bluuebunny/crossref_metadata_2025_split huggingface dataset:
297-OR: Triglyceride Reduction and Effect on Lipoprotein Metabolism in Patients with Type 2 Diabetes Mellitus Receiving Fixed-Dose Combination of Insulin Degludec and Liraglutide
Authors: PAPPA ELENI , KOSTARA CHRISTINA , DIMOU AIKATERINI , BAIRAKTARI ELENI T. , TSIMIHODIMOS VASILIS 
Published: June 2021

Aim: To compare the effect of fixed-dose combination of Insulin Degludec and Liraglutide (IDegLira) on anthropometric, carbohydrate metabolism and lipid parameters, as well as on apoB-containing lipoprotein subclasses and HDL lipidome, in patients with type 2 diabetes (T2DM) regarding changes in triglyceride (TG) levels.
Methods: Seventy-two uncontrolled patients with T2DM on oral antidiabetics were randomized to receive IDegLira or Insulin Degludec (IDeg) for a 12-week treatment. In the present study, 42 patients receiving IDegLira were included. Twenty-one presented a decrease, while the remaining an increase in TG levels. ApoB-containing lipoprotein subclasses levels were measured by LDL-Lipoprint method, whereas HDL lipidomic analysis via 1H-NMR spectroscopy.
Results: In patients experiencing a decrease in TG levels after IDegLira administration, a significant decrease in body weight and BMI, by 4.4kg and 1.59kg/m2 respectively, was observed. Fasting glucose, HbA1c and HbA1c Glycation Index noted a decrease by 35 mg/dl, 1.4% and 1.1 respectively (p=0.018, p=0.004, p=0.004). IDegLira administration in this subgroup resulted in a significant reduction of total (TC) and LDL cholesterol (LDLC) by 22.5mg/dl and 13.2mg/dl, respectively. Small-dense LDLC (sdLDLC) levels significantly correlated with changes in TG levels (r=0.496, p=0.02). Furthermore, IDegLira administration resulted in significant enrichment of HDL particle core in esterified cholesterol, depletion of TG content and an atheroprotective shift in fatty acid pattern of HDLs. The aforementioned changes were significantly greater than those observed in patients receiving IDegLira and did not experience a TG reduction.
Conclusions: TG reduction as a result of IDegLira administration is accompanied by greater changes in anthropometric and carbohydrate metabolism parameters, TC, LDLC, sdLDLC and HDL lipidome.

Disclosure
E. Pappa: None. C. Kostara: None. A. Dimou: None. E. T. Bairaktari: None. V. Tsimihodimos: None.
3-OR: Racial/Ethnic Disparities in Diabetes Technology Use in Young Adults (YA) with Type 1 Diabetes (T1D): Multidisciplinary Stakeholder Perspectives and Solutions
Authors: AGARWAL SHIVANI , CRESPO-RAMOS GLADYS , LEUNG STEPHANIE , FINNAN MOLLY , PARK TINA , GONZALEZ JEFFREY S. , LONG JUDITH A. 
Published: June 2021

Background: Black and Hispanic YA with T1D are less likely to use insulin pumps and continuous glucose monitors than White peers, which may be contributing to disparities in glycemic and long-term outcomes.
Methods: We conducted a series of interactive focus groups to elicit perspectives on racial/ethnic disparities in diabetes technology use, patient-centered barriers and facilitators, and solutions to enhance uptake. We invited multidisciplinary panels of stakeholders to participate, including YA T1D patients, physicians, nurses, psychologists, and community health workers. Sessions were recorded and analyzed for common themes.
Results: We convened 7 virtual 2-hour workshops and recruited 32 stakeholders from 11 states (5 Black and 7 Hispanic YA, 20 other stakeholders). Notably, many patients stated that they had never been offered technology until recent engagement in a specialized YA T1D clinic. Once offered technology, multiple barriers were present across a chronological journey consisting of three phases: 1) learning about and deciding to get technology; 2) initiating use; and 3) managing ongoing problems. Some barriers included a lack of knowledge about devices, mismanaged expectations for device wearability and use, and insurance coverage benefits. Facilitators included family support, T1D peer partnership, and a supportive healthcare team. Co-created solutions to address barriers were categorized into four main themes: 1) more equitable system of offering technology; 2) visual and hands-on education; 3) peer support; and 4) insurance navigation assistance.
Discussion: Engaging multiple stakeholders with lived experience of the problem is an important approach to diabetes disparities research. Inadvertent provider bias may be preventing equal access to technology for minority YA with T1D, while extra support for device use through the technology journey is needed to sustain use.

