bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host Genetic Background and Gut Microbiota Contribute to Differential Metabolic Responses to High Fructose Consumption in Mice
Authors: AHN IN SOOK , LANG JENNIFER , YING ZHE , BYUN HYAE RAN , ZHANG GUANGLIN , OLSON CHRISTINE , HSAIO ELAINE , LUSIS ALDONS , GOMEZ-PINILLA FERNANDO , YANG XIA 
Published: June 2018

Both host genotypes and gut microbiota play a role in dietary responses and the control of host phenotypes. High fructose consumption has been strongly implicated in metabolic disorders including obesity, insulin resistance and diabetes, but individual variability in susceptibility has not been examined in diverse genetic backgrounds. We investigated the strain-specific response to fructose in terms of the shifts in gut microbiota as well as host phenotypes related to body mass, glycemic traits, and glucose intolerance using three mouse strains, C57BL/6 (B6), DBA, and FVB. After treatment with 8% fructose water for 12 weeks, the DBA mice demonstrated increased body weight, adiposity, plasma insulin, and glucose intolerance, whereas B6 and FVB mice were resistant to fructose-induced metabolic alterations. We also conducted 16S rRNA-sequencing analysis of gut microbiota and found that DBA had higher Firmicutes/Bacteriodetes ratio and lower basal levels of Turicibacter, Akkermansia, and S24-7_g compared to B6 and FVB. These microbes were correlated with body weight, adiposity, or glucose tolerance. To test the influence of gut microbiota on metabolic phenotypes, we performed fecal transplant by administering the B6 fecal content to DBA mice and vice versa. DBA mice with B6 fecal transplant stayed glucose tolerant and lean with fructose treatment, suggesting that B6 microbes attenuated fructose response in DBA mice. Our findings suggest that fructose induces strain-specific metabolic and microbiota responses, and gut microbiota are partially responsible for fructose sensitivity among mice with different genetic backgrounds.

Disclosure
I. Ahn: None. J. Lang: None. Z. Ying: None. H. Byun: None. G. Zhang: None. C. Olson: None. E. Hsaio: None. A. Lusis: None. F. Gomez-Pinilla: None. X. Yang: None.
Weight-Centric Management of Type 2 Diabetes Mellitus
Authors: MANDEL LINDSAY , SHUKLA ALPANA , KUMAR REKHA , WAITMAN JONATHAN , ARONNE LOUIS 
Published: June 2018

Background: Obesity and type 2 diabetes mellitus (T2DM) are inextricably linked. Obesity is the pathophysiologic driver of T2DM, and as such, the treatment of obesity can improve glycemic control. Although there is some data from phase 3 trials of anti-obesity pharmacotherapy in patients with T2DM, there is currently a paucity of data related to the weight-centric management of T2DM in clinical practice. Data from clinical trials of these medications suggests that weight loss outcomes in patients with T2DM are inferior, likely due to the weight gain promoting effects of concomitant antidiabetic therapies.
Methods: In a retrospective study, electronic medical records of 359 consecutive new patients seen at the Weill Cornell Comprehensive Weight Control Center from 4/1/14-4/1/15 were reviewed and data related to demographics, medications, weight, and HbA1c was recorded.
Results: 48 of 359 patients had T2DM. Baseline age and BMI were 56.2±10.6 years and 39.5±7.6 kg/m2 in patients with T2DM and 48±14.7 years and 35.6±6.8 kg/m2 in patients without T2DM; 54.2% and 70.7% were female, respectively. Management strategies in patients with T2DM included the addition and dose escalation of metformin, GLP-1 agonists, and SGLT2 inhibitors, discontinuation of sulfonylureas and TZDs, and dose reduction of insulin when possible. 56.3% of patients with T2DM were started on anti-obesity pharmacotherapy including lorcaserin, phentermine, topiramate and bupropion. At 12 months, weight loss was 8.9±7.8% in patients with T2DM and 8.6±7.7% in those without T2DM. In patients with T2DM, HbA1c was 7.1±1.1% at initial visit and 6.7±1.3% at 12 months.
Conclusions: In this review, weight loss outcomes were similar in patients with and without T2DM. We show that by using a weight-centric approach to diabetes management, patients can achieve glycemic control with concomitant weight loss.

