bluuebunny/crossref_metadata_2025_split huggingface dataset:
871-P: One-Year Real-World Evidence of Effectiveness of Carbohydrate Restricted Nutrition Therapy in Adults with Type 2 Diabetes across Age and Gender
Authors: ROBERTS CAROLINE G.P. , ADAMS REBECCA N. , ATHINARAYANAN SHAMINIE J. , VOLK BRITTANIE M. , ZOLLER ALISON R. , MCKENZIE AMY L. 
Published: June 2024

Type 2 diabetes (T2D) affects 12% of US adults, with a growing presence in young adults. Virta Health provides carbohydrate restricted nutrition therapy (CRNT) through continuous remote care (CRC) to US adults with T2D, but the impact of the program across age and gender groups is unknown. This retrospective real-world study assessed differences in health marker change over one year between age groups, and secondarily between genders, with linear mixed effects models. One year retention was high across age groups (64%, 76%, 76%; ages 18-44, 45-64, 65+) and gender (76% male, 73% female), and a random sample (N=750) of patients enrolled one year was selected for this analysis. Broadly, all age groups and both genders improve over time in multiple health markers (weight, A1c, triglycerides, HDLc, liver enzymes) with no change in Total Cholesterol or LDLc, and with few differences between groups. Mean A1c in all age groups and both genders is &lt;7% at one year. These results provide real-world evidence that CRNT favorably impacts glycemic control, cardiometabolic health, and hepatic function in adults with T2D across age groups and in both men and women. The A1c reduction in the youngest age group is notable, as early glycemic control may confer legacy effects on complication rates for many decades.

Disclosure
C.G.P. Roberts: Other Relationship; Virta Health Corp. R.N. Adams: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. S.J. Athinarayanan: Employee; Virta Health Corp. B.M. Volk: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. A.R. Zoller: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. A.L. McKenzie: Employee; Virta Health Corp. Stock/Shareholder; Virta Health Corp. Employee; Abbott.
882-P: A Novel Angiogenesis Role of GLP-1(32-36) to Rescue Diabetic Ischemic Lower Limbs via GLP-1R–Dependent Glycolysis
Authors: ZHANG YIKAI , WANG SHENGYAO , ZHOU QIAO , XIE YI , ZHENG CHAO 
Published: June 2024

Our initial experiments revealed that GLP-1(32-36), an end-product of GLP-1, did not affect insulin secretion, but could significantly rescue angiogenic function and blood perfusion in ischemic limb of STZ-induced type 1 diabetes mellitus (T1DM) mice, a function similar to its parental GLP-1. We hypothesized that GLP-1(32-36) might exert its angiogenetic effects by an unknown mechanism independent of the insulinotropic activity. We demonstrate that GLP-1(32-36) ameliorated high glucose (HG)-induced excessive mitochondrial fission by resorting to aerobic glycolysis. GLP-1(32-36)-mediated angiogenesis in T1DM mice after hindlimb ischemia (HLI) were dependent on GLP-1R expression. GLP-1R, though not involved in GLP-1(32-36) entry into the cells, was required for GLP-1(32-36)-mediated pro-angiogenetic activities, including mitochondrial homeostasis, activation of the eNOS/cGMP/PKG pathway, and enhanced glycolysis via PFKFB3. Thus, our study provides a novel mechanism with which GLP-1(32-36) acts in modulating metabolic reprogramming towards glycolytic flux in partnership with GLP-1R for improved angiogenesis in HG-exposed EPCs and T1DM murine models. We propose that GLP-1(32-36) could be used as a monotherapy or add-on therapy with existing treatments for peripheral arterial disease.

Disclosure
Y. Zhang: None. S. Wang: None. Q. Zhou: None. Y. Xie: None. C. Zheng: None.

