bluuebunny/crossref_metadata_2025 huggingface dataset:
2243-PUB: Association between Blood Pressure, Adiposity, and Lifestyle Behaviors in Schoolchildren
Authors: HIRSCHLER VALERIA , GROUP DIOSES STUDY , MOLINARI CLAUDIA , LAPERTOSA SILIVA , GARCIA CONCEPCION
Published: June 2020

Background: Childhood blood pressure (BP) is known to be associated with weight status. However, the association between BP and adiposity and lifestyle behaviors in normal-weight (NW) versus overweight/obese (OW/OB) schoolchildren should be further explored.

Objective: To determine the association between schoolchildren’s BP with adiposity and lifestyle behaviors.

Methods: Data for age, sex, BMI, waist circumference (WC), and BP were recorded. OW/OB was defined as a BMI > 85%ile or > 95%ile respectively. A 5-level index that ranked participants’ daily consumption of vegetables or fruits, milk, sweetened beverages, and TV viewing were performed.

Results: Schoolchildren (n = 1249, 554M) aged 9.4 ± 2.1 years from 9 elementary schools in five states of Argentina were examined. The prevalence of OW was 265 (21.2%) o and OB 265 (21.2%). All came from a low socio-economic background; 62% of the parents had an elementary school education or less. Children were divided into NW and OW/OB. Systolic BP was significantly associated with age (r=0.18), WC (r=0.17), and BMI (r=0.34) in NW children. However, systolic BP was significantly associated with age (r=0.37), WC (r=0.42), WC/height (r=0.24), BMI (r=0.19), low fruit intake (r=0.14), and TV watching (r=0.12) in OW/OB children. Diastolic BP was significantly associated with age (r=0.40), WC (r=0.37), WC/height (r=0.18), and BMI (r=0.33) in OW/OB children. Multiple linear regression analyses showed that systolic BP was only significantly associated with age in NW children (R2=0.02); but with age, WC, and TV watching (R2=0.22) in OW/OB children. In addition, diastolic BP was significantly associated with age and WC (R2=0.17) in OW/OB children but no association was found in NW children.

Conclusion: These results suggest that BP levels in schoolchildren were associated with adiposity and unhealthy lifestyle behaviors. Future longitudinal studies should be performed to confirm these findings.

Disclosure

V. Hirschler: None. C. Molinari: None. S. Lapertosa: None. C. Garcia: None.
2244-PUB: Quantifying Adverse Childhood Experiences in a Pediatric Cohort with Type 1 Diabetes
Authors: ZAKHEIM EMMANUELLE , GILDENGORIN GINNY , AHMAD TARIQ
Published: June 2020

Social determinants impacting health has been widely established in the pediatric population, but there is a paucity in the literature quantifying psychosocial stressors in children with chronic conditions. We administered the Pediatric Adverse Childhood Experiences and Related Life Events Screener (PEARLS) to a cohort of pediatric patients with type 1 diabetes (T1D), with at least 1 year duration, at UCSF Benioff Children’s Hospital Oakland. This two-section validated survey quantifies experiences such as (but not limited to): Section 1 (S1), abuse, neglect, and domestic dysfunction and Section 2 (S2), domestic hardship (eg food scarcity, housing). Our cohort included 38 males and 43 females, aged 4 to 21 years old. Scored surveys were compared to social determinants (insurance status, clinic location, and race) and health factors (HbA1c and BMI). Statistical analyses were performed using t-tests, chi-square tests, and multivariate regression models. Results revealed an average PEARLS score for the group as 1.16 ±1.79 and 0.63 ±1.05 for S1 and S2 respectively. There was a statistical difference between Caucasians and non-Caucasians for S1 (p=0.01), and for those patients who were seen in Oakland versus an upper-middle-class suburban clinic (San Ramon, CA) for both Sections (p=0.01 and p=0.007, for S1 and S2 respectively). For those with a HbA1c > 10% there was a statistical difference for S2 (p=0.004). This is the first study quantifying adverse childhood experiences in a T1D cohort, as far as we know. As a group, those with T1D do not experience significant toxic stress, but statistically relevant risk factors for elevated PEARLS scores included being non-caucasian, having a HbA1c > 10% and being seen in an urban clinic. Implementation of the PEARLS survey can help providers and diabetes care teams focus on stressors that may be impeding glycemic control and impacting current and future health, particularly in those risk groups mentioned prior. Use of larger cohorts may elucidate other associations.

Disclosure

E. Zakheim: None. G. Gildengorin: None. T. Ahmad: None.
2262-PUB: Association of Adipokines with Diabetes: Measurements in Blood and Saliva
Authors: VINITHA RAMACHANDRAN , RAGHAVAN KUNCHITHAPATHAM , ARUN VASUDEVAN K. , SUSAIRAJ PRISCILLA , RAGHAVAN ARUN , NANDITHA ARUN , SATHEESH KRISHNAMOORTHY , SNEHALATHA CHAMUKUTTAN , RAMACHANDRAN AMBADY
Published: June 2020

The association of adiponectin, apelin, visfatin and vaspin with different glycaemic states (normal glucose tolerance (NGT), (impaired glucose tolerance (IGT) and type 2 diabetes (T2D)) and in the presence of periodontits were studied in saliva and blood (serum) samples. The utility of saliva and serum in measuring these adipokines was also compared. Prescreening was done to identify persons with ≥ 3 risk factors for T2D among; age 35 -55 years, overweight/obesity, high waist circumference, family history of T2D, hypertension or sedentary habits. They were then categorised as having no diabetes (NGT + IGT, Group A) and having diabetes (T2D, Group B) based on oral glucose tolerance test. Presence of periodontitis was assessed by a periodontist. Samples were analysed using ELISA. Of the 615 persons screened, 136 (22.1%) had 3 or more risk factors. Ninety (14.6%) persons (NGT (n = 48), IGT (n = 17) T2D (n = 25)) were enrolled. Concentrations of adipokines in groups A and B are presented in the table. Higher salivary vaspin and lower visfatin were observed in the presence of periodontitis. The utility of serum and saliva in the measurement of adipokines for diabetes vary considerably. In Asian Indians, lower adiponectin and higher visfatin in serum and increased salivary visfatin and apelin are useful biomarkers of diabetes, illustrating the involvement of inflammation in the pathogenesis of T2D.

