bluuebunny/crossref_metadata_2025 huggingface dataset:
396-P: The Humanistic Burden of Type 1 Diabetes in U.S. Adults With or Without Recurrent Severe Hypoglycemic Events—A Qualitative Interview Study
Authors: BOATENG-KUFFOUR ADRIANA , CALLAHAN PATRICK , CHANDARANA KEVAL , GAGLIA JASON L. , PHINNEY MICHAEL , GUZMAN ORTEGA ERICK , KRUPNICK ROBERT N. , REANEY MATTHEW , POLONSKY WILLIAM H.
Published: June 2023

Introduction: Despite advances in technology, many people with type 1 diabetes (T1D) still experience severe hypoglycemic events (SHEs). This study explored the perceived humanistic burden of T1D in adults using continuous glucose monitor (CGM) in the US with or without recurrent SHEs.

Methods: In 60-minute semi-structured interviews, adult CGM users with self-reported T1D diagnosis (≥5 yrs.) described the burden of TID on quality of life (QoL). Participants ranked the ‘top 3’ negative impacts of T1D on QoL. Subgroup analyses were conducted in participants with recurrent SHE (rSHE; ≥2 SHEs last yr.) and without recurrent SHE (nSHE; ≤1 SHEs last yr.).

Results: Participants (N=31; 42% rSHEs, 58% nSHEs) were 74% female and 81% were married. Mean age of T1D diagnosis was 28 yrs. Median SHEs in the past year in the rSHE group were 3 and in the nSHE group were 0. Both groups had mean HbA1c of 7.1%. rSHE and nSHE participants used hybrid closed loop systems (hCLS) (53.8% vs. 44.4%), multiple daily injections (23.1% vs. 33.3%) and continuous subcutaneous insulin infusion pump without hCLS (23.1% vs. 22.2%), respectively. All participants reported negative impacts on physical health, mental health, sleep, relationships, leisure activities, work/studies, and sex life. The ‘top 3’ ranked impacts for the rSHE cohort were physical health and sleep (tied at first) followed by leisure activities. Impacts to physical health, mental health, and relationships were ‘top 3’ for the nSHE cohort.

Conclusions: Recurrent severe hypoglycemia is observed to persist despite use of advanced diabetes technology. Negative impacts on physical health ranked as the primary concern in both rSHE and nSHE cohorts. However, moderate variability in ranked negative impact order was observed between the cohorts.

Disclosure

A.Boateng-kuffour: None. P.Callahan: Consultant; Rhythm Pharmaceuticals, Inc., Abbott Diabetes, HealthCore Inc., BMS, Employee; Vertex Pharmaceuticals Incorporated, Genesis Research. K.Chandarana: Employee; Vertex Pharmaceuticals Incorporated, Stock/Shareholder; Vertex Pharmaceuticals Incorporated. J.L.Gaglia: Advisory Panel; Dompé, Consultant; Vertex Pharmaceuticals Incorporated, Abata Therapeutics, Avotres Inc., Current Health, Research Support; Avotres Inc., Dompé, Imcyse, Stock/Shareholder; Vertex Pharmaceuticals Incorporated. M.Phinney: None. E.Guzman ortega: Research Support; Vertex Pharmaceuticals Incorporated. R.N.Krupnick: Consultant; Vertex Pharmaceuticals Incorporated. M.Reaney: None. W.H.Polonsky: Consultant; Abbott Diabetes, Boehringer Ingelheim and Eli Lilly Alliance, Eli Lilly and Company, Insulet Corporation, Intuity Medical, Inc., MannKind Corporation, Provention Bio, Inc., Sanofi-Aventis U.S., Vertex Pharmaceuticals Incorporated.
401-P: Effects of Teneligliptin on Lipotoxicity in High-Fat Diet–Induced Diabetic Kidney Disease Model
Authors: KYUNG KIM HAE , KIM RYEONG-HYEON , YANG YURIM , PARK HYUNKI , JEON NARA , LEE MINYOUNG , LEE HYANGKYU , JIN LIM BEOM , YOUNG CHOI HOON , SEOK KANG EUN
Published: June 2023

Lipotoxicity contributes to diabetic kidney disease (DKD), impairing function of glomerulus and podocyte, consequently causing albuminuria. Dipeptidyl peptidase-4 (DPP-4) inhibitors demonstrated renoprotective effects in DKD, but the mechanism for protection in DKD regarding lipid metabolism is unclear. Here, we investigated the effects of teneligliptin in high-fat diet (HFD)-induced DKD model. 5-week-old male C57BL/6J mice were supplemented with HFD for 24 weeks to develop DKD. Teneligliptin was administrated orally by pre-mixing with HFD for 16 weeks. Body weight, blood glucose levels, and glucose and insulin tolerance test were evaluated at 12 weeks and albuminuria was evaluated at 6 and 12 weeks after teneligliptin administration. Lipid panels were evaluated and the renal cortex was collected for histologic examination at 16 weeks. Body weight, random and fasting blood glucose was not significantly different but total cholesterol and triglyceride were reduced in teneligliptin group. Glucose and insulin tolerance test showed significant improvement in teneligliptin group compared with HFD group (p<0.001 and p=0.009, respectively). Changes in albuminuria between 6 and 12 weeks during treatment period group were lower in teneligliptin group compared with HFD group (p=0.07). In immunohistochemistry studies, glomerular volume and mesangial expansion were attenuated in the teneligliptin group by 26.9% and 32.15% respectively (p=0.011 and p=0.043, respectively). Glomerular basement membrane thickness and foot process width were decreased by 43.2% and 9.32% in teneligliptin group (p=0.0007 and p=0.035, respectively). Teneligliptin attenuated diabetic kidney disease in HFD-induced DKD by preserving integrity of glomerulus and podocyte, with decreased albuminuria. Further investigations for detailed mechanisms about the association between DPP-4 inhibitor and lipotoxicity induced glomerulus and podocyte injury in DKD are warranted in the future.

