bluuebunny/crossref_metadata_2025 huggingface dataset:
1427-P: Long-Term Treatment with Testosterone Leads to Profound Weight Loss in Men with Hypogonadism and Type 2 Diabetes: Update of Real-World Data from a Registry Study
Authors: HAIDER AHMAD , HAIDER KARIM S. , SAAD FARID
Published: May 2022

Background: Prevalence of hypogonadism in men with T2DM has been reported as high as 50%. ADA Guidelines recommend measuring testosterone in men with T2DM.

Methods: Of 370 men with hypogonadism and T2DM, 302 (81.6%) were obese, 62 (16.8%) overweight and 6 (1.6%) had normal weight. 190 received injections of testosterone undecanoate 1000 mg/12 weeks (T-group) following an initial 6-week interval, 180 opted against treatment (CTRL) . Means and standard deviations of absolute measures over 13 years of treatment are reported.

Results: Mean baseline age: 62.0±5.2 years, mean (median) follow-up: 9.3±3.1 (10) years. Waist circumference (cm) decreased from 117.9±14.8 to 98.2±4.3 in the T-group (p<0.0001) and increased in CTRL from 116.9±13.5 to 119.0±8.4 (p<0.0001) . Difference between groups at 13 years: 21.8 (p<0.0001) . Weight (kg) decreased from 114.4±13.8 to 88.3±7.6 in the T-group (p<0.0001) and increased in CTRL from 102.7±14.1 to 104.5±10.2 (p<0.0001) . Difference between groups: 21.4 (p<0.0001) .

BMI (kg/m²) decreased from 36.5±4.4 to 28.5±2.4 in the T-group (p<0.0001) and increased in CTRL from 32.8±4.7 to 33.3±3.6 (p<0.0001) . Difference between groups: 6.9 (p<0.0001) .

Weight change from baseline was -21.5±5.2% in the T-group and 9.3±3.0% in CTRL (p<0.00for both) . Difference between groups: 30.4% (p<0.0001) .

Waist:height ratio decreased from 0.67±0.to 0.56±0.03 in the T-group and increased from 0.66±0.to 0.67±0.05) in CTRL (p<0.00for both) . Difference between groups: 0.12 (p<0.0001) .

Visceral adiposity index (VAI) decreased from 5.9±3.1 to 1.8±0.4 in the T-group and increased from 5.2±2.6 to 9.1±4.4 in CTRL (p<0.00for both) . Difference between groups: 7.6 (p<0.0001) .

Adherence to testosterone therapy was 100%.

Conclusions: Long-term treatment with testosterone undecanoate injections results in profound weight loss maintained over up to 13 years. Untreated hypogonadal patients gain weight.

Disclosure

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

Funding

Bayer AG
1437-P: Waist-to-Height Ratio Is a Better Indicator Instead of Waist Circumference for Diagnosing Metabolic Syndrome in Type 2 Diabetes
Authors: KE JIANGFENG , WANG JUNWEI , MA YILIN , WANG YUJIE , LI LIAN-XI
Published: May 2022

Waist circumference (WC) is currently one of the components of metabolic syndrome (MetS) , but the cutoff points of WC for diagnosing MetS vary between races and genders. Therefore, the aim of this study is to search an anthropometric indicator instead of WC that would be applicable across races and genders. Our previous study found that a waist-to-height ratio (WHtR) >= 0.52 has excellent diagnostic value for MetS in both men and women with type 2 diabetes mellitus (T2DM) . We therefore selected 8525 T2DM patients with complete clinical data in the present study. Agreement between a WHtR >= 0.52 and different WC diagnostic criteria for men (>=90cm) and women (>=80cm) was almost perfect (Kappa=0.911) . As a component of MetS instead of WC, the AUC of new criteria using WHtR to diagnose MetS was 0.963 in T2DM patients. Using a WHtR cut-off of 0.52 most closely associated with the prevalence of MetS in man (98.0% sensitivity and 94.7% specificity) and women (95.7% sensitivity and 98.0% specificity) participants and. Taken together, the use of WHtR instead of WC is a simple and practical indicator for the diagnosis of MetS in T2DM.

Disclosure

J.Ke: None. J.Wang: None. Y.Ma: None. Y.Wang: None. L.Li: None.

Funding

National Natural Science Foundation of China (81770813, and 82070866) .
1439-P: Association between Sleep Duration, Bedtime, and Hyperglycemia or Overweight/Obesity among Japanese Children
Authors: SHIOZAKI HARUKA , FUJIHARA KAZUYA , YAMADA MAYUKO H. , OSAWA TAEKO , KITAZAWA MASARU , MATSUBAYASHI YASUHIRO , YAGUCHI YUTA , YAMAMOTO MASAHIKO , SATO TAKAAKI , YAMADA TAKAHO , SONE HIROHITO
Published: May 2022

In adults, short sleep duration and late bedtime were associated with hyperglycemia and obesity, but these relationships in children are little known. We evaluated the association of bedtime and sleep duration with overweight/obesity or hyperglycemia in children by sex, considering the effects of diet, physical activity, and screen time. A cross-sectional study was conducted for 1139 Japanese children (553 boys) aged 10-y. Overweight was as defined by the International Obesity Task Force. Cutoff value for hyperglycemia was HbA1c ≥5.6%. Variables associated with hyperglycemia or overweight were based on logistic regression analysis. Multivariate logistic regression analysis showed that compared with an early bedtime (˜21:59) and long sleep duration (weekdays ≥8.67 h, weekends ≥9 h) , short sleep duration (weekdays <8.67 h, weekends <9 h) was associated with overweight in boys but not late bedtimes (22:00˜) . The significant association seen disappeared in girls when adjusted for screen time. For hyperglycemia, in both sexes wake time and sleep duration on weekends were significant in univariate analysis, but not in multivariate analysis adjusted for diet and physical activity. In Japanese boys, short sleep duration was significantly associated with overweight. Sleep ≥8.67 on weekdays and ≥9 h on weekends may be essential to prevent overweight. Table. Adjusted odds ratios for overweight

Disclosure

H. Shiozaki: None. K. Fujihara: None. M.H. Yamada: None. T. Osawa: None. M. Kitazawa: None. M. Yamamoto: None. T. Sato: None. T. Yamada: 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.

