bluuebunny/crossref_metadata_2025 huggingface dataset:
257-OR: Pen-Administered Low-Dose Dasiglucagon vs. Usual Care for Prevention and Treatment of Nonsevere Hypoglycemia in People with Type 1 Diabetes during Free-Living Conditions: A Phase 2, Randomized, Two-Period, Crossover Outpatient Study
Authors: LAUGESEN CHRISTIAN , RANJAN AJENTHEN G. , SCHMIDT SIGNE , NØRGAARD KIRSTEN
Published: May 2022

Objective: To evaluate the efficacy, safety and feasibility of pen-administered low-dose dasiglucagon for prevention and treatment of non-severe hypoglycemia in people with type 1 diabetes during free-living conditions.

Methods: Twenty-four adults with insulin pump-treated type 1 diabetes completed a phase 2, randomized, open-label, 2-period cross-over study with 2-week periods. During the usual care (UC) and dasiglucagon (DASI) period, participants managed impending and manifest episodes of hypoglycemia with regular carbohydrate consumption or pen-administered low-dose (80 µg) s.c. dasiglucagon, respectively. Glycemic control was evaluated using continuous glucose monitoring (Dexcom G6) and event-registration of prevention and treatment episodes. Patient-reported outcomes (PRO) were collected following study completion.

Results: Participants administered dasiglucagon (IQR: 7-15) times during the 2-week period. Compared with UC, the mean difference (±SEM) in time in range (70-180 mg/dL) was 2.4%-point (±1.5%) (UC: 61.5%, DASI: 63.9%, p=0.129) , difference in time below range (<70 mg/dL) was 0.5%-point (±0.4%) (UC: 3.1%, DASI: 2.6%, p=0.170) , while total daily carbohydrate intake was significantly reduced (UC: 192 g, DASI: 172 g, p=0.007) . Dasiglucagon use was safe and well tolerated with nausea being the most frequent adverse effect (no. of participants: UC: 4, DASI: 8, p=0.206) . PRO demonstrated that 96% (p<0.001) of participants were likely to include dasiglucagon as part of their future routine management of hypoglycemia.

Conclusion: Utilization of pen-administered, low-dose dasiglucagon for prevention and treatment of non-severe hypoglycemia during free-living conditions was safe and efficacious while significantly reducing the total daily carbohydrate intake and yielding high treatment satisfaction.

Disclosure

C.Laugesen: None. A.G.Ranjan: None. S.Schmidt: None. K.Nørgaard: Advisory Panel; Medtronic, Novo Nordisk A/S, Consultant; Novo Nordisk A/S, Research Support; Dexcom, Inc., Medtronic, Novo Nordisk A/S, Zealand Pharma A/S, Speaker's Bureau; Medtronic, Stock/Shareholder; Novo Nordisk A/S.

Funding

SteDiabetes Center Copenhagen is the sponsor of this investigator-initiated trial. Zealand Pharma provided financial support to the conduct of the study and supplied the study medication.
260-OR: iGlarLixi vs. Basal plus Rapid-Acting Insulin in Adults with Type 2 Diabetes Advancing from Basal Insulin Therapy: The SoliSimplify Real-World Study
Authors: MCCRIMMON RORY J. , CHENG ALICE Y. , GALSTYAN GAGIK R. , DJABALLAH KHIER , LI XUAN , COUDERT MATHIEU , FRIAS JUAN PABLO
Published: May 2022

Introduction: Indirect evidence suggests iGlarLixi is as efficacious as basal insulin (BI) + rapid acting insulin (RAI) for management of type 2 diabetes (T2D) . However, there are no direct comparisons of iGlarLixi (once-daily [QD]) vs. a BI+RAI regimen (multiple daily injections [MDI]) . SoliSimplify compared these treatments using real-world data from a US database.

Methods: Electronic medical records were analyzed retrospectively using propensity score matching (PSM) to compare therapy advancement with iGlarLixi or BI+RAI in adults ≥18 years with T2D on BI and ≥1 HbA1c available value at baseline and 6-month follow-up. The primary objective was non-inferiority of iGlarLixi to BI+RAI in HbA1c change from baseline to 6 months (margin 0.3 %) .

Results: PSM generated cohorts with balanced baseline characteristics (N=814 in each group; Table) . HbA1c reduction from baseline to 6 months with iGlarLixi was non-inferior to BI+RAI (p<0.025) . Weight gain was significantly lower with iGlarLixi than with BI+RAI (p<0.for the difference) . At 6 months, achievement of HbA1c <7 % without hypoglycemia and weight gain was similar between groups. Hypoglycemia was low in both groups, likely due to underreporting.

Conclusions: In this real-world study, QD iGlarLixi was as effective as MDI BI+RAI in HbA1c reduction and had a favorable body weight benefit.

Disclosure

R.J.Mccrimmon: Advisory Panel; Novo Nordisk, Sanofi, Research Support; Diabetes UK, European Union, MedImmune. A.Y.Cheng: Advisory Panel; Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, HLS Theraoeutics, Insulet Corporation, Janssen Pharmaceuticals, Inc., Medtronic, Novo Nordisk, Sanofi, Board Member; Type 1 Diabetes Think Tank Network, Other Relationship; Diabetes Canada, Speaker's Bureau; Bausch Health, Canada, Merck & Co., Inc. G.R.Galstyan: n/a. K.Djaballah: Employee; Sanofi. X.Li: Employee; Eisai Co., Ltd., Sanofi. M.Coudert: Employee; Sanofi. J.Frias: Advisory Panel; Altimmune, Becton, Dickinson and Company, Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi, Consultant; 89bio, Inc., Akero Therapeutics, Inc., Altimmune, Becton, Dickinson and Company, Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Afimmune Limited, Akero Therapeutics, Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Carmot Therapeutics, Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Ionis Pharmaceuticals, Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Speaker's Bureau; Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi.

Funding

Sanofi
262-OR: Recruiting Historically Underrepresented Individuals into Clinical Trials: Key Lessons from Project ECHO Diabetes
Authors: ADDALA ANANTA , ROQUE XANADU , FIGG LAUREN , ANEZ-ZABALA CLAUDIA , CLARK CATHERINE , LAL RAYHAN , HALLER MICHAEL J. , MAAHS DAVID M. , WALKER ASHBY F.
Published: May 2022

Background: Individuals underrecruited in diabetes studies include those not seen by an endocrinologist and those from rural, low socioeconomic, and racial/ethnic minority groups. Project ECHO Diabetes aimed to recruit historically excluded participants with insulin-requiring diabetes.

