bluuebunny/crossref_metadata_2025 huggingface dataset:
47-LB: Inverse Association of Vegetable Consumption with Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus
Authors: GU XUEJIANG
Published: June 2023

Objective: We aimed to investigate the association of fruit and vegetable consumption with nonalcoholic fatty liver disease (NAFLD) in Chinese patients with type 2 diabetes mellitus (T2DM).

Methods: This cross-sectional study included 2667 Chinese patients with T2DM aged 18 to 76 years. Dietary intake was assessed by food frequency questionnaire, and prevalent NAFLD was diagnosed with abdominal ultrasonography. The primary outcome measurement was multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the prevalence of NAFLD in relation to the highest fruit and (or) vegetable intake compared with the lowest. Secondary analyses were conducted to assess the effects of either fruit or vegetable intake on the fatty liver index (FLI) using multivariable linear regressions.

Results: There were 1445 (54.06%) participants had prevalent NAFLD in this study. Patients with high fruit-vegetable intake (≥500 g/day) had a lower prevalence of NAFLD (52.04% vs. 56.48%), but this difference was not statistically significant (p = 0.065). Vegetable intake had a significantly inverse association with NAFLD (OR: 0.68, 95% CI: 0.52-0.90), but this association was not pronounced with fruit intake (OR: 1.23, 95% CI: 0.89-1.69) or fruit-vegetable intake (OR: 0.90, 95% CI: 0.73-1.10). Additional analyses showed that an increase in vegetable intake was linearly associated with a significant reduction in FLI (β: −1.028, 95% CI: −1.836, −0.219).

Conclusions: Higher vegetable consumption was associated with lower odds of NAFLD in Chinese patients with T2DM, which suggested that increased vegetable intake might protect patients with diabetes against NAFLD.

Disclosure

X. Gu: None.
470-P: Elevated NT-ProBNP Is Associated with Significant CT Left Anterior Descending Coronary Artery Calcification Score in T2DM
Authors: GUPTA VISHAL , TELI VAISHALI
Published: June 2023

Aims & Objectives: Establish the relationship between N-terminal Pro B-type natriuretic peptide (NT-ProBNP) & CT-Coronary calcium score (CAC) in patients with T2DM.

Methodology: Between Oct'19 & Dec'19, 62 asymptomatic T2DM patients, aged 18-75yrs, irrespective of A1c, on regular F/U who had NT-ProBNP ≥ 125pg/ml (Group-G1) & who had undergone CAC & 2D-Echocardiogram (2D) were retrospectively analysed & compared to 62 T2DM patients (Group-G2) with corresponding NT-ProBNP < 125 along with CAC & 2D. Cardio-renal (CR) biomarkers & CAC were compared at the point NT-ProBNP ≥ 125 for Gr-1 with Gr-2. Patients with only preserved ejection fraction (EF) were included. Patients were receiving standard glucose lowering, lipid lowering & BP lowering therapy optimised for CR biomarkers (BMI, HbA1c, Systolic-BP, Diastolic-BP, Lipid profile, highly sensitive C-reactive protein {HSCRP}, Creatinine, urine microalbumin/creatinine ratio {UACR}). Exclusion: low-EF, H/O of IHD, recent (<6mths) hospitalisation &/or coronary intervention. Data analysis: SPSS version 26 & represented as Mean ± 2(SD) with 95% Cl. Pearson co-relation was used & p-value <0.05 was considered significant (S).

Results: There was a S difference between Gr-1 & Gr-2 in mean Age yrs (Gr1: 64.35 ± 6.874yrs Vs Gr2: 61.15 ± 6.840, p-0.010), BMI kg/m2 (Gr1: 32.25 ± 5.59 Vs Gr2: 29.66 ± 4.81, p-0.007), NT-ProBNP pg/ml (Gr1: 167.31 ± 159.46 Vs Gr2: 33.98 ± 20.64, p-0.000) & CAC score HU {LAD: Gr1: 286.35 ± 376.83 Vs Gr2: 167.63 ± 234.47, p-0.0393). Total CAC between both groups (Gr1: 471.13 ± 622.81 Vs Gr2: 420.92 ± 659.77, p-0.6638) remained non-significant. There was also no difference seen in SBP, DBP, Lipid Profile (TC, LDL, TG, HDL, Apo B), hs-CRP, serum creatinine, eGFR & UACR.

Conclusion: NT-ProBNP ≥125 is related to greater CAC in LAD & may represent an ischemic signal requiring optimal cardiovascular risk factor management inT2DM patients. These patients are older & have a greater BMI.

Disclosure

V.Gupta: None. V.Teli: None.
471-P: The Visceral Adiposity Index Predicts MACE Both in Cardiovascular Disease Patients with and in Those without Diabetes
Authors: MAECHLER MAXIMILIAN , SPRENGER LUKAS , MADER ARTHUR , LARCHER BARBARA , VONBANK ALEXANDER , PLATTNER THOMAS , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2023

The Visceral Adiposity Index (VAI) is calculated based on waist circumference, BMI, triglyzeride and HDL-cholesterol levels and is a validated measure of visceral adiposity. In the general population, the VAI has been shown to be an independent risk factor for premature mortality. Its power to predict MACE in patients with established cardiovascular disease (CVD) with or without type 2 diabetes mellitus (T2DM) is not known and is addressed in the present study. We prospectively recorded MACE in 601 of 1499 patients with either angiographically diagnosed CAD (n=1261) or sonographically verified PAD (n=238) over a mean follow-up time of 9.6±5.1 years. At baseline, the VAI was significantly higher in patients with T2DM (n=489) than in those who did not have diabetes (6.7±6.0 vs. 4.7±4.5; p<0.001). Prospectively, the VAI significantly predicted the incidence of MACE both univariately (standardized HR 1.01 [1.00-1.03]; p=0.037) and after adjustment for age, gender, smoking, LDL cholesterol, hypertension and T2DM (standardized adjusted HR 1.01 [1.00-1.03]; p=0.011); also T2DM significantly predicted MACE in this fully adjusted model (adjusted HR 1.55 [1.31-1.84]; p<0.001). We conclude that the VAI and T2DM are mutually independent predictors of MACE in patients with CVD.

