bluuebunny/crossref_metadata_2025 huggingface dataset:
423-P: Altered Microvascular Perfusion of the Pain-Processing Areas of the Brain during the Experience of Spontaneous Neuropathic Pain
Authors: GREIG MARNI , SLOAN GORDON P. , SHILLO PALLAI RAPPAI , SELVARAJAH DINESH , WILKINSON IAIN D. , TESFAYE SOLOMON
Published: June 2021

Objective: We have previously reported increased thalamic vascularity in painful diabetic peripheral neuropathy (PDPN) but the microvascular perfusion characteristics of the other pain processing areas of the brain (Pain Matrix - PM) with or without pain at the time of scanning have not been assessed. The aim thus was to measure the cerebral perfusion of the PM areas using MR-Dynamic Susceptibility Contrast (MR-DSC).

Methods: 55 T1DM subjects (20 PDPN, 23 painless-DPN, 13 no-DPN) and 19 healthy volunteers (HV) underwent clinical, neurophysiological and MR-DSC of the passage of IV-gadolinium-chelate through the cerebral vascular bed (3-Tesla, Philips, Netherlands) at rest. The PDPN group was further divided into those that had neuropathic pain during scan - P+ and no pain - P-) and the intensity of pain at the time of scanning was recorded. The Mean Transit Time -MTT and the time-to-peak -TTP concentrations of gadolinium in PM areas (Thalamus, Insular Cortex - IC, Anterior Cingulate Cortex - ACC) were measured. Results: Subjects experiencing spontaneous neuropathic pain (P+, n=10, VAS score≥4) during scanning had shorter mean TTP at the Right-Thalamus: P+ vs. painless-DPN p=0.017, P+ vs. HV p=0.033; Right-IC: P+ vs. painless-DPN p=0.048; and POWM: P+ vs. P- p=0.009, P+ vs. painless-DPN p=0.034, P+ vs. HV p=0.011. The MTT at the Right-Thalamus: P+ vs. HV p=0.043 and at the Left-IC: HV vs. No-DPN p=036, were also significant.

Conclusion: This is the first study to show there is altered cerebral perfusion in the pain processing areas of of the brain, with shorter TTP during spontaneous pain at the time of scanning. This seems to be related to a bolus dispersal factor as MTT, and CBF do not match the TTP and the control area is also affected. However, whether this altered perfusion is primary or secondary to the experience of pain is yet to be determined. This novel finding may serve as objective marker of spontaneous neuropathic pain, and a target for the development of novel treatments.

Disclosure

M. Greig: None. G. P. Sloan: None. P. Shillo: None. D. Selvarajah: None. I. D. Wilkinson: None. S. Tesfaye: Advisory Panel; Self; Angellini, Bayer AG, Eva Pharma, Wörwag Pharma, Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, MSD Corporation, Novo Nordisk, Pfizer Inc.

Funding

European Foundation for the Study of Diabetes
427-P: Prevalence and Treatment of Diabetic Macular Edema and Vision-Threatening Diabetic Retinopathy among Commercially Insured Adults Aged <65 Years
Authors: LUNDEEN ELIZABETH A. , KIM MINCHUL , REIN DAVID B. , WITTENBORN JOHN , CAI CINDY , SAADDINE JINAN B.
Published: June 2021

While diabetes prevalence in U.S. adults has increased in the last three decades, less is known about trends in ocular complications of diabetes, particularly in adults aged <65 years. We examined trends in prevalence and treatment of diabetic macular edema (DME) or vision-threatening diabetic retinopathy (DR) among commercially insured adults with diabetes. We analyzed claims from 2012 to 2018 using the IBM® MarketScan® Database, a national convenience sample of employer-sponsored health insurance. Analyses for each cross-sectional year included adults (18-64 years) with type 1 or 2 diabetes continuously enrolled for the calendar year (range: n=980,705 to n=1,715,815). Outcomes included the annual prevalence of those with ≥1 claim for: 1) DME or vision-threatening DR (severe non-proliferative DR or proliferative DR), 2) DME of any type, alone or with any stage of DR, and 3) treatment (anti-vascular endothelial growth factor [VEGF] injection, laser surgery/photocoagulation, vitrectomy, or retinal detachment repair). From 2012 to 2018, annual diabetes prevalence ranged from 7.3% to 7.8%. Annual prevalence of adults with diabetes who had ≥1 claim for DME or vision-threatening DR increased from 1.9% to 3.1% (Annual percent change [APC]: 0.23); any type of DME increased from 0.9% to 2.4% (APC: 0.29). Among those with DME or vision-threatening DR, annual prevalence of having ≥1 claim for treatment increased for anti-VEGF injection (21.9% to 31.2%; APC: 1.81) and decreased for laser surgery/photocoagulation (33.6% to 18.9%; APC: -2.65), vitrectomy (6.5% to 3.8%; APC: -0.48), and retinal detachment repair (3.9% to 2.9%; APC: -0.15). P-values for all trends were <0.01. From 2012 to 2018, among commercially insured adults aged <65 years, the annual prevalence of those with claims for DME or vision-threatening DR and DME of any type increased, coinciding with an increase in the use of anti-VEGF injection, a contemporary first-line treatment.

Disclosure

E. A. Lundeen: None. M. Kim: None. D. B. Rein: None. J. Wittenborn: None. C. Cai: None. J. B. Saaddine: None.
441-P: The Association between Time-in-Range %, Measured by Continuous Glucose Monitoring (CGM) and Physical and Functional Indices amongst Older People with Type 2 Diabetes: A Cross-Sectional Study
Authors: BASSON-SHLEYMOVICH YAMIT , CUKIERMAN-YAFFE TALI , YAHALOM-PERI TAL , AZMON MICHAL , PELTZ-SINVANI NAAMA
Published: June 2021

People with diabetes have an increased risk for mobility disability and a more rapid decline in muscle mass (sarcopenia) compared to those without diabetes. Studies have demonstrated an association between A1C and Sarcopenia. Less is known regarding the relationship with Time In Range (TIR).