Objective: The purpose of this descriptive analysis is to outline and evaluate our recruitment efforts at 9 sites affiliated with the University of Florida.

Results: In total, 340 participants with type 1 diabetes and 1225 participants with type 2 diabetes were eligible and approached for recruitment. Local community health centers were funded to recruit for and participate in Project ECHO. Participants were contacted on average 2 times (range 1-13 times) to finalize a consent disposition: Yes, No, or No Response (Table 1) . For those individuals who we categorized as “No Response,” the most common reason was lack of reliable contact information.

Conclusions: Recruiting historically underrepresented populations is feasible with repeated touch points. Funding the partnerships with community health centers, who have the trust of the local community and are equipped to address local needs, was key in our recruitment strategy. Language, a common exclusion criteria and barrier to diverse recruitment, was overcome through multi-lingual study staff.

Disclosure

A.Addala: None. X.Roque: None. L.Figg: None. C.Anez-zabala: None. C.Clark: None. R.Lal: Advisory Panel; Provention Bio, Inc., Consultant; Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Deep Valley Labs, Gluroo, Morgan Stanley, Tidepool. M.J.Haller: Advisory Panel; SAB Biotherapeutics , Consultant; MannKind Corporation, Sanofi. D.M.Maahs: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Consultant; Aditx Therapeutics, Inc., Biospex. A.F.Walker: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
272-OR: Weight Loss with Time-Restricted Feeding or Treatment with Obeticholic Acid/Semaglutide Combination Have a Different Impact on Nonalcoholic Steatohepatitis in Diet-Induced Obese Mice
Authors: BRIAND FRANCOIS , GRASSET ESTELLE , BREYNER NATALIA , SULPICE THIERRY
Published: May 2022

Introduction: Combination of therapies is a promising strategy for the treatment of NASH and liver fibrosis. Here we evaluated whether the Farnesoid X Receptor agonist obeticholic acid (OCA) combined with the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (SEMA) would show superior effects than weight loss induction with time-restricted feeding (TRF) in mice.

Methods: Mice were fed a 60% high fat/2% cholesterol diet with 10% fructose supplemented drinking water (HFCF diet) for 25 weeks to induce obesity and NASH/liver fibrosis. After the diet-induction period, mice were kept on HFCF diet and treated with vehicle (control) or OCA 30mg/kg p.o. QD + SEMA 0.06mg/kg s.c. QD, or placed on TRF from the last 3 hours of the dark cycle till the end of the light cycle, without access to food, but free access to normal drinking water (i.e. without fructose) every day, for 6 weeks.

Results: OCA+SEMA induced a 20% lower caloric intake, which led to a 27% lower body weight (p<0.0vs. control) . TRF had a weaker effect on caloric intake (-9%) but also reduced body weight (-11%, p<0.vs. control) . Both OCA+SEMA and TRF reduced the HOMA-IR index of insulin resistance and significantly reduced plasma ALT and AST levels, but these effects were more pronounced with OCA+SEMA. TRF, and to a greater extent OCA+SEMA, significantly reduced liver weight, hepatic fatty acids, triglycerides, and total cholesterol levels. Both OCA+SEMA and TRF led to significantly lower NAFLD activity score. However, OCA+SEMA did not alter liver fibrosis, while TRF showed a clear anti-fibrotic effect in the liver, with lower % Sirius Red labelling (p<0.vs. control) .

Conclusion: OCA+SEMA combination reduced body weight and NAFLD activity score but did not improve hepatic fibrosis, while TRF improved both NASH and liver fibrosis. These TRF benefits should be further investigated in obese NASH patients.

Disclosure

F.Briand: None. E.Grasset: None. N.Breyner: None. T.Sulpice: None.
28-OR: Effects of Time-Restricted Eating vs. Low-Carbohydrate Diet on Mean Glucose in Type 2 Diabetes Patients
Authors: CARBONEL ALEXANDER , VELIS ESTEPHANY , CALINAWAN TESS L. , KIWAN RASHA , SMITH CAITLIN , SVID CHANNEL , SHUBROOK JAY H.
Published: May 2022

Background: Time restricted eating (TRE) and Low Carbohydrate Diets (LCD) have become popular dietary patterns with potential metabolic benefits for T2DM patients. The objective of this study is to evaluate TRE on glucose control compared to LCD for individuals with T2DM after completing a 72 hour medically supervised induction fast.

Methods: Participants completed a 72 hour medically supervised induction fast and were randomized to TRE (n=14, 8-hour daily feeding period) or LCD (n=10, <45 grams total per day) for 4 weeks. Blood glucose was captured by FreeStyle Libre pro continuous glucose monitors (CGM) . GMI at 1 month post fast was compared to A1C values measured within 6 months prior to treatment.

Results: A total of 24 participants completed the protocol (mean age = 53.9, range 35-72) . GMI was reduced from 8.99% to 7.30% (p=0.002) in TRE and 7.99% to 6.77% in LCD (p=0.001) . Reductions in GMI range were greater in the first 2 weeks compared to last 2 weeks. The TRE group spent less time within the target range (67.7% vs. 74.8%, p=0.32) , more time hyperglycemic (29.4% vs. 21.0% p=0.25) , and less time hypoglycemic (2.8% vs. 4.2%, p=0.42) . Hypoglycemia was numerically less common in the TRE group (3/14 participants) compared to the LCD (6/participants) in CGM data beyond the induction fast. Glucose variability was similar in TRE (28.6%) and LCD (28.2%) . There were no SAEs experienced in either group. When surveyed, participants believed TRE and LCD were realistic nutritional therapies.

Conclusion: These results suggest that both TRE and LCD supplemented by a medically supervised induction fast are efficacious and safe nutritional therapies to improve blood glucose in patients with T2DM. The participants will be followed for 12 months to analyze long-term effects.