Disclosure
S. Agarwal: None. G. Crespo-ramos: None. S. Leung: None. M. Finnan: None. T. Park: None. J. S. Gonzalez: None. J. A. Long: None.

Funding
National Institutes of Health (K23DK115896)
30-LB: Effect of Intense Lifestyle Therapy in People with Obesity and Type 2 Diabetes
Authors: YOSHINO MIHOKO , YOSHINO JUN , BITTEL ADAM J. , BITTEL DANIEL , REEDS DOMINIC , STEIN RICHARD , SINACORE DAVID R. , CADE WILLIAM T. , OKUNADE ADEWOLE L. , PATTERSON BRUCE W. , KLEIN SAMUEL 
Published: June 2021

Weight loss and exercise are the cornerstones of therapy for patients with obesity and type 2 diabetes (T2D). However, successful compliance with therapy is difficult to achieve. We conducted an 8-month randomized, controlled trial in persons with obesity and T2D to determine the effect of intensive lifestyle therapy (ILT), delivered at a worksite setting, on body weight, cardiometabolic function, and cellular metabolic pathways. Subjects were assigned to Standard Care (SC; n=8, BMI:38±5, fasting blood glucose [FBG]:161±19 mg/dl, HbA1c:7.6±1.1%) or ILT (n=10, BMI:37±6, FBG:150±32 mg/dl, HbA1c:7.0±1.1%), which involved weekly diet-behavior therapy sessions and 4 d/wk of supervised resistance and endurance exercise training. Weight loss was greater in the ILT than SC group (17±7% vs. 1±2%, P&lt;0.05). All cardiometabolic outcomes improved more in the ILT than SC group: i) insulin sensitivity (glucose disposal rate during a hyperinsulinemic-euglycemic clamp increased by 116±78% vs. 15±9%, P&lt;0.05); ii) β-cell function (insulin secretion in response to an oral glucose load relative to insulin sensitivity increased by 194±205% vs. 12±20%, P&lt;0.05); and iii) cardiorespiratory fitness (VO2 peak during cycle ergometer exercise increased by 28±22% vs. -2±15%, P&lt;0.05). The most upregulated biological pathways enriched in differentially expressed genes (DEGs) in skeletal muscle, assessed by RNA-seq, after ILT involved mitochondrial function and sirtuin signaling pathways. Upstream regulators of these DEGs included NAD dependent deacetylase sirtuin-3 (SIRT3) and NAMPT (FDR&lt;0.05). In addition, ILT increased muscle NAD content by 51±46% (P&lt;0.05). FBG and HbA1c decreased to 108±31 mg/dl and to 6.1±0.9%, despite a 60% decrease in the use of diabetes medications after ILT, but did not change with SC. We conclude that marked diet-induced weight loss and exercise training can be achieved in a structured worksite setting and has profound therapeutic cardiometabolic effects in people with obesity and T2D.

Disclosure
M. Yoshino: None. B. W. Patterson: None. S. Klein: Advisory Panel; Self; Altimmune, Merck & Co., Inc., Novo Nordisk Inc., ProSciento, Research Support; Self; Janssen Research & Development, LLC. J. Yoshino: None. A. J. Bittel: None. D. Bittel: None. D. Reeds: None. R. Stein: None. D. R. Sinacore: None. W. T. Cade: None. A. L. Okunade: None.

