bluuebunny/crossref_metadata_2025 huggingface dataset:
338-OR: Regulation of Pancreatic Beta-Cell Survival and Function during Aging
Authors: PARK JIMIN , HUANG MENGHAO , LIANG JINGRU , CHARLIE DONG X.
Published: June 2024

Introduction & Objective: Type 2 diabetes is often associated with pancreatic beta cell impairment or failure. However, it is poorly understood how beta cells are adapted or maladapted to both intrinsic and extrinsic stresses during aging. The objective of this work is to investigate the role of SIRT6, an NAD-dependent deacetylase, in the regulation of beta cells during aging.

Methods: Both gain-of-function and loss-of-function approaches were used to illustrate the function of SIRT6 in the regulation of beta cell survival and function in cell and animal models. Glucose tolerance and insulin secretion analyses were performed to assess the underlying pathophysiology. Immunofluorescence microscopy was performed to illustrate cell survival or death. RNA-seq analysis was performed to profile transcriptomic changes.

Results: We performed glucose tolerance tests in beta cell-specific Sirt6 knockout and transgenic mice at young and old ages. Our results show a strong beneficial effect of Sirt6 on systemic glucose tolerance in the transgenic mice and deteriorated glucose tolerance in the knockout mice compared to wild-type mice of young and old ages. Our RNA-seq and imaging data reveal a key role of Sirt6 in the protection against beta cell senescence and death. Among numerous potential target genes of Sirt6, we evaluated RRAD and GEM like GTPase 2 (REM2, an endogenous inhibitor of high-voltage-activated calcium channels) as a key downstream player. Indeed, knockdown or knockout of Rem2 in beta cells significantly improve Sirt6 deficiency-induced cellular senescence and death. Additionally, beta cell-specific Rem2 knockout mice exhibit improved glucose tolerance.

Conclusion: This study demonstrates that SIRT6 is a critical regulator of beta cell survival and function during aging. Boosting SIRT6 levels and/or activities could be a strategy for maintaining healthy beta cells into the late ages.

Disclosure

J. Park: None. M. Huang: None. J. Liang: None. X. Dong: None.

Funding

National Institute on Aging (R21AG072288)
342-OR: Systemic Identification of Functionally Conserved lncRNA Metabolic Regulators between Humans and Mice
Authors: JIANG CHENGFEI , LI ZHE , MA YONGHE , CAO HAIMING
Published: June 2024

Mounting genetic and clinical evidence supports the critical role of human long non-coding RNA metabolic regulators (hLMRs) in metabolic homeostasis. Yet, most human lncRNAs are non-conserved, hindering their functional characterization for clinical translation in a physiological context. In this study, we investigated the hypothesis that non-conserved hLMRs and mLMRs may have shared functions, forming functionally conserved LMRs (fcLMRs), which could define the physiological role of hLMRs in mice. To test this hypothesis, we have developed a sequence-independent strategy to select fcLMRs and validated their functional similarity in vivo. Knocking down mLMRs in mouse livers demonstrated that concurrent hLMR expression rescued their functions, confirming the pipeline's effectiveness. Using fcLMR1 (h/mLMR1) as an example, we further demonstrated that h/mLMR1 share similar in vivo metabolic function via a conserved docking mechanism. Specifically, both h/mLMR1 robustly regulated triglyceride levels through modulating the expression of a similar set of lipogenic genes in mice. Mechanistically, h/mLMR1 binds to PABPC1 via a short motif on either lncRNA that have divergent sequences but similar structures. The h/mLMR1-PABPC1 interaction inhibits protein translation, which subsequently activates an amino acid-mTOR-SREBP1 axis to regulate lipogenic gene expression. In light of the elevated expression of h/mLMR1 in humans and mice with hepatic steatosis, the PABPC1-binding motif on hLMR1 represents a potential non-conserved human drug target whose function can be fully validated in a physiologically relevant setting before any clinical studies. Hence our study indicates that fcLMRs represent a novel and prevalent biological phenomenon, and deep phenotyping of genetic mLMR mouse models constitutes a powerful approach to understand the pathophysiological role of hLMRs before translating them to actionable drug targets in humans.

Disclosure

C. Jiang: None. Z. Li: None. Y. Ma: None. H. Cao: None.
343-OR: Identifying Nogo-B Receptor as a Resilience Factor in Preventing Obesity-Associated Type 2 Diabetes
Authors: SARIF MOHIUDDIN MOHAMMAD , HU WENQUAN , BARUA RASHU , TIRUMALASETTY MUNICHANDRA B. , CHOUBEY MAYANK , MIAO QING
Published: June 2024

Obesity is a well-known risk factor for type 2 diabetes (T2D), with over 90% of T2D patients being overweight or obese. However, only approximately 30% of obese individuals develop T2D, suggesting the existence of resilience factors in non-T2D obese individuals that protect against obesity-related T2D. Our research aimed to identify these protective factors by comparing gene expression profiles between obese T2D patients and obese individuals without T2D. Our findings suggest that the Nogo-B receptor (NgBR) may be a key resilience factor in preventing obesity-induced T2D. We observed that obesity-induced loss of NgBR in the liver disrupts the regulation of hepatic gluconeogenesis and insulin sensitivity. This was further supported by decreased NgBR expression in the livers of diabetic mice and T2D obese patients, compared to non-T2D obese and lean subjects. NgBR hepatocyte-specific knockout mice exhibited a moderate increase in blood glucose levels, which was significantly augmented by high-fat diet (HFD) feeding to T2D levels. Our data demonstrated that NgBR plays a crucial, previously unrecognized role in maintaining AMPK activation. NgBR binds to the farnesylated form of liver kinase B1 (LKB1), a key regulator of AMPK. The depletion of NgBR in hepatocytes disrupts the localization of LKB1 in the plasma membrane, impairing AMPK activation, a critical signal for adiponectin-mediated insulin sensitivity. The loss of NgBR in the obese liver disrupts adiponectin-dependent regulation of hepatic gluconeogenesis and insulin sensitivity. NgBR hepatocyte-specific knockout mice display many prediabetes characteristics and are more susceptible to HFD-induced T2D onset.

In conclusion, our findings indicate that NgBR is a critical resilience factor necessary for maintaining hepatic gluconeogenesis regulation and preventing insulin resistance in obesity-associated T2D.