Disclosure

A.Carbonel: None. E.Velis: None. T.L.Calinawan: None. R.Kiwan: None. C.Smith: None. C.Svid: None. J.H.Shubrook: Consultant; Abbott, AstraZeneca, Bayer AG, Eli Lilly and Company, Novo Nordisk.
297-OR: TXNIP DNA Methylation (DNAme) and Long-Term HbA1c in Type 1 Diabetes (T1D)
Authors: MILLER RACHEL G. , MYCHALECKYJ JOSYF , ONENGUT-GUMUSCU SUNA , ORCHARD TREVOR J. , COSTACOU TINA
Published: May 2022

DNAme is associated with past HbA1c in DCCT/EDIC but these associations were examined when there was separation in HbA1c distribution by trial intervention arm. Thus, we performed an epigenome-wide association study (EWAS) of DNAme and HbA1c in a T1D cohort without intervention or risk factor exclusion to identify loci with DNAme associated with concurrent and future HbA1c over 28 years. Whole blood DNAme was assayed via Illumina EPIC beadchip in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset (<17 years) T1D (n=411; mean age 29, T1D duration 21 yrs) . After quality control DNAme at 683,597 CpGs were analyzed. We performed cross-sectional EWAS with baseline HbA1c in linear models adjusted for T1D duration, sex, smoking pack-years, estimated blood cell composition, and batch covariates and longitudinal repeated measures analyses of HbA1c (2, 4, 6, 8, 16, 23, and 28 yrs post-baseline) . DNAme was significantly inversely associated with current HbA1c at two CpGs: cg19693031 (Chr 1, TXNIP locus, p=9.5x10-11) and cg21534330 (Chr 17, CSNK1D locus, p=3.3x10-10) . In GWAS, we further identified 34 methylation quantitative trait loci (meQTLs) in the SLC2A1 - SLC2A1-AS1 linkage-disequilibrium block (Chr 1: 43408279-43438299) associated with cg19693031 DNAme. All cg19693031 meQTLs identified were also reported as whole blood expression QTLs (eQTLs) in GTEx. For cg21534330, none of 15 trans meQTLs were eQTLs in GTEx. In repeated measures analysis, cg19693031 DNAme was consistently associated with lower average HbA1c over 28 years (-0.26 per 5% DNAme, p<0.0001, no time interaction) . DNAme at cg21534330 was not associated with HbA1c after baseline. Our results replicate prior findings that DNAme at cg19693031 in TXNIP relates to glycemic control in T1D and extend this association prospectively over 28 years. These findings strengthen the potential for interventions targeting TXNIP to improve glycemic control in T1D through its role in SLC2A1/GLUT1-mediated glucose regulation.

Disclosure

R.G.Miller: Stock/Shareholder; Becton, Dickinson and Company. J.Mychaleckyj: None. S.Onengut-gumuscu: None. T.J.Orchard: None. T.Costacou: None.

Funding

American Diabetes Association (1-19-JDF-109) ; NIH/NIDDK (R01-DK034818) , Rossi Memorial Fund
309-OR: Lipocalin 2 Deficiency Impairs Mitochondrial Dynamics and Phospholipid Metabolism in Brown Adipocytes
Authors: SU HONGMING , GUO HONG , QIU XIAOXUE , LIN TE-YUEH , CHEN XIAOLI
Published: May 2022

Impaired mitochondrial bioenergetics in brown adipocytes links to the disrupted energy metabolism and thermogenesis in obesity. Phospholipids, particularly cardiolipin and phosphatidic acid (PA) are critical regulators of mitochondrial membrane architecture and dynamics. Mitochondria-associated endoplasmic reticulum membranes (MAMs) serve as the platform for phospholipid biosynthesis. MAM dysfunction disturbs phospholipid metabolism, thereby disrupting mitochondrial function. However, little is known about the participating factors that regulate MAM phospholipid metabolism. We have previously characterized the role of lipocalin 2 (Lcn2) in thermogenesis and mitochondrial function in adipocytes. Herein, we found that Lcn2 was located at MAMs and had a specific PA binding capability. The mitochondrial fusion-fission process induced by the fasting-refeeding cycle was impaired in Lcn2 knockout (KO) brown adipocytes. We also observed that the levels of phosphorylated Drp1 (Ser616) and Opa1 were decreased in brown adipose tissue (BAT) of Lcn2 KO mice compared to WT controls upon acute cold stimulation, whereas Lcn2 overexpression in BAT led to an increase in Drp1 phosphorylation and Opa1 level. Moreover, Lcn2 deficiency significantly enhanced the cold-stimulated accumulation of Opa1 as well as MAM markers SigmaR1, Ip3R1, and Facl4 at MAMs in BAT, suggesting impaired MAM function. CL316,243, a β3-adrenergic receptor agonist has a cold mimic effect on mitochondrial bioenergetics. In brown adipocytes, Lcn2 deficiency significantly attenuated the CL316,243 induction of Drp1 phosphorylation. Intriguingly, lipidomic analysis of BAT mitochondria isolated from mice treated with CL316,243 for 14 days showed that Lcn2 deficiency blunted CL316,243-induced cardiolipin biosynthesis and altered phospholipid metabolism. Together, we discovered a role of Lcn2 as a novel PA transfer protein in mitochondrial bioenergetics via regulating phospholipid metabolism.

Disclosure

H.Su: None. H.Guo: None. X.Qiu: None. T.Lin: None. X.Chen: None.

Funding

This work was supported by NIDDK Grant (RDK123042) awarded to Xiaoli Chen.
340-OR: LY3437943 (LY) , a Novel Triple GIP/GLP-1/Glucagon Receptor Agonist, Provides Glucose Lowering and Weight Loss in Patients with T2DM after 12 Weeks of Treatment
Authors: URVA SHWETA , LOH MEI TENG , COSKUN TAMER , DU YU , BENSON CHARLES , LOGHIN CORINA , HAUPT AXEL , MILICEVIC ZVONKO
Published: May 2022

