bluuebunny/crossref_metadata_2025 huggingface dataset:
1070-P: Blood Glucose Reduction and Long-Term Sustainability in High-Risk Patients with Type 2 Diabetes over Three Years of Using Digital Platform
Authors: HERSHCOVITZ YIFAT , YANIV NOGA , BUDMAN SOFIA , MANEJWALA OMAR
Published: June 2023

Introduction: Long-term management of type 2 diabetes (T2D) and sustaining glycemic control remains a challenge and crucial for reducing clinical complications and subsequent economic costs. This study followed glycemic outcomes, average blood glucose (BG avg) and high readings ratio, over 3 years in persons using a digital therapeutic platform.

Objective: To investigate blood glucose (BG) levels in persons with T2D in high-risk who used a digital therapeutic platform to manage their BG levels over three years. Additionally, to compare outcomes between consistently engaged users over 3 years versus less consistent population.

Method: A retrospective data analysis was performed on users with T2D in high-risk (baseline BG avg>169 mg/dL in month1; equivalent to A1C 7.5) who activated between 2017-2020 and measured their BG using Dario platform over 3 consecutive years (months 1,6,12,24 and 36). The ratios assessed were BG avg and high BG readings ratio (>180 mg/dL). Digital engagement was assessed by additional parameters including measurement type (fasting/premeal/post meal/bedtime), carbs intake, meal type, and physical activity alongside glucose measurement.

Results: A group of 1,239 users significantly reduced their BG avg consistently over 3 years by 15.6% (179±55 vs. 212±42) (p<0.05) and high readings ratio by 39% (p<0.05). A subset of users completed at least one engagement type following months 12, 24, and 36 (N=433) demonstrated significantly greater reductions versus the complementary group (N=806): BG avg by 18.8% (172±51 vs. 212±45) and high readings ratio by 45% (p<0.05).

Conclusion: A digital diabetes platform has the potential to affect and sustain glycemic control improvements over 3 years. Moreover, it appears highly likely that engagement to app features in chronic condition management may help users with T2D consistently pay attention to their life behaviors to maintain better clinical outcomes.

Disclosure

Y.Hershcovitz: Employee; DarioHealth Corp. N.Yaniv: Employee; DarioHealth Corp. S.Budman: Employee; DarioHealth Corp. O.Manejwala: Employee; DarioHealth Corp., Stock/Shareholder; DarioHealth Corp.
1154-P: Racially and Ethnically Inclusive Recruitment Strategies from the CoYoT1 to California (CTC) Study
Authors: GONZALEZ FRANCES , REID MARK W. , SALCEDO-RODRIGUEZ ELIZABETH , FLORES GARCIA JAQUELIN , HIYARI SARAH , TORRES SANCHEZ ALEJANDRA , PYATAK ELIZABETH , STEVEN FOX D. , RAYMOND JENNIFER
Published: June 2023

Background: The prevalence of type 1 diabetes (T1D) is increasing within racially and ethnically marginalized populations, highlighting the need for effective recruitment strategies that not only address healthcare disparities but also rebuild trust in medical research. Recently, the CoYoT1 to California (CTC) study evaluated a person-centered care model designed to support racially and ethnically diverse young adults (YA) who receive care at a hospital-based pediatric T1D clinic. In addition to treatment effectiveness, the study examined the success of recruitment strategies.

Methods: Potential YA participants were approached in-person or remotely (by phone, email, or text). Those with clinic appointments during study recruitment were approached in-person, with recruiters focusing on cultural humility to connect with families; the concept and process of research was introduced, and families were allowed to ask questions as needed. Remote recruitment utilized multiple pre- and post-appointment messages with basic descriptions of the study or follow-up details as needed. Categorical data were compared using chi-squared tests.

Results: The study approached 338 potential participants and recruited 68 (20%). Reflecting successful recruitment of diverse YA, study participants were representative of the clinic population in terms of racial and gender identities, and identified as Latinx (29, 43%) more often than those who declined (100, 37%; P=0.40). Recruitment strategy was significantly associated with participation, as most participants were recruited in-person (40, 59%), while most who declined did so remotely (200, 74%; P<0.0001).

Conclusion: In-person recruitment is more effective for enrolling diverse YA and their families, as it allows recruiters to build rapport, and empowers families with information and choice. Internal and external barriers may prevent diverse YA from attending clinic appointments in-person, ultimately impacting research equity.

Disclosure

F.Gonzalez: None. M.W.Reid: None. E.Salcedo-rodriguez: None. J.Flores garcia: None. S.Hiyari: None. A.Torres sanchez: None. E.Pyatak: Research Support; Abbott Diabetes. D.Fox: None. J.Raymond: None.

Funding

Patrick and Catherine Weldon Donaghue Medical Research Foundation
1205-P: Abnormal Fetal Growth and Adverse Neonatal Outcomes in Pregnancies Affected by Both Gestational Diabetes and Hypertensive Disorders of Pregnancy
Authors: ONUOHA CHIOMA A. , THAWEETHAI TANAYOTT , HSU SARAH , SCHULTE CAROLIN C.M. , JAMES KAITLYN , KAIMAL ANJALI , POWE CAMILLE E.
Published: June 2023

Objective: We evaluated how the co-occurrence of gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP) influence fetal growth and neonatal outcomes.

Methods: In a retrospective study of 47720 singleton deliveries from a US medical center, we compared the incidence of appropriate for gestational age birthweight (AGA) in pregnancies affected by GDM alone, HDP alone, or both GDM and HDP (GDM/HDP) to that in pregnancies affected by neither disorder (Control) using generalized estimating equations (covariates: maternal age, parity, BMI, insurance type, race, marital status, and prenatal care site). Secondary outcomes were small for gestational age birthweight (SGA), large for gestational age birthweight (LGA), and a neonatal composite outcome (stillbirth, hypoglycemia, hyperbilirubinemia, respiratory distress, encephalopathy, preterm delivery, neonatal death, NICU admission).