Disclosure

M. Mohiuddin: None. W. Hu: None. R. Barua: None. M.B. Tirumalasetty: None. M. Choubey: None. Q. Miao: None.

Funding

NIDDK (DK132056, DK112971)
347-OR: Plasma Lipidome in People with Insulin-Sensitive and Insulin-Resistant Obesity
Authors: PETERSEN MAX C. , SMITH GORDON I. , ARMANDO AARON , QUEHENBERGER OSWALD , DENNIS EDWARD A. , KLEIN SAMUEL
Published: June 2024

Insulin-resistant glucose metabolism is common in obesity. However, some people with obesity are insulin-sensitive. It is not clear whether obesity and insulin sensitivity have independent effects on the plasma lipidome. We evaluated plasma complex lipids (including phospholipids, glycerolipids, sphingolipids, acylcarnitines, and cholesteryl esters) by using UPLC-MS/MS and assessed insulin sensitivity as the glucose disposal rate (GDR) per kg fat-free mass divided by plasma insulin concentration during a hyperinsulinemic-euglycemic clamp procedure in 14 adults with insulin-sensitive obesity [ISO, GDR 99.0 ± 8.1 (mg/kg FFM/min)/(µU/mL), 14 adults with insulin-resistant obesity [IRO, GDR (31.8 ± 1.7 mg/kg FFM/min)/(µU/mL)], and 14 adults who were insulin sensitive and lean [ISL, GDR (101.3 ± 5.5 mg/kg FFM/min)/(µU/mL)]. The ISO and IRO groups were matched on age, sex, and body mass index. A total of 780 lipid species in 15 classes were identified. No plasma lipids were significantly different between the ISL and ISO groups, but 52 lipids were significantly different between the ISO and MUO groups (≥1.25 fold-change and false discovery rate <0.05). For all lipid classes, total concentration (sum of species) was not different between the ISL and ISO groups, whereas phosphatidylethanolamine, phosphatidylglycerol, triglyceride, and diacylglycerol (DAG) concentrations were greater and alkyl-phosphatidylcholine (PC) concentration was lower in the IRO than the ISO group (all P < 0.05). The ten lipid species most strongly correlated with insulin resistance included six DAGs, three sphingomyelins, and one ceramide species (r = -0.55 to -0.66, all P <0.0005). The ten lipids most correlated with insulin sensitivity included five lyso-PC, three alkyl-PC, and two plasmenyl-PC species (r = 0.58 to 0.70, all P <0.0001). These results indicate that insulin resistance, rather than obesity per se, is associated with alterations in the plasma lipidome.

Disclosure

M.C. Petersen: None. G.I. Smith: None. A. Armando: None. O. Quehenberger: None. E.A. Dennis: None. S. Klein: Consultant; Alnylam Pharmaceuticals, Inc. Advisory Panel; Altimmune Inc., Merck Sharp & Dohme Corp.

Funding

National Institutes of Health (KL2TR002346)
35-PUB: Glycemic Control and Quality of Life in Patients with Type 1 Diabetes from Brazil Treated with Automated Insulin Delivery Systems
Authors: DA SILVA MESSIAS LARYSSA , VENTURA GABRIELLA L. , DANTAS MARIA EDUARDA P. , DANTAS JOANA R. , SOUTO DÉBORA L. , DE LOURDES MACHADO MARIA , OLIVEIRA TÁSSIA , SANTOS EDSON P. , SOARES THIAGO M. , ZAJDENVERG LENITA , RODACKI MELANIE
Published: June 2024

Automated insulin delivery systems (AID) such as AAPS or Medtronic's 780G™ pump may reduce the burden of decision-making for patients with type 1 diabetes (T1D). This study aims to compare quality of life (QOL) and glycemic control between patients with T1D that receive AID systems and other treatments in the Brazilian population.This was a study that included T1D patients reached through an online survey via social media. Remote data was collected with an AirTable form, including questions about education, glucose control and QOL questionnaire (DQOL-Brazil).The study groups comprised 228 patients with a mean age and disease duration of 30.4 ± 11.4 and 13.5 ± 10.7 years, respectively. They were divided in groups: 78 with automation (Group A) and 150 without automation (Group B). Group A had a higher proportion of patients or caregivers with higher education (p < 0.01; 74.7 vs 48% and 88.9 vs 51.5%, respectively), lower A1c (6.6± 0.8% vs 7.5± 2.3%; p<0.001), more A1c < 7% (65.8 vs 56.1%; p < 0.001), lower severe hypoglycemic events in a year (0.5 ± 1.1 vs 1.8 ± 1.9; p < 0.001) and better DQOL scores (93.1 ± 27.4 vs 120.8 ± 28.7; p< 0.001) than group B. Weekly mean reported hypoglycemia rates were similar between groups (3.51 ± 2.09 in A vs 3.4 ± 1.9 in B; p=0.73). More patients in group A reported being moderately of very satisfied with time spent to manage diabetes (52.6 vs 12.7%; p<0.001) and being moderately/very happy with current treatment (67.9 vs 18%; p < 0.001) than in group B. Similar results were seen when only patients using sensors were included, except for the difference in A1c (6.6 ± 0,8% vs 7.1 ± 1.7%; p=0.12) and % A1c < 7% (66.7 vs 54.3; p=0.13), which did not persist.In this sample, patients with T1D and AID had better QOL and glycemic control, with a lower rate of severe hypoglycemia than others. Although A1c did not differ between patients who did not use AID systems but had sensors and those in AID systems, differences in QOL and hypoglycemia rates were still seen.