Disclosure
L. Mandel: None. A. Shukla: None. R. Kumar: Speaker's Bureau; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc.. J. Waitman: None. L. Aronne: Board Member; Self; Myos Corporation, Jamieson Wellness. Consultant; Self; Aspire Bariatrics, Eisai Inc., Novo Nordisk Inc.. Research Support; Self; Pfizer Inc.. Consultant; Self; Takeda Pharmaceuticals U.S.A., Inc.. Research Support; Self; Zafgen. Other Relationship; Self; BMIQ, Gelesis, ERX Pharmaceuticals, Inc.. Research Support; Self; AstraZeneca. Consultant; Self; Sanofi, Janssen Pharmaceuticals, Inc., UnitedHealth Group.
The Common Food Additive Carrageenan Increases Intestinal Permeability without Affecting Whole-Body Insulin Sensitivity in Humans—Results from a Randomized, Double-Blind Crossover Study
Authors: WAGNER ROBERT , BÜTTNER JANINE , HENI MARTIN , FRITSCHE LOUISE , KULLMANN STEPHANIE , WAGMÜLLER MORITZ , PETER ANDREAS , PREISSL HUBERT , MACHANN JUERGEN , PAPE ULRICH-FRANK , VAN HALL GERRIT , PLOMGAARD PETER , KLEIN REINHILD , FRITSCHE ANDREAS , HAERING HANS-ULRICH , STEFAN NORBERT 
Published: June 2018

It is not known whether food additives associated with western lifestyle, such as the widely used carrageenan, also play a role in the pathogenesis of diabetes. Animal data suggest that increased carrageenan consumption causes insulin resistance and diabetes, mainly by interfering with hepatic insulin signaling. This is the first trial in humans that tested whether carrageenan added to the diet affects key metabolic traits.
We conducted a randomized, double-blind, placebo-controlled, cross-over trial (registered as NCT02629705). Healthy males (N=20) were randomly allocated to 14 days of carrageenan (250 mg twice daily) or matching placebo. After a washout-period of 30±7 days, they received the other compound. At the end of each treatment phase, participants underwent an oral glucose tolerance test (OGTT), a hyperinsulinemic-euglycemic clamp with labeled glucose, whole-body MR-tomography and 1H-MR-spectroscopy, blood immune cell phenotyping and a lactulose-mannitol test for investigating intestinal permeability.
Participants had a mean (±SD) age of 27.6±4.8 years and a BMI of 24.4±2.6 kg/m2. Intestinal permeability significantly increased after carrageenan vs. placebo exposure (lactulose-mannitol-ratio 0.0196 vs. 0.015, p=0.03). Whole-body insulin sensitivity index (ISI) did not differ between placebo and carrageenan exposure (p=0.5 for both ISIclamp and ISIOGTT). No changes of hepatic fat content, body fat mass, distribution, liver transaminases and inflammatory cytokines were observed (all p&gt;0.4).
In young healthy males, short-term carrageenan intake resulted in increased gut permeability. This was not accompanied by changes of whole-body insulin sensitivity, body fat mass, distribution and liver fat content. Further investigations of hepatic and brain insulin sensitivity, immune phenotyping will reveal whether carrageenan intake affected these variables.

Disclosure
R. Wagner: None. J. Büttner: None. M. Heni: Research Support; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Novo Nordisk Inc.. L. Fritsche: None. S. Kullmann: None. M. Wagmüller: None. A. Peter: None. H. Preissl: None. J. Machann: None. U. Pape: None. G. van Hall: None. P. Plomgaard: None. R. Klein: None. A. Fritsche: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH, Novo Nordisk A/S, Eli Lilly and Company, Boehringer Ingelheim GmbH. H. Haering: None. N. Stefan: Consultant; Self; Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca, OmniaMed Ltd..
Neighborhood Walkability and Diabetes-Related Complications
Authors: SHAH REEMA , LUO JIN , GERSTEIN HERTZEL C. , BOOTH GILLIAN 
Published: June 2018

