bluuebunny/crossref_metadata_2025_split huggingface dataset:
170-OR: Hypothalamic Gliosis Predicts Decline in Insulin Sensitivity over One Year in People with Obesity
Authors: ROSENBAUM JENNIFER L. , SCHOEN STEFAN , MELHORN SUSAN J. , LEON MARY ROSALYNN DE , WEBB MARY , UTZSCHNEIDER KRISTINA , SCHUR ELLEN 
Published: June 2021

Studies demonstrate evidence of gliosis in the mediobasal hypothalamus (MBH) of people with obesity and T2D or impaired glucose tolerance (IGT), but whether MBH gliosis predicts worsening glucose homeostasis is unknown.
The study evaluated 38 subjects with obesity (68% female, 76% White). Mean age was 47±11 y and BMI was 35±3.9 kg/m2. MRI, DXA, and 75 g OGTT were performed at baseline and DXA and OGTT repeated at 1y. Mean bilateral T2 relaxation time (ms) in the MBH and 3 control regions was measured as a marker of gliosis. Serial blood samples from OGTT were used to calculate glucose area under the curve (incremental [iAUC] and total [totalAUC]) and to model insulin sensitivity (OGIS) and beta-cell function (beta-cell glucose sensitivity). Generalized estimating equations tested associations and interactions by region.
On average, measures of glucose tolerance (iAUC and totalAUC), OGIS, and beta-cell glucose sensitivity were stable over 1 y. Baseline bilateral mean MBH T2 relaxation time was not associated with changes in glucose tolerance (Δ iAUC β: -5.8 ms, 95% CI -21.0, 9.4, P=0.45; Δ totalAUC β: 1.3 ms, 95% CI -33.5, 36.0, P=0.94, adjusted for sex, age) or change in glucose sensitivity (β: 0.3 ms, 95% CI -1.0, 1.6, P=0.66) nor were interactions present. Change in OGIS over 1y was significantly negatively associated with bilateral mean MBH T2 relaxation time at baseline (β: -0.94 ms, 95% CI -1.7, -0.2, P=0.02, adjusted for sex, age); subjects with longer MBH T2 relaxation times at baseline reduced OGIS over 1 y. A formal interaction by region was not significant (chi2(7)=7.11, Pint=0.42). The relationship within the MBH was attenuated when also adjusted for change in fat mass (β: -0.70 ms 95% CI -1.4, 0.02, P=0.056).
Subjects with greater radiologic evidence for MBH gliosis exhibited declines in insulin sensitivity over 1 y which were not fully accounted for by changes in adiposity. These longitudinal findings are consistent with a role for MBH gliosis in T2D pathogenesis in people with obesity.

Disclosure
J. L. Rosenbaum: None. S. Schoen: None. S. J. Melhorn: None. M. De leon: None. M. Webb: None. K. Utzschneider: None. E. Schur: None.

Funding
American Diabetes Association (1-17-ICTS-085 to E.S.)
172-OR: Perinatal Exposure to a Western Diet Alters Hypothalamic Gene Expression and Predisposes to Diabetes in Adult Male Mice
Authors: ELGAZZAZ MONA , LAZARTIGUES ERIC D. , MAUVAIS-JARVIS FRANCK 
Published: June 2021