Disclosure

H.Kim: None. E.Kang: None. R.Kim: None. Y.Yang: None. H.Park: None. N.Jeon: None. M.Lee: None. H.Lee: None. B.Lim: None. H.Choi: None.
404-P: Single-Cell RNA Profiling Changes in Glomerular Cells in Diabetic Nephropathy (DN)
Authors: FU JIALIN , LI QIAN , PARK KYOUNGMIN , HUANG QIAN , WU I-HSIEN , KING GEORGE L.
Published: June 2023

Hyperglycemia, the main risk factor for DN, causes complex pathological damages in glomeruli. To characterize detail changes in cell differentiation and gene expressions induced by diabetes, we performed unbiased single-cell RNA sequencing (scRNA-seq) on glomerular cells from diabetic and nondiabetic mice of long duration. Glomerular cells were isolated from C57 mice after 7-months of STZ-induced diabetes, when clear glomerular pathologies have been documented. Total number of 48,337 high-qualitied glomerular cells were isolated and sequenced from WT and STZ-treated mice. Based on clustering analysis and cell-type specific markers, 12 different cell types were identified, including endothelial cells (EC), podocytes, mesangial cells (MC), proximal tubule cells, parietal epithelial cells (PEC), collecting duct cells, ascending loop of Henle, macrophages, B cells, T cells, NK cells and neutrophils. Over 90% of the cells were from glomeruli (41% EC, 34 % podocytes, 14% MC, 2% of PEC), and 6% immune cells. Interestingly, gene profiling identified 9 clusters of EC, 5 clusters of MC and 7 clusters of podocytes. Diabetes did not change the total cell numbers for EC, MC and podocytes, although macrophage and B cell numbers were increased from 2.2% to 4.8% and 0.35% to 1%, respectively. Cluster subset analysis of EC, MC and podocytes showed that diabetes induced substantial changes. For podocytes, diabetes increased those clusters (5% to 37%) with high expressions of stressed proteins such as Hspa1a, Hspa1b and Hsp90aa1, while decreased those clusters with high expressions of ECM production and CDC42 GTPase cycle, that were involved in cytoskeleton stabilization and foot process formation. Findings from scRNA-seq of glomeruli showed there were multiple subsets of podocytes, EC and MC, which appear to have different functions and their distributions were changed by diabetes. Understanding the mechanism for the distribution changes of the subsets may provide new insight in the pathogenesis of DN.

Disclosure

J. Fu: None. Q. Li: None. K. Park: None. Q. Huang: None. I. Wu: None. G.L. King: Research Support; Janssen Research & Development, LLC.
405-P: ROCK2 Activation and Its Role in Folic Acid–Induced Murine Model of Nephropathy
Authors: SEKIGUCHI KENSUKE , MATOBA KEIICHIRO , OHASHI SHINJI , MITSUYOSHI ETSUKO , NAGAI YOSUKE , TAKEDA YUSUKE , NISHIMURA RIMEI
Published: June 2023

Over 2 million people currently receive treatment with dialysis or a kidney transplant throughout the world. Thus, developing a new strategy to treat chronic kidney diseases is significant from the perspective of a health economic and the prevention of cardiovascular death. The small GTPase Rho and its effector Rho-kinase (ROCK) are involved in the pathogenesis of diabetic nephropathy. In chronic kidney diseases including diabetic nephropathy, tubulointerstitial fibrosis is known to be highly associated with renal outcome. We have previously reported that ROCK inhibition prevented the progression of diabetic nephropathy in murine models. With regards to ROCK, there are two isoforms, which are ROCK1 and ROCK2. ROCK1 has been shown to be involved in the endocytosis of albumin in tubular epithelial cells via megalin/cubilin-dependent mechanism. However, the role of renal tubular ROCK2 remains to be elucidated. The aim of this study is to reveal the role of renal tubular ROCK2 in the pathogenesis of chronic kidney disease. To this end, we used a tubulointerstitial injury model known as folic acid-induced nephropathy (FAN). Importantly, ROCK2 was elevated at protein levels in FAN group compared with vehicle-treated group. We next generated tubular specific ROCK2 knockout mouse (TR2KO) by crossing Ksp-Cre mice with mice containing two loxP sites flanking in Exon 3 of ROCK2. In the Ksp-Cre transgenic mice, Cre recombinase has been demonstrated to be expressed in tubules, collecting ducts, and thick ascending limbs. Compared with vehicle-treated group, collagen deposition in the kidneys of FAN group was highly elevated as revealed by Masson’s trichrome staining. The increased collagen deposition was significantly improved in TR2KO. Our findings indicate that ROCK2 regulates the progression of tubulointerstitial fibrosis. ROCK2 may be a potential therapeutic target for the prevention of chronic kidney disease.

Disclosure

K.Sekiguchi: None. K.Matoba: None. S.Ohashi: None. E.Mitsuyoshi: None. Y.Nagai: None. Y.Takeda: None. R.Nishimura: Speaker's Bureau; Sanofi K.K., Medicure Inc., Boehringer Ingelheim Inc., Takeda Pharmaceutical Company Limited, Kissei Pharmaceutical Co., Ltd., Novartis Pharma K.K., Eli Lilly Japan K.K., Novo Nordisk, Merck & Co., Inc., Abbott Japan Co., Ltd., Astellas Pharma Inc., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., AstraZeneca.
413-P: Intensive Insulin Therapy Delays the “Breakpoint” to Progressive Kidney Function Decline—New Findings and Implications of eGFR Trajectory Analysis in DCCT/EDIC Data
Authors: IHARA KATSUHITO , SKUPIEN JAN K. , SATAKE EIICHIRO , PERKINS BRUCE A. , KROLEWSKI ANDRZEJ
Published: June 2023