Aims: To assess among older people with diabetes type 2, the cross sectional association between: TIR and aerobic capacity, gait speed, strength, balance and frailty indices.

Methods: A cross sectional study, conducted amongst people with diabetes over the age of 60. Participants were provided with a blinded CGM system- (I Pro2 carelink, Medtronic) for 1 week and underwent elaborate physical-functional assessment in the beginning and at the end of that week. The association between the % of time in range (TIR) and several physical indices was determined using linear regression.

Results: This analysis pertains to 81 men and women. After adjustment for age and gender, a 1% higher TIR (70-180) was associated with a 0.246 higher score on the 6-minute walk score, a measure of aerobic capacity and endurance (P-value=0.019) and 0.212 lower score on the Timed Up and Go(TUG), a measure of fall risk and balance (P-value=0.045).

Conclusion: Higher % TIR is associated with better scores on indices of aerobic capacity and a measure predicting falls. Future studies are needed in order to elucidated if glucose levels are merely a marker of disease severity, or if there is possibly a causal relationship.

Disclosure

Y. Basson-shleymovich: None. T. Cukierman-yaffe: Advisory Panel; Self; AstraZeneca, Research Support; Self; Medtronic, MSD Corporation, Speaker’s Bureau; Self; Eli Lilly and Company, Medtronic, MSD Corporation, Novo Nordisk, Sanofi. T. Yahalom-peri: None. M. Azmon: None. N. Peltz-sinvani: None.

Funding

European Foundation for the Study of Diabetes; Medtronic
443-P: Outcomes of Bedside Diabetic Foot Amputation by a Diabetologist
Authors: FERON FLORINE , RIVELINE JEAN-PIERRE , GAUTIER JEAN-FRANÇOIS , KEVORKIAN JEAN-PHILIPPE
Published: June 2021

Complying with simple operating rules, a diabetologist might perform Bedside Toe Amputation (BTA) for necrosis complicating diabetic foot ulcer (DFU) in case of inappropriate delay scheduled or disagreement with the amputation level proposed by the surgeon. We conducted a monocentric, retrospective, observational study in our diabetes department. Patients with DFU and isolated toe necrosis indicating a transphalangeal amputation (TPA), a metatarsophalangeal disarticulation (MPD) or a single transmetatarsal amputation (TMA) decided during a multidisciplinary DFU team were included. The primary endpoint was the need for reoperation or reamputation (partial/complete TMA, transtibial (TTA) or transfemoral (TFA)) performed by a surgeon. From May 2016 to September 2020, 147 out of 709 patients admitted for DFU required a surgical treatment (21%). After DFU team agreement and patient’s informed consent obtained, 101/147 patients needed TPA, MPD or TMA (69%) and 43/101 were performed at bedside by the diabetologist (43%). The characteristics of the population were: men=75%, age=65±14 years, type 2 diabetes=95%, duration of diabetes=19±11 years, preoperative arteriography=84%, preoperative revascularization=30%, mean number of permeable arteries at the time of the procedure=2±0.9, permeable dorsal arch=58%, permeable plantar arch=45%. Type of BTA: TPA=28%, MPD=65%, TMA=7%. Median follow-up=12 months. Secondary conventional surgery was needed for 13 patients (30%) (TMA/TTA/debridement respectively in 54, 30 and 16% cases). Poor vascular arterial bed was the significant determinant of failure (≤ 1 leg artery, p=0.006). Annual mortality rates in the groups with or without the need for a surgeon were respectively 15 and 10% (p=0.6). Performed by a diabetologist, BTA might be an option to treat limited toe necrosis complicating DFU in case of ≥ 2 leg arteries permeable at the time of the procedure. A head-to-head comparison with conventional surgery is now required.

Disclosure

F. Feron: None. J. Riveline: None. J. Gautier: None. J. Kevorkian: None.
448-P: Serum Inflammatory Markers Are Not Correlated with Detection of Osteomyelitis by 99mTC-WBC SPECT/CT Imaging in Subjects with Diabetes and Foot Infection
Authors: SHERWOOD AMBER , RUBITSCHUNG KATIE L. , KILLEEN AMANDA L. , CRISOLOGO PETER , GRIGOROPOULOS KATERINA , PAJOUH AMANDA , KEP JENNIFER , WUKICH DANE , FONTAINE JAVIER LA , LAVERY LAWRENCE A. , OZ ORHAN K.
Published: June 2021

