bluuebunny/crossref_metadata_2025 huggingface dataset:
827-P: 2022 Update on the BCG Clinical Trial Programs in Advanced Type 1 Diabetes
Authors: KUHTREIBER WILLEM , HOSTETTER EMMA , LEE AMANDA H. , NG NATHAN , WOLFE GRACE , ARISTARKHOVA ANNA , ZHENG HUI , FAUSTMAN DENISE L.
Published: May 2022

The bacillus Calmette-Guerin (BCG) vaccine was first introduced a century ago for tuberculosis prevention and is today being tested in double-blinded, randomized clinical trials for treatment of diverse forms of autoimmunity, including type 1 diabetes (T1D) and multiple sclerosis (MS) . At our institution, multiple clinical protocols are underway to test various aspects of BCG’s ability to lower HbA1c, reduce insulin requirements and change day-to-day fluctuations in blood sugars. Clinical trial subjects are in study groups including: 1) Long-term follow up of a Phase I study of BCG vaccination in longstanding T1D to study the durability of lowered HbA1c values after BCG treatment; 2) Randomized, double-blinded Phase II clinical trial testing the BCG vaccine in adults with longstanding T1D to demonstrate the reproducibility of BCG’s effects seen in the Phase I trial; 3) Radiologic study to quantify and identify through FDG-CAT scans the organs and organ systems that utilize more sugar after BCG treatment; 4) Study in adults with longstanding T1D to evaluate the effects of two doses of BCG compared to 6 doses of BCG over 5 years of observation; and 5) A soon-to-launch multi-center clinical trial of adolescents with > 2 years since T1D diagnosis to evaluate the potential benefits of BCG vaccination in this cohort. Basic science studies at our institution continue to show that, even in subjects with no pancreas reserve, the effects of BCG on blood sugar are mediated by the restoration of regulated sugar transport in the lymphoid system to corrected aerobic glycolysis. Patients are also being monitored by RNAseq, epigenetics, Treg cell numbers and signature gene expression to better define the mechanism of BCG’s effects. Global studies on the beneficial off-target effects of BCG on the immune system show that the impact of multi-dose vaccination in MS and T1D is seen with 2 years of follow-up and that the effects appear durable without further treatment in both MS and T1D to 5+ years.

Disclosure

W.Kuhtreiber: None. E.Hostetter: None. A.H.Lee: None. N.Ng: None. G.Wolfe: None. A.Aristarkhova: None. H.Zheng: None. D.L.Faustman: None.

Funding

Iacocca Foundation
83-LB: Pharmacokinetic and Pharmacodynamic Studies of Supaglutide in Rats and Monkeys
Authors: LIAO YIJING , MA ANRAN , WANG ZHIHONG , ZHOU YUE , ZHANG LI , LIU LIN , ZHANG NA , PRUD’HOMME GERALD J. , WANG QINGHUA
Published: May 2022

Supaglutide, a novel GLP-1-IgG Fc fusion protein, exerts hypoglycemic effects in type 2 diabetic db/db mice and spontaneous diabetic monkeys. In this study, we investigated the pharmacokinetics and pharmacodynamics of supaglutide by single or repeated subcutaneous and intravenous injection (s) in rats and rhesus monkeys. We found that the half-life of supaglutide at 0.1 mg/kg in rhesus monkeys was 39.7 hours and 35.8 hours upon subcutaneous or intravenous administration, respectively. The plasma supaglutide peaked at 8-10 hours, while the plasma drug exposure levels increased with the increase of dose, showing approximately a linear pharmacokinetic characteristic. The elimination kinetics was similar between subcutaneous (∼0.025 in rats and ∼0.018 in monkeys) and intravenous administration (0.021 in rats and 0.020 in monkeys) , whereas the bioavailability was found to be 31.1% in rats and 63.9% in monkeys. In monkeys, the marked glucose-lowering effect of a single dose injection of supaglutide peaked at 14-16 hours and lasted for 72 hours. 125I-supaglutide distributed mainly in the serum and organs rich in blood supply. Urine was found to be the primary excretion route of supaglutide, following by feces, but the least by bile. Our results demonstrate that supaglutide has an excellent pharmacokinetic profile with prolonged hypoglycemic effects and is a potential weekly dosing therapeutic agent for the treatment of type 2 diabetes.

Disclosure

Y. Liao: None. A. Ma: None. Z. Wang: None. Y. Zhou: None. L. Zhang: None. L. Liu: None. N. Zhang: None. G. J. Prud’homme: None. Q. Wang: None.
834-P: Two-Year Effects of Carbohydrate-Restricted Nutrition Therapy Delivered via Continuous Remote Care among Veterans with Type 2 Diabetes: A Nationwide, Real-World Study
Authors: MCKENZIE AMY L. , VANTIEGHEM MICHELLE , FELL BRANDON , RATNER ROBERT E.
Published: May 2022

Type 2 diabetes (T2D) affects about one in four Veterans, a rate nearly three times the general population, and diabetes medications and supplies constitute about one quarter of these Veterans’ pharmacy spend. The Veterans Health Administration partnered with Virta Health to provide carbohydrate restricted nutrition therapy via a continuous remote care model to Veterans in a pilot program. Five-month outcomes demonstrated significant reductions in HbA1c, BMI, diabetes medications and cost, and outpatient visits, but long term sustainability in this population is unknown. This retrospective, real-world, longitudinal analysis assessed the 1- and 2-year effects of the treatment on glycemia, diabetes medications, and body weight using medical record data. Veterans retained at least two years at time of analysis were included (n=254, 58.5% of 434 eligible enrolled, 60±8 years, 12% female) . With initiation of nutritional intervention, glycemia fell necessitating medication titration and elimination to prevent hypoglycemia. The number of diabetes medications prescribed to each person significantly decreased from 2.4±0.9 to 1.3±0.9 and 1.6±0.8 at one and two years, respectively (ps<0.0001) . Despite this significant reduction in pharmacologic therapy, HbA1c was significantly reduced at one year (-0.7±1.6%, p<0.0001) and two years (-0.6±1.7%, p<0.0001) compared to enrollment (8.1±1.5%) . Body weight also declined from 241.1±50.1 lb to 223.2±44.4 lb at one year and 222.1±46.8 lb at two years (ps<0.0001) , reflecting 6.8±7.6% and 7.0±9.4% weight loss per person at one and two years, respectively. These findings demonstrate that sustained improvement in glycemia concurrent with medication deprescription and clinically significant weight loss are achievable in the real world among Veterans who choose this therapy.

