Abbott Diagnostics Research Articles

Persistence of T-Cell Immunity Responses against SARS-CoV-2 for over 12 Months Post COVID-19 Infection in Unvaccinated Individuals with No Detectable IgG Antibodies.

Immune response to SARS-CoV-2 is crucial for preventing reinfection or reducing disease severity. T-cells' long-term protection, elicited either by COVID-19 vaccines or natural infection, has been extensively studied thus far; however, it is still attracting considerable scientific interest. The aim of the present epidemiological study was to define the levels of T-cellular immunity response in a specific group of unvaccinated individuals from the general population with a prior confirmed COVID-19 infection and no measurable levels of IgG antibodies. We performed a retrospective descriptive analysis of data collected from the medical records of consecutive unvaccinated individuals recovered from COVID-19, who had proceeded to a large private medical center in the Attica region from September 2021 to September 2022 in order to be examined on their own initiative for SARS-CoV-2 T-cell immunity response. The analysis of T-cell responses was divided into three time periods post infection: Group A: up to 6 months; Group B: 6-12 months; Group C: >12 months. The SARS-CoV-2 T-cell response was estimated against spike (S) and nucleocapsid (N) structural proteins by performing the T-SPOT. COVID test methodology. SARS-CoV-2 IgG antibody levels were measured by the SARS-CoV-2 IgG II Quant assay (Abbott Diagnostics). A total of 182 subjects were retrospectively included in the study, 85 females (46.7%) and 97 (53.3%) males, ranging from 19 to 91 years old (mean 50.84 ± 17.2 years). Among them, 59 (32.4%) had been infected within the previous 6 months from the examination date (Group A), 69 (37.9%) had been infected within a time period > 6 months and <1 year (Group B) and 54 (29.7%) had been infected within a time period longer than 1 year from the examination date (Group C). Among the three groups, a positive T-cell reaction against the S antigen was reported in 47/58 (81%) of Group A, 61/69 (88.4%) of Group B and 40/54 (74.1%) of Group C (chi square, p = 0.27). T-cell reaction against the N antigen was present in 45/58 (77.6%) of Group A, 61/69 (88.4%) of Group B and 36/54 (66.7%) of Group C (chi square, p = 0.02). The median Spot-Forming Cells (SFC) count for the S antigen was 18 (range from 0-160) in Group A, 19 (range from 0-130) in Group B and 17 (range from 0-160) in Group C (Kruskal-Wallis test, p = 0.11; pairwise comparisons: groups A-B, p = 0.95; groups A-C, p = 0.89; groups B-C, p = 0.11). The median SFCs count for the N antigen was 14.5 (ranging from 0 to 116) for Group A, 24 (ranging from 0-168) in Group B and 16 (ranging from 0-112) for Group C (Kruskal-Wallis test, p = 0.01; pairwise comparisons: groups A-B, p = 0.02; groups A-C, p = 0.97; groups B-C, p = 0.03). Our data suggest that protective adaptive T-cellular immunity following natural infection by SARS-CoV-2 may persist for over 12 months, despite the undetectable humoral element.

Prognostic significance of chronic myocardial injury diagnosed by three different cardiac troponin assays in patients admitted with suspected acute coronary syndrome.

Chronic myocardial injury (CMI) is defined as stable concentrations of cardiac troponin T or I (cTnT or cTnI) above the assay-specific 99th percentile upper reference limit (URL) and signals poor outcome. The clinical implications of diagnosing CMI are unclear. We aimed to assess prevalence and association of CMI with long-term prognosis using three different high-sensitivity cTn (hs-cTn) assays. A total of 1,292 hospitalized patients without acute myocardial injury had cTn concentrations quantified by hs-cTn assays by Roche Diagnostics, Abbott Diagnostics and Siemens Healthineers. The median follow-up time was 4.1 years. The prevalence of CMI and hazard ratios for mortality and cardiovascular (CV) events were calculated based on the URL provided by the manufacturers and compared to the prognostic accuracy when lower percentiles of cTn (97.5, 95 or 90), limit of detection or the estimated bioequivalent concentrations between assays were used as cutoff values. There was no major difference in prognostic accuracy between cTnT and cTnI analyzed as continuous variables. The correlation between cTnT and cTnI was high (r=0.724-0.785), but the cTnT assay diagnosed 3.9-4.5 times more patients with having CMI based on the sex-specific URLs (TnT, n=207; TnI Abbott, n=46, TnI Siemens, n=53) and had higher clinical sensitivity and AUC at the URL. The prevalence of CMI is highly assay-dependent. cTnT and cTnI have similar prognostic accuracy for mortality or CV events when measured as continuous variables. However, a CMI diagnosis according to cTnT has higher prognostic accuracy compared to a CMI diagnosis according to cTnI.

A-351 Reliability of POCT AccuChek Inform II® Performance Assessed with The Laboratory Method. A Practical Example for a System with Fourteen Facilities Monitored for Nine Years