Osteomyelitis is a common complication in diabetic foot ulcers. Accurate and early detection of diabetic foot osteomyelitis (DFO) is key to optimizing clinical outcomes and avoiding amputation. Using bone biopsy histopathology as the gold diagnostic standard, we evaluate the sensitivity and specificity of radiolabeled white blood cell imaging combined with CT (99mTc-WBC SPECT/CT) for the evaluation of DFO. We also assess the ability of the inflammatory markers CRP and ESR to predict osteomyelitis diagnosis by 99mTc-WBC SPECT/CT imaging. Subjects with diabetes and foot ulcerations presenting to a large tertiary care facility were examined by podiatry. Of the 48 subjects who consented to participation, 44 completed imaging, labwork, and underwent biopsy. Serum CRP and ESR were collected within three days of consent. In all cases, WBC imaging studies were performed prior to biopsy. The WBC SPECT/CT scans were read by an experienced Nuclear Medicine radiologist. Pathology was performed in the hospital laboratory and interpreted by a pathologist experienced in MSK infections. SPECT/CT and pathology reads were coded as either positive or negative for osteomyelitis. Sensitivity and specificity of 99mTc-WBC SPECT/CT for DFO diagnosis was 90.9% and 73.7%, respectively. WBC imaging had a PPV of 80.0%, and 87.5% NPV (n=41). CRP and ESR serum levels were grouped according to positive or negative DFO diagnosis as determined by WBC scan. Neither CRP (p=0.9895) nor ESR levels (p=0.8382) were correlated with DFO diagnosis based on WBC imaging results. Using bone biopsy results as the reference standard, radiolabeled 99mTc-WBC SPECT/CT demonstrates sensitivity for DFO. However, CRP and ESR were not found to be predictive in the diagnostic interpretation of 99mTc-WBC SPECT/CT imaging for the diagnosis of DFO.

Disclosure

A. Sherwood: None. L. A. Lavery: None. O. K. Oz: n/a. K. L. Rubitschung: None. A. L. Killeen: None. P. Crisologo: None. K. Grigoropoulos: None. A. Pajouh: None. J. Kep: None. D. Wukich: Consultant; Self; Orthofix Medical Inc., Wright Medical Group, Other Relationship; Self; Arthrex, Inc. J. La fontaine: None.

Funding

American Diabetes Association (1-17-ICTS-056 to O.K.O.)
450-P: Increasing Trends in Major Amputations among Patients with Diabetes in Kentucky, 2008-2018
Authors: SOHN MIN-WOONG , KIM WOOK-JOONG , LACY MARY ELIZABETH
Published: June 2021

Objective: CDC’s recent data (Harding et al. 2020) showed that rates of major lower-extremity amputations (ankle or above) rapidly decreased in 2000 - 2010 and then stabilized at slightly lower than 0.1% of Medicare beneficiaries with diabetes since then. We examined the commonwealth of Kentucky (KY) inpatient data to track trends in diabetic major amputations in 2008 - 2018.

Methods: We used KY HCUP inpatient data to identify all patients with diabetes using ICD9/10 codes and those who have underwent major amputations using CPT codes.

Results: The number of hospitalizations by patients with diabetes in KY decreased by 8% in 2008 - 2018 but the number of major amputations increased from 560 to 795 limbs, representing a 42% increase in the same period. Medicare paid for 44% of these surgeries in 2008 and 61% in 2018, while Medicaid covered 38% in 2008 but only 31% in 2018 despite the expansion in Medicaid coverage since 2014. KY inpatient users with diabetes had 46% higher odds of having a major amputation in 2018 compared to those in 2008, adjusting for age, sex, and race/ethnicity. Compared to pre-2014 era, the odds of having a major amputation was 27% higher after the Medicaid expansion in 2014.

Conclusion: It is concerning that, while the rest of the country showed decreasing or stationary trends in major amputation rates, KY experienced continuously increasing number of major amputations in the last two decades. Although Medicaid expansion era had a significantly higher odds of major amputations compared to the pre-expansion era, it is not clear whether this reflects the effect of policy or is part of a secular trend since 2010. More careful analysis is needed to better understand the underlying causes of this trend and what needs to done to reverse it.

Disclosure

M. Sohn: None. W. Kim: None. M. Lacy: None.
452-P: Effect of Virtual Education on Glycemic Control in Patients with Type 1 Diabetes during Fasting Ramadan
Authors: KHOGEER GHOFRAN S. , ALAMOUDI REEM , ALOTIBI MARYAM N.
Published: June 2021

Managing patients with T1DM who fast Ramadan is challenging. The COVID-19 related strict imposed curfew in Saudi Arabia affected access to healthcare and made virtual education (VD) a necessity.

Objective: To assess the impact of VD on glycemic control and self-management in T1DM during Ramadan fasting.

Methods: Pre-post Ramadan survey at endocrine clinics of National Guards Hospital, Jeddah, Saudi Arabia. Patients were contacted by phone due to COVID 19 restrictions. The VD methods (video + booklet) were sent to patients via WhatsApp. HbA1c was measured before and after Ramadan.

Results: 89 patients enrolled: 51.2% males, DM duration 13.8 ±7.7 years, age 24.4 ±8.1 years. > 90% stated that VD used was well done/acceptable, and 57% confirmed using it as reference. During Ramadan 88% complied with frequent SMBG, 72.6% reported breaking the fast at the recommended threshold of <70mg/dl, but only 22.6% broke fasting if >300 mg/dL. 61% followed the recommended insulin adjustments to basal and sahoor doses, and to adjustment of meal timings (delay of sahoor), and fluid intake. 43% complied with eating proteins at sahoor. Baseline HbA1c 8.46 ±1.85 and decreased to 8.32 ±1.47 after the intervention process (P=0.004).

Conclusion: Diabetes virtual education was well received and improved glycemic control and self-care among patients with T1DM during Ramadan fasting.

Disclosure

G. S. Khogeer: None. R. Alamoudi: None. M. N. Alotibi: None.
457-P: Effectiveness of an Empowerment-Based Self-Management Intervention on Glycemic Control, Self-Management Behaviors, and Psychological Distress in Middle-Aged Patients with Poorly Controlled Type 2 Diabetes
Authors: CHENG LI , SIT JANET WH , XIE QINQIN
Published: June 2021

Objectives: This study aimed to evaluate the effectiveness of an empowerment-based, self-management intervention among middle-aged patients with poorly controlled type 2 diabetes.