Patterns of kidney function decline vary among those with T1D. End-stage kidney disease (ESKD) develops after progressive kidney function decline that begins when kidney function is normal, regardless of albuminuria. We aimed to determine if these findings were observed in the DCCT/EDIC cohort, which enrolled 1,441 individuals and randomly assigned them to intensive insulin therapy (n=711) or conventional insulin therapy (n=730). Baseline mean eGFR and AER were 125 ml/min/1.73m2 and 12 mg/24 hours, respectively. During 27 years of follow-up 129 individuals reached reduced eGFR <60ml/min/1.73m2 or ESKD. For these individuals we applied latent class trajectory analysis minimizing sum of squares of linear spline models with varying knot placement to identify patterns of eGFR decline. We identified two patterns: i) slow decline without eGFR breakpoint (n=56) and ii) fast decline with clear breakpoint (n=73). Slow decliners reached reduced eGFR but rarely ESKD (2%), while many fast decliners progressed to ESKD (35%) within 5-15 years after the breakpoint. Fast decline was less frequent in intensive compared to conventional insulin therapy [26 (3.7%) vs 47 (6.4%), respectively, p=0.022] and had longer median time from enrollment to breakpoint (18 vs 13 years, respectively, p=0.0004). However, the slope of annual loss of eGFR after breakpoint did not differ. In conclusion, we identified a unique phenotype - the “breakpoint” to fast decline in eGFR - as the main predictor of ESKD in T1D. This breakpoint started while eGFR was normal, subsequent decline was linear, and the onset of the breakpoint was substantially delayed by intensive insulin therapy rather than the slope of decline itself. Research on biomarkers that predict the onset of the eGFR ‘breakpoint’ is needed.

Disclosure

K.Ihara: None. J.K.Skupien: None. E.Satake: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). A.Krolewski: None.
419-P: Glucose-Induced Cellular Resistance to Methylglyoxal Is Lost in Patients with Diabetes Complications and Further Deteriorated after Caloric Restriction
Authors: RAUCHHAUPT EKATERINA V. , RODEMER CLAUS , KLIEMANK ELISABETH , KOPF STEFAN , HERZIG STEPHAN , NAWROTH PETER , SZENDROEDI JULIA , ZEMVA JOHANNA , SULAJ ALBA
Published: June 2023

Aim: Glucose stress can be protective against dicarbonyl-mediated toxicity. This study aimed to investigate cellular resistance against methylglyoxal (MG) after glucose stress in healthy humans (CON), patients with (T2D+) and without diabetes complications (T2D-) and whether this is affected by caloric restriction. Fibroblast growth factor 21 (FGF21) and β- hydroxybutyrate (β-HB) were analyzed as marker for metabolic adaptation to stress response and ketogenesis.

Methods: Peripheral blood mononuclear cells were isolated before and 2h after oGTT and incubated at each time-point with increasing MG-levels for 24hrs. Cell viability was measured with CellTiter-Glo to determine changes of MG-resistance at 2h after oGTT (ΔEC50). Experiments were repeated after a 5-day fasting-mimicking diet (FMD). FGF21 and β-HB were measured in venous blood.

Results: Thirty participants (18m/12f, age 64.6 [62.2, 67.0] y, BMI 28.6 [27.2, 30.0] kg/m2) were included. HbA1c was higher in T2D+ (7.4 [6.9, 7.9] %) and T2D- (7.0 [6.2, 7.7] %) compared to CON (5.5 [5.1, 5.8] %, p<0.001), age and BMI were comparable. ΔEC50 of MG increased in CON before and after FMD (12.9% vs. 12.6%), was unaffected in T2D- (1.8% vs. -1.7%) and decreased in T2D+ after FMD (-3.9% vs. -19.0%, p<0.01) and when compared to T2D- and CON (p<0.05). ΔFGF21 increased in CON after FMD (7.7% vs. 115.0%, p<0.05) and tended to be higher compared to T2D- and T2D+ (115.0% vs. 69.3% vs. 47.5%, p=0.5). ΔFGF21 correlated with β-HB (r = 0.48, p<0.01), with strongest correlation for T2D+.

Conclusion: Acute glucose stress induces cellular resistance to MG in healthy humans, a response which is lost in T2D with diabetic complications and aggravates after caloric restriction. Our data suggest for an association between loss of capacity for handling dicarbonyl stress and the presence of diabetic complications. FGF21 might play an important role in the metabolic adaptation to dicarbonyl stress and ketosis.

Disclosure

E.V.Rauchhaupt: None. C.Rodemer: None. E.Kliemank: None. S.Kopf: Advisory Panel; Novo Nordisk, Bayer Inc., Recordati Rare Disease, Speaker's Bureau; Novo Nordisk, Boehringer-Ingelheim. S.Herzig: Consultant; Novo Nordisk, Actimed, Research Support; Novo Nordisk, Boehringer-Ingelheim, Almac. P.Nawroth: None. J.Szendroedi: None. J.Zemva: None. A.Sulaj: None.

Funding

DFG; German Research Foundation (236360313-SFB, 1118DZD); German Center for Diabetes Research (82DZD07C2G)
42-LB: Low-Carbohydrate Diet Compared with Canagliflozin for the Treatment of Diabetes—A Randomized Noninferiority Trial
Authors: GU YUNJIE , XIA XINYI , XU MIAO , LI LI , YIN JUN
Published: June 2023

Aims and Introduction: A low-carbohydrate diet (LCD) is effective for glycemic control in patients with diabetes. However, most previous studies have compared LCD with a low-fat or low-calorie diet. In this study, we used canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, as the positive control drug and aimed to establish the non-inferiority of LCD to canagliflozin in terms of blood glucose control.

Methods: We conducted a 3-month, multicenter, randomized, open-label, parallel-controlled clinical trial involving patients with type 2 diabetes. Participants were randomly assigned in a 1:1 ratio to receive canagliflozin (100 mg/day) or LCD (carbohydrate intake < 20% of the total energy intake). The primary outcome was the change in HbA1c level, and the secondary outcomes were Continuous Glucose Monitoring (CGM)-measured time in the target glucose range of 3.9-10 mmol/L and the cost of antidiabetic agents.

Results: In total, 121 participants from three hospitals were enrolled; 61 were administered canagliflozin and 60 were administered LCD. After the 3-month intervention, the mean change in HbA1c levels was -1.76% with canagliflozin and -2.23% with LCD (estimated difference, -0.47%; 95% confidence interval [CI], -0.85-0.08; P = 0.0180). Time in range (TIR) increased from 48.96% at baseline to 80.21% at 3 months in the canagliflozin group and from 52.08% to 93.75% in the LCD group. The TIR in the LCD group was significantly higher than that in the canagliflozin group (P = 0.0026). Additionally, in the LCD group, 10 of 52 patients who had been using antidiabetic drugs (19.2%) discontinued one oral antidiabetic drug or reduced their insulin doses.