Abstract Background Reliability is acceptable performance over time and by location. The reliability of AccuChek Inform II® glucose meters was assessed in fourteen Sentara Healthcare (SH) facilities for nine years by comparison with the laboratory method. Methods Nine hundred and twenty-one patient specimens collected in parallel by fingerstick and by phlebotomy in lithium heparin tubes (Becton Dickinson) were assayed with the AccuChek Inform II glucose meter (Roche Diagnostics) and cobas c-501® (Roche Diagnostics). The data were stored in RALS® (Abbott Diagnostics) and electronically transferred to Minitab® (Version 19, Minitab Inc.) statistical software. The data, in the interval 30–600 mg/dL, were analyzed with orthogonal, ordinary least squares (OLS), weighted least squares polynomial (WLSP) and locally weighted scatter plot smoother (lowess) regression models. The aptness of the OLS model was evaluated by comparison with the orthogonal model and that of the WLSP model was evaluated with the standardized deleted residuals (Std.Del.Res) diagnostics. The equality of the regression lines, as obtained for each year and for each location, was assessed with the F statistical test. The linearity of the relationship of the two methods was assessed with the pure error test. The absolute and relative differences between the paired values as obtained with the two methods were evaluated using CLIA's acceptance limits (target value ±6 mg/dl or 10%, greater). Results The regression lines obtained with the OLS model (Inform II = 3 + 0.97 c-501) and the orthogonal model (Inform II = 2 + 0.97 c-501) were very similar and the differences were not clinically significant. The standardized residuals for both models showed an increase in variance for increasing levels of the values as obtained with the c-501 method. Consequently, a WLSP model was employed. The analysis of the Std.Del.Res. for the WLSP model showed a quasi-normal distribution with twelve possible outliers (Std.Del.Res.&amp;gt;|3|) and no influential observations (Leverage &amp;lt; 0.5). The test for equality of regression lines did not show probabilistically significant differences for either year (P = 0.93) or facility (P = 0.46). The pure error test showed no probabilistically significant lack-of-fit (P = 0.07). The lowess of the Std.Del.Res. plotted by the fitted value showed a quasi-linear relationship between 30 and 500 mg/dL. For values between 30 and 100 mg/dL the majority of the differences between methods was within ± 6 mg/dL. Similarly, for values between 101 and 600 mg/dL the majority of the relative differences were within ±10%. Comments The reliability of the POCT method has been demonstrated. The POCT and the laboratory methods demonstrated a linear, similar and within the CLIA's acceptance limits of total error performance in fourteen SH facilities for nine years. The application of regression models to a large data base was possible due to the availability of Minitab statistical software. Additionally, these results demonstrated the organizational reliability of the SH POCT protocols for QC, QA, acceptance of new reagents and instruments, designed by the POCT leadership and performed by the POCT personnel and nurses. This reliable performance could not have been possible without the POCT team dedication to quality.

A-086 Vitamin D and its Variation in a Pandemic Context: Pre-pandemic—Intra-pandemic—Post-pandemic Analysis in the Province of Buenos Aires - Argentina

Abstract Background The determination of 25 OH Vitamin D3 is a frequently requested measurement for the purpose of evaluating its deficiency, which would be related to various diseases. The behavior of monthly mean values (X̅) was analyzed in 984 514 patients from Buenos Aires (Argentina) in the period from January 2014 to December 2022, in order to evaluate how seasonality influences and verify the effect of the mandatory isolation due to the SARS-CoV-2 virus pandemic in 2020. Methodology We used the Chemiluminescence Assay (QLIA) ADVIA Centaur Vitamin D Total Assay (Siemens) on an Advia Centaur (2014–2020) and Aliniti I 25 OH VITAMINE D3 (Abbott Diagnostics) on an Aliniti I (2020–2022), reference values are Optimal: &amp;gt;30.0 ng/mL, Insufficiency: 20.0–30.0 ng/mL Deficiency: &amp;lt;20.0 ng/mL. Results Conclusions From the analysis of the data, a decrease in the winter months is observed, as already described, caused by less exposure to sunlight. In 2020, it was also observed that due to confinement, there was a slight increase in mean values (26.40 ng/mL (P &amp;lt; .001)), which was the highest of the years analyzed. One hypothesis is that this could be caused by the increased free time of the population resulting in greater exposure to sunlight. At the same time, the insufficiency of Vitamin D3 in the studied population is evident, as only in 2 out of the 108 months analyzed did it slightly exceed the optimal level of 30.0 ng/mL. We believe that it would be important to evaluate the implementation of a Vitamin D3 supplementation policy for the general population and subsequently conduct further studies of this type to verify the effectiveness of such implementation.

Prevalence and Association of Transfusion-Transmissible Infections with Age of Blood Donors: A Regional Transfusion Centre Study in Northern Pakistan.

To evaluate the prevalence and association of Transfusion-Transmissible Infections (TTIs) with age of blood donors in a regional transfusion centre located in Northern Pakistan. Descriptive study. Place and Duration of the Study: Armed Forces Institute of Transfusion, Rawalpindi, Pakistan, from January 2017 to December 2021. All blood donors who qualified institutional blood donation criteria were initially screened for HBsAg, Anti-HCV Ab, HIV antigen-antibody combination and syphilis by an automated chemiluminescent microparticle immunoassay analyzer (Architect Plus i 2000 SR, Abbott Diagnostics, Abbott Park, IL). Initially, all seronegative donor blood samples were subjected to nucleic acid amplification test (NAAT). All TTI-positive donors were immediately informed and counselled to consult the medical physicians for further treatment. Descriptive statistics and significance of association were determined. The prevalence of TTIs among blood donors was calculated to be 3.33% among 308,767 donors. HCV (1.4%) was the most prevalent TTI followed by syphilis (0.9%), HBV (0.68%) and HIV (0.26%), respectively. TTIs were most prevalent in the 26 to 35-year-old group, accounting for 5,143 (50.0%) positive donors (p<0.05). The prevalence of TTIs among blood donors was found to be 3.33%. HCV was the most common TTI, followed by syphilis, HBV, and HIV. The 26 to 35 year-old group had a significantly high prevalence of TTIs. Transfusion-transmissible infections, Hepatitis B virus, Hepatitis C virus, Human immunodeficiency virus, Treponema pallidum, Syphilis, Automated chemiluminescent microparticle immunoassay analyzer, Nucleic acid amplification test.

Validation of metrological traceability of the new generation of Abbott Alinity alkaline phosphatase assay.

Recently, Abbott Diagnostics marketed a new generation of Alinity enzyme assays, introducing a multiparametric calibrator [Consolidated Chemistry Calibrator (ConCC)] in place of or in addition to factor-based calibrations. For alkaline phosphatase (ALP), both calibration options are offered, i.e.,with ConCC (ALP2) and with an experimental calibration factor (ALP2F). Both options are declared traceable to the 2011 IFCC reference measurement procedure (RMP). Before to replace the old generation (ALP1) with the new one, we decided to validate the trueness of ALP2/ALP2F. Three approaches were employed: (a)preliminary comparison on 48 native frozen serum samples with ALP1, of which traceability to RMP was previously successfully verified; (b)examination of three banked serum pools (BSP) with values assigned by RMP; (c)direct comparison with RMP on a set of 24 fresh serum samples. Bias estimation and regression studies were performed, and the standard measurement uncertainty associated with ALP measurements on clinical samples (uresult) was estimated and compared with established analytical performance specifications (APS). ConCC commutability was also assessed. A positive proportional bias was found with both ALP2 and ALP2F when compared to ALP1 and RMP. This positive bias was confirmed on BSP: in average, +13.1 % for ALP2 and +10.0 % for ALP2F, respectively. uresult were 13.28 % for ALP2 and 10.04 % for ALP2F, both not fulfilling the minimum APS of 4.0 %. Furthermore, ConCC was not commutable with clinical samples. Our results unearth problems in the correct implementation of traceability of Alinity ALP2/ALP2F, with the risk for the new assay to be unfit for clinical purposes.