Funding
National Natural Science Foundation of China(82100862, 82070833)
889-P: Type 2 Diabetes Treatment Algorithm Study
Authors: MOHAN RAMANARAYANAN SHIVAA 
Published: June 2024

Clinical inertia is a global challenge affecting &gt;50% of individuals with type 2 diabetes(T2DM). T2TA study is an initiative towards Algorithm development for T2DM treatment initiation or intensification based on FBS and PPBS outcomes to avoid clinical inertia. This study included individuals (N=200) with uncontrolled, untreated Newly diagnosed T2DM (NDDM) and Previously diagnosed T2DM (PDDM) on treatment, aged &gt;18 years subjected to various drug combinations on Day 0. Therapy included DPP4 inhibitor (DPP4i), SGLT2 inhibitor (SGLT2i), Sulfonylurea (SU), Metformin (MET), Insulin (INS). Difference between Day 0 and Day 5 FBS, PPBS values were termed Glycemic reduction capacity (GRC) of a therapy. Therapy achieving a GRC frequently was termed the treatment of choice for initiation/intensification. GRC values were categorized into 9 glucose ranges from 1-449mg/dl. In NDDM the mean FBS, PPBS values on Day 0 were 243 ± 81 mg/dl, 350 ±106 mg/dl.On Day 5 of treatment it was 136 ± 30 mg/dl, 187 ± 69 mg/dl, with a significant reduction of mean glucose by 107 ± 82 mg/dl,164 ± 104 mg/dl. Among PDDM the mean FBS, PPBS values on Day 0 were 206 ± 62 mg/dl, 304 ± 87 mg/dl. On Day 5 of treatment it was 131 ± 35 mg/dl, 191 ± 50 mg/dl with a significant reduction of mean glucose by 76 ± 48 mg/dl, 114 ± 76 mg/dl. High GRC treatment of T2TA study can be used to develop an algorithm for treatment initiation or intensification in T2DM with significant glycemic reduction as early as Day 5 to avoid clinical inertia

Disclosure
S. Ramanarayanan: None.
89-OR: GPSM1 Regulates ER Ca2+-Myosin II Axis and Promotes Adipocyte Browning and Metabolic Health
Authors: YAN JING , HU CHENG 
Published: June 2024

Introduction & Objective: Adaptive thermogenesis offer crucial potential to combat metabolic diseases. We have proved G-protein-signaling modulator 1 (GPSM1) regulated metabolic inflammation in macrophages, however, it remains unclear whether GPSM1 mediates thermogenic fat function.
Methods: We generate adipocyte-specific GPSM1 KO and transgenic mice, subject them to a NCD or HFD to monitor thermogenic and metabolic phenotypes. By using molecular, biochemical analyses, and primary cell culture to reveal the role of GPSM1 in adipocytes and elucidate the underlying mechanisms of GPSM1 in regulating thermogenesis.
Results: Adipocyte-specific KO of GPSM1 in mice impairs a broad thermogenesis of adipocytes, including decreased energy expenditure, cold tolerance and UCP1 levels, exacerbates diet-induced obesity, insulin resistance, glucose dysregulation and hepatic steatosis. Mechanistically, GPSM1 controls ER Ca2+ store, resulting in enhanced intracellular Ca2+ levels and consequential promoting Ca2+-dependent myosin II activation, thus mediating mitochondrial respiration and thermogenesis in adipocytes. In contrast, mice with transgenic overexpression of GPSM1 show improved energy expenditure, better cold tolerance, and ameliorated metabolic dysfunctions.
Conclusions: we uncover a novel function of GPSM1 as a positive regulator of adipocyte thermogenesis and metabolic homeostasis.

Disclosure
J. Yan: None. C. Hu: None.

Funding
the National ScienceFoundation of China (82370879); Shanghai Rising-Star Program (23QA1407400)
891-P: 18F-FDG PET/CT Mapping Identifies Spleen as Dominant Site for Blood Glucose Uptake in BCG-Treated Patients with Type 1 Diabetes
Authors: DIAS HANS F. , FANGLU FU JESSIE , ZHENG HUI , KUHTREIBER WILLEM , PRICE JULIE , CATANA CIPRIAN , FAUSTMAN DENISE L. 
Published: June 2024