Cardiometabolic diseases are among the most prevalent diseases worldwide. Maternal epigenetic imprinting affects gene expression in offspring, leading to increased disease susceptibility later in life. We showed previously that perinatal exposure to high fat diet (HFD) leads to obesity, fasting hyperglycemia, glucose intolerance, elevated heart rate and hypertension, exclusively in male mice. Here, we hypothesize that epigenetic maternal programming alters gene expression in the hypothalamus to promote the cardiometabolic disturbances seen in male offspring. To investigate this, C57BL6/J dams were fed a HFD or regular diet (RD) for 1 month and mated with RD-fed males. All offspring were maintained on RD after weaning. At 3 months of age, hypothalami from programmed (HFD-RD) and control (RD-RD) offspring were harvested for mRNA sequencing (Illumina NextSeq). Results show 11 differentially expressed genes (DEG) in HFD-RD males in comparison to RD-RD males. Using iPathway analysis, some of the DEGs were involved in insulin secretion and synaptic vesicle cycle pathways. Among the DEG, Snap25, coding a protein of the exocytosis machinery important for neurotransmitters, and insulin release was upregulated (p= 2.31E-06). Additionally, Nnat gene, involved in appetite suppression and regulation of synaptic plasticity in the hypothalamus, as well as insulin secretion was downregulated (p= 0.04955). MiRNA6236 (p= 2.28E-09) and Rn45s (p= 0.002), whose deficiency in islets is known to be associated with prediabetes in mice, were both downregulated in programmed males. Interestingly, with exception of Nnat gene downregulation (p= 0.001), all the male DEGs were unaltered in HFD-RD females compared to RD-RD females.
In conclusion, perinatal exposure to HFD programs sex-specific alterations in gene expression in the hypothalamus, possibly impairing the central metabolic regulation and predisposing to type 2 diabetes.

Disclosure
M. Elgazzaz: None. E. D. Lazartigues: None. F. Mauvais-jarvis: None.

Funding
American Diabetes Association (1-19-IBS-291 to E.D.L.); U.S. Department of Veterans Affairs (BX004294)
179-LB: Association of Leptin and Adiponectin with the Incidence of Type 2 Diabetes Independent of Visceral Adiposity and Liver Fat
Authors: SHIBATA IZUMI , SHIBATA MIKIKO , SATO KYOKO K. , UEHARA SHINICHIRO , NISHIDA NORIMITSU , OKAMURA KAORI , YUYAMA YOSHIHIKO , KOH HIDEO , HIKITA YONEZO , FUJIMOTO WILFRED Y. , BOYKO EDWARD J. , HAYASHI TOMOSHIGE 
Published: June 2021

Leptin and adiponectin are two major adipocytokines reported to be associated with type 2 diabetes. However, it is unknown whether their associations with the risk of incident type 2 diabetes are independent of visceral adiposity and liver fat in a prospective cohort study. We included 787 Japanese men aged 28 to 77 years without type 2 diabetes at baseline. The subjects were classified into four groups based on leptin-adiponectin profile at baseline, with the median concentration value as the cut-off point (median levels of leptin and adiponectin were 4.8 ng/dL and 5.7 µg/mL, respectively): low-high, low-low, high-high, and high-low group. Visceral fat was measured by computed tomography (CT) as intra-abdominal fat area at the umbilicus level. Liver fat was assessed by liver-to-spleen attenuation ratio measured by CT. Type 2 diabetes was diagnosed as fasting plasma glucose level ≥126 mg/dL, HbA1c ≥6.5%, or taking oral hypoglycemic medications or insulin. Cox proportional hazard models were used to estimate hazard ratios (HR) for developing type 2 diabetes. During 5215 person-years of follow-up, 72 subjects developed type 2 diabetes. Incidence rates of type 2 diabetes per 1000 person-years were 3.2, 9.2, 18.6, and 26.1 for the low-high, low-low, high-high, and high-low group, respectively. After adjustment for age, smoking status, alcohol consumption, regular physical activity, family history of diabetes, visceral fat, and liver fat, multiple-adjusted HRs (95% CI) of incident type 2 diabetes were 1.87 (0.63-5.50), 2.90 (1.02-8.21), and 3.41 (1.23-9.47) for the low-low, high-high, and high-low group compared with the low-high group. In conclusion, leptin and adiponectin were associated with incident type 2 diabetes independent of both visceral fat and liver fat.