The Cross Reactivity of Cannabinoid Analogs (Delta-8-THC, Delta-10-THC and CBD), their metabolites, and Chiral Carboxy HHC metabolites in Urine of Six Commercially Available Homogeneous Immunoassays.

There has been an exponential surge in the presence and use of cannabinoids since the federal legalization of hemp (Agricultural Improvement Act of 2018). This growth is attributed to Delta-9-tetrahydrocannabinol (Delta-9-THC) and cannabidiol (CBD), the most abundant phytocannabinoid components of cannabis and hemp, respectively, but with many other emerging THC analogs. Structurally, these analogs are similar to Delta-9-THC, yet very little information is available about their potency and even less information is available regarding their detectability using commercially available cannabinoid screening kits. Due to their structural similarity, current cannabinoid homogeneous immunoassay screening methods may be able to detect these emerging cannabinoid analogs and their metabolites. Six urine immunoassay kits (Abbott Cannabinoids - Abbott Diagnostics, LZI Cannabinoids (cTHC) Enzyme Immunoassay - Lin-Zhi International, DRI® Cannabinoid Assay and CEDIA™ THC - Thermo Fisher Scientific, ONLINE DAT Cannabinoid II - Roche Diagnostics, and Syva EMIT®II Plus - Siemens Healthineers) were evaluated at two different cutoff concentrations: 50ng/mL and 20 or 25ng/mL, assay dependent. The analysis was performed on an Abbott Architect Plus c4000 (Abbott Diagnostics). Delta-8-THC, CBD, olivetol and their major metabolites, and Delta-10-THC and HHC carboxylic acid chiral analogs were evaluated. The cross reactivity was evaluated by preparing each analyte at 20, 50, 100, and 1000ng/mL in urine. Analytes that did not cross react at 1000ng/mL for a cutoff were considered not detectable. If detected, the lowest concentration was used as the decision point to determine the precision at the immunoassay's cutoff. The six commercially available urine cannabinoid homogeneous immunoassay screening kits cross reacted with the following analogs: Delta-8-THC, 11-OH-Delta-8-THC, 11-COOH-Delta-8-THC, 6-OH-CBD, 7-OH-CBD, all Delta-10-THC and HHC carboxylic acid chiral analogs, and olivetol with varying selectivity depending on the screening kit and cutoff concentration. The kits did not cross react with the following analogs: CBD, 7-COOH-CBD, Abnormal CBD, CBDA-A, and olivetolic acid.

The plasma separation card as a novel solution for enhancing central laboratory capability for HIV-1 viral load monitoring in limited-access settings.

Measurement of HIV-1 viral load (VL) is essential for monitoring antiretroviral treatment (ART) efficacy. The preferred specimen type for VL is plasma, but in remote settings where collection and preservation of plasma many not be possible, dried blood spots (DBS) are often used instead. A new specimen collection matrix, the cobas plasma separation card (PSC, Roche Diagnostics Solutions), enables specimen preparation from a finger prick or venous blood, using a multi-layer absorption and filtration design that results in a specimen similar to dried plasma. We sought to confirm the correlation between VL results obtained using PSC prepared from venous blood to those from plasma or DBS, as well as PSC prepared with capillary blood from a finger prick. PSC, DBS and plasma were prepared with blood from HIV-1 infected persons attending a primary care clinic in Kampala, Uganda. VL in PSC and plasma was measured using cobas HIV-1 (Roche Diagnostics), while VL in DBS was measured with RealTime HIV-1 (Abbott Diagnostics). The correlation between VL from plasma and PSC made from capillary or venous blood was high (regression coefficient of determination r2 between 0.87 and 0.91), and there was good agreement based on mean bias (-0.14 to 0.24 log10 copies/mL) and classification of VL above or below 1000 copies/mL (91.4% agreement). In contrast, VL from DBS was lower than plasma or PSC (mean bias 0.51 to 0.63 log10 copies/mL) and not as well correlated (r2 0.78 to 0.81, 75.1-80.5% agreement). These results confirm the utility of PSC as an alternative specimen type for HIV-1 viral load measurement in areas where preparation and optimal storage or shipment of plasma is an obstacle to provision of treatment and care of HIV-1 infected people.

Sex differences in the evaluation of proteinuria using the urine dipstick test.

The urine protein dipstick test is widely used, but false-positive and false-negative results may occur. This study aimed to compare the urine protein dipstick test with a urine protein quantification method. The data were extracted using the Abbott Diagnostic Support System, which analyzes the inspection results using multiple parameters. This study included 41,058 specimens tested using the urine dipstick test and protein creatinine ratio from patients aged ≥18 years. The proteinuria creatinine ratio was classified according to the Kidney Disease Outcomes Quality Initiative guidelines. Urine protein on the dipstick test was negative in 15,548 samples (37.9%), trace in 6,422 samples (15.6%), and ≥1+ in 19,088 samples (46.5%). Among the trace proteinuria samples, A1 (<0.15 g/gCr), A2 (0.15-0.49 g/gCr), and A3 (≥0.5 g/gCr) category proteinuria accounted for 31.2, 44.8, and 24.0% of samples, respectively. All trace proteinuria specimens with a specific gravity of <1.010 were classified as A2 and A3 category proteinuria. In the trace proteinuria cases, women had a lower specific gravity and a higher percentage of A2 or A3 category proteinuria than men. The sensitivity in the "dipstick proteinuria" ≥ trace" group was higher than that in the "dipstick proteinuria ≥ 1+" group within the lower specific gravity group. The sensitivity in the "dipstick proteinuria ≥ 1+" group was higher for men than for women, and the sensitivity in the "dipstick proteinuria ≥ trace" group was higher than that in the "dipstick proteinuria ≥ 1+" group for women. Pathological proteinuria assessment requires caution; this study suggests that evaluating the specific gravity of urine specimens with trace proteinuria is essential. Particularly for women, the sensitivity of the urine dipstick test is low, and caution is needed even with trace specimens.