Introduction & Objective: In randomized clinical trials in patients with type 1 diabetes (T1D), bacillus Calmette-Guérin (BCG) vaccinations gradually lower blood sugar to near-normal levels, which appears to be driven by a BCG-induced shift in lymphoid cells’ glucose metabolism from oxidative phosphorylation to aerobic glycolysis. Here we investigated whether the BCG bacterium establishes residence in organs and alters their glucose metabolism.
Methods: In an open-label clinical trial in patients with longstanding T1D (n=6; T1D duration &gt;13 years at time of baseline BCG injection), we used positron emission tomography (PET) and x-ray computed tomography (CT) to map organs with increased uptake of the glucose analogue 18F-fluorodeoxyglucose (18F-FDG) after BCG vaccinations (Tokyo 172 BCG strain, Japan BCG Laboratory, Tokyo, Japan). Patients received a total of 6 BCG doses over a 2-year period. The first PET/CT scan was performed prior to receipt of BCG; each patient’s subsequent scans were compared to their baseline scan. We also injected BALB/c mice with BCG to test for BCG’s presence in various organs.
Results: The human and murine studies identified the spleen as the dominant site for glucose uptake and BCG residence after vaccination. Overall, the spleen showed a 47% increase in glucose uptake compared to baseline (p-value=0.03; mixed linear effects model statistics), which correlated in time with a systemic drop in blood sugar. The spleen’s activity steadily and significantly increased over the course of 2-years of 18F-FDG mapping, and the microbe persisted there over a 20-week period in the mice.
Conclusion: These findings suggest that the spleen, triggered by BCG vaccinations, assumes a critical role in systemic glucose regulation in the absence of a functional pancreas. This data fits with surgical data wherein splenectomy can cause diabetes in patients due to glucose dysregulation.

Disclosure
H.F. Dias: None. J. Fu: None. H. Zheng: None. W. Kuhtreiber: None. J. Price: None. C. Catana: None. D.L. Faustman: None.
893-P: Real-World Effectiveness of Finerenone in Chinese Patients with Type 2 Diabetes Mellitus (T2MD) and Chronic Kidney Disease (CKD)
Authors: LI ANG , GAO YING , GUO XIAOHUI , ZHANG JUNQING 
Published: June 2024

Background: Given the inconsistence of real-world treatment with randomized controlled trials (RCTs) and guidelines, the risk of cardiovascular-renal events remains in patients with T2DM and CKD. This study aimed to assess the real-world effectiveness of finerenone in patients with T2DM and CKD in Peking University First Hospital.
Methods: This retrospective study included patients with T2DM and CKD treated with finerenone. Urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and serum potassium were recorded at baseline and post-finerenone treatment.
Results: Of the 93 patients, mean age was 59.5±8.5 years, 55 (59.1%) were male, and mean duration of T2DM was 13.0±7.2 years. Of these patients, 83.9% were on sodium-glucose co-transporter type-2 inhibitors, 43.0% on glucagon-like peptide-1 receptor agonists, 48.4% on insulin and 85.3% on renin-angiotensin system inhibitors. Baseline UACR was 408.0±449.4 mg/g, and 66% of patients had microproteinuria (30-299 mg/g). With finerenone administered mean daily dose at 14.6 mg for averagely 3.4 months, UACR decreased by 22.3% to 317.3±294.5 mg/g. eGFR decreased from 83.7±11.4 to 74.4±12.9 mL/min/1.73 m2 in patients with baseline eGFR&gt;60 mL/min/1.73 m2 (75.3% of the total population). In patients with baseline eGFR&lt;60 mL/min/1.73 m2 (24.7% of the total population), eGFR remained stable (49.2±6.6 vs. 49.0±6.1 mL/min/1.73 m2). Serum potassium slightly increased from 4.3±0.4 to 4.5±0.6 mmol/L and no adverse event of hyperkaliemia occurred.
Conclusion: Despite the different treatment background and finerenone use between the real-word clinical practice and RCTs, similar UACR reduction was observed in this study compared to FIGARO-DKD trials. Finerenone might improve proteinuria control and could be a promising treatment option to reduce the risk of cardiovascular-renal events in patients with T2DM and CKD in the integrated management.

