bluuebunny/crossref_metadata_2025 huggingface dataset:
381-P: Studying the Impact of Nasal Glucagon on Real-Life Experiences of Severe Hypoglycemia Treatment (SIMPLEST)
Authors: MITCHELL BETH , PONCE-IBARRA ALFONSO , MOENNIG ELISABETH , ODAK SHARDUL , MCSORLEY DAVID J. , SPAEPEN ERIK , JACKSON LAURIN , ZOGRAFOS LAURIE , YAN YU
Published: June 2023

Background: Severe hypoglycemia (SH) is feared by people with diabetes (PwD) and those who care for them due to its impact on everyday life. Studies have shown that ready-to-use nasal glucagon (NG) is preferred over reconstitutable injectable glucagon; however, real-life experiences that PwD and health care providers (HCPs) have with NG are unknown.

Objective and Methods: A cross-sectional, web-based study was conducted in the US and Germany among: i) insulin-treated adults who owned NG for at least 2 months to assess impact of NG on everyday life, and ii) HCPs who prescribed NG within 6 months of study initiation to assess HCPs’ experiences with NG in meeting their patients’ needs. Data were analysed descriptively, and US results are presented.

Results: Of 292 PwD (mean age 42, 47% T1D, 86% high fear of hypoglycemia total screener score, 37% impaired hypoglycemia awareness), 68% had been treated with NG. Over 90% agreed that NG had positively impacted quality of life (QoL) items (Figure). Of 71 HCPs (endocrinologists 87%), 90% were satisfied with NG meeting patients’ needs. Over 80% of HCPs were satisfied with training time on NG and confident with patient and caregiver’s ability to apply the training for a SH event.

Conclusion: The positive impact of NG on QoL, less fear of hypoglycemia, and high confidence in caregiver’s ability to use NG may help improve PwD’s everyday life related to hypoglycemia management.

Disclosure

B.Mitchell: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Ponce-ibarra: Employee; Lilly Deutschland GmbH, Stock/Shareholder; Eli Lilly and Company. E.Moennig: Employee; Lilly Deutschland GmbH, Stock/Shareholder; Eli Lilly and Company. S.Odak: Other Relationship; Eli Lilly and Company. D.J.Mcsorley: Other Relationship; Eli Lilly and Company, Sage Pharmaceuticals, Novavax, Bristol-Myers Squibb Company, Seattle Genetics, Inc., Boston Scientific Corporation, Blood Centers of America, Inc. E.Spaepen: Consultant; Eli Lilly and Company. L.Jackson: Other Relationship; Eli Lilly and Company. L.Zografos: Other Relationship; Eli Lilly and Company. Y.Yan: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Funding

Eli Lilly and Company
390-P: Improving Quality of Life and Self-Efficacy through a Hypoglycemia Management Program—The HARPdoc Randomised Controlled Trial
Authors: AMIEL STEPHANIE A. , TOSCHI ELENA , HELLER SIMON R. , STADLER MARIETTA A. , CHOUDHARY PRATIK , DE ZOYSA NICOLE
Published: June 2023

Background: A significant minority (15-18%) of adults with type 1 diabetes (T1D) continue to experience problematic hypoglycemia despite access to structured education in flexible insulin therapy and advanced technologies. Many have impaired awareness of hypoglycemia, now recognised to be associated with significant mental health burden. The HARPdoc trial (Hypoglycemia Awareness Restoration Program for people with problematic hypoglycemia Despite Optimised Care) showed that a group programme focused on cognitions and motivation improved scores for diabetes distress, anxiety and depression compared to BGAT (blood glucose awareness training, which addresses education and behaviours), with similarly reduced rates of severe hypoglycaemia.

Methods: This exploratory study addresses the further impact of these programmes on quality of life and mental health. Quality of life was measured at baseline with EQ-5D-5L and it and service use (Adult Service Utilisation Schedule) were measured at 12 and 24 months after randomised participation to either HARPdoc or BGAT.

Results: Mean EQ-5D scores rose by 14%, +0.1 HRQoL utility score (HUS), over 24 months in HARPdoc and fell by 1%, -0.007 HUS in BGAT. Use of mental health services after HARPdoc or BGAT was 26 vs 56 contacts with a psychiatrist, psychologist or counsellor in months 0-12 and 1 vs 17 contacts in months 13 - 24 respectively.

Conclusions: We conclude that HARPdoc reduces previously treatment-resistant severe hypoglycaemia in adults with type 1 diabetes but also enhances quality of life, whilst reducing use of mental health services. We hypothesise that the psychosocial aspects of HARPdoc increase self-efficacy and coping skills, thereby reducing disease burden and the need to access general and mental healthcare provision.

Disclosure

S.A.Amiel: Advisory Panel; Medtronic, Other Relationship; Sanofi, Novo Nordisk. E.Toschi: Advisory Panel; Eli Lilly and Company. S.R.Heller: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Other Relationship; Eli Lilly and Company, Research Support; Dexcom, Inc., Speaker's Bureau; Novo Nordisk, Medtronic. M.A.Stadler: None. P.Choudhary: Advisory Panel; Medtronic, Novo Nordisk, Dexcom, Inc., MannKind Corporation, Insulet Corporation, Research Support; Abbott Diabetes, Speaker's Bureau; Sanofi, Lilly. N.De zoysa: None.