Conclusions: Our study showed that LCD was non-inferior to canagliflozin in glycemic control. Patients in the LCD group showed greater decline of HbA1c levels and higher TIR than those in the canagliflozin group. LCD reduced the cost of antidiabetic drugs.

Disclosure

Y. Gu: None. X. Xia: None. M. Xu: None. L. Li: None. J. Yin: None.

Funding

National Natural Science Foundation of China (82070885); Shanghai Municipal Education Commission (20172025); Xuhui Joint Research Projects on Important Diseases (XHLHGG202110)
42-OR: The Impact of a Digital Health Coaching Program on a Rural Population
Authors: MOORE JASMINE , RUTLAND SARAH , TRAN VANESSIA T. , STEPHEN BURTON B.
Published: June 2023

Compared to urban areas, the prevalence of diabetes is higher in rural areas. The effects of diabetes are compounded by barriers endemic to rural populations, such as limited access to care and health education. A digital health coaching (DHC) program may address these barriers. This retrospective analysis explored how a DHC program influenced outcomes among patients with T2DM who live in a rural area. Individuals with T2DM were enrolled in a 6-month condition-specific DHC program via an employer/payor program or physician. A comparative analysis assessed changes in physical, mental, and emotional health metrics among those living in a rural area, defined as areas located outside of a U.S. Census Bureau Urbanized Area (an urban area of 50,000 or more people). Paired t-tests were used to determine differences between the overall average baseline and month 6 scores. From January 1, 2021, to September 30, 2022, 584 rural participants were enrolled in the DHC program. Most participants were female (75%) with an average age of 55. At 6 months, there were significant improvements in diabetes distress scores (2.6 to 2.0, P=0.0007) and HbA1c (8.3 to 7.2, P=0.0071). Participants in the program showed improved outcomes for diabetes-related quality of life measures at 6 months. This analysis suggests that implementing a DHC program that addresses modifiable behaviors and barriers can help reduce the burden of diabetes in a rural population.

Disclosure

J.Moore: None. S.Rutland: None. V.T.Tran: None. B.Burton: None.
423-P: Urinary Extracellular Vesicles in African Americans with Chronic Kidney Disease With and Without Type 2 Diabetes Mellitus
Authors: THETHI TINA K. , BILAL ANIKA , ZAINO MATTHEW S. , ILIUK ANTON , PRATLEY RICHARD E. , NUNEZ LOPEZ YURY O.
Published: June 2023

Introduction: Type 2 diabetes (T2D) is the leading cause for chronic kidney disease (CKD). Novel biomarkers are critical in early detection of CKD.

Methods: Healthy Eatonville Project (HEP) was a prospective study (n=300, females (F)=71%, T2D 32%, CKD 25%) in historically black community of Eatonville, FL. We characterized EVtrap®-isolated urinary extracellular vesicles (uEV) proteins from a balanced HEP cohort of 48 African Americans (mean age 62y, F=73%, BMI 32.2 kg/m2, T2D 46%) with CKD risk ranging from low, intermediate, to high-very high (H-VH), with and without T2D. Differential expression and coexpression network analyses were implemented.

Results: We detected 5265 uEV proteins, 46 of which were significantly (fold change>1.5, P<0.05, FDR<0.1) differentially expressed (DE) in CKD risk groups. Of those, 24 were significantly upregulated in H-VH risk CKD (Figure Module Pr.1). A set of 15 DE proteins appeared to represent a protective pathway against CKD (Figure Module Pr.2). Key biomarkers of acute kidney injury IGFBP7, TIMP2, and IL18 had significant negative correlations with CKD risk (-0.59 ≤ r ≤ -0.44, P<0.002). Supporting our findings, several of these biomarkers had been previously reported in kidney disease studies.

Conclusion: The uEV proteomic landscape is representative of kidney pathophysiology and suggests potential biomarkers of CKD in Africans Americans.

Disclosure

T.K.Thethi: Other Relationship; Bayer Inc., Novo Nordisk. A.Bilal: None. M.S.Zaino: None. A.Iliuk: None. R.E.Pratley: Other Relationship; Bayer Inc., Corcept Therapeutics, Dexcom, Inc., Gasherbrum Bio, Inc., Hanmi Pharm. Co., Ltd., Hengrui (USA) Ltd., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. Y.O.Nunez lopez: None.
424-P: Diabetic Kidney Disease (DKD) Worsens CV Outcomes after First-Ever Major Cardiovascular Event in Type 2 Diabetes (T2D)
Authors: GAROFOLO MONIA , LUCCHESI DANIELA , GIAMBALVO MASSIMO , CAPOBIANCO MARTINA , FRANCESCONI PAOLO , PENNO GIUSEPPE , DEL PRATO STEFANO
Published: June 2023

Aim: CV prognosis worsens in T2D after a first CV event. We assessed impact of DKD on mortality and subsequent CV events after a first CV event.

Methods: Death rate was recorded over a median 14.1 (IQR 13.8-14.5) years follow-up in 961 T2D subjects. Vital status (Italian Health Card Database) was censored on December 31, 2017 (major CV events available for 947 participants). Effect of DKD (ACR <30/≥30 mg/g) and/or CKD-EPI eGFR ≥60/<60 ml/min/1.73 m2) was determined by Kaplan-Meier (K-M) curves and hazard ratios (HR, 95% CI) by unadjusted and adjusted Cox regression models (age, diabetes duration (DD), sex, smoking, retinopathy, hypertension, dyslipidemia, prior CVD; no-DKD as reference).

Results: At census, 229 subjects were dead (23.8%) and 298 participants out of 947 (31.5%) had a first CV event during a median 13.8 year pre-event follow-up. Compared with free-CV event subjects, those with CVD were older, more often men, with longer diabetes duration, worse CV risk profile, more microvascular complications and CVD before recruitment. During a median 6 yr post-first CV event follow-up 99 subjects died: 57 (27.4%) no DKD, 42 (46.7%) DKD (K-M, p=0.005). Compared to no DKD the latter had an unadjusted HR of 1.76 (1.18-2.63, p=0.005; adjusted 1.69, 1.13-2.52, p=0.011). Death rate increased with DKD worsening with statistically significant HR (unadjusted 3.31, 1.73-6.31, p<0.0001; adjusted 3.32, 1.65-6.64, p=0.001) for ACR≥30/eGFR<60. During a median 3.1 post-first CV event follow-up, a new CV event occurred in 124 subjects: 82 (39.4%) no DKD and 42 (46.7%) DKD (K-M, p=0.019) with unadjusted HR for a new CV event in DKD of 1.40 (0.96-2.03, p=0.077). Rate of a secondary CV event increased across DKD phenotypes with unadjusted (HR 3.42, 95% CI 1.76-6.65, p<0.0001) and adjusted HR of 3.18 (1.57-6.44; p=0.001) for ACR≥30/eGFR<60, respectively.

