bluuebunny/crossref_metadata_2025_split huggingface dataset:
1340-P: The Insulin Sensitivity Index Derived from Euglycemic Clamps Is Correlated to Liver Fat Content Determined by Magnetic Resonance Spectroscopy In Type 1 Diabetes
Authors: MERTENS JONATHAN , BRASPENNING RIE , VANHEVEL FLORIS , SPINHOVEN MAARTEN , FRANCQUE SVEN , DE BLOCK CHRISTOPHE 
Published: May 2022

Background: NAFLD is strongly associated with type 2 diabetes. Insulin resistance is proposed as a major contributor. NAFLD is increasingly reported in type 1 diabetes (T1D) , but whether insulin resistance is linked to NAFLD in this population needs elucidation. Furthermore, T1D is an excellent model to investigate insulin resistance in relation to NAFLD without confounding by autologous insulin production.
Aims and Methods: We aimed to assess whether insulin resistance is correlated with liver fat content (LFC) in adults with T1D without causes of secondary liver fat accumulation. A hyperinsulinemic-euglycemic clamp (HEC) was performed according to DeFronzo et al. LFC was measured by magnetic resonance spectroscopy (MRS) and calculated as the mean of three independent regions of interest. NAFLD was diagnosed by LFC &gt; 6.0 % and NAFLD subjects were matched 1:1 to no-NAFLD controls based on age and sex.
Results: 20 subjects with an age of 48 ± 17 y, a BMI of 27.3 ± 4.3 kg/m2, and a HbA1c of 7.3 ± 0.8 % were included. Mean M-index (HEC-derived index of insulin sensitivity) was 5.12 ± 3.03 mg/kg/min. Mean LFC was 15.6 ± 8.3 % (NAFLD) versus 2.8 ± 1.4 % (controls) , p &lt; 0.001. Mean M-index differed significantly (2.88 ± 1.58 [NAFLD] vs. 6.74 ± 2.[controls] mg/kg/min, p &lt; 0.001) . BMI was significantly higher in the NAFLD group (29.6 ± 3.6 vs. 25.1 ± 3.8 kg/m2, p = 0.014) . There was a strong correlation between the M-index and LFC (r = -0.85, p &lt; 0.001) . Linear regression showed a significant association between LFC (dependent) and M-index (B = -1.504, 95% CI: (-2.9to -0.101) , p = 0.037) and BMI (B = 0.879, 95% CI: (0.047 to 1.711) , p = 0.040) but not age or HbA1c level as independent variables.
Conclusion: HEC-derived measures of insulin resistance are strongly correlated to LFC in people with T1D, independently from BMI. These data support the pivotal role of insulin resistance in NAFLD pathophysiology and as a target for NAFLD therapy in T1D.

Disclosure
J.Mertens: None. R.Braspenning: None. F.Vanhevel: None. M.Spinhoven: None. S.Francque: None. C.De block: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk, Research Support; Indigo Diabetes, Speaker’s Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk.
1346-P: Obesity and Type 2 Diabetes in Patients with NAFLD Are Independently Associated with the Risk of Liver Fibrosis, Insulin Resistance, and Atherogenic Dyslipidemia
Authors: MATHEWS APRIL , KALAVALAPALLI SRILAXMI , GODINEZ EDDISON , LOMONACO ROMINA , DILLARD RACHEL E. , GONZALEZ MARIA A. , MARANGI STEPHEN A. , SHETTY SHWETHA S. , SHRESTHA SULAV , MANSOUR LYDIA , CONNELLY MARGERY A. , CHUN KELLY Y. , BARB DIANA , CUSI KENNETH 
Published: May 2022