Multi-receptor incretin agonists are being developed for several metabolic disorders. LY is an investigational triple agonist with potent activity on glucose-dependent insulinotropic polypeptide (GIP) , glucagon-like polypeptide-1 (GLP-1) , and glucagon receptors. LY was safely studied in a prior first-in-human study and pharmacokinetics properties supported once weekly dosing. The primary objective of this randomized, double-blind, placebo-controlled, Phase 1 proof-of-concept study was to assess the safety and tolerability of multiple ascending doses of LY in patients with type 2 diabetes (T2D) . Seventy-two patients were randomized (9:3:1) to 5 rising dose cohorts of subcutaneous LY, placebo, and dulaglutide 1.5mg, respectively. Within cohort, dose-escalation was implemented at highest 2 cohorts. Vital signs, laboratory data and adverse events (AEs) were monitored to assess safety and tolerability. Efficacy was assessed by monitoring change in glycated hemoglobin (HbA1c) and body weight at week 12. The most common treatment-emergent AEs were gastrointestinal (nausea and diarrhea) , which were mostly mild in severity. By week 12, mean systolic and diastolic blood pressure decreased from baseline in LY compared to placebo group, while pulse and heart rate increased from baseline within most LY cohorts and dulaglutide, but not with placebo. By week 12, mean HbA1c decreased from baseline in all groups, with higher doses of LY showing statistically significant placebo-adjusted decreases of up to 1.56%. Except at the initial cohort, dose-dependent decreases in mean placebo-adjusted body weight of up to 8.96 kg were observed with LY. LY3437943 exhibits safety and tolerability profile similar to other incretins. Promising glycemic and body weight loss efficacy within this study highlights the potential for LY to provide additional benefit versus existing therapies in treatment of T2D and obesity.

Disclosure

S. Urva: Employee; Eli Lilly and Company. M. Loh: Employee; Eli Lilly and Company. T. Coskun: Employee; Eli Lilly and Company. Y. Du: None. C. Loghin: Employee; Eli Lilly and Company. A. Haupt: Employee; Lilly. Stock/Shareholder; Lilly. Z. Milicevic: Employee; Eli Lilly and Company.

Funding

Eli Lilly and Company
350-OR: The Oral Disposition Index (ODI) Predicts Type 1 Diabetes (T1D) in Autoantibody-Positive (Ab+) Individuals
Authors: ISMAIL HEBA M. , CUTHBERTSON DAVID D. , REDONDO MARIA J. , JACOBSEN LAURA M. , ATKINSON MARK A. , SOSENKO JAY ,   DIABETES PREVENTION TRIAL TYPE 1, TYPE 1 DIABETES TRIALNET
Published: May 2022

The ODI is a measure of β-cell function accounting for insulin sensitivity. ODI has primarily been studied in adults and shown to be inversely predictive of type 2 diabetes (T2D) ; however, little is known about ODI’s prediction of T1D. We thus used data from Ab+ Trialnet Pathway to Prevention (PTP) and Diabetes Prevention Trial Type 1 (DPT-1) cohorts (relatives of T1D patients) to study this. Data were analyzed from 33PTP participants: age (mean±SD) 15.8±12.1 yrs; BMI 21.1±13.1 kg/m2; 50.1% female, and 2from DPT-1: age 14.8±10.0 yrs; BMI 21.8±6.1 kg/m2; 51.2% female. Insulin measures at baseline included insulin sensitivity [ (1/Fasting Insulin) ; 1/FI) ], β-cell function [C-peptide index: (30 min C-pep-0 min C-pep) / (30 min glucose-0 min glucose) ], and ODI [ (1/FI) x (C-peptide Index) ]. Spearman correlations of C-peptide Index vs. 1/FI were r=-0.47 (p<0.001) in PTP, and r=-0.22 (p=0.001) in DPT-1. The figure shows cumulative incidence curves according to ODI quartiles (Q) for progression to T1D in both PTP and DPT-1. The diagnosis of T1D was inversely related to ODI, with Q4 vs. Q1 hazard ratios and 95% CIs of [0.13 (0.10, 0.16) , p=0.006] for PTP and of [0.13 (0.06, 0.29) , p=0.002] for DPT-1.

In conclusion, ODI is inversely predictive of T1D among Ab+ individuals. Thus, as with predicting T2D, insulin sensitivity should be taken into account when β-cell function is used to predict T1D in Ab+ populations.

Disclosure

H.M.Ismail: n/a. D.D.Cuthbertson: None. M.J.Redondo: Advisory Panel; Provention Bio, Inc. L.M.Jacobsen: None. M.A.Atkinson: None. J.Sosenko: None. Diabetes prevention trial type 1: n/a. Type 1 diabetes trialnet: n/a.

Funding

NIH
37-LB: Feasibility of a Remote Clinical Trial in People with Type 2 Diabetes—Findings from the MOTIVATE T2D Trial
Authors: DAVIES ANDREW P. , HESKETH KATIE , LOW JONATHAN , SPRUNG VICTORIA S. , JONES HELEN , MCMANUS ALI M. , COCKS MATTHEW ,   MOTIVATE TEAM
Published: May 2022

The execution of clinical trials can be expensive and present logistical challenges regarding recruitment and retention of participants. Innovative research design fostering convenience by eliminating research facility visits may enhance recruitment and retention. We examined the feasibility of a remote clinical trial in people living with type 2 diabetes (T2D) . People with recently diagnosed T2D were recruited across the UK and Canada to the MOTIVATE T2D trial (NCT04653532) ; a feasibility randomised controlled trial investigating two exercise and physical activity interventions. Participants received a self-testing kit, via mail, at baseline and post-intervention (6 months) . Measures included, HbA1c, lipid profile, anthropometrics and blood pressure and 14-day flash glucose and physical activity monitoring. Between Jan 2021 and Jan 2022 286 patients were eligible, of whom 110 (UK n=63, Can n=47, male n=58, white n=95) consented. Mean journey time from research facilities was ≤1h in 18%, 1-2h in 50% and >2h in 33% of participants. Availability of outcome data is presented in Table 1. Remote testing resulted in benefits to recruitment and good participant retention and protocol adherence. As such, remote clinical trials are feasible in people with T2D and future clinical trials should consider a remote clinical trial based approach as an alternative to conventional designs.

Disclosure

A. P. Davies: None. K. Hesketh: None. J. Low: None. V. S. Sprung: None. H. Jones: None. A. M. Mcmanus: None. M. Cocks: None. Motivate team: n/a.

Funding

UK Medical Research Council (MR/T032189/1) , Canadian Institute for Health Research (UCD-170587)
372-P: Predicting Real-World Severe Hypoglycemia in Americans with Diabetes (iNPHORM)
Authors: RATZKI-LEEWING ALEXANDRIA , HARRIS STEWART B. , BLACK JASON E. , ZOU GUANGYONG , WEBSTER-BOGAERT SUSAN , RYAN BRIDGET L.
Published: May 2022

Most prediction models for diabetes-related iatrogenic severe hypoglycemia (SH) have derived from trial/administrative records subject to poor generalizability, ascertainment bias, and incomplete data capture. Redressing this gap, iNPHORM leveraged the clinical and methodological advantages of prospective self-report to develop and internally validate a 1-year SH prediction model for use in real-world clinical contexts.