Funding

Patient Centered Outcomes Research Institute
190-OR: Increased Risk of Incident Diabetes after Therapy with Immune Checkpoint Inhibitor Compared with Conventional Chemotherapy: A Longitudinal Trajectory Analysis Using a Tertiary Care Hospital Database
Authors: JEONG KYEONG SEOB , LEE MINYOUNG , PARK YU RANG , RHEE YUMIE
Published: May 2022

Immune checkpoint inhibitors (ICI) have been emerged as a promising option for cancer treatments. However, ICI use induces immune-related adverse events including diabetes mellitus. We investigated the risk of new-onset diabetes in patients receiving ICI compared with conventional chemotherapy (CC) . Using a tertiary care hospital database, we included cancer patients without previous history of diabetes and treated with either CC or ICI. One-to-five nearest neighbor propensity matching was applied, and the risk for diabetes was estimated using a Cox proportional hazards model. Latent class growth modeling was performed in a trajectory approach to determine distinct clusters following a similar glucose trajectory pattern over time. Of 1,326 subjects, 1,1received CC, and 221 received ICI. The ICI group had a significantly higher cumulative incidence of diabetes compared with those in the CC group (log-rank p < 0.001) . In addition, the risk of new-onset diabetes was significantly increased in the ICI group compared to the CC group (adjusted hazard ratio 2.454, 95% confidence interval 1.528-3.940; p < 0.001) . The proportion of subjects in the trajectory cluster with an increasing glucose pattern was higher in the ICI group than in the CC group (10.4% for the ICI group and 7.4% for the CC group) . Among the ICI group, subjects with an increasing glucose pattern were predominantly male and associated with enhanced lymphocytosis after ICI administration.

In conclusion, ICI therapy is associated with an increased risk of incident diabetes compared with CC. Glucose levels in the subjects treated with ICI need to be regularly monitored for earlier detection of ICI-associated diabetes, especially males and those with prominent lymphocytosis after ICI treatment.

Disclosure

K.Jeong: None. M.Lee: None. Y.Park: None. Y.Rhee: None.

Funding

Grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) , funded by the Ministry of Health & Welfare, Republic of Korea. (grant number: HI19C0189) , and the Bio & Medical Technology Development Program of the National Research Foundation (NRF) , funded by the Korean government (MSIT) (NRF2019M3E5D4064682) .
208-LB: Sensory Nerve Neuropeptide Calcitonin Gene–Related Peptide (CGRP) in Adipose Tissue Changes According to Metabolic Status
Authors: MISHRA GARGI , WILLOWS JAKE
Published: May 2022

White adipose tissue (WAT) is the chief energy storage site in the body and is densely innervated by sensory and sympathetic nerves that enable bi-directional neural communication with the central nervous system. The sympathetic neurotransmitter norepinephrine is the best-studied nerve product in WAT, and is known to stimulate lipolysis, browning (development of brown adipocytes in WAT) , thermogenesis, and other metabolically favorable processes. Conversely, sensory nerves in WAT secrete neuropeptides such as calcitonin gene related peptide (CGRP) , a vasodilatory neuropeptide that also impacts lipolysis, but has been vastly understudied. Circulating CGRP levels are known to be increased in obese humans, but given the beneficial metabolic effects of CGRP this may be a case of CGRP receptor resistance, similar to the observed leptin and insulin resistance with obesity. Therefore, a more comprehensive investigation into CGRP’s roles in adipose tissue and the importance of the sensory nerve supply for WAT function and insulin sensitivity is warranted. Using intravital calcium imaging in WAT of mice, we have observed activation of tissue nerves after application of lipids such as 13-HODE, which is an agonist of sensory nerves and leads to CGRP release. Thirty minutes after 13-HODE administration to WAT there was a significant increase in CGRP levels in WAT (by tissue ELISA) , which were reduced at 120min post-treatment. This suggests local lipid levels in WAT may trigger release of this sensory neuropeptide as an interoceptive response. With obesity, in both diet-induced and genetic ob/ob mice, we see increased WAT CGRP, which fits with reports in humans and may be due to chronically elevated tissue lipids. Exercise also increases tissue CGRP levels, perhaps due to an acute need for lipid fuels in this negative energy balance state. Taken together, CGRP is a novel factor in adipose that may be relevant for changing energy balance status and likely contributes to metabolic health.

Disclosure

G. Mishra: None. J. Willows: None.
230-OR: Hepatic TORC2 Signaling Facilitates Glucagon-Receptor Enhancement of Insulin-Stimulated Glucose Homeostasis in Mice
Authors: KIM TEAYOUN , NASON SHELLY , ANTIPENKO JESSICA P. , FINAN BRIAN , SHALEV ANATH , DIMARCHI RICHARD , HABEGGER KIRK M.
Published: May 2022

Long term glucagon receptor (GCGR) agonism is associated with hyperglycemia and glucose intolerance, while acute GCGR agonism enhances whole-body insulin sensitivity and hepatic AKTSer473 phosphorylation. These divergent effects establish a critical gap in knowledge surrounding GCGR action. mTOR Complex 2 (mTORC2) is composed of seven proteins, including RICTOR, which dictates substrate binding and allows for targeting of AKTSer473. We utilized a liver specific Rictor knockout mouse (RictorΔLiver) to investigate whether mTORC2 is necessary for insulin-receptor (INSR) and GCGR crosstalk. RictorΔLiver mice were characterized by impaired Akt signaling and glucose intolerance. Intriguingly, RictorΔLiver mice were also resistant to GCGR-stimulated hyperglycemia. Consistent with our prior report, GCGR agonism increased glucose infusion rate and suppressed hepatic glucose production during hyperinsulinemic-euglycemic clamp of control animals. However, these benefits to insulin sensitivity were ablated in RictorΔLiver mice. We observed diminished AKTSer473 and GSK3α/β Ser21/9 phosphorylation in RictorΔLiver mice, whereas phosphorylation of AKTThr3was unaltered in livers from clamped mice. These signaling effects were replicated in primary hepatocytes isolated from RictorΔLiver and littermate control mice, confirming cell autonomous crosstalk between GCGR and INSR pathways.

In summary, our study reveals the necessity of RICTOR, and thus mTORC2, in GCGR-mediated enhancement of liver and whole-body insulin action.