Methods: This is a secondary data analysis of an assessor-masked, multi-center, randomized controlled trial. A total of 166 middle-aged patients with poorly controlled type 2 diabetes were randomized to either intervention or control group. Participants in the intervention group received a patient-centered self-management intervention program guided by the Empowerment Process Model with emphasis on personally-meaningful goal-setting and action-reflection dynamics. Generalized estimating equation (GEE) was used to compare the changes in glycemic control, self-management behaviors, and psychological distress over the study periods.

Results: Participants in the intervention (n= 80) and control (n= 86) groups were homogeneous at the baseline. The intervention group demonstrated a significant and clinical meaningful reduction in HbA1c value mean (SD) from baseline (10.11% [1.76]) to 3-month (9.19% [2.06]) post-intervention (p< 0.001). Participants in the intervention groups showed significant between-group differences in diet management (p= 0.001), frequency of blood glucose self-monitoring (p= 0.005), and distress level (p< 0.001) at three-month after the completion of the intervention. However, GEE showed non-significant differences on outcome parameters.

Discussion: Middle-aged patients with poor diabetes control did not benefit from the empowerment-based self-management intervention. Considering the deteriorated consequence of poor glycemic control and expected long-term trajectory of disease management, special attention should be paid to optimize the biochemical and patient-centered outcomes of middle-aged patients with poor diabetes control.

Disclosure

L. Cheng: None. J. Sit: None. Q. Xie: None.
467-P: Immediate and Sustained Trends in Glycemic Control during Remote Patient Monitoring in People with Type 2 Diabetes
Authors: SHENG TONG , BABIKIAN SARINE , SINGH VIKRAM , CLEMENTS MARK A.
Published: June 2021

Technologies that let patients share diabetes data with care teams can help care teams identify patients with deteriorating glycemic control and facilitate timely and remote-based interventions outside of routine clinic visits. In the current study, we investigated whether people with type 2 diabetes (PWT2D) demonstrate improved glycemia after enrolling in remote patient monitoring (RPM) pilot programs that incorporated remote data syncing and coaching. All program participants were instructed to sync their blood glucose meters with either a mobile app or a computer-based software regularly during program participation. Synced blood glucose data were available to the RPM teams via a web-based dashboard, and remote coaching was administered either regularly and/or as needed. Data from 384 PWT2D (42% female; median age: 50 years) were included in cross-sectional comparisons at baseline and at 3, 6, and 12 months of RPM program participation. Overall trends of immediate (i.e., at 3 months) and sustained (at 6 and 12 months) improvements were observed for mean blood glucose levels (baseline: 178 mg/dL to ~155 mg/dL at 3, 6, 12 months; all Ps <.05), and mean proportion of in-range (70-180 mg/dL; baseline: 60% to ~74% at 3, 6, 12 months; all Ps <.05) and high SMBG readings (>250 mg/dL; baseline: 14% to ~8% at 3, 6, 12 months; all Ps <.05), with no differences in the proportion of low (<70 mg/dL) readings.

In summary, glycemic improvements are seen within 3 months of program participation and are sustained with continued engagement. These findings indicate that RPM programs that incorporate remote data sharing and coaching can make a substantial impact on glycemic control for people with type 2 diabetes.

Disclosure

T. Sheng: Employee; Self; Glooko, Inc. S. Babikian: Employee; Self; Glooko, Inc. V. Singh: Employee; Self; Glooko, Inc. M. A. Clements: Employee; Self; Glooko, Inc., Other Relationship; Self; Glooko, Inc.
469-P: Health Care Providers’ Experiences with a Virtual Reality Program Focused on Diabetes, Social Determinants of Health, and Appalachian Culture
Authors: BEVERLY ELIZABETH A. , LOVE CARRIE , LOVE MATTHEW
Published: June 2021

The prevalence of diabetes in southeastern Appalachian Ohio is 19.9%, nearly double the national average of 10.5%. Here, people are more likely to be diagnosed late, have limited access to healthcare, and lower health literacy. Moreover, people in southeastern Ohio are more likely to be unemployed, food insecure, have lower educational achievement, and limited access to transportation. These social determinants of health (SDoH) contribute to the diabetes disparities observed in the region. One approach to address these disparities is to develop tailored continuing education for healthcare providers. We developed a 3-hour cinematic virtual reality (cine-VR) program to educate providers about diabetes, SDoH, and Appalachian culture. We conducted 20 in-depth interviews with providers (age=43.8±11.8 years; 90.0% female; 95.0% white, 20.0% nurses) to explore their experiences with the cine-VR program. Three researchers independently coded the interviews, resolved discrepancies, and agreed on themes. Qualitative analysis revealed three themes: 1) Feeling Like You Are in the Room: Providers commented on the realism of cine-VR. They had access to the whole environment via a 360-degree headset and felt fully immersed in the simulations as if they were in the room with the patient. 2) Empathizing with People’s Stories: Providers identified with the content in the cine-VR, specifically the clothing, cars, houses, and the notion of “taking care of everyone else but yourself.” They understood the patient’s frustrations, disappointments, and competing priorities. 3) Highlighting the Strengths of Appalachia: Providers noted the program’s emphasis on family, caregiving, loyalty, and generosity, and how these cultural values can be utilized in diabetes care. These qualitative findings demonstrate the value of culturally tailored digital storytelling as engaging content for providers to learn about diabetes, SDoH, and Appalachian culture.

