bluuebunny/crossref_metadata_2025 huggingface dataset:
699-P: Association between Exercise Capacity and All-Cause Mortality in Taiwanese Adults
Authors: LAI YUN-JU
Published: June 2020

Background: Exercise improves insulin sensitivity, inhibits inflammatory cytokines, and reduces the risk of cardiovascular disease. But the effect of exercise capacity on all-cause mortality in Taiwanese adults has not been fully explored.

Methods: We used data from the National Health Interview Survey and the National Health Insurance research database in Taiwan. Baseline participants’ characteristics including socioeconomic status and health behaviors were obtained by standardized face to face interviews in 2001, 2005, 2009, and 2013. Comorbidities were confirmed by National Health Insurance research database 2000-2016. Participants were followed up until December 31 2016. All-cause mortality was ascertained from the National Registration of Death. Kaplan-Meier curves and Cox proportional hazard analysis were used to evaluate the relationship between exercise capacity and all-cause mortality.

Results: In total, 65,126 adults aged more than 18 years old were analyzed; 32,563 (50%) were male and with a mean (SD) age of 42.90 (16.17) years. Kaplan-Meier curves of all-cause mortality stratified by exercise capacity demonstrated significant findings (Log-rank P<0.01). Multivariate Cox regression analysis showed that those with higher exercise capacity had a significantly decreased risk of all-cause mortality, compared with those with no exercise habits (moderate exercise with 0-800 kcal/week HR = 0.78, 95% CI: 0.71-0.85, high exercise with more than 800 kcal/week HR = 0.73, 95% CI: 0.67-0.79) after adjusting for potential confounders. A significant trend (P for trend<0.01) was also noted.

Conclusions: People with increased exercise capacity had a significant decreased risk of all-cause mortality. Further studies should investigate the type and dose of exercise that is most helpful for the general population to prolong life expectancy.

Disclosure

Y. Lai: None.
7-OR: Comparison of Two Recent Ceramide-Based Coronary Risk Prediction Scores: CERT and CERT-2
Authors: LEIHERER ANDREAS , MUENDLEIN AXEL , SAELY CHRISTOPH H. , LAAKSONEN REIJO , LAAPERI MITJA , VONBANK ALEXANDER , FRAUNBERGER PETER , DREXEL HEINZ
Published: June 2020

The Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories. This test has recently been updated (CERT-2), now additionally including phosphatidylcholine concentrations. We investigated the power of CERT and CERT-2 to predict cardiovascular mortality in 999 patients with cardiovascular disease (CVD). Overall, comparing survival curves (Figure) for over 12 years of follow up and the predictive power of survival models using net reclassification improvement (NRI), CERT-2 was the best predictor of cardiovascular mortality, surpassing CERT (NRI=0.456; p=0.01) and also the 2019 ESC-SCORE (NRI=0.163; p=0.04). Patients in the highest risk category of CERT as compared to the lowest category had a HR of 3.63[2.09-6.30] for cardiovascular death; for CERT-2 the corresponding HR was 6.02[2.47-14.64]. Among patients with T2DM (n=322), the HR for cardiovascular death was 3.00[1.44-6.23] using CERT and 7.06[1.64-30.50] using CERT-2; the corresponding HRs among nondiabetic subjects were 2.99[1.20-7.46] and 3.43[1.03-11.43], respectively. We conclude that both, CERT and CERT-2 scores are powerful predictors of cardiovascular mortality in CVD patients, especially in those patients with T2D. Performance is even higher with CERT-2.

Disclosure

A. Leiherer: None. A. Muendlein: None. C.H. Saely: None. R. Laaksonen: None. M. Laaperi: None. A. Vonbank: None. P. Fraunberger: None. H. Drexel: None.
700-P: Mechanism for the Beneficial Effects of Maternal Exercise to Improve Offspring Metabolic Health
Authors: KUSUYAMA JOJI , WAGNER ANA B. , CONLIN ROYCE H. , MAKAREWICZ NATHAN S. , MØLLER MAGNUS , MIELE EMILY M. , MIDDELBEEK ROELAND , JESSEN NIELS , OVESEN PER G. , HIRSHMAN MICHAEL F. , ADAMO KRISTI B. , GRAYCK EVA N. , GOODYEAR LAURIE J.
Published: June 2020

Poor maternal diet and obesity increase the risk of obesity and type 2 diabetes in offspring, fueling the worldwide epidemic of these diseases. Recent animal studies have shown that maternal exercise (MatEx) improves the metabolic phenotype of offspring in adulthood, including improved glucose tolerance and liver function. Here, we determined the molecular mechanisms responsible for these critical effects of MatEx. Female mice were fed a chow or high fat diet and housed in cages with (Trained) or without (Sedentary) running wheels for 2 wks prior to breeding and during gestation. Offspring were sedentary and chow-fed. MatEx improved glucose tolerance and liver function in adult offspring. Beginning at embryonic day 13.5, MatEx increased expression of TCA cycle and fatty acid oxidation genes in offspring liver, and increased DNA demethylation at promoters of these hepatic genes. Next, we identified a novel MatEx-induced AMPK/isocitrate dehydrogenase/αketoglutarate/Tet axis in offspring liver controlling DNA demethylation. Primary hepatoblasts treated with serum from trained dams, but not sedentary dams or trained non-pregnant females stimulated this pathway, suggesting the effects of MatEx on offspring stem from a placenta-derived serum factor(s). LC-MS/MS of serum and RNAseq of placenta from trained dams identified this factor as superoxide dismutase 3 (Sod3), and recombinant SOD3 treatment of hepatoblasts increased AMPK-Tet signaling and hepatic gene expression. The effects of MatEx to increase liver AMPK-Tet signal, alter liver DNA methylation and gene expression, and improve offspring glucose tolerance in vivo were ablated in placenta-specific Sod3 KO mice. Finally, SOD3 was increased in serum and placenta from highly physically active pregnant women. Sod3 is an exercise-induced, placenta-derived protein that improves glucose homeostasis via epigenetic changes in offspring liver, defining a novel paradigm for the beneficial effects of exercise on metabolic health.