Disclosure
I. Shibata: None. W. Y. Fujimoto: None. E. J. Boyko: None. T. Hayashi: None. M. Shibata: None. K. K. Sato: None. S. Uehara: None. N. Nishida: None. K. Okamura: None. Y. Yuyama: None. H. Koh: None. Y. Hikita: None.
186-LB: T1D Exchange Registry: Current Insights on Participant Outcomes
Authors: LEON CAROLINA , LIU JINGWEN , RAVELSON JULIA , CHAPMAN KATHERINE S.M. , HUGHES ALLYSON , WOLF WENDY 
Published: June 2021

The T1D Exchange Registry was launched June of 2019 to increase participation in research and probe a diverse set of topics impacting the type 1 diabetes (T1D) population. The Registry is an online platform that recruits adults and parents/guardians of children with T1D who live in the U.S. Participants complete screening questions, sign informed consent, and answer an initial questionnaire regarding health and diabetes management. Subsequently, participants complete an annual questionnaire to track changes in diabetes management and outcomes. As of March 2021, the Registry encompasses 7630 participants who have completed their initial questionnaire and 1063 who have completed their one-year annual questionnaire. This report focuses on the cohort of participants who have completed their annual questionnaire. These participants reported an average age of 45.2 years, ranging from 4 to 85.7 years, and an average T1D duration of 25.8 years. This cohort is more technology-oriented than other reported cohorts, with 88.8% of participants using a CGM (an increase from 82.5% at their time of enrollment) and 78.6% using an insulin pump (an increase from 74.7% at their time of enrollment). Additionally, 58.2% carry a glucagon kit and 11.2% use medications other than insulin to lower blood sugar. At the time of the initial questionnaire the cohort reported an average A1c of 7.2 and subsequently 6.8 at the one-year questionnaire. However, 15.0% reported experiencing severe hypoglycemia, defined as a change in mental and/or physical functioning and needing help from another person, while 6.7% reported diabetes-related ketoacidosis (DKA) symptoms over the last 12 months. This subset of Registry participants who are highly engaged, heavy technology users, and meet target A1cs, still report severe hypoglycemia and DKA symptoms, suggesting that there is potential for improvement in diabetes management and care.

Disclosure
C. Leon: None. J. Liu: None. J. Ravelson: None. K. S. M. Chapman: None. A. Hughes: None. W. Wolf: None.
187-OR: Advanced Glycation End Products Predict Loss of Renal Function and High-Risk Chronic Kidney Disease in Type 2 Diabetes in the ACCORD Trial
Authors: KOSKA JURAJ , GERSTEIN HERTZEL C. , BEISSWENGER PAUL J. , REAVEN PETER 
Published: June 2021

Individual advanced glycation end products (AGEs) have been implicated in the development of chronic kidney disease (CKD). We evaluated the prognostic utility of a comprehensive multicomponent AGE panel in predicting long-term renal function loss and CKD when added to routine clinical measures in persons with type 2 diabetes (T2D) followed for 12.5 years (including risk factor intervention and observation phases). The five key AGEs (carboxymethyl and carboxyethyl lysine, and methylglyoxal, 3-deoxyglucosone and glyoxal hydroimidazolone) were measured via LC-MS/MS in baseline serum from 1,151 the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants. A composite AGE score was calculated as the mean of individual AGE z-scores. Outcomes were (1) renal function loss (≥40% decline in estimated glomerular filtration rate [eGFR]), (2) macroalbuminuria (MAU), and (3) high-risk CKD (hrCKD, KDIGO classification). Higher AGE score predicted greater risks of renal function loss (n=260 events, hazard ratio 1.49 [95%CI 1.24-1.79], p&lt;0.0001), MAU (n=96, 1.45 [1.06-1.98], p=0.005) and hrCKD (n=128, 1.95 [1.47-2.57], p&lt;0.0001), independent of baseline eGFR, urine albumin:creatinine, randomization arms, other standard risk factors and hemoglobin A1c. Higher AGE score predicted renal function loss even in those with normal renal function (1.40 [1.06-1.84], p=0.02). When added to routine risk factors, AGE score improved net-reclassification and integrated discrimination for renal function loss (by 19% and 17%, p=0.002) and hrCKD (by 34% and 4.9%; p=0.02), but not MAU (0.8% and 1.3%, p=0.6). There is a strong independent association between AGE burden and progression of CKD in T2D. Adding AGE measures to standard clinical parameters improves the prediction of multiple kidney outcomes, indicating its potential as prognostic biomarker of diabetes nephropathy.