Disclosure

M.Maechler: None. C.H.Saely: None. L.Sprenger: None. A.Mader: None. B.Larcher: None. A.Vonbank: None. T.Plattner: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None.
473-P: Differences in Carotid Arteriosclerosis according to Waist Circumference and Thigh Circumference Appear Differently in Diabetic Patients and Prediabetic Patients
Authors: SIK KIM CHUL , JANG SEOL A. , MIN KIM KYOUNG , WON PARK SEOK
Published: June 2023

This study investigated the relationships of thigh and waist circumference with the glycemic variability and carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM) and prediabetes. This observational study included 3,453 Korean patients with T2DM and prediabetes, in whom anthropometric measurements and carotid ultrasonography were conducted. Carotid plaque was defined as focal structures encroaching the arterial lumen by ≥ 0.5 mm or 50% of the surrounding IMT value or a thickness ≥1.5 mm. In men with T2DM, it was found that the larger the thigh circumference, the lower the risk of carotid plaque after adjustment for potential confounding variables. In women with T2DM, a similar tendency was observed before adjustment, but no statistically significant relationship was seen after adjustment. In women with T2DM, the presence of carotid plaque was higher in the thickest waist group compared to the reference group, but there is no statistical significance after adjustment. However, no difference in carotid arteriosclerosis according to waist and thigh circumference was found in both men and women in prediabetic patients. It suggests that the risk of cardiovascular disease according to the difference in body type such as waist circumference and thigh thickness may appear differently depending on the glucose status. However, further longitudinal studies are warranted.

Disclosure

C.Kim: None. S.A.Jang: None. K.Kim: None. S.Park: None.
488-P: Subclinical Autonomic Neuropathy in Uncomplicated Type 2 Diabetes
Authors: JOHNSTON ASPEN , ABUSHAMAT LAYLA A. , ENGE DANIEL , BARKER ALEX J. , CLARK ETHAN W. , RAFFERTY DEIRDRE , REGENSTEINER JUDITH G. , REUSCH JANE E.B.
Published: June 2023

Cardiac autonomic neuropathy (CAN), a common complication of type 2 diabetes (T2D), is often not detected until late in disease progression. Autonomic nervous system (ANS) dysfunction impairs control of heart rate (HR) and vascular dynamics, manifesting as decreased HR variability (HRV) and impaired blood pressure (BP) regulation. We hypothesized that ANS function is impaired in participants with uncomplicated T2D and correlates with cardiac measures. We measured HRV during cycled breathing and Valsalva and postural HR and BP on overweight physically inactive adults aged 22-70 years with (N=53) and without (N=56) T2D. HRV with cycled breathing and Valsalva was lower in participants with T2D (p=0.007 and 0.005, respectively). HRV with respiration was lower with age >50 years (p=0.0001). HRV with respiration correlated with increased age in T2D but not in overweight control participants. There were no significant changes in postural BP or HR with age >50 years or T2D. Significant correlations between ANS measures and cardiac function were only seen in those with T2D. Valsalva ratio was positively correlated with end-diastolic volume (Pearson’s r 0.58, p=0.02) and stroke volume (Pearson’s r 0.55, p=0.03). HRV with respiration was positively correlated with longitudinal, diastolic peak strain rate (SR) (Pearson’s r 0.68, p=0.007). Postural BP was positively correlated with circumferential and longitudinal, systolic peak SR (Pearson’s r =0.45 and 0.48 and p-value=0.05 and 0.04, respectively) and negatively correlated with radial and circumferential peak strain (Pearson’s r =-0.49 and -0.48 and p-value=0.03 and 0.03, respectively). These data suggest subclinical CAN associated with cardiac dysfunction is present in people with otherwise uncomplicated T2D and is exacerbated with age. Detecting CAN changes early may identify people at risk for cardiac disease and inform targeted intervention to restore cardiometabolic health in people with T2D.

Disclosure

A.Johnston: None. L.A.Abushamat: None. D.Enge: None. A.J.Barker: None. E.W.Clark: None. D.Rafferty: None. J.G.Regensteiner: None. J.E.B.Reusch: Advisory Panel; Medtronic.

Funding

American Diabetes Association (1-21-CMF-003 to L.A.A.); National Institutes of Health (T32DK120520-01A1); U.S. Department of Veterans Affairs (CX001532)
49-OR: Genetic Variants Influencing Insulin Deficiency and Resistance Are Associated with Adverse Pregnancy Outcomes
Authors: HSU SARAH , JAMES KAITLYN , MEDINA BAEZ ARANTXA , SMITH KIRK , MERCADER JOSEP M. , UDLER MIRIAM , POWE CAMILLE E.
Published: June 2023

Background: We tested maternal genetic determinants of insulin deficiency (ID) and insulin resistance (IR) for association with hyperglycemia-related adverse pregnancy outcomes.

Methods: We applied non-negative matrix factorization to GWAS data (325 type 2 diabetes [T2D]-associated variants, 135 T2D-related traits) to derive 2 trait/variant clusters. We verified associations between cluster polygenic scores (PGSs) and ID/IR-related traits in non-pregnant women (n=35341). In pregnant women (n=1521) we tested for associations between cluster PGSs and infant birthweight (BW) percentile for gestational age and secondary outcomes (gestational diabetes [GDM], large/small for gestational age BW, hypertensive disorders, neonatal ICU admission, preterm birth) using models adjusted for age, insurance, parity, race, and principal components. Effect sizes are for a 1-SD PGS increase.

Results: Cluster 1 had ID-related traits/variants (e.g., decreased insulin response and disposition index, increased fasting glucose, variants near MTNR1B, CDKAL1, C2CD4A/B SLC30A8). Outside pregnancy, the ID cluster PGS was associated with T2D (OR=1.2, p=2×10-7) and HbA1c (β=0.05%, p=2.8×10-9). In pregnancy, the ID cluster PGS was associated with higher BW percentile (β=1.7, p=0.04) and GDM (OR=1.3, p=0.004), but not other outcomes. Cluster 2 had IR-related traits/variants (e.g., decreased HDL and insulin sensitivity, increased triglycerides [TG] and fasting insulin, variants near IRS1, GRB14, LPL, FTO). Outside pregnancy, the IR cluster PGS was associated with T2D (OR=1.1, p=2×10-5), HbA1c (β=0.06 %, p=1.2×10-14), TG (β =4.2 mg/dL, p=4.4×10-15) and inversely associated with HDL (β=-1.7mg/dL, p=5.5×10-32). In pregnancy, the IR cluster PGS was associated with preterm birth (OR=1.3, p=0.006), but not BW percentile or GDM.