Adults (18-90 years old) with insulin- and/or secretagogue-treated type 1 or 2 diabetes (T1D, T2D) were recruited from a US-wide probability-based internet panel and followed for one year. Monthly emailed questionnaires assessed SH incidence and related factors. To model recurrent 1-year SH (daytime + nocturnal) , Andersen-Gill Cox proportional hazards regression was performed on participants completing ≥1 follow-up. Missing data were multiply imputed with chained equations. Machine learning penalized regression with lasso was used to select clinically plausible predictors.

A total of 986 (T1D: 17%) participants were analyzed (retention rate: 86.2%) . The mean age was 51 (SD: 14.3) years, 49.6% were male, and the median duration of T1D/T2D was 12 (IQR: 14) years. Among T2D participants, 38% were on insulin (without secretagogues) , 38% on secretagogues (without insulin) , and 24% on insulin plus secretagogues. Across follow-up, 35.1% (95% CI: 32.2-38.1%) reported ≥1 SH, and the annual rate was 4.97 (95% CI: 4.13-5.99) . Combination insulin-secretagogue therapy; use of an insulin pump and continuous glucose monitoring; decreased age; increased previous SH requiring healthcare utilization; chronic kidney disease; and food insecurity predicted 1-year SH risk. The optimism adjusted c-statistic was 0.75.

iNPHORM is the first long-term, prospective study on SH prediction in the general US population with T1D and T2D. Our 7-variable model can be used to identify patients at high-risk of SH, leading to more valid, cost-effective prevention strategies in the real world.

Disclosure

A.Ratzki-leewing: Consultant; Eli Lilly and Company, Other Relationship; Sanofi. S.B.Harris: Consultant; Abbott, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Other Relationship; Abbott, AstraZeneca, Bayer Inc., Dexcom, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Applied Therapeutics Inc., AstraZeneca, Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF) , Novo Nordisk, Sanofi, The Lawson Foundation. J.E.Black: None. G.Zou: None. S.Webster-bogaert: None. B.L.Ryan: None.

Funding

Sanofi Global
397-P: eGFR Changes from Adolescence into Young Adulthood in Type 1 Diabetes: Evaluation of Novel eGFR Formulae
Authors: BABALOLA FUNMBI , SOCHETT ETIENNE B. , CURTIS JACQUELINE , MOINEDDIN RAHIM , ELIA YESMINO T. , SCHOLEY JAMES W. , CHERNEY DAVID , WHITE CHRISTINE A. , MAHMUD FARID H.
Published: May 2022

Background: Diabetic kidney disease (DKD) is one of the leading causes of CKD and ESRD. Decline in eGFR represents an early marker of DKD that may precede microalbuminuria. The optimal eGFR formula during transition from adolescence into adulthood remains unclear.

Objective: To assess longitudinal change in eGFR in youth with T1D transitioning to young adulthood using CKiDU25 creatinine-sex-adjusted (CKiDU25-1) , CKiDU25 combined-creatinine-cystatin (CKiDU25-2) , and CKDEPI40 eGFR formulas.

Methods: eGFR was calculated at four time points. Subsequently, linear mixed effect model was used to calculate subject specific eGFR slopes. The percentage of decliners, defined as eGFR slope </= -3ml/min/1.73m2/year, corresponding to larger eGFR decline was determined. Relationships between eGFR slope and average A1C, ACR, sex, and diabetes duration was assessed using linear regression.

Results: There were 99 participants, of which 45% were male, assessed over an average of 7.4 ± 1 years, beginning at 14 ±1.7 to 21.3 ± 2.1 years. Mean eGFR for CKiDU25-1 was 108.1 ± 13.1, slope of -2.9 ± 2.9, and 44% decliners. Mean eGFR for CKiDU25-2 was 104.8 ± 11.9, slope of -2.7 ± 2.2 and 42% decliners. Mean eGFR for CKDEPI40 was 114.8 ± 6.9, slope of 0.8 ± 0.9 and no eGFR decliners. Comparison of all three eGFRs and slopes showed no significant difference between CKiD-1 and CKiD-2, however there was significant differences between CKDEPI40 and both CKiDU25 eGFR and slopes. There was a significant relationship between sex and eGFR slope with males having greater decline in eGFR with all formulae. No significant relationship was found between eGFR slope and ACR, A1C and diabetes duration.

Conclusion: CKiDU25-1 and CKiDU25-2 formulae provide similar eGFRs and eGFR slopes while the CKDEPI40 had a higher mean eGFR and no change in eGFR over time. If cystatin-C is not available, CKiDU25-1 provides a suitable alternative for assessment of eGFR changes in youth with type 1 diabetes transitioning into early adulthood.

Disclosure

F.Babalola: None. E.B.Sochett: None. J.Curtis: None. R.Moineddin: None. Y.T.Elia: None. J.W.Scholey: n/a. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. C.A.White: None. F.H.Mahmud: None.
416-P: Mortality, Major Adverse Cardiovascular Events (MACE) and Diabetic Complications in Men with Hypogonadism and Type 2 Diabetes on Long-Term Testosterone Treatment: An Update from a Urological Registry Study
Authors: HAIDER KARIM S. , HAIDER AHMAD , SAAD FARID
Published: May 2022

Background: Men with hypogonadism are at increased risk of MACE and mortality. Studies in men with T2DM show that testosterone therapy reduces both MACE and mortality.

Methods: In a registry of 883 men with hypogonadism, 370 men (41.9%) have T2DM. 190 received TU 1000 mg/12 weeks (T-group) , 180 opted against treatment (CTRL) . All patients received standard diabetes treatment including lifestyle courses at a diabetes center. MACE, mortality, and diabetic complications were recorded and compared between groups.