Results: Median [IQR] birthweight (BW) percentile in GDM/HDP (50 [24, 78], N=179) was similar to Control (50 [27, 73], N=35885), while GDM had increased (60 [35, 83], N=1322) and HDP had decreased (43 [18, 71], N=2749) BW percentiles. GDM (OR 0.8, P<0.001), HDP (OR 0.7, P<0.001), and GDM/HDP (OR 0.7, P=0.04) each had decreased odds of AGA. GDM had decreased SGA odds (OR 0.7, P=0.02) and increased LGA odds (OR 1.7, P<0.001). HDP had increased SGA odds (OR 2.0, P<0.001) and no difference in LGA odds (OR 0.99, P=0.914). While unadjusted rates of abnormal growth in GDM/HDP suggested that reduced AGA was due to excess LGA (14.5%) without excess SGA (7.3%), adjusted models suggested that both SGA (OR 1.3, P=0.33) and LGA (OR 1.4, P=0.12) contributed. GDM/HDP conferred the highest risk of neonatal morbidity (OR 3.4, P<0.001 compared to Control).

Conclusion: Although pregnancies with GDM/HDP co-occurrence have a similar median birth weight to unaffected pregnancies, they carry an increased risk of abnormal fetal growth and neonatal morbidity.

Disclosure

C.A.Onuoha: None. T.Thaweethai: None. S.Hsu: None. C.C.M.Schulte: None. K.James: None. A.Kaimal: None. C.E.Powe: Consultant; Mediflix, Inc., Other Relationship; Wolters Kluwer Health.
1223-P: Frequency and Predictors of Level 2 Time Above Range (TAR) in Older Adults with Type 2 Diabetes on Insulin Therapy—Data from the HYPOAGE Prospective Study
Authors: CARIOU BERTRAND , HADJADJ SAMY , SOPHIE BOUREAU ANNE ,   HYPOAGE STUDY GROUP
Published: June 2023

Background: Although type 2 diabetes (T2D) is very common in older patients, there is a lack of real-life data on blood glucose control in this specific population. We aimed to determine the frequency and predictors of hyperglycemia in older patients with T2D on insulin therapy by using continuous glucose monitoring (CGM).

Methods: HYPOAGE is prospective multicenter study including 146 insulin-treated older adults aged 75 and older, with T2D for at least 1 year and treated with insulin for at least 6 months. All patients benefited from ambulatory blinded CGM for 28 consecutive days with FreeStyle Libre Pro® sensor. All participants underwent a geriatric and diabetic assessment. Multivariable logistic regressions were used to identify factors associated with level 2 time above range (TAR)[glucose concentration >13.9 mmol/L] > 10%.

Results: The mean age of the 141 analyzed patients was 81.5±5.3 years and 56.7% were male, 102 participants (72.3%) were considered as complex and 39 (27.7%) as healthy after geriatric assessment. The mean baseline HbA1c was 7.9±1.0% and 43 patients (30%) had TAR (level 2) > 10%. Compared to patients with level 2 TAR ≤ 10%, patients with higher TAR were older (83.5 [5.7] vs 80.6 [4.9] years), with lower BMI (28.0 [5.5] vs 31.3 [6.1] kg/m2), higher HbA1c (8.6 [0.9] vs 7.6 [0.9] %), and a less frequent healthy geriatric status (14.0 vs 33.7%). In multivariate analyses, TAR (level 2) > 10% remains only significantly associated with HbA1c (OR: 3.08 for 1% increase [1.72-5.50], p=0.0002) and BMI (OR: 0.92 [0.84-1.00], p=0.0496). Conversely, HbA1c was not significantly associated with hypoglycemia (i.e. level 2 time below range [glucose concentration < 3.0 mmol/L]).

Conclusions: In this real-life study, 30% of older patients are above the TAR target recommended by the ATTD 2019 consensus (< 10% for level 2) HbA1C is a better predictor of time spent in hyperglycemia than of hypoglycemia in older patients on insulin therapy.

Disclosure

B.Cariou: Board Member; Eli Lilly and Company, Novartis, Research Support; Sanofi, Speaker's Bureau; Abbott, AstraZeneca, Novo Nordisk, Sanofi. S.Hadjadj: Consultant; Bayer Inc., Novo Nordisk, Valbiotis, Research Support; AstraZeneca, Novartis, Speaker's Bureau; Abbott Diagnostics, Boehringer-Ingelheim. A.Boureau: Board Member; Pfizer Inc. Hypoage study group: n/a.

Funding

Sanofi
128-OR: The Effect of Tirzepatide during Weight Loss on Food Intake, Appetite, Food Preference, and Food Craving in People with Obesity
Authors: MARTIN CORBY K. , RAVUSSIN ERIC , SANCHEZ-DELGADO GUILLERMO , NISHIYAMA HIROSHI , LI JING , URVA SHWETA , PRATT EDWARD J. , MILICEVIC ZVONKO , HAUPT AXEL , COSKUN TAMER
Published: June 2023

Tirzepatide (TZP) promotes significant and clinically meaningful weight loss. In a randomized blinded clinical trial in people with obesity undergoing caloric restriction, we investigated the effect of TZP vs Placebo (PBO) on food intake during ad libitum lunch and dinner, appetite, food preference and craving. In this 18wk phase 1 study, 55 people with obesity, with baseline body weight of 102.8 kg were randomized (1:1) to TZP 15 mg or PBO. Food intake was measured during ad libitum lunch (664 kcal, PBO and 682 kcal, TZP) and dinner (1178 kcal, PBO and 1190 kcal, TZP) at baseline and after 18wk of treatment. We measured appetite during fasting and standardized mixed meal tolerance test (sMMTT) with visual analogue scale (VAS) and retrospective VAS (average ratings over the previous week). Food cravings and preferences were measured with the Food Craving Inventory (FCI) and Food Preference Questionnaire (FPQ) at baseline, 8wk and 18wk. At 18wk, mean body weight loss was 16.7 kg with TZP and 8.3 kg with PBO (p<0.001). TZP significantly decreased food intake from baseline during lunch (-285±42 kcal) and dinner (-631±58 kcal) compared to PBO (60± 42, and -116±58 kcal, respectively). TZP significantly lowered appetite at fasting and at each time point during the sMMTT, resulting in decreased hunger and prospective food consumption and increased fullness. Based on retrospective VAS, appetite changes started at 1wk. TZP significantly decreased food preference scores in 10 of 12 FPQ metrics at 8wk and 18wk compared to PBO. TZP significantly decreased the overall FCI score and the sweets, carbohydrates and starches, and fast-food fats sub scores, but not the high fat and fruit and vegetable sub scores, at 8wk and 18wk, compared to PBO. In conclusion, TZP decreased food intake, appetite and food craving and preference. TZP appears to reduce body weight via reductions in food intake and the drive to eat.