Disclosure

J. Kusuyama: None. A.B. Wagner: None. R.H. Conlin: None. N.S. Makarewicz: None. M. Møller: None. E.M. Miele: None. R. Middelbeek: None. N. Jessen: None. P.G. Ovesen: None. M.F. Hirshman: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen, Colgate-Palmolive, Eli Lilly and Company, Medtronic. K.B. Adamo: None. E.N. Grayck: None. L.J. Goodyear: None.

Funding

National Institutes of Health (DK101043)
702-P: Daily Sedentary Time and Continuous Metabolic Risk Score in Very Active Older Adults
Authors: MADDEN KENNETH M. , CHASE JOCELYN M.
Published: June 2020

Background: Increasing evidence suggests that time spent sedentary (ST) predicts increasing cardiometabolic risk independent of other activity. We objectively measured activity levels in active older adults, and examined the association between ST and the continuous Metabolic Syndrome Risk Score (cMSy).

Methods: Older adults (age >= 65) were recruited from a Master’s Ski Team, a group of active older adults that undergo organized group training. Daily activity levels (sedentary, ST; light, LT; moderate/vigorous activity, MT) were recorded with accelerometers (SenseWear) worn for 7 days continuously. Waist circumference, triglycerides, high-density lipoprotein, systolic blood pressure and fasting glucose were measured and cMSy was calculated using principal component analysis (sum of eigenvalues ≥ 1.0).

Results: 54 subjects (age=71.4±0.6 years, 30 women and 24 men) were recruited. Subjects demonstrated high levels of physical activity (LT= 2.6±0.2 and MT=3.9±0.2 hours per day). In our final parsimonious model, ST showed a significant positive association with increasing cMSy (Standardized β=0.312±0.115, R2 = 0.36, p<0.001), independent of age, biological sex and other measures of physical activity (LT and MT).

Conclusions: Despite high levels of activity, ST demonstrated a strong association with cMSy. This suggests that even in active older adults, ST is associated with increasing cardiometabolic risk.

Disclosure

K.M. Madden: None. J.M. Chase: None.

Funding

Allan M. McGavin Foundation
703-P: Exercise-Stimulated Resolvin Biosynthesis in Adipose Tissue Is Abrogated by Obesity-Induced Adrenergic Dysfunction
Authors: HELLMANN JASON , LYNCH WILL , CALDERIN ERNESTO P. , SANSBURY BRIAN , SPITE MATTHEW , BHATNAGAR ARUNI , HILL BRADFORD
Published: June 2020

Adipose tissue (AT) inflammation is associated with obesity-induced insulin resistance. Exercise (Exe) prevents the development of chronic inflammatory diseases and insulin resistance largely through unknown mechanisms. We sought to determine if changes in specialized pro-resolving lipid mediators (SPM) in AT contribute to the anti-inflammatory effect of exercise. When compared with sedentary controls (Sed), normal chow fed mice exposed to 4 wk of Exe showed elevated AT expression of SPM biosynthetic enzyme Alox15 (Sed 1.12±0.18 vs. Exe 1.68±0.13 relative expression, n=5-7), SPM levels (Sed vs. Exe; RvD1 156.7±12.02 vs. 223.0±24.71; 17R-RvD1 354.0±35.86 vs. 534.4±98.92; RvD4 31.31±6.93 vs. 123.1±30.69; and 17R-RvD3 2.92±1.08 vs. 8.20±1.70 pg/g, n=5-7), and anti-inflammatory macrophages (F4/80+CD301+; Sed 17.5±3.2 vs. Exe 40.9±4.5 %F4/80+, n=4-6). These changes were diet-dependent as feeding with high fat diet (60% kcal from fat; HFD) abrogated the pro-resolving effect of exercise in AT when compared with low fat diet (10% kcal from fat; LFD) controls. Exercise-stimulated upregulation of 15-LO expression was localized to AT macrophages in a diet-dependent manner (LFD Sed 0.11±0.03 vs. LFD Exe 0.23±0.03; HFD Sed 0.10±0.04 vs. HFD Exe 0.08±0.02 relative expression, n=3-6), as adipocytes from exercised mice showed no difference in 15-LO expression compared with sedentary controls. Given that epinephrine stimulates macrophage 15-LO expression and RvD1 production, we questioned if catecholamine biosynthesis was affected by HFD feeding. Adrenal glands from mice fed HFD show diminished expression of phenylethanolamine N-methyltransferase when compared with controls (LFD 1.0±0.25 vs. HFD 0.36±0.15, n=4). Similarly, db/db mice also displayed reduced catecholamines and expression of biosynthetic enzymes in the adrenal glands.

These results suggest that obesity-induced adrenergic dysfunction abrogates exercise-stimulated resolvin production in AT.

Disclosure

J. Hellmann: None. W. Lynch: None. E.P. Calderin: None. B. Sansbury: None. M. Spite: None. A. Bhatnagar: None. B. Hill: None.