Disclosure

A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. B.Fell: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp.
839-P: Pharmacological Inhibition of Mammalian INDY Ameliorates Western Diet–Induced NASH in Mice: Possible Implication of Fgf21-AMPK Signaling
Authors: EL-AGROUDY NERMEEN , ZAHN GRIT , HERRMANN CHRISTINE , MINGRONE GELTRUDE , ALVES TIAGO C. , BIRKENFELD ANDREAS L.
Published: May 2022

Background: Recent data proposed a role of the citrate transporter INDY (I’m Not Dead Yet) in the development of obesity, insulin resistance and NAFLD suggesting its potential as a therapeutic target for metabolic-related disorders. The aim of our study is to determine if mammalian INDY (mINDY) inhibitors can be introduced as a new therapeutic option for NAFLD/NASH.

Methods: Six-week-old C57Bl/6N mice were fed a western diet (WD) for 18 weeks to induce NASH. After 12 weeks of feeding, mice received mINDY inhibitor (PF-06649298, mINDYi; 100 mg/kg) or vehicle bid until end of week 18. During the treatment period, body weight and composition were monitored. ipGTT and FACS analysis of liver inflammatory cells were performed.

Results: mINDYi-treated mice exhibited lower body weight, fat mass and higher lean mass compared to vehicle-treated mice. Results from ipGTT revealed improved glucose tolerance and insulin sensitivity. The latter was further confirmed through increased insulin-stimulated Akt phosphorylation in liver, gonadal WAT and BAT. Treatment with mINDYi attenuated WD-induced hepatic injury, steatosis and inflammation as shown histologically and biochemically by reduction in plasma ALT and AST, decrease in hepatic triglyceride accumulation and reduced hepatic lymphoid and myeloid immune cell populations. Interestingly, these effects were associated with a significant rise in plasma and hepatic Fgf21 together with increased hepatic phosphorylation of LKB1 and AMPK and decreased mTOR. Results from primary mouse hepatocytes revealed that mINDYi-induction of Fgf21 is partially dependent on AMPK activation.

Conclusion: Our study shows for the first time that mINDYi attenuates diet-induced steatohepatitis; offering a promising novel treatment strategy for NAFLD. Further investigations are currently ongoing to elucidate the molecular mechanisms underlying mINDY inhibition and whether it is dependent on Fgf21-AMPK signaling.

Disclosure

N.El-agroudy: None. G.Zahn: Employee; Eternygen GmbH. C.Herrmann: None. G.Mingrone: Advisory Panel; Fractyl Health, Inc., Novo Nordisk, Consultant; ReCor Medical, Inc. T.C.Alves: None. A.L.Birkenfeld: None.
854-P: Statin Use and New-Onset Diabetes in People with Prediabetes
Authors: PARK JEAN Y. , GHAZI ADLINE , PITTAS ANASTASSIOS G. , VICKERY ELLEN , NELSON JASON P. , ARODA VANITA R. ,   D2D RESEARCH GROUP
Published: May 2022

Statins lower the risk of cardiovascular disease, yet may adversely affect glucose metabolism. In the D2d study, which evaluated the effect of vitamin D versus placebo in a contemporary cohort of people with high-risk prediabetes (n=2,423) , we evaluated the association between statin use at baseline and progression to diabetes.

In the D2d study, 1396 participants (58%) were on statin at baseline. Kaplan Meier curves of incident diabetes over 2.5 years by baseline status of statin use and adjusted hazard ratio (95%CI) of the difference in incident diabetes between statin and no statin use were estimated. We tested for a statin use * D2d assignment (vitamin D or placebo) interaction on incident diabetes.

Mean age (SD) was 57±years and 64±8 for those not on vs. on statin; baseline HbA1c was 5.9 ± 0.2% in both groups. 27% of statin users developed diabetes vs. 24% of non-statin users (adjusted HR [95%CI] 1.23 [1.04-1.46]) (Figure) . There was no significant interaction (p=0.67) with vitamin D treatment assignment; therefore, subgroup analyses by D2d treatment assignment are not presented.

Conclusions: In this observational analysis among people at high risk for diabetes, baseline statin use was associated with a 23% higher risk of progression to diabetes after 2.5 years compared to no use. Increased risk of diabetes progression should be considered along with the cardiovascular benefits of statin therapy and diabetes prevention measures re-enforced.

Disclosure

J.Y.Park: None. A.Ghazi: None. A.G.Pittas: None. E.Vickery: None. J.P.Nelson: None. V.R.Aroda: Consultant; Applied Therapeutics, Fractyl Health, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Other Relationship; Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Research Support; Applied Therapeutics, Fractyl Health, Inc., Novo Nordisk, Sanofi. D2d research group: n/a.

