bluuebunny/crossref_metadata_2025 huggingface dataset:
50-LB: Behavior and Learning Challenges in ABCC8-Related Neonatal Diabetes
Authors: BROWN NAIRI , BERRY SHAGUN , HARRIS ANASTASIA , LETOURNEAU-FREIBERG LISA R. , GREELEY SIRI ATMA W.
Published: June 2020

Background: Activating mutations in KCNJ11 or ABCC8 cause neonatal diabetes (NDM) as well as neurodevelopmental difficulties, related to expression of mutated KATP channels in pancreatic beta cells as well as brain. Even individuals with more mildly activating KCNJ11 mutations underperform on many neurodevelopmental measures compared to sibling controls; however, very little information has been available about those with ABCC8 mutations.

Methods: Surveys were used to assess attention-deficit hyperactivity disorder (ADHD), learning and behavioral challenges, sleep disturbances, and other related medical conditions in participants with ABCC8-related NDM from the University of Chicago Monogenic Diabetes Registry.

Results: Baseline data including diagnosis and treatment information, and relevant medical records, were available for 19 of 20 participants with ABCC8-NDM (10 permanent, 9 transient), while 10 completed the ADHD/behavior/sleep survey. Participants with ABCC8-related NDM showed a range of neurodevelopmental and behavioral challenges (Table 1).

Conclusions: Our results suggest that individuals with ABCC8-NDM have a high prevalence of neurodevelopmental, behavioral and sleep challenges and should therefore receive relevant ongoing evaluation and support to address these challenges.

Disclosure

N. Brown: None. S. Berry: None. A. Harris: None. L.R. Letourneau-Freiberg: None. S.W. Greeley: None.

Funding

American Diabetes Association (1-17-JDF-008 to S.A.W.G.); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK104942, P30DK0205950); National Center for Advancing Translational Sciences (UL1TR002389)
501-P: Urinary C-Peptide Creatinine Ratio: A New Marker of Insulin Resistance and Diabetic Kidney Disease
Authors: WANG YANAI , CAI XIAOLING , JI LINONG
Published: June 2020

Introduction: Urinary C-peptide creatinine ratio (UCPCR) is used to access β cell function, but rare study had explored UCPCR in conditions with insulin resistance (IR). Some studies indicated the positive correlation between diabetic kidney disease (DKD) and IR. This study aims to explore the correlation among UCPCR,IR and DKD.

Methods: Chinese hospitalized patients with type 2 diabetes were included (n=1299). Fasting UCPCR was collected in the morning. We divided patients into three groups by the tertile of UCPCR, the characteristics of three groups were compared.

Results: In patients with the highest tertile of UCPCR, they had the lowest percentage of male (223 [51.6%] vs.294 [68.1%] vs. 302 [70.1%], P<0.001), highest homoeostasis model assessment 2 estimates of insulin resistance (HOMA2-IR) (2.0 [1.5,2.6] vs. 1.6 [1.2,2.2] vs. 1.5 [1.0,2.0], P<0.001), urinary albumin creatinine ratio (9.58 [4.67,36.42] vs. 7.14 [4.10,22.43] vs. 6.87 [3.60,22.94]mg/g, P=0.003) level,highest percentage of diabetic kidney disease (DKD) (121 [27.9%] vs. 95 [21.9%] vs. 98 [22.7%], P=0.078), coronary heart disease (CHD) (75 [17.4%] vs. 61 [14.1%] vs. 36 [8.4%], P<0.001) and stroke (77 [17.8%] vs. 55 [12.7%] vs. 46 [10.7%], P=0.007). After the adjustment for sex, age, duration, SBP, DBP, BMI, UA,TG, LDL-c, HbA1c, the history of smoke, hypertension and hyperlipidemia, UCPCR level had a positive correlation with the risk of DKD (OR=1.207,95%CI [1.026,1.419], P=0.023) and CHD (OR=1.302, 95%CI [1.069,1.587], P=0.009).

Conclusions: UCPCR is a practical and non-invasive marker of insulin resistance and associated with increased risk of DKD and CHD.

Disclosure

Y. Wang: None. X. Cai: None. L. Ji: None.
503-P: Association between Triglycerides–Glucose Index and Diabetic Nephropathy in Patients with Type 2 Diabetes
Authors: LIU LI , YUAN GANG
Published: June 2020

Objective: To investigate the association between triglycerides-glucose (TyG) index and diabetic nephropathy (DN) in patients with type 2 diabetes (T2D).

Methods: A total of 682 adult patients with T2D hospitalized at Tongji Hospital from January 2007 to December 2009 were included in this cross-sectional analysis. Multiple logistic regression and ROC analysis were performed.

Results: Two hundred and thirty-two (34.0%) participants were identified as DN. Compared with Non-DN group, DN groups had a longer disease duration and a higher bodyweight, systolic blood pressure, diastolic blood pressure, HbA1C, triglycerides, total cholesterol, serum uric acid, 24h-urinary albumin, TyG index, and HOMA2-IR (P<0.05 for each). TyG index presented the independent risk (OR=1.91, P=0.001) for DN (Table 1). TyG index was stratified into quartiles and taking the highest quartile (Q4) as reference, the odds ratios for DN was decreased in Q3 (0.36), Q2 (0.26), and Q1 (0.48) (P<0.05 for trend). Subgroup analysis showed that TyG index was more significantly associated with DN in patients with HbA1C≥7% (OR=2.18, P=0.002). In addition, TyG index showed a higher AUC of 0.67 (P=0.002) than HOMA2-IR (AUC=0.61, P=0.029) in ROC analysis for DN predicting.

Conclusions: TyG index, as a marker of insulin resistance, was independently associated with DN in patients with T2D. It was a better predictor of DN in T2D than HOMA2-IR.