Funding

American Diabetes Association (1-16-JDF-041 to B.H.); National Institutes of Health (GM127495, GM127607)
714-P: Dietary Pattern and Risk of Type 2 Diabetes In Melbourne Collaborative Cohort
Authors: COURTEN BARBORA DE , KARIM MD NAZMUL , HODGE ALLISON
Published: June 2020

Identification of healthy dietary patterns associated with reduced diabetes risk may contribute to diabetes prevention initiatives. The aim of the current study was to investigate whether there is an association between different dietary patterns and incident diabetes in an Australian population. We analysed data of 5,916 eligible Melbourne Collaborative Cohort Study (MCCS) participants, who contributed 343836.6 person-years of follow up with an average 9.4±3.7 years. Dietary patterns for individuals were assessed with three commonly used indices namely, Dietary Inflammatory Index (DII), the Alternative Healthy Eating Index-10 (AHEI-10) and the Mediterranean Diet Score (MDS). Cox proportional hazard regression was used to assess the associations between dietary indices and diabetes risk, adjusted for plausible confounders both with and without baseline body size. At baseline, the average age of the cohort was 55.1 ±8.7 years and 59.9% were female. The incidence rate of diabetes was 4.8 (95% CI 4.6, 5.1) per 1000 person-years. Adjusting for age, sex, socioeconomic status, ethnicity, family history of diabetes, physical activity status, smoking and alcohol consumption status, DII quintile 5 (HR 1.2; 95%CI 1.1, 1.5) and AEHI quintile 5 (HR 0.63; 95%CI 0.53, 0.75)) showed significant associations with diabetes. After additionally adjusting for BMI (HR 0.75; 95%CI 0.74, 0.76) or WHR (HR 0.72; 95%CI 0.71, 0.74), AHEI showed statistically significant inverse associations with diabetes risk. A healthier diet, as assessed by AHEI-10, was associated with a lower risk of diabetes incidence in the MCCS, and this did not appear to be completely explained by an association between diet quality and body size.

Disclosure

B. de Courten: None. M. Karim: None. A. Hodge: None.
716-P: Reduced Carbohydrate and Increased Protein and Fat in the Diet Augment the Positive Effect of Weight Loss on Glucose Control in Type 2 Diabetes Patients
Authors: THOMSEN MADS N. , SKYTTE MADS J. , SAMKANI AMIRSALAR , CARL MARTIN H. , WEBER PHILIP , ASTRUP ARNE , LARSEN THOMAS M. , FRYSTYK JAN , HOLST JENS J. , HARTMANN BOLETTE , THOMSEN HENRIK , CHABANOVA ELIZAVETA , MADSBAD STEN , HAUGAARD STEEN B. , KRARUP THURE
Published: June 2020

Background: We hypothesized that dietary carbohydrate reduction will add to the effect of a diet-induced 6% body-weight loss on glycemic control and hepatic fat content in patients with type 2 diabetes (T2D).

Methods: Forty-four persons of mean HbA1c 56.4 mmol/mol and 9 years of T2D were randomized 1:1 for 6-weeks full food provision, a hypo-caloric carbohydrate-reduced high-protein (CRHP) or a conventional diabetes (CD) diet (carbohydrate 30E%/50E%, protein 30E%/17E% and fat 40E%/33E%). Body-weight loss was aimed at 6% and reinforced bi-weekly by adjustment of hypo-caloric diets. Hepatic fat content was estimated by Magnetic Resonance (MR) spectroscopy and analyzed by a MR research technician, blinded to the protocol.

Results: Six weeks of a hypo-caloric CRHP diet compared with a CD diet improved HbA1c (mean±SD) by further 2 mmol/mol (-8.7±4.6 mmol/mol vs. -6.7±3.9 mmol/mol, p=0.04) with comparable weight losses, 5.5±1.7 kg (5.6 %) and 5.6±2.2 kg (5.9 %) of body-weight, respectively. Hepatic fat content (median (IQR) was reduced significantly while consuming the CRHP diet (5.2% (1.3-6.9)) and CD diet (2.6% (1.6-6.5)), but with no difference between diets (p=0.40).

Conclusion: Reducing carbohydrate and increasing protein and fat adds clinical relevance to the positive effects of body-weight loss on glucose control in T2D patients.

Disclosure

M.N. Thomsen: None. M.J. Skytte: None. A. Samkani: None. M.H. Carl: None. P. Weber: None. A. Astrup: Advisory Panel; Self; Gelesis, Novo Nordisk A/S, Saniona, Weight Watchers International, Inc. Research Support; Self; Arla Food for Health, Gelesis, Novo Nordisk A/S. Speaker’s Bureau; Self; Arla Food for Health. Stock/Shareholder; Self; Gelesis. T.M. Larsen: Advisory Panel; Self; Advisor for Sense diet programme. J. Frystyk: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. B. Hartmann: None. H. Thomsen: None. E. Chabanova: None. S. Madsbad: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. S.B. Haugaard: None. T. Krarup: None.
717-P: The Levels and Related Factors of Advanced Glycation End Products in Korean Patients with Type 2 Diabetes Mellitus
Authors: YIM JUNG-EUN , KIM YOUNG SEOL , PARK JI SOOK
Published: June 2020

Advanced glycation end-products (AGEs) are known to be produced by the Maillard reaction, ingested through food. AGEs are actively generated and accumulated in the circulating blood and various tissues in diabetes mellitus patients by chronic hyperglycemia. AGEs play an important role in the development of diabetic vascular complications. The aim of this study was to assess levels and related factors of AGEs in Korean patients with type 2 diabetes mellitus.

A total of 310 Korean men (n=177) and women (n=133) with T2DM subjects were participated. This study was measured and analyzed anthrometric data, body composition, and biochemical parameters. Tissue accumulated AGEs can be evaluated a non-invasive methodology by skin autofluorescence reader.

The means age of total subjects was 58.9 ± 11.0 years, BMI was 25.8 ± 4.5 kg/m2. There is no difference between male and female patients in levels of AGEs, pulse wave velocity (PWV) and vein age. There is a significant correlation among AGEs, height, weight, body mass index, skeletal muscle mass, diastolic blood pressure and HDL cholesterol for male patients and among fasting blood sugar, glycated hemoglobin A1c, total cholesterol, LDL cholesterol, and systolic blood pressure for female patients. The correlation of AGEs for both male and female subjects is highly associated with age, duration of diabetes and PWV.