1671-P: T Cell Deficiency of STAT1 Reduces Obesity in Mice with High-Fat Diet or Aging

T cells accumulate in adipose tissue (AT) and change phenotypes, with increased polarization to Th1, in obesity, but the mechanisms for these changes and their contribution to metabolic functions remain incompletely understood. We hypothesize that STAT1, a transcription factor, plays a role in AT T cell polarization, thus impacting obesity and related metabolism. Mice with Stat1 knockout in αβT cells (tStat1-KO) were generated by crossbreeding Stat1fl/fl mice and CD4-cre mice. Strikingly, with high-fat diet (HFD) feeding or aging, tStat1-KO, compared to cre noncarrier wild type (WT) littermates, developed less obesity, with lower body weight and fat mass (body weight: 43 ± 0.5 g in KO [n=33] vs 48 ± 0.8 g in WT [n=32] at 12 weeks on HFD and 32 ± 0.7 g in KO [n=27] vs 37 ± 0.6 g in WT [n=25] at the age of 50 weeks [on normal chow], P&amp;lt;0.001; fat mass: 14 ± 0.5 g in KO [n=6] vs 17 ± 0.7 g in WT [n=4] at 12 weeks on HFD, P=0.02 and 4.6 ± 0.3 g in KO [n=9] vs 8.6 ± 1.5 g in WT [n=4] at the age of 50 weeks, P=0.002). Compared to WT, tStat1-KO had similar food intake, but increased energy expenditure with increased white AT browning indicated by elevated UCP1 and PRDM16 levels in inguinal AT. tStat1-KO vs WT with HFD or aging had improved insulin sensitivity and glucose tolerance. Analyses of AT showed a dramatic phenotypic switch from IFNγ+ Th1 to IL-5+ Th2 cells and increased eosinophils in perigonadal and inguinal AT of tStat1-KO vs WT fed HFD. Antibody neutralization of IL-5 reduced eosinophils but did not reverse less obesity in tStat1-KO fed HFD, suggesting that increased IL-5 and eosinophils may not account for reduced obesity in tStat1-KO. Adoptive transfer of Th1 cells in tStat1-KO and tissue culture studies showed that Th1 cells repressed white AT browning and reduced UCP1 in adipocytes. In summary, T cell ablation of STAT1 led to phenotypic switch from Th1 to Th2 cells in AT, correlated with reduced obesity, in mice with HFD or aging. These data support a role of STAT1 in AT T cell polarization, which may affect obesity development induced by HFD or aging. Disclosure Z.Lian: None. V.O'brien: None. X.D.Perrard: None. P.Saha: None. S.M.Hartig: None. C.M.Ballantyne: Consultant; Alnylam Pharmaceuticals, Inc., Althera Pharmaceuticals, Amarin Corporation, Amgen Inc., Arrowhead Pharmaceuticals, Inc., AstraZeneca, ESPERION Therapeutics, Inc., 89bio, Inc., Abbott Diagnostics, Denka Seiken, Genentech, Inc., Gilead Sciences, Inc., Illumina, Matinas BioPharma Inc, Merck &amp; Co., Inc., New Amsterdam Pharma, Novartis, Novo Nordisk, Pfizer Inc., Regeneron, Roche Diagnostics, Research Support; Abbott Diagnostics, Akcea, Amgen Inc., Arrowhead Pharmaceuticals, Inc., ESPERION Therapeutics, Inc., Ionis Pharmaceuticals, Merck &amp; Co., Inc., Novartis, Novo Nordisk, Regeneron, Roche Diagnostics. H.Wu: None. Funding American Diabetes Association (1-17-IBS-082 to H.W.); National Institutes of Health (R01DK121348, R01AG065197); American Heart Association (968367)

505-P: Real-World Use of Inclisiran in Outpatient Physician Clinics

Objective: In clinical trials, inclisiran, a novel siRNA therapy, reduced LDL-C equally among diabetic and nondiabetic patients. This study aimed to characterize a cohort of obese, prediabetic, and diabetic patients prior to initiating inclisiran in outpatient clinics. Methods: This was a retrospective, longitudinal cohort study of patients referred for treatment with inclisiran between February and November 2022 in 23 clinics in 11 states. Patients with obesity (BMI&amp;gt;30 kg/m2), prediabetes (5.7≤ HbA1c≤ 6.5%), or diagnosed diabetes at the time of referral were assessed. The log rank test was used to identify differences in time from referral to first administration between above groups. Results: Of 81 identified patients, 48.2% were diabetic, 27.2% obese, and 24.7% prediabetic. Median age was 71 (IQR: 68-75) years, 60.5% were male, and 60.5% were Medicare beneficiaries. At referral, 81.4% had a primary diagnosis of atherosclerotic cardiovascular disease (ASCVD), 30.9% were on concurrent statins, 30.9% on ezetimibe, 66.7% had documented statin intolerance, 50.6% had prior PCSK9 monoclonal antibody use, and the median Elixhauser comorbidity score was 6.0 (IQR: 2-15). Elixhauser score was notably higher among the diabetic group (Median: 9, IQR: 3-18) compared to the prediabetic (Median: 4, IQR: 0-13) and obese (Median: 3, IQR: -3-12) patient groups. Median baseline LDL-C was 135 (IQR: 99-166) mg/dL with no differences between groups. Median time to initiation was 27 (IQR: 16-49) days with no notable difference between obese, prediabetic, and diabetic patients. Conclusion: Inclisiran can be promptly initiated in the clinic setting for the management of LDL-C in obese, prediabetic, and diabetic patients. Future work will focus on measuring real-world effectiveness and adherence to inclisiran in each of these groups. Disclosure T.E. Graham: None. T.J. Varisco: Consultant; HEALIX. C.M. Ballantyne: Research Support; Abbott Diagnostics, Akcea, Amgen Inc., Arrowhead Pharmaceuticals, Inc., ESPERION Therapeutics, Inc., Ionis Pharmaceuticals, Merck &amp; Co., Inc., Novartis, Novo Nordisk, Regeneron, Roche Diagnostics. Consultant; Alnylam Pharmaceuticals, Inc., Althera Pharmaceuticals, Amarin Corporation, Amgen Inc., Arrowhead Pharmaceuticals, Inc., AstraZeneca, ESPERION Therapeutics, Inc., 89bio, Inc., Abbott Diagnostics, Denka Seiken, Genentech, Inc., Gilead Sciences, Inc., Illumina, Matinas BioPharma Inc, Merck &amp; Co., Inc., New Amsterdam Pharma, Novartis, Novo Nordisk, Pfizer Inc., Regeneron, Roche Diagnostics. B.J. Iteld: Speaker's Bureau; Amgen Inc. Research Support; Amgen Inc., Novartis AG, Bayer Inc. Speaker's Bureau; ESPERION Therapeutics, Inc. Research Support; BMS. Speaker's Bureau; Boehringer-Ingelheim. H. Serota: Speaker's Bureau; Amarin Corporation. Advisory Panel; Bayer Inc. Speaker's Bureau; Janssen Pharmaceuticals, Inc., Boehringer Ingelheim and Eli Lilly Alliance. S. McElligott: Employee; Novartis. Stock/Shareholder; Janssen Pharmaceuticals, Inc. Employee; Sanofi. Stock/Shareholder; Merck &amp; Co., Inc. X. Niu: Employee; Novartis, Sunovion Pharmaceuticals Inc. L.J. Van Anglen: Research Support; Novartis Pharmaceuticals Corporation, Merck &amp; Co., Inc., ADMA Biologics, Inc., Octapharma USA, Paratek Pharmaceuticals. Funding Novartis Pharmaceuticals Corporation

