tracy
Published: November 2022

Background

Despite newer diabetes medications and technology being available, therapeutic inertia persists and there are more people living with "uncontrolled" diabetes than meeting A1c targets. Here we evaluate how the ECHO© model for diabetes management changed prescribing practices among participating primary care providers (PCPS).

Methodology

Three unique diabetes ECHO programs evaluated comfort or perception of prescribing practice changes for local community PCPs (n=74) in four regions (Illinois, District of Columbia, New Mexico, and Washington). One site representing two regions collected pre- and post-program participant surveys (n=45) while two sites collected post-program surveys only (n=29), in which respondents reported perceptions of changes resulting from participation in ECHO. Participants reported their use of technology (professional and personal continuous glucose monitoring (CGM) and insulin pumps) and medications (insulin and non-insulin).

Results

On a 4-point Likert scale, PCPs’ (n=45) average self-reported prescription use for newer diabetes medications with cardiovascular indications increased from 3.07 (sometimes) to 3.84 (sometimes-always).

Presentation: Tuesday, June 14, 2022 11:00 a.m. - 11:15 a.m.
PSUN171 CORRELATIONS BETWEEN SERUM AND TEAR PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1) AND TISSUE PLASMINOGEN ACTIVATOR (tPA) IN PATIENTS WITH DIABETIC RETINOPATHY
Authors: Jasmiad Nurbadriah , Ghani Rohana Abd , Ghani Rohana Abd
Published: November 2022

Introduction

Diabetic retinopathy (DR) is a leading cause of blindness and visual disability, worldwide. The aim of the study was to investigate the correlation between tears and plasma levels of activity of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in patients with diabetic retinopathy.

Method

Patients with T2DM and DR (n=26) were enrolled in this study. Blood and tears samples were obtained from both groups and analysed for PAI-1 and tPA activities. Anthropometric measurements were also obtained.

Results

There was no correlation between serum and tear PAI-1 levels with a Spearman's coefficient of 0.028 (p=0.928). We were also unable to detect significant correlations between serum and tear tPA levels. However, there was a significant positive correlation between levels of tears PAI-1 and BMI (r=0.555, p=0.026).

Conclusion

This present study demonstrated no significant correlations between tears and serum PAI-1 and tPA, which was most likely due to the small sample size. However, the significant correlation between tear PAI-1 levels with BMI could indicate the potential role of tear biomarkers in diabetic retinopathy in obese patients.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN181 Diabetes-related outcomes following use of basal-bolus insulin vs. premixed insulin in a VA population with Type 2 diabetes: A retrospective chart review.
Authors: Izuora Kenneth , Batra Kavita , Bai Ravisha , Yap Charmaine
Published: November 2022

Background

Treatment of diabetes mellitus (DM) with basal bolus insulin analogs (BB) requires up to five injections a day. The complexity of BB therapy may adversely influence patient compliance. A simpler and cheaper regimen with premixed insulin (PM) typically involves two injections a day but is perceived to be less effective in managing DM. The purpose of this research project was to compare DM-related outcomes between BB regimens (insulin detemir or glargine plus aspart, lispro or regular insulin) and PM insulin regimens (70/30 insulin NPH/regular) among our veteran population with type 2 DM.

Research design and Methods

This is a retrospective chart review that included 140 veterans (70 in BB group and 70 in PM group) with type2 DM. Subjects aged 18 years or above and those having A1C level ≥ 8% were included. Subjects with type 1 diabetes or who switched their insulin regimen during the follow-up period were excluded. The included subjects were followed for a year, after the start of respective insulin therapies to examine change in A1c (primary outcome) levels across groups. Data were analyzed using Chi-square/Fisher exact tests and logistic regression. All analyses were conducted using SPSS version 27 and SAS9.4.

Results

Out of 140 enrolled subjects, 94% were males with average age of 65.7 ± 10.1 years and DM duration of 12.9±9 years. There was no significant difference in age, gender, baseline A1c, BMI or duration of DM between the two groups. Following treatment initiation, there was no statistically significant difference between the BB and PM insulin groups for change in A1c (-1.9±1.8 vs -2.1±1.9%, p = 0.3) or for the rate of hypoglycemia (30% vs 21.4%, p = 0.3) respectively. Although the average BMI increased in both groups, the change was similar for both BB and PM groups (0.84±3.1 vs 0.4±2.2 kg/m2 respectively, p = 0.2). A logistic regression controlling for the confounders of hypoglycemia, found that the type of insulin used did not predict the development of hypoglycemia [OR 0.594, (0.251, 1.404)].

Conclusion

There were no significant differences in A1c change, rate of hypoglycemia, and change in body mass index in patients treated with either BB or PM insulin among our study population. These results suggest that PM insulin is equally effective as the BB and its use can potentially improve patient compliance and reduce the cost of care.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN186 Comparison of Thyroid Function Test Screening in Patients with Diabetes Mellitus Type 2 versus Patients with Diabetes Mellitus Type 1
Authors: Aasim Alina , Cruz Maria , Potluri Sai Deepika , Schroeder Pamela , Yi Crystal
Published: November 2022

Diabetes mellitus (DM) and thyroid dysfunction (TD) are common endocrine diseases that often coexist in clinical practice. Prevalence of TD in individuals with DM type 2 ranges from 9.9 to 48%. There are no screening guidelines for thyroid function in patients with DM type 2 as there are in patients with DM type 1. Our previous electronic medical record (EMR) included an aid that imported diabetes metrics, but the current system does not. A previous study at our institution revealed TSH screening rate to be 86.2% in DM type 1 patients. We examined the rate of screening for TD in patients with DM type 2 versus DM type 1 based on the general population guidelines, and we evaluated the effect of EMR aid versus no aid on screening rate. We also analyzed the underlying etiology of thyroid dysfunction in patients with DM type 2 found to have an abnormal TSH.

We compared practice patterns with Centricity (EMR aid; from June 1, 2013 to May 30, 2016) and MedConnect (no EMR aid; from January 1, 2017 to December 31, 2019) in both primary care and endocrinology clinics in the MedStar hospital system in Baltimore, MD. A retrospective review was performed on 949 patient charts (MedConnect 498, Centricity 451). Inclusion criteria were DM type 2 diagnosis (ICD code E 11.0 to E 11.9) and age ≥18 years with at least one outpatient clinic visit.

Baseline TSH was done in 551 of overall 949 patients (58.1%), with 249 of 451 (55.2%) in Centricity and 302 of 498 (60.4%) in MedConnect. This difference was not significant (P = 0.5). Of the total 551 patients with baseline TSH, 48 (8.7%) had abnormal TSH, of which 35 patients (11.5%) were in MedConnect and 13 (5.2%) were in Centricity (P = 0.01). Of the overall abnormal results, 35 patients (6.3%) had hypothyroidism, 10 (1.8%) had hyperthyroidism, 2 (0.4%) had subclinical hyperthyroidism, and 1 (0. 2%) had subclinical hypothyroidism results. Logistic regression analysis found that the adjusted odds of baseline TSH screening with endocrinologists was 1.54 times higher than with primary care physicians.

No significant difference was found in TSH screening in patients with DM type 2 irrespective of EMR aid. A larger proportion of abnormal results were found in MedConnect than in Centricity. Endocrinologists ordered TSH screening more often than primary care physicians. The screening rate of TSH in patients with DM type 2 was lower than that found in our previous study of TSH screening in patients with DM type 1. This was expected as there are no current screening guidelines for TD specific to DM type 2 patients. Further studies are needed, and consideration should be given to screening all DM type 2 patients with symptoms.

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