Funding

JDRF (4-SRA-2017-266-M-N); National Institute of Health Research UK
398-P: Renal Proximal Tubular Metallothionein 3 Contributes to Diabetic Kidney Lesion
Authors: TAKIYAMA YURI , TAKIYAMA TAKAO , BESSHO RYOICHI , KITSUNAI HIROYA , TAKIYAMA YUMI
Published: June 2023

Metallothionein (MT) is a cysteine-rich protein with an antioxidant. MT3, one isoform of the four MTs, is upregulated in the renal proximal tubular cells in type 2 diabetic subjects. To investigate the role of human MT3, we used the mouse sglt2 promoter for targeting human MT3 gene to renal proximal tubular cells in transgenic mice (MT3TG). MT3TG showed nodular glomerulosclerosis without hyperglycemia. Electron microscopy presented thickened glomerular basement membranes, numerous endoplasmic reticulum in proximal tubules and cytoplasmic swelling of the endothelium of peritubular capillaries accompanied with abnormal capillary formation around the glomerulus, suggesting proximal tubular MT3 induces retrogradely glomerular hypertension. Affymetrix Human Gene 1.0 ST arrays identified 43 upregulated and 81 downregulated genes between control and MT3-knockdown human renal proximal tubular epithelial cells (HRPTECs, Lonza) under hypoxia, an early event in diabetic kidney. Among them, ceruloplasmin (CP) and cytochrome b reductase 1 (CYBRD), the crucial players in the cooper and iron metabolism, were downregulated. In fact, MT3TG presented cytoplasmic co-expression of MT3, CP and CYBRD1 in renal proximal tubules. Hypoxia induced a remarkable increase in MT3 in HRPTECs, and the HIF-1alpha siRNAs abolished that. Despite of no antioxidant response element in the human MT3 promoter, Nrf2 siRNA significantly decreased hypoxia-induced MT3 expression. Moreover, MT3 and Nrf2 siRNAs inhibited hypoxia-induced CP and CYBRD1, but not HIF-1 alpha siRNA. Together with the inhibitory effects of mitochondrial inhibitors, NOX4 inhibitors and antioxidant NAC on hypoxia-induced MT3 expression, hypoxia-induced oxidative stress might be involved in the inductions of CP and CYBRD1. Of note, empagliflozin decreased hypoxia-induced MT3, CP and CYBRD1. Our study suggests that MT3 might contributes to diabetic kidney lesion via CP and CYBRD1against hypoxia-induced oxidative stress.

Disclosure

Y.Takiyama: None. T.Takiyama: None. R.Bessho: None. H.Kitsunai: None. Y.Takiyama: Research Support; Boehringer Ingelheim Japan, Inc., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Abbott Japan Co., Ltd., Roche Diabetes Care, MSD Life Science Foundation, Japan Society for the Promotion of Science, Teijin Pharma Limited, Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly Japan K.K.
4-OR: Impaired Awareness of Hypoglycemia (IAH) in Older Adults with Type 1 Diabetes in the WISDM Study
Authors: BILAL ANIKA , YI FANCHAO , WHITAKER KERI J. , PRATLEY RICHARD E. , CASU ANNA
Published: June 2023

Background: The prevalence of IAH in type 1 diabetes (T1D) varies from 20 - 37%. Risk factors for IAH include advanced age, longer diabetes duration, recurrent hypoglycemic events, and high glucose variability. Little is known about IAH in older adults with T1D.

Methods: Participants with T1D and ≥60 years of age enrolled in the WISDM study were defined as having IAH if their Clarke score was ≥ 4 or normal awareness (NAH) if <4. We compared continuous glucose monitoring (CGM) metrics in those with IAH and NAH at baseline and in those in whom IAH did or did not improve over 26 weeks of observation.

Results: Of the 199 participants (mean age 68 years, 52% females, 96% White), 61 (30.6%) had IAH. Daytime hypoglycemia was more common in those with compared to those without IAH at baseline (Table). After 26 weeks, daytime hypoglycemia and glycemic variability were significantly less in those in whom IAH improved (n=18) compared to those in whom it did not (n=40).

Conclusion: Results of this analysis in older adults with T1D confirm that diabetes duration, c-peptide and %CV are associated with IAH. Among those with IAH, daytime hypoglycemia was significantly more common, while improvements in IAH over 26 weeks were associated with significantly lower rates of daytime hypoglycemia at follow up.

Disclosure

A.Bilal: None. F.Yi: None. K.J.Whitaker: None. R.E.Pratley: Other Relationship; Bayer Inc., Corcept Therapeutics, Dexcom, Inc., Gasherbrum Bio, Inc., Hanmi Pharm. Co., Ltd., Hengrui (USA) Ltd., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. A.Casu: None.
40-LB: The Association between Changes in Physical Activity Before and After Thyroidectomy and Incident Type 2 Diabetes in Patients with Thyroid Cancer
Authors: PARK JIYUN , PARK HYUNJU , KIM SOO-KYUNG , CHO YONG-WOOK , HAN KYUNGDO , KIM KYUNG-SOO
Published: June 2023

Background: Thyroid cancer patients who underwent thyroid-stimulating hormone suppression therapy after thyroidectomy is increased a risk for type 2 diabetes mellitus (T2DM). However, whether the changes in physical activity (PA) before and after thyroidectomy in patients with thyroid cancer are associated with T2DM has not been evaluated yet. We investigated the association between changes in PA before and after thyroidectomy and incident T2DM in patients with thyroid cancer.

Methods: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy between 2010 and 2016 was performed using the Korean National Health Information Database. PA was defined as mid-term or vigorous exercise at least 1 day in a week. PA changes over time were divided into four groups: persistent non-exercisers (n = 18,441), new exercisers (n = 14,599), exercise dropouts (n = 11,023), and exercise maintainers (n = 25,463).

Results: During mean 4.5 years of follow-up, the incidences per 1,000 person years of T2DM were lower in patients who performed PA before or after thyroidectomy than persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the exercise dropout group (adjusted hazard ratio [aHR] 0.81, 95% confidence interval [CI], 0.72-0.91), new exerciser group (aHR 0.87, 95% CI 0.78-0.97), and the exercise maintainer group (aHR 0.84, 95% CI 0.76-0.93) had lower risks of incident T2DM. When we stratified patients according to energy expenditure, PA with < 1,500 metabolic equivalent of task (MET)-min/week in exercise maintainers was associated with lower risk of incident T2DM than non-exercisers, but PA with ≥ 1,500 MET-min/week was not.

Conclusion: In patients with thyroid cancer, PA before or after thyroidectomy was associated with lower risk of incident T2DM.