Obesity (OB) and type 2 diabetes (T2D) are associated with NAFLD and a worse cardiometabolic profile. However, their independent contribution to steatosis, fibrosis, insulin resistance (IR) and atherogenic dyslipidemia are controversial. To this end, we examined the prevalence of NAFLD and hepatic fibrosis in 199 patients (64 with T2D, 135 without T2D) screened from outpatient endocrinology and primary care clinics. NAFLD/fibrosis was assessed by transient elastography (liver fat by controlled attenuation parameter/CAP; fibrosis by liver stiffness measurement/LSM) . Patients were divided into groups either with or without obesity (OB) or T2D. Within each group, patients were well matched for age, BMI, A1c and AST/ALT. The impact of obesity was best observed on the prevalence of steatosis, that increased from pts without OB or T2D (controls = C) to OB/no-T2D (OB) and OB/T2D (C: 40% vs. OB: 64% vs. OB/T2D: 86%, both p&lt;0.vs. C) . The impact of T2D was best observed by the increasing prevalence of liver fibrosis (C: 4% vs. OB: 9% vs. OB/T2D: 25%; p=0.30, 0.01, respectively vs. C) . HOMA-IR (primarily hepatic IR, C: 2.5±0.3 vs. OB: 4.3±0.5 vs. OB/T2D: 6.0±0.6, p&lt;0.vs. C) and adipo-IR (adipose tissue IR, C: 2.8±0.3 vs OB: 4.3±0.6 vs. OB/T2D: 5.4±0.6, p&lt;0.vs. C) followed the worsening impact of OB and T2D. Finally, there was an independent, stepped worsening of HDL-C with obesity and T2D (C: 58±18 vs. OB: 50±vs. OB/T2D: 44±mg/dL; p&lt;0.01) and a worsening trend of TG with T2D (C: 110±78 vs. OB: 110±62; p=0.98, and OB/T2D: 148±79 mg/dL; p&lt;0.vs. C) . LDL-C did not follow this pattern as closely.
In conclusion, obesity and T2D increase the prevalence of NAFLD (more driven by OB) and hepatic fibrosis (more driven by T2D) . This is associated with a continuous worsening of IR and of atherogenic dyslipidemia. The clinical implication is that both factors need to be addressed for the prevention of cirrhosis and of cardiovascular disease in NASH.

Disclosure
A.Mathews: None. L.Mansour: None. M.A.Connelly: Employee; LabCorp. K.Y.Chun: None. D.Barb: None. K.Cusi: Consultant; Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Fractyl Health, Inc., Genentech, Inc., Hanmi Pharm. Co., Ltd., Intercept Pharmaceuticals, Inc., Novo Nordisk. S.Kalavalapalli: None. E.Godinez: None. R.Lomonaco: None. R.E.Dillard: None. M.A.Gonzalez: None. S.A.Marangi: None. S.S.Shetty: None. S.Shrestha: None.

Funding
National Institutes of Health (R01DK120331-01A1 - R01DK120331-02)
1348-P: Roux-en-Y Gastric Bypass Prevents Obesity-Induced Fatty Liver by Modulating Liver Lipocalin Type Prostaglandin D2 Synthase Expression
Authors: SRIVASTAVA ANKITA , STEVENSON MATTHEW , PALAIA THOMAS , HALL CHRIS , LEE JENNY , RAGOLIA LOUIS 
Published: May 2022

The obesity epidemic is associated with an increased prevalence and severity of type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD) . Bariatric surgery has become a widely accepted treatment for individuals with severe obesity and obesity related health problems. Previous studies from our lab have implicated the role of lipocalin-type prostaglandin D2 synthase (L-PGDS) in adipose tissue dysfunction and NAFLD. Our lab has also shown the effect of Roux-en Y gastric bypass (RYGB) on body weight changes, improvement to insulin sensitivity and adipose tissue physiology. In the current study, we examined the effects of L-PGDS using both diet-induced obesity (DIO) and RYGB models. We found reduced expression of L-PGDS in liver of DIO mice after 14 weeks on high fat diet. We then performed RYGB surgery in DIO mice and compared the effects of diets (normal chow and HFD for 6 weeks) on post-operative outcomes of RYGB. Our results show that both surgery and diet contribute to the substantial improvement in liver weight and HOMA-IR. H&E images of liver sections also demonstrate that both diet and surgery play significant roles in reversal of NAFLD. Interestingly, we only found significant increase to liver L-PGDS expression after RYGB when HFD is administered. We conclude that both surgery and diet plays a significant role in modulating the expression of L-PGDS in liver of obese mice. Thus, our study shows that L-PGDS may serve as a novel therapeutic target in treatment of obesity and NAFLD.

Disclosure
A.Srivastava: None. M.Stevenson: None. T.Palaia: None. C.Hall: None. J.Lee: None. L.Ragolia: None.

Funding
American Heart Association: (#15GRNT22420001) and The George Link Foundation
135-OR: Health Care Utilization among Medicare Beneficiaries with Diabetes during the COVID-Pandemic
Authors: ZHOU XILIN , ROLKA DEBORAH B. , ANDES LINDA J. , IMPERATORE GIUSEPPINA 
Published: May 2022