Disclosure

R. Vinitha: None. K. Raghavan: None. V.K. Arun: None. P. Susairaj: None. A. Raghavan: None. A. Nanditha: None. K. Satheesh: None. C. Snehalatha: None. A. Ramachandran: None.
2264-PUB: Progress in Curating Gene–Disease Relationships by the ClinGen Monogenic Diabetes Expert Panel
Authors: POLLIN TONI I. , MAYERS MEGAN A. , GREELEY SIRI ATMA W. , MALONEY KRISTIN A. , NAYLOR ROCHELLE N. , PAKYZ RUTH E. , PATEL KASHYAP A. , UDLER MIRIAM , ZHANG HAICHEN , COLCLOUGH KEVIN , THAXTON COURTNEY
Published: June 2020

Diagnosing and distinguishing monogenic diabetes, including some MODY (maturity-onset diabetes of the young), from type 1 or type 2 diabetes can have profound clinical implications: sulfonylureas vs. insulin or metformin for HNF1A- and HNF4A- diabetes, and no treatment for GCK-diabetes. Since 1996, the number of monogenic diabetes genes has expanded from three to 60 or more, with 14 called MODY genes; however newer evidence has called some of these gene associations into question. Monogenic diabetes is currently underdiagnosed, but the decreasing cost of sequencing and the ability to create multi-gene next-generation sequencing panels may increase access to testing and a proper diagnosis. For the testing to be useful, it is important that the genes chosen for these panels have appropriate evidence as causal genes. The NIH Clinical Genome Resource (ClinGen) Monogenic Diabetes Gene Curation Expert Panel was convened to bring together experts in clinical and laboratory aspects of monogenic diabetes and gene curation to publish curations for the ClinGen website based on evidence from clinical and molecular studies and population databases.

To date, we have published evidence-based gene curation summaries for Gene-Disease Validity for HNF1A and HNF4A (both classified as Definitive for monogenic diabetes) and are in the process of curating and publishing curations for GCK (Definitive for monogenic diabetes), INS (Definitive for monogenic diabetes and permanent neonatal diabetes), HNF1B (Definitive for renal cysts and diabetes), and KLF11 (Disputed for monogenic diabetes due to limited evidence and high population frequencies of variants previously asserted as causative). Curation of additional genes is in progress. Accurate curations will inform appropriate testing panel content to reduce ambiguous results and assure variants identified are clinically relevant for informing the care of diabetes in patients and their families.

Disclosure

T.I. Pollin: None. M.A. Mayers: None. S.W. Greeley: None. K.A. Maloney: None. R.N. Naylor: None. R.E. Pakyz: None. K.A. Patel: None. M. Udler: None. H. Zhang: None. K. Colclough: None. C. Thaxton: None.

Funding

National Institutes of Health (U24HD093486)
227-LB: Dietary Protein Restriction Induced–FGF21 Improves Metabolic Health during Aging
Authors: HILL CRISTAL M. , MCDOUGAL DAVID , MORRISON CHRISTOPHER
Published: June 2020

Aging and obesity are risk factors linked to the impairment of both energy and glucose homeostasis. Conversely, reducing caloric intake or the intake of select macronutrients or amino acids, including dietary protein restriction (DPR) and methionine restriction, defends against the detrimental effects of aging and obesity. Our data demonstrate that DPR increases energy expenditure and improves glucose homeostasis, and that the metabolic hormone FGF-21 coordinates these adaptive responses to protein restriction in young mice. However, the role of FGF-21 in mediating the effects of DPR during aging remains unclear. C57BL6 mice were fed either a normal protein (NP) or a low protein diet (LP), beginning at either young (3-months) or middle (12-months) age. A separate group of middle-aged mice were fed either a high-fat (HFD) diet or a high-fat, low-protein (HFLP) diet. Bodyweight and food intake were assessed weekly in all groups. Energy expenditure and glucose tolerance were assessed at 12 and 20 months of age in young mice and 16 months of age in middle aged-mice. Serum collected at sacrifice was used to measure FGF-21 levels. LP diet increased energy expenditure and food intake, and reduced body weight gain, in both young and middle-aged mice (P<0.05), and HFLP-diet similarly reduced body weight gain relative to HFD-fed controls (P<0.05). Glucose tolerance was improved in LP-fed young mice, and in LP and HFLP fed middle-aged mice (P<0.05). Lastly, FGF-21 levels were increased in both young and middle-aged mice in response to LP-diet (P<0.05), and in response to HFLP in middle-aged mice (P<0.05). These data indicate that the interaction of age or diet-induced obesity does not blunt the effects of DPR to induce-FGF-21, reduce body weight gain, increase energy expenditure, or improve glucose homeostasis.

Disclosure

C.M. Hill: None. D. McDougal: None. C. Morrison: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK105032, F32DK115137); Pennington Biomedical/Louisiana Nutrition Obesity Center (P30DK072476)
2272-PUB: Association between Hypertension and Diabetes Medication Compliance and Complications in Korea
Authors: CHUN KI HONG
Published: June 2020

Purpose: The purpose is to determine whether dosing compliance of person with hypertension(HT) or DM is related to the occurrence of AMI, stroke, and CRF.