Disclosure

L. Liu: None. G. Yuan: None.

Funding

National Natural Science Foundation of China (81770817, 81700727)
520-P: Exenatide Ameliorates Diabetic Kidney Disease by Inhibiting Apoptosis via SIRT1/TXNIP Signal Pathway
Authors: WANG MEIJUN , LIANG RIYING , XU FEN , CAI MENGYIN
Published: June 2020

Recent studies have indicated apoptosis to be a major contributor to the progression of Diabetic Kidney Disease. GLP-1 agonist such as Exenatide, which counteracts insulin resistance in humans with type 2 diabetes, has been shown to ameliorate Diabetic Kidney Disease in experimental models. In this study, we investigated whether exenatide could alleviate Diabetic Kidney Disease by apoptosis through SIRT1/TXNIP signal pathway. Male C57BL/6J mice challenged with a high-fat diet (HFD) for 12weeks were then treated with exenatide (HFD+exe) or normal saline(HFD+sal) by intraperitoneal injection for 8 weeks. The results revealed that Exenatide notably decreased body weight, urine albumin-to-creatinine ratio(ACR) and apoptosis in the kidney induced by HFD challenge. Western blot revealed the level of apoptosis were notably downregulated after exenatide treatment. In addition, the protein expression of SIRT1 was upregulated, whereas TXNIP was downregulated in the HFD+exe group. Collectively, the data indicate that Exenatide ameliorates Diabetic Kidney Disease by inhibiting apoptosis via SIRT1/TXNIP signal pathway.

Disclosure

M. Wang: None. R. Liang: None. F. Xu: None. M. Cai: None.
548-P: Early Liver Dysfunction Predicts Cardiac Autonomic Neuropathy in Adolescents with Type 1 Diabetes
Authors: VELAYUTHAM VALLIMAYIL , BENITEZ-AGUIRRE PAUL Z. , CRAIG MARIA E. , CUSUMANO JANINE , LIEW GERALD , DONAGHUE KIM C.
Published: June 2020

Background: With increasing incidence of obesity, metabolic syndrome is not uncommon in type 1 diabetes (T1D). The association of liver dysfunction and cardiovascular disease is well established in type 2 diabetes but not in T1D. We aim to investigate associations between liver dysfunction and diabetic retinopathy and cardiac autonomic neuropathy (CAN) in adolescents with T1D.

Methods: A longitudinal study of 102 adolescents with T1D with repeated measures of liver function and CAN over 3 years. CAN was defined as 2 or more abnormal heart rate variability measures derived from a 10 minute ECG recording using Labchart Pro (mean HR; Standard deviation of mean NN intervals; root mean squared difference of successive NN intervals; low/high frequency ratio; geometric measure- Triangular index). Generalized estimating equations were used to explore associations between tertiles of liver function enzymes and cardiac autonomic neuropathy and retinopathy after adjusting for known risk factors.

Results: Baseline mean + age was 14.6 + 1.9yrs, HbA1C 8.2 + 1.4 and median duration 7.2yrs (IQR 4.8-9.6), mean BMI 23 + 4.1. Higher ALT was associated with CAN (Table1) but not retinopathy.

Conclusion: Higher ALT was associated with early CAN in youth with T1D. Inflammation might lead to higher ALT. Further studies into the potential role for obesity, liver dysfunction and CAN are required.

Disclosure

V. Velayutham: None. P.Z. Benitez-Aguirre: None. M.E. Craig: None. J. Cusumano: None. G. Liew: None. K.C. Donaghue: None.
559-P: Signs of Early Change in Peripheral Axons in People with Early-Onset Type 2 Diabetes Mellitus
Authors: GU YU , HARMER ALISON R. , DENNIS SARAH M. , LI TIFFANY , TIMMINS HANNAH C. , TIEN LOH PATRICIA CHIN , GARG NIDHI , DHARMADASA THANUJA , WONG JENCIA , GAULD AMANDA , MUNOZ PHILLIP A. , PARK SUSANNA B.
Published: June 2020

Introduction: The prevalence of early-onset type 2 diabetes (EOT2D; diagnosed with T2DM before 40 years old), has increased sharply in recent years. Peripheral neuropathy (DPN) is a common and debilitating complication associated with T2DM, and it is also common in EOT2D, even among adolescents. Nerve excitability studies (NES) examine nerve axonal ion channel function; and may allow early detection of axonal dysfunction. The aim of this study was to explore the differences in NES outcomes between a cohort with EOT2D and matched healthy controls.

Method: Thirteen participants with EOT2D with no clinical evidence of DPN and 14 matched healthy control participants (HC) were included in the study. Nerve conduction studies (NCS) were used to assess amplitude, latency, and conduction velocity in sural (sensory) and peroneal (motor) nerves. Motor and sensory NES were conducted on the median nerve. NES parameters assessed included strength-duration time constant, threshold electrotonus (TE), current-threshold relationship and recovery cycle. HbA1c was measured. Independent sample t-tests were used to compare the group means ± standard deviations.

Results: Participants with EOT2D (F:M 5:8, age 34.1±6.7yr, BMI 31.7±5.4kg∙m-2) differed from matched HC (F:M 6:8, age 32.5±5.1yr, BMI 29.6±4.4kg∙m-2) for HbA1c (EOT2D=6.8±1.0%, HC=5.2±0.3%, p<0.0001). There were no significant between-group differences in any NCS parameters, confirming the absence of clinical neuropathy. Minor changes in sensory axon NES were found in TE, which measures internodal conductances. Sensory depolarizing TE (TEd) at 10-20ms was decreased significantly in the EOT2D group (TEd 10-20ms: EOT2D = 60.1±2.9ms, HC = 62.9±3.0ms, p = 0.02). There were no significant changes in motor NES.

Conclusion: Participants with EOT2D and no clinical evidence of DPN may demonstrate minor changes in sensory axonal function. Prospective studies are required to determine the clinical significance and progression of these changes.

Disclosure

Y. Gu: None. A.R. Harmer: None. S.M. Dennis: None. T. Li: None. H.C. Timmins: None. P. Loh: None. N. Garg: None. T. Dharmadasa: None. J. Wong: Advisory Panel; Self; Sanofi. Speaker’s Bureau; Self; AstraZeneca, Merck & Co., Inc. A. Gauld: None. P.A. Munoz: None. S.B. Park: None.