Disclosure

T.Kim: None. S.Nason: None. J.P.Antipenko: None. B.Finan: Employee; Novo Nordisk. A.Shalev: None. R.Dimarchi: None. K.M.Habegger: Consultant; Glyscend Inc., Research Support; Eli Lilly and Company, Novo Nordisk, Stock/Shareholder; Glyscend Inc.

Funding

1R01DK112934P30DK079626
234-OR: Noninvasive Hypoglycemia Detection during Real Car Driving Using In-Vehicle Data
Authors: LEHMANN VERA , ZUEGER THOMAS , MARITSCH MARTIN , NOTTER MICHAEL , SCHALLMOSER SIMON , BÉRUBÉ CATERINA , ALBRECHT CAROLINE , KRAUS MATHIAS , FEUERRIEGEL STEFAN , FLEISCH ELGAR , KOWATSCH TOBIAS , LAGGER SOPHIE N. , LAIMER MARKUS , WORTMANN FELIX , STETTLER CHRISTOPH
Published: May 2022

Aim: To develop a non-invasive machine learning (ML) approach to detect hypoglycemia during real car driving based on driving (CAN) , and eye and head motion (EHM) data.

Methods: We logged CAN and EHM data in 21 subjects with type 1 diabetes (18 male, 41 ± yrs, A1c 6.8 ± 0.7 % [51 ± 7 mmol/mol]) during driving in eu- (EU) and hypoglycemia (< 3.0 mmol/L, HYPO) . Participants drove in a car (Volkswagen Touran) supervised by a driving instructor on a closed test-track. Using CAN and EHM data, we built ML models to predict the probability of the driver being in HYPO. To make our approach applicable to different generations of cars, we present 3 ML models: first, a model combining CAN+EHM, representing the modern car with integrated camera. Second, a CAN model using driving data only, since modern cars are not generally equipped with EHM tracking. Third, anticipating that autonomous driving will limit the role of CAN data in the future, we tested a model solely based on EHM.

Results: Mean BG in EU and HYPO was 6.3 ± 0.8 mmol/L and 2.5 ± 0.5 mmol/L (p< 0.001) , respectively. The model CAN+EHM achieved an area under the receiver operating characteristic curve of 0.88 ± 0.05, sensitivity of 0.70 ± 0.30, and specificity of 0.83 ± 0.in detecting HYPO. Further results are in Fig. 1.

Conclusion: We propose ML-based approaches to non-invasively detect HYPO from driver behavior, applicable to contemporary cars and anticipating developments in automotive technology.

Disclosure

V.Lehmann: None. E.Fleisch: None. T.Kowatsch: Advisory Panel; Pathmate Technologies AG, Research Support; CSS Insurance, Stock/Shareholder; Pathmate Technologies AG. S.N.Lagger: None. M.Laimer: None. F.Wortmann: None. C.Stettler: None. T.Zueger: None. M.Maritsch: None. M.Notter: None. S.Schallmoser: None. C.Bérubé: None. C.Albrecht: None. M.Kraus: None. S.Feuerriegel: None.

Funding

Swiss National Science Foundation (SNF CRSII5_183569) , Swiss Diabetes Foundation, Diabetes Center Berne, Automobile Club Switzerland (ACS) , Federal Department of Defence, Civil Protection and Sport (DDPS) and Department of Research of the University Hospital Berne
245-LB: An Ankyrin-B–Mediated Protein Chaperone Mechanism Modulates Pancreatic ß-Cell Susceptibility to Proteotoxicity-Induced ER Stress and Apoptosis
Authors: TZENG JOYCE , HOHMEIER HANS-EWALD , LORENZO DAMARIS
Published: May 2022

Impaired insulin secretion contributes to the development and progression of diabetes. β-cells initially cope with the genetic, environmental, and diabetogenic stresses that diminish insulin secretion or the peripheral response to it by increasing insulin production. However, sustained increases in the insulin precursor proinsulin (PI) place additional demand on the secretory and protein quality control (PQC) machineries of β-cells, triggering endoplasmic reticulum (ER) and oxidative stress, mitochondrial dysfunction, and β-cell death. Thus, understanding the mechanisms that regulate β-cell responses to increased insulin secretory requirements is critical to prevent β-cell failure. We reported that the cytoskeletal scaffolding protein ankyrin-B (AnkB) regulates insulin secretion by maintaining normal levels of the inositol-1,4,5-triphosphate receptor (IP3R) at the ER and intracellular calcium in β-cells. IP3R levels and insulin secretion were impaired in knock-in mice carrying the p.R1788W AnkB (AnkB-RW) variant associated with type 2 diabetes (T2D) in Caucasians and Hispanics. Here, we show that selective loss of AnkB or expression of the T2D AnkB-RW variant lead to reduced insulin secretion and accumulation of PI and islet specific amyloid polypeptide in β-cells. These changes are accompanied by enhanced induction of the maladaptive unfolded protein response and apoptosis. Interestingly, the T2D AnkB-RW variant lies within the binding site for the protein chaperone Dnajb1 (Hsp40) . Our results indicate that the Dnajb1-Hspa1a complex, which recognizes and delivers protein clients to Hsp70 chaperones to promote proper folding, refolding, or degradation, is downregulated in β-cells from β-cell-specific AnkB knockout or AnkB-RW mice. Increased proteotoxicity and reduced insulin secretion were also observed upon knockdown of Dnajb1 in rat INS1 832/13 cells. Together, our findings suggest that AnkB and its integration into the Dnajb1-Hspa1a pathway modulates PQC and promotes β-cell survival under diabetogenic conditions.