This study shows possibility of using AGEs as an index for clinical diagnosis, complications prediction, and diabetes management in Korean patients with type 2 diabetes mellitus. However, it is considered that a change in AGEs may be influenced by gender, age, and duration of diabetes.

Disclosure

J. Yim: None. Y. Kim: None. J. Park: None.
72-OR: Proinflammatory Intestinal Macrophages Are Increased in Obesity Potentially by Enhanced Recruitment of Blood Monocytes
Authors: ROHM THERESA V. , FUCHS REGULA , BAUMANN ZORA , KELLER LENA , SCHNEIDER ROMANO , LABES DANNY , CAVELTI-WEDER CLAUDIA
Published: June 2020

Background: Our previous studies in mice showed that high fat diet leads to a pro-inflammatory phenotype of intestinal macrophages. Colon-specific depletion of intestinal macrophages led to improved glycemic control, suggesting a causal link between intestinal macrophages and glycemia. The aim of the current study was to validate our findings in human disease by assessing human gut biopsies and circulating blood monocytes from lean and obese individuals.

Research Design and Method: Peripheral blood monocytes were isolated using a Ficoll gradient and characterized by flow cytometry as classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+CD16++) monocytes. Intestinal macrophages of the stomach, duodenum and colon were isolated from biopsies of lean (BMI <27 kg/m2) or obese (BMI >32 kg/m2) individuals undergoing colonoscopy or gastroscopy. Macrophages were characterized as CD14high or CD14low and further subdivided by HLA-DR, CD163 and CD209 into pro-inflammatory P1, P2, intermediate P3 and resident, anti-inflammatory subpopulations P4, P5.

Results: Depending on the anatomical location, the composition of intestinal macrophages varied: In the stomach of lean subjects, the ratio of CD14high/CD14low macrophages was 80/20%, while the colon comprised more resident, anti-inflammatory macrophages (CD14high/CD14low: 60/40%). Consistent with our results in mice, we detected an increase in the CD14high pro-inflammatory macrophage subpopulation P2 in obese individuals (Corpus: 1.55±0.61-fold, Duodenum: 1.79±0.45-fold, Colon transversum: 1.71±0.72-fold). Interestingly, also human CD14high intermediate blood monocytes were increased in obese patients.

Conclusion: Similar to our mouse data, pro-inflammatory intestinal macrophages are increased in gut biopsies of obese subjects. Higher CD14high blood monocytes suggest enhanced recruitment of monocytes to the gut as the prevailing mechanism.

Disclosure

T.V. Rohm: None. R. Fuchs: None. Z. Baumann: None. L. Keller: None. R. Schneider: None. D. Labes: None. C. Cavelti-Weder: None.

Funding

University of Basel
720-P: Prurigo Pigmentosa: An Acute Complication of Ketogenic Diet
Authors: LEVRAN NERIYA , MAZOR-ARONOVITCH KINERET , GRENBERGER SHOSHANA , LEVEK NOA , SHER BRURIA , MAUDA ELINOR , LANDAU ZOHAR , MONSONEGO-ORNAN EFRAT , PINHAS-HAMIEL ORIT
Published: June 2020

A 22-year old female with type 1 diabetes (T1DM) presented with generalized rash. She was diagnosed at the age of 9 years and is treated with insulin pump and CGMS (continues glucose monitoring sensors), her recent HbA1c was 7.4%. Four weeks prior to her rash presentation she started a low carbohydrate diet (50 gr of carbs per day) in order to improve her glycemic control. Pruritic erythematous papules, papulovesicular, and vesicles appeared on her axillary region, upper back and groins. Lesions were associated with severe pruritus and negatively affected her quality of life. Various therapies were initiated by dermatologist as: antifungal agent, Itraconazole, and Betamethasone Esters, without any improvement. Her serum beta-hydroxybutyrate levels were between 1.1-1.2 mmol/l. Prurigo pigmentosa, a rare pruritic inflammatory dermatosis secondary to her high ketones levels was diagnosed. Her condition resolved after she increased her carbohydrate intake to 75 gr per day. Beta-hydroxybutyrate level decreased concomitantly to 0.1-0.2 mmol/l. When carbohydrate restriction was rechallenged, she again entered ketosis, followed by recurrence of the pruritic lesions. Carbohydrate intake was increased and subsequently all lesions resolved with remaining reticular hyperpigmentation. During the last few years low carb diets have gained popularity among patients with T1DM. This case illustrates the rare side effect of high ketones body levels. Health care providers should be familiar with this side effect.

Disclosure

N. levran: None. K. Mazor-Aronovitch: None. S. Grenberger: None. N. Levek: None. B. Sher: None. E. Mauda: None. Z. Landau: None. E. Monsonego-Ornan: None. O. Pinhas-Hamiel: None.
723-P: Effect of Low-Carbohydrate High-Fat vs. High-Carbohydrate Low-Fat Diet on HbA1c Control in Chinese Patients with Type 2 Diabetes
Authors: AN LINGWANG , WANG DANDAN , SHI XIAORONG , LIU CHENHUI , YEH KUEICHUN , LEE TAO-CHUN , JI LINONG
Published: June 2020

Aims: To explore the effect of LCHF (C<50%; F≥35%) diet vs. HCLF (C≥50%; F<35%) diet on HbA1c control in patients with T2D in 3 Chinese diabetes hospitals.

Methods: Patients were enrolled if they had been assessed by professional dietitians and had electronic medical record on a diabetes share-care management database. A total of 1017 patients were eligible for this study with 44.1% in group LCHF and 55.9% in group HCLF.