Funding
American Egg Board; National Dairy Council (T32DK07296DK007120)
302-OR: Medical Prescriptions for Vegetables Are Associated with Reduced Consumption of Unhealthy Foods, Improved Food Security, and Lowered Cardiometabolic Risk among Adults with or at Risk of Type 2 Diabetes
Authors: GLANTZ NAMINO M. , CONNEELY CASEY , LAREZ ARIANNA J. , BEVIER WENDY C. , KERR DAVID 
Published: June 2021

Previously, we have reported that improving access to fresh vegetables reduces cardio-metabolic risk for predominantly Mexican American adults with or at risk of type 2 diabetes (T2D). This analysis examined changes in self-reported consumption of less healthy foods (soda, sugary drinks, and tortillas) and the association with medical prescriptions for locally sourced fresh vegetables.
In this observational cohort study, 202 adults (152 female, 80% Hispanic/Latino, mean ±SD age of 53.8 ±12.6 years) with (n=62) or at risk (American Diabetes Association risk calculator) of T2D received 21 servings per week of locally sourced fresh vegetables prescribed by a physician for 10 weeks. No nutrition education was provided. For participants with paired data, there were reductions in waist circumference (-0.9 ±3.7 cm, p=0.003); systolic blood pressure for those with baseline ≥ 130 mmHg (-8.9±16.5 mmHg, p=0.001); and HbA1c values for participants with a baseline &gt;7.0 % (-0.4 [-0.8, -0.1] %, p=0.016). Fewer participants had low or very low food security (USDA 6-item Food Security Module) after the intervention (25 versus 76, p&lt;0.0001), associated with reductions in consumption of tortillas (p&lt;0.00001); soda and other sugar-sweetened fruit drinks, sweet tea, and sports or energy drinks (p&lt;0.001); and their weekly frequency of eating out (p=0.01). The improvement in food security was also associated with better sleep (ρ=0.22, p=0.007).
The use of medical prescriptions for vegetables is associated with greater food security and lower cardiometabolic risk in predominantly Mexican-American adults with or at risk of T2D, possibly related to less consumption of unhealthy foods.

Disclosure
N. M. Glantz: Research Support; Self; Abbott, Eli Lilly and Company. C. Conneely: Research Support; Self; Abbott, Eli Lilly and Company. A. J. Larez: Research Support; Self; Abbott, Eli Lilly and Company. W. C. Bevier: Research Support; Self; Abbott Diabetes, Eli Lilly and Company. D. Kerr: Advisory Panel; Self; Novo Nordisk, Sanofi-Aventis, Research Support; Self; Abbott Diabetes, Elsevier, Lilly Diabetes, Stock/Shareholder; Self; Glooko, Inc.

Funding
U.S. Department of Agriculture (2018-33800-28404)
312-OR: Comparison of Processes of Care and Acute Care Utilization for Medicaid Enrollees with Type 2 Diabetes in Federally Qualified Health Centers vs. Other Sites of Primary Care
Authors: KNITTER ALEXANDRA C. , MURUGESAN MANORADHAN , SAULSBERRY LOREN , WAN WEN , NOCON ROBERT , HUANG ELBERT , BOLTON JOSH , CHIN MARSHALL , LAITEERAPONG NEDA 
Published: June 2021

Background: Adults with type 2 diabetes and Medicaid insurance are a highly vulnerable population. Despite the vital role of primary care for diabetes management, few studies have examined how the type of primary care setting affects quality of care for this population, and existing studies have not examined data across the US. Since federally qualified health centers (FQHCs) are the primary care safety net for many Medicaid patients, we compared process of care outcomes and acute care utilization for non-elderly adult Medicaid enrollees with type 2 diabetes at FQHC vs. non-FQHC primary care settings.
Methods: We analyzed 2012 Medicaid fee-for-service and managed care claims data in all 50 states and DC in order to compare 8 processes of care and acute care utilization for patients receiving care at FQHCs (N=121,977) vs. non-FQHCs (N=700,401). We used propensity score overlap weighting to obtain groups balanced on covariates, then used generalized estimating equation models to compare the two groups.
Results: FQHC patients had 2.6-3.6% lower rates of each measure compared to non-FQHC patients, with the exception of a higher rate of diabetes education (relative risk, 1.09 [95% CI, 1.03-1.16]). Compared to non-FQHC patients, FQHC patients had more overall (incident rate ratio, 1.06 [1.05-1.07]) and diabetes-related emergency department (ED) visits (1.10 [1.08-1.13]), but fewer overall (0.87 [0.86-0.88]) and diabetes-related hospitalizations (0.79 [0.77-0.81]).
Conclusions: Our findings suggest that Medicaid enrollees with type 2 diabetes receiving primary care at FQHCs may have limited access to both preventative and urgent diabetes care. FQHC patients with diabetes may visit EDs more frequently as a result of limited appointment availability or access to specialists at FQHCs. These results underscore the need for increased support and funding for Medicaid patients with type 2 diabetes, especially in FQHCs.