Conclusion: Maternal genetic determinants of ID are associated with increased BW; genetic determinants of IR are associated with preterm birth.

Disclosure

S.Hsu: None. K.James: None. A.Medina baez: None. K.Smith: None. J.M.Mercader: None. M.Udler: None. C.E.Powe: Consultant; Mediflix, Inc., Other Relationship; Wolters Kluwer Health.
490-P: Gallbladder Function in Diabetes Assessed by Ultrasound
Authors: JOULEH TARANEH , NORDAAS INGRID K. , TJORA ERLING , MELING SONDRE , DIMCEVSKI GEORG , GILJA ODD H. , SØFTELAND EIRIK
Published: June 2023

Background: Gastrointestinal complaints are common in diabetes mellitus (DM), and may be associated with gastrointestinal autonomic neuropathy. However, reliable methods for investigating gastrointestinal autonomic function are lacking. Could gallbladder dysfunction indicate gastrointestinal autonomic neuropathy as a complication of DM?

Aim: To compare stimulated gallbladder emptying in people with long-standing type 2 DM, early diabetes (early DM), and healthy controls (HC). Methods: This study included 62 subjects (19 with DM, 15 with early DM, and 28 HCs) who underwent 3D ultrasound imaging before and after intake of a high-fat meal. Gallbladder volumes, ejection volumes (EV), and ejection fractions (EF) were calculated.

Results: Maximum preprandial volume was significantly different between the three groups (p=0.04) and higher in the DM group compared to HCs (33.8 mL vs. 23.0 mL, p=0.01). The DM group had significantly higher EV than the HCs (19.4 mL vs. 13.6 mL, p=0.05). Median EF did not differ significantly between the groups.

Conclusion: Higher preprandial gallbladder volume and altered gallbladder function, expressed through higher EV in patients with DM may indicate gastrointestinal neuropathy. Ultrasonographic assessment of gallbladder emptying may prove a useful biomarker for this condition.

Disclosure

T.Jouleh: None. I.K.Nordaas: None. E.Tjora: None. S.Meling: Consultant; Novo Nordisk, Lilly, AstraZeneca, Boehringer-Ingelheim, Sanofi. G.Dimcevski: None. O.H.Gilja: None. E.Søfteland: None.
493-P: SCS for the Treatment of Painful DPN—Consistent Outcomes from Multiple RCTs
Authors: BODE BRUCE W. , GRUNBERGER GEORGE , FISHMAN MICHAEL , MURPHY MELISSA , VIGERSKY ROBERT A. , JOHANEK LISA , LARUE MADDIE
Published: June 2023

Pain associated with diabetic peripheral neuropathy (DPN) is treated medically with gabapentin/pregabalin, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors1 which are often not satisfactory long-term. Spinal Cord Stimulation (SCS) is an effective alternative per 3 randomized controlled trials (RCTs)2,3,4. We reviewed and compared 3 published RCTs2,3,4 comparing SCS to conventional treatments for painful DPN in subjects with mostly type 2 diabetes (Table 1). Study outcome measures included a composite primary endpoint where patients could be identified as treatment responders by reduction in pain diary scores or Patient Global Impression of Change, ≥50% reduction in VAS measurement for pain, and a compound primary endpoint of ≥50% reduction in pain score and no neurologic decline. EQ5D questionnaires were used to assess Quality of Life. The difference in treatment success between SCS and control for the primary endpoint in the Intention-to-Treat populations ranged from 52 - 58%. Improvement in EQ5D index scores at 6 months ranged from 0.124 - 0.380. The similarity of outcomes in 3 RCTs2,3,4 demonstrate that SCS is an effective treatment modality for DPN pain compared with conventional medical approaches. Patients from 1 study4 have been followed-up to 18 months8 and patients in another2 up to 10 years9 with similar outcomes, demonstrating long-term benefits of SCS for patients with painful DPN.

Disclosure

B.W.Bode: Advisory Panel; Ascensia Diabetes Care, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Research Support; Abbott Diabetes, Abvance Therapeutics, Better Therapeutics, Inc, Dexcom, Inc., Diasome, Dompé, Insulet Corporation, Lilly Diabetes, Medtronic, Novo Nordisk, Sanvita Medical, Senseonics, Provention Bio, Inc., REMD Biotherapeutics, ViaCyte, Inc., Xeris Pharmaceuticals, Inc., vTv Therapeutics, Speaker's Bureau; Abbott Diabetes, American Diabetes Association, Boehringer Ingelheim and Eli Lilly Alliance, Insulet Corporation, Lilly Diabetes, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; Glytec, LLC. G.Grunberger: Advisory Panel; CeQur SA, Nevro Corp., LifeScan Diabetes Institute, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. M.Fishman: Consultant; Abbott, Biotronik, Medtronic, Nevro Corp., Other Relationship; Medtronic, Abbott, Research Support; Abbott, Boston Scientific Corporation, Medtronic, Nalu, SGX Medical, Thermaquil, Biotronik, Stock/Shareholder; Celeri Health, Thermaquil. M.Murphy: Consultant; Medtronic, Relievant. R.A.Vigersky: Employee; Medtronic. L.Johanek: Employee; Medtronic. M.Larue: Employee; Medtronic.

Funding

Medtronic
494-P: The Role of Serum 25-Hydroxyvitamin D in Diabetes-Associated Cognitive Impairment
Authors: ZHU WEN , WANG SHAOHUA , NIU TONG , LIU KUNYU
Published: June 2023

Objective: 25-hydroxyvitamin D (25[OH]D) has received attention being involved in exerting effects in diabetes-associated mild cognitive impairment (MCI). We aimed to examine the relationship between 25(OH)D and the risk of incident MCI, and the exact mechanism to regulate MCI in diabetes.