Funding

American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)
856-P: Cardiovascular (CV) and Kidney Outcomes with Canagliflozin (CANA) According to Type 2 Diabetes (T2D) Treatment Targets at Baseline (BL) : Data from the CANVAS Program and CREDENCE
Authors: WOO VINCENT C. , TSOUKAS MICHAEL , TOBE SHELDON , SLEE APRIL , RAPATTONI WALLY , ANG FERNANDO , SEUFERT JOCHEN , WHEELER DAVID C.
Published: May 2022

In T2D, treatment targets include maintaining HbA1c ≤7.0%, LDL-C <2 mmol/L (<77 mg/dL) , and BP <130/80 mmHg. It is also recommended to improve urinary albumin:creatinine ratio (UACR) , a marker of renal damage and CV risk. We examined effects of CANA vs. placebo on CV and kidney outcomes in patients with T2D and high CV risk and/or chronic kidney disease according to BL treatment targets and risk factors. Pooled data from the CANVAS Program (N=10,142) and the CREDENCE trial (N=4401) were analyzed according to treatment target achievement and by number of targets achieved at BL. Hazard ratios and 95% CIs were estimated using Cox regression models. Of 14,432 participants at BL, 3683 (26%) had achieved 0, 5851 (41%) had achieved 1, 3680 (25%) had achieved 2, and 1218 (8%) had achieved either 3 or 4 targets. At BL, 8415 (58%) participants had UACR >2 mg/mmol. CANA consistently reduced risk of MACE, HHF/CV death, and ESKD or doubling of serum creatinine vs. placebo, regardless of whether BL targets were met or if UACR was elevated (Figure) . The number of uncontrolled targets at BL did not impact the beneficial effect of CANA on CV and kidney outcomes (all P interaction >0.17) .

In conclusion, CANA demonstrated consistent CV and renal benefits in patients with T2D, regardless of risk factor control.

Disclosure

V.C.Woo: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Speaker's Bureau; Janssen Pharmaceuticals, Inc. M.Tsoukas: Speaker's Bureau; AstraZeneca, Bausch Health, Canada, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Johnson & Johnson, Novo Nordisk Canada Inc. S.Tobe: Other Relationship; Bayer AG, Speaker's Bureau; AstraZeneca, Otsuka Pharmaceutical Co., Ltd. A.Slee: Consultant; Alydia Health, Elixir Medical , IHP Therapeutics , iLumen Scientific, Intuitive Surgical, Janssen Global Services, LLC, Laborie, Providence Medical, Pulse Biosciences, SonoMotion. W.Rapattoni: Employee; Janssen Pharmaceuticals, Inc. F.Ang: Employee; Bristol-Myers Squibb Company, Janssen Pharmaceuticals, Inc. J.Seufert: Advisory Panel; Abbott, Sanofi-Aventis Deutschland GmbH, Research Support; Boehringer Ingelheim International GmbH, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. D.C.Wheeler: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., GlaxoSmithKline plc., Janssen Global Services, LLC, Merck Sharp & Dohme Corp., Mundipharma, Tricida, Inc., Vifor Pharma Management Ltd., Consultant; AstraZeneca, Speaker's Bureau; Amgen Inc., Astellas Pharma Inc.

Funding

Janssen Inc., Toronto, ON, Canada
879-P: Effect of Combined SGLT2 Inhibitor and DPP-4 Inhibitor Therapy on the Production of Advanced Glycation End Products
Authors: KUSUNOKI MASATAKA , WAKAZONO NAOMI , HISANO FUMIYA , MIYATA TETSURO
Published: May 2022

SGLT2 inhibitors (SGLT2is) prevent disease progression in diabetic patients with atherosclerotic disease. On the other hand, a similar beneficial effect on disease progression has not been reported for DPP-4 inhibitors (DPP-4is) , which are, however, widely used. To clarify the differences in effects between these two classes of drugs in diabetic patients, we focused on the production of advanced glycation end products (AGEs) and studied the effects of pretreatment with DPP-4i on the production of AGEs in patients who subsequently received SGLT2i. In the present study, Japanese patients with type 2 diabetes mellitus with unchanged glycemia control status for at least 6 months were administered SGLT2i (n = 11) for 3 months and then divided into a group that had already been receiving DPP-4i (n = 11) at the start of administration of the SGLT2i and the SGLT2i monotherapy group. We measured the blood levels of methylglyoxal-derived hydroimidazolone-1 (MG-H1) , which is an AGE, and also diabetes-related parameters before the start and after 3 months’ treatment with the SGLT2i. As a result, significant decreases of both HbA1c (from 8.6 ± 1.4 to 7.2 ± 1.4, P < 0.01) and circulating MG-H1 levels (from 0.48 ± 0.to 0.44 ± 0.07, P < 0.05) were observed in the SGLT2i monotherapy group. On the other hand, in the group that received SGLT2i in addition to a DPP-4i, the HbA1c value decreased significantly (from 7.2 ± 0.4 to 6.8 ± 0.5, P < 0.01) , whereas no significant change of the MG-H1 level was observed after the SGLT2i therapy. In conclusion, SGLT2i monotherapy decreased both the HbA1c and blood MG-H1 levels. However, no significant effect on the blood level of MG-H1 was observed in the combined DPP4i plus subsequent SGLT2i therapy group, suggesting that DPP4i possibly suppress the effect of the SGLT2i in reducing the production of MG-H1.

Disclosure

M.Kusunoki: Other Relationship; Taisho Pharmaceutical Holdings Co., Ltd. N.Wakazono: None. F.Hisano: None. T.Miyata: None.
88-LB: Safety, PK, PD, and Efficacy of Weekly Dosing Supaglutide in Patients with T2D
Authors: ZHOU YUE , JIANG XIN , LOU YAN-RU , MA ANRAN , LI JIA , ZHAO YING , PRUD’HOMME GERALD J. , WANG QINGHUA
Published: May 2022

Supaglutide (Supa) is a weekly dosing GLP-1 analog. We conducted a randomized, double-blind, placebo-controlled, multiple dose-escalation study to investigate the safety, PK/PD and efficacy of Supa in patients with T2D. 40 subjects were randomized in a 4:1 ratio to receive Supa (sc., 1, 2, 3 and 4mg) or placebo. We performed intensive PK blood sampling for two weeks after the first dose, followed by weekly repeated dosing for 4 consecutive weeks. The 4mg group received an adaptive dose of 1mg to reduce gastrointestinal reactions. The PK results revealed that the T1/2 of Supa was ∼207 h with median Tmax of 60∼84 h. The PD results showed that after 7 weeks of therapy, Supa significantly reduced fasting blood glucose, and HbA1c decreased by 1.3%. Supa increased fasting insulin/C-peptide while decreasing body weight. OGTT results showed significantly reduced glucose excursion, and the glucose-stimulated insulin secretion assay demonstrated significantly increased insulin secretion, suggesting improved glucose tolerance and enhanced β-cell function. AEs identified during the study were mainly mild to moderate gastrointestinal symptoms. None of the subjects developed anti-drug antibodies. Safety assessments including AEs, vital signs, ECGs and laboratory parameters, revealed that Supa was safe and well-tolerated. These data suggest Supa is a novel alternative therapy for T2D and metabolic disorders.