Results: Compared with group HCLF (Carb 59%: Fat 28%: Pro 13%), group LCHF (41%: 44%: 15%) had higher calorie intake (1845 vs. 1691 kcal/day), higher proportions of patients exceeding calorie recommendation (69.5% vs. 52.3%) and lower baseline HbA1c levels (8.29 vs. 8.52 %). HbA1c improvements were found in both groups after diabetes share-care management with significantly lower HbA1c (7.87 vs. 7.36 %) and higher proportions of patients reaching HbA1c target (31.4% vs. 47.3%) in group HCLF. Binary logistic regression analysis showed that exceeding calorie recommendation [OR(95%CI): 0.703 (0.514∼0.961)]was a risk factor at baseline and LCHF diet was a risk factor [OR(95%CI): 0.549 (0.327∼0.924)] at follow up visit for reaching HbA1c target.

Conclusions: There were higher proportions of patients reaching HbA1c target in group HCLF than in group LCHF after share-care model management. LCHF diet was associated with lower likelihoods of achieving HbA1c target.

Disclosure

L. An: None. D. Wang: None. X. Shi: None. C. Liu: None. K. Yeh: None. T. Lee: None. L. Ji: None.
725-P: Effect of a Continuous Remote Care Intervention on Glycemic Target Achievement and Medication Use among Adults with T2D: A Post Hoc Analysis
Authors: ATHINARAYANAN SHAMINIE J. , ADAMS REBECCA N. , HALLBERG SARAH , PHINNEY STEPHEN , MCKENZIE AMY
Published: June 2020

Background: Only about half of patients with type 2 diabetes (T2D) achieve the HbA1c <7% target, and maintenance often requires medication intensification over time. A continuous remote care intervention (CCI) including ketosis via carbohydrate restriction nutrition therapy was previously demonstrated to improve glycemic outcomes in adults with T2D for at least two years; here, we assess the proportion of patients meeting glycemic targets and accompanying medication use.

Methods: Adults with T2D selected to receive the CCI (n=262) or usual care (UC; n=87). We utilized GEE to assess change in the proportion of patients at HbA1c <7% target and accompanying medication use at 1 and 2 years compared to baseline. Analyses were conducted among completers and on an intent-to-treat basis with missing data considered as missing the HbA1c target.

Results: The proportion of CCI patients meeting the HbA1c <7% target significantly increased at 1 and 2 years (Table 1). A similar improvement trend was seen among those treated with a single drug (monotherapy), and the proportion of patients at target without the use of medication approximately tripled. No changes occurred among patients who selected UC.

Conclusion: This suggests the CCI is an effective means to help more patients achieve the HbA1c <7% target, including with monotherapy or no medication, among those who choose it.

Disclosure

S.J. Athinarayanan: Employee; Self; Virta Health Corp. R.N. Adams: Employee; Self; Virta Health Corp. S. Hallberg: Advisory Panel; Self; Atkins Nutritionals, Inc. Employee; Self; Virta Health Corp. Stock/Shareholder; Self; Virta Health Corp. S. Phinney: Advisory Panel; Self; Atkins Nutritionals, Inc. Stock/Shareholder; Self; Beyond Obesity LLC (publishing), Virta Health Corp. A. McKenzie: Employee; Self; Virta Health Corp. Stock/Shareholder; Self; Virta Health Corp.
730-P: At-Home Randomized Crossover Comparison of Automated Insulin Delivery vs. Conventional Therapy with Scheduled Meal Challenges
Authors: PINSKER JORDAN E. , DESHPANDE SUNIL , CHURCH MEI MEI , PIPER MOLLY , ANDRE CAMILLE C. , MASSA JENNIFER S. , DOYLE FRANCIS J. , EISENBERG DAVID M. , DASSAU EYAL
Published: June 2020

Automated Insulin Delivery (AID) hybrid closed-loop systems have not been well studied in the context of prescribed meals. We evaluated our interoperable artificial pancreas system (iAPS) with scheduled meal challenges in a randomized crossover trial in an at-home setting.

Ten adults with type 1 diabetes completed two weeks of AID-based control and two weeks of conventional therapy (sensor-augmented pump/predictive low-glucose suspend) at home in random order. During each period, subjects consumed pasta or white rice as part of a complete dinner meal on six different occasions (each meal three times in random order).

The AID system increased time in range 70-180 mg/dL from 70.6 to 74.0% (3.4, 95% CI -2.3 to 9.1, p=0.22), while sensor time <70 mg/dL significantly decreased from 3.5 to 2.3% (-1.2, 95% CI -2.1 to -0.2, p=0.02). Postprandial glucose AUC difference between meals in conventional therapy was 10,919.0 mg/dL x min (95% CI 3,190.5 to 18,648.0, p=0.009) while for AID it was 6,522.1 mg/dL x min (p=0.24), highlighting the ability of AID to minimize glycemic excursions postprandially. The AID system decreased insulin delivery at 0-2h by 0.45 units (p=0.001) for pasta, while it increased at 2-4h by 0.47 units (p=0.18) for white rice (Table 1).

The AID system improved postprandial glucose control over conventional therapy in the handling of challenging meals in the at-home setting.

Disclosure

J.E. Pinsker: Advisory Panel; Self; Medtronic. Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Tandem Diabetes Care. Speaker’s Bureau; Self; Tandem Diabetes Care. S. Deshpande: None. M. Church: None. M. Piper: None. C.C. Andre: None. J.S. Massa: None. 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. D.M. Eisenberg: Consultant; Self; Barilla Center For Food and Nutrition, Italy. 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.