Funding

Diabetes Australia; Sydney Local Health District
586-P: Characteristics of 24-Hour Urinary Electrolyte Excretion and Its Correlation with Renal Function in Type 2 Diabetics
Authors: WANG YANRU , LI NAN , BU LE , SUN HANG , ZHU BING , LI HONG , QU SHEN
Published: June 2020

Objective: There are few studies on the characteristics of 24-hour urinary electrolyte excretion in patients with type 2 diabetes mellitus (T2DM),and it is unclear whether the level of 24-hour urinary electrolyte excretion is related to poor renal prognosis.This study aimed to explore associations between 24-hour urinary electrolyte excretion and renal function in T2DM patients.

Methods: A total of 479 patients with T2DM in our hospital from 2018 to 2019 were enrolled. According to the estimated glomerular filtration rate (eGFR), patients were divided into normal group(eGFR≥90 mL/min/1.73m`2,n=317)and abnormal group(eGFR<90 mL/min/1.73m`2,n=162). The correlation between 24-hour urinary electrolyte excretion and eGFR in T2DM patients was analyzed. In addition, the 24-hour urine electrolyte excretion was compared with gender, diabetic duration, and HbA1c.

Results: The levels of 24-hour urinary potassium, sodium and chlorine excretion in abnormal group were higher than normal group, the levels of calcium and phosphorus excretion were lower. Therein, levels of sodium(P=0.037) and calcium (P<0.001) had significant difference. The levels of 24-hour urinary potassium, sodium, chloride, calcium and phosphorus excretion in the male group were higher than female group, among which potassium (P<0.001), sodium (P=0.001), chloride (P=0.002), and phosphorus (P<0.001) were statistically significant. In addition, duration of disease and HbAlc was not related to 24-hour Urinary Electrolyte Excretion.

Conclusion:There is a certain correlation between 24-hour urinary electrolyte excretion in T2DM and renal function. With the increase of 24-hour urinary sodium excretion and decrease of urinary calcium excretion, eGFR decreased, which was related to gender. Therefore, in patients with T2DM of the same gender, 24-hour urinary sodium and calcium excretion may be useful metabolic parameters for predicting poor renal prognosis, which needs further study.

Disclosure

Y. Wang: None. N. Li: None. L. Bu: None. H. Sun: None. B. Zhu: None. H. Li: None. S. Qu: None.

Funding

National Key Research and Development Program of China (2018YFC1314100); National Natural Science Foundation of China (81970677)
6-OR: Blood Pressure as Predictor of Coronary Artery Disease (CAD)/Cerebrovascular Disease (CVD) According to Glucose Tolerance Status (GTS): Implications for Updated Guidelines
Authors: YAMADA MAYUKO H. , FUJIHARA KAZUYA , YAGUCHI YUTA , OSAWA TAEKO , KITAZAWA MASARU , MATSUBAYASHI YASUHIRO , IWANAGA MIDORI , YAMADA TAKAHO , YAMANAKA NAUTA , SEIDA HIROYASU , OGAWA WATARU , SONE HIROHITO
Published: June 2020

Despite recent tightening of cutoffs for hypertension (HT) in major global guidelines, guidelines, especially according to GTS, remain debatable. We analyzed data from a nationwide claims database on 293,396 participants without prior CAD or CVD from 2008-16. Multivariate Cox regression model identified risks of CAD and CVD events. Hazard ratios (HRs) were compared among 5 levels of systolic blood pressure (SBP) (≤119, 120-129, 130-139, 140-149, ≥150) according to GTS [i.e., normal glucose tolerance (NGT), prediabetes (pre-DM), diabetes (DM)]. During the study period, 1099 CAD and 1990 CVD events occurred. Those with SBP levels ≥120 mmHg had a significantly higher risk of incident CAD/CVD than those with lower levels. The incidence of CAD and CVD did not differ significantly between NGT and pre-DM in those with SBP ≤119 whereas HRs for incident CAD for DM was almost 2.7, which was similar to NGT and pre-DM with SBP ≥150 mmHg (Table). Compared with NGT and SBP ≤119 mmHg, the HR for incident CAD among DM and SBP ≥150 mmHg was 5.91 (4.22-8.26), while SBP ≥150 mmHg significantly increased the risk of CVD about 4 fold regardless of GTS. These results based on a large database implied the need for even lower BP targets regardless of GTS. The impact of BP was stronger in DM in preventing CAD.

Disclosure

M.H. Yamada: None. K. Fujihara: None. Y. Yaguchi: None. T. Osawa: None. M. Kitazawa: None. Y. Matsubayashi: None. M. Iwanaga: None. T. Yamada: None. N. Yamanaka: None. H. Seida: None. W. Ogawa: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharma GmbH & Co.KG, Eli Lilly Japan K.K., Kowa Company, Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Other Relationship; Self; Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.

Funding

18K17897
61-LB: Use of Functional Near-Infrared Spectroscopy (fNIRS) to Assess Cognitive Effort in KATP-Related Neonatal Diabetes (KATP-NDM)
Authors: LETOURNEAU-FREIBERG LISA R. , MEIDENBAUER KIMBERLY L. , DENSON ANNA M. , TIAN PERSEPHONE , CHOE KYOUNG WHAN , BERMAN MARC G. , GREELEY SIRI ATMA W.
Published: June 2020