Disclosure

J. Tzeng: None. H. Hohmeier: None. D. Lorenzo: None.
254-LB: EndoC-ßH5 Human Beta Cells—A Unique “Thaw and Go” Model for Accelerating Diabetes Research with Highly Functional and Ready-to-Use Human Beta Cells
Authors: OLLEIK HAMZA , BLANCHI BRUNO
Published: May 2022

In 2021, 537 million adults were living with diabetes worldwide (90% T2D) , a number that is predicted to rise to 643 million by 2030. The need for physiologically relevant human cellular models to study human beta cell function, insulin secretion and diabetes is thus greater than ever. To date, human pancreatic islets present many drawbacks related to lack of availability and reproducibility that limit their use. While animal models remain far from human reality. Newly developed EndoC-βH5® cells represent an extremely promising tool both for drug discovery and disease modeling. They take the best out of native cells from which they were derived, with high sensitivity to physiological concentrations of glucose and robust response to insulin secretagogues. They also leave the rest, thanks to direct availability as frozen stocks, ready-to-use format, batch-to-batch reproducibility and maintaining stable function for weeks. Specifically, EndoC-βH5® is a pure population of insulin expressing cells (100% INS/92.3% PDX1/90% NKX6.1) . Insulin content is close to that of native pancreatic beta cells (> 5µg/million cells) . EndoC-βH5® cells dose dependently respond to physiological concentrations of glucose (highest potentiation of insulin secretion between 2.8 and 8 mM glucose) with elevated absolute insulin secretion values (hundreds of ng/hr/106 cells) similar to native islets. Furthermore, they dose dependently respond to GLP1R agonists, GIPR agonist, and dual agonist Tirzepatide® with reproducible EC50 and increased insulin secretion >3-fold over high glucose. In addition, Endoc-BH5® cells can be assayed in 384-well plates paving the way for HTS and have been validated as 3D spheroids with extremely robust functional data. Finally, expression of diabetes related genes can be modified to produce relevant disease models. Overall, EndoC-βH5® represent a novel human pancreatic beta cell solution with very high potential for developing human diabetes models, unraveling diabetes mechanisms in human cells and developing antidiabetic drugs.

Disclosure

H. Olleik: None. B. Blanchi: None.
284-OR: Diabetes Technology Access for Youth with T1D and High Social Risk: Comparing Intervention Outcomes
Authors: LELY JUSTINE , HARRIS MICHAEL A. , NARANJO DIANA , JENISCH CELESTE , MANABAT ANN JELINE F. , CRUZ CRISTIAN , BENSEN RACHEL , OSPINA ANDREA BONILLA , WAGNER DAVID V.
Published: May 2022

Objective: Health disparities exist in diabetes technology access for those youth with T1D who experience high social risk, despite likely benefits. Novel Interventions in Children’s Healthcare (NICH) , designed to improve health for youth with T1D experiencing such disparities, has previously been associated with improved diabetes technology access. This study compares diabetes technology use prior to and after NICH referral, and is the first such study to include a control group.

Methods: Youth with T1D served by NICH (n=65) and referred youth (“controls”: n=73) across 3 sites were included. EHR data included DKAs, hospitalizations, ED visits, and presence of diabetes technology 1 year prior and 2 years after NICH initiation. No significant demographic differences.

Results: Compared to the controls, NICH youth were significantly more likely to gain a CGM and experience significantly greater reductions in hospital admits, DKAs, and ED visits. After accounting for prior differences, only DKA event reduction and CGM access continued to be significant. Youth in NICH also averaged more years with tech access.

Conclusion: This study demonstrates that while youth referred to NICH experience substantial barriers to accessing diabetes technology, youth in NICH were more likely to gain CGM access and have fewer DKA events than controls - and neither group approached national averages in technology access.

Disclosure

J.Lely: None. M.A.Harris: None. D.Naranjo: None. C.Jenisch: None. A.F.Manabat: None. C.Cruz: None. R.Bensen: None. A.Bonilla ospina: None. D.V.Wagner: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
298-OR: Variant-to-Gene Mapping at the Childhood Obesity Locus on chr12q13 and Subsequent Luciferase Assay Analyses Implicate rs71329as a Causal Variant within the 3’ UTR of FAIM2
Authors: LITTLETON SHERIDAN H. , BRADFIELD JONATHAN , PIPPIN JAMES A. , SU CHUN , CHESI ALESSANDRA , WELLS ANDREW D. , BERKOWITZ ROBERT I. , PAHL MATTHEW C. , GRANT STRUAN F.
Published: May 2022

A key limitation of genome-wide association studies (GWAS) is that they do not specify either the underlying causal variant (s) or the effector gene (s) at a given locus. The widely reproduced obesity FAIM2 locus, named arbitrarily after the nearest gene, is relatively understudied given it is more strongly associated in children than in adults. Our previously reported trans-ancestral GWAS meta-analysis of childhood obesity enabled fine-mapping of the FAIM2 locus; in the ‘credible set’ of 6 SNPs, rs71329 had the highest probability of being causal. This non-coding variant resides in the 3’ untranslated region (UTR) of FAIM2. Given that obesity-related GWAS signals have been reported to be enriched in genes relevant to neuronal function, we generated ATAC-seq and high-resolution promoter-focused Capture C data in both primary astrocytes and ESC-derived hypothalamic neurons to carry out variant-to-gene mapping at this locus. We observed that rs71329 occupied a region of open chromatin, therefore a putatively functional element, and made physical contact with the FAIM2 promoter. These findings were also supported by both GTEx testes eQTL data and a transcriptome-wide association study in brain tissue. We sought to determine in vitro if the rs71329alleles influence enhancer activity in primary astrocytes. Using technical replicates repeated 8 times, the non-risk allele region increased luciferase reporter expression relative to the FAIM2 promoter alone by a fold change of 1.87, while the risk allele decreased expression by a fold change of 0.68 (non-risk allele+FAIM2 promoter vs. risk allele+FAIM2 promoter P<0.0001) . Our results show that rs71329resides in an enhancer element and suggest that the risk allele within the 3’ UTR of FAIM2 decreases the expression of this putative effector gene, which then confers risk of childhood obesity and in turn type 2 diabetes later in life.

Disclosure

S.H.Littleton: None. J.Bradfield: None. J.A.Pippin: None. C.Su: None. A.Chesi: None. A.D.Wells: Stock/Shareholder; Johnson & Johnson. R.I.Berkowitz: Research Support; Eisai Inc., Novo Nordisk. M.C.Pahl: None. S.F.Grant: None.

Funding

National Institutes of Health (HD056465)
322-OR: ECG-Derived QRS-T Angle Is an Independent Predictor of Sudden Cardiac Death in Patients with Type 2 Diabetes: From the SURDIAGENE Prospective Study
Authors: GARCIA RODRIGUE , TAVERNIER MARINE , GAND ELISE , DE KEIZER JOE , ALOS BENJAMIN , BOULETI CLAIRE , DEGAND BRUNO , HADJADJ SAMY , SAULNIER PIERRE-JEAN ,   THE SURDIAGENE STUDY GROUP
Published: May 2022

Diabetes is associated with a high risk of sudden cardiac death (SCD) but the risk of non-SCD is even higher. We aimed to assess cardiac electrical markers for predicting SCD in patients with T2D.