Funding

Barilla Center for Food & Nutrition Foundation; National Institutes of Health (DP3DK104057, DP3DK113511); Harvard Accelerator; Dexcom, Inc. (IIS-2018-019)
731-P: Impact of 3 Weeks of a Low-Carbohydrate Diet and Exercise on Overweight and Obese Adults: A Randomized Clinical Trial
Authors: ZHOU JIAN , CAI LINGLI , YIN JUN , MA XIAOJING , MO YIFEI , CHENG LI , LU WEI , BAO YUQIAN , JIA WEIPING
Published: June 2020

Background: Lifestyle interventions, including dietary adjustment and exercise, are important for weight loss in the context of obesity.

Objective: This study aimed to compare the short-term effects of a low-carbohydrate diet (LCD) and exercise nondiabetic overweight and obese adults.

Design: A total of 45 eligible subjects were randomized into a low-carbohydrate diet group (LC, n=22) and an exercise group (EX, n=23); the participants adopted a LCD (carbohydrate intake < 30 mins/day) for 3 weeks. Weekly follow-ups were conducted and flash glucose monitoring sensors were used.≥50 g/day) or performed moderate-to-vigorous exercise (

Results: After the 3-week intervention, body mass index, total fat% and total fat mass (FM), waist circumference, visceral fat area and subcutaneous fat area decreased significantly in both the LC and EX, but the LC lost 2.32 kg more weight than the EX. Total fat-free mass (FFM) and total body water (TBW) in the LC were significantly reduced but remained unchanged in the EX. Triglycerides (TGs), total cholesterol and low-density lipoprotein cholesterol (LDL-c) decreased in the EX, while TGs decreased and LDL-c increased in the LC. Glycemic variability and insulin resistance were improved in both groups, but the effect in the LC was faster and greater. Mean sensor glucose declined significantly in the LC. Three days after stopping the intervention, body weight, FM and FFM increased significantly in the LC, and most of the FFM regained was TBW, which remained stable in the EX.

Conclusion: A short-term LCD was more effective for weight loss and glycemic stability than exercise, and it mainly reduced body fat and body water. However, body weight was regained to a greater extent after stopping the LCD, which was due to body water retention. Exercise was less effective for fat loss than LCD and had no significant influence on body water.

Disclosure

J. Zhou: None. L. Cai: None. J. Yin: None. X. Ma: None. Y. Mo: None. L. Cheng: None. W. Lu: None. Y. Bao: None. W. Jia: None.
734-P: Prevalence of Low and Borderline Levels of Vitamin B12 in Type 2 Diabetic Patients Treated with Metformin: A Cross-Sectional Study in Argentina
Authors: CELA CINTHIA , LANGUS MARIANA
Published: June 2020

Background: Vitamin B12 deficiency, a common cause of megaloblastic anemia, has been associated with cognitive decline and increasing risk of depression. Metformin therapy has been associated with vitamin B12 (B12) deficiency in several populations. However, information regarding this adverse effect in Argentina populations is limited. The aim of this study was to examine the relation between metformin use and B12 status in individuals with type 2 diabetes mellitus (T2DM) in Argentina.

Design and Setting: Cross-sectional study at a public university hospital.

Results: At present 190 patients were included (See Table 1). Serum vitamin B12 levels were low (< 200 ngl/mL) in 28 patients (14.7%) and borderline (200-300 ng/ml in 48 patients (25.26 %). Only one patient showed laboratory findings consistent with anemia megaloblastic.

Conclusions and Future Directions: Our study showed low or borderline levels of vitamin B12 in 14.7.3% and 25.26 % of patients, respectively. This large number of patients with low o borderline levels of B12 suggests that a high proportion of patients may be at risk of B12 deficiency related conditions. Close monitoring of B12 level, and measurement of other biomarkers of cellular B12 deficiency may help to identify these patients at risk.

Disclosure

C. Cela: None. M. Langus: None.
735-P: Visible and Invisible Spousal Support in Daily Diabetes Self-Care
Authors: SORIANO EMILY , LAURENCEAU JEAN-PHILIPPE
Published: June 2020

Aim: Prior research has yielded inconsistent findings on the effects of spousal support in type 2 diabetes (T2D) management, yet most studies were cross-sectional and relied exclusively on patient perceived support. This study aimed to examine the within-person effects of daily perceived and enacted spousal support in T2D self-care on glycemic control.

Method: Adults with T2D (N = 63; age M = 61; 67% male; 70% Caucasian) and their spouses participated in a parent study. Patients wore continuous glucose monitors (CGM) for 7 days and concurrently, each evening, both partners responded to the following item: Did you/your partner say or do anything TODAY to try to influence your/spouse/partner’s behavior with regard to managing your/his/her diabetes? The patient item version represents perceived and spouse version enacted support, respectively. CGM data were used to calculate 4 indices of daily glycemic control: mean (M), standard deviation (SD), coefficient of variation (CV), and time in range (TR).

Results: A multilevel dynamic structural equation model was estimated for each outcome. Within-person effects of perceived and enacted support were allowed to vary between persons and time was a covariate. Enacted support significantly predicted better glycemic control across all outcomes (βM = -.32, βSD = -.30, βCV = -.19, βTR = .42, ps < .05). Conversely, perceived support was unrelated to most outcomes (βM = .06, βSD = .17, βCV = .12, ps > .05), but significantly related to lower TR (βTR = -.40, p = .004).

Conclusion: Results echo research on invisible (enacted, not perceived) versus visible (enacted, perceived) support: the former is consistently linked to positive outcomes, whereas visible support is often ineffective or detrimental. Indeed, perceiving support receipt may undermine patient self-efficacy for T2D management and in turn, reduce self-care adherence (e.g., medication, diet). Replication and more research are needed to determine the extent to which the support visibility model applies to the context of T2D.