Individuals with KCNJ11 or ABCC8 mutations express over-activated KATP channels both in pancreatic beta cells as well as in the brain, and consequently exhibit a spectrum of neurodevelopmental difficulties. Even those with milder mutations exhibit more difficulty than sibling controls on a wide range of measures including executive functioning and IQ measures; but how this relates to channel dysfunction is unknown. fNIRS is a non-invasive technique increasingly used to assess brain activity as reflected by hemoglobin concentrations. fNIRS can be used to quantify fractal scaling of brain hemodynamics to estimate cognitive effort, which we hypothesized would be increased at rest or during tasks in KATP-NDM. Participants completed fNIRS assessment during a 7 minute resting state; executive function was assessed by Stroop task. Scaling phenomena may be fully described by a single Hurst exponent (H), with higher H indicating greater scale-free signal. Sixteen participants completed the resting state and Stroop task (6 affected, 10 controls, 50% female, age 7-40 years). All participants performed worse (lower accuracy and increased reaction time) on incongruent versus congruent trials of the Stroop task (accuracy: p=0.005, reaction time: p=0.02). KATP-NDM participants performed worse than controls (lower accuracy, slower reaction time), with mutation severity correlating significantly with overall accuracy (p=0.009). During resting state, affected participants had lower H than controls, possibly related to increased cognitive effort. Overall, higher H at rest corresponded to better performance on the Stroop task. Our data suggest that those with KATP-NDM experience increased cognitive effort even at rest, which may contribute to greater difficulty with task engagement and learning potential. fNIRS assessment of fractalness or other measures will help to clarify the role of KATP channel dysfunction in a range of cognitive processes.

Disclosure

L.R. Letourneau-Freiberg: None. K.L. Meidenbauer: None. A.M. Denson: None. P. Tian: None. K. Choe: None. M.G. Berman: None. S.W. Greeley: None.

Funding

National Institutes of Health (R01DK104942)
653-P: An Interdisciplinary Team Approach to Managing Diabetes in a Patient-Centered Medical Home: Year 2 Results
Authors: LAMIE STEVEN M. , ROCKAFELLOW STUART D. , SCHEPPERLY DEBRA
Published: June 2020

Background: Our private practice Patient-Centered Medical Home (PCMH) clinic proposed a pilot team-based program where patients would be seen between physician visits by an interdisciplinary team comprised of our CDE, Clinical Pharmacist, and Care Manager with the goal of helping to improve glycemic goals.

Methods: Patients age 18 or older with an A1c greater than 8.0 were identified through registry review and invited to participate. Team providers were under the supervision of the project lead physician. Number of visits was individualized for each patient. Visits centered on diabetes education, goal setting, and motivational interviewing. The project was pre-defined to have been successful if 15% of patients achieved improved control.

Results: A recruitment goal of 100 was targeted and initial 107 patients were identified and enrolled. One hundred and six patients completed year one, and 90 patients completed the second year. Nine patients were no longer followed through our clinic, and seven patients had died. Forty four (41%) patients achieved an A1c less than 8.0% at the end of the first year. At the end of year two, forty nine (54%) of the active patients achieved an A1c less than 8.0%. Starting in year 2, a second cohort of 46 patients with initial A1c greater than 8.0% were enrolled. The average A1c for this cohort was 9.39%. Thirty-nine patients continued to be actively followed at the end of year 2. The average A1c had dropped to 7.2% and 27 (69%) of this group had achieved an A1c less than 8.0%.

Conclusion: Most participants achieved diabetic control during Year 1 and maintained A1c at goal in Year 2 of the program. A greater percent of the second cohort was able to achieve A1c goal. This project demonstrates our interdisciplinary approach to help patients achieve and maintain glycemic control over a two-year period.

Disclosure

S.M. Lamie: Speaker’s Bureau; Self; Novo Nordisk Inc., Sanofi US. S.D. Rockafellow: None. D. Schepperly: None.
670-P: Effectiveness of Using Simulation to Train Nursing Students in Providing Preconception Counseling to Women with Diabetes
Authors: THURHEIMER-CACCIOTTI JENNIFER L. , CHARRON-PROCHOWNIK DENISE
Published: June 2020

Nurses can be pivotal to providing diabetes education, including, preconception counseling (PC) to prevent pregnancy-related complications in women with diabetes. However, many health professionals, including nurses, have reported self-deficits in these areas due to a lack training or knowledge. Simulation is an effective educational strategy utilized in schools of nursing to enhance critical thinking, decision-making, skills building and increase knowledge. However, little is known about the effectiveness of using simulation to train nursing students in providing diabetes education and preconception counseling to patients. Therefore, this study examined the effectiveness of a newly developed diabetes education/PC simulation training program developed for nursing students. The sample was 30 junior level baccalaureate nursing students who completed pretest and posttest measures on their awareness and knowledge of diabetes, pregnancy and PC. We used the 45 min video of READY-Girls (Reproductive-health Education and Awareness of Diabetes in Youth for Girls) PC program during the simulation training session because it is a validated evidenced-based, theory-driven program that targets female adolescents, and is endorsed by the American Diabetes Association. They also observed a live 10 minute simulation of actors portraying a diabetic educator and a diabetic female adolescent and their clinical interaction. Data were analyzed using a paired t-test. The mean pretest score was 9.33, while the mean posttest score was 15.00 with a statistically significant gain (t = 15.89; p = .000). Therefore, it appears that PC simulation may be an effective educational strategy to train nursing students on caring for women with diabetes.

Disclosure

J.L. Thurheimer-Cacciotti: None. D. Charron-Prochownik: None.
694-P: Effect of Exercise on Sleep and Nocturnal Glucose in Type 1 Diabetes (T1D)
Authors: JACOBS PETER G. , LI ZOEY , CALHOUN PETER , GAL ROBIN L. , BECK ROY , CASTLE JESSICA R. , CLEMENTS MARK A. , DASSAU EYAL , DOYLE FRANCIS J. , GILLINGHAM MELANIE B. , MARTIN CORBY K. , RICKELS MICHAEL R. , PATTON SUSANA R. , RIDDELL MICHAEL
Published: June 2020

Exercise increases nocturnal hypoglycemia risk which may impact sleep in T1D. Adults with T1D (n=25; 19 CSII; age 33±14yrs; HbA1c 7.6±1.3%; T1D duration 15yrs [IQR: 10, 22]) were divided into 3 exercise groups: aerobic, interval, or resistance, performed twice/week using instructional videos for 4 weeks. Participants used CGM, and wore an activity/sleep monitor (Garmin Vivosmart 3). Sleep duration was lower on nights following interval exercise compared to nights following sedentary days (p=0.04, Figure 1a). Participants experienced hypoglycemia earlier in the night following interval or aerobic exercise, compared to sedentary or resistance exercise (Figure 1b). Exercise types differentially impact sleep loss and nocturnal hypoglycemia.