Disclosure
J. Koska: None. H. C. Gerstein: Advisory Panel; Self; Novo Nordisk Inc., Pfizer Inc., Sanofi, Consultant; Self; Abbott, Covance Inc., Eli Lilly and Company, Kowa Company, Ltd., Sanofi, Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., DKSH, Eli Lilly and Company, Sanofi, Zuellig, Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. P. J. Beisswenger: Stock/Shareholder; Self; PreventAGE Healthcare LLC. P. Reaven: Research Support; Self; AstraZeneca, Dexcom, Inc.

Funding
National Institutes of Health (R21HL150268)
191-LB: Impact of Subsistence and Genetics on Lipid Profiles in Ethnically Diverse Africans
Authors: MA RONG , HANSEN MATTHEW , RANCIARO ALESSIA , THOMPSON SIMON R. , BEGGS WILLIAM , MPOLOKA SUNUNGUKO W. , MOKONE GAONYADIWE G. , NYAMBO THOMAS B. , MICHAILIDIS GEORGE , LI HONGZHE , BURANT CHARLES , TISHKOFF SARAH A. 
Published: June 2021

African Americans are at higher risk for cardiometabolic disease relative to individuals with European ancestry. Yet, populations with African ancestry are greatly under-represented in human genomics studies. To alleviate this bias and better distinguish the roles of genetics and environment on cardiometabolic traits, we conducted targeted metabolomics to measure levels of &gt;700 lipids in 718 Africans and integrated with genomic data from &gt;7M single nucleotide polymorphisms genotyped in the same individuals. These individuals are from 14 ethnic groups from diverse regions of Africa (Botswana, Cameroon, Ethiopia, Tanzania) and with diverse subsistence patterns (agriculturalists, pastoralists, hunter-gatherers). In contrast to US populations, most individuals were sampled from rural areas with relatively homogenous diets and, thus, we could better quantify lipids typically found at low levels in US individuals. Furthermore, several groups have similar genetic ancestry but distinct diets, and vice versa, enabling us to distinguish the role of genetic ancestry and environment on lipid variation. We identified 305 independent genetic variants associated with 103 lipid species, &gt;50 of which have not previously been reported in similar studies of European/US populations (e.g. at ROCK2, ARHGEF28, DHODH, ALDH1A2). We observe correlations between subsistence and lipid profiles but show that genetic ancestry also plays an important role in variation within and between populations. For example, Eastern African pastoralists with a diet rich in milk and blood have relatively high levels of di-and tri-glycerides, but within each lipid class, levels are influenced by genotype. The Fulani pastoralists from Cameroon, with a high incidence of hypertension and diabetes but low BMI, also have relatively high levels of triglycerides, suggesting diet is predominantly influencing lipid levels and that genetic factors unrelated to lipid metabolism are influencing risk for disease in that population.

Disclosure
R. Ma: None. H. Li: Consultant; Self; Eli Lilly and Company. C. Burant: None. S. A. Tishkoff: None. M. Hansen: None. A. Ranciaro: None. S. R. Thompson: None. W. Beggs: None. S. W. Mpoloka: None. G. G. Mokone: None. T. B. Nyambo: None. G. Michailidis: None.

Funding
American Diabetes Association (1-19-VSN-02 to S.A.T.); National Institutes of Health (GM134957-01)
195-OR: A Comparison of Inpatient Glycemic Control Using Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Injections in Persons with Type 1 Diabetes
Authors: YE YUTING , IZARD STEPHANIE , MYERS ALYSON 
Published: June 2021