Disclosure

J. Park: None. H. Park: None. S. Kim: None. Y. Cho: None. K. Han: None. K. Kim: None.
403-P: Profiling of Circulating MicroRNAs (miRNAs) Associated with Progression to End Stage Kidney Disease (ESKD) in Diabetes—Preanalytical and Analytical Considerations
Authors: SATAKE EIICHIRO , MD DOM ZAIPUL , KOBAYASHI HIROKI , RICCA JOSEPH , O'NEIL KRISTINA , KROLEWSKI BOZENA , PEZZOLESI MARCUS G. , KROLEWSKI ANDRZEJ
Published: June 2023

Background: miRNAs are short non-coding RNA molecules involved in gene regulation. Previously, we identified 17 plasma miRNAs (8 risk and 9 protective miRNAs) associated with progression to ESKD in diabetes (JASN 2021). Factors that influence the measurement of miRNA concentrations, and thus could impact replication of these findings, including extraction method, miRNA profiling method, and the miRNA source biofluid, have not been investigated.

Methods: Plasma and serum were obtained from patients who participated in the Joslin Kidney Study. Extraction-free plasma and serum miRNA profiles were obtained using the HTG EdgeSeq platform. RNA was also extracted from plasma and used to measure miRNAs by RNA sequencing (RNASeq) and quantitative RT-PCR (qRT-PCR).

Results: Out of 2,083 miRNAs on the EdgeSeq platform, almost all of them (96%) were detected in plasma without RNA extraction, while only 45% of these miRNAs were detected in RNA extracted from the same plasma specimens. The content of miRNAs detected in extracted RNA was significantly enriched for GC sequences in comparison with miRNAs that were lost during RNA extraction. In the specimens with RNA extracted, significantly lower number of miRNAs were detected by RNASeq or qRT-PCR (31% and 26%, respectively) in comparison with the EdgeSeq platform. Regarding the 17 miRNAs associated with ESKD, many of them had different concentrations in serum samples than in plasma and had lower concentration or were not detected in plasma samples with profiled following RNA extraction.

Conclusion: This study demonstrates very strong effects of pre-analytical and analytical factors on concentration of circulating miRNAs. To replicate our findings for 17 circulating miRNAs, it is critical that plasma specimens be used and that miRNAs be measured using the EdgeSeq platform or other platforms that do not require prior extraction of RNA.

Disclosure

E.Satake: None. Z.Md dom: None. H.Kobayashi: Research Support; Bayer Inc. J.Ricca: None. K.O'neil: None. B.Krolewski: None. M.G.Pezzolesi: Research Support; Renalytix. A.Krolewski: None.

Funding

National Institutes of Health (DK131061-01)
415-P: Reduction in the Risk of Peripheral Neuropathy and Preservation of Kidney Function with Metformin, Linagliptin, or Their Fixed-Dose Combination, Compared with Placebo in Prediabetes—A Randomized Controlled Trial
Authors: GABRIEL RAFAEL , TUOMILEHTO JAAKKO
Published: June 2023

Objective: To compare the effect of glucose-lowering drugs plus lifestyle modification with lifestyle alone on peripheral nerve and kidney function in people with prediabetes.

Methods: Multicenter, randomized, placebo-controlled trial in 658 individuals aged 45-74 years with prediabetes (IFG or IGT), were randomized to either metformin monotherapy, linagliptin monotherapy, fixed-dose combination of linagliptin/metformin or masked placebo. Main outcomes: 1-year reduction in the risk of small fiber peripheral neuropathy (SFPN) estimated by foot electrochemical skin conductance <70 µSiemens, measured with the SUDOSCAN® and estimated glomerular filtration rate (eGFR).

Results: The percentage of people at high-risk of SFPN increased by 29.6% in the placebo group, while the increase was significantly lower in the three active-drug groups:1.8% in the metformin group, 4.3% in the linagliptin group, and 3.9% in the combination linagliptin/metformin group (p<0.001 for all three comparisons). eGFR remained significantly higher with the fixed-dose combination linagliptin/metformin (3.3 mL/min; 95% CI: 0.38; 6.22, p = 0.03) than with placebo. FPG was significantly lower with metformin monotherapy (-0.3 mmol/L: 95%CI: -0.48; 0.12, p=0.0009), and with the fixed-dose combination metformin/linagliptin (-0,2 mmol/L; 95% CI: -0.37; -0.03, p = 0.0219) than with placebo. Reduction in body weight was significantly greater (-2.0 kg/year, 95% CI:-5.65; -1.65, p=0.0006) with metformin monotherapy, and with the combination metformin/linagliptin (-1.9 kg/year; 95% CI: -3.02; -0.97, p=0.0002) than with placebo.

Conclusion: In people with prediabetes, 1-year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a better preservation of kidney function than with placebo.

Disclosure

R.Gabriel: None. J.Tuomilehto: Stock/Shareholder; Orion pharma.

Funding

European Commission (FP7EC-GA 279074); Boehringer Ingelheim Germany (1218.166); Merck Healthcare KGaA (EMR200084_621); Instituto de Salud Carlos III (PI11/01653)
44-LB: The Effect of Substituting Water for Diet Beverages on CGM Metrics in People with Type 2 Diabetes (T2D)—The Study of Drinks with Artificial Sweeteners (SODAS)
Authors: ODEGAARD ANDREW , BANTLE ANNE , SEAQUIST ELIZABETH R. , REIKES ANDREW , PEREIRA MARK A.
Published: June 2023

Objectives: Diet beverages (DB) are the largest contributor to artificial sweetener intake in the U.S. diet. People with T2D are the highest consumers of DB, tending to consume them in place of added sugar, especially sugar-sweetened beverages. However, there is little evidence on the health impact of habitual DB consumption by people with T2D. To inform this topic we conducted a randomized trial.

Methods: The SODAS study is a two-arm parallel trial with a run-in period of 2 weeks and 24 week intervention that randomized 181 adults with T2D (HbA1c 6.5 - ≤ 8.5%), age 35+ years, who were usual consumers of commercial DB to receive and consume either: 1) A commercial DB of choice (24 oz. daily); or 2) Unflavored sparkling or flat bottled water of choice (H2O) (24 oz. daily). Outcomes include measures of clinical diabetes control and mechanisms that may alter clinical risk. Here we report preliminary secondary outcome results from continuous glucose monitor (CGM) metrics. Participants wore a blinded, Abbott Freestyle Libre CGM for 3, 2-week periods (run-in, week 12, week 24). We conducted an intent to treat analysis to assess the between-arm difference in change of CGM metric from baseline-week 12- week 24 via linear mixed regression models.