Methods: This cross-sectional study was conducted from 103 patients with type 2 diabetes (aged 40-75years), focusing on cognitive function. After adjustment for age, gender and education level, the partial correlation analysis were used to estimate the relationship of 25(OH)D level with multiple neuropsychological tests and metabolism profile, including glucose and lipid metabolism, blood pressure, coagulation and thyroid function. The mediating effects of metabolism profile on the relationship 25(OH)D with cognitive function were were performed by the simple mediating effect model of Model 4.

Results: These participants were finally divided into two groups basing on MoCA: MCI group (n=31) and healthy group (n=72). MCI group showed a lower 25(OH)D level and unfavorable metabolic profiles characterized by higher levels of HbA1c and LPa, but lower levels of INR and FT3 (all p<0.05). The partial correlation analysis found there were positive correlation between 25(OH)D and MoCA, VFT, CDT, LMT, AVLT-IR and AVLT-DR (respectively, r=0.023, p=0.0; 02; r=0.272, p=0.006; r=0.280, p=0.005; r=0.241, p=0.016; r=0.319, p=0.001; r=0.242 p=0.015), primarily reflecting memory, execution and attention. Decreased 25(OH)D level was also correlated with lower FT3 and higher HbAc1 and LPa (respectively, r=0.361, p<0.001; r=-0.223, p=0.026; r=-0.260, p=0.009). In addition, the association between 25(OH)D and MoCA was found to be mediated by FT3 and LPa, with the mediation effect calculated to be 25.57% and 16.69%.

Conclusion: Decreased 25(OH)D increased the risk of incident MCI, especially memory, execution and attention dysfunction in diabetes, and their relationship were may mediated by FT3 and LPa.

Disclosure

W.Zhu: None. S.Wang: None. T.Niu: None. K.Liu: None.
499-P: Leveraging the Technological Advances of Virtual Reality (VR) to Foster Engaging and Interactive Learning, Ultimately Impacting Patient Quality of Care
Authors: ALLEN RUSSIE , WELCH LAUREN K.
Published: June 2023

Leveraging the technological advances of virtual reality (VR) to foster engaging and interactive learning, ultimately impacting patient quality of care.

With continual information evolution, staying current with relevant updates and guideline recommendations can be challenging. Innovative approaches, such as the VR Experience - a cylindrical room showcasing 360-degree wrap around animated content - enlivens education through concise, yet memorable subject matter immersion, transforming the intangible to tangible.

VISION RELIEF is an educational initiative focused on the timely diagnosis and appropriate application of guideline-based treatment for retinal diseases, including diabetic retinopathy (DR). Available in live and digitized formats, learners engage with visual illustrations of retinopathy essentials in screening, detection, and multidisciplinary management, guided by expert faculty dialogue and holographic elements to enhance the 10-minute encounter.

Results: A total of 1040 learners from the 2022 American Diabetes Association Conference engaged with both the live (n=712) and virtual (n=328) educational formats. Of learners that completed pre-/post-testing (n=644), there was a mean 21% competence gain in ability to recognize the importance of early detection and referral of diabetic eye disease, potential visual benefit from early initiation of DR treatment and value of multidisciplinary management. Additionally, 99% of respondents (n=573) reported that VR enhanced their learning experience, with increased likelihood for retinopathy screening referral (82%) and multidisciplinary care of DR patients (80%) (N=527).

Conclusions: Use of innovative technologies can enhance continued learning, advancing the ability to provide high-quality, integrated care.

Disclosure

R.Allen: None. L.K.Welch: None.

Funding

Regeneron Pharmaceuticals Inc.
5-LB: Rescuing Alpha-Cell Function in Type 1 Diabetes
Authors: PANZER JULIA , PUGLIESE ALBERTO
Published: June 2023

Increased glucagon secretion from the pancreatic alpha cell is the first and most important defense against hypoglycemia. In T1D this defense mechanism is lost. We propose that the loss of the neighboring beta cells causes, and in turn the loss of inhibitory signals they generated, is a key factor in the inability of alpha cells to respond appropriately to blood sugar levels. The sudden cessation of this inhibitory input during hypoglycemia is a necessary signal for the glucagon response. We hypothesize that reactivation of endogenous paracrine and autocrine signaling might restore the alpha cell’s ability to respond to hypoglycemia in T1D. We used isolated islets and tissue slices from non-diabetic organ donors and donors with T1D and measured dynamic hormone secretion and calcium recordings. We found that alpha cell responses are briefer than the sustained beta cell responses. If not reset by inhibitory input, the alpha cell is not able to respond again. Glucagon secretion can be recovered by activation of paracrine signals to inhibit the alpha cell. We found full glucagon recovery if reset for 15 min or longer using high glucose in healthy islets (no reset 0.51 +/- 0.09 vs. 5 min reset 0.99 +/- 0.12 vs. 15 min 1.63 +/- 0.31, fold change to baseline +/- SEM). In tissues from T1D donors, alpha cells failed to respond to decreases in glucose concentration despite normal glucagon content and responses to KCl depolarization. Baseline glucagon secretion was significantly elevated compared to healthy individuals (mean 25.93 +/- SEM 8.55 pM in T1D vs 7.49 +/- 2.21, p<0.05). Furthermore, we found severely diminished Ca2+ responses to both lowering glucose concentration and glutamate receptor stimulation. We demonstrate that alpha cells from T1D donors cannot mount an efficient glucagon response due to deficient glutamate receptor signaling and loss of paracrine inhibitory input. Our results suggest that restoring both signals rescues glucagon secretion.