Disclosure

P.G. Jacobs: Consultant; Self; SFC Fluidics. Research Support; Self; Dexcom, Inc. Stock/Shareholder; Self; Pacific Diabetes Technologies. Other Relationship; Self; AgaMatrix. Z. Li: None. P. Calhoun: Stock/Shareholder; Self; Dexcom, Inc. R.L. Gal: None. R. Beck: None. J.R. Castle: Advisory Panel; Self; Novo Nordisk Inc. Consultant; Self; ADOCIA, Dexcom, Inc., Zealand Pharma A/S. Other Relationship; Self; Pacific Diabetes Technologies, Roche Diabetes Care. M.A. Clements: Consultant; Self; Glooko, Inc. Other Relationship; Self; Glooko, Inc. E. Dassau: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; Roche Diabetes Care. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. F.J. Doyle: Research Support; Self; DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Stock/Shareholder; Self; Mode AGC. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. M.B. Gillingham: None. C.K. Martin: Advisory Panel; Self; EHE Health, NaturallySlim. Consultant; Self; Florida Hospital, Gila Therapeutics, OpenFit, Zafgen, Inc. Research Support; Self; Egg Board, Helmsley Trust, IDEA Public Schools, National Institutes of Health, NIHR, Patient-Centered Outcomes Research Institute, USDA, Weight Watchers International, Inc. Other Relationship; Self; Academy of Nutrition and Dietetics, Louisiana State Univ./Pennington Biomedical Research Center. M.R. Rickels: Consultant; Self; Semma Therapeutics, Inc. Research Support; Self; Xeris Pharmaceuticals, Inc. S.R. Patton: None. M. Riddell: Advisory Panel; Self; Zucara Therapeutics Inc. Consultant; Self; Lilly Diabetes. Research Support; Self; Dexcom, Inc., Insulet Corporation. Speaker’s Bureau; Self; Medtronic, Novo Nordisk A/S.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust (T1-DEXI Main Study)
738-P: Social Support Moderates the Association between Diabetes Distress and Diabetes Self-Care in Adults with Diabetes in Appalachian Ohio
Authors: BEVERLY ELIZABETH A. , RITHOLZ MARILYN D.
Published: June 2020

Background: Social support is associated with better physical and mental health in people with diabetes. Social support may buffer the negative effects of diabetes distress on health outcomes. The purpose of this study was to assess the moderating role of social support in the relationship between diabetes distress and self-care in adults with type 1 (T1D) and type 2 (T2D) diabetes in Appalachian Ohio.

Methods: Participants completed the Diabetes Distress Scale for T2D or T1D, the Medical Outcomes Study Social Support Survey, and the Self-Care Inventory Revised. We conducted hierarchical multiple regression models using SPSS version 26.0. To avoid multicollinearity with the interaction terms, variables were centered.

Results: A total of 325 adults (age=41.6±19.2 years, 62.2% female, 86.5% white; A1C=7.5±1.6%; duration=12.4±9.6 years) participated. Of the 131 participants with T1D, 30.5% reported high diabetes distress. For the 194 T2D participants, 27.7% reported high diabetes distress. In the T1D model, diabetes distress and social support were significantly associated with diabetes self-care: R2 .15, F(2, 103)=8.81, p<.001. However, the interaction term did not account for the variance in T1D self-care (b= -.032, t= -.349, p=.728). In the T2D model, diabetes distress and social support were significantly associated with diabetes self-care: R2 .17, F(2, 182)=18.58, p<.001. The interaction term between diabetes distress and social support accounted for a significant proportion of the variance in T2D self-care: ΔR2=.03, ΔF(1, 296)=6.82, p=.01, b= -.185, t= -2.61, p=.01.

Conclusions: Social support moderated the relationship between diabetes distress and self-care in adults with T2D but not T1D. Further explorations of social support in adults with T1D is warranted. Given the importance of kinship in Appalachian culture, engaging family members and the community in diabetes management may buffer the negative effect of diabetes distress.

Disclosure

E.A. Beverly: None. M.D. Ritholz: None.

Funding

American Osteopathic Association (1291708718)
77-LB: Improved A1C and TIR in Adults with T2D Participating in a CGM-Driven Virtual Diabetes Clinic
Authors: MAJITHIA AMIT R. , KUSIAK COCO , LEE AMY ARMENTO , COLANGELO FRANCIS R. , ROMANELLI ROBERT , ROBERTSON SCOTT , MILLER DAVID P. , ERANI DAVID M. , DIXON RONALD F. , ZISSER HOWARD
Published: June 2020

The Onduo Virtual Diabetes Clinic (VDC) for people with T2D combines a mobile app, remote personalized lifestyle coaching, connected devices and live video consultations with board-certified endocrinologists for medication management and prescription of real-time CGM devices for intermittent use. This prospective single-arm study enrolled adults with a baseline A1c of ≥8.0% to ≤12.0% from 2 primary care centers to participate in the VDC program. The primary outcome was change in A1c from baseline at 4 mo. Secondary outcomes included change in CGM-based (Dexcom G6) glycemic parameters. Participants (n=55) were: 57.3±11.6 yr, 40.0% female and BMI 33.7±7.2. A1c decreased significantly by -1.6%±1.0 (p<0.001) from 8.9%±1.0 to 7.3%±0.9 at 4 mo. Stratified by baseline A1c 8.0% to 9.0% (n=36) and >9.0% (n=19), A1c decreased by -1.2%±0.6 and -2.4%±1.3 (both p<0.001). CGM metrics (n=43) are presented in the Table. Percent time in range (TIR) increased significantly from below target to target levels at follow-up. The results indicate that participation in the VDC for 4 mo was associated with significant improvement in A1c, increased TIR, decreased time in hyperglycemia and no increase in hypoglycemia.