1253-P: Differences in Screening-Detected Type 2 Diabetes—Evidence from Two Campaign Setups in Denmark

Background: Early detection of type 2 diabetes mellitus (T2DM) increases life expectancy of T2DM patients and reduces societal health care costs. Targeted screening campaigns are used for early detection of T2DM, but different campaign setups may yield different detection results. Methods: Between June and November 2022, the Danish Diabetes Association offered free capillary A1c tests to individuals at high risk of developing diabetes based on the Leicester’s Risk Score questionnaire (score ≥ 16 points). Two campaign setups were applied: a) an event-based community screening campaign in 20 of the largest Danish cities using a portable Point of Care Testing analyzer and b) a social media campaign offering at-home self-sampling tests using mailed Hemoglobin Capillary Collection System. Results: A total of 1,337 and 2,655 individuals at high risk were tested through the community and the social media setup, respectively. The proportion of men and women in both setups were evenly balanced across all age groups. However, compared to the social media setup, in the community setup the proportion of individuals aged below 60 years was 14 percentage points lower, while the proportion of individuals aged 70 years or older was 14 percentage point higher. While 2.6% of the participants in both setups had A1c values ≥ 48 mmol/mol, 8.8% in the community setup and 15.6% in the social media setup had A1c values of 42-47 mmol/mol. The relative difference in the proportion of participants with A1c values of 42-47 mmol/mol was balanced across all age groups. Conclusions: Targeted community and social media screening campaigns are complementary. While older individuals (70 years or above) tend to participate in the community screening campaign, younger individuals (below 60) tend to participate in social media screening campaign. However, social media campaigns for at-home self-sampling prove highly efficient in detecting individuals with A1c values of 42-47 mmol/mol compared to community campaigns. Disclosure N.Cayuelas mateu: Other Relationship; Abbott Diagnostics. T.Thybo: Other Relationship; Abbott Diagnostics.

407-P: Efficacy of Finerenone in Patients with Abnormal Markers of Liver Steatosis and Fibrosis—A FIDELITY Subgroup Analysis

Introduction: Finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist, showed cardiorenal benefits vs placebo in patients with chronic kidney disease and type 2 diabetes. Here, we analyzed patients with liver function abnormalities in FIDELITY, a prespecified pooled dataset from the FIDELIO-DKD and FIGARO-DKD trials. Methods: Patients with urine albumin-to-creatinine ratio ≥30-≤5000 mg/g and estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 and type 2 diabetes were analyzed according to elevated transaminases, high risk of steatosis (hepatic steatosis index [HSI] &amp;gt;36), and risk of intermediate to advanced fibrosis (Fibrosis-4 Index [FIB-4] scores &amp;gt;1.30, &amp;gt;2.67, and &amp;gt;3.25). Changes in liver function and in kidney (kidney failure, sustained 57% eGFR decline, or renal death) and cardiovascular (CV; CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite outcomes were assessed. Results: Across 13,026 patients, finerenone reduced the risk of kidney and CV outcomes compared with placebo in patients with elevated transaminases (HR=0.75; 95% CI 0.50-1.13 and HR=0.81; 95% CI 0.62-1.07, respectively), at high risk of steatosis (HR=0.75; 95% CI 0.64-0.88 and HR=0.85; 95% CI 0.77-0.95, respectively), and at high risk of intermediate fibrosis (HR=0.75; 95% CI 0.60-0.93 and HR=0.76; 95% CI 0.67-0.87, respectively), with stronger reductions in the risk of the CV composite outcome at higher FIB-4 scores (HR=0.61; 95% CI 0.41-0.92; p-value for interaction=0.13 and HR=0.48; 95% CI 0.25-0.90; p-value for interaction=0.03 for FIB-4 &amp;gt;2.67 and &amp;gt;3.25, respectively). Liver transaminase levels remained consistent between treatment groups throughout the study. Conclusions: Finerenone demonstrated robust and consistent cardiorenal benefits in patients with abnormal liver function and even more profound CV benefits in patients with higher FIB-4 scores. Disclosure N.Perakakis: Advisory Panel; Bayer Inc., Other Relationship; Novo Nordisk, Novo Nordisk. P.Kolkhof: Employee; BAYER AG. R.Lawatscheck: Employee; Bayer Inc. C.Scott: None. G.Bakris: Advisory Panel; Janssen Pharmaceuticals, Inc., Consultant; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Other Relationship; Bayer Inc. S.R.Bornstein: None. A.L.Birkenfeld: None. A.Linkermann: None. S.Anker: Advisory Panel; AstraZeneca, Novartis AG, Consultant; Bayer Inc., Boehringer Ingelheim Pharma GmbH&amp;Co.KG, Vifor Pharma Management Ltd., Research Support; Abbott, Vifor Pharma Management Ltd. G.Filippatos: Other Relationship; Boehringer-Ingelheim, Bayer Inc., Amgen Inc., Medtronic, Vifor Pharma Management Ltd., Novartis, Servier Laboratories. B.Pitt: Consultant; Bayer Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Vifor Pharma Management Ltd., Lexicon Pharmaceuticals, Inc., PhaseBio Pharmaceuticals, Inc., KBP Bioscience, Merck &amp; Co., Inc. P.Rossing: Other Relationship; Abbott Diagnostics, AstraZeneca, Bayer Inc., Boehringer Ingelheim Inc., Novo Nordisk, Merck KGaA, Gilead Sciences, Inc., Sanofi. L.M.Ruilope: Advisory Panel; Bayer Inc.