Disclosure

L. Messias: None. G.L. Ventura: None. M.P. Dantas: None. J.R. Dantas: None. D.L. Souto: None. M. Machado: None. T. Oliveira: None. E.P. Santos: None. T.M. Soares: None. L. Zajdenverg: None. M. Rodacki: None.
363-OR: Matrix Metalloprotease-2 as a Novel Regulator of Glucose Utilization by Adipocytes and High-Fat Diet-Induced Glucose Intolerance
Authors: LEMPICKI MELISSA D. , GARRIGUES RYAN J. , GARCIA BRANDON , MEHER AKSHAYA K.
Published: June 2024

Obesity and its related comorbidities, such as glucose intolerance and hyperglycemia, pose risks for type 2 diabetes. Studies on the murine models of high-fat diet (HFD)-induced obesity revealed that glucose transporter 4 (GLUT4) expression on white adipocytes is critical for absorption of excess glucose and maintenance of whole-body glucose homeostasis. Matrix metalloproteases (MMPs) play a crucial role in remodeling the white adipose tissue (WAT) during obesity. MMPs have multiple protein substrates, surprisingly, it is unknown if MMPs can directly cleave GLUT4 on adipocyte surface and impair glucose absorption. To determine the highly active MMP expressed in the WAT during obesity, we placed male C57BL/6J mice on an HFD for 5, 9, and 11 weeks or on a standard chow diet, examined the development of hyperglycemia, inflammation, and MMP activity in the gonadal WAT using gelatin zymography. Flow cytometry studies on gonadal WAT confirmed an increase in inflammatory immune cell infiltration, and RT-PCR analysis confirmed elevated TNF-α in late stages of obesity. Zymography identified MMP2 as the highly active MMP in the WAT after HFD. Next, we used the Seahorse extracellular flux analyzer to determine the metabolic fitness of differentiating 3T3-L1 adipocytes after treatment with MMP2 for 2 hours. Glycolysis stress tests revealed MMP2, even at 200 ng/ml, attenuated glucose utilization, as indicated by 30% decreased basal glycolysis, 50% decrease in glycolytic capacity, and blunted glycolytic reserve. Further, in silico structural analysis using AlphaFold identified a potential MMP2 cleavage site on the extracellular domain of both murine and human GLUT4. This encouraged us to hypothesize that MMP2 reduces glucose utilization in differentiating adipocytes by cleaving GLUT4 extracellular domains. This is a novel mechanism that may add to insulin resistance to promote hyperglycemia and suggests inhibition of MMP2 would promote healthy obesity.

Disclosure

M.D. Lempicki: None. R.J. Garrigues: None. B. Garcia: None. A.K. Meher: None.
380-P: Safety of SGLT2 Inhibitors in People with Diabetes With or Without Background Insulin—Data from DAR Global Survey
Authors: ABDELGADIR ELAMIN I.E. , HASSANEIN MOHAMED
Published: June 2024

Introduction: A considerable number of studies have assessed the safety of Ramadan fasting in people with diabetes mellitus. This global survey from various region in the middle east and north Africa is tailored to fill further gaps in safety of SGLT2i during Ramadan fasting.

Methods: The participating countries from 5 geographical regions were as follows: Southeast Asia, Gulf nations, Maghreb countries, Middle East and Turkey. All participating physicians interviewed people with diabetes who intended to fast Ramadan, the biometric and biochemical data was extracted from the electronic medical files

Results: The overall survey population was 5865 people with T2D on oral injectable. Out of those patients 2379 were on SGLT2i plus other hypoglycaemic agents. 705 were on GLT2i without Sulfonylurea (SU) or insulin, 927 were on SGLT2i and insulin but without SU, and 169 patients were on combination of theSGLT2i, SU, and insulin. Only 5.4 % did break their fast in the SGLT2i group compared to 13.6% in the triple combination. Hypoglycemia was least encountered in the SGLT2i (8%), 16.4% in the dual combination, and 20.9% in the triple combination therapy. Majority of hypoglycemia episodes were between 3 pm and Maghrib time (estimated 6-8 PM) in the SGLT2i group (72.5%), while in the group with insulin and/or SU had hypoglycemia predominance from 12 mid-day till maghrib. In terms of emergency room attendance due to hypoglycemia doubled when insulin was added and increased to 3.5 folds when both insulin and SU was added to SGLT2i (3.4 and 6.9%, respectively compared to 1.9% in the SGLT2i group).

Conclusion: In this study, SGLT2i without insulin and/or SU is associated with less hypoglycemia, less days with broken fasting due to diabetes related complications. The emergency room attendance increased up to 3.5 folds when Insulin and/or SU to SGLT2i.

Disclosure

E.I.E. Abdelgadir: None. M. Hassanein: Research Support; Novo Nordisk A/S. Advisory Panel; Sanofi. Speaker's Bureau; Abbott, Boehringer-Ingelheim, Medtronic. Advisory Panel; Eli Lilly and Company.
382-P: Clinical Characteristics of Insulinoma Patients with Secondary Adrenal Insufficiency
Authors: WANG XIA , YU LUO , CHEN YAO , HUI XIE J.
Published: June 2024

Objective: The purpose of this study is to investigate the clinical characteristics and high-risk factors of insulinoma combined with secondary adrenal cortical insufficiency.

Methods: This was a retrospective study including 44 surgically confirmed insulinoma patients and 16 diabetes patients with hypoglycemia. IBM SPSS Statistic 27 was used for statistical analysis.

Results: The proportion of low morning cortisol levels was significantly higher in insulinoma patients than in diabetes patients with hypoglycemia. Compared to diabetes patients with hypoglycemia, insulinoma patients had lower blood glucose levels during hypoglycemia. Additionally, serum cortisol levels in the morning and midnight were lower in insulinoma patients, with a significantly greater decrease in morning serum cortisol levels (Fig.1). In insulinoma patients group, both the insulin release index(IRI) >1.2 group and the insulin levels >38.6uIu/ml group had larger tumor diameters than the IRI <0.3 group and the insulin levels 18.8-38.6uIu/ml group, respectively. The tumor diameters ≥1cm group had lower morning serum cortisol and ACTH than the tumor diameters<1cm group.

Conclusion: Our study suggests that larger tumors may be associated with secondary adrenal insufficiency in insulinoma patients, thereby increasing perioperative risks of insulinoma patients.

Disclosure

X. Wang: None. L. Yu: None. Y. Chen: None. X.J. Hui: None.
394-P: Empagliflozin Ameliorate Renal Fibrosis in DKD
Authors: CAI XIANG , CAO HUANYI , WANG MEIJUN , YU PIAOJIAN , LIANG XIAOQI , LIANG HUA , XU FEN , CAI MENGYIN
Published: June 2024

Introduction & Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve renal outcomes in diabetic kidney disease (DKD), but the mechanisms underlying this effect are not fully elucidated. Renal fibrosis is an important cause leading to renal failure in DKD. The purpose of this study is to investigate whether SGLT2 inhibitor empagliflozin can improve renal fibrosis in DKD models.