Method: Since Korea’s health insurance is social insurance for all citizens and is operated by a separate act, there are data that claim the medical expenses of all citizens. This study uses the full medical expenses claims data of all citizens. As of 2011, all persons with HT or DM were enrolled in the year, and a retrospective cohort data was added to follow-up by 2018, adding new dosing patients each year. Since 2016, complications have been observed by year, and previous occurrences were excluded from the study. For those who took medications from 2011, we calculated the annual compliance rate of the medications up to the previous year of occurrence, and excluded those who are less than 3 years before 2018. By the age group, the annual incidence of 2016-2018 according to complications was calculated according to the average dose compliance rate and the ratio of the odds of complications among those in the 1/5 quintile and the odds of complications among others were analyzed by year.

Result: HT or DM medication compliance rates were highly associated with all complications in their 30s and 40s. Above 70 years of age was associated with stroke. In the fifties and sixties, DM or HT compliance were closely related to all complications, except that DM compliance was not associated with AMI.

Discussion: It is important for persons with HT or DM in their 30s and 40s to increase their dosing compliance to minimize their complications occurrence. It is necessary to thoroughly monitor DM compliance because this is highly related to the occurrence of the most expensive CRF. In the 50s and 60s, HT and DM compliance are closely related to the occurrence of all complications, which can significantly reduce future costs through thorough dosing of population.

Disclosure

K. Chun: None.
2276-PUB: Fecal Profile of Short-Chain Fatty Acids: Associations with Environmental Factors in the First Year of Life of Women Participating in the Nutritionist’s Health Study
Authors: BARBOSA MARINA G. , SOLAR ISABELA , FREITAS RENATA G. , RIBEIRO FRANCIELI B. , RAMOS CAMILA O. , SANT’ANA MARCELLA R. , HANADA ALFREDO S. , CROUCHAN NAJLA S.K. , XAVIER CAMILA M. , NETO BRUNO G. , FOLCHETTI LUCIANA G.D. , SILVA ISIS T. , ALMEIDA-PITITTO BIANCA , FERREIRA-VIVOLO SANDRA ROBERTA G. , VASQUES ANA CAROLINA J.
Published: June 2020

Introduction: Many studies report that environmental factors occurring in childhood may modulate the composition of the gut microbiota in adulthood, which in turn, produces short chain fatty acids (SCFA) with metabolic effects on inflammatory cascades associated with glycemic homeostasis.

Objective: This study aims to analyze associations between type of delivery (vaginal/cesarean section), type of breast-feeding (maternal/artificial) and solid food introduction (start and quality) with fecal SCFA concentrations in women.

Method: A cross-sectional study including 106 women, 28±5 years old and BMI 25±5 kg/m2, a questionnaire regarding from birth until the first year of life. For quantification of acetate, butyrate and propionate it was used gas chromatography-mass spectrometry in fecal samples.

Results: Of the women surveyed 63% were cesarean delivered and 93% received maternal breast milk at some point. There was no correlation between SCFA concentration and type of delivery (p>0.05). Positive correlation was found between breastfeeding time and butyrate (r=0.24; p=0.02), there was a tendency with propionate (r=0.20; p=0.06). There was no correlation between time received infant formula and SCFA. There was a tendency of correlation between butyrate and beginning of cow’s milk intake (r=0.194; p=0.052). Age at solid food introduction correlates with propionate (r=0.22; p=0.026) and butyrate (r=0.25; p=0.012), and report a tendency with the acetate (r=0.18; p=0.07). In the first year of life, individuals who prefer salty crackers and pasta/potatoes had less concentration of propionate and acetate, respectively (p=0.026).

Conclusion: The type of delivery was not associated with SCFA, but there was a favorable association with prolonged breastfeeding, late beginning of cow’s milk intake, introduction of solids starting after 6 months of age and lower intake of refined cereals.

Disclosure

M.G. Barbosa: None. I. Solar: None. R.G. Freitas: None. F.B. Ribeiro: None. C.O. Ramos: None. M.R. Sant’Ana: None. A.S. Hanada: None. N.S.K. Crouchan: None. C.M. Xavier: None. B.G. Neto: None. L.G.D. Folchetti: None. I.T. Silva: None. B. Almeida-Pititto: None. S.G. Ferreira-Vivolo: None. A.J. Vasques: None.

Funding

São Paulo Research Foundation (2017/10185-9, 2019/05450-0)
2279-PUB: High Prevalence and Suboptimal Management of Diabetes in India: Findings from a Community-Based Study
Authors: MOHAN SAILESH , JARHYAN PRASHANT , SHARNNGADHARAN GANESH KUMAR , PRABHAKARAN DORAIRAJ
Published: June 2020

Purpose: Diabetes is rapidly increasing in India. This study aimed to determine the current prevalence of diabetes and its management in rural and urban India.

Methods: We conducted a large population based cross-sectional survey among 12284 participants aged ≥30 years residing in rural and urban North and South India. Participants were selected using a multistage cluster random sampling technique. Trained personnel collected the data using a questionnaire, measured blood pressure, conducted anthropometry and collected bio-samples. Diabetes was defined as FPG ≥ 126 mg/dl or HbA1C ≥ 6.5% or self-reported physician diagnosis or being on treatment. Control was defined as HbA1C < 7%.

Results: The mean (±SD) age of participants was 49.2 (±12.6) years, women comprised 53% of the sample. The age-standardized prevalence of diabetes was 17.4% (95% CI: 16.7-18.1). The prevalence was higher among men [19.3% (18.3-20.3)], elderly i.e., ≥ 60 years [26.8% (25.1-28.6)], urban residents [23.1% (22.1-24.2)] and in those with higher socioeconomic status [22.5% (21.0-24.1)]. Nearly, one-third participants had prediabetes [29.7% (28.9-30.5)] and there were no rural-urban, gender or socioeconomic differences. The awareness and treatment [49.1% (46.8-51.4), 43.3% (41.0-45.5)] rates respectively, were poor among diabetics, who were young (41.9%, 36.0%), rural residents (37.8%,31.5%) and those with lower socioeconomic status (30.1%,28.4%). Overall control rate was 45.5% (42.9-48.1) with no significant differences between the aforementioned groups.