Disclosure

J. Panzer: None. A. Pugliese: Consultant; Provention Bio, Inc.

Funding

American Diabetes Association (4-22-PDFPM-12 to J.P.); The Leona M. and Harry B. Helmsley Charitable Trust (2018PG-T1D053, G-2108-04793)
50-OR: First-Trimester Dietary Phenolic Compounds and Lipids Are Associated with Hyperinsulinism at Birth in Type 1 Diabetes Pregnancy
Authors: MEEK CLAIRE L. , STEWART ZOE A. , FEIG DENICE , KOULMAN ALBERT , MURPHY HELEN R.
Published: June 2023

Objective: Type 1 diabetes in pregnancy is associated with perinatal complications attributed to offspring hyperinsulinism. Conventional management prioritises glycaemia in mid/late pregnancy to reduce hyperinsulinism, but the timing and pathophysiology of hyperinsulinism remains unclear. We assessed if hyperinsulinism, quantified by cord C-peptide at birth, was associated with early pregnancy metabolism.

Methods and Outcomes: 111 women in the Continuous Glucose Monitoring (CGM) in Pregnant women with Type 1 diabetes Trial (CONCEPTT) had a livebirth with measurement of cord C-peptide. Liquid chromatography-mass spectrometry of maternal serum (12, 24, 34 wks; n=101) and cord blood (n=93) measured 2105 metabolites. Statistical analysis: linear regression of Cord C-peptide and metabolites with adjustment for maternal age, BMI, parity, ethnicity, education, intervention and glycemia (and birth gestation for offspring metabolites). Significance limit was p=0.001.

Results: In maternal blood at 12 weeks, positive associations were noted between nine metabolites and cord C-peptide, including lipids (monoglycerides, triglycerides and phospholipids), saccharin and three other dietary phenolic compounds. At 24 weeks, two dietary phenols and several lipids maintained positive associations. At 34 weeks, 124 species in maternal blood showed positive associations with cord C-peptide, including saccharin, free fatty acids, monoglycerides, diglycerides, triglycerides, phospholipids. The profile was distinct from that of large-for-gestational age and neonatal hypoglycemia, despite the perceived pathophysiological overlap in these conditions. In cord blood, carnitines and betonicine were associated with C-peptide.

Conclusions: Lipids, saccharin and other dietary phenols in early pregnancy warrant further investigation as potentially modifiable contributors to offspring hyperinsulinism in type 1 diabetes pregnancy.

Disclosure

C.L.Meek: Research Support; Dexcom, Inc. Z.A.Stewart: None. D.Feig: Advisory Panel; Novo Nordisk Canada Inc., Speaker's Bureau; Sanofi, Novo Nordisk Canada Inc. A.Koulman: None. H.R.Murphy: Advisory Panel; Medtronic, Research Support; Dexcom, Inc.

Funding

Diabetes UK; JDRF
510-P: Tissue Nanotransfection–Based Endothelial-Targeted Epigenetic Gene Editing In Vivo to Rescue Diabetic Ischemic Wounds
Authors: VERMA SUMIT S. , KACAR SEDAT , GNYAWALI SURYA C. , FEHME LEILA S. , SEN CHANDAN K. , SINGH KANHAIYA
Published: June 2023

Our previous work (PMID: 35192691) has identified that genetically silenced phospholipase Cγ2 (PLCγ2) hinders VEGF therapy of the diabetic ischemic limb. Hyperglycemia caused hypermethylation of endothelial specific gene promoter. Given that epigenetic changes are reversible, this work tests the significance of gene-targeted therapeutic DNA demethylation in improving blood flow to diabetic ischemic wounds. Bipedicle ischemic wounds were placed in streptozotocin (STZ) induced acute diabetic C57BL6 mice. Diabetic VWF+ dermal endothelial cells were isolated using flow sorting. In wound tissue, PLCγ2 promoter CpG methylation levels were analyzed using bisulfite sequencing. Next, to specifically demethylate PLCγ2 promoter in endothelial cells, a demethylation cocktail was designed: (i) (scFv)-TET1 catalytic domain (TET1CD) system capable of inducing targeted DNA methylation, and (ii) endothelial promoter driven gene specific guide RNAs. This demethylation cocktail was delivered at the diabetic ischemic wound-edge employing non-viral topical tissue nano-transfection (TNT) technology. PLCγ2 protein expression outcomes were assessed using flow cytometry. Functional outcome of such demethylation was assessed using Laser Speckle Perfusion imaging (Perimed Inc.) and ultrasonography (Vevo 2100) at days 3, 7&10. Overall DNA hyper methylation was prominent in murine ischemic flaps as demonstrated by the increased ratio of 5-methylcytosine (methylation mark) to 5-hydroxymethylcytosine (demethylation mark) (n=5). Specifically, the PLCγ2 promoter was hypermethylated (n=5). TNT mediated endothelial-targeted demethylation of the PLCγ2 promoter increased its expression (n=4). Such demethylation-based upregulation of PLCγ2 improved wound tissue blood flow with increased abundance of VWF+/PLCG2+ vascular elements (n=4). TNT-based endothelial demethylation of the PLCγ2 gene promoter improved perfusion of cutaneous diabetic wounds.

Disclosure

S.S.Verma: None. S.Kacar: None. S.C.Gnyawali: None. L.S.Fehme: None. C.K.Sen: n/a. K.Singh: None.

Funding

U.S. Department of Defense (W81XWH-22-1-0146)
516-P: Lineage Tracing of Vasculogenic Fibroblasts In Vivo and Their Significance in the Rescue of Diabetic Ischemic Tissue
Authors: KACAR SEDAT , SINGH KANHAIYA , VERMA SUMIT S. , REESE DIAMOND , KUMAR MANISHEKHAR , ROY SASHWATI , SEN CHANDAN K.
Published: June 2023

Our recent work reported on the identification of the vasculogenic fibroblast (VF) that is capable of generating new blood vessels during tissue repair (Pal et al. Nat Com, 2023). While these cells are physiologic and injury-inducible, the generation of VF is blunted under conditions of diabetes. Such barrier may be overcome by the inhibition of fibroblast miR-200b using tissue nanotransfection technology (PMIDs: 28785092, 34837085, 35819852, 36380587). To understand the mechanisms underlying VF function and significance, in this work we developed miR-200b-429fl/fl COL1A2creER GT(ROSA)mT/mG mice. In these mice, miR-200b regions in fibroblasts (COL1A2+ cells) are knocked out in response to tamoxifen. To gain insight into the significance of VF in vivo, ischemic hind limb studies were performed. Tamoxifen treatment not only led to Cre excision of miR-200b-429 in these mice, but also induced the constitutive expression of ROSA driven tdTomato in fibroblasts with onset of permanent GFP expression. Significant lowering of miR-200b was noted in laser capture dissected dermal fibroblast tissue elements from the wound-edge of tamoxifen treated mice (n=4). Tamoxifen treatment led to significantly enhanced perfusion in animals subjected to ischemic injury as determined by laser speckle perfusion imaging (Perimed Inc.) (n=8). This rescue was associated with increased abundance of GFP+CD31+ VF (n=5) which accounted for 26% of all CD31+ vascular cells in the laser captured blood vessels (n=9). Thus, targeted lowering of miR-200b abundance within fibroblasts resulted in substantial augmentation of VF in vivo which was associated with improved blood flow.