Disclosure
A. C. Knitter: None. M. Murugesan: None. L. Saulsberry: None. W. Wan: None. R. Nocon: None. E. Huang: None. J. Bolton: None. M. Chin: Advisory Panel; Self; Bristol-Myers Squibb Company. N. Laiteerapong: Other Relationship; Self; American Diabetes Association.

Funding
Health Resources and Services Administration (HHSH250201300025I); National Institute of Diabetes and Digestive and Kidney Diseases (P30DK092949)
333-OR: Regulation of Adiponectin Receptor 2 Expression and Function in the Liver
Authors: HADLEY JASON , SCRUGGS DARAH A. , RYU JIYOON , DONG LILY Q. 
Published: June 2021

Adiponectin, an adipokine, has been implicated in improving lipid and glucose metabolism and preventing diet-induced inflammation. Adiponectin transduces its effects by binding to its cognate receptors, AdipoR1 and AdipoR2. Compared to AdipoR1, AdipoR2 is specifically and heavily expressed in liver tissues, but its function in regulating Adiponectin-mediated signaling remains controversial. Our study indicates that AdipoR2 expression levels are reduced under feeding conditions as compared to fasting, suggesting that nutrition status regulates AdipoR2 expression. We also found that the levels of AdipoR2 in liver tissue are significantly less in mice fed with high fat diets compared to mice on chow diets, indicating down-regulation of AdipoR2 expression is associated with overnutrition-induced insulin resistance. Interestingly, we found that AdipoR2 undergoes protein palmitoylation, a diet-induced post-translational modification important in regulating protein trafficking and stability. By checking potential palmitoylation sites in AdipoR2, we identified several cysteine residues near the N-terminus that could be potential sites of palmitoylation. Site-direct mutagenesis studies indicated that C11A mutant, which mimics de-palmitoylation status at this residue, was more stable and had less plasma membrane located compared to the wild type receptor. Together, our results suggest that diet-induced palmitoylation of AdipoR2 is one of the mechanisms underlying high fat diet-triggered down-regulation of AdipoR2. This study provides critical information for understanding regulation of adiponectin signaling in liver and the potential theraputical values for treating insulin resistance and type 2 diabetes.

Disclosure
J. Hadley: None. D. A. Scruggs: None. J. Ryu: None. L. Q. Dong: None.
35-OR: Epigenetic Regulation of White Adipose Tissue Browning by HMGN Proteins
Authors: NANDURI RAVIIKANTH , FURUSAWA TAKASHI , LOBANOV ALEXEI , GAVRILOVA OKSANA , BUSTIN MICHAEL 
Published: June 2021

Chromatin architecture proteins HMGNs (High Mobility Group Nucleosome-binding) affect local and global chromatin structure and colocalize with cell-specific regulatory sites and regulate cell identity. The role of HMGN proteins in adipocyte function and energy metabolism is yet to be investigated. Here we report that HMGN1 and HMGN2 double knock-out (DKO) mice on chow diet exhibited decreased weight gain (10%) and total activity with increased food intake and energy expenditure compared to control mice. DKO mice on a high-fat diet also displayed increased food intake and decreased weight gain. We have observed that DKO mice possess less fat mass, which is correlated with decreased WAT size, but not BAT. Histological analysis of WAT from mice revealed smaller adipocytes and increased numbers of cells in DKO, while immunofluorescence analysis indicated more UCP1 in DKO, suggestive of increased WAT browning in DKO mice. Investigations on white preadipocytes or MEF cells differentiation by adipogenic cocktail revealed faster differentiation and elevated UCP1 in DKO cells. Time course RNA seq analysis on in-vitro differentiated adipocytes also confirmed enhanced browning in DKO cells. We further investigated the distribution of active histone marks such as H3K9 acetylation and H3K27 acetylation in adipocytes differentiated from preadipocytes. Our time-course ChIP seq analyses indicated that HMGN’s absence altered both H3K9 and H3K27 acetylation patterns in DKO cells compared to WT. Interestingly, correlation analysis of ChIP seq and RNA seq suggests that DKO preadipocytes and adipocytes lost active chromatin marks at certain white adipocyte-specific enhancers.
In summary, loss of HMGN attributes thermogenic character to WAT in DKO mice, thereby contributing to increased energy expenditure, which might protect mice from metabolic disorders—increased white adipocyte browning in DKO is partly by reducing the active histone marks at white specific enhancers, thereby altering white adipocyte identity.