829-P: Outcomes with Finerenone in People with CKD and T2D by Baseline Insulin Resistance—A FIDELITY Subgroup Analysis

Introduction Insulin resistance (IR) is associated with increased risk of T2D, CV disease and CKD. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, has shown cardiorenal benefits in people with CKD and T2D. We investigated if IR is associated with risk of cardiorenal outcomes and if IR modifies finerenone efficacy in the pooled FIDELITY dataset. Methods People with T2D and CKD (UACR ≥30-&amp;lt;300 mg/g + eGFR ≥25-≤90 mL/min/1.73 m2 or UACR ≥300-≤5000 mg/g + eGFR ≥25 mL/min/1.73 m2) and optimized RAS blockade were randomized to finerenone or placebo. Estimated glucose disposal rate (eGDR), an inverse marker of IR, was calculated by 21.158 + (-0.09 × waist circumference [cm]) + (-3.407 × presence of hypertension) + (-0.551 × HbA1c [%]). Risk of CV (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney (time to kidney failure, sustained ≥57% eGFR decline, or renal death) composite outcomes, and safety, were assessed by eGDR. Results Median baseline eGDR was 4.1 mg/kg/min in 12,964 participants. Analysis by continuous baseline eGDR showed a significantly lower risk of CV events at 3.5 years with increasing eGDR (HR 0.88 [95% CI 0.86-0.91] p&amp;lt;0.01); whereas eGDR was not associated with kidney outcomes. Analyses by eGDR subgroups showed no significant heterogeneity for the effect of finerenone on CV (eGDR &amp;lt;median: HR 0.82 [95% CI 0.72-0.92]; eGDR ≥median: HR 0.91 [95% CI 0.78-1.06]; p-interaction=0.29) or kidney outcomes (eGDR &amp;lt;median: HR 0.85 [95% CI 0.70-1.04]; eGDR ≥median: HR 0.69 [95% CI 0.57-0.84]; p-interaction=0.18). Consistent strength and direction of the associations were observed across sensitivity analyses. Adverse events were similar across eGDR subgroups; hyperkalaemia events were higher with finerenone than placebo. Conclusions A higher risk of CV, but not kidney, outcomes was observed with greater IR in people with T2D and CKD. Finerenone efficacy and safety were not modified by baseline IR. Disclosure T.Ebert: Advisory Panel; Sanofi, Bayer Inc., Research Support; AstraZeneca, Speaker's Bureau; CME-Verlag, Santis, Fresenius Medical Care. K.Rohwedder: Employee; Bayer Inc., AstraZeneca. P.Rossing: Other Relationship; Abbott Diagnostics, AstraZeneca, Bayer Inc., Boehringer Ingelheim Inc., Novo Nordisk, Merck KGaA, Gilead Sciences, Inc., Sanofi. S.Anker: Advisory Panel; AstraZeneca, Novartis AG, Consultant; Bayer Inc., Boehringer Ingelheim Pharma GmbH&amp;Co.KG, Vifor Pharma Management Ltd., Research Support; Abbott, Vifor Pharma Management Ltd. L.M.Ruilope: Advisory Panel; Bayer Inc. P.Fioretto: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Bayer Inc. V.Fonseca: Consultant; Abbott, Corcept Therapeutics, Eli Lilly and Company, Other Relationship; BRAVO4HEALTH, LLC, Research Support; Fractyl Health, Inc., Stock/Shareholder; Amgen Inc. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter. A.L.Birkenfeld: None. R.Lawatscheck: Employee; Bayer Inc. C.Scott: None.

771-P: Tirzepatide Reduces HbA1c and Body Weight Significantly More than Placebo or Semaglutide Irrespective of Baseline Beta-Cell Function—Post Hoc Analysis from SURPASS-1 and SURPASS-2

Tirzepatide (TZP), a once-weekly GIP/GLP-1 receptor agonist, achieved significantly greater HbA1c and body weight (BW) reductions with all doses (5, 10, 15 mg) vs placebo (SURPASS-1 [S-1]) and semaglutide (SEMA) 1 mg (SURPASS-2 [S-2]) in randomized Phase 3 trials in people with type 2 diabetes controlled by diet and exercise (S-1) or metformin (S-2). Exploratory post hoc analyses examined changes from baseline in HbA1c and BW in these studies at 40 weeks across HOMA2-B (C-peptide) and HOMA2-IR (insulin) quartiles (Q) from low (lower beta-cell function/insulin resistance) (Q1) to high (Q4) as assessed by mixed model repeated measures (MMRM). HbA1c reductions were greater with all TZP doses than placebo or SEMA within each HOMA2-B and HOMA2-IR baseline Q. HbA1c reductions were largest in people within HOMA-2B Q1, yet similar across all HOMA2-IR Qs (Fig). BW reductions were greater across Qs with all TZP doses (ranging from 6%-14%) than placebo (up to 2%) or SEMA (up to 7%). TZP was more efficacious than placebo or SEMA in reducing HbA1c and BW across a spectrum of pancreatic beta-cell function, notably achieving greater glycemic improvement in people with markers of diminished pancreatic beta cell function at baseline. Disclosure J.M.Maldonado: Employee; Eli Lilly and Company. C.De block: Advisory Panel; Abbott Diagnostics, Indigo Diabetes, Insulet Corporation, Eli Lilly and Company, Novo Nordisk, Research Support; Boehringer-Ingelheim, AstraZeneca, Indigo Diabetes, Eli Lilly and Company, Speaker's Bureau; Novo Nordisk. J.P.Frias: Advisory Panel; Becton, Dickinson and Company, Pfizer Inc., Sanofi, Consultant; Akero Therapeutics, Inc., 89bio, Inc., Aimmune, Boehringer Ingelheim Inc., Eli Lilly and Company, Carmot Therapeutics, Inc., Echosens, Merck &amp; Co., Inc., Metacrine, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Employee; Ionis Pharmaceuticals, Research Support; Akero Therapeutics, Inc., 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Carmot Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck &amp; Co., Inc., Metacrine, Inc., Novo Nordisk, Oramed Pharmaceuticals, Novartis, Pfizer Inc., Sanofi, Speaker's Bureau; Eli Lilly and Company, Sanofi. C.Lee: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. K.Brown: Employee; Eli Lilly and Company. H.Wang: None. M.K.Thomas: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