Results: 179 participants will have complete data when study finishes collection in late March 2023, and 166 had provided complete data at the time of analysis. Participants were a mean age of 58 years, and 55% were men. Time in range (TIR, % of readings 70-180 mg/dL) decreased in both arms and at week 24 the mean TIR for DB was 71.3 (SE 2.8) v. 64.3 (SE 2.8) for H2O, difference of means 7.0 (95% CI -0.7, 14.8), P=0.08). Glycemic variability (%CV) was 27.0 (SE 0.8) for DB at week 24 v. 28.7 (SE 0.8) for H2O, difference in means 1.6 (95% CI -3.8, 0.5), P=0.13.

Conclusions: Preliminarily, in people with T2D who habitually consumed DB, there were no significant differences in CGM metrics when substituting H20 intake for DB.

Disclosure

A. Odegaard: None. A. Bantle: None. E. R. Seaquist: Consultant; Zucara Therapeutics. A. Reikes: Other Relationship; GlaxoSmithKline plc. M. A. Pereira: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK117028)
440-P: Complications of Diabetes after 15 Years—Comparing Telemedicine with Conventional Care
Authors: KESAVADEV JOTHYDEV , SHANKAR ARUN , JOTHYDEV KRISHNADEV , JOSHI SHASHANK R. , KRISHNAN GOPIKA , SANAL GEETHU , BASANTH ANJANA , CHANDRAN GOPIKA B. , JOTHYDEV SUNITHA
Published: June 2023

Diabetes Tele-Management System (DTMS®), a telemedicine (TM)-based intervention and follow-up program for diabetes management comprising of a multidisciplinary team performs drug titration, provides dietary advice & educates the patients and their caregivers periodically with the help of customized software and user interface. The study was done to examine the long-term effect of TM consultation along with face-to-face consultation (F-F) in metabolic control & prevention of complications. A total of 495 T2D (62.91 ± 11.64 years (Y); 62.2% males, duration of diabetes: 8.41 ± 2.78 Y), were de-identified. The treatment group [TG- 63.41±11.73 Y; 62.92% males; 8.04±1.82 Y of T2D] included T2D with ≥1F-F and ≥5 TM consultations per year. The propensity score-matched control group [CG-62.17±11.50 Y; 58.69% males; 7.98±2.96 Y of T2D] included T2D who were not on regular follow-up with compromised F-F and TM visits. Data of 15±5 years were collected from DTMS and statistically analyzed. Significant improvement (p < 0.001) in clinical parameters including HbA1c, FBS, lipid profile, BP & weight from baseline to 10 Y of follow up was observed in TG. 9.8% in TG and 82.1% in CG had diabetic complications (Table 1). This 15 year long real-world experience reveals a robust difference between the 2 arms providing compelling evidence to fund TM consultations.

Disclosure

J.Kesavadev: None. A.Shankar: None. K.Jothydev: None. S.R.Joshi: Advisory Panel; Biocon, Zydus Cadila, Torrent Pharmaceuticals Ltd, Franco India, Consultant; Glenmark Pharmaceuticals, Twin Health, Speaker's Bureau; Abbott Nutrition, Sanofi, Abbott, Novo Nordisk, Lupin Pharmaceuticals, Inc. G.Krishnan: None. G.Sanal: None. A.Basanth: None. G.B.Chandran: None. S.Jothydev: None.
443-P: Two-Year Results from a Novel, Patient-Centered, Team-Based Intervention for Patients with Type 2 Diabetes at High Cardiovascular Risk
Authors: ARAFAH ALA , NEELAND IAN , BOURGES-SEVENIER BRENDAN M. , ALBAR ZAINAB , SULLIVAN CLAIRE , AL-KINDI SADEER G. , RAJAGOPALAN SANJAY
Published: June 2023

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of death in patients with type 2 diabetes (T2D). CINEMA is a novel, patient-centered, team-based intervention for patients with T2D/prediabetes with high risk for ASCVD. We present the outcomes from the first 2 years of the CINEMA program.

Methods: Patients with T2D or prediabetes at high risk for CV events (established ASCVD, coronary artery calcium >100 AU, chronic heart failure, chronic kidney disease, and/or metabolic syndrome) were included. Linear mixed effects and generalized linear mixed models were used to assess changes in ASCVD risk factors and guideline-based medication prescriptions over time, respectively.

Results: From May 2020 to September 2022, 426 patients were enrolled in CINEMA; 47% were women and 37% Black, with mean age 60 yrs, mean BMI 36kg/m2, and 48% with established ASCVD. 54% had ≥ 1 follow up visit with median follow up time of 3 months. There were significant reductions in risk factors including HbA1c (-12.1%), LDL-C (-14.2%), BP (-1.8%), and BMI (-2.2%) (P<0.001 for all). SGLT2 inhibitor and GLP-1 RA prescriptions increased from during follow up (20% to 56% and 17% to 66%, respectively).

Conclusion: A multidisciplinary approach to treating patient with type 2 diabetes with the CINEMA program improves ASCVD risk factors and guideline-based medication adherence.