Disclosure
R. Nanduri: None. T. Furusawa: None. A. Lobanov: None. O. Gavrilova: None. M. Bustin: None.

Funding
National Cancer Institute
353-P: Safety and Tolerability of Sodium-Glucose Cotransporter 2 Inhibitors during Ramadan Fasting
Authors: EID ELSAYED M.A. , HUSSEIN ABDELAZIZ , GHAZI HOSSAM A. 
Published: June 2021

Background: Diabetic management during Ramadan fasting is a significant clinical challenge. Sodium glucose co-transporter -2 (SGLT-2) inhibitors are new class of antidiabetic medications known for low frequency of associated hypoglycemia. The present study aimed to evaluate efficacy, safety and tolerability of SGLT-2 inhibitors in diabetic patients practicing Ramadan fasting.
Patients and Methods: The study included 94 patients. They comprised 51 patients who received metformin and sulfonylureas: Glimepiride (1mg-6mg/d) or Gliclazide MR (60-120mg/d) and 43 patients who received SGLT2 inhibitors: Empagliflozin (25 mg), Dapagliflozin (10 mg) or Canagliflozin (300 mg). The study outcome parameters were frequency of hypoglycemia episodes, volume depletion episodes, number of days with early breaking of fasting and missed fasting days.
Results: It was found that patients in SGLTI group experiences significantly fewer symptomatic (9.3 % versus 35.3 %, p=0.003) and documented (7.0 % versus 25.5 %, p=0.017) hypoglycemic episodes as compared to the SU group. However, there were no significant differences between the studied groups regarding the frequency of patients with volume depletion episodes (5.9 % versus 16.3 %, p= 0.1). Moreover, there were no significant differences between groups regarding the frequency of patients with early breaking of fasting (11.8 % versus 9.3 %, p=0.7) or missed fasting (3.9 % versus 2.3 %, p=0.66). None of the studied patients discontinued the prescribed medications.
Conclusions: SGLT-2 inhibitors combined with metformin for diabetic patients during Ramadan fasting are effective, safe and well-tolerated with the advantage of reduced hypoglycemic events.

Disclosure
E. M. A. Eid: None. A. Hussein: None. H. A. Ghazi: None.
355-P: Decreased BCAAs and Elevated Fatty Acids during Repeated Episodes of Hypoglycemia in Individuals with Type 1 Diabetes
Authors: SHE RUI , AL-SARI NABA , SEJLING ANNE-SOPHIE , MATTILA ISMO , HENRIKSEN PETER , PEDERSEN JENS , LEGIDO-QUIGLEY CRISTINA , PEDERSEN-BJERGAARD ULRIK 
Published: June 2021

