bluuebunny/crossref_metadata_2025 huggingface dataset:
462-P: DPP-4 Deficiency Suppresses the Progression of Atherosclerosis via Inducing M2 Macrophage Polarization
Authors: ZHOU YUQI , MATSUMURA TAKESHI , YAGI YOSHITAKA , YOSHINAGA TOMOAKI , SENOKUCHI TAKAFUMI , ISHII NORIO , KONDO TATSUYA , ARAKI EIICHI
Published: June 2023

Background: Dipeptidyl peptidase-4 (DPP4) inhibitors suppressed progression of atherosclerosis in atherosclerotic mouse models. However, the role of DPP4 on the progression of atherosclerosis is not clear. We investigated the effect of DPP4 deficiency on the progression of atherosclerosis in DPP4 and apolipoprotein-E double knockout (DPP4/ApoE-DKO) mice.

Methods: Both ApoE-KO mice and DPP4/ApoE-DKO mice were fed with normal chow until 20 weeks of age. Whole aorta and aortic sinus were stained with Oil red O. Bone marrow-derived macrophages (mφ) from wildtype or DPP4-KO mice were used in in vitro study. Expression of iNOS, MCP-1, TNF-α and IL-1β (M1 markers), and arginase-1, Mgl2 and Ym1 (M2 markers) mRNA were evaluated by real-time RT-PCR, and mφ polarization was evaluated by flowcytometry.

Results: There were no differences on food intake, body weight, lipid profiles and the blood glucose levels by insulin tolerance test between each group, but the blood glucose levels by glucose tolerance test were significantly decreased in DPP4/ApoE-DKO mice. Oil-Red-O staining demonstrated that the size of atherosclerotic lesions was significantly smaller in DPP4/ApoE-DKO mice. In in vitro assay, LPS+IFNγ induced the mRNA expression of M1 markers and there was no difference between wildtype mφ and DPP4-KO mφ. On the other hand, the mRNA expression of M2 markers were significantly increased in DPP4-KO mφ. Flowcytometry revealed that the number of iNOS (M1 marker)-positive cells were increased by LPS+IFNγ, which was comparable between wildtype mφ and DPP4-KO mφ. On the other hand, the number of CD206 (M2 marker)-positive cells was higher in DPP4-KO mφ than that in wildtype mφ.

Conclusion: This study suggests that DPP4 deficiency suppresses the progression of atherosclerosis in apoE-KO mice. Moreover, DPP4 deficiency increases the polarization of M2 mφ. These findings may indicate the involvement of DPP4 at least in part on the development of diabetic macrovascular complications.

Disclosure

Y.Zhou: None. T.Matsumura: Research Support; Shimadzu Corporation, Speaker's Bureau; Eli Lilly Japan K.K., Boehringer Ingelheim Japan, Inc. Y.Yagi: None. T.Yoshinaga: None. T.Senokuchi: None. N.Ishii: None. T.Kondo: None. E.Araki: Research Support; Eli Lilly Japan K.K., Nippon Boehringer Ingelheim, Mitsubishi Tanabe Pharma Corporation, Speaker's Bureau; AstraZeneca, Merck & Co., Inc., Ono Pharmaceutical Co., Ltd., Kowa Company, Ltd., Sumitomo Pharma Co., Ltd., Daiichi Sankyo, Novo Nordisk Pharma Ltd.
466-P: Appendicular Skeletal Muscle Mass and Grip Strength in Relation to the Progression of Carotid Plaque Score in Patients with Type 2 Diabetes
Authors: YEL SHIN JANG
Published: June 2023

Sarcopenia is suggested to be associated with increased cardiovascular (CV) risk and mortality in old adults. We investigated longitudinal associations of appendicular skeletal muscle mass (ASM) and hand grip strength (GS) with carotid plaque score progression (PSP) in patients with type 2 diabetes (T2D). A total of 1507 patients with T2D were recruited from January 2018 to June 2020 in the out-patients clinic. Finally, 1187 patients (Mean age = 62.6 ± 9.7 years, BMI=25.1 ± 3.4 kg/m2) completed the follow-up (fu) study. Mean fu duration (fuD) was 3.5±0.9 years. ASM and GS were measured at baseline using dual-energy X-ray absorptiometry and digital dynamometer. Carotid PS (0 to 12) was measured at baseline and fu (after≥2 years). PSP was defined as PS at fu≥1 point increase compared with one at baseline. Out of 1187 patients, 389 patients (32.8%) had PSP. Mean PS were 2.9 ± 2.8 and 3.4 ± 3.2 at baseline and fu. Patients with PSP were more likely to be old, male, and hypertensive and had higher systolic BP, diabetes duration, intima-medial thickness, and PS, but lower diastolic BP, HDL cholesterol, eGFR, ASM/BMI, and GS than those without PSP. Prevalence of PSP increased progressively with decreasing ASM/BMI and GS terile (Highest vs. Middle vs. Lowest=18.5% vs. 30.8% vs. 49.0% and 18.0% vs. 30.9% vs. 50.1%, p < 0.001). The hazard ratios and 95% CI for PSP after adjusting for age and sex were 1.53 (1.08 - 2.16) and 2.90 (2.06 - 4.08) in the middle and the lowest ASM/BMI tertile groups and 1.50 (1.06 - 2.14) and 2.66 (1.85 - 3.84) in the middle and the lowest GS tertile groups. The association of ASM/BMI and GS with PSP remained significant after further adjusting for multiple potential confounders. This study showed that low baseline ASM/BMI and low GS were longitudinally associated with PSP in patients with T2D regardless of variable metabolic and CV risk factors. Our findings suggest that low muscle mass and strength may be predicting factors for PSP.

Disclosure

J.Shin: None.
468-P: Use of New Glucose-Lowering Drugs and the Risk of Major Adverse Cardiovascular Events in People with Type 2 Diabetes and Prior Stroke
Authors: HYUN BAE JAE , CHOI JIMI , HOON KIM NAM , GON KIM SIN
Published: June 2023

Background: It remains uncertain whether the use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and incretin-based drugs is associated with a reduced risk of major adverse cardiovascular events (MACE) compared with that of thiazolidinediones (TZDs) in people with type 2 diabetes and stroke.