Disclosure

A.Arafah: None. I.Neeland: Consultant; Nestlé Health Science, Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance, Bayer Inc. B.M.Bourges-sevenier: None. Z.Albar: None. C.Sullivan: None. S.G.Al-kindi: None. S.Rajagopalan: Advisory Panel; Novartis, Novo Nordisk, Speaker's Bureau; Novo Nordisk.
445-P: Health Literacy in Patients With Type 2 Diabetes Undergoing Coronary Angiography
Authors: VOGEL JOHANNES , RATZ MAGDALENA , PLATTNER THOMAS , VONBANK ALEXANDER , MADER ARTHUR , SPRENGER LUKAS , MAECHLER MAXIMILIAN , LARCHER BARBARA , LEIHERER ANDREAS , MUENDLEIN AXEL , FRICK MATTHIAS , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2023

Health literacy reflects the ability to make appropriate health decisions and affects health outcomes. It therefore is an important parameter in patient care but also for health care providers. No health literacy data are available for patients undergoing coronary angiography, the standard procedure for the definite evaluation of coronary artery disease (CAD). We therefore recruited 273 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD in a tertiary care setting in central Europe. Health literacy was measured using the validated HLS-EU-Q16 questionnaire. A response rate of 83.9% was achieved. Overall, the median health literacy score (HLS) was 13 (interquartile range (IQR): 10.00-15.00), with 61.9% of patients showing adequate (HLS 13-16), 26.0% problematic (HLS 9-12) and 12.1% inadequate (HLS 0-8) health literacy. From the investigated patients, 94 (34.4%) had type 2 diabetes (T2DM) according to ADA criteria. Comparing patients with T2DM vs. subjects who did not have diabetes, no significant differences in median HLS (13, IQR: 4.3 vs. 13.0, IQR: 5.00; p=0.247) could be observed; similarly, there was no significant difference in the proportion of subjects with adequate (60.6% vs. 62.6%; p=0.755), problematic (28.7% vs. 24.6%; p=0.458) and inadequate (10.6% vs. 12.8%; p=0.594) health literacy. We conclude that among patients undergoing coronary angiography for the evaluation of established or suspected stable CAD, health literacy is suboptimal both in patients with T2DM and in nondiabetic subjects.

Disclosure

J. Vogel: None. M. Ratz: None. T. Plattner: None. A. Vonbank: None. A. Mader: None. L. Sprenger: None. M. Maechler: None. B. Larcher: None. A. Leiherer: None. A. Muendlein: None. M. Frick: None. H. Drexel: None. C.H. Saely: None.
457-P: Ceramides and the Ceramide-Based Risk Scores CERT1 and CERT2 Are Elevated in Patients with the Metabolic Syndrome
Authors: PLATTNER THOMAS , SAELY CHRISTOPH H. , MUENDLEIN AXEL , VONBANK ALEXANDER , MADER ARTHUR , SPRENGER LUKAS , MAECHLER MAXIMILIAN , LARCHER BARBARA , DREXEL HEINZ , LEIHERER ANDREAS
Published: June 2023

Plasma ceramides, phosphatidylcholines (PC) and the ceramide- and PC-based Coronary Event Risk Test scores CERT1 and CERT2 have recently been shown to predict cardiovascular risk. Their association with the metabolic syndrome (MetS) is unclear and is addressed in the present study. We measured ceramides (Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), and Cer(d18:1/24:1)) and PCs (PC(36:6), PC(38:5), and PC(32)) in a cohort of 1306 high-risk patients, of whom 580 had the MetS and 728 did not have the MetS. All investigated ceramides and PC(36:6) as well as CERT1 (4.6±3.3 vs. 3.4±3.0) and CERT2 (5.9±2.5 vs. 5.3±2.5) were elevated in patients with the MetS vs. those who did not have the MetS (p<0.001 for all comparisons). In regression analyses adjusting for age, sex, smoking, BMI and LDL-C CERT1 and CERT2 proved to be independent predictors of the MetS, with ORs of 1.14 [95% CI 1.09-1.19] and 1.09 [1.04-1.15], respectively. From our data we conclude that ceramides Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), and Cer(d18:1/24:1), phosphatidylcholine PC(36:6) and the ceramide- and PC derived risk scores CERT1 and CERT2 are elevated in Patients with the MetS.

Disclosure

T.Plattner: None. A.Leiherer: None. C.H.Saely: None. A.Muendlein: None. A.Vonbank: None. A.Mader: None. L.Sprenger: None. M.Maechler: None. B.Larcher: None. H.Drexel: None.
464-P: The Triglyceride–Glucose Index and Type 2 Diabetes Are Mutually Independent Predictors of Major Cardiovascular Events in Patients with Coronary Artery Disease
Authors: PLATTNER THOMAS , VONBANK ALEXANDER , MADER ARTHUR , SPRENGER LUKAS , MAECHLER MAXIMILIAN , LARCHER BARBARA , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2023

The triglyceride-glucose index (TyG) is a validated biomarker of insulin resistance. Its power to predict major cardiovascular events (MACE) in patients with established coronary artery disease (CAD) is unclear and is addressed in the present study. We enrolled 1032 consecutive patients with angiographically proven CAD. Prospectively, cardiovascular events were recorded over a mean follow-up period of 10.1±5.1 years. At baseline, the TyG index was significantly higher in patients with T2DM (n=346) than in nondiabetic subjects (9.3±0.7 vs. 8.7±0.5; p<0.001). During follow-up, 435 of our patients suffered MACE. The event rate was significantly higher in patients with T2DM than in nondiabetic subjects (48.7 vs. 39.4%; p=0.005). The TyG index in Cox regression models adjusting for age, sex, hypertension, smoking, body mass index, and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.40 [1.20-1.65], p<0.001); HRs in patients with T2DM and in nondiabetic subjects were 1.51 [1.18-1.93], p=0.001 and 1.16 [0.89-1.50], p=0.271, respectively, with no evidence of an interaction between TyG and T2DM (p=0.440). With T2DM additionally entered into the regression model, TyG on tee total study population predicted MACE independently from the presence of T2DM (HR 1.32 [1.10-1.57], p=0.003) while T2DM remained independently predictive of MACE after adjustment for TyG (HR 1.29 [1.04-1.59]; p=0.020). From our data we conclude that the TyG index and T2DM are mutually independent predictors of MACE in patients with established CAD.

Disclosure

T. Plattner: None. A. Vonbank: None. A. Mader: None. L. Sprenger: None. M. Maechler: None. B. Larcher: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
469-P: Direct Medical Costs Associated with Cardiovascular Complications for Adults with Type 2 Diabetes—Evidence from a U.S. Retrospective Study
Authors: BAE JAY P. , THIEU VIVIAN , LAGE MAUREEN J. , BOYE KRISTINA
Published: June 2023

Introduction: Cardiovascular (CV) disease is a major cause of morbidity and mortality for people with diabetes. This study examines the annual medical costs of newly identified CV complications for adults with type 2 diabetes (T2D).