Disclosure

E. A. Beverly: None. C. Love: None. M. Love: None.
472-P: Online Patient Education on GLP-1 Receptor Agonists in Patients with T2D and CVD Prompts Real-Life Changes
Authors: LARKIN AMY , LE ANNE
Published: June 2021

We sought to measure the impact of online education for patients on knowledge, confidence, and prompting change in daily life. Two educational activities were available online, comprised of text and integrated visuals as well as either a patient or clinician video. Demographic questions were asked prior to starting the education. A knowledge question was asked both before and after the activity to assess learning gains, as well as intent to change and confidence questions at the end. Absolute improvements were calculated for pre/post questions. The activities launched in August, 2020, and preliminary data collected through November, 2020. Activity 1: To date, 28,983 learners have participated in the patient/caregiver activity, “How is Diabetes Related to Heart Disease?” Of which, 4,912 completed all questions (included in outcomes analysis): 51% male; 51% white, non-Hispanic; 66% over the age of 54; 71% have diabetes, 18% were interested in learning more about diabetes and heart disease. Intent-to-act: 85% plan to talk to their HCP about their risk for heart disease. Confidence changes: 87% reported increased confidence talking to my doctor or healthcare provider about how to lower their risk for heart disease. Activity 2: To date, 40,812 learners have participated in the patient/caregiver activity, “How Can I Make my Heart Healthier and Control my Sugar Better at the Same Time?” Of these, 10,233 completed all questions (included in outcomes analysis): 52% female; 53% white, non-Hispanic; 66% over the age of 54; 69% have diabetes, 22% were interested in learning more about ways to treat diabetes and heart disease. Knowledge changes: 54% improvement in recognizing GLP-1 RAs can treat T2D and lower the risk for heart disease (12% pre to 66% post). The metrics and outcomes gathered in this assessment are a strong indicator that these patient-focused online educational activities improved knowledge, confidence, and prompted intent to act by patients related to T2D and CVD risk reduction.

Disclosure

A. Larkin: None. A. Le: None.

Funding

Novo Nordisk
48-OR: Changes in Global Cerebral Blood Flow in Response to Hypoglycemia in Type 1 Diabetes Do Not Influence Awareness Status
Authors: JACOB PETER , ODALY OWEN , AMIEL STEPHANIE A. , CHOUDHARY PRATIK
Published: June 2021

Changes in global cerebral blood flow (gCBF) have been suggested as a mechanism for mitigating the functional impact of hypoglycemia on the brain. The impact of type 1 diabetes (T1D) or hypoglycemia awareness status is not clear. We measured gCBF during progressive lowering of plasma glucose in people with and without T1D, and with retained or impaired awareness of hypoglycemia.

Methods: Fifty-one participants (15 with no diabetes (ND), 15 with T1D and normal awareness of hypoglycemia (NAH) and 21 with T1D and impaired awareness of hypoglycemia (IAH)) underwent a two-step hyperinsulinemic hypoglycemic clamp. gCBF was estimated using pseudocontinuous arterial spin labelling magnetic resonance imaging at 6 timepoints: 2 euglycemic, two in the descent phase and two hypoglycemic. gCBF was extracted using a global grey matter mask in SPM12. Statistical analysis and thresholded linear models were performed in R.

Results: The mean (+ SD) glucose values at the six timepoints were 95.8 (8.0), 95.5 (9.2), 55.0 (8.3), 50.8 (5.3), 45.7 (4.3) and 45.8 (4.0) mg/dL. Symptom responses to hypoglycemia were absent in IAH. There was a significant increase in CBF in response to hypoglycemia (3-way ANOVA p = 0.04). This was driven by responses in NAH (+7.3%, p < 0.05) and IAH (+10.6% p < 0.01) with no response in ND (+3.5% p = 0.16). The response was not linear, with glucose thresholds of 55.8 mg/dL in NAH and 54.0 mg/dL in IAH (pNAH vs IAH = 0.9) with no threshold in ND.

Conclusion: In people with T1D, there is a non-linear relationship between falling glucose and rising gCBF which is not related to awareness status and is not seen in health. The threshold glucose between 54 and 56 mg/dL corresponds closely with level 2 hypoglycemia cut-offs used in current clinical practice. We propose that there is a failure of cerebral vascular autoregulation in response to hypoglycemia in T1D. gCBF responses to hypoglycemia in T1D are independent of symptomatic responses and not responsible for lack of hypoglycemia awareness.

Disclosure

P. Jacob: None. O. Odaly: None. S. A. Amiel: Advisory Panel; Self; Diabetes UK, Medtronic, Other Relationship; Self; Sanofi, Research Support; Self; Diabetes UK, European Union, JDRF. P. Choudhary: Advisory Panel; Self; Abbott Diabetes, Insulet Corporation, Lilly Diabetes, Medtronic, Sanofi-Aventis, Speaker’s Bureau; Self; Dexcom, Inc., Novo Nordisk.

Funding

JDRF (3-SRA-2017-484-S-B)
494-P: Canagliflozin Prevents Hyperglycemia-Associated Muscle Extracellular Matrix Accumulation and Restores the Adaptive Response to Aerobic Exercise
Authors: MACDONALD TARA , PATTAMAPRAPANONT PATTARAWAN , LESSARD SARAH J.
Published: June 2021