Objectives: To compare the effectiveness of SGLT2is, incretin-based drugs, and TZDs on MACE in people with type 2 diabetes and prior stroke.

Methods: We did a population-based cohort study involving 117,355 individuals who underwent health checkups under the Korean National Health Insurance Service from 2014 to June 2021 and followed up until December 2021. The primary outcome was MACE, defined as a composite of myocardial infarction, ischemic stroke, and all-cause death. We used propensity score weighting for balancing baseline covariates between treatment groups. Weighted cox proportional regression analyses were used to estimate the association of treatments with MACE after adjusting confounders.

Results: In a new-user cohort, the incidence rate of MACE was 547, 679, and 625 per 1,000 person-years in the SGLT2i, incretin-based drug, and TZD groups, respectively. Compared with the TZD group, the risk of MACE was significantly reduced in the SGLT2i group (adjusted hazard ratio [HR] 0.87; 95% CI 0.79-0.96) but increased in the incretin-based drug group (adjusted HR 1.11; 95% CI 1.03-1.19). No significant differences were observed in the risk of myocardial infarction and ischemic stroke between the groups. The risk of all-cause death was significantly increased in the incretin-based drug group (adjusted HR 1.14; 95% CI 1.03-1.25) compared with the TZD group.

Conclusion: In this population-based study of people with type 2 diabetes and stroke, SGLT2is were associated with a reduced risk of MACE compared with incretin-based drugs and TZDs. Incretin-based drugs were associated with an increased risk of MACE compared with TZDs.

Disclosure

J.Bae: None. J.Choi: None. N.Kim: None. S.Kim: None.
476-P: Analysis of Upstream Signaling Pathway of Erk2 following Transient High-Glucose Exposure in Coronary Artery Endothelial Cells
Authors: OKADA JUNICHI , YAMADA EIJIRO , SAITO TSUGUMICHI , OKADA SHUICHI
Published: June 2023

Using an experimental approach, we investigated the mechanisms by which brief high-glucose exposure activates extracellular signal-regulated kinase 2 (Erk2) in cultured human coronary artery endothelial cells. The cells were cultured in standard medium for 14 days (5.5 mM D-glucose). Thereafter, transient glucose elevation was achieved by adding either 183 mg/dL L-glucose or 183 mg/dL D-glucose to the culture medium for 1 h. The Erk2 activation status was measured by western blot analysis of phospho-Erk2. As part of the analysis of the upstream signaling pathway of Erk2, Rap1 and Ras activation status were examined. Furthermore, guanine nucleotide-binding protein G (i) α2 (Giα2) protein and microRNA-138 (miR-138) levels were measured. Ras and Erk2 were activated, whereas Rap1 was deactivated following addition of 183 mg/dL D-glucose to the culture medium and incubation for 1 h. Furthermore, Giα2 protein levels increased and miR-138 levels decreased. The addition of 183 mg/dL L-glucose did not affect the results. In general, our findings suggest that transient exposure to high amounts of D-glucose decreased miR-138 levels, resulting in an increase in Giα2 protein levels, Rap1 deactivation, Ras activation, and Erk2 activation. Here we report a novel mechanism that links transient high-glucose levels to Erk2 activation in cultured human coronary artery endothelial cells.

Disclosure

J.Okada: None. E.Yamada: None. T.Saito: None. S.Okada: None.
478-P: Brain Volume Changes after Long-Term Opioid Treatment in Painful Diabetic Peripheral Neuropathy
Authors: SLOAN GORDON P. , TEH KEVIN , RAPPAI SHILLO PALLAI , TESFAYE SOLOMON , SELVARAJAH DINESH , WILKINSON IAIN D.
Published: June 2023

Aim: Opioid medications are commonly used to treat Painful-Diabetic Peripheral Neuropathy (Painful-DPN). However, opioids are associated with significant adverse effects, including prescription opioid use disorder which has reached epidemic proportions in the United States. There is an urgent need to determine the effect of long-term opioid treatment (>6-months) on cerebral structure in Painful-DPN.

Methods: A total of 56 participants with Painful-DPN were recruited (17 on long-term opioid treatment [O+] and 39 not on opioid treatment [O-]). Participants underwent detailed clinical and neurophysiological assessments and cerebral imaging (3T, Phillips Medical Systems, Holland). Brain morphometric analysis was performed using Freesurfer.

Results: O+ participants were prescribed: codeine (n=3, 18%), tramadol (n=5, 29%), morphine modified release (n=1, 6%), buprenorphine (n=1, 6%), and combination treatment (n=5, 29%). O+ participants had a longer duration of diabetes, greater HbA1c, higher pain severity and higher scores on Hospital Anxiety and Depression scales compared to the O- group. Participants in the O+ group had a greater mean caudate volume (O+ 3.5mL ± 0.4; O- 3.2 ± 0.4mL, p=0.034); mean insula volume (O+ 6.3 ± 0.8; O- 5.9 ± 0.6, p=0.049) and mean insular vertices (O+ 3,286 ± 411; O- 3055 ± 282, p=0.018).

Conclusion: This is the first study to examine the impact of long-term opioid use on cerebral structure in Painful-DPN. Our findings suggest that chronic opioid use may alter affective/attentional pain processing (insular cortex) and brain regions associated with binge/intoxication (caudate nucleus). These results may have important clinical implications for uncovering the effects of long-term prescription opioid use on brain structure in Painful-DPN. Clearer clinical utility will come from future longitudinal modelling of the prognostic characteristics of opioid use disorder from the neuroimaging features identified in this study.

Disclosure

G.P.Sloan: None. K.Teh: None. P.Shillo: None. S.Tesfaye: Advisory Panel; Bayer Inc., Wörwag Pharma GmbH & Co. KG, Angelini, Speaker's Bureau; Viatris Inc., Nevro Corp., Procter & Gamble, Novo Nordisk, Berlin-Chemie AG. D.Selvarajah: None. I.D.Wilkinson: None.