Disclosure
A. Li: None. Y. Gao: None. X. Guo: None. J. Zhang: None.
902-P: GlucoLo Plus, a Complementary and Alternative Medicine (CAM) Used in Type 2 Diabetes Management, Is Associated with Lipid Profile Improvement
Authors: ZARRUK ALEXANDRO R. 
Published: June 2024

Introduction & Objective: Diabetes is a chronic disease associated with many comorbidities and a higher risk of all-cause and cardiovascular mortality. The GLEEN Study is a previously reported double-blind randomised placebo-controlled trial that evaluated the efficacy and safety of daily GlucoLo Plus, a Complementary and Alternative Medicine (CAM). The secondary outcome of lipid profile improvement will now be presented.
Methods: The GLEEN Study was composed of 60 individuals with type 2 diabetes with a mean HbA1c 6.98% [52.8 mmol/mol], mean age 67.3 years [SD 9.5], 26 [43%] women, mean diabetes duration was 3.2 years, and meanbody mass index 27.9 kg/m2. Participants were randomly assigned to GlucoLo Plus (n=32 [53%]), or placebo (n=28 [47%]). The primary outcome of a significant HbA1c reduction of 0.843% was previously reported. The lipid profile including Total Cholesterol, Triglycerides, High-Density Lipoprotein (HDL) and Low-Density Lipoprotein (LDL) were measured at randomization and at the end of the 3-month trial.
Results: At 12 weeks, GlucoLo Plus decreased Total Cholesterol by 4.47 % while placebo increased it by 0.62%. The active arm had a decrease in Triglycerides by 10.33 % while the placebo arm had a Triglycerides lowering of 12.44%. GlucoLo Plus further improved the lipid profile by reducing LDL by 7.45 % while placebo increased it by 2.70% and it increased HDL by 14.52% while placebo reduced it by 0.38%.
Conclusion: GlucoLo Plus showed favorable effect regarding lowering Total Cholesterol, lowering LDL cholesterol and increasing HDL cholesterol. These results suggest that GlucoLo Plus could be, in addition to its’s proven glucose lowering abilities, an alternative and/or an addition to type 2 diabetes management in people who are reluctant to initiate or add new antidiabetic agents while providing them with some lipid profile benefits at the same time.

Disclosure
A.R. Zarruk: Consultant; Sanofi. Speaker's Bureau; Sanofi. Consultant; Bausch Health. Speaker's Bureau; Bausch Health. Consultant; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Consultant; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim, Abbott. Consultant; Abbott.

Funding
Groupe Nature Pharma
905-P: Increased GDF15 Levels Are Unrelated to Anterior Pituitary Hormone Shifts in Metformin Use
Authors: HEWLETT JENNIFER R. , YANNAMANI AISHWARYA , SREEKUMARAN NAIR K. 
Published: June 2024

Metformin is a widely used medication in the management of type 2 diabetes, and its weight-lowering effects involve the central nervous system. Growth differentiation factor 15 (GDF15) acts on the mid-brain, is increased with metformin, and is positively correlated with weight loss. Pituitary hormones can also be altered by metformin and in states of stress. We sought to understand the relationship between GDF15 and pituitary function with metformin use. Data was collected from a randomized, double-blinded, cross-over study of 9 adult patients with prediabetes who received metformin or placebo for two weeks. GDF15, thyroid stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH), cortisol, free T3, total T3, and total T4 were collected at baseline and following metformin. In this small study, GDF15 levels were significantly increased with metformin, however there was no association between the blood level of metformin and the degree of GDF15 increase (R2=0.339, P=0.1). Metformin was associated with an isolated TSH increase (p=0.024) without a significant change in thyroid hormones. TSH was negatively correlated with free T3 values (R2=0.558, P=0.021). A similar correlation was noted with the change in total T3 and total T4 which did not reach significance (R2=0.374, P=0.08; R2=0.389, P=0.073). Metformin was associated with an isolated increase in cortisol (P=0.012) without a significant change in ACTH (P=0.664). There was no correlation between ACTH and cortisol (R2=0.064, P=0.511). There was no relationship identified between GDF15 and TSH (R2=0.171, P=0.17) or GDF15 and cortisol (R2=0.201, P=0.226). Short-term metformin use is associated with isolated increases in TSH, which is likely physiologic, and cortisol, which is unrelated to ACTH. It remains to be determined whether metformin's effect on cortisol is due to altered adrenal steroidogenesis. Our findings suggest that the changes in TSH and cortisol with metformin are not due to GDF15 or a direct effect on the pituitary.