Methods: The DKD models used in this study include CD-1 mice treated with streptozotocin (STZ), C57/BL6J mice fed with high-fat diet (HFD), and ob mice fed with methionine/choline-deficient diet (MCD) /ob mice. Mice were administered empagliflozin (10mg/kg) daily by gavage for 4 to 8 weeks. Renal fibrosis was examined by pathological staining, immunofluorescence staining and western blot.

Results: After DKD induction, renal fibrosis was observed in three DKD mouse models indicated by PAS staining and Masson staining. Collagen III α1 chain (COL3A1) and alpha-smooth muscle actin (αSMA) were upregulated in DKD mouse models detected by immunofluorescence staining and western blot. Empagliflozin significantly ameliorated pathological changes of renal fibrosis and downregulated COL3A1 and αSMA.

Conclusion: Empagliflozin ameliorate renal fibrosis in DKD.

Disclosure

X. Cai: None. H. Cao: None. M. Wang: None. P. Yu: None. X. Liang: None. H. Liang: None. F. Xu: None. M. Cai: None.
397-P: The C/EBPß-XOR Axis and Genetic Risk for Diabetic Kidney Disease
Authors: EKPERIKPE UBONG , YU LIPING , DAEHN ILSE S.
Published: June 2024

Introduction & Objective: Diabetic kidney disease (DKD) is the leading single cause of end-stage renal disease in the United States. Approximately 30% of diabetics develop DKD with comparable blood glucose levels, indicating a significant genetic predisposition. However, the underlying mechanisms that contribute to differential susceptibility are unclear. The glomerulus is the primary site of injury with hypertrophy and podocyte depletion being the hallmarks for progressive DKD. We have demonstrated that mitochondrial oxidative damage in glomerular endothelial cells (GECs), leads to podocyte loss via GEC-to-podocyte crosstalk in DKD susceptible DBA/2J (D2) mice compared to DKD resistant C57BL/6J (B6) mice.

Methods: We mapped potential genetic loci associated with podocyte depletion after long-term diabetes (6mth using 39 strains of BXD, parental B6 and D2 mice). We identified a significant cis-acting variant in the promoter of xanthine oxidoreductase (Xor). XOR catalyze the oxidation of purine substrates to uric acid and reactive oxygen species (ROS). Using CRISPR/Cas9 to knock-in the Xor risk variant into DKD-resistant B6 mice, we generated mutant B6-Xorem1 mice with significantly higher XOR activity than B6.

Results: This risk variant is a transcription factor binding site to C/EBPβ. We observed higher C/EBPβ expression in GECs from diabetic B6-Xorem1 mice. B6-Xorem1 mice had increased mitochondrial oxidative stress in GECs, podocyte depletion, basement membrane thickening, albuminuria, glomerulosclerosis and tubular injury. These changes were prevented with XOR inhibition. Interestingly B6-Xorem1 mice developed age-associated glomerulosclerosis. In vitro studies support a Xor and mitochondrial ROS interplay in endothelial cells that resulted in GEC dysfunction.

Conclusion: Xor promoter variants are causal for DKD susceptibility and may predispose to aging and other diabetic complications.

Disclosure

U. Ekperikpe: None. L. yu: None. I.S. Daehn: None.

Funding

National Institutes of Health (R01DK097253)
408-P: Long-Term Improvement in Renal Function following Intensive Lifestyle Intervention in Patients with Diabetes and Obesity—A 15-Year Longitudinal Study
Authors: SALAH TAREQ , AL-BADRI MARWA , ALMASIH BARBAR ASKAR ABD , KHATER ABDELRAHMAN , DHAVER SHILTON E. , MOTTALIB ADHAM , HAMDY OSAMA
Published: June 2024

Nearly 30% of patients with diabetes mellitus (DM) develop diabetic nephropathy over time. The long-term effect of weight loss, through lifestyle intervention, on kidney function remains unknown.We evaluated 94 patients with obesity and DM (12.8% type 1 DM and 87.2% type 2 DM, age 53.9±9.9 years, diabetes duration 10.9±10.3 years, weight 108.0±18.8 kg, and BMI 38.1±5.0 kg/m2) who enrolled in a 12-week multidisciplinary intensive lifestyle intervention (ILI) conducted in real-world clinical practice. Patients were prospectively followed for over 15 years. At one year, we stratified participants according to their percentage weight loss into: group A, who maintained ≥7% weight loss (48.9%) and group B, who maintained <7% weight loss (51.1%). At 15 years, the full cohort maintained an average of 8.0±2.8 kg weight loss (10.1±19.6%, p<0.0001). Group A lost 12.8±4.1 kg (15.1±21.9%, p<0.0001) and group B lost 3.9±3.4 kg (5.5±17.6%, p=0.024). A1C did not change from baseline in group A, but increased in group B (0.6±0.5%, p=0.027). Systolic blood pressure did not change in both groups. Diastolic blood pressure decreased only in group A from 77±3 mmHg to 73±3 mmHg (p=0.03). LDL-cholesterol and HDL-cholesterol significantly improved in both groups, however, triglycerides significantly increased in both groups. Estimated glomerular filtration rate (eGFR) increased in group A from 79.5±12.5 to 92.5±15.3 mL/min/1.73 m2 (p=0.02) and in group B from 80.5±7.5 to 90.8±13.3 mL/min/1.73 m2 (p=0.02). There was no significant change in urinary albumin/creatinine ratio from baseline or serum creatinine in both groups.We conclude that 12 weeks of ILI have a sustained improvement of renal function for up to 15 years after intervention. This improvement is more pronounced in those who maintained ≥7% weight loss at one year.

Disclosure

T. Salah: None. M. Al-Badri: None. A. Barbar Askar: None. A. Khater: None. S.E. Dhaver: None. A. Mottalib: None. O. Hamdy: Research Support; Eli Lilly and Company, Novo Nordisk. Consultant; Abbott Nutrition. Stock/Shareholder; Healthimation. Research Support; Gilead Sciences, Inc. Advisory Panel; Nemaura Medical, Twin Health, L-Nutra Inc.
410-P: Evaluating the Performance of the 2021 CKD–EPI Equation in People with Diabetes
Authors: KWOK RODNEY , MACISAAC RICHARD , KISHORE KARTIK , ZAFARI TINA , HACHEM MARIAM , KOYE DIGSU , RESEARCH GROUP DCCT/EDIC , SCHAEFFNER ELKE , JEONG TAEDONG , MIN WON-KI , BJORNSTAD PETTER , CHURILOV LEONID , EKINCI ELIF I.
Published: June 2024

Introduction: In 2021, CKD-EPI equation without the race coefficient (2021 CKD-EPI equation) was recommended for use in clinical practice by international guidelines. The performance of the 2021 equation in people with diabetes is unknown. This study aims to assess and compare the performance of the 2021 CKD-EPI equation to the 2009 CKD-EPI equation in individuals with type 1 and/or type 2 diabetes.