In conclusion, the VDC has potential to support people with T2D and their clinicians between office visits by increasing access to specialty care and advanced diabetes technology including CGM.

Disclosure

A.R. Majithia: Consultant; Self; Onduo. C. Kusiak: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC. A. Armento Lee: None. F.R. Colangelo: None. R. Romanelli: Advisory Panel; Self; Novo Nordisk Inc. S. Robertson: Other Relationship; Self; Verily Life Sciences LLC. D.P. Miller: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC. D.M. Erani: None. R.F. Dixon: Employee; Self; Onduo. H. Zisser: Employee; Self; Verily Life Sciences LLC. Stock/Shareholder; Self; Verily Life Sciences LLC.
789-P: Self-Care for Blood Glucose Monitoring (BGM) in Teens with Type 1 Diabetes (T1D): Impact of Real-Time Positive and Negative Affect
Authors: SHAPIRA AMIT , VOLKENING LISA K. , BORUS JOSHUA , LAFFEL LORI M.
Published: June 2020

Aim: Teens with T1D often report negative emotions related to diabetes self-care. Affect tends to vary throughout the day and may provide an explanatory pathway to poor diabetes self-care and suboptimal glycemic control in teens. We used momentary sampling to examine associations between affect and BGM adherence in teens with T1D.

Methods: Over 2 weeks, 32 teens (ages 14-18 years) used handheld computers to self-report positive (POS) and negative (NEG) affect (Positive and Negative Affect Schedule) and BGM adherence 4 times daily. Teens selected the times to receive the messages based on their usual BGM times. There were 225 paired affect and BG adherence reports. Z-scores were calculated for the NEG and POS subscales to reflect deviations from each teen’s overall affect. Separate logistic generalized estimating equations, adjusted for age, sex, T1D duration, and pump therapy assessed associations between POS and NEG affect and BGM adherence.

Results: Teens (56% female) were (M±SD) 16.6±1.4 years old with T1D duration of 8.8±4.2 years; 63% were pump treated and A1c was 8.8±1.4%. Teens reported checking BG 59% of the time. In adjusted models, greater NEG affect was associated with lower odds of BGM (OR=0.5, 95% CI: 0.4-0.8, p=.001). POS affect was not significantly associated with BGM. Age, sex, T1D duration, and pump therapy were not significantly associated with BGM.

Conclusions: In a sample of teens with T1D receiving multiple daily prompts to check BG, positive affect did not relate to BGM frequency; however, negative affect was associated with being half as likely to check BG. These findings suggest a need to provide teens with strategies for maintaining diabetes self-care behaviors when they are experiencing negative emotions.

Disclosure

A. Shapira: None. L.K. Volkening: None. J. Borus: None. L.M. Laffel: Advisory Panel; Self; Roche Diabetes Care. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Insulogic LLC, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi US.

Funding

JDRF International; National Institutes of Health (P30DK036836, K12DK094721)
862-P: A Machine Learning Model Predicts Engagement with a Mobile Health (mHealth)-Based Remote Patient Monitoring (RPM) Program among Persons with Diabetes (PWDs)
Authors: BABIKIAN SARINE , SINGH VIKRAM , CLEMENTS MARK A.
Published: June 2020

We developed a machine learning model that predicts risk of declining engagement (churn) with an mHealth app (Glooko) that supports diabetes self-management. The model uses self-monitored blood glucose (SMBG), demographic, and app engagement data.

We selected 7134 PWD using meter and/or insulin pump devices who used the Glooko diabetes management app in a remote (outside of the clinic) setting between 1/1/2019-7/1/2019 (40,349 total weekly predictions). We trained a gradient boosting algorithm to predict risk of churn in the next 28 days.

We built features using data from the prior 28 days; features included outcomes (counts of glucose checks, hypo/hyperglycemia occurrences, mean blood glucose), app engagement (counts of app clicks and meter and/or insulin pump uploads, duration of sessions), and demographics (diabetes type, gender, age).

The training cohort had median age=22 years (IQR:11-49), 52% female, 60% type 1 diabetes (T1D). We performed out-of-sample validation using 4647 individuals (8646 total weekly predictions). The validation cohort had median age=20 years (IQR:11-49), 52% female, 60.5% T1D. The algorithm predicted individuals at risk of churning with a precision of 0.67 and a recall of 0.8. This correlates to sensitivity=80%, specificity=58%, and positive predictive value=67%.

The present model indicates that it is feasible to predict declining engagement with an mHealth app to support diabetes self-management. The ability to predict churn may help clinics design effective mHealth-based RPM programs. These predictions can allow clinicians to proactively reach out to PWDs at risk of program dropout. Future research should examine whether dropout from RPM programs predicts worsening diabetes-related outcomes.

Disclosure

S. Babikian: Employee; Self; Glooko, Inc. V. Singh: Employee; Self; Glooko, Inc. M.A. Clements: Consultant; Self; Glooko, Inc. Other Relationship; Self; Glooko, Inc.
866-P: Estimated HbA1c Discordance: Should Estimated HbA1c Be Derived from Time-in-Range or Mean Glucose Levels?
Authors: TAKEISHI SOICHI , TSUBOI HIROKI
Published: June 2020