1310-P: Causes of Death among Australians with Type 1 or Type 2 Diabetes, 2002–2019

Objective: We sought to explore the conditions driving the diversification in causes of death among people with diabetes. Methods: We linked Australians with type 1 or type 2 diabetes of all ages on the National Diabetes Services Scheme (Diabetes Registry) to the National Death Index for 2002-2019. We investigated causes of death over time across eight categories of causes of death. Underlying causes of death were classified according to the International Classification of Diseases, Tenth Revision codes. Results: Between 2002-2019, there was a shift in the underlying cause of death among Australians with diabetes. The proportion of deaths attributed to cardiovascular disease declined in both sexes (Ptrend &amp;lt; 0.001), most substantially among females with type 2 diabetes from 48.2% in 2002 to 30.7% in 2019 (Figure). Among males, cancer overtook cardiovascular disease as the leading cause of death. The proportion of deaths due to dementia increased among all people with diabetes, from 2% in 2002 to 7% in 2019, across all age-groups, notably from 1% to 4% in those aged 70-79. The proportion of deaths due to falls also increased. Conclusions: We are seeing a shift of causes of death among those with diabetes away from cardiovascular and renal disease towards conditions such as dementia, falls, and respiratory disease, which may have serious consequences for health systems and will require consideration in resource allocation. Disclosure D.Tomic: None. L.Chen: None. D.J.Magliano: None. J.E.Shaw: Advisory Panel; Abbott Diagnostics, Lilly, Zuellig Pharma Holdings Pte. Ltd., Mylan, Research Support; AstraZeneca, Speaker's Bureau; AstraZeneca, Roche Diagnostics, Lilly, Amgen Inc., Sanofi, Zuellig Pharma Holdings Pte. Ltd.

1460-P: Prevalence of Chronic Kidney Disease Associated with Type 1 Diabetes in the U.S.

Background: Chronic kidney disease (CKD) is associated with an increased risk of kidney failure, cardiovascular events, and mortality in patients with type 1 diabetes (T1D). However, the prevalence of CKD associated with T1D in the US is unclear. The aim of this study was to estimate the prevalence of CKD in people with T1D in the US using data collected in the National Health Examinations Survey (NHANES). Methods: People with T1D were identified from NHANES using an established algorithm (Mosslemi et al. Cardiovasc Endocrinol Metab. 2020). Adults aged ≥18 years with CKD in this group were identified by single measurements of estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g. The NHANES data were used to create corresponding weighted variables to represent the US Results: During 2015 to 2018, diabetes was identified in 1647 of 19,225 adults surveyed in NHANES. Among those with diabetes, CKD was present in 20 out of 47 people with T1D with evaluable eGFR and UACR, corresponding to an unweighted estimate of 43%. CKD status was uncertain in 7 patients with T1D as their eGFR and/or UACR measurements were not available (unweighted estimate). In the CKD and T1D group, 59% were male and 60% were non-Hispanic White (weighted characteristics). Mean eGFR (SD) was 57 (4) mL/min/1.73 m2 and median UACR (IQR) was 89 (8-875) mg/g (weighted characteristics). Since the weighted overall number of adult people with T1D in the US was estimated at 1,202,739 (95% CI: 681,820-1,723,657), the corresponding number with T1D and CKD with evaluable eGFR and UACR was 258,196 (95% CI: 71,189-445,203), corresponding to a weighted estimate of 21%. Conclusions: CKD was common in people with T1D and evaluable eGFR and UACR based on recent US data. Since the absolute number in NHANES was small, these prevalence estimates should be interpreted cautiously and validated in other cohorts. Disclosure P.Rossing: Other Relationship; Abbott Diagnostics, AstraZeneca, Bayer Inc., Boehringer Ingelheim Inc., Novo Nordisk, Merck KGaA, Gilead Sciences, Inc., Sanofi. P.Groop: Advisory Panel; Boehringer-Ingelheim, Bayer Inc., Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Bayer Inc., Merck Sharp &amp; Dohme Corp., Medscape, Nestlé Health Science. R.Singh: None. R.Lawatscheck: Employee; Bayer Inc. K.R.Tuttle: Consultant; Lilly, AstraZeneca, Gilead Sciences, Inc., Research Support; Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Novo Nordisk, Goldfinch Bio, Inc., Traveere Pharmaceuticals. Funding Bayer AG

1274-P: High Prevalence of Type 2 Diabetes without Traditional Risk Factors among Men Who Inject Drugs in Chennai, India