Results: Mean baseline age in the T-group and CTRL was 61.0±5.3 and 63.0±4.9 years. Mean follow-up in T-group and CTRL was 9.0 and 9.7 years. 71 patients (37.4%) in the T-group and 74 (41.1%) in CTRL had a history of cardiovascular disease (myocardial infarction MI, stroke, or coronary artery disease diagnosis) (p<0.05) . Baseline smoking prevalence was 41.6% (79 men) in the T-group and 37.4% (67 men) in CTRL (p=0.415) . The T-group had a worse baseline risk factor profile than CTRL: BMI (36.5±4.4 vs. 32.8±4.7 kg/m²) , systolic blood pressure (163.0±13.3 vs. 145.5±14.5 mmHg) , LDL (4.7±0.8 vs. 4.1±1.4 mmol/L) , HbA1c 9.5±1.4 vs. 7.8±0.7% (p<0.00for all) . Mortality: during the entire observation period, 21 patients (11.1%) died in the T-group vs. 62 (34.4%) in CTRL (p<0.0001) . Major adverse cardiovascular events (MACE) : in the T-group, there were no cases of MI or stroke. In CTRL, there were 62 cases of MI (34.4%) and 51 cases of stroke (28.3%) . Diabetic complications: in the T-group and CTRL, the incidence of retinopathy was 4 (2.1%) vs. 30 (16.7%) (p<0.0001) , nephropathy 1 (0.01%) vs. 7 (0.4%) (p=0.05) , polyneuropathy (5.3%) vs. 97 (53.9%) (p<0.0001) , diabetic foot syndrome 0 (0%) vs. 17 (9.4%) (p<0.0001) .

Conclusions: Long-term treatment with TU in men with hypogonadism and T2DM reduces mortality, MACE, and diabetic complications, compared to untreated controls.

Disclosure

K.S.Haider: Other Relationship; Bayer AG. A.Haider: Other Relationship; Bayer AG. F.Saad: Consultant; Bayer AG, Stock/Shareholder; AbbVie Inc., Bayer AG, GlaxoSmithKline plc.

Funding

Bayer AG
440-P: Suboptimal Blood Pressure in Adolescents and Young Adults with Type 1 Diabetes: Data from the Australasian Diabetes Data Network (ADDN) Registry
Authors: JAMES STEVEN , PERRY LIN , LOWE JULIA , COLMAN PETER G. , CRAIG MARIA E. ,   ADDN STUDY GROUP
Published: May 2022

Hypertension increases complication risk in type 1 diabetes (T1D) . We examined blood pressure (BP) in young people with T1D from ADDN, a prospective clinical diabetes registry in Australia and New Zealand. Inclusion criteria: T1D (duration ≥1 year) and age 16-25 years at last visit (2011-2020) . Hypertension was defined as (on ≥3 occasions) systolic BP (SBP) and/or diastolic BP (DBP) >95th percentile for age <18 years, and SBP >130 and/or DBP >80 mmHg for age ≥18 years. Data from 6,338 young people (male 52.6%) attending 24 participating centres across 36,655 T1D healthcare visits were included; 2,812 (44.4%) had BP measured at last visit (Table 1) . Across all visits, 19.4% of youth aged <18 years and 21.7% of those aged ≥18 years met criteria for hypertension. Using multivariable Generalised Estimating Equations that included all visits, BP in the hypertensive range was associated with: male gender (B=0.36; 95% CI 0.01-0.24, p<0.001) , injection vs. pump therapy (B=0.16; 0.05-0.28, p<0.001) , higher HbA1c (B=0.10; 0.12-0.70, p<0.001) and overweight/obesity (B=0.56; 0.45-0.67, p<0.001) . We demonstrate that hypertension is common in young people with T1D, highlighting the importance of monitoring and treating BP in this at-risk population.

Disclosure

S.James: None. L.Perry: None. J.Lowe: None. P.G.Colman: None. M.E.Craig: None. Addn study group: n/a.
461-P: Prevalence and Patient Recognition of Distal Symmetric Neuropathy (DSP) in a Predominantly Low-Income U.S. Patient Population
Authors: GAGNE ALEXANNDRA , MARCUS HUDA , DAWOOD THAIR , BACHUWA GHASSAN , KVALSUND MICHELLE , FELDMAN EVA L. , SKOLARUS LESLI , CALLAGHAN BRIAN C. , ELAFROS MELISSA
Published: May 2022

Introduction: DSP is a disabling, painful condition among individuals with glucose intolerance. Patient awareness of DSP is essential to reduce the risk of infection and amputation. While DSP risk factors, such as glucose intolerance, are more common among Black people and those with low-income, these populations are underrepresented in DSP studies. The Flint Neuropathy Study is assessing glucose intolerance and DSP in a predominantly Black, low-income setting.

Methods: Patients >40 years presenting to the Hurley Medical Center Outpatient Internal Medicine Residency Clinic in Flint, Michigan were enrolled. Demographics, clinical characteristics including medication use, anthropomorphic measurements, fasting lipids, fasting glucose, and Hemoglobin A1C were obtained. Glucose intolerance was defined using the 2021 ADA diagnosis and classification of diabetes mellitus criteria. DSP was defined using the Michigan Neuropathy Screening Instrument Questionnaire Index (MNSIQI) . Descriptive statistics were assessed using means and frequencies.

Results: 81 participants (62% female, 57.5yrs (SD 8.7) . 67% Black, 53% Medicaid, 22% <high school education) have enrolled. 40 (49%) had a history of glucose intolerance, 4 (5%) denied a history of glucose intolerance despite a prior diagnosis, and 7 (9%) were diagnosed as glucose intolerant through study labs. (23%) reported a history of neuropathy. Mean MNSIQI score was 2.65 (SD 1.56) ; 46 (57%) had DSP. 28 (55%) participants with glucose intolerance had DSP. Among participants with a history of glucose intolerance and DSP, 16/21 (76%) were unaware they had DSP. 7/ (64%) participants who did not know they had glucose intolerance prior to participation had DSP.

Conclusions: DSP is extremely common and underrecognized in this patient population with low incomes. Improving awareness of glucose intolerance and DSP is imperative to ensure appropriate foot care and reduce the risk of amputation.

Disclosure

A.Gagne: None. H.Marcus: None. T.Dawood: None. G.Bachuwa: None. M.Kvalsund: None. E.L.Feldman: None. L.Skolarus: None. B.C.Callaghan: None. M.Elafros: None.