Methods: Datapoints (n=16,182) were collected from people with type 1 and type 2 diabetes from six international cohorts (Diabetes Control and Complication Trial [DCCT, USA], Colorado [USA], Germany, Korea, Spain, and Australia), with mGFR assessed using exogenous filtration markers. The intra-class correlation coefficient between mGFR and eGFR for 2009 CKD-EPI equation and 2021 CKD-EPI equation was estimated using (a) a one-step intra-individual participant data meta-analysis approach, and (b) a four-level mixed-effect linear model which included studies and individual participants as first and second level random effects, method of measurement as third level fixed effect and time as fourth level random effect.

Results: Overall performance of the 2009 CKD-EPI equation was excellent (ICC: 0.96, 95%CI: 0.88, 0.99) and 2021 CKD-EPI equations (ICC: 0.87, 95%CI: 0.77, 0.93) was good. However, subgroup analyses based on clinically relevant GFR ranges (<30, 30-59, 60-89 ml/min/1.73m2) revealed poor agreement between mGFR and eGFR measurements for the 2009 CKD-EPI equation (ICC: 0.41, 0.43, 0.40 respectively) and excellent agreement for GFR ≥90 ml/min/1.73m2 (ICC: 0.92). The 2021 CKD-EPI equation revealed poor agreement across GFR ranges <30, 30-59 and 60-89 (ICC: 0.38, 0.41, 0.39 respectively) and moderate agreement for GFR ≥90 ml/min/1.73m2 (ICC: 0.55).

Conclusion: These findings suggest that the 2009 CKD-EPI equation still performs better than the 2021 CKD-EPI equation without the race co-efficient, especially in higher GFR ranges for people with diabetes.

Disclosure

R. Kwok: None. R. MacIsaac: None. K. Kishore: None. T. Zafari: None. M. Hachem: None. D. Koye: None. E. Schaeffner: Consultant; AstraZeneca. Other Relationship; National Kidney Foundation. T. Jeong: None. W. Min: None. P. Bjornstad: Consultant; AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Lilly Diabetes, Novo Nordisk, Bayer Inc., Horizon Therapeutics plc. L. Churilov: None. E.I. Ekinci: Advisory Panel; Lilly Diabetes. Research Support; Novo Nordisk, Boehringer-Ingelheim, Eli Lilly and Company. Board Member; Eli Lilly and Company. Advisory Panel; Abbott. Research Support; Endogenex, Versanis, AstraZeneca.

Funding

Australian Government Research Training Program (RTP) Scholarship
428-P: Discordance between Hemoglobin A1c and CGM-Assessed Glycemia in CKD
Authors: TANG MENGYAO , DE BOER IAN , KALIM SAHIR
Published: June 2024

Background: Hemoglobin A1C’s accuracy and precision decrease in CKD, and there is an increased interest in using CGM as an alternative method for glycemic monitoring. However, most CGM data stems from type 1 or insulin-treated type 2 diabetes (T2D) patients with normal eGFR. We conducted a pilot study to evaluate CGM metrics in CKD, including patients with T2D not using insulin and those without diabetes.

Methods: We enrolled 10 CKD patients (6 with T2D and 4 without diabetes) who wore blinded CGM (DexCom G6) for 20 days. A1C was measured at the end. Discordance was defined as an absolute difference between A1C and glucose management indicator (GMI) >=0.5%.

Results: Participants had a mean age of 68 and mean eGFR was 35 mL/min/1.73m². In participants with T2D (A1C range: 5.4-6.9%), there was wide range of CGM metrics: range of mean glucose was 115-215mg/dL, GMI 6.1-8.4%, CV 16-29%, TIR 13-96%. In participants without diabetes (A1C range: 5.2-6.1%), the range of mean glucose was 117-158mg/dL, GMI 6.1-7.1%, CV 16-29%, time-in-tight-range (70-140mg/dL) 37-86%. For several participants with similar A1C values, glycemic patterns differed substantially. Seven (70%) participants had A1C-GMI discordance, with A1C underestimating GMI (Fig).

Conclusion: Among CKD patients, large variations in CGM metrics existed and A1C-GMI discordance was common. Our findings warrant further investigation into the prevalence and predictors of such discordance.

Disclosure

M. Tang: Research Support; Dexcom, Inc. I. de Boer: Consultant; Boehringer-Ingelheim, Lilly Diabetes, AstraZeneca, Novo Nordisk, Alnylam Pharmaceuticals, Inc., George Clinical. Research Support; Dexcom, Inc., Novo Nordisk. S. Kalim: Advisory Panel; Alnylam. Speaker's Bureau; Fresenius Kabi.

Funding

American Heart Association (23POST1010825); DexCom (IIS-2023-007)
436-P: Stringent Glycemic Control and Long-Term Macrovascular Outcomes in People with Type 2 Diabetes in China—A Retrospective Study
Authors: PAN QI , SUN FENG , ZHANG MENG , SHEN PENG , SUN YEXIANG , LIN HONGBO , ZHAN SIYAN , GUO LIXIN
Published: June 2024

Introduction & Objective: Safely achieving stringent glycemic control at hemoglobin A1c (HbA1c) ≤ 6.5% is recommended in some diabetes guidelines, and HbA1c < 5.7% is considered a normal level. We aim to examine the association between stringent glycemic control and long-term macrovascular outcomes using real world data in China.