Conclusions: In T2D subjects, DKD still worsens the risk of mortality and secondary CV events after the occurrence of a first CV event.

Disclosure

M.Garofolo: Consultant; Novo Nordisk, Employee; Eli Lilly and Company. D.Lucchesi: None. M.Giambalvo: None. M.Capobianco: None. P.Francesconi: None. G.Penno: Advisory Panel; Eli Lilly and Company, Bayer Inc., Consultant; Novo Nordisk, AstraZeneca, Boehringer Ingelheim Inc. S.Del prato: Advisory Panel; Abbott Diagnostics, Altimmune, Amarin Corporation, Applied Therapeutics Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Vertex Pharmaceuticals Incorporated, Novartis, Consultant; A. Menarini Diagnostics, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi.
425-P: Renin-Angiotensin System Inhibition in Combination with Glucagon-Like Peptide 1 Receptor Agonist Treatment Improve Levels of a Kidney Fibrosis Biomarker in Persons with Type 2 Diabetes
Authors: MØLLER ALEXANDRA , THÖNI STEFANIE , LAURSEN CLARA F.G. , KARSDAL MORTEN A. , GENOVESE FEDERICA , GULDAGER KRING RASMUSSEN DANIEL
Published: June 2023

Background: The drug combinations for rewriting trajectories of renal pathologies in type 2 diabetes (DC-ren) study focuses on DKD, a complication of diabetes often accompanied by cardiovascular disease. Novel biomarkers for identifying persons at increased risk of disease progression and predicting treatment response are currently needed. Levels of urinary C3M, a marker of type III collagen degradation, have been shown to correlate with CKD progression, and dulaglutide treatment improved levels of this biomarker compared with insulin glargine in persons with type 2 diabetes (T2D). We investigated the effect of combination therapy on urinary C3M in persons with T2D.

Method: We measured urinary C3M in urine collected at baseline and after years 1, 2, and 3 from 229 individuals with T2D enrolled in the DC-ren study. All persons were on renin-angiotensin system inhibitor (RASi) treatment at baseline and during follow-up. While some persons remained on RASi treatment (n = 184), others received glucagon-like peptide-1 receptor agonist (GLP-1 RA) on top of RASi (n = 45).

Results: The cohort consisted of 48% males (age of 66 ± 8 years and eGFR was 65 ± 17 ml/min/1.73 m2). Lower baseline levels of urinary C3M were associated with lower eGFR, and this relation remained consistent over time. Levels of urinary C3M were higher in persons after treatment with GLP-1 RA in combination with RASi compared to RASi alone (P = 0.034). In adjusted linear models (for the RASi group), an association of current urinary C3M with future eGFR was found (P < 0.01), indicating that urinary C3M is a prognostic risk marker for kidney function decline.

Conclusion: RASi in combination with GLP-1 RA treatment was associated with increased type III collagen degradation, suggesting a potential effect to reduce kidney fibrosis. This anti-fibrotic effect could be a mechanism for the beneficial effects observed with GLP-1 RA treatment on CKD in T2D.

Disclosure

A.Møller: None. S.Thöni: None. C.F.G.Laursen: None. M.A.Karsdal: Speaker's Bureau; Pfizer Inc. F.Genovese: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. D.Rasmussen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S.
426-P: Semaglutide, Empagliflozin, and Cagrilintide Reduce Levels of Serum Endotrophin in Type 2 Diabetic Rats
Authors: MØLLER ALEXANDRA , MELANDER SIMONE A. , LARSEN ANNA T. , LAURSEN CLARA F.G. , GENOVESE FEDERICA , KARSDAL MORTEN A. , GULDAGER KRING RASMUSSEN DANIEL , HENRIKSEN KIM
Published: June 2023

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) demonstrated cardiovascular (CV) and kidney outcomes benefit in persons with type 2 diabetes (T2D). The long-acting amylin analogue, cagrilintide, is under investigation for the treatment of obesity and T2D. Endotrophin, a pro-fibrotic fragment derived from collagen type VI, is an independent risk marker of mortality, CV and kidney outcomes, and dulaglutide treatment decreased levels of this biomarker compared with insulin glargine in persons with T2D. We investigated for the first time the effect of semaglutide, empagliflozin, and cagrilintide on endotrophin in type 2 diabetic rats.

Method: We measured endotrophin (by the rodent PRO-C6 ELISA) in serum collected at baseline and study end from diabetic ZDF rats treated with either vehicle (n = 10), semaglutide (n = 7), empagliflozin (n = 4), or cagrilintide (n = 10). The dose chosen for semaglutide (50 nmol/kg), empagliflozin (30 mg/kg), and cagrilintide (10 nmol/kg) was based on previous research.

Results: Levels of endotrophin increased significantly during the study in vehicle-treated rats, reflecting the disease progression (median [95% CI] for increase: 182.5 [55.87-298.0], P < 0.01). Interestingly, treatment with semaglutide, empagliflozin, and cagrilintide each attenuated this increase, resulting in significantly lower levels of endotrophin compared to vehicle at study end (P < 0.01), (P < 0.05), and (P < 0.01), respectively.

Conclusion: We developed a novel, robust assay to detect the clinically relevant endotrophin biomarker in rodents. Levels of serum endotrophin increased over time in vehicle-treated rats, which is in line with endotrophin predicting disease progression in persons with T2D. In addition to the beneficial effects on metabolic factors, semaglutide, empagliflozin, and cagrilintide each reduced levels of endotrophin, suggesting a potential effect to reduce fibrosis.