Disclosure

Y. Zhou: None. X. Jiang: None. Y. Lou: None. A. Ma: None. J. Li: None. Y. Zhao: None. G. J. Prud'homme: None. Q. Wang: None.
883-P: Associations of State Earned Income Tax Credits with Self-Reported Health Status among U.S. Adults with Diabetes, 2000–2016
Authors: TANG SHICHAO , CHEN YU , ROLKA DEBORAH B. , IMPERATORE GIUSEPPINA , HOLLIDAY CHRISTOPHER S. , ZHANG PING
Published: May 2022

Persons with low socioeconomic status are disproportionately affected by diabetes and among people with diabetes, those with lower incomes tend to have poorer health status than those with higher incomes. Few studies have examined whether policies to improve the financial status of low-income populations can improve health outcomes among people with diabetes. Using data on state earned income tax credit (EITC) policies from the National Bureau of Economic Research and self-reported health status from the 2000-2016 Behavioral Risk Factor Surveillance System (BRFSS) , we examined the association of state EITC with poor health status among United States (US) adults with self-reported diagnosed diabetes. Poor overall health was defined as self-reported general health status of “fair” or “poor” in BRFSS. Poor mental and physical health were defined as having at least 14 self-reported days in poor mental or poor physical health in the past 30 days, respectively. State EITC was defined as the state’s EITC amount as a percentage of the federal EITC. We used weighted logistic regression to model the effect of EITC variation across states and over years and calculated the marginal effects of state EITC on health status, controlling for poverty, race, education, unemployment, state gross domestic product (GDP) , state Medicaid expansion, and state minimum wage policy. Poisson regression models were conducted as a sensitivity analysis. A 10-percentage point increase in the state EITC was associated with a 3% lower rate of poor mental health status (-2,759 per 100,000, 95% CI = -5,494, -25) . The associations of the state EITC with physical health and overall health status were not statistically significant. The results were robust to choice of model based on the sensitivity analysis. Policies that increase income retained may help to improve self-reported mental health status of US adults with diabetes.

Disclosure

S.Tang: None. Y.Chen: None. D.B.Rolka: None. G.Imperatore: None. C.S.Holliday: None. P.Zhang: None.
886-P: Development and Validation of the Diabetes Outcome Model for the U.S. (DOMUS)
Authors: WINN AARON N. , HUANG ELBERT , CLARKE PHILIP , KARTER ANDREW J. , WAN WEN , MILLER DONALD R. , FRANCO MELISSA , DECKARD AMBER , LAITEERAPONG NEDA
Published: May 2022

Purpose: The purpose of this study is to develop a diabetes outcomes model for the US (DOMUS) using a multi-ethnic, real-world-data cohort of newly diagnosed Type II diabetics that can predict outcomes for a U.S. multi-ethnic type 2 diabetes population.

Methods: The Kaiser Permanente Northern California (KPNC) Diabetes Registry, which is a well-described epidemiologic cohort with up to 13 years of follow-up from EMR and claims, were used to identify over 150,000 newly diagnosed diabetes patients between 2005-2016 with up to 13-year follow-up. The DOMUS model integrates separate, but interdependent risk equations to predict events for each of the micro and macro-vascular events, hypoglycemia, dementia, depression, and death, and predictive models for eight biomarker levels. Model accounted for static demographic factors (e.g., race) , neighborhood deprivation, and dynamic factors, such as age, duration of diabetes, fifteen-possible glucose -lowering treatment combinations, biomarker levels, and history of diabetes-related events. Moreover, the models explicitly allow for a legacy effect (average A1c in the first year after diagnosis) for all outcomes.

Results: Data were randomly split into 75,000, 18,750, and 18,750 patients to perform estimation, out-of-sample calibration, and validation respectively. Model predictions in the validation sample closely aligned with the observed longitudinal trajectory of biomarkers and outcomes. Moreover, we examine the model performance within by age, race/ethnicity, and sex and found excellent predictive performance within subgroups.

Conclusion: The DOMUS Model is able to simulate event histories and biomarker trajectories that closely match observed outcomes in a real-world, multi-ethnic population of newly diagnosed diabetics. DOMUS has the potential to carry out many complex analyses that examine the effectiveness and cost-effectiveness of new medications, value of diabetes prevention, and serve as decision support tools in health care settings.

Disclosure

A.N.Winn: Consultant; Takeda Pharmaceutical Company Limited. E.Huang: Advisory Panel; Twin Health, Stock/Shareholder; AbbVie Inc. P.Clarke: None. A.J.Karter: Research Support; Dexcom, Inc. W.Wan: n/a. D.R.Miller: None. M.Franco: None. A.Deckard: None. N.Laiteerapong: None.
893-P: Incremental Health Care Utilizations and Medical Expenditures Associated with Cognitive Impairment among Older Adults with Diabetes
Authors: GUAN DAWEI , ZHANG PING , TANG SHICHAO , BROWN JOSHUA D. , FANG RUOGU R. , GUO JINGCHUAN , ZHANG YONGKANG , SHAO HUI
Published: May 2022