Disclosure
J.R. Hewlett: None. A. Yannamani: None. K. Nair: None.
908-P: Use of DPP4i/SGLT2i Fixed Dose Combinations in Indian Clinical Practice—A KAP Survey
Authors: SABOO BHARAT , PRAJAPATI CHARMY M. , SHETTY PARVAN A. , MURALIDHARAN PARTHASARATHY , QAMRA AMIT 
Published: June 2024

Introduction & Objective: The Asian-Indian phenotype presents with increased insulin resistance, reduced Beta-Cell function, abdominal adiposity & clustering of CV risk factors. In India generic DPP4i/SGLT2i Fixed Drug Combinations (FDCs) are prescribed to enhance compliance amongst patients with T2DM. We aimed to study attitude & practice of Indian Physicians pertaining to patient populations benefitting from these FDCs.
Methods: We designed and utilized a 6-question survey during an Indian Medical Congress. Convenience Sampling was used to reach out to at least n=150 physicians. Descriptive Statistics was used to analyze data using MS-Excel 2019.
Results: Amongst 185 surveyed physicians, 48% respondents (n=89) reported over 40% of newly-diagnosed, treatment-naïve patients presenting with baseline HbA1c &gt;8%. 52% (n=97) had more than 40% patients with HbA1c &gt;8.5% despite Metformin monotherapy. Considering glycemic control in 3 clinical scenarios, 66% (n=122) physicians preferred DPP4i/SGLT2i FDCs for all scenarios namely (a) patients uncontrolled on Metformin monotherapy with HbA1c &gt;8.5% (b) treatment-naive patients with contraindication/intolerance to Metformin & HbA1c &gt;8% (c) add-on to insulin. Also 60.5% (n=112) physicians favored DPP4i/SGLT2i FDC for all 4 given reasons i.e. CV benefits, lower hypoglycemia risk, weight loss promotion & targeting multiple pathophysiological pathways. 85% (n=158) reported reduced Genito-Urinary Tract Infections (GUTI) with concurrent administration of DPP4i with SGLT2i or FDC. Most favored FDC was Sitagliptin/Dapagliflozin (36%, n=67).
Conclusion: In India there is significant burden of patients with T2DM who present with high HbA1c (newly diagnosed or despite metformin monotherapy). Generic DPP4i/SGLT2i FDCs are preferred in these patients also considering their extra-glycemic benefits. Most physicians (85%) noted reduction in SGLT2i associated GUTIs with use of DPP4i/SGLT2i FDCs. Further studies may validate these findings.

Disclosure
B. Saboo: None. C.M. Prajapati: Employee; Macleods Pharmaceuticals Ltd. P.A. Shetty: Employee; Macleods Pharmaceuticals Ltd., Eisai Inc. P. Muralidharan: Employee; Macleods Pharmaceuticals. A. Qamra: Employee; Macleods Pharmaceuticals Ltd.
91-OR: Selenite-Induced Glutathione Peroxidase 3 in the Control of Insulin Receptor Expression in Adipocytes
Authors: HAUFFE ROBERT , KLEINRIDDERS ANDRE 
Published: June 2024