The COVID-pandemic has abruptly impacted health care systems. Using data from Medicare claims we examined the pandemic-related changes in health care utilization among fee-for-service beneficiaries with diabetes. We included persons with diabetes who were aged ≥ 67 and enrolled in both Part A and B programs for all months of the index year and the previous year. Diabetes was identified by having at least one inpatient or two outpatient claims that were diabetes related. We considered utilization by setting (acute inpatient, emergency room, hospital outpatient [HOP], physician office, and ambulatory surgery center [ASC] procedures) and by media (telehealth and in-person) . Utilization was measured as per person use of each type of health care service for each month from Jan. 2018 to Jun. 2021. We quantified the changes in utilization with a fixed-effect model for all post-pandemic months (3/2020-6/2021) and three phases (3/2020-5/2020; 6/2020-12/2020; and 1/2021-6/2021) . We found that health care services usage by setting was 8% to 18% lower than the pre-pandemic level (Table) . Phase 1 had the largest decrease in utilization. In phase 3, utilization was still lower than the pre-pandemic level for most service types, except HOP visits and ASC procedures. We also found a large increase in telehealth visits, although the increase was not large enough to compensate for the decrease in in-person office visits.

Disclosure
X.Zhou: None. D.B.Rolka: None. L.J.Andes: None. G.Imperatore: None.
1353-P: Activation of Brown Adipose Tissue by Low-Protein Diet Ameliorates Hyperglycemia in Lipodystrophic Diabetic Mice Model
Authors: MUNOZ MARCOS D. , ZAMUDIO ALEXA , MCCANN MAXIMILIAN A. , LIEW CHONG WEE 
Published: May 2022

Long-term ad libitum dietary restriction such as low-protein diet (LPD) improves metabolic health and extends the life span of mice and possibly humans. However, most studies conducted thus far have focused on the preventive, but not therapeutic, potential of LPDs. Previously we shown that LPD (5.1% kcal from protein) was able to improve postprandial blood glucose values of the lipodystrophic IRFKO (adipose-specific insulin receptor knockout) mice after 14 days with strong activation of interscapular brown adipose tissue (iBAT) and increase energy expenditure. To determine whether iBAT activation was responsible for the hyperglycemia normalization after the LPD treatment, we surgically denervated iBAT of IRFKO mice before LPD treatment. Blood glucose were measured twice a week for up to 4 weeks, at the end of the monitoring mice were subjected to indirect calorimetry assessment (Promethion, Sable Systems) . Our data showed that surgical denervation of iBAT abolished the hyperglycemia normalization effect of LPD in the IRFKO mice. Morphologically, surgical denervation also prevented the ‘browning’ effect of LPD on the whitening iBAT observed in IRFKO mice. In line with the morphological data, LPD failed to induce thermogenic markers including UCP1 and BMP8b in denervated iBAT. In contrast, iBAT denervation has lesser effects on the LPD-induced energy expenditure and circulating FGF21 level, possibly due to compensation by beige fat formation in the inguinal WAT. Together, our data confirms that hyperglycemia normalization caused by LPD on IRFKO is iBAT activation dependent. Our observation suggests that blood glucose could be utilized to fuel LPD-induced iBAT activation as a mechanism for amino acid homeostasis. Further experimentation needs to be done in order to narrow down the mechanism driving this phenomenon. Taken together, our data suggest that short-term LPD could be a potential strategy for the treatment of metabolic syndrome.

Disclosure
M.D.Munoz: None. A.Zamudio: None. M.A.Mccann: None. C.Liew: None.

Funding
NIH RDK109015A1
1365-P: Intermittent Fasting Modifies Pancreatic Glucosensor Mechanism In Diabetic Mice
Authors: VILCHES-FLORES ALONSO , PADILLA-ROMERO YAZMIN 
Published: May 2022

Background: A specific feature in type-2 diabetes is beta-cell dysfunction, associated to reduction in glucose-stimulated insulin secretion. This function is high-regulated by the glucose sensor mechanism, conformed by GLUT2 and glucokinase, and their expresión is decreased in type-2 diabetes. Intermittent fasting is a recent option in diet control, with alternate cycles of fasting and feeding. In this study we evaluated intermittent fasting in diabetic mice, and its long-term effect in pancreatic GLUT2 and glucokinase expression.
Methods: C57BL6 mice were fed with high fat diet for eight weeks, and then intermittent fasting cycles among four weeks. Weight, total caloric intake, fasting and glucose tolerance were determinated. Changes in insulin and glucokinase expression were evatualed by immunohistochemistry assays. Glucose-stimulated insulin secretion, and PDX1, insulin, GLUT2 and glucokinase mRNAs were analyzed in isolated islets.
Results: Intermittent fasting caused weight loss, reduction in total caloric intake decrease and enhanced glucose tolerance. In diabetic mice, glucose-stimulated insulin secretion was restored after intermittent fasting, without significant changes in hormone content. Treated groups with fasting increased gene expression of PDX1, insulin and GLUT2, but decreased glucokinase mRNA and localization in beta-cells, but enhanced alpha-cell possitive presence.
Conclusion: Intermittent fasting modifies glucosensor mechanism in pancreatic islets from diabetic mice, through GLUT2, PDX1 and insulin expression, but glucokinase. On future studies we will determine changes glucokinase enzymatic activity, and another transcription factors involved in these effects.