Cognitive impairment (CI) poses a large economic burden on the US health care system, but little is known about how CI impacts health care (HC) utilization and medical expenditures among people with diabetes. Using data from the 2016-20Medical Expenditure Panel Survey, we quantified the incremental HC utilization and medical expenditures associated with CI among adults aged ≥ 60 years with diabetes. Diabetes status was based on self-report. Participants who reported having difficulty concentrating, remembering, or making decisions were defined as having CI. We used negative binomial regressions to model the number of ambulatory visits, prescriptions, and home health care days; logistic regressions to model the probabilities of ER visits and hospital admissions; and gamma regressions to model medical expenditures in total and by category. All models were adjusted for age, sex, race and ethnicity, income, education, and comorbidities. We included 6,714 adults ≥ 60 years with diabetes, of which 1,025 (15.27%) had CI. CI was associated with additional ambulatory visits (+4.7 [95% CI, 3.5-5.8]) , drug prescriptions (+10.6 [8.1-13.1]) , and home health care days (+32.6 [19.2-52.2]) ; and higher odds of ER visits (Odds Ratio (OR) : 1.55 [95% CI, 1.27-1.89]) and hospital admissions (OR: 1.27 [1.02-1.58]) . CI was also associated with additional expenditures for outpatient care (+$12[$731-$1720], or 28% higher than those without CI [17%-40%]) , prescription drugs (+$17[$1103-$2372], or 31% higher [20%-43%]) , and home health care (+$25[$445-$7060], or 197% higher [35%-555%]) . Overall, those with CI spent $70[$5168-$8835], or 42% [31%-53%] more than those without CI. All p < 0.05. CI is associated with higher HC utilization and medical expenditures among older adults with diabetes. Early detection of CI and additional assistance to those with CI may lower CI-related HC utilization and expenditure in this population.

Disclosure

D.Guan: None. P.Zhang: None. S.Tang: None. J.D.Brown: None. R.R.Fang: None. J.Guo: None. Y.Zhang: None. H.Shao: Board Member; BRAVO4HEALTH, LLC.
90-OR: FreeStyle Libre (FSL) Time in Range (TIR) and Time Below Range (TBR) : Impact on HbA1c, Diabetes-Related Distress (DRD) , and Resource Utilisation in the Association of British Clinical Diabetologists (ABCD) National Audit
Authors: DESHMUKH HARSHAL , PIERI BEATRICE , WILMOT EMMA G. , CHOUDHARY PRATIK , SHAH NAJEEB , TSATLIDIS VASILEIOS , LUMB ALISTAIR N. , RYDER ROBERT E. , WALTON CHRISTOPHER , SATHYAPALAN THOZHUKAT
Published: May 2022

Introduction: With increasing access to intermittently scanned continuous glucose monitoring (isCGM) , with the FSL, it is essential to understand the effect of TIR and TBR on HbA1c, DRD, and resource utilisation in people living with diabetes

Methods: Clinicians from 1NHS UK hospitals submitted FSL user data for16,034 participants, (96% type 1 diabetes) of whom 6859 had follow-up data, collected during routine clinical care and submitted to a web-based secure tool. Linear regression analysis was used to estimate the age, gender and baseline HbA1c adjusted reduction in HbA1c in the TIR categories.

Results: Follow up TIR data were available for 3250 (47%) participants of which, 1241 (38%) reported TIR in line with the international consensus (3.9-mmol/l) . After adjustments for age gender, baseline HbA1c and duration of diabetes follow-up TIR ≥50% was associated with an 0.8% (8.75 mmol/mol) reduction in HbA1c (P<0.0001) and -0.29 reduction in DRD (P<0.0001) , while follow-up TIR ≥70% was associated with a 1.3% (14.mmol/mol) reduction in HbA1c (P<0.0001) and 0.40 reduction (P<0.0001) in DRD vs. those with TIR <50%. With the use of FSL, there was a 67% reduction in hospital admissions due to hypoglycaemia (none in those with TIR≥50) , a 63% reduction in hospital admissions related to hyperglycaemia/DKA and an 85% reduction in paramedic outcalls. The reduction in hospital admissions for hyperglycaemia/DKA and paramedic callouts was independent of the TIR achieved during follow-up. The incidence of severe hypoglycaemia was lower in those with TBR ≤5% as compared to those with TBR >5% (7% vs. 11%) but was not statistically significant (P=0.31) .

Conclusion: In a large cohort of UK FSL users, we demonstrate a significant reduction in HbA1c, diabetes-related distress and resource utilisation which was associated with improved TIR

Disclosure

H.Deshmukh: None. T.Sathyapalan: n/a. B.Pieri: None. E.G.Wilmot: Advisory Panel; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Sanofi, Research Support; Insulet Corporation, Novo Nordisk, Speaker's Bureau; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Sanofi. P.Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic, Research Support; Novo Nordisk, Speaker's Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. N.Shah: None. V.Tsatlidis: None. A.N.Lumb: Advisory Panel; Abbott, Dexcom, Inc., Research Support; Abbott, Novo Nordisk, Speaker's Bureau; Abbott, Dexcom, Inc., Insulet Corporation, Novo Nordisk. R.E.Ryder: None. C.Walton: None.

Funding

NIHR clinical lectureship
900-P: Patterns of Drug Utilization for Cardio- and Renal-Protective Antihyperglycemic Agents in a Commercially Insured Population
Authors: COOK DAVID J. , DEFAIL ANTHONY , MACFARLANE ELIZABETH , PEDERSON DEREK
Published: May 2022

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter-2 inhibitors (SGLT2i) have cardioprotective and kidney-protective effects in select patients with type-2 diabetes (T2D) . Appropriate use, and cost-effectiveness, is essential to realize these benefits as well as to manage total healthcare spending.

Methods: For a commercially insured population (≥18 years old) enrolled in a virtual accountable care organization (Level2) , we examined de-identified administrative claims in a research database for Type-2 diabetes medications from 12/01/20to 11/30/2021. We determined the TCoC for this population, as well as changes in spending and utilization by medication class.

Results: Among 7,361 individuals attributed to Level2, 1,735 members (23.6%) had a cardiovascular or renal indication for an GLP-1RA or SGLT2i. In this population, 447 were prescribed a GLP-1RA and 385 were prescribed a SGLT2i, representing 25.8% and 22.2% of those with comorbidity indications for each drug, respectively. Additionally, 1,214 individuals were prescribed a GLP-1RA and 1,214 were prescribed a SGLT2i without cardiovascular or renal indications, representing 35% of these prescriptions combined.