Disclosure

S.Kacar: None. K.Singh: None. S.S.Verma: None. D.Reese: None. M.Kumar: None. S.Roy: None. C.K.Sen: n/a.
518-P: Prior to Development of Neuropathy, People with Diabetes Have Altered Morphological and Mechanical Properties of the Ankle Joint, Tendons, and Muscles
Authors: HOVEIZAVI ROYA , GAO FAN , FISHER SIMON
Published: June 2023

Diabetes-related anatomical changes to the foot that foment ulcer formation are attributed to diabetic neuropathy. We hypothesized that prior to development of neuropathy, diabetes is associated with biomechanical changes in the ankle joint. To test this hypothesis, morphological properties of Achilles tendon, soleus, medial and lateral gastrocnemius muscles were evaluated by a LOGIQ ultrasound device at preset ankle (−30, −15,0,10) and knee (90,180) positions in both subjects with diabetes without neuropathy (DM; n=11, age 53±11, 3M, 8F, 87±16 kg, HbA1c 7.37±1.80, disease duration 75±79 months) and nondiabetic controls (CON; n=12, age 45±17, 5M, 7F, 75±14 kg). Monofilament (5.07/10 g) testing confirmed absence of neuropathy. As compared to CON, DM demonstrated significantly shorter Achilles length (p=0.002), smaller cross section area (p=0.018), higher Achilles stiffness (p=0.006), shorter muscle fascicles across the soleus muscle (p=0.03), higher stiffness in the soleus (p=0.001) and lateral gastrocnemius (p=0.002), and higher pennation angles for all three muscles (p<0.05). The current study demonstrates altered muscle-tendon unit mechanical properties in subjects with diabetes without neuropathy. These changes indicate a pathological process that may contribute to plantar ulcer formation even in absence of diabetic neuropathy.

Disclosure

R. Hoveizavi: None. F. Gao: None. S. Fisher: None.
520-P: Bedside Amputation Surgery for Isolated Toe(s) Necrosis in a Diabetes Department—Prognostic after One-Year Follow-up
Authors: FÉRON FLORINE , RIVELINE JEAN-PIERRE , GAUTIER JEAN-FRANÇOIS , KEVORKIAN JEAN-PHILIPPE
Published: June 2023

For isolated toe(s) necrosis complicating diabetic foot ulcers (DFU), level of amputation is a frequent topic of disagreement between diabetologists and surgeons. Bedside Amputation Surgery (BAS) performed by a diabetologist might be an option to get rid of a major surgery (complete transmetatarsal amputation [TMA] or transtibial amputation [TTA]) usually and initially recommended by the surgeon in this case. Indications of this practice need to be specified. This monocentric, retrospective, observational study assessed the outcome at 1 year of patients with diabetes mellitus (DM) after an accessible BAS performed by the diabetologist for isolated and delimited toe(s) necrosis consisting of transphalangeal amputation, metatarsophalangeal disarticulation or TMA of one axis. The primary endpoint is the one-year healing rate without secondary surgery performed by a surgeon in the operating room. Out of 783 patients admitted for DFU (05/2016-10/2021), 66 underwent BAS (8.5%). One-year follow-up was achieved for 55 patients (5 deaths from other causes and 6 lost of follow-up): males 82%, type 2 DM 96%, DM median duration 18 years, median HbA1C 9%. One-year healing rate was 62% (34/55). Among 21/55 patients with no healing at 1 year, 19 received secondary surgery in the operating room (TTA 32% (6/19), complete TMA 37% (7/19) and revision surgery gesture 31% (6/19), median delay: 41 days). Failure was observed in patients with more severe leg arteriopathy (1 vs 2 vascular leg axes, p=0.03) with no significant difference in foot vascularization. Soft tissue infection at the time of BAS was significantly more present in the unhealed group (80% vs 47%, p=0.02) with a higher CRP level (84 vs 23mg/L, p= 0.001). BAS allows optimal care in about 2 out of 3 cases, avoiding the need to perform major surgeries. The number of vascular leg axes (<1) as well as degree of soft tissue infection need to be assessed before suggesting the indication.

Disclosure

F.Féron: None. J.Riveline: Board Member; Abbott Diabetes, Medtronic, Dexcom, Inc., Novo Nordisk, Eli Lilly and Company, Sanofi. J.Gautier: Advisory Panel; Bayer Inc., Eli Lilly and Company, Sanofi, Other Relationship; Novo Nordisk. J.Kevorkian: None.
523-P: Identifying Risk Factors Associated with Diabetic Foot Wounds Outcomes within a Safety-Net Hospital System
Authors: GUNAWAN FELONA , JOHNNY BLESSING , GUNASEKARAN UMA
Published: June 2023

Dallas county has a high prevalence of diabetes and increasing rates of diabetic foot wound related lower extremity amputations in the past few years. The healthcare spending associated with diabetic foot wounds and its complications is significant, with an average cost of hospitalization for lower extremity amputation of $91,000 at Parkland Health. To better understand the risk factors for developing diabetic foot wounds and its complications, we performed an electronic medical record review of patients with diabetic foot wounds who had a visit at the Parkland Diabetes Clinic between 2019-2022. We identified 78 patients (average age 51 years, 81% male, 68% Hispanic, 21% Black, 10% Caucasian, 68% receiving charity care) with type 2 diabetes and diabetic foot wounds. The average diabetes duration was 13 years, and the average A1c was 11.1% at diagnosis and improved to 8.5% within 3-6 months. The wounds completely healed in 42% (33/78) of the patients by 4 months, with an average time to healing of 72 days. Patients with healed wounds had lower average final A1c (8.3 vs 8.7%), shorter duration of diabetes (12 vs 14 years), and lower rate of peripheral vascular disease (52 vs 60%) compared to those with non-healed wounds. In conclusion, diabetic foot wounds were particularly prevalent among uninsured male Hispanic population within our safety-net health system. Better glycemic control and earlier detection of diabetes may lead to improved diabetic foot wound outcomes. Identifying these risk factors will help us better tailor educational and clinical interventions to prevent the development of diabetic foot wounds and improve clinical outcomes for patients with diabetic foot wounds.