Methods: Optum’s de-identified Clinformatics® Data Mart data from 1/1/2015 - 6/30/2021 was used to examine a cohort of adults with T2D identified with a CV complication, with first such date identified as the index date. Descriptive statistics examined the direct medical costs (inpatient, emergency, and outpatient) associated with each complication in the 1st and 2nd year post index date. Complications included heart failure (HF), myocardial infarction (MI), stroke (STRK), hospitalization with a diagnosis of unstable angina (HUA), coronary revascularization (CR), and hypertension (HTN).

Results: There were 167,046 patients with an average of 1.2 conditions of interest each. HTN (12.3%), STRK (12.1%), and HF (10.6%) were the most common complications. In the 1st year post index date, HUA, MI, and HF were the most expensive complications. In the 2nd year post index date, costs of each complication ranged from 1.7% (CR) to 65.0% (HTN) of 1st year costs (see Figure).

Conclusion: Results illustrate the costs associated with CV-related complications for T2D and helps to quantify the economic burden that T2D imposes on U.S. healthcare systems.

Disclosure

J.P.Bae: None. V.Thieu: None. M.J.Lage: Consultant; Eli Lilly and Company. K.Boye: Employee; Eli Lilly and Company.
477-P: Thalamic Mitochondrial and Neuronal Function Is Preserved in Painful Diabetic Peripheral Neuropathy—A Multimodal Magnetic Resonance Imaging Study
Authors: SLOAN GORDON P. , TEH KEVIN , SELVARAJAH DINESH , TESFAYE SOLOMON
Published: June 2023

Aims: Previous neuroimaging studies have demonstrated cerebral structural, functional, and vascular alterations in Painful-Diabetic Peripheral Neuropathy (DPN). We present a multi-modal Magnetic Resonance Imaging (MRI) study to determine the structure, and neuronal and mitochondrial function of the thalamus in Painful-DPN.

Methods: A total of 49 participants were enrolled, 38 with type 2 diabetes (9 without DPN [No-DPN]; 11 with Painless-DPN; and 18 with Painful-DPN) and 11 healthy volunteers (HV). Participants underwent detailed clinical and neurophysiological assessments, and multi-modal MR imaging of the thalami bilaterally including: Proton-Magnetic Spectroscopy (1H-MRS); 31-Phosphorus MRS (31P-MRS); and brain morphometric analysis. We calculated the N-acetyl aspartate to choline (NAA:Cho), a measure of neuronal function, and inorganic phosphate (Pi) to ATP (Pi:ATP), a measure of mitochondrial function.

Results: There were no significant differences in thalamic volume between groups (ANOVA, p=0.927). There was a significant group effect in both metabolite ratios: NAA:Cho (ANOVA, p=0.013); Pi:ATP (p=0.021). The NAA:Cho was numerically the lowest in Painless-DPN, reaching significance compared with HV (p=0.001) and Painful-DPN (p=0.019). Additionally, the Pi:ATP was significantly higher in Painless-DPN compared with HV (p=0.013) and Painful-DPN (p=0.008). There was also a significant correlation between the NAA:Cho and Pi:PCr (Pearson’s r -0.336, p=0.034).

Conclusion: This is the first study to determine perform cerebral 1H- and 31P-MRS in human DPN. We have demonstrated altered 1H- and 31P-MRS ratios in Painless- but not Painful-DPN, suggesting that mitochondrial dysfunction may underlie thalamic neuronal dysfunction in Painless-DPN. Conversely, in Painful-DPN, preservation of thalamic mitochondrial and neuronal function may be involved in the maintenance of neuropathic pain signaling.

Disclosure

G.P.Sloan: None. K.Teh: None. D.Selvarajah: 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.
481-P: 10kHz SCS Restores Mechanical and Thermal Neural Processing in a Rodent Model of Painful Diabetic Neuropathy
Authors: LEE KWAN , LEE DONGCHUL , WANG DONG , KAGAN ZACHARY B. , BRADLEY KERRY
Published: June 2023

A recent randomized controlled trial of 10 kHz spinal cord stimulation (SCS) in patients with painful diabetic neuropathy (PDN) has demonstrated significant and durable improvements in neurologic status, particularly sensory restoration of the foot (Petersen et al 2021, Argoff et al 2023). In order to gain further mechanistic insight into the improvements in sensory processing by 10kHz SCS, we analyzed the receptive field (RF) size and responses of spinal dorsal horn (DH) neurons to mechanical and thermal stimuli of the paw in a PDN rat model. For PDN-model, Rats were given a single effective dose of streptozotocin (STZ), while Naïve animals were injected with 0.9% saline. Four groups were studied: Naïve, STZ, STZ+ShamSCS, and STZ+10kHzSCS. Rats were anesthetized with urethane and a laminectomy was performed for DH neurons recording. We analyzed RF size and the response of DH neurons to vibrotactile stimulation and thermal sensation. Both the Naïve and STZ+10kHzSCS groups had significantly smaller RFs than the STZ Control and STZ+ShamSCS groups. In response to a 1 Hz vibration frequency, Naïve and STZ+10kHzSCS groups had higher peak power spectral density (PSD) of DH firing than STZ+ShamSCS, and PSD for the STZ+10kHzSCS group was statistically higher than for the STZ Control group. Response of DH neurons showed no significant differences between groups during the thermal stimulation, but the post-stimulus firing rates for the STZ+10kHzSCS group were significantly higher compared to STZ Control and STZ+ShamSCS. These data suggest that 10 kHz SCS amplified the DH response to large fiber (vibration) and small fiber (warm) signals and normalized the receptive field of the paw (acuity) in PDN rats. In diabetes, where peripheral sensory compromise from chronic hyperglycemia can lead to loss of protective sensation, such ‘tuned amplification’ as provided by 10 kHz SCS in the central nervous system may compensate for the reduced functionality seen in the peripheral sensory systems.