Disclosure

C.K.Martin: Board Member; EHE Health, Wondr Health, Other Relationship; ABGIL, Research Support; Pack Health, Evidation Health, Lilly, WW International, Inc. T.Coskun: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. E.Ravussin: Advisory Panel; Novartis, Research Support; Eli Lilly and Company, Novartis AG. G.Sanchez-delgado: Research Support; Eli Lilly and Company, Novo Nordisk, Abbott, Maastricht instruments, Vyaire Medical, ParvoMedics, Cosmed, Speaker's Bureau; Eli Lilly and Company. H.Nishiyama: None. J.Li: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. S.Urva: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. E.J.Pratt: Employee; Eli Lilly and Company. Z.Milicevic: Employee; Eli Lilly and Company. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly.

Funding

Eli Lilly and Company
130-LB: GWave—A Novel Noninvasive Glucose Blood Monitoring Radio Wave–Based Technology
Authors: HIRSCH IRL B. , NAVON AMI
Published: June 2023

Attempts to achieve an accurate noninvasive glucose monitor to date have been unsuccessful. The GWave device (Hagar, Israel) filters out the “white noise” and uses radiofrequency that detects capillary blood glucose across the physiological range. Measuring blood as opposed to interstitial fluid glucose, allows elimination of the “lag time” and poor accuracy seen in the first day of the current invasive continuous glucose monitors. Calibration of the GWave device is not required. Original data with the first prototype device revealed a 96% and 97% zone A (N = 53) in the Clarke Error Grid (CEG) comparing to venous and capillary blood, respectively. Initial results with second generation devices in non-diabetic subjects compared to capillary blood noted 99% in CEG Zone A and a MARD of 7.1% (N = 120 measurements) (Figure). These data were reproducible with two GWave devices (MARD 5.1%). Combining first and second-generation devices (N = 43 measurements) with a range of glucose of 69 to 400 mg/dL), CEG in Zone A was 98%. Subjects with both type 1 and type 2 diabetes are now being studied to examine accuracy at a wider physiological range of glycemia. Early results from the GWave glucose monitor shows promise as the first noninvasive technology. The current on-going studies will provide more insight for its use in diabetes care.

Disclosure

I. B. Hirsch: Consultant; Abbott Diabetes, Lifecare, Inc., Hagar, Research Support; Beta Bionics, Inc., Insulet Corporation, Dexcom, Inc. A. Navon: Consultant; GWave.

Funding

Hagar Technologies
1321-P: Screening for Liver Fibrosis in Diabetes—Assessing the Performance of Current Recommendations in a Large Unselected Population
Authors: BRIL FERNANDO , GRAY MEAGAN
Published: June 2023

American Diabetes Association’s Standard of Care 2023 recommended screening patients with T2D for significant liver fibrosis with FIB-4 and transient elastography (TE). However, the evidence supporting this approach is controversial. The aim of this study was to assess the use of FIB-4, and its correlation with TE, in an unselected population of patients with diabetes. Adult patients from NHANES 2017-2020 with complete data on FIB-4 and TE were included. Diabetes was defined based on FPG, A1c or prior history. Patients with secondary causes of liver steatosis were excluded. NAFLD was defined as a controlled attenuation parameter ≥274 dB/m, while clinically significant and advanced liver fibrosis were defined as TE ≥9.6 and ≥12 kPa, respectively. Among 1193 patients with diabetes (Age: 61 ± 13; BMI: 32.6 ± 7.3 kg/m2; A1c: 7.4 ± 1.7%), the prevalence of NAFLD, clinically significant liver fibrosis, and advanced fibrosis were 68%, 15% and 8%, respectively. These were significantly higher than in patients without diabetes even after stratifying for BMI (all p<0.001). Liver fibrosis worsened with increasing insulin resistance (HOMA-IR), but were not associated with A1c levels. FIB-4 performed poorly to predict significant or advanced liver fibrosis in diabetes (AUC: 0.59 [0.54-0.64] and AUC: 0.63 [0.56-0.69], respectively). Moreover, it performed numerically worse than plasma AST alone (AUC: 0.63, p=0.10 and AUC: 0.68, p=0.10, respectively). Among patients with significant and advanced fibrosis based on TE, FIB-4 was <1.30 (suggested cut-off for screening) in 51% and 47% of patients (i.e., false negatives), suggesting a significant disagreement between these tests. Patients with diabetes are at high risk of liver disease, and therefore, screening for liver fibrosis is warranted. However, our results suggest that current screening strategies based on FIB-4 and TE may not be adequate, as they may miss a significant number of patients with advanced fibrosis.