Background: Continuous subcutaneous insulin infusion (CSII) therapy is increasingly being used in the outpatient setting, but there is little known information about its efficacy in the inpatient setting. This study compares inpatient glycemic control of persons with type 1 diabetes (T1D) using CSII, multiple daily injections (MDI), or both.
Method: This retrospective chart review assessed the glycemic control of adult patients with T1D who used CSII, MDI or a combination of both during their hospitalization between January 1, 2017 and December 31, 2019. Those who were pregnant and/or treated with continuous intravenous insulin infusion were excluded. Variables were summarized descriptively using means and frequencies. Continuous variables were compared across groups using the ANOVA or Kruskal-Wallis test, and categorical variables were compared using the Fisher’s Exact test.
Results: We analyzed records of 65 patients who were mostly male (53.8%) and white (72%) with a mean age of 51.7 ± 16.0 years. The mean hemoglobin A1c was 7.80 ± 1.08%. Though not statistically significant, both mean blood glucose and proportion of hyperglycemic events (proportion of blood glucose measures &gt; 300 mg/dL) were lowest in the CSII group. Mean blood glucose for CSII, MDI, and both was 172.88 ± 40.14, 195.40 ± 43.90, and 199.50 ± 49.99 mg/dL, respectively (p=0.17). The proportion of hyperglycemic events for CSII, MDI, and both was found to be 0.11 ± 0.11, 0.26 ± 0.20, and 0.27 ± 0.27, respectively (overall p=0.0267, pairwise comparisons not significant).
Conclusion: Glycemic control of patients with CSII is not significantly different than patients with MDI or a combination of both in persons with T1D, thus suggesting that patients can remain on CSII therapy while inpatient.

Disclosure
Y. Ye: None. S. Izard: None. A. Myers: None.
196-OR: Digital Insulin Therapy Protocol in the Postoperative Period of Coronary Artery Bypass Graft Surgery: A Prospective Randomized Study
Authors: CAMARA DE SOUZA ALEXANDRE B. , TOYOSHIMA MARCOS T. 
Published: June 2021

Introduction: Adequate glycemic control with intravenous insulin therapy in the postoperative period of coronary artery bypass grafting (CABG) in an intensive care unit (ICU) reduces unfavorable clinical outcomes, such as mortality, acute kidney injury (AKI), arrhythmias and nosocomial infection. After discharge from ICU, even still hospitalized, adherence to consensus on inpatient insulin therapy is low, and about 50% of patients do not receive adequate subcutaneous insulin therapy in the ward, consequently in-hospital hyperglycemia (IH) is frequent. Medical apps are increasingly facilitating the medical routine. InsulinAPP is a digital protocol for inpatient glycemic management and already validated. A 16% reduction in blood glucose (BG) has been demonstrated in clinical patients with this protocol.
Method: Prospective randomized trial was performed on diabetic patients in CABG postoperative period, after discharge from ICU. The groups were randomized according to the glycemic control protocol: InsulinAPP group (APP) or protocol defined by the assistant team (ST - standard group). The aim is to compare the groups regarding the composite outcome of AKI, nosocomial infection and atrial fibrillation.
Results: A total of 41 patients were evaluated (15 in APP and 26 in ST). There was no difference between APP vs. ST group in age (65.1±9.8 vs. 65.1±9.8 years), female gender (40 vs. 46%), body mass index (28.5±4.9 vs. 27.3±5.1 Kg/m2) and estimated glomerular function (68.0±24.1 vs. 69.1±24.5 mL/min, respectively). APP had better BG than ST group (162±28.6 mg/dL vs. 183±34.4 mg/dL, respectively; p = 0.036). Besides, in APP there was a significant reduction of the composite outcome (27% vs. 77%, p=0.002), infection (20% vs. 61%, p&lt;0.001) and AKI (13% vs. 50%, p=0.019).
Conclusion: The InsulinAPP protocol was more effective in glycemic control and in reducing unfavorable outcomes in the postoperative period of cardiac surgery after discharge from the ICU.

Disclosure
A. B. Camara de souza: None. M. T. Toyoshima: None.
198-OR: The Stimulatory Effect of Glucagon on Insulin Secretion Is Glucose Dependent in Healthy Human Subjects
Authors: GRAY SARAH M. , ZHANG GUO-FANG , BENNETT WILLIAM , TONG JENNY , CAMPBELL JONATHAN , D’ALESSIO DAVID A. 
Published: June 2021