Funding

European Foundation for the Study of Diabetes; Novartis Knowledge Exchange Support Fund (X/162218); Efficacy and Mechanism Evaluation Programme (NIHR129921); Medical Research Council/National Institute for Health Research Partnership
479-P: Natural Course of Declining Nerve Function during the First 10 Years of Well-Controlled Type 2 Diabetes
Authors: STROM ALEXANDER , STRASSBURGER KLAUS , SIPOLA GUNDEGA , ZIEGLER DAN , WAGNER ROBERT , RODEN MICHAEL , BÖNHOF GIDON J. ,   GDS GROUP
Published: June 2023

There is a lack of evidence on the long-term changes of nerve function in individuals with type 2 diabetes (T2D) compared to those with normal glucose tolerance (NGT). Therefore, we assessed motor and sensory nerve conduction velocities (MNCV, SNCV), sensory nerve action potentials, vibration perception threshold (VPT) and thermal detection threshold of lower extremities in 45 individuals with T2D (known diabetes duration [mean±SD]: 164±95 days) and NGT from the German Diabetes Study (GDS) at baseline (BL) and 5-year follow-up. Individuals were matched pairwise for age (T2D/NGT: 52.9±10.4/52.9±10.3 years) and sex (64/64% male). In addition, 103 individuals with T2D were followed over 10 years. At BL, 1/6 indices was lower in T2D vs NGT (peroneal MNCV: 45.6±4.0 vs 47.2±2.8 m/s; P<0.05). After five years, one index deteriorated in T2D (peroneal MNCV: 45.3±4.1 vs 43.5±3.8 m/s) and one in NGT (malleolar VPT: 1.29±1.88 vs 2.25±3.06 µm) (all P<0.05). After adjustment for BL values and pairwise matching, nerve function similarly declined over the first five years in T2D and NGT (e.g. Δperoneal MNCV; figure). A comparable deterioration was observed in individuals with T2D over 10 years (figure). Parallel decline in small and large fiber function in both NGT and well controlled T2D indicates that the main events leading to impaired nerve function in well controlled T2D might occur earlier than previously assumed.

Disclosure

A.Strom: None. K.Strassburger: None. G.Sipola: None. D.Ziegler: None. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi. G.J.Bönhof: None. Gds group: n/a.

Funding

German Federal Ministry of Health; Ministry of Innovation, Science, Research and Technology of the state North Rhine-Westphalia; German Federal Ministry of Education and Research
48-LB: Changes in Plasma Levels of Nonnutritive Sweetener Erythritol Are Related to Two-Year Changes of Insulin Sensitivity in Response to Weight-Loss Diets—The POUNDS Lost trial
Authors: HEIANZA YORIKO , XUE QIAOCHU , ROOD JENNIFER , BRAY GEORGE , SACKS FRANK , QI LU
Published: June 2023

Evidence on the benefits of non-nutritive sweeteners for weight management and improving insulin sensitivity and glucose metabolism is inconsistent. Recently, high levels of circulating erythritol, a sugar alcohol used as one of the non-nutritive sweeteners, have been linked to increased risks of type 2 diabetes and its vascular complications. Whether changes in circulating erythritol levels are related to insulin sensitivity and glucose metabolism remains unknown. Here, we investigated whether changes in plasma erythritol induced by weight-loss diet interventions were related to improved insulin sensitivity and glucose metabolism. This study included overweight or obese participants without diabetes or unstable cardiovascular disease from the POUNDS Lost trial with available data on circulating erythritol at baseline (n=805) and its changes from baseline to 6 months (n=670) and 2 years (n=533) during weight-loss diet interventions. At baseline, higher plasma levels of erythritol were related to hyperinsulinemia and greater degrees of insulin resistance assessed by HOMA-IR, even after adjusting for covariates, including BMI (P <0.05 for all). In response to weight-loss dietary interventions, a greater decrease in plasma erythritol was significantly associated with larger reductions of fasting insulin (p= 0.0001) and HOMA-IR (p=0.039) at 6 months, regardless of the initial levels of BMI, erythritol, and the respective outcome. Similarly, we found a significant association between long-term changes in erythritol and a 2-year reduction of fasting insulin (p=0.0027).

In conclusion, circulating plasma erythritol, a marker of non-nutritive sweetener consumption, was significantly associated with hyperinsulinemia and insulin sensitivity among adults with overweight or obesity. Weight-loss diet-induced decreases in plasma erythritol were related to improved insulin sensitivity.

Disclosure

Y. Heianza: None. Q. Xue: None. J. Rood: None. G. Bray: Advisory Panel; Medifast, Inc., Herbalife International of America, Inc. F. Sacks: None. L. Qi: None.

Funding

National Institutes of Health (DK091718, DK100383, DK115679, 2P20GM109036-06A1-7233)
483-P: Heterogeneous Treatment Effects of Metformin on the Risk of Dementia in People with Type 2 Diabetes—A Longitudinal Observational Study
Authors: TANG HUILIN , GUO JINGCHUAN , ELIZABETH SHAABAN C. , FENG ZHENG , WU YONGHUI , MAGOC TANJA , DONAHOO WILLIAM T. , DEKOSKY STEVEN T. , BIAN JIANG
Published: June 2023

Background: Previous studies have reported conflicting results on the association between metformin and risk of dementia which might be caused by varied drug responses of metformin in different population subgroups. We aimed to examine the heterogeneous treatment effects (HTEs) of metformin on dementia risk in the population with type 2 diabetes (T2D).

Method: Using 2005-2021 data from the National Alzheimer’s Coordinating Center (NACC), we identified individuals with diabetes (≥50 years old, ≥2 clinic visits) and normal cognition at baseline. The primay outcome was incident dementia. We applied a causal machine learning approach - doubly robust learning - to estimate the conditional average treatment effects (CATEs) in the overall cohort and then the HTE subgroups based on the identified important features using a summary decision tree model.