Methods: Data were retrospectively extracted from a regional data platform (2006/1/1-2021/10/31) in Yinzhou, Ningbo, China. Adult T2D patients with ≥ 1 HbA1c record from 2007/01/01-2016/10/31 were included to ensure ≥ 5 years of follow-up. Index date was the first HbA1c occurred ≥ 90 days after the initial T2D diagnosis. Index and sustained stringent glycemic control were defined as achieving HbA1c at ≤ 6.5% or < 5.7% at index or every measurement during follow-up, respectively. Cox proportional hazard model was used to examine the association between stringent glycemic control and 3-point major adverse cardiovascular event (3P-MACE) occurred during follow-up, adjusting for demographic and clinical characteristics.

Results: A total of 7,049 patients (mean age 61.4±11.4 years, 3,751 [53.7%] female) were analyzed. Over a median follow-up of 6.7 years (interquartile range 5.5-7.9), 3P-MACE occurred in 1565 (22.2%) patients at an incidence rate of 3.4 per 100 person-years. Index and sustained stringent glycemic control were significantly associated with 3P-MACE risk reduction (all p<0.05). For index stringent glycemic control, the adjusted hazard ratio (aHR) was 0.88 [0.79-0.98] for HbA1c ≤ 6.5% and 0.84 [0.70-1.00] for HbA1c < 5.7%. For sustained stringent glycemic control, the aHR was 0.74 [0.63-0.86] for HbA1c ≤ 6.5% and 0.58 [0.42-0.79] for HbA1c < 5.7%.

Conclusion: Stringent glycemic control was associated with significant risk reduction in long-term macrovascular outcomes in Chinese people with T2D. Intensive diabetes therapies may have long-term benefits for cardio-cerebrovascular outcomes in T2D patients.

Disclosure

Q. Pan: None. F. Sun: None. M. Zhang: None. P. Shen: None. Y. Sun: None. H. Lin: None. S. Zhan: None. L. Guo: Consultant; Abbott, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Eli Lilly and Company, Hengrui (USA) Ltd., Dreisamtech, Dongbao, Gan & Lee, Hansoh.

Funding

Eli Lilly and Company, Shanghai, China
437-P: Three Decades of Lipid-Lowering Therapy in Type 2 Diabetic Patients with Angiographically Proven Stable Coronary Artery Disease
Authors: VOGEL JOHANNES , RATZ MAGDALENA , ELSNER PASCAL , PLATTNER THOMAS , VONBANK ALEXANDER , MADER ARTHUR , LARCHER BARBARA , LEIHERER ANDREAS , MUENDLEIN AXEL , FRICK MATTHIAS , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2024

Lipid-lowering therapy (LLT) is key to reducing the burden of macrovascular diabetes complications. Here, we aim to assess long-term trends in LLT and LDL-C levels among patients with type 2 diabetes (T2DM) with angiographically proven coronary artery disease (CAD). We investigated T2DM patients (n=590), who were referred to elective coronary angiography and were diagnosed with CAD in one of three observational cohort studies (OS) spanning 25 years: OS1: 1999-2000 (n=190); OS2: 2005-2008 (n=241); OS3: 2022-2023 (n=159). These studies were conducted at the same cardiology unit of a tertiary care hospital in Central Europe. The proportion of patients receiving statin therapy (C10AA and C10AB) increased significantly from 57.9% in OS1 to 64.3% in OS2 and 78.6% in OS3 (ptrend<0.001). Further, there was an increase in patients receiving high-intensity statin therapy, rising from none in OS1 to 8.5% in OS2 and 73.4% in OS3 (ptrend<0.001). The proportion of patients receiving more than one LLT compound also increased (OS1: 2.1%; OS2: 2.1%; OS3: 35.2%; ptrend<0.001). Use of ezetimibe (C10AX09) increased (OS1: 0.0%; OS2: 1.2%; OS3: 39.0%; ptrend<0.001) and fibrate use (C10AB) decreased (OS1: 5.3%; OS2: 3.3%; OS3: 0.6%; ptrend=0.015). Newly approved compounds (C10AX13 - C10AX16) were prescribed for 3.8% of patients in OS3. Among statin combination therapies, ezetimibe was predominantly used (93.5%). Mean LDL-C levels declined significantly from 123±38 mg/dL (OS1) to 115±39 mg/dL (OS2) and 77±38 mg/dL (OS3; ptrend<0.001). However, only 2.2% of patients in OS1, 2.5% in OS2 and 32.1% in OS3 reached an LDL-C target of <55 mg/dL (ptrend<0.001). This analysis suggests an upward trend in treatment intensity and a substantial improvement in LDL-C levels among T2DM patients with CAD. However, the majority of these patients still does not reach their LDL-C target.

Disclosure

J. Vogel: None. M. Ratz: None. P. Elsner: None. T. Plattner: None. A. Vonbank: None. A. Mader: None. B. Larcher: None. A. Leiherer: None. A. Muendlein: None. M. Frick: None. H. Drexel: None. C.H. Saely: None.
444-P: Machine Learning Driven Prediction of Hyperglycemia, Acute Kidney Injury, and Atrial Fibrillation after Cardiac Surgery Using High-Resolution Metabolomics
Authors: KU DOHYUN , SAM VARGHESE JITHIN , SMITH MATTHEW R. , PEREZ-GUZMAN MIREYA , GUERRERO ARROYO LIZDA I. , BARTELT JACKSON , ZAHEDI TAJRISHI FARBOD , LI JING , PASQUEL FRANCISCO J.
Published: June 2024

Stress hyperglycemia (SH), acute kidney injury (AKI), and atrial fibrillation (AF) are common complications after cardiac surgery. We examined the predictive value of metabolite changes on inpatient outcomes in participants undergoing coronary artery bypass graft surgery. Methods: We analyzed 8,631 and 10,919 metabolites from C18 chromatography and hydrophilic interaction liquid chromatography (HILIC) to predict SH, AKI, and AF. The study included 61 participants (mean age: 62.5; 16.1% female) with one missing SH. We imputed zero values in the metabolites with half the minimum value. For SH and AF, we utilized the log-ratios of metabolite measured during and before surgery as features, while for AKI, we employed those measured exclusively during surgery. We used the Mann-Whitney U-test to select significant features and the Partial Least Squares (PLS) regression for dimension reduction. PLS components, along with covariates such as age, sex, and BMI, were incorporated into machine learning (ML) classifiers, and the Random Forest classifier emerged as the most effective based on leave-one-out cross-validation (LOOCV) performance. Finally, we aggregated significant feature contributions across all LOOCV iterations to identify the most influential features.