Disclosure

F.Gunawan: None. B.Johnny: None. U.Gunasekaran: None.
525-P: Droid Audio Visual Educator–Diabetes Nutrition (DAVE-DN) Randomized Controlled Trial
Authors: O'CONNOR SADHBH , BIRDIE SHI QI ONG JANE , WAY WERN LIM BRYAN , COLEMAN SEAN , WORLIKAR HEMENDRA , CONNOLLY CORNELIA , MCGAREL SIAN E. , O'BRIEN TIMOTHY , O'KEEFFE DEREK T.
Published: June 2023

Background: Worldwide, demand for health care services far outpaces the availability of staff. The use of robots in healthcare has advanced in recent years as robots are seen as a viable solution to address the shortage of healthcare staff. We propose the use of a humanoid robot to provide basic nutritional education to patients with diabetes in the waiting room, hence freeing up time for dieticians to address more complex issues. We hypothesize that use of this intervention will be more effective than the current standard of care i.e. A leaflet, in educating and empowering patients with diabetes.

Methods: We conducted a single-centre, randomized controlled trial to determine whether a humanoid robot would improve patient’s knowledge of nutrition. The primary outcome of the trial is improvement in patient knowledge score based on 36 items from a validated nutrition questionnaire. Each patient’s prior knowledge of nutrition was assessed by a validated questionnaire prior to the intervention. Patients were randomized to current standard of care i.e. physician-led education plus a leaflet (n=40) or standard of care plus Droid Audio Visual Educator (n=40). Following the trial, both groups had their knowledge of nutrition reassessed using the same validated questionnaire. The performance of patients in each group was compared and effectiveness of the intervention in improving education objectively determined.

Results: A total of 90 patients underwent randomization. 10 withdrew before completion. The mean age was 53.7 years. The change in score in the intervention group was 3.2 of 36 points higher than control group on average (95% confidence interval [CI] 0.9 to 5.4; P= 0.006).

Conclusions: This trial suggests there is potential for humanoid robots to deliver basic nutritional education

Disclosure

S.O'connor: None. J.Ong: None. B.Lim: None. S.Coleman: None. H.Worlikar: None. C.Connolly: None. S.E.Mcgarel: None. T.O'brien: None. D.T.O'keeffe: None.

Funding

Health Services Executive, Intern Network Academic Track
529-P: A Tale of Two States—Lessons Learned from Diabetes in School Health (DiSH) Telementoring Collaborative Sessions
Authors: POLLOCK ALLISON J. , BEATON WHITNEY N. , BURGESS BOBBI A. , EITEL KELSEY B. , LOGEL SANTHI , ONDECK LYNNETTE J. , SUNDBERG ERIN
Published: June 2023

School nurses are central to the health of children with diabetes (DM). In two states, a novel telementoring program, Diabetes in School Health (DiSH), was designed to support DM education for school nurses. Aims were to increase school nurse knowledge & comfort with routine DM care, and to build a network for sharing experiences & challenges with DM care. Sessions include brief didactic presentations followed by practical discussion and sharing of scenarios to collaborate and learn strategies to improve DM care. Recruitment of school nurses was via email. DiSH sessions started in Jan 2020 (WI) & Apr 2021 (WA) and are ongoing. This study reviewed the first 3 years of data from 25 DiSH-WI & 16 DiSH-WA sessions. Session attendance: mean 58 WI & 108 WA school health personnel, mostly nurses. Qualitative data included highlights from sessions’ didactics and discussions. In both WI and WA, recurrent themes included importance of communication, building relationships, and meeting students where they are. Table 1 reports challenges shared and lessons learned. Regional differences include applying regulations governing care in school. DiSH, a novel format for DM education of school nurses, provides a platform for locally relevant discussion of complex yet practical themes, which can be difficult to address in traditional educational modules. Dissemination of DiSH programs to other states is underway.

Disclosure

A.J.Pollock: None. W.N.Beaton: None. B.A.Burgess: None. K.B.Eitel: None. S.Logel: None. L.J.Ondeck: None. E.Sundberg: None.
530-P: Capillary Blood Ketone Level and the Prediction of Future Diabetic Ketoacidosis Risk in Type 1 Diabetes
Authors: SONG CIMON , DHALIWAL SHARON , BAPAT PRIYA , BAKHSH ABDULMOHSEN M.K. , BUDHRAM DALTON R. , SCARR DANIEL , WEISMAN ALANNA , FRALICK MICHAEL , IVERS NOAH , CHERNEY DAVID , MUMFORD DOUG , TOMLINSON GEORGE , ERIK LOVBLOM LEIF , PERKINS BRUCE A.
Published: June 2023

Identification of those at risk of diabetic ketoacidosis (DKA) in T1D is challenging. Rather than during illness while DKA is developing, we aimed to determine if levels of routine point-of-care capillary blood ketones could predict DKA months prior to the event. In exploratory analysis, we examined 484 participants randomly assigned to placebo in an adjunct-to-insulin medication trial program (NCT02414958 and NCT02580591). Participants provided morning fasted capillary blood ketone levels twice per week via electronic logbook, and we calculated the maximum and mean level for each individual during a 2-month baseline period. Outcome was the 6 to 12-month occurrence of trial-adjudicated DKA. Area under the Curve (AUC) for the Receiver Operator Characteristic curves were generated. In sensitivity analysis we applied supervised machine learning methods (gradient-boosted trees). Participants had median age 43 [IQR 33, 54], mean HbA1c 8.2±0.6 percent, and provided 2 [1, 4] ketone measurements per week. Twelve DKA events occurred at median 105 [43, 199] days. Maximum and mean ketone levels were higher at baseline for the 12 cases compared to controls (for example, maximum ketone level 0.8 [0.6, 1.2] compared to 0.3 [0.2, 0.7] mmol/L, p=0.002). Maximum ketone level had AUC of 0.769 (95% CI 0.655-0.883). Maximum ketone ≥0.8 mmol/L had sensitivity 64%, specificity 78%, and likelihood ratios positive and negative of 2.9 and 0.5. Machine learning methods outperformed the single-metric analyses. Results provide proof-of-concept that routine capillary ketone surveillance can identify individuals at high-risk of future DKA. Simple or complex machine learning algorithms could be implemented in ketone meters or in future continuous ketone measurement technology.