Results: Of 1,505 individuals with T2D, 822 (55%) were taking metformin at baseline and 683 (45%) were not. 109 participants (7.2%) developed dementia over a median follow-up of 4.0 years. In the estimation of CATEs in the overall cohort, metformin was associated with a lower risk of dementia (Risk difference [RD], -2.9%; 95% confidence interval [CI], -5.9% to -0.002%). We identified four subgroups with varied risks for dementia in those on metformin therapy, defined by neuropsychiatric disorders, alcohol abuse, and antidepressant use. Metformin was significantly associated with a lower risk of dementia in the subgroup with no neuropsychiatric disorders and no alcohol abuse (-5.9%; -9.6% to -2.3%); however, it was associated with a greater risk in those with neuropsychiatric disorders and no antidepressant use (7.4%; 0.8% to 14.0%).

Conclusion: Metformin use was significantly associated with lower risk of dementia in individuals with T2D, with significant variability among subgroups. Data-driven subgroup analyses may guide personalized treatment for diabetes care.

Disclosure

H.Tang: None. J.Guo: Consultant; Pfizer Inc., Research Support; PhRMA Foundation, NIH - National Institutes of Health. C.Shaaban: None. Z.Feng: None. Y.Wu: None. T.Magoc: None. W.T.Donahoo: None. S.T.Dekosky: Advisory Panel; Acumen Pharmaceuticals, Cognition Therapeutics, Other Relationship; Biogen, Prevail Pharmaceuticals, UpToDate, Up-To-Date. J.Bian: None.

Funding

National Institute on Aging (1R01AG076234-01); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK133465)
49-LB: A Low Biologically Available Glucose Diet Reduces Hemoglobin A1c in Type 2 Diabetes Mellitus—A Randomized Controlled Trial
Authors: ANDERSON JULIE D. , HANSON MICHELLE A. , LYSNE LESIA F. , EBERLY LYNN E. , SEAQUIST ELIZABETH R. , KNIGHTS DAN , CHOW LISA S. , WANG QI , BANTLE ANNE
Published: June 2023

Introduction: The Low Biologically Available Glucose (LoBAG) diet was designed to improve glycemic control of type 2 diabetes mellitus (T2D). This study tested the effectiveness of the diet in free-living participants with T2D.

Methods: A 12-week randomized controlled trial in participants with T2D compared the LoBAG30 diet (30% low starch carbohydrate, 30% protein, 40% fat) to a control diet (55% carbohydrate, 15% protein, 30% fat). Participants were taking metformin at a stable dose or no glucose-lowering medication. Diets were prescribed to be weight neutral and participants were asked to keep physical activity level constant. Diet instruction and dietitian support were provided to both study groups; food was not provided. The primary outcome was hemoglobin A1c (HbA1c) at the end of the intervention, compared between groups.

Results: Forty-eight participants were enrolled (30 female/18 male; 77% white, 15% Black/African American, 2% Asian, 2% American Indian, 4% not reported; 15% Hispanic/Latino). The majority (88%) took metformin. Baseline characteristics were mean (SD) age 57.4 (10.4) years, HbA1c 7.7 (0.6) %, weight 101.5 (19.7) kg, and BMI 35.4 (5.9) kg/m2 with no significant differences between groups. Thirty-eight participants completed the entire intervention; 4/10 non-completers were withdrawn due to the COVID-19 pandemic. HbA1c decreased in both groups over 12 weeks: mean (SD) -1.0 (0.8) % for the LoBAG diet (p<0.01) and -0.6 (0.7) % for control (p<0.01). The final HbA1c was 6.6 (0.6) % in the LoBAG diet group versus 7.2 (0.8) % for control (p=0.01 for comparison between groups). Both groups lost weight: -6.0 (6.9) kg with the LoBAG diet versus -4.3 (3.5) kg for control (p=0.34 for comparison between groups).

Conclusion: Participants with T2D consuming the LoBAG diet had greater reduction in HbA1c over 12 weeks than those consuming a control diet. The LoBAG diet is an effective option for dietary management of blood glucose in patients with T2D.

Disclosure

J. D. Anderson: None. M. A. Hanson: None. L. F. Lysne: None. L. E. Eberly: None. E. R. Seaquist: Consultant; Zucara Therapeutics. D. Knights: None. L. S. Chow: Research Support; Dexcom, Inc. Q. Wang: None. A. Bantle: None.

Funding

University of Minnesota Department of Medicine; National Center for Advancing Translational Sciences (UL1TR002494, KL2TR002492); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK115906)
491-P: Corneal Nerve Sensitivity—Early Detection of Diabetic Peripheral Neuropathy (DPN)
Authors: YOREK MARK A. , CORREIA MARCELO , KARDON RANDY , POOLMAN PIETER
Published: June 2023

Introduction: Density of sub-epithelial corneal nerves have been promoted as a surrogate marker for early diagnosis of DPN. As an alternative, we developed an objective functional test of corneal sensitivity (Invest Ophthalmol Vis Sci. 2016, 57: 2412-9). In this study we provide verification of this methodology in human subjects with DPN.

Methods: Following verification of DPN, response to a drop of isotonic vs. 5% NaCl (hypertonic) solution was recorded (primary endpoint). Ratio of time that the eyelids were closed from 10s to 60s following application of each solution were quantified using an image analysis program.

Results: We examined 24 subjects with type 2 diabetes and 12 age-matched controls. The presence of DPN in diabetes vs. control subjects was verified by completing the Michigan Neuropathy Screening Instrument questionnaire and lower extremity examination including amplitude and conduction velocity of the sural nerve. The presence of eye discomfort was examined for each subject by completing the DEQ5 and Ocular Surface Disease Index (OSDI) questionnaires. DPN was confirmed in all subjects with diabetes as well as presence of mild to moderate ocular surface disease. Two control subjects had mild ocular surface disease but no peripheral neuropathy. Cochet-Bonnet filament esthesiometer examination revealed significant corneal sensitivity impairment in subjects with diabetes vs. control subjects (5.64 ± 0.08 vs. 5.97 ± 0.03 cm, respectively). Corneas of subjects with diabetes were also significantly less sensitive vs. controls to application of hypertonic solution (0.18 ± 0.01 vs. 0.29 ± 0.04, respectively). Data is presented as mean ± S.E.M. There was no difference in sensitivity to the isotonic solution.