SURDIAGENE is a French prospective cohort of T2D patients. Baseline 12-lead ECG of 1285 (64±years; 43% female) patients were concordantly evaluated by 2 cardiologists to measure 15 ECG-derived markers. Causes of death were adjudicated by an independent committee. The primary outcome was SCD which was defined as a sudden, natural, and unexpected death, with preceding duration of symptoms <24 hours for witnessed cases and <1 hour witnessed cases. Bonferroni-adjusted cause-specific Cox proportional hazards and Fine and Gray competing-risk models were performed to identify independent predictors (adjustment for age, sex, HbA1c, NT-proBNP, eGFR, ACR, history of myocardial infarction, diuretic, and insulin) . At baseline, mean diabetes duration was 14±years and mean HbA1c 7.8±1.6%. During a median follow up of 7.4 years, 446 deaths occurred including 83 (18.6%) SCD. In univariate analysis, R wave voltage ≥mm in aVL lead, corrected QT interval and QRS-T angle ≥90° were associated with SCD risk at the Bonferroni-adjusted level of significance (P < 0.0033) . Using competing-risk multivariate analysis, QRS-T angle ≥90° only was significantly associated with a higher risk of SCD (sHR 1.63 [1.01-2.62]; P=0.045) but interestingly not with non-SCD (sHR 1.02 [0.78-1.33], P=0.87) . Discrimination of SCD prediction model was improved by QRS-T angle beyond multivariate Cox model parameters (C-statistic improved from 0.798 to 0.805, P<0.0001) .

ECG-derived QRS-T angle is an independent predictor of SCD in patients with T2D and improves SCD-risk model prediction accuracy.

Disclosure

R.Garcia: Other Relationship; Abbott, Boston Scientific Corporation, Medtronic, Microport. The surdiagene study group: n/a. M.Tavernier: None. E.Gand: None. J.De keizer: None. B.Alos: None. C.Bouleti: Consultant; AstraZeneca, Novartis Pharmaceuticals Corporation, Research Support; Pfizer Inc. B.Degand: None. S.Hadjadj: Consultant; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novartis AG, Novo Nordisk, Sanofi, Servier Laboratories, Valbiotis, Other Relationship; Janssen Pharmaceuticals, Inc. P.Saulnier: Consultant; Grünenthal Group, Research Support; AstraZeneca, Novo Nordisk, Sanofi.
335-OR: Dapiglutide, a Once-Weekly GLP-1R/GLP-2R Dual Agonist, Was Safe and Well Tolerated and Showed Dose-Dependent Body Weight Loss over Four Weeks in Healthy Subjects
Authors: OLSEN MINNA B. , HÖVELMANN ULRIKE , GRIFFIN JON , KNUDSEN KIM M. , ERIKSSON PER-OLOF , AGERSNAP MIKKEL A.
Published: May 2022

Dapiglutide is a first-in-class peptide with dual activity on the GLP-1 and GLP-2 receptors and with potential to treat several metabolic/gastrointestinal (GI) diseases. In a multiple ascending dose cohort trial, 40 healthy subjects (mean BMI 24.6 kg/m2) received once weekly s.c. injections of dapiglutide (1, 2.25, 3.5 or 6 mg) or placebo for 4 weeks. There were no serious or severe adverse events (AEs) and no withdrawals. The most frequent related AEs reported were GI disorders and metabolism and nutrition disorders similar to marketed GLP-1RAs. No subject developed anti-drug antibodies. The pharmacokinetics (PK) showed dose proportionality with a low inter-subject variability and a mean half-life of 123-129 hours across the 4 dose cohorts. Dose-response was shown for plasma glucose, insulin, triglycerides, and gastric emptying after a mixed meal test. Mean body weight loss was 0.1%, 0.5%, 2.4% and 4.5% after 4 weeks of treatment in each cohort (fig 1) . Multiple doses of dapiglutide were well-tolerated and the safety profile is similar to GLP-1 and GLP-2 receptor agonists. The PK results support that dapiglutide is suitable for once-weekly dosing. The clinical potential of dapiglutide as a novel treatment for obesity and NASH should be explored in trials of longer duration.

Disclosure

M.B.Olsen: Employee; Zealand Pharma A/S, Stock/Shareholder; Novo Nordisk A/S, Zealand Pharma A/S. U.Hövelmann: None. J.Griffin: Employee; Zealand Pharma A/S, Stock/Shareholder; Zealand Pharma A/S. K.M.Knudsen: Employee; Zealand Pharma A/S. P.Eriksson: Employee; Zealand Pharma A/S. M.A.Agersnap: Employee; Zealand Pharma A/S.
356-OR: DNA Methylation Suggests Accelerated Biological Age and Specific Biomarkers Correlate with the Speed of Aging in Diabetes Mellitus
Authors: CORTEZ BRIANA N. , PAN HUI , AGUAYO-MAZZUCATO CRISTINA
Published: May 2022

Type 2 Diabetes (T2D) correlates with increased biological age (BA) as indicated by clinical biomarkers. Chronological age (CA) is the total years lived, while BA depicts cellular level changes. Our prior data showed that BA was accelerated in Type 1 Diabetes (T1D) and T2D with a large spread of individual BA within these groups. It is unknown whether accelerated age in diabetes mellitus (DM) is also seen at the DNA methylation (DNAm) level, the gold standard to determine BA, and which variables regulate the speed of aging in individuals. We hypothesized that DNAm would reflect accelerated aging in tissues from people with T2D and that specific biomarkers would associate with the speed of aging. The DNAm Phenotypic Age Clock was used to determine BA and showed accelerated aging in whole blood (p=0.01) and pancreatic islets (p=0.03) from people with T2D. Linear regression was used to find associations between biomarkers and speed of aging using the NHANES 2017-18 and ACCORD Trial cohorts. Avoidance of fried foods (p=0.02) and fat intake (p=0.01) , and vigorous activity (p=0.001) correlated with decreased BA in T2D. Biomarkers associated with slower aging (BA<5 years from CA) were higher albumin (p<0.04) , lower globulin (p=5.7x10-5) , lower blood pressure (p<0.005) , higher hemoglobin (p<0.03) and older age at DM diagnosis (p=0.04) . Faster aging (BA>5 years from CA) was associated with higher total and LDL-cholesterol (p<0.003) , pulse (p=0.002) , platelet count (p<0.03) , glycohemoglobin (p<3.6x10-5) and fasting glucose (p<0.04) , and lower self-perception of health (p=0.005) . Normal aging (BA within 5 years of CA) associated with greater ferritin (p=0.03) and moderate-intensity activity at work (p=0.005) .