Results: To predict SH, our ML pipeline achieved an AUC of 0.82, accuracy of 0.77, sensitivity of 0.84, and specificity of 0.71 identifying five significant features across all LOOCV iterations. For AF prediction, we achieved an AUC of 0.85, accuracy of 0.82, sensitivity of 0.91, and specificity of 0.77, with 97 significant features identified. For AKI, we attained an AUC of 0.74, accuracy of 0.72, sensitivity of 0.79, and specificity of 0.70 identifying 20 significant features.

Conclusion: Machine learning algorithms may aid in the identification of multiple potentially relevant biomarkers linked to adverse cardiometabolic outcomes after cardiac surgery.

Disclosure

D. Ku: None. J. Varghese: None. M.R. Smith: None. M. Perez-Guzman: None. L.I. Guerrero Arroyo: None. J. Bartelt: None. F. Zahedi Tajrishi: None. J. Li: None. F.J. Pasquel: Research Support; Tandem Diabetes Care, Inc., Insulet Corporation, Dexcom, Inc., Ideal Medical Technologies, Novo Nordisk. Consultant; Dexcom, Inc., Medscape.

Funding

National Institutes of Health (K23GM128221)
448-P: The A Body Shape Index and Type 2 Diabetes Are Mutually Independent Predictors of Cardiovascular Events In Patients with Established Coronary Artery Disease
Authors: PLATTNER THOMAS , LARCHER BARBARA , MADER ARTHUR , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2024

The A Body Shape index (ABSI) is a validated measure of visceral adiposity that is calculated based on waist circumference, height and BMI. Its power to predict cardiovascular events in patients with coronary artery disease (CAD) is unclear and is addressed in the present study. We prospectively recorded cardiovascular events in a cohort of 938 patients with CAD over a mean follow-up time of 8.1±4.2 years. At baseline, the ABSI was higher in patients with type 2 diabetes (T2DM; n=308) than in those who did not have diabetes (8.4±0.6 vs. 8.3±0.5; p=0.032). Prospectively, the ABSI significantly predicted the incidence of cardiovascular events (n=389) after adjustment for age, gender, smoking, hypertension, LDL cholesterol, HDL cholesterol, and T2DM (standardized adjusted HRs 1.12 [1.03-1.22]; p=0.009, respectively). T2DM in turn also significantly predicted cardiovascular events in this model with a HR of 1.23 [1.02-1.49]; p=0.034 after adjustment for ABSI.

We conclude that ABSI and T2DM are mutually independent risk factors for cardiovascular events in patients with established CAD.

Disclosure

T. Plattner: None. B. Larcher: None. A. Mader: None. A. Vonbank: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
449-P: Liraglutide Rapid Effects on Glucose and Adipose Tissue during and after CABG
Authors: IACOBELLIS GIANLUCA , FRASCA DANIELA
Published: June 2024

Introduction: Optimization of glucose control during coronary artery by-pass grafting (CABG) is a major goal to reduce intra and post-op morbidity and mortality in subjects with coronary artery disease (CAD) and type 2 diabetes (T2DM). Glucagon like peptide-1 receptor analogs (GLP-1RAs) reduce cardiovascular risk. However, the short-term effects of GLP1RA on intra and post CABG metabolic control is unknown.

Objective: was to evaluate if pre-operative treatment with liraglutide can improve intra and post CABG glucose and metabolic control

Methods: This was a 12-week randomized, double-blind, placebo-controlled interventional study in 38 patients with T2DM and CAD with an acceptable glycemic control (HbA1c <8%) who required elective CABG. Subjects were started on either liraglutide or placebo in addition to current treatment for a minimum of 4 up to 12 weeks prior to CABG. Fat samples were collected during CABG; blood and clinical data were obtained before starting either liraglutide or placebo, intra-op and 1-month post-op.

Results: The two groups were very homogenous prior to the CABG. Patients who were randomized to liraglutide had significantly better intra-op glucose control during the CABG than those on placebo (146±21 vs 160±21 mg/dl, p<0.01). BMI and body weight significantly decreased at 1-month post-op when compared to baseline in patients who were randomized to liraglutide (from 32.7±6 to 30.5±5 kg/m2; from 214±39 to 208±38 lbs p< 0.05 for both), whereas placebo had no significant BMI or body weight changes. Post-op HbA1c improved in both liraglutide and placebo group (from 6.9 to 5.9% and from 7.2 to 6.1% respectively, p<0.01). Coronary epicardial fat (EAT) inflammatory transcriptome was significantly different than subcutaneous fat (p<0.01).

Conclusions: This RCT shows for the first time that short-term pre-CABG liraglutide induces significant beneficial cardio-metabolic effects, such as better intra- and post-operative glucose control, EAT changes and post-operative weight loss.

Disclosure

G. Iacobellis: None. D. Frasca: None.

Funding

NCT03260881
451-P: Different Cardioprotective Efficacy of Metformin, Empagliflozin, and Semaglutide to Attenuate High Glucose–Oxidative Stress via Nrf2/Keap1 in Murine Cardiomyocytes
Authors: SENESI PAMELA , FERRULLI ANNA , GALLAZZI MATTEO , BASSANI BARBARA , BRUNO ANTONINO , LUZI LIVIO
Published: June 2024

SGLT2 inhibitors (SGLT2is) and GLP-1R agonists (GLP-1RAs) represent the innovative drugs in the management of failure and ischemic heart disease. Moreover, new studies are evaluating metformin (M) action on heart. However, cardiac cellular mechanisms regulated by glucose-lowering drugs have yet to be adequately investigated. This study aimed to compare M, E and GLP-1RA semaglutide (S) impact on i) mitochondrial reactive oxygen species (mtROS) production, ii) Nrf2/Keap1 axis, and iii) cellular damages induced by high glucose in H9c2 rat cardiomyocytes. H9c2 were exposed to normal (NG, 5.5 mM) or high glucose (HG, 33 mM) for 48 h and treated with 400 uM M (MHG), 500 nM E (EHG) or 100 nM S (SHG) for 24 h. H9c2 cells were cultured in NG or HG as controls. E and S reduced HG-induced mtROS production whereas M action was ineffective. Consistent with these results, E and S significantly activated Nrf2/Keap1 axis promoting Nrf2 translocation into the nuclei and the anti-oxidant response. In MHG cells, Nrf2 translocation was limited. As known, Nrf2/Keap1 is modulated by AKT and AMPK pathways that are inhibited by HG. E significantly improved AMPK activation whereas S increased AKT signaling. M weakly rise AMPK activation. HG induced-mtROS is associated to ERKs up-activation and structural alterations. In HG medium, H9c2 became hypertrophic and acquired rounded morphology. Both E and S significantly downregulated ERKs activation and restored fusiform morphology and size. M only counteracted hypertrophic process. All drugs have a similar effect only on cellular viability rescuing the reduction of H9c2 proliferation caused by HG. Overall, our results suggest that i) E and S are more effective in mitigating HG-induced cardiac injury that M, ii) E and S seem act in similar manner, reducing mtROS via Nrf2/Keap1 axis, and restoring respectively AMPK and AKT signaling. This study suggests potential combined therapy in diabetic patients.