Disclosure

F.Bril: None. M.Gray: Advisory Panel; Takeda Pharmaceutical Co., Ltd., Theratechnologies, Consultant; Novo Nordisk.
1492-P: IL-8/CXCL8 May Identify a New Type 1 Diabetes Endotype
Authors: ALHAMAR GHADEER , FALLUCCA SARA , PIERALICE SILVIA , VALENTE LUCIANA , POZZILLI PAOLO
Published: June 2023

Recent research focused on identifying mechanisms explaining the observed heterogeneity of type 1 diabetes (T1D) in age at onset, residual β-cell function and rate of disease progression. Mechanisms include changes in both the immune system and β-cells, leading to the loss of tissue-specific immune tolerance and disease onset. Interleukin-8 (IL-8; CXCL8) is a pro-inflammatory chemokine released by macrophages, endothelial, epithelial and airway smooth muscle cells playing a major role in the innate immune response. Macrophages release IL-8 at the site of an injury where they recruit and activate neutrophils by interacting with the IL-8 receptors CXCR1 and CXCR2. An increase in circulating IL-8 has been shown in several autoimmune disorders. IL-8 levels, but not IL-6 or TNF-α, are elevated in adolescents with T1D, and also associated with insulin resistance, suggesting a role for IL-8 beyond acute inflammation in this setting. In vitro experiments revealed that IL-8 transcription is induced by hyperglycaemia. In the present study newly diagnosed T1D patients within the first year of disease onset (mean age 16.2 ± 7.6 yrs and % HbA1c of 10.7 ± 2.7) (N=42) were studied. Clinical and laboratory features included age, gender, body mass index (BMI), disease duration, HbA1c, and C-peptide. Serum IL-8 and myeloperoxidase (MPO) were measured with commercial enzyme-linked Immunosorbent assays. When compared to normal subjects, T1D patients showed a significantly higher IL-8 values (median [IQR] 112.0 [64.74-311.8] vs 43.05 [30.94-49.70], p-value= 0.002, respectively). Furthermore, T1D patients showed a significantly higher MPO levels than controls (median [IQR], 95327 [55718 - 168974] vs 42729 [24147 - 95327], p-value= 0.0349, respectively). This study shows for the first time that IL-8 and MPO are elevated in patients with recent onset T1D compared to normal subjects. There is also a trend for a positive correlation between IL-8 and HbA1c levels suggesting that elevated IL-8 values are associated with poor metabolic control.

Disclosure

G.Alhamar: None. S.Fallucca: Consultant; Dompé. S.Pieralice: None. L.Valente: None. P.Pozzilli: None.
150-OR: Mean HbA1c and Glycaemic Variability Are Associated with Adverse Outcomes following Infrainguinal Bypass for Peripheral Arterial Disease (PAD)—A Retrospective Cohort Study
Authors: DHATARIYA KETAN , BENNETT PHILIP C. , FARNDON DANIEL J.
Published: June 2023

Introduction: Glycemic variability (GV) is associated with increased risk of several adverse outcomes in people with diabetes (DM). However, on the impact of GV on graft patency following infra-inguinal bypass (IIB) for peripheral arterial disease (PAD) is unknown.

Methods: A 3-year single centre retrospective case notes analysis of those undergoing IIB 2017-2019. HbA1c values for 5 years pre-procedure (minimum of 3) were used to calculate a mean (±SD) HbA1c (MH) and GV. Time to re-intervention, ipsilateral amputation or death were recorded to determine primary (PP) and secondary patency (SP).

Results: 193 IIB outcomes were analysed: mean (±SD) age 68.9 (9.2) years; 135 (69.9%) male. 156 (80.8%) had pre-operative HbA1c for analysis and 88 (45.6%) had DM; 87 (45.1%) were current smokers; 107 (55.4%) underwent emergency procedures. Those without diabetes were more likely to smoke (P=0.011), but those with DM had higher Rutherford stage (p<0.01), underwent more distal bypasses (p<0.01) and more emergency procedures (p=0.04). Those with DM had longer mean [IQR] hospital stays 9 [5-21] vs 7 [4-15] days (p=0.017), lower PP 335 [184-542] vs 883 [436-1437] days (p=0.04) and lower SP 751 [387-1108] vs 1079 [895-1593] days (p=0.037). Both MH and GV were associated with amputation free survival time (r=-0.232, p=0.004 and r=-0.243, p=0.011 respectively). A GV>9.1% was associated with significantly lower PP than GV<9.1%, 198[105-377] vs 713 [313-1287] days (p=0.02). On multivariate adjustment, GV >9.1% and level of bypass remained independent predictors of primary patency, HR 1.96 (95% CI:1.12-3.42, p=0.018) and HR 2.54 (95%CI:1.24-5.22, p=0.038) respectively.

Conclusions: We have shown a significant relationship between MH and GV and risk of adverse outcomes in people undergoing IIB. Lowering glycemic variability should be an additional therapeutic target together with lowering mean HbA1c.

Disclosure

K.Dhatariya: Other Relationship; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company. P.C.Bennett: None. D.J.Farndon: None.
1552-P: Homeostasis Model Assessment of ß-Cell Function for Diagnosis of Insulinoma
Authors: BÓDIS KÁLMÁN , SCHÖN MARTIN , DAUBEN LAURA , WILKER MIRIAM , STRASSBURGER KLAUS , BURKART VOLKER , RODEN MICHAEL , MÜSSIG KARSTEN
Published: June 2023

Insulinoma is characterized by uncontrolled hypersecretion of insulin and is currently diagnosed by the 72-h fasting test. Guidelines by Endocrine Society (ES), European (ENETS) and North American (NANETS) Neuroendocrine Tumor Societies provide divergent diagnostic criteria at the end of the fasting test, but parameters assessing ß-cell function noninvasively are not included. This study tested whether homeostasis model assessment of ß-cell function (HOMA-B) as a surrogate for insulin secretion at the end of the fasting test, provide comparable sensitivity and specificity for diagnosis of insulinoma and thus might help to improve current diagnostic guidelines. In 104 persons with suspected insulinoma, 72-h fasting tests were performed with frequent assessment of glucose, insulin, and C-peptide in venous blood. HOMA-B was calculated at time of lowest glucose concentration at the end of fasting test. Follow-up data of patients were collected to exclude false-negative diagnosis of insulinoma. The HOMA-B at the end of the fasting test was >6.5-fold higher in persons with than without insulinoma (insulin and C-peptide, both p<0.001). ENETS/NANETS and ES criteria (insulin and C-peptide) reached a diagnostic sensitivity of ≤0.83 (≤0.61-0.95) and ≤0.96 (≤0.78-1.00) as well as specificity of ≤1.00 (≤0.96-1.00) and ≤0.85 (≤0.76-0.92). The HOMA-B provided high diagnostic sensitivity (cut-off using insulin >253 a.u. and C-peptide >270 a.u.; both 0.96, 0.78-1.00) and specificity (≥0.96, ≥0.89-0.99) at the end of the fasting test for diagnosis of insulinoma (n=23). Using both insulin and C-peptide for HOMA-B, sensitivity even tended to be higher than that of ENETS/NANETS using insulin only (p=0.063) and specificity was higher than that of ES using both insulin and C-peptide (p≤0.002). HOMA-B with defined cut-offs using insulin and C-peptide at the end of the fasting test showed excellent diagnostic sensitivity and specificity and might represent an alternative and precise tool to diagnose insulinoma.