Conclusions: Despite the increasing burden of both diabetes and prediabetes in India, the awareness, treatment and control rates remain suboptimal. Active screening and tailored public education to increase awareness, are essential for promoting early detection and improving management, especially among poor rural populations.

Disclosure

S. Mohan: None. P. Jarhyan: None. G. Sharnngadharan: None. D. Prabhakaran: None.
228-LB: Chronic Treatment with a Vasodilator Augments the Effectiveness of Endurance Training to Improve Exercise Capacity and Increases Microvascular Blood Flow in Obese Mice
Authors: CAPPEL DAVID A. , WASSERMAN DAVID
Published: June 2020

Peripheral vascular disease is a frequent co-morbidity of type-2 diabetes that impairs exercise capacity. We hypothesized that chronic treatment with a vasodilator would increase microvascular flow and exercise capacity. To test this hypothesis, we chronically treated obese mice with the vasodilatory agent Sildenafil during exercise training. Obese mice were fed a high fat diet (HFD) for 6 weeks prior to the study and remained on the diet for its duration. Mice performed an initial treadmill stress test to assess exercise capacity and injected twice daily with either vehicle or Sildenafil. Groups were matched to initial stress test run distance (Sildenafil 379±74 m vs. Vehicle 373±65 m n=17). Mice were exercise trained for 5-weeks with a 5-days per week 1-hour run at 40% of maximal stress test exercise intensity. After the training period, mice were subjected to a second exercise stress test. Sildenafil treated but not vehicle treated HFD-fed mice showed increased exercise capacity based on stress test run distance (Sildenafil 520±130 m vs. Vehicle 402±164 m n=17). Treating obese mice with a single acute dose of Sildenafil did not alter run distance on a treadmill stress test (Sildenafil 406±64 m vs. Vehicle 460±136 m n=8). To determine the effect of chronic Sildenafil treatment on vascular function, we measured blood flow in the microvasculature of the gastrocnemius muscle by intravital microscopy within one week of the final exercise test. Sildenafil treated mice showed increased vascular flow rate (Sildenafil 671±106 microns/s vs. Vehicle 527±198 microns/s, n=10-11) and vessel perfusion (Sildenafil 96±4% vs. Vehicle 92±4%, n=10-11). Overall, these results indicate that chronic treatment with a vasodilatory agent augments the effect of exercise training to improve exercise capacity in the context of obesity and increases blood flow rate and blood vessel perfusion in the microvasculature of skeletal muscle.

Disclosure

D.A. Cappel: None. D. Wasserman: None.

Funding

National Institutes of Health (DK059637, DK054902); American Heart Association
228-OR: Decoding Human Postprandial Responses to Food and Their Potential for Precision Nutrition: The PREDICT 1 Study
Authors: FRANKS PAUL W. , BERRY SARAH , VALDES ANA M. , DREW DAVID A. , DAVIES RICHARD J. , MERINO JORDI , CHAN ANDREW T. , SEGATA NICOLA , SPECTOR TIM D.
Published: June 2020

Metabolic responses to food influence diabetes risk, but data suitable for determining personalized nutritional advice are lacking. PREDICT 1 (n=1102 twins and unrelated healthy UK/U.S. adults) examined genetic, metabolic, microbiome, and meal composition/context contributions to postprandial metabolic responses in clinic and at home. This 2-week interventional trial included the administration of standardized meals/beverages and monitored of ad libitum food intake. Objective assessments of sleep and physical activity were made. Blood glucose was continuously assessed and triglycerides and C-peptide were measured repeatedly. Large and consistent differences between individuals in blood triglyceride, glucose, and insulin responses to identical meals were observed. Person-specific factors, including variation in the gut microbiome, had a greater influence than meal macronutrients; genetic variants had a modest impact on predictions. Modifiable factors such as meal timing had large effects, highlighting avenues to improve postprandial responses. As predictors of CVD risk, postprandial triglyceride and glucose improved on traditional fasting markers. Machine learning was utilized to derive personalized predictions for both triglyceride (r=0.47) and glycemic (r=0.77) responses.

Disclosure

P.W. Franks: Advisory Panel; Self; Zoe Global Ltd. Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk A/S, Sanofi, Servier. S. Berry: Consultant; Self; Zoe Global. A.M. Valdes: None. D.A. Drew: None. R.J. Davies: Employee; Self; Zoe Global Ltd. J. Merino: None. A.T. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Pfizer Inc. N. Segata: Consultant; Self; Zoe Global Ltd. T.D. Spector: Stock/Shareholder; Self; Zoe Global Ltd.

Funding

Zoe Global Ltd.; UK Wellcome Trust (212904/Z/18/Z); Medical Research Council/British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (M016560/1); European Research Council (CoG-2015_681742_NASCENT to P.W.F.); UK Wellcome Trust; Medical Research Council; European Union; Chronic Disease Research Foundation; Zoe Global Ltd.; National Institute for Health Research-funded BioResource, Clinical Research Facility and Biomedical 511 Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London
2282-PUB: Impact of Demographic and Socioeconomic Factors on Glycemic Control
Authors: FOLAWEWO KEHINDE M. , HODGE MAKENZIE U. , NUNLEE-BLAND GAIL , OSMAN NADA , ZENEBE ANTENEH , ODONKOR WOLALI , GANTA VIJAYA , OGUNTI RICHARD
Published: June 2020

Objective: Evaluate the impact of demographic and socio-economic factors on diabetic control (Hba1c) among patients in an outpatient setting.

Methods: A prospective study from January 2015 to May 2017 involving 211 patients with diabetes mellitus managed at an outpatient endocrinology clinic. Serial measurements of HbA1c were collected at baseline, 3 and 6 months. HbA1c was treated as a continuous variable and presented as mean ± standard deviation. Baseline HbA1c level was compared among dichotomized socio-economic variables (married vs. not married; employed vs. unemployed; health literacy (using the REALM survey) and educational level using t-test. A multivariable linear regression model was used to examine the association between Hb1Ac control and patient demographic and socio-economic characteristics.