Conclusion: In 2019-21, use of GLP-1RA and SGLT2i remained limited to approximately 1 in 4 commercially insured patients with T2D and a cardiovascular or renal indication for their selection. Further, they were commonly used in the absence of cardiovascular or renal indication for these classes of agents. While nondiabetes indications for these drugs (weight-loss and renal disease) have expanded recently (April-June 2021) , those broader indications were not in place for the majority of the study period. In a time of limited resources, guideline-concordant therapy is critical to improving the health of those with indications as well as reducing less-than-appropriate use.

Disclosure

D.J.Cook: None. A.Defail: Employee; Level2. E.Macfarlane: Employee; Level2. D.Pederson: Employee; Level2.
901-P: Population Characteristics and Spending Patterns of High-Expenditure Patients among Medicare Beneficiaries with Diabetes
Authors: WANG YU , ZHANG PING
Published: May 2022

Knowledge of Medicare beneficiaries with high medical expenditures can help identify target populations for intervention and strategies to reduce overall Medicare expenditures. Using 100% Medicare fee-for-service claims, we examined characteristics and spending patterns of high spenders among Medicare beneficiaries with diabetes (DM) . We defined high spenders as those whose expenditures in a year were in the top 10% of beneficiaries with DM. We identified 7,321,228 high spenders in 2015 and followed them through 2017. We grouped high spenders in 2015 into three groups: those who died during 2015-2017 (group 1) , were alive and a high spender in all 3 years (group 2) , and alive but a high spender for 1/2 years (group 3) . We used regression models to identify factors associated with each group. In 2015 high spenders accounted for 48% of all medical expenditures in Medicare beneficiaries with DM. Of the high spenders, 34% were in group 1, 20% in group 2, and 46% in group 3. High spenders in group 1 had a mean annual expenditure of $110,429 and were more likely to be male, be older, have dual eligibility for Medicaid, and have a higher number of comorbid conditions compared with groups 2 and 3. Over 60% of the expenditures in group 1 were spent on either acute inpatient care (39%) or on skilled nursing facility (23%) . Groups 2 and 3 had mean annual expenditures of $83,2 and $42,527, respectively. High spenders in group 2 were more likely to be male, be older, have dual eligibility for Medicaid, and have a higher number of comorbid conditions compared with group 3. Compared to those in group 3, high spenders in group 2 spent a higher proportion on hospice (13.3% vs. 7.9%) and inpatient care (16.7% vs. 9.9%) , but less on acute inpatient care (19.5% vs. 31.3%) . High-spender Medicare beneficiaries with DM had different characteristics and spending patterns. Future studies could identify modifiable factors and develop strategies to lower Medicare expenditures among high spenders with DM.

Disclosure

Y.Wang: None. P.Zhang: None.
91-OR: Association between Complexity of Glucose Time Series and All-Cause Mortality in Patients with Type 2 Diabetes Mellitus: A Prospective Cohort study
Authors: CAI JINGHAO , LU JINGYI , SHEN YUN , LU WEI , ZHU WEI , ZHOU JIAN
Published: May 2022

Background: Continuous glucose monitoring (CGM) can comprehensively reflect the dynamic changes of blood glucose varying with time. CGM data with more patterns of change represents glucose time series with higher complexity. However, the relationship between complexity of glucose dynamics and clinical outcomes of diabetes remains unknown.

Objective: To investigate the association between complexity of glucose time series, quantified by multiscale entropy (MSE) analysis, and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) in a prospective cohort study.

Methods: Data of 6,001 adult inpatients with T2DM included from January 2005 to December 2015 in a single center was analyzed. Complexity of glucose index (CGI) of glucose time series from CGM was measured by MSE analysis at baseline. Participants were stratified by the tertiles of CGI: < 2.15,2.15∼2.99, and ≥ 3.00. Cox proportional hazards regression models were used to estimate the association between different levels of CGI and the risks of all-cause mortality.

Results: During a median follow-up of 6.8 years, 799 deaths were identified. Multivariate Cox regression analysis revealed that the increase of CGI was associated with a lower risk of all-cause mortality (P for trend = 0.021) . The multivariable-adjusted HRs for all-cause mortality at different CGI levels [< 2.15 (reference group) , 2.15∼2.99, and ≥ 3.00] were 1.00, 0.49 (95%CI 0.30-0.79) , and 0.56 (95%CI 0.36-0.87) in patients with HbA1c < 7.0% (P for trend = 0.015) , while the association was nonsignificant in those with HbA1c ≥ 7.0%. And a significant interaction between HbA1c and CGI (P for interaction = 0.032) was noted in the study.

Conclusion: Lower CGI is associated with an increased risk of all-cause mortality in T2DM achieving HbA1c target, which suggests that the improvement of CGI may further reduce the risk of long-term adverse outcomes in T2DM at an early stage or with good glycemic control.

Disclosure

J.Cai: None. J.Lu: None. Y.Shen: None. W.Lu: None. W.Zhu: None. J.Zhou: None.

Funding

The Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (20161430)
921-P: Diabetes Preventive Care for Medicare Beneficiaries: Comparing Efficiency between the Diabetes Belt and Surrounding Areas
Authors: KANG HYOJUNG , KIM SOYOUN , LOBO JENNIFER M. , SOHN MIN-WOONG
Published: May 2022

Objective: Evidence-based preventive care services are crucial for people with diabetes to improve their health outcomes, but the utilization of the services among older adults is suboptimal. Our objective is to compare relative performance of the Diabetes Belt and surrounding counties in the uptake of preventive services among Medicare beneficiaries with diabetes given available health care resources in the counties. The Diabetes Belt includes 644 counties in the Appalachian and deep south areas of the US that have high diabetes prevalence.