Disclosure
A.Vilches-flores: None. Y.Padilla-romero: None.

Funding
UNAM PAPIIT IN225819
137-LB: Unmet Social Needs and Uptake of Recommended Diabetes Processes of Care in a High-Need, High-Cost Medicaid Population
Authors: DURU O. KENRIK , KLOMHAUS ALEXANDRA M. , MANGIONE CAROL , MOIN TANNAZ 
Published: May 2022

Diabetes patients with unmet social needs (e.g., housing instability, food insecurity) may be less able to complete recommended processes of care than patients without these challenges. We examined survey data from a multi-state sample of Medicaid patients with diabetes (n=6,087) identified by UnitedHealthcare as high-cost, high-need based on utilization over the past year, who were enrolled in a comprehensive care coordination intervention by Optum. Before receiving any intervention services, patients reported whether they experienced housing instability, food insecurity, transportation problems, need for help with utilities, or feared for their interpersonal safety at baseline. We used data from administrative claims to measure whether these patients had 4 recommended processes of care completed within the last 18 months: 1) retinal exam, 2) ACE/ARB medication or nephropathy screening, 3) A1c testing, or 4) statin prescription ordered. We examined the cross-sectional association between unmet social needs and processes of care using multivariate logistic regression, controlling for clustering by zip code. The analytic sample was 50% White and 61% female, with 5.6 documented comorbidities on average. Overall, rates of unmet social need varied from 4% for concerns about interpersonal safety to 16% for transportation problems. Only 52% of patients had a retinal exam during the study window, 69% were prescribed a statin, 88% had their A1c checked, and 95% were taking an ACE/ARB medication or had nephropathy screening. In the regression analyses, we did not find statistically significant associations between any of the unmet social needs and the processes of care (all p values &gt;0.05) . In this analysis of high-cost, high-need Medicaid patients, barriers other than unmet social needs may underpin difficulties with achieving recommended processes of care for diabetes, particularly retinal exams and statin use that are completed at lower rates.

Disclosure
O. Duru: None. A. M. Klomhaus: None. C. Mangione: n/a. T. Moin: None.

Funding
Centers for Disease Control and Prevention U18DP006128
137-OR: A Genetic Approach to Detangling the Heterogeneity of Fasting Insulin Levels
Authors: SEVILLA MAGDALENA , GOODARZI MARK O. , DICORPO DANIEL A. , ROTTER JEROME I. , MEIGS JAMES B. , UDLER MIRIAM , MANNING ALISA 
Published: May 2022

Fasting insulin (FI) is a heterogeneous trait with high variability between individuals and populations. Increased FI is associated with an increased risk of type 2 diabetes (T2D) and its complications, including coronary artery disease (CAD) and hypertension (HTN) . We hypothesize that we could use a genetic approach to cluster FI-associated variants, characterize the clusters in terms of insulin processes within the Mexican American Cardiovascular Disease Study (MACAD; N=821) , and test for association of polygenic scores (PS) created from these clusters with T2D, CAD and HTN in three cohorts: Mass General Brigham Biobank (MGBB; N=18,127) , Aspirin in Reducing Events in the Elderly (ASPREE; N=13,349) , and Framingham Heart Study (FHS; N=7,145) . We identified six clusters using a soft clustering approach with 446 FI-increasing genetic alleles and 27 FI-related traits. Associations in two of the clusters, allowed us to characterize them and show their impact on T2D and T2D-associated complications. The first cluster had alleles associated with increased subcutaneous and visceral adiposity and was characterized by reduced insulin sensitivity (from euglycemic clamp; P=0.02) , increased insulin secretion (from oral glucose tolerance test [OGTT]; P=0.04) , and increased insulin clearance (from euglycemic clamp; P=0.02) in MACAD. This cluster’s PS was associated with HTN (MGBB Odds ratio (OR) = 1.04, P=0.013) , T2D (MGBB OR = 1.04, P =0.001) and CAD (MGB OR=1.07, P =0.008; ASPREE OR=1.04, P =0.036) The second cluster had alleles associated with a lipodystrophy phenotype and was characterized by increased insulin secretion (from OGTT P =0.019) in MACAD. We observed associations of the PS with T2D (MGBB OR= 1.13, P =2.3x10-10) and HTN (MGBB OR = 1.06, P =0.001) which were replicated in ASPREE and FHS. Our results suggest the presence of two different FI-associated genetic domains and elucidate the deleterious mechanisms by which increased FI is associated with T2D and T2D complications.