Results: Among study participants, 96% were African American, 63.5% female, with mean age of 53 ± 14.7) and baseline mean Hb1Ac of 8.80 ± 2.30. In univariate analysis, higher baseline Hb1Ac was observed in patients with REALM score below 7 vs. above 7, (9.30%±2.36 vs. 8.49% ± 2.27, p-value = 0.01), unemployed vs. unemployed (9.17%± 2.46 vs. 8.56%± 2.23, p-value = 0.08), and high school or lower vs. college and above (9.08% ± 2.36 vs. 8.7%± 2.28, p-value = 0.10). Single and divorced patients had higher baseline HbA1C (8.94 ± 2.4 and 8.90 ± 2.4 respectively) compared to their married counterpart (8.65%±2.4)Adjusting for baseline Hb1Ac level, gender, race marital status, employment status and educational level, multivariable regression analysis showed that higher educational level was significantly associated with change in HbA1c values. Patients with college education and above showed significant reduction in HbA1C (regression coefficient -0.75, 95% CI -1.27 to -0.230, p=0.005) compared to those with high school attainment and lower.

Conclusion: In this prospective study involving predominantly African Americans, higher educational attainment was independently associated with better glycemic control.

Disclosure

K.M. Folawewo: None. M.U. Hodge: None. G. Nunlee-Bland: None. N. Osman: None. A. Zenebe: None. W. Odonkor: None. V. Ganta: None. R. Ogunti: None.
2284-PUB: Overweight/Obesity in Young T1D Patients Is Differently Associated to First Degree Relatives’ History or Features According to Their Gender
Authors: VALENTE FERNANDO , VALENTE TATIANA , DIB SERGIO A.
Published: June 2020

Introduction: Obesity is increasing in T1D patients worldwide and is related to cardiovascular (CV) disease.

Objective: To identify the background characteristics linked to overweight/obesity and CV risk factors during insulin treatment in T1D patients.

Methods: We performed anthropometric, laboratory and genetic analysis - FTO rs9939609 and visfatin rs9770242 of young Brazilian T1D. This study was approved by the Ethic Committee.

Results: From 181 T1D patients (age 23.6±5.5 y, diabetes duration 12.1±7.2 y, A1c 8.9±1.9%), 87 were female - 64.4% normal weight (NW), 26.4% overweight (OW) and 9.2% obese (OB) - and 94 male (77.7% NW, 14.9% OW and 7.4% OB).

Male: OB were older (OB: 29.4±3.7 y vs. OW: 23.2±5.8 vs. NW: 22.5±5.3, p=0.01), had higher prevalence of blacks (57.1% vs. 7.1 vs. 7, p=0.01), higher triglycerides levels (180.3±140.2 mg/dL vs. 74.4±34.4 vs. 87±57.1, p=0.03), diastolic BP (85±8.4 mmHg vs. 78.9±9.2 vs. 73.4±9.6, p=0.009) and lower eGDR (5.4±1.9 mg/Kg/min vs. 6.8±1.9 vs. 7.9±1.7, p=0.003). Higher prevalence of AH (100% vs. 57.1 vs. 50.7, p=0.03) and early CV disease (28.6% vs. 7.1 vs. 2.7, p=0.02) in their first-degree relatives (FDR) were also found in OB. A1c, insulin dose (U/kg/day), diabetes duration, physical activity, high molecular weight (HMW) adiponectin, visfatin, FTO and visfatin genes polymorphisms were not different in NW and OW/OB.

Female: We found no difference between groups in A1c, insulin dose, diabetes duration, physical activity, HMW adiponectin, visfatin or FTO and visfatin genes polymorphisms. OW and OB had lower eGDR (5.4±2.4 mg/Kg/min vs. 6.1±2.1 vs. 8±2.1, p=0.0002). OB women had FDR with obesity more frequently (62.5% vs. 47.8 vs. 25.5, p=0.03).

Conclusion: FDR with obesity is a risk factor to OW/OB in female T1D as well as FDR with early CV disease or AH in male T1D. These specifics familiar background must be considered for early prevention of CV risk factors during natural history of T1D.

Disclosure

F. Valente: Consultant; Spouse/Partner; Sanofi Genzyme. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk Inc. T. Valente: None. S.A. Dib: None.
2293-PUB: Epigenomic Analysis of AgRP Neurons Reveals That Leptin Induces Satiety via IRF3
Authors: HEYWARD FRANKIE D. , IVISON RACHAEL , TSAI LINUS T.Y. , ROSEN EVAN
Published: June 2020

AgRP neurons in the arcuate nucleus (ARC) of the hypothalamus play a dominant role in maintaining energy balance and are dysregulated in obesity, but prior studies examining their transcriptional regulation have been confounded by the rich cellular diversity of the ARC and the low abundance of these neurons. We have employed AgRP neuron-specific Translating Ribosomal Affinity Purification followed by RNA-sequencing (TRAP-seq) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) to determine the transcriptomic and epigenomic landscape of these neurons during the fed, fasted and leptin-treated states. These rich datasets were computationally integrated to identify candidate transcription factors (TFs) potentially mediating the homeostatic control of food intake, of which the Interferon Regulatory Factor (IRF) family of TFs were enriched during the leptin-treated state. Cell-type specific functional studies have revealed that IRF3 plays a key role in mediating the satiety-inducing effects of leptin. Thus, we have identified a novel role for AgRP-neuron expressed IRF3 in regulating the satiety-evoking effects of leptin.

Disclosure

F.D. Heyward: None. R. Ivison: None. L.T.Y. Tsai: None. E. Rosen: None.