Hypoglycemia is a major limiting factor in achieving recommended glycemic target for patients in insulin treatment and can indirectly lead to diabetic complications, morbidity and mortality. While counterregulatory hormonal responses have been studied extensively in patients with type 1 diabetes, a more comprehensive assessment of the metabolic responses has not been done previously. This post-hoc study explored potential responses of the metabolome to hypoglycemia. Twenty-one patients with type 1 diabetes were examined using a hypoglycemic clamp at day one, and 24 hours later, at day two. Blood samples were taken during normoglycemia (5.0-6.0 mmol/L) and hypoglycemia (2.0-2.5 mmol/L). Non-targeted plasma metabolomic analyses was conducted using two-dimensional gas chromatography/time-of-flight mass spectroscopy. Metabolites were analyzed by a linear mixed effect model, adjusting for age and sex. P-values were adjusted for multiple testing using the Benjamini-Hochberg method. A total of 79 metabolites were identified. At day one, two amino acids decreased in response to hypoglycemia, leucine (β±SE: -0.78±0.18, p = 0.004) and isoleucine (β±SE: -0.72±0.16, p = 0.002). At day two, five amino acids including all three branched-chained amino acids decreased: Leucine (β±SE: -0.62±0.13, p = 0.002), isoleucine (β±SE: -0.59±0.19, p = 0.026), valine (β±SE: -0.52±0.12, p=0.002), methionine (β±SE: -0.62±0.19, p = 0.026) and phenylalanine (β±SE: -0.65±0.20, p = 0.026). Two fatty acids were elevated, oleic acid (β±SE: 0.50±0.14, p = 0.016) and tetradecanoic acid (β±SE: 0.63±0.17, p = 0.013). No significant changes were observed between the two days.
In conclusion, this study found that the metabolome alternates in response to insulin-induced hypoglycemia resulting in decrement of several amino acids and increment of two fatty acids, contributing to the knowledge of human physiology in individuals with type 1 diabetes.

Disclosure
R. She: None. N. Al-sari: None. A. Sejling: Employee; Self; Novo Nordisk A/S. I. Mattila: None. P. Henriksen: None. J. Pedersen: None. C. Legido-quigley: None. U. Pedersen-bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis, Consultant; Self; Abbott, Speaker’s Bureau; Self; Novo Nordisk A/S.
382-P: Thyroid Hormone Is Associated with Arterial Stiffness in Chinese Patients with Type 2 Diabetes Mellitus
Authors: CHEN YAO , HONG ZHAI , MA BINGWEI , WANG XINGCHUN , QU SHEN 
Published: June 2021

Objectives: Thyroid hormone has effects on cardiovascular system other than metabolism. This study aimed to investigate the association between thyroid hormone and Arterial stiffness (AS) in type 2 diabetes mellitus (T2DM).
Methods: 1064 T2DM patients were included in the cross-sectional study. They were divided into two groups: AS group (baPWV≥1550cm/s) and Non-AS group (baPWV&lt;1550cm/s) or PAD group (ABI≤0.9)or Non-PAD group(ABI&gt;0.9).
Results: 1) FT3, FT4, TT3 and TT4 were comparable (all P&gt;0.05) while TSH were significantly higher in PAD group than Non-PAD group(2.19±1.86μIU/mL vs. 1.85±1.95μIU/mL, P=0.031). FT3 was significantly lower while TSH was significantly higher in AS group than Non-AS group (4.52±0.74 pmol/L vs.4.72±1.45pmol/L, P=0.007; 2.28±2.03μIU/mL vs.1.95±1.38μIU/mL, P=0.009). FT4, TT3 and TT4 had no difference between the two groups. 2) ABI was significantly positively associated with TT3(r=0.091, P=0.006) while baPWV was significantly negatively associated with TT3 and FT3(r=-0.065, P=0.049; r=-0.149, P&lt;0.001). Multiple linear regression showed that FT3 were the negatively influencing factor of baPWV (β=-75.24, P&lt;0.001). 3) baPWV was significantly higher in patients with subclinical hypothyroidism than without subclinical hypothyroidism (1831.11±347.39 cm/s vs.1729.32±377.12, P=0.027). 4) Logistic regression showed that FT3 was protective factor of AS assessed by baPWV (OR:0.708, 95% CI: 0.506-0.990, P=0.044).
Conclusions: T2DM patients with Arterial stiffness defined by ABI or baPWV have higher TSH and lower FT3 while baPWV was higher in patients with subclinical hypothyroidism. FT3 was negatively influencing factor of baPWV and protective factor of AS assessed by baPWV.

Disclosure
Y. Chen: None. Z. Hong: None. B. Ma: None. X. Wang: None. S. Qu: None.

Funding
National Natural Science Foundation of China (81970677)