Disclosure

P. Senesi: None. A. Ferrulli: None. M. Gallazzi: None. B. Bassani: None. A. Bruno: None. L. Luzi: Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. Research Support; Boehringer-Ingelheim. Advisory Panel; Medtronic. Research Support; MOVI. Advisory Panel; SUNSTAR. Speaker's Bureau; SAVIO, Amgen Inc.
458-P: Whole Left Ventricular Cardiac MRI in High-Risk People with Type 1 Diabetes Reveals Pathological Extracellular Volume Fraction and T1 Relaxation Times
Authors: NOVODVORSKY PETER , DUBSKY MICHAL , MARHEFKOVÁ NATÁLIA , ADLA THEODOR , ROLAND ROBERT , PAZDERNIK MICHAL , HALUZIK MARTIN , GARG PANKAJ
Published: June 2024

Introduction: Diffuse myocardial fibrosis is a negative CV prognostic marker. We employed advanced cardiac MRI (CMR) techniques for detailed left ventricular myocardial tissue characterization people with type 1 diabetes (PwT1D) and high CV risk.

Methods: Quantitative native T1 mapping (T1) and extracellular volume fraction (ECV) calculation of the whole left ventricular myocardial volume (LVMV) was done (1.5T Avanto Fit, Siemens) in PwT1D and high CV risk (CAC score >400 and/or presence of ≥2 atherosclerotic plaques in the carotids) but without clinical diagnosis of CVD or heart failure. Percentage of LVMV above the normal values for T1 (>1100 ms) and ECV (>28 %) was calculated.

Results: Twelve PwT1D (8/12 women) with mean (SD) [range] age 65 (2) [60 - 67] years, diabetes duration 36 (12) [16 - 56] years, HbA1c 7.5 (0.9) [6.0 - 8.8] %, LV EF 66 (7) [54 - 77] % were analyzed. Mean (SD) [range] native T1 time was 1060 (41) [996 - 1138] ms and the % of LVMV >1100 ms was 27 (11) [14 - 47] % (Fig. 1A). Mean (SD) [range] ECV was 28.6 (3.5) [23 - 33] % and the % of LVMV >28 % was 47 (21) [7 - 78] % (Fig. 1B).

Conclusion: This is the first CMR study which has applied threshold values to native T1 and ECV data for the whole LVMV in PwT1D. We demonstrate large myocardial areas which are above the normal values. Clinical implications of our findings will require further evaluation on larger populations.

Disclosure

P. Novodvorsky: Speaker's Bureau; Sanofi, Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Novo Nordisk A/S. Research Support; Sanofi. Speaker's Bureau; Abbott, Medtronic, Berlin-Chemie AG, Viatris Inc., Novartis AG. M. Dubsky: None. N. Marhefková: None. T. Adla: None. R. Roland: None. M. Pazdernik: None. M. Haluzik: Advisory Panel; Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Johnson & Johnson Medical Devices Companies. Consultant; Merck & Co., Inc., Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies, Novatin. Research Support; Sanofi. Speaker's Bureau; Sanofi, Novo Nordisk. P. Garg: Consultant; Edwards Lifesciences, Anteris. Advisory Panel; Pie Medical, Medis.

Funding

National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, Project No. LX22NPO5104); Funded by the European Union; Next Generation EU
478-P: Preventing Peripheral Neuropathy in Adults with Type 2 Diabetes—A Meta-analysis of Randomized Clinical Trials
Authors: GUNAWAN SOPHIA , ANTONY THERESA , NICHOLSON ANDREW , NATARAJAN SUNDAR
Published: June 2024

Background: Diabetic Peripheral Neuropathy (DPN) is a debilitating complication of diabetes. Current diabetes management guidelines recommend targeting modifiable risk factors like glycemia, blood pressure (BP), lipids, obesity, and smoking to prevent DPN, but their individual effectiveness is unclear.

Aim: To quantify the effectiveness of interventions targeting modifiable risk factors to prevent DPN in adults with Type 2 diabetes (T2D).

Methods: The PubMed database was searched for randomized clinical trials (RCTs) from 1980 to 2023 focused on DPN prevention in adults with T2D. Eligible studies evaluated glycemic control, BP control, lipid control, obesity, or smoking cessation interventions against placebo or usual care, and reported DPN incidence for intervention and control groups. Meta-analysis for each therapy was conducted using a random-effects model in R. Heterogeneity was assessed using the I2 statistic.

Results: Seven RCTs for glycemic control and three RCTs for BP control were identified for adults with T2D. There was no significant difference in the incidence of DPN between intervention and control groups for glycemic control (Odds Ratio [OR]=0.96, 95% Confidence Interval [CI] [0.88, 1.05], p=0.38, I2=0%) and BP control (OR=0.86, 95% CI [0.39, 1.88], p=0.70, I2=78%). We were unable to identify enough high-quality RCTs to conduct meta-analysis evaluating the effect of lipid control, smoking cessation, or obesity reduction on preventing DPN.

Conclusions: While glycemic and BP control are recommended in clinical guidelines to prevent DPN, they have not been definitively shown to prevent incident DPN in adults with T2D. Identifying high-risk DPN groups using genomics or other markers and conducting high-quality RCTs in these high-risk groups using the aforementioned therapies calibrated to reach clearly specified risk factor levels may be needed to develop personalized treatments that are effective in preventing DPN in T2D.

Disclosure

S. Gunawan: None. T. Antony: None. A. Nicholson: None. S. Natarajan: None.