Disclosure

K.Bódis: None. M.Schön: None. L.Dauben: None. M.Wilker: None. K.Strassburger: None. V.Burkart: None. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi. K.Müssig: None.
1576-P: Hepatic Ketogenesis Insufficiency Improves Glycemia in Type 1 Diabetes
Authors: GOPAL REDDY MOOLI RAJA , RAMAKRISHNAN SADEESH KUMAR
Published: June 2023

Type 1 diabetes (T1D) is a chronic autoimmune disease and is increasing by approximately 2-3% per year. One characteristic feature of T1D is the increased production of ketone bodies. However, the role of ketone bodies and/or ketogenesis in the pathogenesis of T1D remains unknown. We generated mice with conditional ketogenic insufficiency by knocking out the ketogenic enzyme 3-hydroxy methylglutaryl CoA synthase 2 (Hmgcs2) in the liver. Six to eight-week-old Hmgcs2ΔLiv and Hmgcs2F/F(littermates that do not express Alb-Cre) were injected with tamoxifen @200 mg/kg body weight. One week later, Hmgcs2ΔLiv and Hmgcs2F/F mice were injected with strep tozotocin (STZ; 50mg/kg B.W for 5 consecutive days) to induce hyperglycemia. We found that Hmgcs2ΔLiv mice had significantly lower blood glucose than their littermate controls. The improvement in glycemia is not due to a change in food intake or body weight. Moreover, no difference in serum insulin levels and Akt phosphorylation in the liver suggested that ketogenic insufficiency does not improve glycemia in T1D via the insulin signaling pathway. When we assessed glucose production by pyruvate tolerance test, Hmgcs2ΔLiv mice showed lower glucose levels. Further, the mRNA and protein levels of gluconeogenic genes such as G6PCand PCK1 were significantly decreased in the livers of Hmgcs2ΔLivmice. We also observed a significant reduction in PGC-1α, the transcriptional regulator of gluconeogenesis, suggesting that ketogenic insufficiency in T1D reduces hepatic gluconeogenesis. The metabolism of ketone bodies in peripheral tissues impairs their ability to utilize glucose. Our indirect calorimetry analysis showed a trend toward increased respiratory exchange ratio (RER) in STZ-treated Hmgcs2ΔLiv mice, suggesting that ketogenic insufficiency increases carbohydrate metabolism in T1D. Our data show that ketogenesis may contribute to hyperglycemia in T1D by regulating hepatic glucose production and peripheral glucose utilization.

Disclosure

R.Mooli: None. S.Ramakrishnan: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (DK110537)
162-OR: Diabetes Stigma and Use of Diabetes Technologies among U.S. Adults Living with Type 1 Diabetes
Authors: GARZA MATTHEW , SHOGER ERIK , HOLMES-TRUSCOTT ELIZABETH , JOINER KEVIN , ADDALA ANANTA , NARANJO DIANA , BEVERLY ELIZABETH A. , SPEIGHT JANE
Published: June 2023

Nearly 80% of adults living with diabetes report experiences of diabetes stigma. We aimed to examine associations between diabetes stigma and the use of diabetes technologies among adults with type 1 diabetes (T1D). In August 2022, 594 adults with T1D (mean age: 55±15 years; duration T1D: 29±17 years; 71% women) from the dQ&A US Patient Panel completed an online survey. Questions included the Type 1 Diabetes Stigma Assessment Scale (DSAS-1) and diabetes and demographic characteristics. DSAS-1 Total and subscale (Treated Differently, Blame and Judgment, Identity Concerns) scores were compared by device use (independent samples t-test). Individuals who did not use diabetes technologies reported greater stigma (Total; Treated Differently; Identity Concerns) but did not differ from those using technologies on Blame and Judgment (Table). The relationship between diabetes stigma and technology use is a novel finding, warranting further investigation with larger, more heterogeneous samples to determine whether diabetes stigma may be a barrier to device use or whether it is mitigated by device use.

Disclosure

M.Garza: Other Relationship; Sanofi. E.Shoger: Other Relationship; Dexcom, Inc., Abbott Diabetes, Tandem Diabetes Care, Inc., Beta Bionics, Inc., Xeris Pharmaceuticals, Inc., MannKind Corporation. E.Holmes-truscott: Research Support; Sanofi, AstraZeneca. K.Joiner: None. A.Addala: None. D.Naranjo: None. E.A.Beverly: None. J.Speight: Research Support; Sanofi, Medtronic, Abbott Diabetes, Lilly, Novo Nordisk A/S, Speaker's Bureau; Sanofi.
1681-P: RNA Binding Protein HuR Is Essential for Adaptive Thermogenesis
Authors: PARK KUN-YOUNG , CHOI SUNGWOO , MYOUNG SUH JAE
Published: June 2023

Brown adipose tissue (BAT) plays a key role in the regulated production of heat in response to cold temperatures, known as adaptive thermogenesis. While the transcriptional mechanisms underlying the thermogenic function of BAT has been widely studied, the role of posttranscriptional processes in BAT thermogenesis remain largely unexplored. RNA binding proteins are central to the control multiple aspects of posttranscriptional RNA biology. Here, we identify brown fat HuR as a critical regulator of adaptive thermogenesis. Mice with adipocyte-specific HuR deletion (AKO) were unable to increase energy expenditure in response to a cold challenge, resulting in marked hypothermia. HuR AKO mice housed at thermoneutrality also failed to increase energy expenditure upon beta-3 adrenoreceptor agonist treatment, indicating a defect in thermogenic BAT. HuR-deleted brown adipocytes displayed impaired mitochondrial respiration under β-adrenergic stimulation. RNA sequencing data revealed that loss of HuR led to downregulation of genes associated with TCA cycle, β-oxidation, and mTORC1 signaling in BAT. Our findings reveal an essential role for RNA binding protein HuR in thermogenic programs of the brown adipocyte and highlight the importance of posttranscriptional processes in BAT thermogenesis.