Disclosure

A.Møller: None. S.A.Melander: None. A.T.Larsen: Employee; Nordic Bioscience A/S. C.F.G.Laursen: None. F.Genovese: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. M.A.Karsdal: Speaker's Bureau; Pfizer Inc. D.Rasmussen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. K.Henriksen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S.
432-P: Role of Patatin-Like Phospholipase Domain–Containing 3 Gene for Kidney Dysfunction in Diabetes Endotypes
Authors: ZAHARIA OANA P. , STRASSBURGER KLAUS , KNEBEL BIRGIT , KUPRIYANOVA YULIYA , KOTZKA JORG , BÓDIS KÁLMÁN , SCHÖN MARTIN , BOMBRICH MARIA , MÖSER CLARA , PRYSTUPA KATSIARYNA , AL-HASANI HADI , SCHRAUWEN-HINDERLING VERA , JANDELEIT-DAHM KARIN , WAGNER ROBERT , RODEN MICHAEL
Published: June 2023

Recent studies identified distinct endotypes of diabetes with differences in metabolic features and in risk for diabetes-related comorbidities. Of note, persons allocated to the severe insulin resistant diabetes (SIRD) endotype, who show increased prevalence of nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), are more frequently carriers of the G-allele in the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase domain containing 3 (PNPLA3) gene. This SNP associates with increased risk of NAFLD yet the association between the presence of the PNPLA3 SNP and CKD remains controversial. The present study examined whether this SNP differently associates with CKD in endotypes of recent-onset diabetes. Participants with newly diagnosed diabetes (n=707) from the prospective German Diabetes Study underwent k-means clustering, genotyping, magnetic resonance spectroscopy to determine hepatocellular lipid content (HCL) and laboratory analyses to calculate the glomerular filtration rates (eGFR). SIRD had the lowest eGFR and highest HCL compared to severe insulin deficient, moderate obesity-related, moderate age-related and severe autoimmune diabetes clusters (all p<0.05). HCL was negatively associated with eGFR (r=-0.287, p<0.01) across all groups. Further stratification by PNPLA3 G-allele carrier status did not reveal any association between HCL and eGFR in any of the diabetes types, irrespective of G-allele carrier status. However, with declining eGFR the proportion of G-allele carriers increased from 44% for eGFR >60 ml/min to 52% for eGFR <60 ml/min (p<0.05). In conclusion, increased hepatic lipid content is associated with reduced kidney function across all diabetes endotypes. This association is independent of the presence of the PNPLA3 polymorphism in newly diagnosed diabetes, but there might be role for PNPLA3 for the severity of CKD.

Disclosure

O.P. Zaharia: None. K. Strassburger: None. B. Knebel: None. Y. Kupriyanova: None. J. Kotzka: None. K. Bódis: None. M. Schön: None. M. Bombrich: None. C. Möser: None. K. Prystupa: Other Relationship; Berlin-Chemie AG. H. Al-Hasani: None. V. Schrauwen-Hinderling: None. K. Jandeleit-Dahm: None. R. Wagner: Speaker's Bureau; Novo Nordisk, Sanofi. Advisory Panel; Daiichi Sankyo. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis. Consultant; TARGET PharmaSolutions, Inc. Research Support; Sanofi.

Funding

German Research Foundation; European Foundation for the Study of Diabetes; German Diabetes Association; German Federal Ministry of Education and Research; Heinrich Heine University
435-P: Remnant-C as an Independent Risk Factor for End-Stage Renal Disease in Patients with Type 2 Diabetes—A Nationwide Population-Based Cohort Study
Authors: ROH EUN
Published: June 2023

Few studies have investigated the association between remnant-C and the progression of diabetic nephropathy. We aimed to evaluate the association between remnant-C and the risk of newly developed end-stage renal disease (ESRD) in patients with type 2 diabetes in a nationwide cohort of Korean adults. The risk of incident ESRD according to remnant-C levels was analyzed by Cox proportional hazard models. During the median follow-up period of 9 years, 11,615 individuals (1.4% of the total population) developed ESRD. The serum concentrations of remnant-C was associated with 7% higher risk of ESRD per every 10 mg/dL increase. In multivariable-adjusted analyses, participants in the upper quartile of remnant-C had a higher risk of ESRD, with hazard ratios of 1.15 (95% CI 1.09-1.22) in the second quartile, 1.26 (95% CI 1.20-1.33) in the third quartile, and 1.47 (95% CI 1.40-1.55) in the fourth quartile, compared with the lowest quartile. Furthermore, the magnitude of the increased risk for incident ESRD in individuals with higher remnant-C quartiles was significant in participants aged 50 years or older. These results suggest that remnant-C concentration is an independent risk factor for the development of ESRD in patients with type 2 diabetes.

Disclosure

E.Roh: None.
447-P: Using the Cambridge Risk Score to Predict New Hyperglycemia and Complications in Surgical Patients without Diabetes
Authors: LEE HANNAH , HARTFIELD PHILLIP J. , SINSON GRANT , WANG MARJORIE C. , DAWSON APRILL Z. , THORGERSON ABIGAIL , MENDEZ CARLOS E.
Published: June 2023

Perioperative hyperglycemia is associated with adverse surgical outcomes and increased mortality, and when occurring in patients without history of diabetes, this is termed new hyperglycemia (NH). The Cambridge Risk Score (CRS) is a screening tool for type 2 diabetes that is associated with NH, yet its application in a surgical population has not been studied. Our study examined the association between CRS, NH, and complications in patients undergoing elective surgery. In this retrospective cross-sectional study of adult surgical patients admitted to a tertiary care center over 4 years, subjects with NH (blood glucose ≥140 mg/dL in nondiabetics) were identified, and the CRS was calculated. CRS, NH, and clinical outcomes were adjusted for race/ethnicity, payor type, and Elixhauser Comorbidity Index. Patients were stratified by surgery type (cardiac/vascular, general, orthopedic, and neurologic), and multivariate regression analyses assessed the association between CRS, NH, and clinical outcomes. Of 10,531 subjects included in the study, 24% developed NH. After adjusting for covariates, the CRS was significantly associated with the development of complications (odds ratio [OR], 2.09 [1.69, 2.59]; p<.001) and NH (OR, 1.95 [1.66, 2.29]; p<.001). When stratifying by surgery type, CRS was significantly associated with NH, length of stay, and complications in the neurosurgery and orthopedic surgery cohorts, but not cardiac/vascular or general surgery. NH, when adjusted for covariates, was associated with 30-day readmission rates (OR, 1.52 [1.23, 1.86]; p<.001) and length of stay (linear model estimate, 0.61 [0.57, 0.66]; p<.001), but not with complication outcomes. CRS was associated with the development of NH and complications in elective neurological and orthopedic surgery patients and could help identify high-risk surgical patients. Further study should evaluate if treatment of NH is associated with better outcomes in CRS high-risk patients.