Funding

NIH NINDS (5R25NS089450) ; NIH NCATS (UL1TR002240) ; NIH NIDDK (P30-DK-02926) ; NIH NIDDK (P30-DK089503)
470-P: Mitochondrial Long Noncoding RNA and the Compromised Electron Transport Chain Machinery in Diabetic Retinopathy
Authors: KOWLURU RENU , MOHAMMAD GHULAM , KUMAR JAY
Published: May 2022

Purpose: Diabetic retinopathy has a complex pathogenesis, and mitochondrial damage is considered to play a central role. Diabetes dysfunctions the mitochondria and damages their DNA (mtDNA) , decreasing the transcription of mtDNA-encoded genes including Cytochrome B (CYTB) , which is important for the functioning of complex III of the electron transport chain system (ETC) . This propagate the vicious cycle of free radicals. Diabetes also decreases mtDNA-encoded long non-coding RNA Cytochrome B (LncCytB) . Although long noncoding RNAs have no open reading frame for translation, they can bind to the DNA or RNA in a sequence specific manner and alter the gene expression. Our aim was to investigate the role of LncCytB in regulating CYTB-ETC system in diabetic retinopathy.

Methods: Human retinal endothelial cells, incubated in 5mM (normal) or 20mM (high) D-glucose, were used to quantify the expressions of LncCytB (by strand-specific PCR) and CYTB (qRT-PCR) . The binding of LncCytB at CYTB promoter was determined by Chromatin isolation by RNA Purification method. Role of LncCytB in regulating CYTB expression and mitochondrial damage was performed in the cells overexpressing LncCytB.

Results: Compared to cells in normal glucose, LncCytB and CYTB levels were decreased by over 50% in the cells exposed to high glucose, the binding of LncCytB at CYTB promoter was reduced by ∼40% and the activity of the complex III was inhibited. Overexpression of LncCytB ameliorated glucose-induced decrease in CYTB gene transcripts, and increase in mtDNA damage and in mitochondrial reactive oxygen species.

Conclusions: Due to decreased interactions between LncCytB-CYTB in hyperglycemic milieu, CYTB transcripts are decreased, and this compromises the ETC system, resulting in increased mitochondrial ROS. Thus, regulating LncCytB levels in diabetes could halt the self-propagating cycle of free radicals, and prevent the development of diabetic retinopathy.

Funding

EY014370, EY017313, and EY022230
471-P: Glycated Haemoglobin in the First Year after Diagnosis of Type 1 Diabetes Is an Independent Risk Factor for Diabetic Retinopathy: The IMDIAB 25 Years Follow-Up Study
Authors: MADDALONI ERNESTO , CARLONE ANGELA , PITOCCO DARIO , LEANZA GIULIA , SURACI CONCETTA , ALTOMARE MARIA , CAVALLO MARIA G. , BARCHETTA ILARIA , MORANO SUSANNA , MORETTI CHIARA , VISALLI NATALIA , TRAMONTANA FLAVIA , CRINO ANTONINO , SCHIAFFINI RICCARDO , BUZZETTI RAFFAELLA , POZZILLI PAOLO ,   IMDIAB STUDY GROUP
Published: May 2022

Background: Intensive glycemic control reduces the risk of diabetic retinopathy (DR) in people with type 1 diabetes (T1D) . However, the impact of glycemic control during the peri-diagnostic period on the long-term risk of DR is not known.Aim: To evaluate the association between the glycemic control obtained within the first year after T1D diagnosis and the long-term risk of DR.

Methods: We retrospectively studied a cohort of 150 subjects enrolled within 1 year of T1D diagnosis in intervention trials conducted by the IMmunotherapy DIABetes (IMDIAB) group between 1994 and 20 and still attending follow-up visits in one of the IMDIAB centers. Data regarding clinical and biochemical features at T1D onset and during the first year of the disease were collected at the time of enrollment in the IMDIAB studies. Follow-up data about clinical features including presence of chronic complications were collected between January 2020 and January 2021 through the consultation of medical records.

Results: After a median follow-up of 25 [25th-75th percentiles: 22-28] years, 26 (17.3%) people had developed DR. People with DR showed significantly higher updated first-year HbA1c (6.8 [6.2-7.8] % vs. 6.3 [5.7-7.2] %, p=0.037) and higher HbA1c at follow-up (8.0 [6.9-8.9]% vs. 7.2 [6.5-7.8]%, p=0.005) compared to people free from DR. Higher updated first-year HbA1c was also a significant predictor of higher HbA1c at follow-up (beta-coefficient: 0.24, p=0.015) . The association between the updated first-year HbA1c and DR did not significantly change after adding HbA1c at follow-up and disease duration in the multivariate model.

Conclusion: Glycemic control obtained during the very first year after T1D onset is associated with long-term risk of diabetic retinopathy independently from subsequent glycemic control and other confounders.

Disclosure

E.Maddaloni: Consultant; Merck KGaA, Speaker's Bureau; Abbott, Medical Technology & Devices, PIKDARE S.p.A. C.Moretti: None. N.Visalli: Consultant; Sanofi. F.Tramontana: None. A.Crino: None. R.Schiaffini: Advisory Panel; Abbott, Sanofi. R.Buzzetti: Board Member; Lilly, Novo Nordisk, Sanofi, Speaker's Bureau; Abbott, AstraZeneca. P.Pozzilli: Advisory Panel; Dompé, Consultant; Abbott, Speaker's Bureau; Dompé, Lilly Diabetes, Medtronic, Sanofi. Imdiab study group: n/a. A.Carlone: None. D.Pitocco: None. G.Leanza: None. C.Suraci: None. M.Altomare: None. M.G.Cavallo: Advisory Panel; Eli Lilly and Company, Board Member; Novo Nordisk, Speaker's Bureau; AstraZeneca, Sanofi. I.Barchetta: None. S.Morano: None.