Disclosure
M.Sevilla: None. M.O.Goodarzi: None. D.A.Dicorpo: None. J.I.Rotter: None. J.B.Meigs: Consultant; Quest Diagnostics. M.Udler: None. A.Manning: None.

Funding
UM1DK078616
1373-P: Changes in Body Composition Are Associated with Improvement of ß-Cell Function and Insulin Sensitivity after Short-Term Intensive Insulin Therapy in Patients with Newly Diagnosed Type 2 Diabetes
Authors: XU CHANGLIU , LI YANBING , LIU LIEHUA 
Published: May 2022

Objective: To investigate the change of muscle strength and body composition during short-term intensive insulin therapy (SIIT) and their association with treatment effects in patients with newly diagnosed type 2 diabetes (T2DM) .
Research Design and Method: Patients with newly diagnosed T2DM were treated with SIIT to normalized blood glucose for at least 1 week. Physical examination including measurement of body diameters (neck circumference, upper arm circumference, waist circumference, hip circumference, thigh circumference, and calf circumference) , muscle strength (grip strength, the five-repetition sit-to-stand test, and the 30-second sit-to-stand test) , and body composition (body fat mass, muscle mass) , were performed. HbA1c and standardized mixed meal challenge tests were performed before and after the therapy.
Results: A total of 53 patients were included. After SIIT, the muscle strength of the lower limbs was significantly enhanced. The average time of the five-repetition sit-to-stand test was shortened from 7.24s±1.58s to 6.15±1.21 (P&lt;0.001) , and the average number of the 30-second sit-to-stand test increased from 24.23±5.56 to 27.69±5.96 (P&lt;0.001) . The HOMA-IR and β-cell function also improved after SIIT. And the baseline thigh circumference was correlated with the change of both HOMA-IR (rs=-0.296 P=0.035) and the insulinogenic index (IGI) (rs=0.373 P=0.006) after SIIT. The fat mass at baseline was also correlated with improvements in both HOMA-IR (rs=-0.368 P=0.021) and the IGI (rs=0.424 P=0.007) after therapy.
Conclusion: The muscle strength of the lower limbs was promoted after SIIT. Improvements in β-cell function and insulin sensitivity after SIIT in newly diagnosed T2DM patients are associated with changes in body composition but there are no relations with muscle strength.

Disclosure
C.Xu: None. Y.Li: None. L.Liu: None.

Funding
the National Natural Science Fund of China (81800716) , the science and technology program of Guangzhou, (202002020053)
1378-P: Chronic Sleep Deprivation Impaired Bone Formation in Growing Rats and Downregulated PI3K/AKT Signaling in Bone Tissues
Authors: DUAN XIAOYE , GUO LIXIN 
Published: May 2022

Background: Sleep deprivation (SD) , recognized as a public health epidemic, impaired glucose metabolism, yet little is known about the association between sleep and bone health.
Methods: Twenty 5-week-old male Wistar rats and randomly divided into the CSD and normal control (NC) groups after one-week acclimatization. After a 6-week intervention of sleep deprivation, the distal femurs of both groups were harvested for micro-computed tomography scans and histological analysis. Meanwhile, the femur tissues were measured the mRNA and protein expression via RNA sequencing and immunohistochemical analysis. Serum bone turnover markers were evaluated at 0, 2, 4, and 6 weeks.
Result: CSD impaired the bone growth, showing an imbalance of bone turnover status, dysphasia in the metaphysis growth plate, and deterioration of bone microarchitecture. Further, CSD suppressed bone formation, showing that the expression of osteogenesis-related proteins (col1α1 and osteocalcin) and mRNA (igf1, bglap, runx2, col1α1, pth1r) are down-regulated. Differentially expressed genes were detected, and functional enrichment analyses revealed that the PI3K/AKT pathway was significantly down-regulated in the CSD group. While Diabetic cardiomyopathy, Oxidative phosphorylation, and Neurodegenerative disease-related pathways were up-regulated.
Conclusion: These results suggest that CSD can significantly impaired bone health, and it may exert these effects in part by suppressing bone formation and osteoblast differentiation, and inactivating the PI3K/AKT signaling pathway.

Disclosure
X.Duan: None. L.Guo: None.

Funding
National Natural Science Foundation of China (Grant No. 81670763 and 81471050)