Funding

American Diabetes Association (1-19-PMF-008 to F.D.H.); Burroughs Wellcome Fund; American Heart Association
2306-PUB: Serum CXCL14 Levels Are Associated with Plasma C-Peptide and Fatty Liver Index in T2DM Patients: A Retrospective Analysis
Authors: MATSUSHITA YURIKO , HASEGAWA YUTAKA , TAKEBE NORIKO , ISHIGAKI YASUSHI
Published: June 2020

Objective: Recent studies have shown that Chemokine (C-X-C motif) ligand 14 (CXCL14), a newly secreted by brown adipose tissue, plays an important role in the pathogenesis of metabolic syndrome. However, clinical significance has not been elucidated in human. The aim of this study is to assess correlations between serum CXCL14 levels and clinical parameters among the patients with type 2 diabetes mellitus (T2DM).

Method: A total of 176 subjects with T2DM were recruited. Serum CXCL14 concentration was determined by ELISA. We examined the association of serum CXCL14 levels with the anthropometric parameters and laboratory values, abdominal CT image information, surrogate markers used for evaluating the pathological state of DM, obesity and atherosclerosis.

Result: Serum CXCL14 levels correlated positively with body mass index and waist circumference, subcutaneous and visceral fat area, estimated glomerular filtration rate, serum levels of ALT, UA, TC, LDL-C, TG, FT3, C-peptide (CPR), neuregulin 4, fibroblast growth factor 21, urine levels of CPR, 8-hydroxy-2’-deoxyguanosine. In contrast, those were inversely correlated with age and pulse wave velocity, plasma levels of adiponectin. Multiple linear regression analysis revealed plasma levels of CPR (β=0.227, p=0.038) and fatty liver index (FLI; β=0.205, p=0.049) to be the only parameters showing independent statistically significant association with serum CXCL14 levels.

Conclusion: Serum CXCL14 levels were independently associated with plasma CPR and FLI in patients with T2DM. In this case, high concentration of plasma CPR might reflect insulin resistance rather than β-cell function, because CXCL14 showed simple correlations with obesity-related parameters. Collectively, these data suggested serum CXCL14 levels in type 2 DM might be useful predictors of insulin resistance and abdominal fat accumulation.

Disclosure

Y. Matsushita: None. Y. Hasegawa: None. N. Takebe: None. Y. Ishigaki: None.
2311-PUB: Metformin Improves Hepatic Inflammation in Diet-Induced Obese Mice through Downregulating CYP7B1
Authors: GUO WANRONG , WANG WEI , ZHENG XIAOBIN , XU FEN
Published: June 2020

Metformin is an antidiabetic drug widely used to treat type 2 diabetes. Although it has been found for a very long time, its mechanism remains to be discovered. Recently, metformin has been reported to be effective in other disease, such as obesity and tumor. However, whether metformin is beneficial in nonalcoholic fatty liver disease remains controversial. CYP7B1, a cholesterol hydroxylase, has been reported to be upregulated in the inflammatory diseases. We investigated whether CYP7B1 plays an important role in the effect of metformin on the hepatic inflammation in diet-induced obese mice. In this study, eight-week-old C57BL/6 mice were subjected to a chow diet or a high fat diet (HFD) for 12 weeks. After the diet intervention, mice on an HFD were randomly divided into HFD group and HFD+Metformin group (HFDM group) for 4 weeks. The results showed that the body weight, fasting blood glucose, body fat mass, glucose metabolism and insulin sensitivity were remarkably improved by metformin. The histological results including H&E staining and oil red O staining showed that metformin significantly ameliorated fatty liver induced by HFD. And the quantification of liver triglyceride also proved that. The histological results also revealed that adipocytes of epididymal adipose tissue and subcutaneous adipose tissue were smaller after metformin treatment. Meanwhile, metformin also ameliorated the whitening of brown adipose tissue according to the H&E staining. Compared to HFD group, the mRNA levels of CYP7B1 and pro-inflammatory markers (TNFα, IL-1, F4/80 and MCP1) in liver were downregulated in HFDM group. How CYP7B1 functions in the beneficial effect of metformin on improving hepatic inflammation is going to be further studied.

Disclosure

W. Guo: None. W. Wang: None. X. Zheng: None. F. Xu: None.
2312-PUB: Orthostatic Instability in a Patient with Type 1 Diabetes Mellitus after Bariatric Surgery
Authors: CARDONA ZULMA , HAIDER YASSER
Published: June 2020

Orthostatic Intolerance (OI) refers to a heterogeneous group of disorders of hemodynamic regulation characterized by insufficient cerebral perfusion resulting in symptoms during upright posture relieved by recumbency. To our knowledge this would be the first case to describe a patient with type 1 diabetes mellitus (T1DM) who underwent bariatric surgery and developed debilitating OI. We describe the case of a 46 year old with class III obesity (BMI 42.9), T1DM, complicated by microalbuminuria, diabetic retinopathy, carpal tunnel syndrome, and HTN status post gastric sleeve surgery who presented to the emergency department 10 days after surgery for a syncopal episode, which resulted in head trauma. He endorsed multiple episodes of lightheadedness and falling after surgery. He lost 20 lbs in the first 10 days. His systolic blood pressure was 70 mmHg, however no other physical exam, laboratory, or imaging abnormalities were found. Thereafter he continued to have similar episodes and was only found to have a positive Tilt Test after extensive outpatient workup. He was started on midodrine 5 mg three times a day, fludrocortisone acetate 0.1 mg daily, and Pyridostigmine 60 mg three times a day with resolution of symptoms. There is a relationship between obesity and hypertension, possibly associated to its effect on the renin angiotensin aldosterone system, up regulation of sympathetic nervous system and simultaneous down regulation of parasympathetic nervous system. Bariatric surgery increases the risk of developing OI through the effects of weight loss itself, the type of procedure chosen and ultimately, vitamin deficiencies. Patients with diabetes are also at risk of developing OI following these procedures due to underlying Diabetic Autonomic Neuropathy (DAN) that had been masked by obesity related HTN. Physicians should be mindful of the risk of OI after bariatric surgery, especially in patients with possible underlying DAN. Close follow up is advised for these patients to avoid falls and trauma.