Disclosure

K.Park: None. S.Choi: None. J.Suh: None.
17-LB: Diabetic Nephropathy Prediction with Machine-Learning Models for Patients with Type 1 Diabetes
Authors: SRIPADA SRISHTI , SRIPADA SHREYA , BELAPURKAR SONALI
Published: June 2023

Cardiovascular disease (CVD) is the leading cause of global mortality in type 1 Diabetes (T1D). This risk remains largely under-managed, leading to a future significant CVD burden. Diabetic nephropathy (DN) is considered a risk factor for CVD and overall mortality in patients with T1D. Identifying risk factors that contribute to the development and progression of DN is therefore important in T1D. Early identification of DN may support earlier intervention for patients with T1D and in turn, reduce future risk for CVD. Using the T1D Exchange Registry database of individuals with T1D in the USA, we sought to develop a machine-learning algorithm to predict patients with DN. With performance metrics of F1-score = 0.67, AUC = 0.78, in our Random Forest model, and F1-score= 0.66, AUC = 0.77 in our Logistics Regression model demonstrates the potential to assist in mitigating DN development and progression.

Disclosure

S. Sripada: None. S. Sripada: None. S. Belapurkar: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. Other Relationship; T1D Exchange. Research Support; Medtronic.
1713-P: Dietary Manganese (Mn) Intake Is Independently Associated with a Lower BMI in Younger Japanese with Type 2 Diabetes Mellitus (T2DM)
Authors: MON KHIN LAY , FUJIHARA KAZUYA , HATTA MARIKO , TAKEDA YASUNAGA , MORIKAWA SAKIKO Y. , HORIKAWA CHIKA , KATO NORIKO , KATO MITSUTOSHI , MAEGAWA HIROSHI , SONE HIROHITO ,   JDDM STUDY GROUP
Published: June 2023

We analyzed the association between dietary Mn intake and obesity measured by BMI after adjustment for intake of nutrients and food groups in people with T2DM in Japan. Participants were 1567 people, 63% male, aged 30 to 89 y who were in the Japan Diabetes Clinical Data Management Study Group (JDDM), one of the largest cohorts of Japanese with diabetes. Intake of food groups was determined by a validated self-administered food frequency questionnaire based on food groups. Obesity was defined as BMI ≥25 kg/m2. Multivariate logistic regression analysis assessed the relationship between quartiles of dietary Mn intake and obesity stratified by age. Participants aged 30 to 89 y were grouped according to the following quartiles for age: 30-54 y, 55-63 y, 64-71 y, and 72-89 y. Compared to the lowest quartile (Q1) for Mn, a significant negative association between Mn and BMI was found in males for all quartiles of Mn (OR [95%CI] of Q2= 0.643 [0.424 - 0.973], Q3= 0.607 [0.374 - 0.986], Q4= 0.398 [0.218 - 0.728], p trend = 0.028) with adjustment for characteristics such as age, sex, current smoking, drinking, insulin, oral hypoglycemic agents treatment, activity, energy intake and macronutrients intake. However, statistical significance disappeared after adding total fiber as a covariate. Compared to the lowest quartile for Mn, the highest quartile of Mn was inversely associated with BMI in the younger age group (30-54 y [OR= 0.296 [0.088 - 0.996]]) even after total fiber adjustment. Multivariate analysis of food groups (rice, vegetables, soy products) that were highly correlated with Mn as covariates showed that the relationships between Mn intake and obesity were maintained (p trend for rice, vegetables, soy = <0.001, 0.187, 0.010) in all participants. In summary, higher dietary Mn intake was independently associated with a lower BMI, especially in the younger group and males. Future prospective or intervention studies are expected to confirm this result.

Disclosure

L.Khin: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. Jddm study group: n/a. K.Fujihara: None. M.Hatta: None. Y.Takeda: None. S.Y.Morikawa: None. C.Horikawa: None. N.Kato: None. M.Kato: None. H.Maegawa: None.
173-OR: CGM-Measured Differences in Pregnancies With vs. Without Gestational Diabetes (GDM) and Adverse Perinatal Outcomes (APO)
Authors: DURNWALD CELESTE , BECK ROY , LI ZOEY , NORTON ELIZABETH , BERGENSTAL RICHARD M. , BANFIELD MATTHEW , JOHNSON MARY L. , DUNNIGAN SEAN , SIBAYAN JUDY , CALHOUN PETER , CARLSON ANDERS L.
Published: June 2023

An objective of the study was to characterize if continuous glucose monitor (CGM) glycemic patterns throughout pregnancy are indicative of gestational diabetes (GDM) and adverse pregnancy outcomes (APOs). A prospective observational cohort of 760 pregnant patients enrolled <17 weeks with A1c <6.5% wore a blinded CGM sequentially during pregnancy. Patients with ≥14 days of CGM data overall with ≥10 days in the 2nd trimester, oral glucose tolerance test (OGTT), and an APO assessment were included. The primary outcome was GDM diagnosis by abnormal OGTT. Large gestational age (LGA) birthweight >90% and hypertensive disorder of pregnancy (HDP) were analyzed. Glycemic metrics using CGM between those with and without GDM and each APO were compared. Participants had a mean±SD of 112±42 days of CGM data. Prevalence of GDM, LGA, and HDP were 7%, 16%, and 27%. Mean glucose, glucose standard deviation, time > 120 mg/dL and > 140 mg/dL were significantly higher during the entire gestational period prior to OGTT (mean 27 ± 2 weeks) in those who developed GDM. TIR 63-120 mg/dL and 63-140 mg/dL were significantly lower in those who developed GDM (Table 1). Similar findings were noted for the diagnosis of LGA and HDP. CGM use during pregnancy revealed glycemic differences between those with vs without GDM, LGA, and HDP throughout gestation. Higher glucose levels during pregnancy are associated with these APOs.