In rodent models and humans, hyperglycemia is associated with an impaired adaptive response to aerobic exercise, which includes blunted improvements in aerobic capacity and impaired aerobic remodeling of skeletal muscle. To test whether glucose lowering therapy can restore the response to exercise, aerobic training studies were performed on hyperglycemic mice treated with or without the SGLT2 inhibitor, Canagliflozin (CANA) for 16-wks. Hyperglycemia was induced using two injections of streptozotocin (STZ; 40 mg/kg). A cohort of STZ-treated mice were administered CANA in their food (30 mg/kg/day), which normalized blood glucose to the level of untreated normoglycemic controls. The adaptive response to aerobic exercise training was blunted in STZ compared to control, but was restored by CANA treatment. Following training, CANA had improved aerobic exercise capacity (VO2peak), higher capillary density in cardiac and skeletal muscle, and a more oxidative fiber-type in skeletal muscle, compared to STZ. Recent work implicates glucose-induced accumulation of the skeletal muscle extracellular matrix (ECM), leading to hyper-activation of JNK/SMAD2 mechanical signaling after acute exercise as potential mechanisms underlying low exercise response. Consistent with this, STZ had significant accumulation of muscle ECM compared to control which was prevented by treatment with CANA, as assessed by histological staining. In addition, hyper-activation of JNK/SMAD2 mechanical signaling after a bout of acute exercise was 2-fold higher in STZ compared to control, but was normalized by CANA. These data demonstrate that hyperglycemia-associated impairments in exercise adaptation can be ameliorated by Canagliflozin treatment. Moreover, we identify skeletal muscle ECM accumulation and JNK/SMAD2 hyper-activation as potential mechanisms for impaired aerobic adaptation with hyperglycemia.

Disclosure

T. Macdonald: None. P. Pattamaprapanont: None. S. J. Lessard: None.

Funding

National Institutes of Health (R01DK124258)
508-P: Correlations between Burden and Quality of Life for Caregivers of Children Living with Type 1 Diabetes
Authors: JEWELL VANESSA D. , LEE GILLIANE , HARMON KASEY , GALLEGOS ERICA
Published: June 2021

Providing continuous care to a child living with type 1 diabetes impacts not only the child’s well-being, but also a caregiver’s quality of life and overall feelings of burden from this omnipresent disease. The hypervigilance required for diabetes management can cause declines in a caregiver’s physical, emotional, and social health. Therefore, it is imperative that practitioners understand the impact of diabetes management on caregivers to develop and implement appropriate family-centered interventions. The purpose of this descriptive, cross-sectional survey was to examine the relationships between caregiver burden and quality of life of caregivers of children living with type 1 diabetes. Caregivers (n=212) who had provided care to a child with type 1 diabetes for a minimum of six months completed an electronic survey that included demographic information, the Zarit Burden Interview Scale, and the WHOQoL-BREF. Most of the respondents were female (98%), aged 36-45 years (56%), married (82%), and had completed at least some college (82%). Caregiver burden was reported by all respondents, with the majority reporting moderate to severe burden (68%). One-way ANOVA analysis indicated a significant weak, negative correlation between caregiver burden and quality of life domains, including physical health (r = 0.360, p<0.001), psychological health (r = 0.460, p<0.001), social relationships (r = 0.394, p<0.001), and environment (r = 0.462, p<0.001). It is not surprising that respondents who reported increased caregiver burden also reported lower quality of life, indicating that managing a chronic condition may lead to increased stress and declined overall health and well-being. As it is known that improved quality of life is related to improved blood glucose control and overall health, interprofessional endocrinology healthcare teams are encouraged to provide family-centered approaches to care to address both the child and caregiver concerns related to diabetes management.

Disclosure

V. D. Jewell: Research Support; Self; Dexcom, Inc. G. Lee: None. K. Harmon: None. E. Gallegos: None.
522-P: Perception Regarding Marriage in Unmarried Diabetics in Central India
Authors: SABOO BHARAT , SHRIVASTAVA ABHISHEK , SABOO BANSHI D.
Published: June 2021

Background: Marriage is an integral part of Indian society. In spite of the large number of people with diabetes mellitus (DM) in India, India is not a diabetes-friendly society. This survey highlights perceptions of diabetes patient population with regards to marriage, associated diabetes distress, and suggests potential solutions. If Diabetic patients consider them unfit to marry and think that people don’t accept diabetics as a bride or groom and they can’t have a family, it’s a serious issue. There is no survey till date on this topic with surveyed population.

Methods: 68 randomly selected unmarried diabetes patient, males and females, from rural and urban areas of central India were asked to fill a survey questionnaire online. The inclusion criteria were age 18-35, having T1DM or T2DM and no history of mental disorder.

Results: Responses were analyzed and plotted. Most of the respondents (85 %) were not willing to accept a diabetic groom or bride, the acceptability was more in males, in urban dwellers, with higher academic qualification, and parents without diabetes. Most were worried about the complication of the disease. Majority of responders (76 %) think diabetes affect future progeny. (87 %) think they will become burden for their life partner, (T1DM > T2DM).

Conclusion: Misconception regarding social, occupational, marital abilities, fertility, genetics, quality of life in young people living with DM raises major barriers to marriage, People with DM are wrongly assumed to be sick, disabled, dependent persons, unsuitable for marriages, and likely to have complicated pregnancies with the possibility of having children with diabetes. Diabetes distress and psychological issues are major problems related to marriage in young people with DM. Counseling of patients, family, relatives, prospective spouse, and increasing social awareness regarding diabetes through mass communication will serve as the keys to their resolution.

Disclosure

B. Saboo: None. A. Shrivastava: None. B. D. Saboo: None.
524-P: Diabetes Device Use Linked with Lower Family Conflict in Teens with Type 1 Diabetes
Authors: MOORE HAILEY R. , JASER SARAH S. , STREISAND RANDI , INVERSO HAILEY , MORROW TROY
Published: June 2021

Introduction: Use of hybrid closed-loop insulin delivery systems have been associated with better glycemic control and lower hemoglobin A1c (HbA1c) values, and better glycemic control is linked with less diabetes-specific family conflict among adolescents with type 1 diabetes (T1D). Little is known, however, about how the use of closed-loop systems relates to diabetes family conflict.