In conclusion, DNAm of blood and islets from people with T2D age faster than those without. Further analysis of specific variables associated with the speed of aging will identify crucial intervention nodes to alter the aging speed in a population with DM.

Disclosure

B.N.Cortez: None. H.Pan: n/a. C.Aguayo-mazzucato: Consultant; eGenesis.
389-P: A Six-Month Periodic Fasting Reduces Microalbuminuria and Improves Metabolic Control in Patients with Type 2 Diabetes and Diabetic Nephropathy: A Randomized Controlled Study
Authors: SULAJ ALBA , KOPF STEFAN , RAUCHHAUPT EKATERINA V. , KLIEMANK ELISABETH , BRUNE MAIK , KENDER ZOLTAN , BARTL HANNELORE , GARCIA-CORTIZO FABIOLA , KLEPAC KATARINA , HAN ZHE , KUMAR VARUN , LONGO VALTER , TELEMAN AURELIO , OKUN JUERGEN G. , MORGENSTERN JAKOB , FLEMING THOMAS H. , SZENDROEDI JULIA M. , HERZIG STEPHAN
Published: May 2022

Aim: To assess whether periodic fasting reduces albuminuria and activates nephropathy-driven pathways in patients with type 2 diabetes and diabetic nephropathy.

Methods: Forty patients with type 2 diabetes (HbA1c 7.8±0.2% [62.1±2.3 mmol/mol]) and increased albumin-to-creatinine ratio (ACR) were randomized to fasting-mimicking diet (FMD) (n=21) or Mediterranean diet (n=19) for six months with three-month follow-up. Primary endpoint was the difference of the change in ACR from baseline to after six months between groups. Subgroup analysis for patients with micro- versus macroalbuminuria at baseline was performed. Secondary endpoints comprised HOMA-IR, circulating markers of dicarbonyl detoxification (MG-H1, glyoxalase-1 and hydroxyacetone) , lipid oxidation (acylcarnitines AC) , DNA-damage/repair, (yH2Ax) and senescence (suPAR) . Comparison was done by ANCOVA adjusted for age, sex, weight loss and baseline values of the respective outcome.

Results: Difference of change in ACR between FMD and control group after six months was 110.3mg/g (95% CI 99.2, 121.5mg/g; P=0.45) in all patients, -30.3mg/g (95% CI -35.7, -24.9mg/g; P≤0.05] in patients with microalbuminuria, and 434.0mg/g (95% CI 404.7, 463.4mg/g; P=0.23) in those with macroalbuminuria at baseline. FMD led to change in HOMA-IR of -3,8 (95% CI -5,6, -2.0; P≤0.05) and in suPAR of -156.6pg/ml (95% CI -172.9, -140.4pg/ml; P≤0.05) after six months, while no change was observed in markers of dicarbonyl detoxification or DNA-damage/repair. Change in AC profile was related to patient responsiveness to ACR improvement. At follow-up only HOMA-IR reduction (-1.9 [95% CI -3.7, -0.1], P≤0.05) was sustained.

Conclusions: When accompanied by intensive diabetes care, FMD improves microalbuminuria, HOMA-IR and suPAR. Lack of changes in markers of dicarbonyl detoxification and DNA-damage/repair might explain the relapse of albuminuria at follow-up.

Disclosure

A.Sulaj: None. Z.Han: None. V.Kumar: None. V.Longo: Stock/Shareholder; L-Nutra Inc. A.Teleman: None. J.G.Okun: None. J.Morgenstern: None. T.H.Fleming: None. J.M.Szendroedi: Consultant; Boehringer Ingelheim International GmbH. S.Herzig: None. S.Kopf: Board Member; Novo Nordisk, Speaker's Bureau; AstraZeneca, Recordati S.p.A. E.V.Rauchhaupt: None. E.Kliemank: None. M.Brune: None. Z.Kender: None. H.Bartl: None. F.Garcia-cortizo: None. K.Klepac: None.

Funding

German Research Foundation DFG (236360313 and 255156212) German Center for Diabetes Research DZD (82DZD07C2G)
40-OR: 4T Study: Tighter Glucose Target Settings with Early CGM Initiation Further Improves A1C in Youth with T1D
Authors: PRAHALAD PRIYA , DING VICTORIA , ZAHARIEVA DESSI P. , ADDALA ANANTA , BISHOP FRANZISKA K. , SCHEINKER DAVID , JOHARI RAMESH , DESAI MANISHA , HOOD KOREY K. , MAAHS DAVID M. ,   4T STUDY GROUP
Published: May 2022

In the Pilot 4T study (diagnosed July 2018 to May 2020, A1c target <7.5%, n=135) , early CGM initiation and remote patient monitoring (RPM) was associated with lower A1c. We hypothesized that tightening A1c targets to <7% would further lower A1c.

All youth with newly diagnosed T1D from June 2020 to December 2021 were offered CGM initiation in the first month of diagnosis and RPM (4T cohort, n=115) . We compared A1c outcomes in the 4T cohort with the Pilot 4T cohort and the Historical cohort who were not offered early CGM (diagnosed 2014-2016, n=272) . We visualized population-based A1c trajectories using locally estimated scatter plot smoothing (LOESS, Fig) .

Mean A1c at diagnosis was similar in the 4T and Pilot 4T cohorts (12.3% v 12.2%) and higher than the Historical cohort (10.7%) . The median age of diagnosis was 11.2 years [7.1, 14], 53% male, 35% non-Hispanic White, and 65% with private insurance in the 4T cohort. CGM initiation occurred within 30 days of diagnosis in 98.3% of youth. At 3, 6, and 9 months post-diagnosis, those in the 4T cohort had LOESS-based mean A1c differences of 0.33%, 0.36%, and 0.42% lower than the Pilot 4T cohort and 0.39%, 0.62%, and 0.96% lower than the Historical cohort.