Methods: We used data envelopment analysis (DEA) to compute technical efficiency of counties for 2009-2015. Technical efficiency measures how many outputs a decision-making unit produces given a set of inputs. Inputs included the number of physicians and nurses per 1000 adults in the counties, and outputs included the number of foot exams, a1c tests, and microalbumin tests per 1000 Medicare beneficiaries with diabetes. The Diabetes Belt includes counties in the Appalachian and deep south areas of the US that have high diabetes prevalence. We performed t-tests to compare efficiency between the Diabetes Belt and surrounding counties. We excluded counties with 0 doctors or 0 nurses for >1 year in 2009-2015.

Results: Of 1057 counties, 861 (496 in the Belt and 365 in surrounding areas) were included. During the study period, the average technical efficiency of the counties ranged from 79% to 83%, with only 2.- 3.4% of counties achieving 100% technical efficiency. Diabetes Belt counties had consistently lower efficiency than surrounding counties during the study period (p <0.05) . The mean efficiency was 78-81% in the Diabetes Belt and 81-85% in the surrounding counties.

Discussion: Our results suggest that the degree of inefficiencies was higher in the Diabetes Belt compared to surrounding counties. Given relatively low available resources in these areas, more attention to improve diabetes preventive care is needed.

Disclosure

H.Kang: None. S.Kim: None. J.M.Lobo: n/a. M.Sohn: None.

Funding

National Institutes of Health (1R01DK113295-01A1)
93-LB: A Randomized Clinical Trial of Safety, Pharmacokinetics, and Pharmacodynamics of Weekly Dosing Supagutide in Healthy Chinese Subjects
Authors: MA ANRAN , ZHOU YUE , LOU YAN-RU , LIAO YIJING , SHAO ANNA , WANG ZHIHONG , JIANG YAOJING , CUI QIAOLI , ZHAO YING , LI JIA , PRUD’HOMME GERALD J. , ZHU DALONG , WANG QINGHUA
Published: May 2022

Supaglutide (Supa) is a novel once-weekly, human-derived long-acting GLP-1 analogue developed for patients with type 2 diabetes. In this study, we investigated the safety, pharmacokinetics (PK) , pharmacodynamics (PD) and potential immunogenicity of single-dose subcutaneous injections of Supa in healthy subjects. In this double-blind, single dose-escalation, 14-week trial, 48 healthy subjects were randomized to subcutaneous Supa treatment (ranging from 0.375 to 9 mg) or placebo arms for 2 weeks. PK profile and safety parameters were assessed. PD parameters (glucose and insulin concentrations) were measured following an oral glucose tolerance test (OGTT) (Day 3) . The half-life of Supa was approximately 120 h with a median Tmax ranging from 48 to 72 h (Table 1) . Supa treatment significantly reduced body weight compared to placebo in a dose-dependent and time-dependent fashion. OGTT results showed that Supa at all doses investigated significantly decreased glucose levels during the test, suggesting increased glucose tolerance. Supa was safe and well-tolerated in healthy subjects with some increase in mild to moderate gastrointestinal symptoms with escalating doses. No subjects developed anti-Supa antibodies. The safety, PK and PD profiles supported Supa as a long-acting injectable medication for glycemic control and weight loss, as an alternative GLP-1 therapy.

Disclosure

A. Ma: None. J. Li: None. G. J. Prud’homme: None. D. Zhu: n/a. Q. Wang: None. Y. Zhou: None. Y. Lou: None. Y. Liao: None. A. Shao: None. Z. Wang: None. Y. Jiang: None. Q. Cui: None. Y. Zhao: None.

Funding

Ministry of Science and Technology (No. 2011ZX09102, No. 2017ZX09303001) , Shanghai Science and Technology Department (No. 2017ZX09303001)
935-P: Impact of Social Determinants of Health (SDoH) on Participation in a Remote Monitoring Diabetes Program (RDMP) to Improve Glycemic Control
Authors: KOMPALA TEJASWI , LU WEI , PAINTER STEFANIE L. , JAMES ROBERTA , SALEHI ATOUSA , LIU HAU
Published: May 2022

Introduction: Socioeconomic and educational status impact diabetes self-management and are believed to affect utilization of digital health programs, which could widen healthcare disparities. The objective of this study was to examine SDoH within members of Livongo for Diabetes, a RDMP, and impact on program engagement and glycemic control.

Methods: Members enrolled in the RDMP for 12-18 months were surveyed to capture education level, income, and member characteristics. Zip code was used to identify area deprivation index. Program engagement assessed by self-monitoring blood glucose values (SMBG) , application access, and coaching was evaluated during 12-months prior to survey, and glycemic control was defined as an estimated A1c < 7% based on mean SMBG values within 90-days of survey. Multivariable logistic regression models were used to evaluate the impact of SDoH variables on high program engagement and glycemic control.

Results: Of 1,3respondents, mean (SD) age was 51 (11) , 54% female, 13% Black, 5% Asian, 12% Hispanic, and 84% type 2 diabetes. SDoH variables (see table) were not associated with either outcome.

Conclusions: Evaluated SDoH do not appear to impact high RMDP utilization known to improve A1c by addressing individualized needs through education and coaching designed to address health literacy levels.