Conclusion: Corneal nerves that penetrate the epithelium and sprout near the surface of the eye and are the first to exhibit the "dying-back" phenomenon associated with DPN. Clinical evaluation of the sensitivity of these nerves could be a valuable method for early detection of DPN.

Disclosure

M.A.Yorek: Consultant; Novo Nordisk. M.Correia: Research Support; Eli Lilly and Company, Novartis, Novo Nordisk. R.Kardon: None. P.Poolman: Stock/Shareholder; FaceX LLC.

Funding

U.S. Department of Veterans Affairs (RX000889)
498-P: Prevalence and Impact on Quality of Life of Diabetic Retinopathy in African Americans with End-Stage Kidney Disease on Hemodialysis
Authors: ZABALA ZOHYRA E. , MOAZZAMI BOBAK , EGEOLU MICHELLE , CALEON RAMONCITO L. , GERGES AMANY Y.G. , GALINDO RODOLFO J. , MCCOY ROZALINA G. , PENG LIMIN , UMPIERREZ GUILLERMO
Published: June 2023

Background: The prevalence, severity, and quality of life (QoL) impact of diabetic retinopathy (DR) among African Americans (AA) with end-stage-kidney disease (ESKD) receiving dialysis are unknown.

Methods: We conducted a prospective cross-sectional study in 93 AA adults with type 1 (n=9) and type 2 (n=84) diabetes with ESKD on hemodialysis. The diagnosis of DR was based on a review of medical records and/or having a positive photograph with a portable hand-held device (Optomed Aurora retinal camera) reviewed by both artificial intelligence software (AEYE Health’s retinal screening system) and a retinal specialist. Visual acuity was assessed with the Snellen Chart. Associations with QoL (ascertained using kidney disease QoL and depression questionnaires), physical disability (ascertained using visual impairment questionnaire), and social determinants of health (SDoH) including personal and household income, marital status, health insurance, education, food insecurity, or employment status assessed by standardized questionnaires.

Results: The overall prevalence of DR was 75%, with 33% of patients having mild, 9.6% moderate and 57.4% severe DR. A total of 43% had normal visual acuity, 45% had moderate and 12% severe visual impairment. We found high burden of disease, multiple SDoH challenges, and low QoL among all patients, with most unemployed or disabled, living below poverty line, mainly receiving public health insurance, reporting poor general health, and substantial time spent dealing with kidney disease interfered with daily and family activities. However, the presence of DR had no significant impact on physical health and QoL compared to subjects without DR.

Conclusion: DR is present in 75% of AA patients with diabetes and ESKD on hemodialysis. ESKD has a significant burden on general health and QoL; however, DR has a minor additional impact on the overall physical health and QoL in people with ESKD and diabetes.

Disclosure

Z.E.Zabala: None. B.Moazzami: None. M.Egeolu: None. R.L.Caleon: None. A.Y.G.Gerges: None. R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. R.G.Mccoy: Consultant; Emmi. L.Peng: None. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter.
500-P: Causal Effect of SGLT2 Inhibition on Diabetes-Related Retinopathy (DR) and Macular Edema (DME)
Authors: STEVENS HENRY , BREEN JAMES M. , COOPER BLAKE A.
Published: June 2023

Background: SGLT2 inhibitors have been shown to slow cardiac and renal disease progression. Currently, there is limited literature on the impact of SGLT2 inhibitors on DR and more specifically DME. Objective: Evaluate the effect of SGLT2 inhibitors on central subfoveal thickness (CST) in patients with T2D and on the need and frequency of intravitreal injections (IVI) for DME.

Methods: A retrospective matched cohort study with propensity score matching to reduce confounding and determine treatment effect.

Covariates: age, sex, type of DM, last A1c, level of retinopathy, insurance, IVI, Visual Acuity (VA).

Treatment: SGLT2i use. Primary Outcome: CST on Optical Coherence Tomography (OCT).

Secondary Outcomes: IVI use and frequency for DME. By ICD-10 codes 10,026 patients were found to have diabetes and were seen in 2021 at Retina Associates, LLC Kansas City. Retrospectively screened 1,000 consecutive patient medical records from this cohort and included those with T2D and on an SGLT2i. We excluded those with incomplete records, T1D, and those who had a second diagnosis that could cause macular edema. Results: 321 patients had DR; 280 with T2D of which 71 were on an SGLT2i and included for analysis. Baseline cohort characteristics: mean age (SD): 62.2 yr (11.4); 58.9% were male; 76.1% White, 11.1% Black, 6.8% Hispanic/Latino; 13.2% used tobacco; 75.4% had HTN; last recorded A1C 7.6 (1.6); Visual Acuity in ETDRS letters OD: 74.1 (12.9) OS: 73.8 (14.7); CST OD: 279.9 (56.6) OS: 279.6 (54.7). Comparing CST and the need for IVI to those not on an SGLT2i the CST OD/OS was 280.1 (32)/280.3 (36.3) vs 279.9 (62.8)/279.4 (59.7) and 40.8% vs 36.8% required IVI with a risk ratio of 1.13 and a risk difference of 0.03 and p-value of 0.55 95% CI [-0.07, 0.14]. After Propensity Score Matching: ATE risk difference was 0.04 and a p-value of 0.37 and 95% CI [-0.05, 0.14].

Conclusions: No positive or negative effect on mean CST or difference in the average treatment effect for DME was found for those taking an SGLT2 inhibitor.