Disclosure

C.Durnwald: None. P.Calhoun: None. A.L.Carlson: Advisory Panel; MannKind Corporation, Novo Nordisk, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Insulet Corporation, UnitedHealth Group, Sanofi. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. Z.Li: None. E.Norton: None. R.M.Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. M.Banfield: None. M.L.Johnson: Research Support; Abbott, Lilly, Insulet Corporation, NIH - National Institutes of Health, Patient-Centered Outcomes Research Institute, Novo Nordisk, Tandem Diabetes Care, Inc., Medtronic, Hemsley Charitable Trust, Jaeb Center for Health Research. S.Dunnigan: None. J.Sibayan: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust; United Health Group
1732-P: Correlation of Cyclin D2 with Cell Proliferation in Human Pancreatic Beta Cells and Possible Regulation by CCND2-AS1
Authors: OSONOI SHO , SASAKI TAKANORI , TAKEUCHI YUKI , MIZUKAMI HIROKI
Published: June 2023

Though Cyclin D2 (CCND2) has been considered to be essential for rodent beta cell proliferation, its expression in human beta cells is controversial. We reported CCND2 protein was abundantly expressed also in human perinatal beta cells at ADA 2019. This exclusive expression of CCND2 in the perinatal period would implicate a relationship with beta cell proliferation which is by far rare in human adults, while its regulation mechanism is unclear. GWAS studies identified rs76895963 in CCND2 locus as a genotype that reduced the susceptibility for type 2 diabetes by 50%. The SNP is also located in the sequence of CCND2-AS1, an anti-sense RNA. In this study, we explored the relationship between CCND2 and beta cell proliferation in humans, figuring out any possible regulations associated with CCND2-AS1. We obtained 49 pancreas samples from autopsies. Subjects were divided into 6 groups by age; fetus (F: gestational age 24 to 40 weeks), newborn (N: 0 days to1 month), infant (I: 2 to 12 months), toddler (T: 3 months to 4 years), child (C: 5 to 12 years), and adolescent (A: 13 to 19 years). Formalin-fixed paraffin-embedded sections were used for immunostaining and in situ hybridization analysis. Beta cell proliferation labeled with Ki67 was most abundant in N and rapidly decreased after T. Nuclear CCND2 expression was the highest in F followed by I and was almost not detected in C and A, showing a positive correlation with Ki67 though their peaks were different (p<0.01). CCND2 mRNA was abundant in F and N but was also detectable in C and A. The correlation between CCND2 mRNA and protein was linear (p=0.0513). On the other hand, the expression of CCND2-AS1 was significantly correlated with CCND2 protein and Ki67 (p<0.01 and <0.05). Antisense RNAs are reported to show a variety of post-transcriptional regulations on their corresponding mRNA and protein. Our results suggest that CCND2-AS1 may positively regulate CCND2 expression and be a provisional therapeutic target for beta cell proliferation.

Disclosure

S.Osonoi: None. T.Sasaki: None. Y.Takeuchi: None. H.Mizukami: None.
1739-P: Ontogeny of Bihormonal Islet Cells within the Human Pancreas
Authors: HAHM JIWON , FERNANDEZ ANDRADE JUAN A. , ARANY EDITH , HILL DAVID J.
Published: June 2023

Bi-hormonal islet endocrine cells have been proposed to represent an intermediate state during cellular trans-differentiation, enabling plasticity of islet beta-cells in response to metabolic stress. Beta-cell plasticity and regenerative capacity are thought to decrease with age. We investigated bi-hormonal islet endocrine cell populations present throughout the human lifespan between 11 days to 79 years of age. Immunohistochemical staining was performed on paraffin-embedded sections of pancreata from 24 individuals without diabetes for insulin, glucagon, and somatostatin. The sections were imaged with epifluorescence microscopy, and hormone-positive cells were manually counted using ImageJ software considering cells where more than 50% of the area was immunopositive. The mean proportional presence of glucagon-, insulin-, and somatostatin-immunopositive cells within islets was 28.8%, 65.1%, and 13.8% respectively, similar to previous reports for human islets. The relative presence of alpha- and beta-cells increased, and for delta-cells decreased, with advancing age. With respect to bi-hormonal cells the overall presence of glucagon+/insulin+ cells was 3.3%, for somatostatin+/insulin+ cells was 2.4%, and for glucagon+/somatostatin+ cells was 1.7% relative to total islet cell number. The proportion of glucagon+/somatostatin+ cells in the islets of female individuals, in particular, diminished with age (r2=0.43), whereas the other cell types remained largely constant with age in both sexes. The prevalence of tri-hormonal islet cells was low (0.45%). The findings suggest that bi-hormonal islet cells are present within human pancreatic islets throughout life, perhaps reflecting an ongoing potential for endocrine cell plasticity.

Disclosure

J.Hahm: None. J.A.Fernandez andrade: None. E.Arany: None. D.J.Hill: None.

Funding

Lawson Foundation
1767-P: “Leader” ß-Cells within the Pancreatic Islet Are a Functionally Stable Subpopulation In Vitro and In Vivo
Authors: DELGADILLO SILVA LUIS F. , RUTTER GUY A. , CHABOSSEAU PAULINE L. , PROVENCHER-GIRARD AUDREY , PRAT ALEXANDRE , LOPEZ NORIEGA LIVIA
Published: June 2023

β-cell coordination within the islet is critical for normal glucose-stimulated insulin secretion. Recently, we and others have identified a subpopulation of β-cells termed “leaders” which are the first cells to show an increase intracellular Ca2+ during glucose-induced Ca2+ waves. In the Zebrafish, photo ablation of leader cells disrupts pan-islet coordination identifying these as likely pacemakers alongside connected “hub” cells. Our earlier studies were conducted over relatively short time windows (~1hr), leaving open the possibility that leader cells may simply reflect the emergence of a transient functional state rather than a stable subpopulation. To address this question, we used islets from Ins1Cre:GCaMP6ffl/fl transgenic mice which express the Ca2+ sensor GCaMP6f selectively in β-cells. Fast (3-6 Hz) confocal imaging and cell-tracking were used to record calcium dynamics with cellular resolution during stimulation in vitro at 11 mM glucose. Adenoviral delivery of photo-activable PA-mCherry, and excitation with UV light, allowed the identification and labelling of leader cells. Re-imaged 24 h later, 80% (8/10; 4 mice in 2 separate experiments) of islets had the same leader cell as in the earlier session. Correspondingly, after islet engraftment into the anterior chamber (ACE) of the mouse eye, and revascularization, multi-photon imaging revealed calcium waves that were initiated from the same region of the islet in vivo in imaging sessions 24 h apart. These findings establish leader β-cells as a stable subpopulation in vitro and in vivo whose dysfunction may contribute to defective insulin secretion in some forms of diabetes.