Disclosure

Z. Cardona: None. Y. Haider: None.
232-OR: Long-Term Safety and Efficacy of Ultra-Rapid Lispro (URLi) in PRONTO-T1D
Authors: KLAFF LESLIE J. , CHO JANG IK , DELLVA MARY A. , SCHLOOT NANETTE C. , TOBIAN JANET , MIURA JUNNOSUKE , DAHL DOMINIK , BUE-VALLESKEY JULIANA M.
Published: June 2020

PRONTO T1D was a phase 3 study evaluating ultra rapid lispro (URLi) in adults with type 1 diabetes (T1D) for 52 weeks. Subjects were randomized to double-blind mealtime URLi, Humalog, or open-label postmeal URLi with insulin degludec or glargine for the first 26 weeks. Subjects on URLi (n=451) and Humalog (n=442) given 0-2 minutes before meals continued for another 26-weeks to assess long-term safety and efficacy. Mean HbA1c at 52 weeks (7.47% URLi; 7.54% Humalog) increased significantly (p<.001) from baseline in both groups (+0.13% [URLi] vs. +0.20% [Humalog]) and showed an estimated treatment difference (ETD) [95% confidence interval (CI)] (ETD: -0.06 [-0.16, 0.03]) that was similar to that previously reported at 26-weeks. Proportions of patients with HbA1c <7% at Week 52 were similar (URLi, 26.8%; Humalog, 24.5%). At Week 52, self-monitored blood glucose profiles (mg/dL) showed that 1-hour (ETD: -13.5 [-19.4, -7.5]) and 2- hour (ETD: -8.4 [-14.1, -2.7]) postmeal daily mean glucose (and corresponding excursions) as well as the daily mean glucose (ETD: -6.1 [-10.6, -1.6]) were statistically significantly (p<.01) lower during treatment with URLi than Humalog. Mean total insulin dose was 0.80 U/kg (URLi) vs. 0.78 U/kg (Humalog). No difference was observed for body weight change (+0.8 kg [URLi] vs. +0.9 kg [Humalog]; ETD: -0.1 kg [−0.5; 0.4]). Adverse events were similar between URLi and Humalog. No difference was observed for severe hypoglycemia (12.28 events/patient-100yr [URLi] vs. 15.96 [Humalog]) or documented symptomatic hypoglycemia rates (glucose <54 mg/dL) with URLi (4.84 events/patient-year) vs. Humalog (5.18) with a relative rate: 0.93 [95% CI: 0.75;1.16]). No long-term safety issues were identified with URLi. Overall glycemic control and improved postprandial glucose via self-monitoring was maintained after 52 weeks with URLi vs. Humalog suggesting that the efficacy and rapid onset of action of URLi is preserved during long-term treatment in patients with T1D.

Disclosure

L.J. Klaff: Research Support; Self; Abbott, Ascensia Diabetes Care, Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, REMD Biotherapeutics, Roche Diabetes Care, Sanofi-Aventis, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. J. Cho: None. M.A. Dellva: Employee; Self; Eli Lilly and Company. N.C. Schloot: Employee; Self; Lilly Diabetes. J. Tobian: Employee; Self; Eli Lilly and Company. J. Miura: None. D. Dahl: Advisory Panel; Self; Berlin-Chemie AG. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novartis AG, Novo Nordisk A/S. J.M. Bue-Valleskey: Employee; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
233-LB: Spinal Cord Injury Inhibited-FGF21 Signaling Is Associated with Dysregulation of Metabolic Gene Expression in Mouse Liver and Adipose Tissue
Authors: LIU XIN-HUA , HARLOW LAUREN , GRAHAM ZACHARY , YARROW JOSHUA F. , CUSI KENNETH , BAUMAN WILLIAM A. , CARDOZO CHRISTOPHER P.
Published: June 2020

Spinal cord injury (SCI) causes deleterious changes in the metabolic profile due to muscle atrophy and sedentary lifestyle. SCI is associated with increased risk for cardiovascular disease, liver disorders and type 2 diabetes mellitus (T2DM). Understanding of the mechanisms for these disorders in those with SCI is poor. Fibroblast growth factor 21 (FGF-21), a hepatic hormone, is reported to have beneficial effects on glucose/lipid metabolism in animal models and human subjects with T2DM. However, the expression levels and the potential effect of FGF-21 on SCI related metabolic dysfunction have not been studied. To address this issue, we compared FGF-21 serum and hepatic mRNA levels in sham and SCI mice fed control or high fat diet (HFD) at 84d after SCI. SCI reduced serum FGF-21 levels by 60% and hepatic FGF-21 mRNA levels by 50% compared to sham mice; levels were further suppressed by HFD. These changes were associated with elevated serum levels of alanine aminotransferase, a liver damage marker. In adipose tissue (AT), SCI decreased mRNA expression of FGF-21 receptor (FGFR1), β-Klotho, adiponectin, PPARγ, and leptin. In addition, SCI reduced IRS1 and Glut4 mRNA levels in AT, indicating impaired insulin signaling. Moreover, elevated levels of TNFα in AT and CD11b (a macrophage marker) in the liver were observed, implying a proinflammatory state after SCI. Finally, post-SCI mice fed a HFD had elevated free fatty acid (FFA) levels in serum and liver compared to sham-mice fed a HFD, suggesting defective FFA uptake and metabolism. These data suggest that reduced FGF-21 signaling after SCI may, at least in part, be contributing to the metabolic dysfunction after SCI, and that FGF-21 may be a candidate for the treatment of SCI-related metabolic dysfunction.