Methods: Participants included 60 teens ages 13-17 who had been diagnosed with T1D for ≥1 year and who reported at least moderate diabetes distress (M age= 16.15±1.4, 68% white, non-Hispanic 68% female), and their parents (78% white, non-Hispanic, 78% Married, 83% female). As part of baseline data collection of an ongoing two-site trial of a behavioral intervention, parents and teens each reported on diabetes device use and diabetes-related family conflict. HbA1c values were obtained from teens’ medical records or mail-in kits. Nonparametric (Mann-Whitney) tests were conducted to examine differences between parent and teen-reported diabetes family conflict and HbA1c in relation to use of closed-loops systems.

Results: Of the participants, 12 teens (20%) were using a closed-loop system. The use of closed-loop systems was associated with lower levels of parent-reported diabetes-related family conflict (z= -2.372, p=0.018). Use of closed-loop systems was also associated with lower HbA1c values (z= -2.865, p=.004). However, teens’ own report of family conflict was not significantly related to use of the closed-loop systems (z= -1.331, .183).

Conclusion: Results suggest that the use of closed-loop systems is associated with both lower HbA1c and lower parent perceptions of diabetes-related family conflict. While future studies are needed to replicate these findings in larger samples and over time, our findings further support that closed-loop systems may reduce the burden of diabetes - particularly for parents - and improve both psychosocial and glycemic outcomes in families of youth with T1D.

Disclosure

H. R. Moore: None. S. S. Jaser: None. R. Streisand: None. H. Inverso: None. T. Morrow: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK121316)
526-P: Prevalence and Predictors of Spiritual/Existential Distress among Adults with Uncontrolled Diabetes
Authors: RAJAEE GEILA , HEISLER MICHELE , PIETTE JOHN , RESNICOW KENNETH , SHI XU , SMITH ALYSSA N. , SONG PETER X. , PATEL MINAL R.
Published: June 2021

Purpose: Spiritual and/or existential (S/E) distress is the experience of strain or conflict within a person’s religious, spiritual, or existential framework and is associated with worse psychological and health outcomes among individuals with acute illness. Little is known about S/E distress among individuals with a chronic condition, such as diabetes mellitus (DM). We explored the prevalence of S/E distress among adults with DM and examined patient factors associated with S/E distress.

Methods: Data came from the 2019-2020 baseline assessment of participants in an ongoing trial of an intervention addressing social determinants of health among people with DM (n=286). Participants had HbA1cs ≥ 7.5 (18-70 years) or ≥ 8.0 for (71-75 years). We measured S/E distress in two ways: 1) with an abbreviated version of the Religious and Spiritual Struggle Scale (RSSS-14); and 2) with three screening questions adapted from the Rush Religious Struggle Screening Protocol (3Q). Bivariate analyses examined the association between patient factors, including health behaviors, DM distress, social support, and S/E distress.

Results: Mean age of the sample was 53 years (SD:13.3). Prevalence of S/E distress was 20% (3Q) and 22% (RSSS-14). Both screeners found that compared to those without S/E distress, those with S/E distress reported a poorer general diet, lower social support, higher levels of DM distress, and higher psychological distress (all p <0.05). The RSSS-14 also identified elevated levels of HbA1c, more chronic conditions, and greater unmet social needs among those with potential S/E distress (all p <0.05). The 3Q identified poorer medication adherence (p=0.03) in those with S/E distress.

Conclusions: One-fifth of adults with poor glycemic control have potential S/E distress, and such distress is associated with worse mental health and functional status. Future interventions should seek to address S/E distress as part of efforts to improve DM patient-centered and clinical outcomes.

Disclosure

G. Rajaee: Consultant; Self; UnitedHealth Group. M. Heisler: None. J. Piette: None. K. Resnicow: None. X. Shi: None. A. N. Smith: None. P. X. Song: None. M. R. Patel: None.

Funding

National Institutes of Health (R01DK116715)
532-P: Artificial Intelligence Identifies a Modest Influence of Character and Emotions on Blood Glucose in Type 1 Diabetes
Authors: SHOHAM GON , HOCHBERG IRIT , ELDOR ROY , GILAD-BACHRACH RAN
Published: June 2021

Introduction: People with T1DM and their healthcare providers perceive that mood and sleep quality influence blood glucose (BG). Artificial pancreas algorithms use only BG estimates to predict future BG and determine insulin requirements. We aimed to improve the understanding of the effect of emotional states and personality on temporal BG changes using machine learning.

Methods: Patients with T1DM using continuous glucose monitoring (CGM) completed questionnaires on demographic, socioeconomic and medical information and personality characteristics. For several days, using a mobile app, patients recorded their present valence, arousal state and sleep quality. The data was synced with patient CGM readings and evaluated using gradient boosting decision tree (GBDT) over 5-fold cross-validation. Area under the receiver operating characteristic curve (AUROC) and marginal contribution were used to determine model feature importance. BG was divided into three classes: normal (70-180), high (>180), low (<70). For normal BG values, models were trained to predict BG class in the next 15, 30, and 45 minutes.

Results: A total of 64 participants (age 48±15 years SEM, years of T1D 18±13, 59% women) from two medical centers participated for 17.3±15.2 SEM days, each reporting valence and arousal 56±53 times. Models using personality and emotional features to predict future BG outperformed models using only BG, albeit by a small margin. Following BG and time-of-day features, both neuroticism and arousal were found to be predictive. Neuroticism levels and sleep were significantly different between participants with HbA1c values under 7.6% and over 9.5%. (p=0.001, p=0.02, respectively).

Discussion: Our results show that personality and present arousal are associated with BG fluctuations, while the effect of valence, while detectible, is minute. Integrating personality trait information using standard questionnaires may improve artificial pancreas algorithms.