Disclosure

K.Lee: Employee; Nevro Corp. D.Lee: Employee; Nevro Corp. D.Wang: Employee; Nevro Corp. Z.B.Kagan: Employee; Nevro Corp. K.Bradley: Employee; Nevro Corp.
482-P: Behavioral Assessment of 10kHz Spinal Cord Stimulation–Mediated Pain Relief in a Rat Model of Painful Diabetic Neuropathy
Authors: WANG DONG , LEE DONGCHUL , LEE KWAN , KAGAN ZACHARY B. , BRADLEY KERRY
Published: June 2023

Painful diabetic neuropathy (PDN) is a serious complication of diabetes and occurs in approximately 20% of diabetic patients. In a recent RCT, 10kHz spinal cord stimulation (10kHz SCS) was shown to be a promising therapy for PDN, in both pain reduction and possible neurological improvements (Petersen et al 2021). In this study, we aimed to observe the behavioral effects of 10kHz SCS on PDN using streptozotocin (STZ)-induced diabetic rats.

We established four testing groups: Naïve controls, STZ controls, STZ+Sham SCS, and STZ+10kHz SCS. A single effective dose (60 mg/kg) of the cytotoxic agent STZ caused the rats to become hyperglycemic within 72 hours and lasted for several weeks. These STZ-injected rats also showed a significant and continuous reduction in body weight in comparison to Naïve control rats. Using the von Frey test for mechanical allodynia, we observed that 14 days of 24h/day low-intensity (30% of motor threshold) 10kHz SCS significantly elevated the mechanical pain withdrawal thresholds compared to STZ controls or STZ+Sham SCS animals, reaching statistical equivalence to Naïve controls. In a thermal preference assay, all animals exhibited a training effect towards less activity and more preference to the room temperature side vs the non-painful heat side of a two-temperature chamber over the several-week protocol. We found that STZ-injected animals demonstrated significantly less exploration activity in the 10min testing periods compared to Naïve controls but neither the thermal preference nor the total distance they traveled were restored after 14 days of 10kHz SCS.

Our results demonstrate that 10 kHz SCS resulted in behavioral outcomes reflective of the mechanical pain reduction in the PDN rodent model. These findings provide supporting evidence for the recent RCT data and underscore the conclusion that 10kHz SCS can effectively treat patients with refractory PDN.

Disclosure

D.Wang: Employee; Nevro Corp. D.Lee: Employee; Nevro Corp. K.Lee: Employee; Nevro Corp. Z.B.Kagan: Employee; Nevro Corp. K.Bradley: Employee; Nevro Corp.
487-P: Cardiovascular Autonomic Function in Long COVID-19 Individuals With and Without Diabetes
Authors: FLEISCHER JESPER , GUNARATNAM SEJAL V.G. , HUANG YIYUAN , ANG LYNN , CHARLES MORTEN , KATONA AIMEE , BAKER NICOLE , MIZOKAMI-STOUT KARA R. , KUEI LIN YU , VASBINDER ALEXI , HAYEK SALIM , BUSUI RODICA
Published: June 2023

Coronavirus disease 2019 (COVID-19) has been associated with a broad spectrum of long-term complications. These include the development and progression of severe autonomic dysfunction, particularly among people with diabetes. We evaluated cardiovascular autonomic (CAN) function in a cross-sectional study in 47 adults with long COVID-19 with (N=21, mean age 61 years, 43% women, mean A1c 6.2%) and without type 2 diabetes mellitus (T2DM) (N=26, mean age 58 years, 65% women) and compared them with T2DM without COVID-19 (N=45, mean age 57 years, 42% women, mean A1c 7.8%). CAN was assessed with cardiovascular autonomic reflex tests (30:15 ratio, E.I ratio, Valsalva ratio) and indices of heart rate variability (SDNN, RMSSD). We used pairwise comparison and Analysis of Covariance (ANCOVA) both adjusted for age, gender, race, and BMI to compare the groups. In a pairwise comparison higher heart rate (HR) and lower CAN measures (SDNN, RMSSD, Valsalva) were found in T2DM with COVID-19 compared to T2DM without COVID-19. Lower HR and lower Valsalva were found in COVID-19 individuals without T2DM compared to T2DM without COVID-19. When comparing the three groups, lower Valsalva were found in COVID-19 individuals with and without T2DM compared to T2DM without COVID-19 (Figure). These data suggest that COVID-19 exacerbates CAN in patients with T2DM and impacts CAN in people without T2DM at a magnitude similar to that of T2DM patients.

Disclosure

J.Fleischer: None. A.Vasbinder: None. S.Hayek: None. R.Busui: Board Member; American Diabetes Association, Consultant; Averitas Pharma, Inc., Lexicon Pharmaceuticals, Inc., Nevro Corp., Novo Nordisk, Roche Diagnostics, Procter & Gamble, Research Support; Novo Nordisk, Medtronic, National Institutes of Health. S.V.G.Gunaratnam: None. Y.Huang: None. L.Ang: None. M.Charles: Research Support; Novo Nordisk Foundation, Speaker's Bureau; Novo Nordisk A/S, Boehringer-Ingelheim. A.Katona: None. N.Baker: None. K.R.Mizokami-stout: None. Y.Lin: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (U01DK119083, P30DK020572); Steno North American Fellowships 2021; Novo Nordisk Foundation (21OC0072180)
496-P: Diabetic Retinopathy in Youth with Type 2 Diabetes—Data from Three Academic Health Centers
Authors: CHANNA ROOMASA , SHAH AMY S. , SHAH VEERAL S. , BAHRAINIAN MOZHDEH , BROWN ELIZABETH A. , ALVIN LIU T.Y. , MAGELLA BLISS , LEHMANN HAROLD , ABRÀMOFF MICHAEL D. , WOLF RISA M.
Published: June 2023

Diabetic retinopathy (DR) is a microvascular complication of type 2 diabetes (T2D) and a major cause of vision loss worldwide. The TODAY study reported a DR prevalence of 51% among patients with youth onset T2D (average T2D duration 13.3 years, mean age of 26.4 years). Prevalence rates of DR in youth-onset T2D with shorter duration and younger age is unclear.