In patients with hypoglycemia, estimated HbA1c (eA1c) derived from the percentage of time in range [TIR] (reference range, 70-180 mg/dL) using reported formulae may be overestimated. We examined eA1c derived from TIR (TIR-eA1c) and eA1c derived from mean glucose levels (mean-eA1c). In this cross-sectional study, we analyzed 24-h glucose levels measured from 00:00 to 24:00 during hospitalization using a continuous glucose monitor (iPro2) in 119 patients with type 2 diabetes. We calculated TIR-eA1c and mean-eA1c for these 119 patients using the reported following formulae: TIR-eA1c 1 = 10.31 - 0.048 × TIR; TIR-eA1c 2 = (TIR - 155.4) ÷ -12.762; mean-eA1c 1 = (mean glucose level + 46.7) ÷ 28.7; and mean-eA1c 2 (proposed as the glucose management indicator) = 3.31 + 0.02392 × mean glucose level. The values of TIR-eA1c 1 - mean-eA1c 1 [Δ1], TIR-eA1c 2 - mean-eA1c 1 [Δ2], TIR-eA1c 1 - mean-eA1c 2 [Δ3], and TIR-eA1c 2 - mean-eA1c 2 [Δ4] were also evaluated. An increase in the percentage of time below range (< 70 mg/dL) [TBR < 70] was significantly associated with increased Δ1, Δ2, Δ3, and Δ4. The presence of hypoglycemia was significantly associated with Δ1 > 0.5%, Δ2 > 0.5%, Δ3 > 0.5%, and Δ4 > 0.5% (Table). Overall, our results show that mean-eA1c should be used as the indicator of HbA1c in patients with hypoglycemia.

Disclosure

S. Takeishi: None. H. Tsuboi: None.
907-P: Impact of Using a Digital Therapeutic and Blood Glucose Meter on Glycemic Control and Variability
Authors: KRISHNAKUMAR ARJUN , KUMAR VASANTH , SABOO BANSHI D. , KHATRY VARSHA , JOSHI SHILPA , ADHIKARY RISHI R. , KOLWANKAR SIDDDHESH , MATTOO VINOD
Published: June 2020

Background: High out of pocket expenses have led to poor diabetes self-management and glycemic control in India. This study evaluates the impact of an iPDM (integrated personalized diabetes management) on blood glucose (BG) control.

Methods: Study participants (n=286) used an iPDM consisting of the Accu-Chek® Active BG meter and the Wellthy Care™ digital therapeutic platform (WDTx), which allowed them to log BG values while receiving artificial intelligence-powered real-time feedback and self-management education. The BG values at baseline (M0), month 2 (M2), month 4 (M4), and month 6 (M6) were analyzed. Mean BG (MBG), Fasting BG (FBG), Post-meal BG (PBG), number of hypoglycemia logs (<70 mg/dl), and in-range logs (FBG: 70-130 mg/dl; MBG/PBG: 70-180 mg/dl) were evaluated.

Results: The average number of active days and BG logs by the participants was 75.9 days (95% CI: 66.0-85.7 days) and 73 logs (95% CI: 67-79 logs), respectively. The BG values and logs are summarized in Table 1. There was a significant reduction in BG from M0 to M2 after which the BG was stable over M4 and M6. There was also a reduction in the number of hypoglycemia logs and a corresponding increase in the number of in-range BG logs from M0 through M6.

Conclusion: This study shows that an iPDM using SMBG and WDTx can be an effective and affordable tool for improving glycemic control and reducing hypoglycemia events in resource limited countries like India.

Disclosure

A. Krishnakumar: Employee; Self; Wellthy Therapeutics. V. Kumar: None. B.D. Saboo: None. V. Khatry: None. S. Joshi: Consultant; Self; Wellthy Therapeutics. R.R. Adhikary: Employee; Self; Wellthy Therapeutics. S. Kolwankar: Employee; Self; Wellthy Therapeutics. V. Mattoo: None.
944-P: HbA1c Change Is Associated with Retinopathy Outcomes during GLP-1RA CVOT Follow-Up
Authors: BETHEL ANGELYN , DIAZ RAFAEL , CASTELLANA NOELIA , GERSTEIN HERTZEL C. , LAKSHMANAN MARK
Published: June 2020

Long-term glucose control reduces retinopathy risk. We examine the association between HbA1c change and retinopathy in the first year or at final follow-up in GLP-1 RA cardiovascular outcomes trials (CVOTs). A random-effects model meta-analysis included 6 CVOTs reporting retinopathy events, using within-trial event definitions. Univariate meta-regression analyses describe the association between HbA1c change and retinopathy events. Meta-analysis showed no significant effect of GLP-1 RA on retinopathy risk (odds ratio [OR] 1.10; 95% CI 0.93, 1.30), with moderate heterogeneity between studies (I2=52.2%; Q-statistic p-value=0.063). HbA1c change and retinopathy were significantly associated at 1-year (slope=1.40, p-value=0.002) and overall (Figure), with 0.1% HbA1c reduction associated with 15% increased OR in the first year, declining to 8.0% increase over longer follow-up. In these studies of varying duration (1.3 to 5.4 years), GLP-1 RA treatment was not significantly associated with increased retinopathy risk. HbA1c reduction rate is correlated with risk for retinopathy in people with diabetes and additional CV risk factors. Clinicians should consider retinopathy status when initiating any therapy that rapidly lowers HbA1c.

Disclosure

A. Bethel: Employee; Self; Eli Lilly and Company. R. Diaz: None. N. Castellana: None. H.C. Gerstein: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Kowa Pharmaceuticals America, Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Sanofi. M. Lakshmanan: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company.