Disclosure

E. Soriano: None. J. Laurenceau: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R21DK098679, F31DK120201)
739-P: The Mediating Role of HbA1c and the Moderating Role of Social Support in the Relation between Peer Victimization and Number of Diabetes-Related ER Visits
Authors: STROMBERG SARAH , FAITH MELISSA A. , FELDMAN MARISSA
Published: June 2020

Objective: Routine screening of diabetes-specific and general psychosocial factors is recommended by ADA. While depression and family functioning have been associated with poorer adherence and metabolic control, research linking peer relations and T1D management is mixed and victimization is not consistently assessed. Youth with T1D are at higher risk of victimization, and those that experience diabetes-specific bullying found to have poorer metabolic control. This study tests a moderated mediation model where peer victimization, moderated by perceived social support, predicts diabetes-related ER visits and whether A1C mediates the relation.

Method and Results: At routine clinic visits, 198 children (ages 7-18) completed the Multidimensional Scale of Perceived Social Support and The Way Kids Are. Chart review was completed. A moderated mediation model explained 18% of the variance in ER visits (p < .001). Social support moderated the relation between victimization and diabetes-related hospitalizations, with strong social support mitigating the relation between victimization and hospitalizations (p = .005). Additionally, A1C mediated the positive relationship between victimization and diabetes-related ER visits; peer victimization was positively related to A1C (p =0.021), which in turn positively predicted ER visits (p < .001).

Conclusions: HbA1C helped explain the positive relationship between peer victimization and diabetes-related ER visits. Additionally, social support appeared to be a protective against hospitalizations. Victimization is a stressor that may directly or indirectly impact blood glucose levels via self-management. Youth who experience greater peer victimization may be less likely to engage in diabetes management in social situations. Victimization should be screened and youth helped to build self-efficacy and confidence related to managing their diabetes around peers.

Disclosure

S. Stromberg: None. M.A. Faith: None. M. Feldman: None.
74-OR: The Effect of SERCA2 Activation on Liver Metabolism and Diet-Induced Steatohepatitis in Mice
Authors: BEDNARSKI TOMASZ , RAHIM MOHSIN , YOUNG JAMEY
Published: June 2020

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease, but its progression to the severe form of nonalcoholic steatohepatitis (NASH) is unpredictable. Hepatocyte steatosis alters endoplasmic reticulum (ER) calcium stores and induces mitochondrial dysfunction leading to hepatocellular inflammation and apoptosis. Moreover, obese mice have impaired sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) function, responsible for transporting Ca2+ from the cytoplasm to ER. We thus hypothesized that restoration of SERCA2 activity may improve hepatocyte function during lipotoxicity. To test this hypothesis, 8-week-old male C57Bl/6J (wild type, WT) or melanocortin-4 receptor knockout (MC4R-/-) mice were placed on either chow or Western diet (WD) for 8 weeks. Half of the WD-fed mice were also given injections of CDN1163 once every two weeks to activate SERCA2. Sodium [13C3]lactate was infused intravenously into conscious, unrestrained mice for 2 hours and 13C-enrichments of plasma glucose and liver metabolites were measured by GC-MS, then used to regress liver metabolic fluxes using the INCA modeling platform. CDN1163 treatment significantly decreased weight and fat mass of both WT and MC4R-/- WD-fed mice without affecting food intake or lean mass. Moreover, CDN1163 improved insulin sensitivity of WT and MC4R-/- mice. CDN1163 decreased NAFLD activity score in WT, but failed to reduce histological features of NASH in MC4R-/- mice. Liver free fatty acids, diglycerides and ceramides were not affected; however, CDN1163 decreased triglyceride content in WT mice. Liver metabolic fluxes analysis revealed that CDN1163 accelerated pyruvate cycling in WT and MC4R-/- mice, which may explain how CDN1163 helped hepatocytes adapt to an excess of energy substrates. Taken together, these data suggest that SERCA2 activation had a protective effect on liver when NAFLD was less severe (WT) but was insufficient to rescue lipotoxicity after progression to NASH had occurred (MC4R-/-).

Disclosure

T. Bednarski: None. M. Rahim: None. J. Young: Board Member; Self; Metalytics. Consultant; Self; Pfizer Inc.

Funding

National Institutes of Health (R01DK106348)
740-P: Effect of Family Support Intervention on Support Roles and Impact of Support on HbA1c among Adults with Type 2 DM
Authors: ZUPA MARGARET , HEISLER MICHELE , PIETTE JOHN , TRIVEDI RANAK B. , STOLL SHELLEY C. , OBROSKY D. SCOTT , LOVELACE ELIJAH Z. , MOR MARIA K. , ROSLAND ANN-MARIE
Published: June 2020

Many adults with DM have a family supporter (FS) involved in their care. Informal support has been linked with better DM management and outcomes. We evaluated the effect of a patient and FS engagement intervention on FS roles in DM care, and the impact of those roles on HbA1c. Two-hundred and thirty-nine adult Veterans with type 2 DM and a FS were randomized to intervention vs. usual care for 12 months. Intervention dyads received one coaching session, biweekly automated calls to prompt action planning on new DM concerns, coaching calls to prepare for clinic visits, and summaries of primary care visits and DM complication risk. All models were controlled for baseline HbA1c, age, sex, insulin use, and FS cohabitation with patient. Over 12 months, participants in the intervention group were more likely to have increased involvement in several FS roles, including: deciding when to contact healthcare providers about concerns (AOR 2.080, 95% CI 1.137,3.804), remembering to go to appointments (AOR 2.852, 95% CI 1.503, 5.412), take (1.853, 95% CI 1.001, 3.428) and refill (AOR 2.193, 1.196, 4.019) medications, and perform (AOR 2.615, 95% CI 1.405, 4.867) and review (AOR 2.822, 95% CI 1.506, 5.290) home testing. Changes in help navigating the healthcare system, and encouraging healthy eating and exercise were not different by intervention arm. Help remembering to take medications at baseline was associated with 0.457% increase in HbA1c over 12 months (95% CI 0.107, 0.807, p=0.011), and no support roles were significantly associated with HbA1c decrease.