Early CGM initiation and RPM combined with tighter glucose targets was associated with a lower A1c compared to historical cohorts. These data support implementation of the 4T program with tight target setting in youth with T1D.

Disclosure

P.Prahalad: None. D.M.Maahs: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Consultant; Aditx Therapeutics, Inc., Biospex. 4t study group: n/a. V.Ding: None. D.P.Zaharieva: Research Support; Insulet Corporation, International Society for Pediatric and Adolescent Diabetes, Leona M. and Harry B. Helmsley Charitable Trust. A.Addala: None. F.K.Bishop: None. D.Scheinker: None. R.Johari: None. M.Desai: None. K.K.Hood: Consultant; Cecelia Health, Havas Health, Insulet Corporation, LifeScan Diabetes Institute.

Funding

Stanford Diabetes Research Center (P30DK116074) and R18DK122422; Dexcom; Lucile Packard Children’s Hospital Auxiliaries Endowment
428-P: Type 2 Diabetes Mellitus and Congestive Heart Failure in Women Are Mutually Independent Predictors of Nonalcoholic Fatty Liver Disease
Authors: MAECHLER MAXIMILIAN , SPRENGER LUKAS , MADER ARTHUR , LARCHER BARBARA , VONBANK ALEXANDER , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: May 2022

Nonalcoholic fatty liver disease (NAFLD) is associated with both type 2 diabetes mellitus (T2DM) and congestive heart failure (CHF) , and T2DM is highly prevalent in CHF patients, in particular among women. However, the single and joint associations of T2DM and CHF with NAFLD in women have not been investigated yet. This issue therefore is addressed in the present study.

We investigated 76 female patients with CHF and 321 female controls who did not have signs or symptoms of CHF and in whom significant coronary artery disease was ruled out angiographically. The presence of NAFLD was determined using the validated fatty liver index (FLI) .

The prevalence of T2DM was 39.5% in women with CHF and 22.1% in controls (p=0.002) . FLI values and prevalence rates of NAFLD (FLI≥60) in non-CHF women without T2DM were 43±28 and 31.6%, respectively. They were significantly higher in non-CHF, but T2DM patients (65±28, p<0.0 and 64.8%, p<0.001, respectively) , in CHF patients without T2DM (67±25, p<0.0 and 63.0%, p=0.002, respectively) and in CHF patients with T2DM (66±31, p<0.0 and 66.7%, p<0.001, respectively) . In multivariate analysis of covariance, T2DM and CHF proved to be mutually independent predictors of FLI after adjustment for age, sex, BMI, LDL-C, history of smoking and hypertension and use of statins (F=7.25; p=0.0 and F=46.89; p<0.001, respectively) ; concordantly, T2DM and CHF independently predicted the presence of NAFLD in logistic regression analyses, with adjusted odds ratios of 3.22 [1.38-7.50]; p=0.0 and 21.71 [6.58-71.59]; p<0.001, respectively.

We conclude that CHF and T2DM are mutually independent predictors of NAFLD in women.

Disclosure

M.Maechler: None. L.Sprenger: None. A.Mader: None. B.Larcher: None. A.Vonbank: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None. C.H.Saely: None.
458-P: Inflammatory Markers and Cardiovascular Autonomic Neuropathy in Type 1 Diabetes
Authors: ANG LYNN , GUNARATNAM SEJAL V.G. , HUANG YIYUAN , MIZOKAMI-STOUT KARA R. , MARTIN CATHERINE , REISS JACOB , BURANT AARON , VASBINDER ALEXI , LAUNIUS CHRISTOPHER , ZHAO LILI , FELDMAN EVA L. , HAYEK SALIM , POP-BUSUI RODICA
Published: May 2022

Objective: We aimed to assess the role of chronic inflammation in the pathogenesis of cardiovascular autonomic neuropathy (CAN) , a serious complication of type 1 diabetes (T1D) .

Methods: We leveraged an ongoing randomized, placebo-controlled clinical trial targeting inflammation with salsalate in individuals with T1D, to measure a panel of 40 inflammatory markers (Figure) in baseline samples. Measures of CAN included standardized cardiovascular autonomic reflex tests (CARTs) (E/I, Valsalva, 30/15 ratios) and indices of heart rate variability (HRV) . We used Spearman-rank to assess the correlations between inflammatory markers and CAN measures, and linear regression to adjust for age and hemoglobin A1c.

Results: The Figure displays the correlation between biomarkers and CAN measures in 58 T1D participants (mean age 51 ± 13 years, and HbA1c 8.4 ± 1.8%) . Amongst all biomarkers, we noted a singular negative correlation between soluble urokinase plasminogen activator receptor (suPAR) and measures of CAN, which remained significant in multivariable analysis (E/I ratio p=0.005, Valsalva p=0.037, RFA p=0.019, LFA p=0.023) .

Conclusion: Amongst a large panel of inflammatory markers, we found suPAR to have a notable association with CAN. SuPAR is an immune-mediated signaling glycoprotein which levels are strong predictors of risk in patients with diabetes, thus its role in CAN warrants further exploration.

Disclosure

L.Ang: None. L.Zhao: None. E.L.Feldman: None. S.Hayek: n/a. R.Pop-busui: Advisory Panel; Averitas Pharma, Inc., Boehringer Ingelheim International GmbH, Nevro Corp., Novo Nordisk, Reata Pharmaceuticals, Inc., Regenacy Pharmaceuticals, Inc. S.V.G.Gunaratnam: None. Y.Huang: None. K.R.Mizokami-stout: None. C.Martin: Advisory Panel; Nevro Corp. J.Reiss: n/a. A.Burant: None. A.Vasbinder: None. C.Launius: None.

Funding

NIH/NIDDK-1-R01-DK-107956-01
480-P: Correlation of Tg/HDL Ratio and Liver Fibrosis in People with Diabetes in a Tertiary Care Center in India
Authors: TEWARI AJOY , TEWARI VINEETA , TEWARI JAY , SABOO BHARAT , SHRIVASTAVA ABHISHEK , DARIYA S S. , CHAVDA VIPUL , HASNANI DHRUVI , INAMDAR ANIKET V. , CHOUDHURY RUPAM
Published: May 2022

Introduction: As per the recent International Diabetes Federation (IDF) atlas, there are 537million adults living with diabetes. Indians with the same body mass index (BMI) have higher central adiposity and insulin resistance compared to Caucasians. High insulin resistance in people with diabetes predisposes them to Nonalcoholic Fatty Liver Disease (NAFLD) . TG/HDL ratio is emerging as a sensitive marker of insulin resistance. Liver stiffness measurements predict advanced fibrosis in people with diabetes. The current study aims to correlate TG/HDL ratio and liver stiffness measurements using fibro scans in people with diabetes.