Disclosure

G. Shoham: None. I. Hochberg: None. R. Eldor: Consultant; Self; Oramed , Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, MSD Corporation, Novo Nordisk, Sanofi. R. Gilad-bachrach: None.
54-OR: Nucleolin Autoantibody Accelerates Atherosclerosis in Type 1 Diabetes
Authors: PARK KYOUNGMIN , LI QIAN , PARK HYUNSEOK , FU JIALIN , KISSLER STEPHAN , MADDALONI ERNESTO , WU I-HSIEN , LICHTMAN ANDREW H. , KING GEORGE L.
Published: June 2021

Hyperglycemia has been evaluated extensively as risk factors for cardiovascular disease (CVD) in people with type 1 diabetes (T1DM). However, the effects of the autoantibody on atherosclerosis and immunogenic trigger are not well understood in T1D. Using the generated several mice models of atherosclerosis including NOD, congenic ApoE-/-/NOD (NDM and no- autoimmune), ApoE-/-/NOD (autoimmunity with insulitis, NDM) and ApoE-/-/NOD autoimmune DM mice, we analyzed immune cells composition of aorta and have observed the increasing numbers of CD3+(CD3+/CD25-), Th1 and Th17 subset of T cells and B cells and decreased Treg (CD3+/CD25+/Foxp3+) in the ApoE-/-/NOD and ApoE-/-/NOD-DM mice vs. control. In addition, we postulate that the identification of specific autoantibody(s) which induce dysregulaton of T-cells, resulting in enhancing its infiltration and accumulation at the plaques could aid new immunotherapies for atherosclerosis. Here we performed autoantigen microarrays to profile and identify specific autoantibodies, enhancing the severe atherosclerosis in subgroups of Medalist patients with chronic duration of T1D due to autoimmunity with positive HLA DR3/4 risk alleles and autoantibodies and compared to the people with monogenic diabetes lacking HLA DR3/4 risk alleles for T1D and autoantibodies. Autoantigen microarrays from the plasma of T1D patients with positive DR3/4 risk and CVD identified 8 autoantibodies changed in the context of atherosclerosis, compared to the people with monogenic diabetes. To confirm the autoantibody profiling data from the patients, we analyzed the autoantibody profiles in the T1D mice models of atherosclerosis described above. Autoantigen microarrays analysis of the plasma of T1D patients and mice showed several common findings that reached significance anti-Nucleolin Ab, p=0.005. These findings indicate autoimmunity may contribute to the progression of atherosclerosis in T1D. Further studies are in progress to replicate these findings in other cohorts of T1D.

Disclosure

K. Park: None. Q. Li: None. H. Park: None. J. Fu: None. S. Kissler: None. E. Maddaloni: Research Support; Self; European Foundation for the Study of Diabetes, Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Merck KGaA. I. Wu: None. A. H. Lichtman: None. G. L. King: Consultant; Self; Agios, Inc., Medtronic, Other Relationship; Self; Janssen Pharmaceuticals, Inc.

Funding

DK036836, DK036836, EY026080
55-OR: Targeted Deletion of Insulin Receptor in Vascular Smooth Muscle Cells Promoted Atherosclerosis and Unstable Plaque
Authors: LI QIAN , FU JIALIN , PARK KYOUNGMIN , WU I-HSIEN , KING GEORGE L.
Published: June 2021

Risks of unstable arterial plaques are increased in diabetes or insulin resistance. We hypothesized that insulin resistance in VSMCs contributes to reduced plaque stability since we have reported that insulin receptors (IR) on VSMCs are potent regulators of its proliferation and apoptosis. Further, insulin induced Akt phosphorylation was decreased in the aorta of diabetic mice. Lipid deposition were increased in the aortas of ApoE-/- and VSMCs IR double knockout (SMIRKO/ApoE-/-) mice vs. control mice. Pathological analysis of the atherosclerotic plaques of SMIRKO/ApoE-/- mice demonstrated features of unstable plaques, including reduced VSMCs proliferation and reduced cap thickness and collagen, but increased VSMCs apoptosis and more macrophages and necrosis area. VSMCs from SMIRKO/ApoE-/- mice exhibited less insulin induced proliferation and more apoptosis which were not inhibited by insulin compared to VSMCs from ApoE-/- mice. Artery relaxation induced by sodium nitroprusside (SNP) (NO donor) was impaired in artery from SMIRKO/ApoE-/- mice vs. control mice. Insulin and SNP induced VASP phosphorylation, a downstream signaling protein of NO in VSMCs, were reduced in SMIRKO/ApoE-/- mice vs. control mice. Expressions of MMP2, THBS1, sFRP3, and COMP were increased in the aorta of SMIRKO/ApoE-/- mice vs. ApoE-/- mice, which were also observed in the aorta of diabetic mice fed with high fat diet or diabetes induced by STZ. Insulin induced Akt and Foxo1 phosphorylation were impaired in cultured VSMCs from SMIRKO/ApoE-/- mice vs. control mice. Overexpression of constitutively activated Akt increased VASP phosphorylation and downregulated THBS1 expression in cultured VSMCs, whereas overexpression of FoxO1 increased THBS1 expression. This is the first report that selective inhibition of IR activation of pAkt in VSMCs is partially causing the elevated risk of unstable atherosclerotic plaques found in insulin resistance or diabetes.

Disclosure

Q. Li: None. J. Fu: None. K. Park: None. I. Wu: None. G. L. King: Consultant; Self; Agios, Inc., Medtronic, Other Relationship; Self; Janssen Pharmaceuticals, Inc.

Funding

National Institutes of Health (R01DK053105)