Disclosure

C.Song: None. D.Cherney: Other Relationship; Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon and Novo-Nordisk, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk. D.Mumford: None. G.Tomlinson: None. L.Lovblom: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). S.Dhaliwal: None. P.Bapat: None. A.M.K.Bakhsh: None. D.R.Budhram: None. D.Scarr: None. A.Weisman: None. M.Fralick: None. N.Ivers: Consultant; Novo Nordisk Canada Inc., IQVIA Inc.

Funding

Diabetes Canada (OG-3-21-5572-BP)
531-P: The Multidisciplinary Team Education for Subjects with DKD Could Affect the Prevention of eGFR Decline
Authors: HITOMI MAMIKO , HIKI NAOKI , SAKAMOTO UMEKO , USUI YUURI , MIYATSUKA TAKESHI , MORIYA TATSUMI
Published: June 2023

Background: It still remains unclear as to whether or not multidisciplinary individual team approach (MTA) affects the decline of kidney function in persons with diabetic kidney disease (DKD). We examined the effects of MTA on 24 DKD subjects compared with effects on 24 control subjects with DKD who are managed by dietitian approach alone (DA) between January 2012 and December 2021.

Methods: The team was composed of doctors, nurses (CDE, RN) and dietitians (CDE, RD). The team provided broad education, including advice on medication, medical diet therapy, management of home blood pressure, SMBG, weight measurement, self-check of edema, foot care, giving information of stage of DKD and medical examinations.

Results: There was no significant difference in types of diabetes (types 1 and 2; 2/22 vs. 1/23), gender (men/women; 15/9 vs.18/6), duration of diabetes (15 ± 9 vs. 19 ± 11 yrs.), observation period (7.9 ± 1.3 vs. 7.3 ± 2.4 yrs.) between MTA and DA. MTA is significantly younger (57 ± 12 years old) than DA (67 ± 9 years old) (p=0.002). Number of interventions per year were 3.6 ± 1.4 vs. 2.6 ± 1.9 times between MTA and DA (p=0.046). Also the initial eGFR (61.0 ± 26.6 vs. 60.1 ± 19.4 mL/min/1.73m2) and albuminuria levels (246 (33-1923) vs. 382 (35-2008) mg/g•Cr) were comparable between the groups. Annual eGFR decline rate in MTA group (−1.38 ± 2.11 mL/min 1.73m2) was significantly lower than that in DA group (−3.89 ± 6.34). Two subjects were initiated hemodialysis only in the DA group (likelihood ratio 2.86, p=0.091). Four subjects died in only the DA group (likelihood ratio 5.91, p=0.015).

Summary: It is possible that MTA affects the prevention of renal function decline compared with the intervention provided by DA alone. Subjects with DKD, even with normal renal function, may be recommended to have MTA to prevent the progression of renal failure.

Disclosure

M.Hitomi: None. N.Hiki: None. U.Sakamoto: None. Y.Usui: None. T.Miyatsuka: Speaker's Bureau; Eli Lilly Japan K.K., Novo Nordisk, Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Sanwa Kagaku Kenkyusho, Daiichi Sankyo. T.Moriya: None.
533-P: The Physiological Effects from Type 2 Diabetes Self-Management Program in a Municipal Setting
Authors: HELGSTRAND LINE A. , HVIDBERG ALBERTE D. , GLÜMER CHARLOTTE
Published: June 2023

There is a lack of knowledge showing the real-life effects of person-centered type 2 diabetes (T2DM) Management programs offered in a municipal setting. The aim of this study is to determine the effectiveness of individualized T2DM management programs for patients with T2DM in a municipal setting on HbA1c and blood pressure (BP). Based on a person-centered and differentiated approach, the intervention consists of education, physical training, cooking classes and/or individual consultations.

Methods: The study was conducted during 2018 to 2021 with citizens referred consecutively for T2DM management programs. A total of 308 patients were included. Of these 308, 172, and 131 completed questionaries and physiological measurements at baseline, at end of the program and at 6 months follow-up, respectively. All physiological data was collected by selected health care professionals trained in standard operations procedures. Results: Respondents consist of 60% men, age range primarily from 55-79, 57% have a short education level. At baseline mean HbA1c was 58.5 mmol/mol (IQR: 48.0-64.0). At end of the program, a statistically significant decrease of −6.5 mmol/mol (95% CI: −9.0; −4.1, p<0.001) was observed. At 6 months follow-up this decrease was unchanged as it was showing a decrease of −5.8 mmol/mol (95% CI: −8.8; −2.8, p<0.001) compared to baseline. At baseline mean systolic and diastolic BP was 147.5 mmHg (IQR: 134.2-158.0) and 86.2 mmHg (IQR: 79.6-93.3), respectively. At end of the program and at 6 months follow-up a significant decrease of −10.7mmHg (95% CI: −15.0; −6.3, p<0.001) and −11.8 mmHg (95% CI: −16.4; −7, 2, p<0.001), respectively, was observed for systolic BP when compared to baseline.

Conclusion: Person-centered T2DM management programs in a large municipal setting significantly reduce HbA1c and BP on long and short term. These results may be caused by person-centered care and a holistic approach.

Disclosure

L.A.Helgstrand: None. A.D.Hvidberg: None. C.Glümer: None.