South Asians with type 2 diabetes (T2DM) are predominately normal- or underweight, due to early loss of beta cell function in addition to insulin resistance. Substances of misuse are an additional stressor on beta cells and may lead to an increased prevalence of T2DM. We determined the prevalence of T2DM and its correlates among people who inject drugs (PWID) in Chennai. We conducted a cross-sectional analysis among male PWID. T2DM was defined as fasting glucose ≥126mg/dL or a prior diagnosis. Logistic regression was used to identify correlates of T2DM. Among 1039 PWID, median age was 38.9 years (IQR 32.1, 44.9) and median BMI was 19.7 kg/m2 (IQR 17.8, 22.9). The most common injected substance was heroin (94.8%, n=998). T2DM prevalence was 8.4% (n=87), among whom 60% were underweight or normal weight and 64% had normal waist circumference. On univariable regression analysis, T2DM was not associated with greater frequency of drug use, type of drug, HIV, or Hepatitis C. On multivariable analysis, age &amp;gt;40 years (OR 3.0, 95% CI 1.3-6.8) and high waist circumference (OR 1.9, 95% CI 1.1-3.2) were associated with T2DM. The prevalence of T2DM among PWID is similar to India as a whole, though most cases would not be detected by screening using weight or waist circumference. Integrating universal metabolic disease screening into substance abuse treatment programs may help reduce morbidity and mortality from T2DM. Disclosure P.Chebrolu: None. S.Mehta: Research Support; Abbott Diagnostics. A.Mcfall: None. T.Brown: Advisory Panel; Merck &amp; Co., Inc., Gilead Sciences, Inc., ViiV Healthcare, Jannsen. A.Srikrishnan: None. M.Kumar: None. H.Iqbal: None. J.S.Mathad: None. G.Lucas: None. S.S.Solomon: Research Support; Gilead Sciences, Inc., Abbott. Funding National Institute on Drug Abuse (R01DA026727); Fogarty International Center (D43TW009337); Weill Cornell Department of Medicine; National Institute of Allergy and Infectious Diseases (K24AI120834 to T.B.)

123-LB: Implementing a Multidisciplinary Model of CGM Care in Real-World Pharmacy Practice—A Clinical Consensus for Canadian Pharmacists

Background: Continuous glucose monitoring (CGM) devices have transformed diabetes care, but there is a lack of guidance for pharmacists to follow when onboarding patients to begin using CGM systems. Our study aimed to develop a blueprint for best practices for pharmacists to support people living with diabetes (PWD) using CGM systems. Methods: We used a modified DELPHI process to gather insights from 11 Key Opinion Leaders (KOLs) across Canada, including two endocrinologists, one family physician, and eight pharmacists. Consensus was reached for each criterion when 75% agreement was achieved. Criteria for CGM device initiation, short-term or episodic CGM use, and best practices for CGM onboarding and monitoring were developed based on the results. Results: Amongst the ideal candidates for CGM use are PWD using insulin, those with type 1 diabetes, individuals not reaching their A1C target, those experiencing frequent hypoglycemia, pregnant individuals, and others at risk of hypoglycemia. Best practices for onboarding and monitoring included shared decision-making conversations, a comprehensive overview of cost and coverage options, customized alerts and alarms, and timely follow-up sessions. Discussion: The KOL group ensured a comprehensive and diverse perspective. The developed blueprint provides a valuable resource for pharmacists to improve the use of CGM devices and enhance diabetes management for their patients. Incorporating these best practices into clinical practice has the potential to transform diabetes care and improve outcomes. Disclosure A. S. Sihota: Consultant; Novo Nordisk Canada Inc., Other Relationship; Becton, Dickinson and Company. S. Sivapalan: Advisory Panel; Novo Nordisk, Pfizer Inc., AstraZeneca, Consultant; Pear Healthcare Solutions Inc., Other Relationship; Boehringer Ingelheim (Canada) Ltd., GlaxoSmithKline plc., Novo Nordisk, Bristol-Myers Squibb Company, Pfizer Inc., AbbVie Inc., Ferring Pharmaceuticals, AstraZeneca. T. Smith: Advisory Panel; Novo Nordisk Canada Inc., Dexcom, Inc., Emergent Biosolutions. I. Halperin: Advisory Panel; Sanofi, Speaker's Bureau; 3Boehringer Ingelheim Canada Ltd. /Ltée, Abbott Diabetes, Dexcom, Inc., Novo Nordisk. A. B. Jain: Advisory Panel; Abbott, Amgen Canada, Dexcom, Inc., AstraZeneca, Novo Nordisk, Bayer Inc., Insulet Corporation, Takeda Canada, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Research Support; Abbott, Amgen Canada, Novo Nordisk, Speaker's Bureau; Abbott, Amgen Canada, Dexcom, Inc., AstraZeneca, Novo Nordisk, Bausch Health, Canada, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Pfizer Inc. A. Chin: Other Relationship; Abbott Diabetes, BMO Bank of Montreal, Diabetes Canada, Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care, Inc., Research Support; Novavax, Centricity Research. W. Chow: Advisory Panel; GlaxoSmithKline plc., Pfizer Inc., Speaker's Bureau; Abbott Diagnostics, AstraZeneca, Bayer Inc., Bausch Health, Canada, Boehringer Ingelheim (Canada) Ltd., Eisai Inc., Novo Nordisk. S. Jin: Advisory Panel; Dexcom, Inc., Eisai Inc., Novo Nordisk Canada Inc., Board Member; Wounds Canada, Consultant; Abbott Diabetes, Boehringer Ingelheim Pharmaceuticals Inc., Canadian Collaborative Research Network, Diabetes Canada, GlaxoSmithKline plc., HLS Therapeutics Inc., MDBriefcase, Novo Nordisk Canada Inc., AstraZeneca, Speaker's Bureau; Eisai Inc., Dexcom, Inc., Novo Nordisk Canada Inc. T. Molberg: None. S. Patil: None. R. Siemens: Consultant; Canadian Collaborative Research Network, Novartis Canada, AstraZeneca, Montmed, Sanofi, MDBriefcase, Other Relationship; Abbott Diabetes, Amgen Canada, Boehringer Ingelheim and Eli Lilly Alliance, GlaxoSmithKline plc., HLS Therapeutics, Novo Nordisk, Dexcom Canada, Diabetes Canada. Funding Dexcom Canada

424-P: Diabetic Kidney Disease (DKD) Worsens CV Outcomes after First-Ever Major Cardiovascular Event in Type 2 Diabetes (T2D)

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 &amp;lt;30/≥30 mg/g) and/or CKD-EPI eGFR ≥60/&amp;lt;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&amp;lt;0.0001; adjusted 3.32, 1.65-6.64, p=0.001) for ACR≥30/eGFR&amp;lt;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&amp;lt;0.0001) and adjusted HR of 3.18 (1.57-6.44; p=0.001) for ACR≥30/eGFR&amp;lt;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 &amp; 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 &amp; Co., Inc., Novo Nordisk A/S, Sanofi.