Disclosure

T.Kompala: Consultant; Eli Lilly and Company, Employee; Teladoc Health. W.Lu: Employee; Teladoc Health. S.L.Painter: Employee; Livongo, Teladoc Health. R.James: Employee; Livongo, Teladoc Health. A.Salehi: Employee; Livongo. H.Liu: Employee; Teladoc Health, Stock/Shareholder; Teladoc Health.
946-P: Multicenter Quality Improvement Project: Increasing Depression Screening across Six Pediatric Endocrinology Centers in the U.S.
Authors: ODUGBESAN ORI , MUNGMODE ANN , RIOLES NICOLE , BRIMBERRY DANIEL , NELSON GRACE , FEUER ALEXIS J. , ILKOWITZ JENIECE , DEI-TUTU SELORM A. , EBEKOZIEN OSAGIE
Published: May 2022

Background: Depression contributes to the suboptimal health outcomes among people with type 1 diabetes (T1D) . American Diabetes Association recommends depression screening in individuals with T1D. We aim to demonstrate the use of QI tools in expanding depression screening in the T1D Exchange Learning Collaborative (T1DX-LC)

Method: Six clinics in the T1DX-LC participated in expanding depression screening utilizing PHQ-2, PHQ-4, or PHQ-9. The clinics applied QI principles to design plan-do-study-act cycles to develop, improve, and adapt interventions. The interventions tested include use of a screener at visits, expanding screening to age 12, pulling weekly data to flag patients that should be screened, peer support group, standardizing screening workflow, use of EHR/health information technology, provider training, monthly meetings to discuss screening protocol, and streamlining referral process. The hospitals shared monthly aggregate data with the T1DX-LC

Result: Participating clinics were successful at implementing depression screening. Screening increased from a baseline of 59% to 72% over 17 months

Conclusion: Utilizing the PHQs for depression screening is feasible and QI principles are useful in expanding screening rates. Continued expansion of depression screening is necessary to improve emotional well-being and diabetes self-care management

Disclosure

O.Odugbesan: n/a. A.Mungmode: None. N.Rioles: None. D.Brimberry: None. G.Nelson: None. A.J.Feuer: None. J.Ilkowitz: None. S.A.Dei-tutu: None. O.Ebekozien: None.

Funding

The QI learning collaborative is supported by Helmsley Charitable Trust
965-P: Factors Associated with Poor Glycemic Control in Persons with Type 2 Diabetes and Employer-Based Health Care Coverage
Authors: ROWLAND CHARLES M. , LOUIE JUDY Z. , SHIFFMAN DOV , GARG RAJESH , BERNAL-MIZRACHI ERNESTO , MCPHAUL MICHAEL J.
Published: May 2022

Lack of healthcare insurance is an important factor for poor glycemic control in persons with diabetes. However, a large proportion of insured people also have inadequate glycemic control. This study was conducted to assess factors associated with poor glycemic control in persons with type 2 diabetics (T2D) who received full healthcare coverage through their employer.The study included employees and spouses with T2D who participated in an annual health assessment in 20 and had medical coverage ≥12 consecutive months prior to the assessment. T2D was defined from ICD codes in claims, self-reported physician diagnosis, or having fasting glucose > 125 mg/dL or HbA1C > 6.4%. A stepwise multinomial logistic regression model was used to assess associations of healthcare engagement, diet, smoking and socioeconomic status with glycemic control. The 2,981 participants included 16% (n=484) with HbA1C > 8.5% and 27% (n=800) with HbA1C 7 to 8.5%. We found that HbA1C > 8.5% was associated with age, sex, years since last physical exam, number of complications, number of medications, and physical activity. The regression model results are shown in the figure. We conclude that poor glycemic control is common among persons with T2D despite good healthcare coverage. We identified factors associated with poor glycemic control in this population that may help design strategies to improve glycemic control.

Disclosure

C.M.Rowland: Employee; Quest Diagnostics, Stock/Shareholder; Quest Diagnostics. J.Z.Louie: None. D.Shiffman: Employee; Quest Diagnostics, Stock/Shareholder; Quest Diagnostics. R.Garg: None. E.Bernal-mizrachi: None. M.J.Mcphaul: Employee; Quest Diagnostics.
97-LB: The DERMIS Study—Preliminary Evaluation of Skin Changes at Continuous Subcutaneous Insulin Infusion (CSII) Sites in Type 1 Diabetes (T1D)
Authors: BARAN JESICA D. , KHAKPOUR DORI , KALUS ANDREA , SHINOHARA MICHI , DONG XIAOFU , HIPPE DANIEL S. , HIRSCH IRL B.
Published: May 2022

Background: CSII is used with increased frequency; however, there are no studies evaluating human skin histology related to its use. Objectives: 1) to investigate the skin histology and metabolite changes at CSII sites and 2) associate possible changes with clinical characteristics in a cohort of patients with T1D.

Methods: We conducted a cross-sectional study which included individuals with T1D using CSII. Skin and blood samples in addition to clinical data were collected. Histological, immunohistochemical (IHC) , and metabolomic analyses were performed using skin biopsies from three sites: 1) current 2) recent and 3) never used site (control) for CSII.

Results: A total of 30 participants were enrolled in the study (age 48.3 ± 17.9 years, female 66.7%, diabetes duration 30.4 ± 16.0 years, insulin pump use 15.7 ± 11.7 years, BMI 25.3 ± 3.4 kg/m2, HbA1c 6.66 ± 0.79%, mean glucose from CGM 150.7 ± 26.4 mg/dL, coefficient of variation 31.2 ± 4.4%, insulin dose 0.53 ± 0.17 IU/kg) . Histologic data showed a significant increase in inflammation, fibrin, fat necrosis, vascularity, eosinophils, and IHC staining of IGF-1 and TGFβ3 at both CSII sites compared to control sites (all p<0.001) . Targeted tissue analysis demonstrated an increase in critical metabolites at current sites compared to control, including histamine (p=0.013) , uracil (p<0.001) , and a trend in UDP-GlcNAc (p=0.063) . Inflammation is positively correlated with insulin dose (p=0.005) , in addition to mean glucose (p<0.01) and coefficient of variation (p<0.01) from the CGM.

Conclusion: Biologic changes were observed in skin histology and metabolites at CSII sites that may be associated with inflammation, oxidative stress response, protein synthesis and wound healing. These could have a clinical impact on insulin availability and diabetes control.

Disclosure

J. D. Baran: n/a. D. Khakpour: None. A. Kalus: None. M. Shinohara: Other Relationship; Aztex, Cabaletta Bio, Elorac. X. Dong: None. D. S. Hippe: Research Support; Canon America Medical Systems, GE Healthcare Systems, Philips Healthcare. I. B. Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic.

Funding

Leona M. and Harry B. Helmsley Charitable Trust