Disclosure

H.Lee: None. P.J.Hartfield: None. G.Sinson: None. M.C.Wang: Consultant; Medtronic, Zimmer Biomet. A.Z.Dawson: None. A.Thorgerson: None. C.E.Mendez: Speaker's Bureau; Siemens.
451-P: Perivascular Adipose Tissue Remodeling Modulates Vascular Mitochondrial Metabolism
Authors: KELLER AMY C. , HENCKEL MELISSA M. , KNAUB LESLIE , POTT GREGORY , JAMES GEORGIA , WALKER LORI A. , REUSCH JANE E.B.
Published: June 2023

Diabetes increases cardiovascular disease (CVD) risk. Diabetes-mediated vascular pathology proceeds differently in men and women. We reported that housing rats at thermoneutral (30°C, TN) conditions alters perivascular adipose tissue (PVAT) phenotype. We also observed related abnormalities in vasoreactivity and mitochondrial function with sex-differences. We hypothesized that TN-mediated PVAT phenotypic transformation alters brown adipose tissue (BAT) regulator PRDM16, fatty acid composition, fatty acid (FA) transporter FATP1, and mitochondrial lipid oxidation in a sex-dependent manner. Male and female Wistar rats were housed at room temperature (24°C, RT) or TN for 16 weeks. Endpoints included PVAT phenotypic characterization, RNA seq analysis, and PVAT mitochondrial respiration. PVAT phenotype was morphologically different between TN and RT rats, with rats housed at TN having 19.7% less BAT phenotype overall (p<0.05). UCP-1 expression was lower in animals housed at TN (p=0.06). PRDM16 was significantly dampened in all animals at TN (p<0.05), and notably decreased in males at TN (80.6%, p<0.05). Loss of BAT markers was associated with changes in FA regulation. Genomic expression of FATP1 was lower in all animals at TN, more prominently in females. Palmitoleic and arachidonic acids were significantly lower in TN females (48.5% and 15.5%, respectively, p<0.05) and males (63.0% and 40.1%, respectively, p<0.05). PVAT of all animals housed at TN showed mitochondrial respiration significantly diminished in lipid substrate experiments for state 3, 4, and uncoupled (p<0.05 for all), aligning with our previous reports in aorta. These data support a model wherein altered PVAT phenotype and FA composition impacts lipid transport and utilization. These changes are associated with differential impact on vascular impairment between females and males. These results provide insights into sex differences in PVAT contributions to vascular disease progression and vascular crosstalk.

Disclosure

A.C.Keller: None. M.M.Henckel: None. L.Knaub: None. G.Pott: None. G.James: None. L.A.Walker: None. J.E.B.Reusch: Advisory Panel; Medtronic.

Funding

National Center for Research Resources (UL1RR025780); U.S. Department of Veterans Affairs (BX002046 to J.E.B.R.), (BX003185 to A.C.K.); National Institutes of Health (R01 DK124344-01A1 to J.E.B.R.); Denver Research Institute; Ludeman Family Center for Women’s Health Research at the University of Colorado Anschutz Medical Campus; Junior Faculty Research Development Grant (to A.C.K.)
454-P: Risk Stratification of Cerebrocardiovascular Disease (CVD) according to HbA1c, Fasting Plasma Glucose (FPG), and Their Combinations in People with Prediabetes (preDM)
Authors: MURAI KOSHIRO , FUJIHARA KAZUYA , YAGUCHI YUTA , YAMADA MAYUKO H. , MATSUBAYASHI YASUHIRO , KITAZAWA MASARU , YAMAMOTO MASAHIKO , YAMADA TAKAHO , KODAMA SATORU , IWANAGA MIDORI , SONE HIROHITO
Published: June 2023

Association between preDM, defined by HbA1c or FPG alone, and CVD has remained controversial whereas impaired glucose tolerance (IGT) defined according to 2-h blood glucose level in the oral glucose tolerance test has been consistently associated with CVD. However, a glucose tolerance test is not practical in all persons. Thus, we attempted to identify a high-risk group for CVD in those with PreDM using HbA1c and FPG combinations. We analyzed data from a nationwide claims database on 1,140,096 Japanese with no CVD history or glucose abnormality from 2008 to 2022. Multivariate Cox regression analysis showed that compared with normal HbA1c (≤5.6%), CVD risk increased significantly and linearly from HbA1c 5.9% to HbA1c 6.8% in the diabetic range. Conversely, compared with normal FPG (70-99 mg/dl), CVD risk did not increase in the preDM range at each FPG level. Analysis of combinations of HbA1c and FPG showed that with FPG levels 70-99 mg/dl compared with HbA1c ≤5.6%, those with HbA1c 6.0-6.4% had an increased risk of CVD. Risk was higher than with HbA1c 6.5-6.8% (hazard ratio [HR] 1.30 [95% CI 1.11-1.52], 1.11 [0.63-1.96]) (Table). Results suggest that preDM with high HbA1c and normal FPG might have potential postprandial hyperglycemia or lack treatment interventions due to undiagnosed diabetes, which could increase risk of CVD.