Disclosure

H.Stevens: None. J.M.Breen: None. B.A.Cooper: Advisory Panel; Genentech, Inc., Speaker's Bureau; Regeneron, Optomed.
506-P: Regulation of ANGPTL3 by SEL1L-HRD1 ER-Associated Degradation
Authors: ZHOU LINYAO , LIN LIANGGUANG , SUN SHENGYI , QI LING
Published: June 2023

Angiopoietin-like 3 (ANGPTL3) is a liver-derived circulating factor critical for systemic lipid metabolism via the inhibition of lipoprotein lipase (LPL). Loss-of-function mutations in ANGPTL3 in humans and mice reduce circulating levels of triglycerides. Here, we report the discovery of a novel mechanism regulating the biosynthesis and maturation of nascent ANGPTL3 in the endoplasmic reticulum (ER). Mice with acute or chronic liver-specific deletion of SEL1L-HRD1, the most conserved branch of mammalian endoplasmic reticulum (ER)-associated degradation (ERAD) machinery, exhibit significantly lower levels of triglyceride and cholesterol in the serum with reduced weights of both epididymal and inguinal white adipose tissues (WAT). Various proteomics screenings have identified ANGPTL3 as a possible link between SEL1L-HRD1 ERAD and hypolipidemia. Indeed, ANGPTL3 is a bona fide endogenous substrate of SEL1L-HRD1 ERAD in the liver and in the absence of ERAD, ANGPTL3 protein is retained in the ER, forming high-molecular weight aggregates. This abnormal ER retention of ANGPTL3 accounts for a reduced circulating level of ANGPTL3, therefore contributing to hypolipidemia in ERAD-deficient mice. Together, this study not only uncovers a novel regulator for ANGPTL3 and novel targets in the treatment of hyperlipidemia in obesity and diabetes.

Disclosure

L.Zhou: None. L.Lin: None. S.Sun: None. L.Qi: None.
51-LB: Race Specific Effects of a Carbohydrate-Restricted Diet on Acute and Maximal C Peptide Response to Glucose in Adults with Type 2 Diabetes
Authors: GOWER BARBARA , GOSS AMY M. , TIMOTHY GARVEY W.
Published: June 2023

Beta-cell response to glucose is compromised in individuals with type 2 diabetes (T2D), possibly due to lipid infiltration of the pancreas from excessive carbohydrate consumption. This study was conducted to determine if a eucaloric carbohydrate restricted diet (~9% energy from carbohydrate, 65% energy from fat), compared to a eucaloric fat restricted diet (~55% energy from carbohydrate, 20%energy from fat), would improve beta-cell response to glucose in participants with T2D. Participants were 43 African American and European American adults with T2D not using insulin. Medications were discontinued 1-2 weeks (depending upon the medication) prior to baseline testing. A hyperglycemic clamp was used to assess the acute (first-phase) and maximal (arginine-stimulated) C-peptide responses to glucose at baseline and after 12 weeks of controlled diet therapy (all food provided). Based on the detection of a race-by-diet interaction (P=0.06), data were analyzed within each race group. At 12 weeks, a significant effect of diet was observed by ANCOVA on acute C-peptide response in African Americans (2-fold greater with the carbohydrate restricted diet, P<0.05), and on maximal C-peptide response in European Americans (50% greater with the carbohydrate restricted diet, P<0.01), after adjusting for change in body weight. Paired t-test revealed an improvement in acute C-peptide response within African Americans on the carbohydrate restricted diet (P<0.01) from baseline to week 12, and an improvement in maximal C-peptide response within European Americans on the carbohydrate restricted diet (P<0.01). No changes in beta-cell function were observed in response to the fat restricted diet. These results suggest that a carbohydrate restricted diet has beneficial effects on beta-cell function that are race-specific and independent of weight loss.

Disclosure

B. Gower: Consultant; Abbott. A. M. Goss: Advisory Panel; Novo Nordisk, Consultant; Weight Watchers International. W. Garvey: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk, Eli Lilly and Company, Merck & Co., Inc., Alnylam Pharmaceuticals, Inc., Fractyl Health, Inc., Inogen, Research Support; Novo Nordisk, Eli Lilly and Company, Epitomee, Pfizer Inc., Neurovalens.

Funding

National Institutes of Health (R01DK116726)
514-P: A 13-Year Retrospective Analysis of an Admission-Avoidance Strategy Using Intramuscular Antibiotics in Treating “Borderline-Severe“ Diabetic Foot Infections
Authors: DHATARIYA KETAN , GOODAY CATHERINE , FUNG ADRIEL H.
Published: June 2023

Aim: To determine the outcomes of using intramuscular (IM) antibiotics as an admittance avoidance strategy in people presenting with a ‘borderline-severe’ diabetic foot infection.

Methods: Methods:122 patients (accounting for 141 episodes) were treated for ‘borderline-severe infection’ between January 2009 and April 2022. Prior to the introduction of this service they would have required an acute hospital admission. Individuals were followed up to determine whether the use of intramuscular antibiotics had prevented acute hospital admission.

Results: Our clinic saw, on average, 420 contacts per month during the study period. Approximately 5 people per week were admitted directly from specialist clinics or the emergency department with a severe infection. Of those seen in the specialist foot clinic, only 1 person per month was deemed appropriate to receive IM treatment. These had a mean age (±SD) of 61 years (13.3), and 83% were male, and 25% had type 1 diabetes. The mean (IQR) number of injections was 5.5 (6.0). Of these, 39/141 subsequently needed hospital admission. The remaining 102 people were successfully treated as outpatients, with 95 ulcers healing. Of the 39 admissions, 20 needed IV antibiotics alone, 14 had a minor amputation, 5 had a major amputation.

Conclusions: Admission avoidance strategies are increasing important in reducing the pressure on hospitals beds. Like others, our hospital increasingly uses outpatient intravenous antibiotic services, but that has its own pressures. We now successfully use either IV or IM administration to treat borderline-severe diabetic foot infections depending on the capacity of either service, thus avoiding acute hospital admission which leads to significant cost savings.