In a multicenter analysis, eye exams or retinal images from patients with youth-onset T2D at Cincinnati Children’s, Johns Hopkins, and University of Wisconsin were assessed for presence of DR using t-tests and fisher’s exact test.

The study included 228 youth (mean age 16.5±3.5years, mean T2D duration 3.0±2.6 years). Seven participants (3%) were positive for DR. Compared to youth negative for DR (n=221), those with DR (n=7) had a longer duration of diabetes (5.3±3.1 v. 2.9±2.6years, p=0.015) and higher hemoglobin A1c at the time of the diabetic eye exam (10.0±2.1 v. 7.5±2.6%, p=0.012). There were no differences in age, race/ethnicity, sex, or types of medication prescribed between those with and without DR. Of those with DED, when compared to all other ethnicities, NH Black youth had a higher rate of positive diabetic eye exams (p=0.04).

Our study found a lower prevalence of DR in youth with T2D at younger age and shorter duration of diabetes. Further work is needed to determine the inflection point when the incidence of DR increases.

Disclosure

R.Channa: None. R.M.Wolf: Research Support; Dexcom, Inc., Boehringer Ingelheim Inc. A.S.Shah: None. V.S.Shah: None. M.Bahrainian: None. E.A.Brown: None. T.Liu: None. B.Magella: None. H.Lehmann: None. M.D.Abràmoff: Board Member; Digital Diagnostics, Consultant; AbbVie Inc., NovaGo Therapeutics AG, Other Relationship; Digital Diagnostics, Stock/Shareholder; Digital Diagnostics.

Funding

National Eye Institute (R01EY033233, 5K23EY030911-03)
501-P: Differences in Disease Severity and Treatment for Diabetes-Related Retinopathy between Type 1 and 2 Diabetes Mellitus
Authors: BREEN JAMES M. , COOPER AMELIA , STEVENS HENRY , COOPER BLAKE A.
Published: June 2023

Background: Diabetes-related retinopathy (DR) is a neurovascular complication of both type 1 (T1D) and type 2 (T2D) diabetes, the prevalence of which strongly correlates to both the duration of diabetes and blood glucose levels. DR severity level has been reported to be worse in patients with T1D than in T2D but few studies have reported on treatment outcomes.

Objective: To determine differences in the level of DR, central subfoveal thickness (CST), and treatment outcomes for those with T1D and T2D.

Methods: A retrospective chart review.

Covariates: age, sex, type of DM, last A1c, level of retinopathy, and visual acuity.

Primary Outcome: Level of DR. Secondary Outcomes: CST, IVI use, and frequency for DME. ICD-10 codes identified 10,026 patients with diabetes who were seen in 2021 at Retina Associates in Kansas City. Retrospectively screened 1,000 consecutive patient medical records from this cohort and excluded those with incomplete records and those who had a second diagnosis that could cause macular edema.

Results: Characteristics of 321 patients with DR and treatment needs are described in the table below and used for analysis. Conclusions: Comparing those with T1D and T2D we found a statistical difference in those with T1D being younger, having less HTN, and higher levels of DR. Despite these findings there was no difference in visual acuity and need or frequency of intravitreal injections.

Disclosure

J.M.Breen: None. A.Cooper: None. H.Stevens: None. B.A.Cooper: Advisory Panel; Genentech, Inc., Speaker's Bureau; Regeneron, Optomed.
503-P: Distinct Effects of a Novel GCK-MODY Mutation on Lipid Profiles and Diabetic Complications
Authors: HUANG YADI , FAN YUXIN , LI XIN , JI SHUHUI , CHEN SHANSHAN , CUI JINGQIU , FENG WENLI , SHU HUA , LIU MING
Published: June 2023

Glucokinase (GK) encoded by glucokinase gene (GCK) is the first rate-limiting enzyme in glucose metabolism. The heterozygous inactivating mutations of GCK cause maturity-onset diabetes of the young (GCK-MODY). Unlike other types of diabetes, GCK-MODY is not associated with increased risks of diabetic complications in young patients. However, the long-term effects of mutant GK on lipid profiles and chronic complications in elder patients remain unknown. Herein, we established a knock-in mouse model heterozygeously expressing a novel GCK mutation encoding GK-Q26L that was identified in a Chinese family with early onset diabetes. GK-Q26L mice developed mild early onset diabetes with moderate elevated blood glucose and decreased serum insulin, confirming diabetogenes of GK-Q26L. To determine age- and diet-related diabetic complications and lipid profiles, we have fed the mice with either chow diet or high-fat diet (HFD) for 28, 40, or 60 weeks. We found that, after 28 week of HFD, GK-Q26L alleviated abnormal lipid profiles in plasma and liver, suggesting beneficial effects of GK-Q26L on lipid metabolism. Surprisingly however, those protective effects were disappeared at 40 weeks, and at 60 weeks of HFD, GK-Q26L mice exhibited even more severe abnormal lipid profiles. Consistent with the distinct trends of lipid profiles, HFD-induced kidney injury (increased urinary albumin/creatinine ratio and renal fibrosis) was also alleviated in GK-Q26L mice at 28 weeks of HFD, but aggravated at 60 weeks of HFD. Similar effects on diabetic retinopathy were observed in GK-Q26L mice. These data reveal for the first time that although inactivating GCK mutations have beneficial effects on HFD-induced abnormal lipid metabolism and diabetes related damages of kidney and retina in short-term, it is strongly associated with long-term diabetic nephropathy and retinopathy. This study suggests that more attention should be paid on the long-term chronic complications in elder patients with GCK-MODY.

Disclosure

Y.Huang: None. Y.Fan: None. X.Li: None. S.Ji: None. S.Chen: None. J.Cui: None. W.Feng: None. H.Shu: None. M.Liu: None.

Funding

National Natural Science Foundation of China (81830025, 82220108014, 82100865, 81800733, 81900720, 82000796, 82070854); National Key R&D Program of China (2019YFA0802502, 2022YFE0131400); Tianjin Key Medical Discipline Construction Project (TJYXZDXK-030A)