Disclosure

X. Liu: None. L. Harlow: None. Z. Graham: None. J.F. Yarrow: None. K. Cusi: Consultant; Self; Allergan plc., AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., Gilead Sciences, Inc., Merck & Co., Inc. Research Support; Self; Cirius Therapeutics, Echosens, Eli Lilly and Company, Inventiva Pharma, Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Poxel SA, Zydus Pharmaceuticals, Inc. W.A. Bauman: None. C.P. Cardozo: None.

Funding

U.S. Department of Veterans Affairs (B9212C, B2020C)
234-OR: Postprandial Glucose Control Using the Medtronic Advanced Hybrid Closed-Loop System: Faster-Acting Insulin Aspart vs. Insulin Aspart
Authors: LEE MELISSA H. , VOGRIN SARA , PALDUS BARBORA , MORRISON DALE , ZAHARIEVA DESSI , LU JEAN , JONES HANNAH , WYATT SUE A. , NETZER EMMA , SIMS CATRIONA M. , MACISAAC RICHARD , GROSMAN BENYAMIN , ROY ANIRBAN , KURTZ NATALIE , JENKINS ALICIA , ONEAL DAVID N.
Published: June 2020

Background: Faster-acting insulin aspart (FiAsp) may improve responsiveness of closed-loop (CL) systems and provide better postprandial glucose (PPG) management due to its more rapid onset and offset compared to insulin aspart (Asp). The Medtronic Advanced Hybrid Closed Loop (AHCL) System features auto-basal and auto-bolus functions.

Aim: To compare PPG control using FiAsp vs. Asp delivered using AHCL.

Methods: Twelve adults with T1D (median HbA1c 7.1% [IQR 6.8, 7.2]; 54mmol/mol [51, 55]) were assigned to FiAsp or Asp (unblinded) in random-order over two-stages (6-weeks duration each) using AHCL. Postprandial periods were defined using set time-blocks for breakfast (06:00-10:00); lunch (11:00-15:00); and dinner (17:00-21:00), based on conventional meal-times and meal distribution. CGM data was analyzed using signed-rank test.

Results: With all postprandial time-block data aggregated, FiAsp demonstrated greater overall time-in-range (TIR) (70-180mg/dL) (p=0.028) and less hyperglycaemia (p=0.041) compared with Asp (Table). TIR was greater during lunch (p=0.034) for FiAsp vs. Asp, with no difference during breakfast or dinner. Over the 6-week duration, FiAsp use trended towards greater TIR vs. Asp (82.7% vs. 80.4%, p=0.07).

Conclusions: FiAsp appears to confer an advantage compared with Asp for PPG control whilst using AHCL even in subjects with high overall TIR.

Disclosure

M.H. Lee: Research Support; Self; Medtronic. Speaker’s Bureau; Self; AstraZeneca, Medtronic. S. Vogrin: None. B. Paldus: Research Support; Self; JDRF. Speaker’s Bureau; Self; Australian Diabetes Society, Medtronic. D. Morrison: None. D. Zaharieva: Speaker’s Bureau; Self; Ascensia Diabetes Care, Insulet Corporation, Medtronic. J. Lu: None. H. Jones: None. S.A. Wyatt: Other Relationship; Self; Medtronic, Ypsomed AG. E. Netzer: None. C.M. Sims: Stock/Shareholder; Self; Medtronic. R. MacIsaac: None. B. Grosman: Employee; Self; Medtronic. A. Roy: Employee; Self; Medtronic. N. Kurtz: Employee; Self; Medtronic. A. Jenkins: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Sanofi-Aventis. D.N. ONeal: None.
237-OR: Insulin Icodec: An Insulin Analog Suited for Once-Weekly Dosing in Type 2 Diabetes
Authors: HÖVELMANN ULRIKE , BRØNDSTED LISE , KRISTENSEN NIELS R. , RIBEL-MADSEN RASMUS , DEVRIES J. HANS , HEISE TIM , HAAHR HANNE
Published: June 2020

Insulin icodec* is a novel basal insulin analog designed for single once-weekly (OW) subcutaneous injection. This randomized, double–blind, double–dummy trial investigated the pharmacokinetics (PK), pharmacodynamics (PD) and safety of insulin icodec. Fifty individuals with type 2 diabetes (insulin treated±metformin; 43 men; mean±SD age 57±5 years, BMI 30.1±2.7 kg/m2, A1C 7.4±0.6%) received OW insulin icodec (12, 20 or 24 nmol/kg) plus once–daily (OD) placebo (N=13, 13, 12) or OD insulin degludec (0.4 U/kg) plus OW placebo (N=12) for 5 weeks in 3 dose level cohorts. PD properties were investigated at close to steady state in 24-h glucose clamps on days 2 and 7 after the last insulin icodec dose. Median tmax,insulin icodec was 16 h and geometric mean t½,insulin icodec was 196 h with no systematic differences between dose levels. The glucose–lowering effect over a weekly dosing interval was derived from the observed PK/PD data using a PK/PD model and showed close to even distribution over the 7 days across all dose levels (Figure). The adverse event (AE) incidence did not increase with increasing insulin icodec dose (100%, 69%, 75%, respectively). There were no serious or severe AEs, severe hypoglycemic episodes or injection site reactions.

In conclusion, insulin icodec was safe and well-tolerated and showed PK/PD properties supporting once-weekly administration at clinically relevant dose levels. * Proposed INN.

Disclosure

U. Hövelmann: None. L. Brøndsted: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. N.R. Kristensen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. R. Ribel-Madsen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J. DeVries: Advisory Panel; Self; Novo Nordisk A/S, Zealand Pharma A/S. Consultant; Self; Metronom Health. Employee; Self; Profil Institute for Clinical Research. T. Heise: Advisory Panel; Self; Mylan, Novo Nordisk A/S. Research Support; Self; ADOCIA, Aerami, Becton, Dickinson and Company, Biocon, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Gan & Lee Pharmaceuticals, MedImmune, Merck KGaA, Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Sanofi, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. H. Haahr: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S.

Funding

Novo Nordisk