Funding

Eli Lilly and Company
948-P: A Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HM15136, a Novel Long-Acting Glucagon Analogue, in Healthy Subjects
Authors: HUH KI YOUNG , SHIN WONJUNG , BAEK EUNHYE , SEO SUJIN , LEE WOOSUN , BAEK SEUNGJAE , LEE HOWARD
Published: June 2020

HM15136 is a novel long-acting glucagon analogue with an extended half-life. In vivo efficacy studies of HM15136 in animal models showed its therapeutic potential in congenital hyperinsulinism, hypoglycaemia post-bariatric surgery, and obesity. We performed a randomized, double-blind, placebo-controlled first-in-human trial to assess the safety, pharmacokinetics, and pharmacodynamics of a single subcutaneous dose of HM15136 in healthy adults. Fifty-six subjects of a mean age, BMI, and HbA1c of 31.1 years, 23.1 kg/m2, and HbA1c 5.2%, respectively, randomly received HM15136 or its matching placebo in a ratio of 6:2 in 7 cohorts (10, 20, 30, 50, 80, 100, and 120 µg/kg). All adverse events were mild in severity and transient. Neither serious adverse event nor discontinuation due to adverse event occurred during the study. The most frequent Treatment Emergent Adverse Event was nausea (7.2%, only in the 100 and 120 µg/kg groups). Injection site erythema, which was barely noticeable and spontaneously subsided without sequelae, was reported in 2 out of 42 subjects who received HM15136. HM15136 was slowly, but steadily absorbed with the peak serum concentration reaching 34.2-65.2 hours after dose. The terminal half-life ranged from 69.8 to 85.6 hours, which was significantly greater than that of glucagon (< 1 hour). HM15136, particularly at doses >50 µg/kg, increased mean serum glucose from baseline by up to 27.7 mg/dL, which was maintained until 17 days after dose.

In conclusion, a single subcutaneous dose of HM15136 at 10-120 µg/kg was safe and well-tolerated. The long half-life of HM15136, coupled with increase in serum glucose for ∼2 weeks, may warrant a weekly dosing regimen.

Disclosure

K. Huh: None. W. Shin: None. E. Baek: None. S. Seo: None. W. Lee: None. S. Baek: Employee; Self; Hanmi Pharmaceutical. H. Lee: None.
959-P: Indirect Treatment Comparison (ITC) of IGlarLixi vs. IDegLira in Adults Inadequately Controlled by GLP-1 Receptor Agonists (GLP-1RAs)
Authors: HOME PHILIP , ARODA VANITA R. , FAZELI MIR SOHAIL , WHITTINGTON CRAIG , GOSWAMI HARDIK , SHAUNIK ALKA , POURRAHMAT MIR-MASOUD , BLONDE LAWRENCE , KALRA SANJAY
Published: June 2020

In people with type 2 diabetes uncontrolled by GLP-1 RAs, fixed-ratio combination (FRC; basal insulin + GLP-1 RA) is a recommended option. A PICO-framework systematic review of RCTs followed by an ITC was performed to compare the efficacy and safety of the FRCs iGlarLixi (insulin glargine 100 U/mL + lixisenatide) and IDegLira (insulin degludec + liraglutide) in this population. A fixed effects model was used on the two eligible RCTs. Outcomes: change from baseline to week 26 in HbA1c, clinic fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG), and body weight; proportion achieving HbA1c <6.5 or <7.0 %; hypoglycemia incidence. Baseline characteristics were similar across studies. Significant mean differences were seen in change in HbA1c and FPG favoring IDegLira, but not pre- or postprandial SMPG (breakfast or daily average) or weight (Table). Similar proportions achieved HbA1c targets. Hypoglycemia comparisons suffered from varying definitions, sulfonylurea (SU) use and eligibility, and few events in the GLP-1 RA arms (incidence: 32% [confirmed ≤3.1 mmol/L, 28% without SU] with IDegLira and 9% or 28% [symptomatic <3.0 or ≤3.9 mmol/L] with iGlarLixi). This ITC shows similar FRC HbA1c glycemic target achievement but suggests divergent differences in other glycemia results and hypoglycemia, likely due to different study design and titration application.

Disclosure

P. Home: Advisory Panel; Self; Roche Diabetes Care. Consultant; Self; Mundipharma International, Novartis AG, Sanofi. Research Support; Self; GlaxoSmithKline plc., Merck & Co., Inc., Sanofi. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim International GmbH. V.R. Aroda: Consultant; Self; Duke, Novo Nordisk Inc., Sanofi. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; Applied Therapeutics, Fractyl Laboratories, Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; IMNE, Medscape. M. Fazeli: None. C. Whittington: Employee; Self; Sanofi US. H. Goswami: None. A. Shaunik: None. M. Pourrahmat: Other Relationship; Self; Sanofi US. L. Blonde: Advisory Panel; Self; AstraZeneca, Gilead Sciences, Inc. Consultant; Self; Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Janssen Scientific Affairs, LLC., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc., Sanofi. S. Kalra: Advisory Panel; Self; Eli Lilly and Company. Speaker’s Bureau; Self; Novo Nordisk A/S, Sanofi-Aventis.

Funding

Sanofi
99-LB: Multiscale Biological Rhythms in Individuals with T1D on DIY Closed-Loop and SAPT
Authors: LEWIS DANA M. , GRANT AZURE D. , KRIEGSFELD LANCE
Published: June 2020

Background: Circadian and ultradian rhythms in BG have been observed in individuals without diabetes and are regulated both by time of day and meal intake, with ultradian fluctuations generally of smaller amplitude than circadian fluctuations. We assessed relative stability of circadian and ultradian rhythms in individuals without T1D (n=16), and individuals with T1D using two different therapies: sensor-augmented pump therapy (SAPT, n=100) and DIY closed loop (n=30).

Methods: Frequency decomposition using continuous morlet wavelet transformation (A to C) were created to assess change in rhythmic composition of normalized blood glucose data.

Results: Example Wavelet (C) in T1D illustrates high power in the 1-6H range, and lower power in the ~24H range for nearly all time points. The ratio of power in the 23-25H (circadian) range to power in the 1-6H (ultradian) range was calculated to estimate relative stability of circadian to ultradian rhythms. Those without T1D showed higher circadian compared to ultradian power, whereas both groups with T1D showed a comparably lower ratio (D).

Conclusion: Wavelet analysis of BG in individuals with and without T1D reveals a difference in relative strength of daily and hourly rhythms, independent of therapy type. These results suggest current therapies do not recreate expected daily rhythmicity in blood glucose, perhaps due the lifespan of rapid-acting insulin and meal patterns.

Disclosure

D.M. Lewis: Research Support; Self; JDRF. A.D. Grant: None. L. Kriegsfeld: None.

Funding

JDRF