Disclosure

K.Murai: None. M.Iwanaga: 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. K.Fujihara: None. Y.Yaguchi: None. M.H.Yamada: None. Y.Matsubayashi: None. M.Kitazawa: None. M.Yamamoto: None. T.Yamada: None. S.Kodama: None.
459-P: Remnant Cholesterol and the Presence of Coronary Artery Disease Are Mutually Independent Predictors for the Development of Type 2 Diabetes Mellitus
Authors: PLATTNER THOMAS , VONBANK ALEXANDER , MADER ARTHUR , SPRENGER LUKAS , MAECHLER MAXIMILIAN , LARCHER BARBARA , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2023

Remnant cholesterol is a predictor of cardiovascular event risk and is associated with the metabolic syndrome as well as with type 2 diabetes (T2DM). Whether this lipid parameter also predicts incident diabetes in subjects who do not yet have diabetes is less clear. We therefore prospectively recorded incident diabetes over 4 years in 864 consecutive nondiabetic Caucasian patients who underwent coronary angiography for the evaluation of established or suspected stable coronary artery disease (CAD). Diabetes was diagnosed according to ADA criteria. At baseline, 54.4% of our patients had significant CAD with lumen narrowing ≥50% at angiography; remnant cholesterol was significantly higher in patients with than in those without significant CAD (24±24 vs 19±18 mg/dl; p<0.001). During follow-up, diabetes was newly diagnosed in 87 patients, i.e. in 10.1% of the study population. Remnant cholesterol strongly predicted diabetes both univariately (OR 1.50 [1.23-1.82]; p<0.001) and after multivariate adjustment including both fasting glucose and HbA1c values (OR 1.47 [1.18-1.80]; p<0.001). When we further adjusted for the presence of significant CAD, remnant cholesterol remained predictive of incident diabetes (OR 1.43 [1.15-1.77]; p<0.001), while CAD predicted incident diabetes in this model independently of remnant cholesterol (OR 1.88 [1.17-3.00]; p=0.009). We conclude that remnant cholesterol and the presence of CAD are mutually independent predictors for the development of T2DM.

Disclosure

T. Plattner: None. A. Vonbank: None. A. Mader: None. L. Sprenger: None. M. Maechler: None. B. Larcher: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
463-P: Risk Stratification of Coronary Artery Disease (CAD) according to LDL-C, HDL-C Levels, and Glucose Status
Authors: YAMADA MAYUKO H. , FUJIHARA KAZUYA , OSAWA TAEKO , KITAZAWA MASARU , YAGUCHI YUTA , SATO TAKAAKI , MITSUMA YURIE , YAMAMOTO MASAHIKO , MATSUBAYASHI YASUHIRO , IWANAGA MIDORI , YAMADA TAKAHO , KODAMA SATORU , SONE HIROHITO
Published: June 2023

Whereas elevated LDL-C is a major risk factor for CAD, the inverse association between HDL-C levels and risk of CAD is well-known. Although insulin resistance, and glucose intolerance are associated with low HDL-C levels, it is not clear whether the association of LDL-C with CAD differs depending on glucose status and HDL-C values. We examined associations of LDL-C with the incidence of CAD according to HDL-C and glucose status using a nationwide claims database on 1,524,289 individuals during 2008-2019 with no history of CAD or familial hypercholesterolemia. Cox proportional hazards model identified risks of CAD events among combinations of 3 levels of HDL-C and 7 levels of LDL-C according to glucose status. During a mean follow-up period of 5.5 years, 8,301 CAD events occurred. CAD risk increased from lower LDL-C levels accompanied by lower HDL-C levels regardless of glucose status (Table). Even in people with LDL-C <80mg/dl, HDL-C <40mg/dl conferred 2.5-fold increased risk of CAD all glucose status. HDL-C and LDL-C values had a synergistic effect on the incidence of CAD in people with normoglycemia, whereas an addictive effect in people with prediabetes and diabetes. Although more strict LDL-C target need to be achieved as worsening of glucose status, results demonstrated that the necessity of modulating the LDL-C target according to HDL-C levels is not affected by glucose status.

Disclosure

M.H.Yamada: None. M.Iwanaga: None. T.Yamada: None. S.Kodama: 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. K.Fujihara: None. T.Osawa: None. M.Kitazawa: None. Y.Yaguchi: None. T.Sato: None. Y.Mitsuma: None. M.Yamamoto: None. Y.Matsubayashi: None.
465-P: Anti-inflammatory Therapies in Patients with Established Cardiovascular Disease or High Cardiovascular Risks
Authors: LIN CHU , LI ZONGLIN , CAI XIAOLING , JI LINONG
Published: June 2023

Background: To evaluate the association between anti-inflammatory therapies and the incidence of cardiovascular events in patients with established cardiovascular disease (CVD) or high cardiovascular risks.

Methods: Literature retrieval was conducted in Pubmed, Medline, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov website from the inception to July 2022. Randomized controlled trials compared anti-inflammatory therapies with placebo in patients with established CVD or high cardiovascular risks were included. The results of the meta-analysis were computed as the odds ratio (OR) with 95% confidence interval (CI).

Results: Compared with placebo, anti-inflammatory therapies were associated with decreased incidence of myocardial infarction (MI) (OR=0.93, 95%CI, 0.87 to 0.98), which was mainly driven by therapies targeting central IL-6 signaling pathway (OR=0.84, 95%CI, 0.76 to 0.94). IL-1 inhibitors treatment was associated with reduced risks of heart failure (OR=0.32, 95%CI, 0.14 to 0.76) while lower incidence of stroke was observed in patients with colchicine treatment (OR=0.46, 95%CI, 0.28 to 0.77). MI events were less frequent in patients over 65 years old (OR=0.90, 95%CI, 0.82 to 0.98) or with follow-up duration over 1 year (OR=0.90, 95%CI, 0.84 to 0.96)when comparing anti-inflammatory therapies with placebo.

Conclusion: Anti-inflammatory therapies, especially those targeting central IL-6 signaling pathway may serve as promising treating strategies to ameliorate the risk of MI. Meanwhile, IL-1 inhibitor and colchicine were associated with decreased risks of heart failure and stroke respectively. MI risk reductions by anti-inflammatory therapies seem to be more prominent in patients who were elderly and with long follow-up duration.

Disclosure

C.Lin: None. Z.Li: None. X.Cai: None. L.Ji: Other Relationship; Eli Lilly and Company, Novo Nordisk, Merck & Co., Inc., Bayer Inc., Sanofi-Aventis U.S., Roche Pharmaceuticals, MSD Life Science Foundation, AstraZeneca, Boehringer Ingelheim Inc., Abbott, Metronics.

Funding

National Natural Science Foundation of China (81970698, 81970708); Beijing Natural Science Foundation (7202216)