Material and Methods: A total of 181 people with diabetes coming for the first time at our center underwent liver stiffness measurements using fibro scans after taking consent, people on prior lipid-lowering therapy and thiazolidinedione therapy were excluded from the study.

Results: Median stiffness ranged from 2.3kpa to 34.8kpa (median of 8.0kpa) , TG/ HDL ratio values ranged from 0.5-29.3 (median of 4.5) . Median stiffness, correlated with TG/HDL ratio correlation coefficient, was 0.2 (p 0.01) . Further 26.5% subjects had advanced fibrosis (Liver stiffness measurement (LSM) >9.1) , 23.7% of male subjects and 30% of female subjects had advanced fibrosis. Males and females with LSM >9.1 had high TG/ HDL ratio, mean 4.9 in males (range 2.5-13.7) and 4.9 in females (range 1.0-17) . These values were much higher than TG/HDL values of 0.9 and 1.2 used in females and males respectively, as cutoffs to predict insulin resistance.

Discussion: Previous studies have correlated TG/HDL ratio with NAFLD in nondiabetic individuals using ultrasonography. Fibro scan is a more sensitive and specific modality to screen for NAFLD. Median stiffness predicts liver fibrosis. There is a high incidence of advanced fibrosis in the index study, which correlated with TG/HDL ratio. All male and female subjects with advanced fibrosis had a high TG/HDL ratio.

Disclosure

A.Tewari: None. R.Choudhury: None. V.Tewari: None. J.Tewari: None. B.Saboo: None. A.Shrivastava: None. S.S.Dariya: None. V.Chavda: None. D.Hasnani: None. A.V.Inamdar: None.
531-P: Continuous Glucose Monitoring Placement during Physical Activity
Authors: THRASHER BRAD J. , DYESS RYAN J. , MCKAY TIM E. , WINTERGERST KUPPER A.
Published: May 2022

Objectives: Individuals living with type 1 diabetes (T1D) are encouraged to participate in physical activity (PA) . It is vital that technology used to manage diabetes, such as a continuous glucose monitor (CGM) , provides reliable results during and after exercise. Currently, the Dexcom G6 CGM is approved to be inserted on the abdomen or upper buttock. The following study compared various location sites to assess reliability of those differing locations during times of moderate intensity PA.

Methods: Thirty adolescents and young adults (age 13-20 years, µ=14.3 years) with T1D performed moderate intensity PA on a treadmill. Intensity was determined by Karvonen heart rate reserve formula. The PA consisted of walking/jogging for 40 minutes, with a 10-minute break occurring at the halfway point. Dexcom G6 CGM and glucometer measurements were collected and analyzed every minutes during and after exercise. Dexcom locations included arm, abdomen, thigh, and upper buttock. Analysis of accuracy metrics included mean absolute relative difference (MARD) and clinical reliability was assessed by Clarke Error Grid Analysis.

Results: Analysis of CGM location sites revealed that CGMs placed on the arm and buttocks, statistically, had a worse MARD in comparison to abdomen. The CGM being placed on the buttocks increased the MARD by a ratio of 2.15 when compared to the abdomen. Additionally, we found that individuals who wore the CGM on their buttocks had an increased risk of having glucoses in Zone D of the Clarke Error Grid in comparison to those wearing it on the abdomen.

Conclusions: The results suggest that CGM location does matter during and after exercise, with the abdomen providing the most reliable results. Furthermore, we found that CGM placement on the buttocks may lead to failure to detect dysglycemia during exercise. We hypothesize this may be due to interstitial fluid changes in actively exercising muscles which alter the accuracy during exercise. However, additional research in this area is needed to support this theory.

Disclosure

B.J.Thrasher: None. R.J.Dyess: None. T.E.Mckay: None. K.A.Wintergerst: None.
59-LB: Outcomes of an Employer-Sponsored Virtual Type 2 Diabetes (T2D) Reversal Program in Working-Age Adults
Authors: CHEN ZHEN , BIRSE CHARLES E. , ARELLANO ANDRE R. , FRAGALA MAREN S. , MCPHAUL MICHAEL J. , BARE LANCE A.
Published: May 2022

Objective: To evaluate short-term outcomes of an employer-sponsored virtual T2D reversal program, conducted through medically supervised nutritional intervention and provider-led telehealth, in working-age adults.

Methods: This pre-post study included 119 employees with T2D and high HbA1c and/or high spending on T2D prescriptions who enrolled in the T2D reversal program October 15, 2020-January 27, 2021. HbA1c, fasting glucose (FG) , body weight, body index mass (BMI) , and waist circumference pre- and post-enrollment were assessed from annual employer-sponsored wellness screening conducted 2019-2021, independently of the T2D reversal program. Program prescriptions (insulin, DPP4, GLP1, meglitinide, sulfonylurea, TZD, SGLT2) were compared pre vs. post (Table footnote 1) . Pharmacy spending for these prescriptions was estimated from a third-party claims database.

Results: The program retention rate was 82% at 6 months and 67% at 1 year. Mean levels of all outcome measures declined significantly from pre to post (Table) . The number of prescriptions decreased for 47 (39.5%) of the 119 participants and increased for 3 (2.5%) . For 89 individuals participating for 6 months or more, average monthly prescription spending declined 18% (to $449 from $547) during the first 6 months after enrollment (vs. the prior 12 months) .

Conclusions: A virtual T2D reversal program helped lower HbA1c, FG, body weight, BMI, and waist circumference in employees with diabetes while reducing prescriptions and pharmacy spending.

Disclosure

Z. Chen: Employee; Quest Diagnostics, Stock/Shareholder; Quest Diagnostics. C. E. Birse: Employee; Quest Diagnostics. A. R. Arellano: Employee; Quest Diagnostics. M. S. Fragala: Employee; Quest Diagnostics, Stock/Shareholder; Quest Diagnostics. M. J. Mcphaul: Employee; Quest Diagnostics. L. A. Bare: Employee; Quest Diagnostics.