In conclusion, this intervention increased FS involvement in diabetes-specific self-management, with less impact on general lifestyle support. Patients with support for taking medication prior to the intervention had significant subsequent increases in HbA1c. This may indicate family are recognizing which patients have challenges with medication taking, but need more training to effectively help improve subsequent patient outcomes.

Disclosure

M. Zupa: None. M. Heisler: None. J. Piette: None. R.B. Trivedi: None. S.C. Stoll: None. D. Obrosky: None. E.Z. Lovelace: None. M.K. Mor: None. A. Rosland: None.

Funding

VA Health Services Research and Development (IIR 14–074-1); Michigan Center for Diabetes Translational Research (5P60-DK09292); Michigan Claude D. Pepper Older Americans Independence Center (AG-024824); VA Ann Arbor Center for Clinical Management Research; University of Pittsburgh (5T32DK007052-45)
741-P: Racial/Ethnic Disparity in Advanced Diabetes Technology Use in Type 1 Diabetes (T1D): Minority Young Adult (YA) Perspectives on Perceived Access
Authors: CRESPO-RAMOS GLADYS , MILLER VICTORIA , GONZALEZ JEFFREY S. , JANG ALYSSA , AGARWAL SHIVANI
Published: June 2020

Previous research has documented racial/ethnic disparity in continuous glucose monitor and insulin pump use in people with T1D. It remains unknown whether disparities result from socioeconomic status or other factors. We recruited 17 YA with T1D from an underserved area (mean age 22, 5 non-Hispanic Black, 12 Hispanic, 88% Medicaid, duration 11 yrs, median HbA1c 9.6%) and conducted semi-structured individual interviews in English or Spanish. We asked questions about how YA were introduced to diabetes technology and what helped them make decisions for use. We developed a standard codebook to direct content analysis and achieved thematic saturation. Our results revealed 3 main themes surrounding information and decisions on technology use: 1) providers were the gateway for information and access; 2) patients were not typically included in decision-making, but were more likely to accept use when they were; and 3) cost was not an issue. Half of participants reported they were never offered or told about diabetes technology in the past despite long diabetes duration. For those with whom technology was discussed, most stated they were not included in the decision process to receive such technology. Some participants reported that providers refused prescription of technology due to lack of demonstration of self-management skills. Still, no alternative options or goal-setting to obtain technology were offered. Some participants desired to learn more about technology but refused to ever start because of perceived extra burden, skepticism of new equipment, or attachment concerns. Very few participants stated they could not afford the technology. Our results suggest that racial/ethnic disparity in technology use may originate at the patient-provider level. Deeper examination of implicit bias in prescribing practices is needed, as well as understanding of minority YA preferences and promotion of shared decision-making.

Disclosure

G. Crespo-Ramos: None. V. Miller: None. J.S. Gonzalez: None. A. Jang: None. S. Agarwal: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K23DK115896)
744-P: Racial Differences in the Contribution of Sociodemographic, Clinical, and Self-Care Factors on Glycemic Control in Adults with Type 2 Diabetes
Authors: OLUKOTUN OLUWATOYIN , WILLIAMS JONI S. , WALKER SHANNON L. , AKINBOBOYE OLAITAN J. , EGEDE LEONARD E.
Published: June 2020

Background: This study evaluated the unique contribution of demographic, social determinants, clinical and self-care factors on glycemic control in a sample of adults with T2DM.

Methods: This analysis used data obtained from 615 adults with T2DM in the Southeastern U.S. Linear regression models were used to assess the incremental contribution of key variables (demographic, social determinants [socioeconomic status, psychosocial and built environment factors], clinical and self-care factors) at varying levels of influence, on glycemic control, after stratifying by race.

Results: For the entire sample, there were significant relationships between glycemic control and age (β = −0.02, p < 0.05), Medicaid (β = −0.69, p < 0.05), diabetes fatalism (β = −0.02, p < 0.05), self-efficacy (β = −0.10, p < 0.001), social support (β = 0.01, p < 0.05), comorbidity (β = −0.09, p < 0.05), insulin use (β = 0.95, p < 0.001), and being a former smoker (β = 0.35, p < 0.05). In the stratified regression model for Non-Hispanic Whites (NHW), there were significant relationships between glycemic control and Medicare (β = −1.27, p < 0.05), “other” insurance type (β = −1.53, p < 0.05), education (β = −0.95, p < 0.05), self-efficacy (β = −0.06, p < 0.001), neighborhood rating (β = −0.58, p < 0.05), neighborhood comparison (β = 0.39, p < 0.05), insulin use (β = 1.04, p < 0.01). In the stratified regression model for Non-Hispanic Blacks (NHB), there were significant relationships between glycemic control and age (β = −0.02, p < 0.05), diabetes distress (β = 0.44, p < 0.05), self-efficacy (β = −0.11, p < 0.001), social support (β = 0.01, p < 0.01), comorbidity (β = −0.13, p < 0.05), and insulin use (β = 1.02, p < 0.001).

Conclusion: In this sample of adults with diabetes, there were racial differences in demographic, psychosocial, built environment and clinical factors associated with glycemic control. Interventions may need to be tailored by race or ethnicity to achieve optimal outcomes.

Disclosure

O. Olukotun: None. J.S. Williams: None. S.L. Walker: None. O.J. Akinboboye: None. L.E. Egede: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K24DK093699, R01DK118038, R01DK120861 to L.E.E.); National Institute for Minority Health and Health Disparities (R01MD013826 to L.E.E., S.L.W.)