Disclosure

L.F.Delgadillo silva: None. G.A.Rutter: Consultant; Sun Pharmaceutical Industries Ltd. P.L.Chabosseau: None. A.Provencher-girard: None. A.Prat: None. L.Lopez noriega: None.
207-OR: Myostatin Inhibition Synergizes with GLP-1R Agonism to Accelerate Weight Loss in Male, Obese Nonhuman Primates
Authors: MASTAITIS JASON , GOMEZ DANIEL , LE ROUZIC VALERIE , STEC MICHAEL , KHAN NAVEEN , NA ERQIAN , MCWILLIAMS TOYA , MIN SOO , SLEEMAN MARK
Published: June 2023

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become standard-of-care for the pharmacological treatment of obesity by inducing clinically meaningful weight loss through a reduction in appetite. While these agents potently reduce fat mass, the caloric restriction also reduces skeletal muscle mass. Strategies to preserve skeletal muscle in the presence of caloric restriction are needed to improve weight loss quality in obese patents. Trevogrumab (∝-MSTN) and garetosmab (∝-ActA) are fully human monoclonal antibodies that potently inhibit two mediators of skeletal muscle atrophy: myostatin (MSTN) and activin A (ActA). We first tested the effects of ∝-MSTN, ∝-ActA and GLP-1RA (Semaglutide [Sema]) on body composition of diet-induced obese mice either alone or in combination. Sema (-29.8%) and ∝-MSTN/∝-ActA (-23.4%) produced significant reduction in fat mass after 4 weeks of treatment vs baseline. Adding MTSN and ActA blockade to Sema produced an additive effect on fat mass (-54.2%). This combination also increased lean mass by 9.8% vs a 1.9% loss with Sema alone. To test this in primates, we performed a 20-week study with the combined administration of either Sema + ∝-MSTN or Sema + ∝-MSTN and ∝-ActA in obese male cynomolgus monkeys. The combination of ∝-MSTN + Sema was sufficient to cause an additive effect on fat mass -43.9% vs -25.1% for Sema alone. The addition of ∝-ActA to the combination produced a similar reduction in fat (-49.6%). The Sema control group also lost -2.5% lean mass after 20 weeks; despite the significant reduction in fat mass, the addition of ∝-MSTN to Sema slightly increased lean mass over the same period (0.5%); the addition of ∝-ActA increased lean mass even further (6.2%). These data suggest the blockade of MSTN and ActA to GLP-1RA treatment could greatly improve the quality of weight loss with this class of anti-obesity agents.

Disclosure

J.Mastaitis: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. D.Gomez: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. V.Le rouzic: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. M.Stec: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. N.Khan: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. E.Na: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. T.Mcwilliams: None. S.Min: Employee; Regeneron Pharmaceuticals Inc., Stock/Shareholder; Regeneron Pharmaceuticals Inc. M.Sleeman: Employee; Regeneron Pharmaceuticals Inc.

Funding

Regeneron Pharmaceuticals Inc.
287-LB: Thiazolidinedione Ameliorates Lipotoxicity-Induced Pancreatic ß-Cell Ferroptosis Partly via ACSL4
Authors: ZHANG MEI , QIN LU , QIN YAO , WEI QIANYING , CHEN XIN
Published: June 2023

Pancreatic β cells death is a major factor driving the deterioration of glucose control in type 2 diabetes mellitus (T2DM). Ferroptosis is a non-apoptotic form of lipid peroxidation-induced cell death. The long-chain acyl-CoA synthetase 4 (ACSL4) contributes significantly to lipid metabolism and determines ferroptosis sensitivity. Accounting for still limited understanding of lipotoxicity-related ferroptosis in β cells, we aim to identify pancreatic β cells ferroptosis in lipotoxicity-induced diabetes and the role of ACSL4 plays in this process. In this study, we found that fatty acids could induce apoptosis in pancreatic β cells, along with a new form of death called ferroptosis. Pancreatic islets of 16-week HFD-fed mice showed reduced mitochondrial cristae, decreased mitochondrial cristae, and increased bilayer membrane density compared to LFD-fed mice. Iron fluorescence staining showed increased intracellular Fe2+ levels in pancreatic islets. Ferroptosis inhibitor fer-1 had a specific protective effect of on HFD-induced β-cell ferroptosis. Through using the Cre-LoxP system, we performed a ACSL4 knockout model of the HFD-induced metabolic diseases, we found that lipid metabolism dictates ferroptosis in pancreatic β cells through ACSL4, which appear to be related to pancreatic β cells dysfunction. ACSL4 knockdown attenuated fatty acids-induced ferroptosis in pancreatic β cells in vivo and in vitro. ACSL4 overexpression induces ferroptosis in MIN6 cells. Moreover, we observed that troglitazone attenuated AA, DHA, PA and erastin induced ferroptosis in MIN6 cells. These results together provide definitive evidence linking β cells with lipotoxicity-induced ferroptosis and suggest the anti-ferroptosis effect of ACSL4 may be a new therapeutic target for the targeted therapy of T2DM.

Disclosure

M. Zhang: None. L. Qin: None. Y. Qin: None. Q. Wei: None. X. Chen: None.

Funding

National Natural Science Foundation of China (81974103)