Selenoproteins are an important modulator of cellular redox homeostasis and metabolic processes. Previously we have demonstrated that mice fed a selenium rich HFD (SRHFD) are protected against diet-induced insulin resistance. Here, SRHFD-fed mice exhibited elevated white adipose tissue (WAT) insulin receptor (IR) expression and improved whole-body insulin sensitivity. This was due to a WAT-specific upregulation of the selenoprotein glutathione peroxidase 3 (GPx3), an important regulator of cellular redox states. Strikingly, we could demonstrate that this effect is blunted in mice with pre-existing obesity, where a failure to increase GPx3 in WAT associates with unaltered IR expression. However, the mechanism behind this interaction is unknown.
Highlighting the translational relevance, we use a human pre-adipocyte cell line to show that GPx3 expression increases IR protein levels, differentiation capacity, and protects against palmitate-induced insulin resistance.
In our current investigation using murine pre-adipocytes (3T3-L1), we show that GPx3 regulates IR expression via the transcription factor SP1, which is known to be susceptible to changes in the cellular redox state. Consequently, we demonstrate that an increase in selenite-induced GPx3 expression is associated with an increased binding of SP1 to the IR promoter. This mechanism involves a change in the oxidized glutathione pool by GPx3. Surprisingly, it is sufficient to provide cells with extracellular recombinant GPx3 to elicit this effect, suggesting either a receptor-mediated effect, or a reuptake of GPx3 into the cells. As a result, in vitro treatment with extracellular GPx3 increases IR expression and enhance mitochondrial function and differentiation capacity of 3T3-L1 cells.
In conclusion, we identify GPx3 as a novel modulator of WAT insulin receptor expression and insulin sensitivity, that potentially acts in a paracrine or autocrine manner, and is responsive to a dietary intervention.

Disclosure
R. Hauffe: None. A. Kleinridders: Speaker's Bureau; Novo Nordisk A/S, Daiichi Sankyo.
910-P: Novel Mechanism of Action Associated with SGLT2 Inhibition, Peripheral Energy Utilization, and CV Benefits in Subjects with Type 2 Diabetes Mellitus and HFrEF
Authors: QIN YUEJUAN , SANCHEZ NOAH D. , ACOSTA FRANCISCA M. , MOODY ALEXANDER , NEPPALA SIVARAM , TRIPLITT CURTIS L. , CLARKE GEOFFREY D. , CERSOSIMO EUGENIO , DEFRONZO RALPH A. , SOLIS-HERRERA CAROLINA 
Published: June 2024

Background: SGLT2i is associated with CV benefits, but the mechanisms are not fully elucidated. We report a novel finding associated with improved CV Health in T2D & HFrEF. Elevated ketones, EF%, & heart remodeling have been reported with SGLT2i. This is likely, in part, due to a switch in cardiac metabolism to ketone oxidation. This switch might be present in peripheral tissues, including skeletal muscle (SkM).
Objective: To examine the effects of SGLT2i on SkM energy production, utilization, exercise recovery, lipid content, and cardiopulmonary function.
Methods n=10(Age= 61.6±3.5, BMI= 31.4±1.8, A1c=7.6%±0.4, EF 32.7%±2.7) were randomized to empagliflozin 25mg vs. placebo 2:1 for 12 wks. SkM 31P & 1H MRS was performed. Cardiopulmonary exercise testing (CPET) was done to assess functional capacity and determine CV prognosis.
Results: After SGLT2i, there was a significant improvement in SkM energy production, utilization at rest, and exercise recovery. The VE/VCO2 slope, significantly improved (p&lt;0.05) (Fig.1)
Conclusion: We show for the first time that, in subjects with T2DM & HFrEF, SGLT2i significantly improve SkM bioenergetics and lipid content. This was associated with a significant improvement in CV prognostic markers. These findings may explain novel mechanisms of improvement in peripheral bioenergetics that translate into Global CV Health.

Disclosure
Y. Qin: None. N.D. Sanchez: None. F.M. Acosta: None. A. Moody: None. S. Neppala: None. C.L. Triplitt: Speaker's Bureau; Novo Nordisk. Consultant; Eli Lilly and Company. Other Relationship; American Diabetes Association. G.D. Clarke: None. E. Cersosimo: None. R.A. DeFronzo: Advisory Panel; AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Intarcia Therapeutics, Inc., Aardvark, Renalytix, Corcept Therapeutics, Alnylam Pharmaceuticals, Inc. Research Support; Boehringer-Ingelheim, AstraZeneca, 89bio, Inc., Amgen Inc., Medality, Corcept Therapeutics. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Renalytix. C. Solis-Herrera: Advisory Panel; Novo Nordisk, Bayer Inc.

Funding
Doris Duke Foundation