Disclosure

K.Dhatariya: Other Relationship; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company. C.Gooday: Speaker's Bureau; AstraZeneca. A.H.Fung: None.
515-P: Study to Evaluate the Relationship between Inpatient Glycemic Control as Measured by CGM and Wound Healing in Patients Admitted for Diabetic Foot Ulcer (DFU)
Authors: ROGERS KAITLYN K. , RASHIED AMMAR A. , SCHECHTER MARCOS , FAYFMAN MAYA
Published: June 2023

We performed a post-hoc analysis of hospitalized patients admitted with DFU enrolled in an inpatient continuous glucose monitor (CGM) study. Bivariate analysis was conducted between those with wound healing vs. non-healing over a 16-week period. Logistic regression was performed to assess the following CGM metrics and likelihood of wound healing: TIR (70-180 mg/dl), TAR (>180 mg/dl) and TBR (<70 mg/dl). Potential confounders included in the multivariate analysis were age, race and sex, history of peripheral arterial disease, renal failure, prior amputation, and ulcer duration. Results of patient characteristics are summarized in the Table. Of 230 patients enrolled in our CGM studies, 62 (27%) were admitted for DFU. Sixteen weeks after discharge, 9 (15%) patients were lost to follow-up, 13 (21%) had healed, and 39 (62%) had not healed. Of the non-healed, 10 (15%) had an amputation, 3 (4.7%) died, and 26 (41%) had a persistent ulcer. We did not find an association between the likelihood of healing and CGM derived glycemic metrics: fully adjusted models for TIR (OR 0.99, 95% CI 0.96-1.02), TAR (1.01 95% CI 0.98-1.04), and TBR (0.85; 95% CI 0.52-1.40). While glycemic control remains an important predictor of diabetes complications, we did not find an association between glycemic control in the hospital based on CGM metric and post-discharge healing.

Disclosure

K.K.Rogers: None. A.A.Rashied: None. M.Schechter: None. M.Fayfman: None.

Funding

Dexcom, Inc.
517-P: Machine Learning Algorithms Using Electronic Medical Record and Ultrasonography of Lower Extremities for 10-Year Risk Assessment of Diabetic Foot Ulcer in China
Authors: WU LIN , LIANG YUNAN , HE XUEMIN , CHEN YANMING
Published: June 2023

Objective: Accurate prediction of diabetic foot ulcer (DFU) occurrence in patients with type 2 diabetes mellitus (T2DM) is crucial for determining appropriate treatment strategy and avoiding amputation and infection. Here, we explored machine learning algorithms (ML) of electronic medical record (EMR) for predicting the incident of DFU.

Methods: In this retrospective longitudinal observational cohort, 26579 cases from T2DM database of The Third Affiliated Hospital of Sun Yatsen University from Jan 2011 to Dec 2019 were screened and finally 2770 patients without DFU were enrolled. During 5.6 years of follow-up, 178 patients occurred DFU. 44 clinical parameters including EMR and imaging finding were used to develop a DFU risk prediction model using XGBoost, RF, and LR.

Results: ML models were established in 178 patients with DFU (110 male, mean 61.1±12.4 years), and 2591 patients without DFU (1424 male, mean 59.0±12.1 years). XGBoost model achieved the best performance in predicting DFU occurrence with an AUC of 0.94, which is better than the performance of RF with AUC of 0.91and LR with AUC of 0.89. A DFU incident significantly increased in high-risk patients (>10%) in the next 10 years.

Conclusion: Our study provided a simple and effective risk tool for the prediction of 10-year DFU risk, which can help professionals clinical screening and decision-making for T2DM patients.

Disclosure

L.Wu: None. Y.Liang: None. X.He: None. Y.Chen: None.
519-P: Randomized Clinical Trial to Compare Cryopreserved and Lyopreserved Placental Cord Tissue to Treat Complex Diabetic Foot Surgical Wounds—A Proof of Concept Study
Authors: LAVERY LAWRENCE A. , KILLEEN AMANDA L. , SULUDERE MEHMET A. , CRISOLOGO PETER
Published: June 2023

Objective: To compare the incidence of infection, healing and time to heal in patients treated with cryopreserved (CPAT) and lyopreserved amniotic tissue (LPAT) in complex diabetic surgical wound (CDFW).

Methods: This single-blinded 12-week randomized clinical trial compared cryopreserved and lyopreserved amniotic cord tissue to treat complex diabetic foot wounds (CDFW). LPAT or CRAT was applied at baseline and again after four weeks. We enrolled subjects with UT2A-D and 3A-D wounds (depth to tendon, muscle, or bone with infection and/or PAD) and excluded subjects with ABI<0.5 or TBI<0.3, untreated osteomyelitis, and autoimmune diseases. We used a 3-D camera to evaluate wound area and volume. The Chi-squared test was used to compare clinical outcomes and the Wilcoxon Ranked Sum Test to compare wound area and volume.

Results: The mean baseline wound areas were 12.9cm2 ±10.7 for CPAT and 11.7cm2 ±7.0 for LPAT. The mean baseline wound volume were 7.5cm3 ±8.1 for CPAT and 9.2cm3±10.2 for LPAT. There was no difference between CPAT and LPAT in healing (36.8% vs. 19.0%, p=0.21) and infection (10.5% vs. 9.5%, p=0.72). There was no difference in mean wound area reduction between CPAT and LPAT (75.9± 32.3% vs. 65.5±38.4%, p=0.41), nor in mean volume reduction (85.0±30.8% vs. 79.9±31.9%, p=0.61). When we stratified wound dimensions, there was no difference between CPAT and LPAT in subjects that had 90-99% wound volume reduction (36.8% vs. 47.6%), 70-89% wound volume reduction (15.8% vs 19.0%) and 0-69% wound volume reduction (10.5% vs. 19.0%). There was no difference between CPAT and LPAT in subjects that had 90-99% wound area reduction 90-99% (10.5% vs. 23.8%), 70-89% (26.3% vs. 19.0%) and 0-69% (26.3% vs. 38.1%).

Conclusion: Cryopreserved and Lyopreserved amniotic tissue provided similar results in patients with complex diabetic foot wounds.

Disclosure

L.A.Lavery: Research Support; AstraZeneca, Tissue tech, American Diabetes Association, PolarityTE, Inc., Microbion, Jarvis, Integra Lifesciences Holdings Corp, Smith+Nephew. A.L.Killeen: Research Support; 3M/KCI, AstraZeneca, BioTissue surgical, Hologenix, LLC, Integra LifeSciences, Kent Imaging Inc., Microbion, PolarityTE, Inc., Smith+Nephew, Stark Enterprises, LLC, Xyken, VasoActiv, ViOptix. M.A.Suludere: None. P.Crisologo: None.