Glucagon is generally considered to be a counter-regulatory hormone with a primary role to raise blood glucose concentrations by increasing endogenous glucose production (EGP). However, recent preclinical findings support a paracrine action of glucagon to act directly on pancreatic beta cells to promote nutrient-stimulated insulin secretion. In mice, the divergent actions of glucagon are dependent on glycemic status: during fasting glucagon acts predominantly at the liver to raise blood glucose, whereas in the fed state when glycemia is elevated, the insulinotropic effects predominate to lower glucose. These mechanistic findings have not been extended to human physiology. Therefore, we designed a study to test the hypothesis that in healthy humans glucagon actions are also dependent on ambient glycemia. Subjects received glucagon (100 ng/kg) during fasting euglyemia or experimental hyperglycemia (~150 mg/dl) on separate days. On both days, glycemia was maintained for 60 min prior to a glucagon infusion for an additional 60 min. Blood glucose was monitored at bedside and plasma samples were analyzed for C-peptide and di-deuterated glucose enrichment to calculate HGP. During fasting euglycemia, blood glucose was 85 mg/dl and glucagon elicited an increase to a 60 minute average of 132 mg/dl with a peak at ~156 mg/dl at the end of the infusion. Concordant with increased glycemia was an immediate increase in HGP (1.8x) and a delayed increase in C-peptide AUC (1.5x). For the hyperglycemia studies, blood glucose was maintained at 150 mg/dl before and during glucagon administration. Here, glucagon caused a rapid and robust increase in C-peptide AUC (4x) and a more gradual increase in HGP (2x). This glycemic-dependent behavior of glucagon suggests a physiologic role to promote prandial insulin secretion in healthy subjects. This raises the possibility that this incretin function of glucagon plays a role in β-cell function in diabetic subjects.

Disclosure
S. M. Gray: None. G. Zhang: None. W. Bennett: None. J. Tong: None. J. Campbell: None. D. A. D’alessio: Advisory Panel; Self; Eli Lilly and Company, Sun Pharmaceutical Industries Ltd., Research Support; Self; Eli Lilly and Company, Merck & Co., Inc.

Funding
National Institutes of Health (F32DK121420, R01DK101991)
21-LB: Development and Validation of the Barriers and Supports Evaluation for Working-Age Adults with Type 1 Diabetes
Authors: COX ELIZABETH D. , PLANALP ELIZABETH M. , KLIEMS HARALD , PALTA MARI , LECAIRE TAMARA J. , CHEWNING BETTY A. 
Published: June 2021

Objective: To optimize type 1 diabetes (T1D) self-management, experts recommend tailoring care to meet people’s needs and preferences. To facilitate this tailoring, we developed and validated the Barriers and Supports Evaluation (BASES) tool to identify working-age adults’ T1D self-management barriers and supports.
Methods: Participants were 25-64 year old adults with T1D recruited from clinics and a community-based registry. Guided by Social Cognitive Theory, content analysis of 33 semi-structured interviews was used to create a comprehensive item pool of 136 items, further refined to 70 candidate items on a 5-point Likert scale through cognitive interviewing and pilot testing. To develop and validate the tool, exploratory and confirmatory factor analyses were applied to 392 participants’ survey responses to the candidate barrier and support items. Additional survey data included demographics and the Diabetes-Specific Quality of Life Scale-Revised. To evaluate concurrent validity, A1c values from medical records and quality of life (QoL) scores were regressed on domain scores.
Results: Factor analyses yielded 5 domains with a total of 30 items: (1) Cognitive Processes, (2) Costs and Insurance, (3) Learning Opportunities, (4) Family and Friend Support, and (5) Diabetes Provider Interactions. Models exhibited good to adequate fit, with Comparative Fit Index (CFI)&gt;0.88 and Root Mean Squared Error of Approximation (RMSEA)&lt;0.06. All domains demonstrated significant associations with A1c and QoL in the expected direction, with the exception of the Family and Friend Support domain. The Cognitive Processes domain exhibited the strongest associations with both A1c (β=0.7; 0.4-0.9) and QoL (β=-19; -21 to -17).
Conclusions: The BASES tool is brief, patient-centered, and demonstrates construct and concurrent validity. The tool could be used in clinical practice to tailor diabetes support and education to individual’s needs, improving effectiveness of services.

Disclosure
E. D. Cox: None. E. M. Planalp: None. H. Kliems: None. M. Palta: n/a. T. J. Lecaire: None. B. A. Chewning: None.

Funding
American Diabetes Association (1-18-ICTS-026 to E.D.C.)