Funding

Italian Ministry of University and Research (PRIN 2017: 20175L9H7H)
475-P: Plasma Fatty Acid Composition Is Associated with Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Patients
Authors: HIGA MARIKO , ICHIJO TAKAMASA
Published: May 2022

Type 2 diabetes is frequently complicated by nonalcoholic fatty liver disease (NAFLD) , which is mainly caused by high-fat and high-calorie diets, and obesity. In this regard, both the quantity and quality of fat accumulating in the liver are important, and in particular, the proportion of each fatty acid may be an important biomarker for NAFLD. We investigated whether serum fatty acid composition, especially n-6 polyunsaturated fatty acid (PUFA) and, saturated fatty acid (MUFA) and desaturase activity are associated with NAFLD in type 2 diabetes patients. Eighty-five type 2 diabetes patients (age: 60.3±13.9 years, BMI 27.5±5.8 kg/m2) who had no history of alcohol drinking, and had a negative result for hepatitis viruses were included as study subjects. Fatty liver (FL) was diagnosed based on liver ultrasonographic findings. Patients with FL were included in the FL group (n=51) , whereas those without FL included in the non-FL group (n=34) . Serum fatty acid levels were measured using gas chromatography. Desaturase activity for n-6 PUFAs was calculated as the ratio of arachidonic acid to dihomo-gamma-linolenic acid (DGLA) for Δ5 desaturase (D5D) . Waist circumference, BMI, serum triglyceride (TG) concentration, and ALT level were significantly higher in the FL group than in the non-FL group. The FL group also demonstrated higher levels of palmitic acid (PAL) and stearic acid (STA) , PAL/STA ratio, and DGLA than the non-FL group. In the FL group D5D activity was significantly lower than that in the non-FL group. PAL level, DGLA, and PAL/STA ratio showed a significant positive correlation with TG and ALT levels. Multiple regression analysis showed that DGLA was independently associated with FL development. These results suggest that type 2 diabetes patients with NAFLD have changes in their blood fatty acid profile, especially increased DGLA and PAL levels. The high levels of blood DGLA indicate downregulation of n-6 PUFA metabolism, probably caused by the decreased activity of D5D.

Disclosure

M.Higa: None. T.Ichijo: None.
506-P: Project ECHO for Diabetes Improves Physician Assistant Students’ Knowledge and Confidence for Complex Diabetes Care
Authors: PHELPS MEGAN , ALDOUS ANNETTE , EHRHARDT NICOLE M.
Published: May 2022

Objective: Assess whether participation in a well-established tele-education mentorship program, ECHO (Extension for Community Healthcare Outcomes) , improves preclinical providers’ self-efficacy, confidence, and knowledge in managing complex diabetes (DM) .

Methods: Over 3 cycles of ECHO sessions from 2018-2021, we engaged 42 physician assistant students (PAS) in efforts to increase knowledge prior to clinical practice. Using didactics and case-based learning via videoconferencing, the ECHO model allowed participants to receive tele-mentoring from an endocrinologist, a diabetes educator, and rotating specialists. Over 14-16 bimonthly sessions, PAS (n=42) received an evidence-based curriculum on complex DM management. Pre and post course surveys measured self-efficacy (13 questions) , confidence in management (6) , factual knowledge (12) and prescribing practices (11) .

Results: Twenty-three PAS completed at least 50% of sessions; 18 completed both evaluations. On a 7-point Likert scale, self-efficacy increased from 3.18 (slightly competent) pre-intervention to 4.78 (competent) post (p<.0001) . PAS’ belief in their competence to be an endocrinology resource in the community increased from 1.94 to 4. (p<.0001) . Confidence increased from 3.32 (neutral) to 5.33 (somewhat confident) (p<.0001) . PAS answered correctly on 3.78 of 12 knowledge questions before the intervention, increasing to 5.76 after (p<0.01) . Students’ anticipated frequency of prescribing diabetes medication increased from 1.73 (rarely) to 3. (sometimes) (p<.001) and of technology from 1.46 to 2.79 (p<.001) on a 4-point scale.

Conclusion: Our ECHO model is the first to evaluate healthcare trainees. PAS showed improved self-efficacy, knowledge, and confidence in DM management and increased comfort in prescribing. However, overall participation in live sessions was low. Further research is assessing incorporation of pre-recorded ECHO sessions into the PA curriculum.

Disclosure

M.Phelps: None. A.Aldous: None. N.M.Ehrhardt: Advisory Panel; Dexcom, Inc., Novo Nordisk, Research Support; Dexcom, Inc., Merck & Co., Inc., Novo Nordisk.

Funding

Merck Foundation, Merck and Novo Nordisk
529-P: Impact of Medication Adherence (MA) to Oral Glycemic Agents (OHAs) on Initiation of Dialysis in Patients with Moderately Impaired Renal Function
Authors: YAGUCHI YUTA , FUJIHARA KAZUYA , YAMADA MAYUKO H. , MATSUBAYASHI YASUHIRO , YAMADA TAKAHO , IWANAGA MIDORI , KITAZAWA MASARU , YAMAMOTO MASAHIKO , KODAMA SATORU , SONE HIROHITO
Published: May 2022

Although we showed a significant association of poor adherence to OHAs with start of dialysis, this relationship according to the estimated glomerular filtration rate (eGFR) was not clarified. Patients with eGFR <60 mL/min/1.73m2 are at high risk for dialysis. To identify the impact of MA by eGFR categories, we analyzed a nationwide claims-based database of 7,862 people with DM and without prior dialysis from 2008-16 aged 18-72 y with available records for OHAs for at least 1 year (mean age 54 y, HbA1c 7.2%) . MA was evaluated by the proportion of days covered (PDC) , and PDC <80% indicated poor adherence. Other factors were also analyzed (Table) . Median follow-up was 5.1 years. Incidence of dialysis per 1000 person-years was 10.7 in the eGFR<60 group and 0.62 in the eGFR ≥60 group. By Cox regression analysis (Table) an increased risk of dialysis was associated with poor MA (HR 2.98[95% CI 1.69-5.23]) , high systolic blood pressure (SBP) (1.27[1.11-1.44]) ], or current smoking (1.98[1.11-3.51]) in the eGFR<60 group and with high SBP (1.41[1.10-1.80]) and high HbA1c (1.45[1.13-1.87]) in the eGFR ≥60 group. Other factors in addition to MA might lead to dialysis, but poor MA was a strong risk factor for dialysis in this short observation period, especially in patients with impaired renal function. Clinicians should pay special attention to MA in these patients to prevent dialysis.

Disclosure

Y.Yaguchi: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. K.Fujihara: None. M.H.Yamada: None. Y.Matsubayashi: None. T.Yamada: None. M.Iwanaga: None. M.Kitazawa: None. M.Yamamoto: None. S.Kodama: None.