Funding

Smith & Nephew
526-P: Increasing the Confidence of Health Care Professionals Treating Patients Living with Type 1 Diabetes through the Support-Pro Online Education Platform
Authors: KATZ ALEXANDRA , RABASA-LHORET RÉMI , TALBO MERYEM K. , HOUSNI ASMAA , HILL LEE , ROY-FLEMING AMÉLIE , HAAG SARAH , BRAZEAU ANNE-SOPHIE
Published: June 2023

Introduction: Support-Pro is a comprehensive online platform that was developed for healthcare professionals (HCP) and covers all technological, treatment and lifestyle needs for type 1 diabetes (T1D) management in short, practical modules. It was developed as studies have demonstrated that HCPs who work in healthcare not specific to T1D, find it difficult to keep up-to-date with new developments that could improve T1D care and management. However, specialized online resources, such as Support-Pro, could help rectify this problem. The objective of the study is to assess whether Support-Pro can increase HCPs confidence in treating and supporting people with T1D (PWT1D) and their satisfaction with the platform.

Methods: Open-label, non-randomized, 3-month trial with 142 HCPs who had access to Support-Pro, and 66 who completed 3 months on the platform (NCT04859205).

Results: On average, the 66 participants (years of practice: 14±10; 90% women; 71% Caucasian; 44% dietitians, 30% nurses, 23% pharmacists, 3% physician or resident physician) reported at 3 months, an average 10% improvement in their confidence (total score 58% to 68%; p<0.0001) and a median satisfaction score of 76%. HCPs most valued features that supported knowledge gain, such as downloadable PDF documents (72%) and case studies (44%). The platform was most used in first month of access (page views 1st month: 50 [5;135] vs. 3rd month: 0 [0;18]).

Conclusions: HCPs who completed 3 months on Support-Pro platform reported increased confidence in treating PWT1D and high appreciation of learning content and modalities. This platform could improve the support and advice provided to PWT1D followed-up outside specialized clinics.

Disclosure

A.Katz: None. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. M.K.Talbo: None. A.Housni: None. L.Hill: None. A.Roy-fleming: None. S.Haag: Other Relationship; Omnipod. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé.

Funding

Strategy Patient-Oriented Research (JT1-157204); JDRF (4-SRA-2018-651-Q-R)
544-P: Effect of Organization Type on Priority Population Outcomes in the National Diabetes Prevention Program (National DPP)
Authors: BOWEN SHELLY-ANN , LANDAU ERIN O. , ELY ELIZABETH
Published: June 2023

In 2012, the CDC Diabetes Prevention Recognition Program approved its first recognized organization. Since then, it has recognized 4,000+ organizations to deliver the National DPP lifestyle change program to 600,000+ participants at type 2 diabetes risk. This analysis examined data from 624,422 participants to determine the impact of 5 organization types on priority population outcomes: community centers, higher education, government, healthcare providers, and for-profit/insurers. Most participants (65.7%) enrolled in for-profit/insurer organizations. Community centers enrolled the highest percentage of participants who identified as Hispanic/Latino (20.8%) and Native Hawaiian/other Pacific Islander (3%), and government organizations the highest percentage of Black/African American (17.7%) and American Indian/Alaska Native participants (10.8%). Higher education organizations enrolled the highest percentage of Asian/Asian American participants (3.4%). Men primarily enrolled in for-profit/insurer organizations (25.3%), and those aged 65+ enrolled mainly in healthcare-based programs (30.6%). Time in the program is associated with type 2 diabetes risk reduction. Those enrolled in higher education organizations stayed in the program the longest, with a mean of 233 days. Community centers and government organizations, which lead in the enrollment of some priority populations, had means of 196 and 218 days, respectively. Native Hawaiian/other Pacific Islander participants stayed in community center programs above the mean of 226 days. In government organizations, Black/African American and American Indian/Alaska Native participants remained for an average of 227 and 219 days, respectively. Understanding which types of organizations better serve priority populations, and assisting them in recruitment and retention, is key to reducing the risk of developing type 2 diabetes among these groups and reducing disparities in outcomes.

Disclosure

S.Bowen: None. E.O.Landau: None. E.Ely: None.
545-P: Impact of Participant Characteristics on Weight Loss in the National Diabetes Prevention Program (2012–2021)
Authors: ZHU RONGSHUN , LANDAU ERIN O. , ELY ELIZABETH
Published: June 2023

The National Diabetes Prevention Program (National DPP) is a partnership of public and private organizations collaborating to build a nationwide delivery system for a lifestyle change program (LCP) proven to prevent or delay the onset of type 2 diabetes in adults with prediabetes. A risk reduction outcome for the LCP is weight loss of at least 5%. This analysis used multivariate logistic regression to assess the association between participant characteristics and 5% weight loss for 470,238 enrolled participants who had the opportunity to attend the 12-month LCP in 2012-2021. Analysis shows that 59% of participants attended the LCP online, 35% in-person, and 6% via distance learning or combination delivery. With respect to demographics, 77% were women, 55% of whom were aged 45-64 and 32% aged 18-44; 61% identified as White, 12% identified as Black or African American, and 12% identified as Hispanic or Latino. The odds of meeting the goal for those aged 65+ and 45-64 were 1.6 and 1.2 times greater than those 18-44, respectively. Those who identified as White had higher odds of meeting the goal than those who identified as Hispanic or Latino, Black or African American with odds ratios (ORs 1.3), or Asian or Asian American (ORs 1.2). Compared with participants enrolled in in-person programs, online participants had the lowest odds of reaching the goal (ORs 0.5), and distance learning participants had odds similar to those of in-person participants (ORs 1.0). The 5% weight loss success was significantly higher among those who attended > 16 sessions (ORs 2.9) for the study population. Women were less likely to meet the goal than men (ORs 0.8). Results of this analysis indicate that participant characteristics strongly impact whether someone meets the 5% weight loss goal. Program delivery strategies tailored to specific populations could be effective in helping participants achieve programmatic goals.

Disclosure

R.Zhu: None. E.O.Landau: None. E.Ely: None.