Neighborhoods that are more conducive to walking are associated with increased levels of physical activity and lower levels of obesity and diabetes, but the effect of neighborhood walkability on the clinical course of patients with diabetes is not known. We conducted a retrospective cohort study in 439,392 adults using population-based administrative health databases to evaluate the effect of neighborhood walkability on the incidence of diabetes related complications. Adults (≥30 years) with diabetes living in Southern Ontario cities were followed from April 1 2007 to March 31 2017. Neighborhood walkability was derived from a validated index and classified into quintiles from lowest (Q1) to highest (Q5). Cox proportional hazards models were used to estimate the hazard of neighborhood walkability on retinopathy (laser photocoagulation/vitrectomy/VEGF therapy), nephropathy (dialysis or kidney transplantation), foot complications (infection/amputation), and avoidable hospitalizations (hyper/hypoglycemia), adjusting for age, sex, ethnicity, income, and comorbid conditions, as well as significant interactions between these and walkability. Overall, baseline characteristics were similar across neighborhoods, however, low walkability areas tended to be wealthier than high walkability areas. The cohort sustained 30457 retinopathy events, 4883 nephropathy events, 40989 foot complications, and 24272 avoidable hospitalizations. There was an increased risk of retinopathy (Q1:Q5 adjusted HR 1.13, 95% CI 1.07-1.19, p&lt;0.001), nephropathy (Q1:Q5 aHR 1.33, 95% CI 1.16-1.52, p&lt;0.001), foot complications (Q1:Q5 aHR 1.27, 95% CI 1.18-1.37, p&lt;0.001), and avoidable hospitalizations (Q1:Q5 aHR 1.49, 95% CI 1.36-1.64, p&lt;0.001) in lower walkability compared to higher walkability neighborhoods. Neighborhood design may have beneficial effects on diabetes complications. This has important implications for policies to promote healthy environments to better manage the burden of chronic metabolic diseases.

Disclosure
R. Shah: None. J. Luo: None. H.C. Gerstein: Research Support; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Sanofi. Advisory Panel; Self; Sanofi. Other Relationship; Self; Sanofi. Advisory Panel; Self; Merck & Co., Inc.. Research Support; Self; Merck & Co., Inc.. Other Relationship; Self; Merck & Co., Inc.. Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Other Relationship; Self; AstraZeneca. Advisory Panel; Self; Novo Nordisk Inc.. Other Relationship; Self; Novo Nordisk Inc.. Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc.. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. G. Booth: None.
Prevalence of Diagnosed Diabetes and Total Diabetes among Asian Americans, 2011–2014
Authors: CHENG YILING J. , KANAYA ALKA M. , SAYDAH SHARON , ARANETA MARIA ROSARIO , KAHN HENRY S. , IMPERATORE GIUSEPPINA 
Published: June 2018

Asian Americans (AAs) comprise ∼6% of the U.S. population. However, there is little national information on the prevalence of diabetes (DM) among AAs. In addition, there are no national estimates of DM prevalence according to AA ancestral subgroups. Among sampled AA adults (age ≥20 years) we estimated the population prevalence of DM for all AAs and major geographic AA ancestral subgroups using data from the U.S. National Health and Nutrition Examination Survey 2011-2014. DM status was categorized as diagnosed (DiagDM), undiagnosed (UndiagDM; no DiagDM but HbA1c ≥6.5% or fasting plasma glucose ≥126mg/dl or 2-hour plasma glucose ≥200 mg/dl), or nondiabetic. We defined 4 AA ancestral subgroups as East AA (Chinese, Japanese, and Korean), South AA (Indian, Pakistani, Sri Lankan, Bangladeshi, Nepali, and Bhutanese), Southeast AA (Filipino, Vietnamese, Cambodian, Laotian, Thai, Indonesian, Malaysian, Singaporean, and Hmong), and other AA. Age-sex adjusted prevalences and prevalence ratios were computed for the 4 AA subgroups, as well as for non-Hispanic whites, non-Hispanic blacks, and Mexican Americans (Table). Compared to non-Hispanic whites, East AAs had a similar prevalence of DiagDM but higher UndiagDM. The elevated prevalence of UndiagDM among AAs suggests the relatively low awareness of their condition and reinforces the importance of diabetes screening in these populations.
Table.Age-sex adjusted prevalence of diabetes and prevalence ratio, NHANES 2011-2014Race/ethnicityn (weighted N, million)Prevalence (%, 95% CI)Prevalence Ratio (95% CI)DiagDMUndiagDMTotalDMDiagDMUndiagDMTotalDMNon-Hispanic AA1517 (12.5)11.2 (9.0, 13.5)9.3 (6.9, 11.8)20.6 (17.4, 23.7)1.4 (1.1, 3.9)2.6 (1.8, 9.0)1.8 (1.5, 2.2)East AA594 (4.8)7.2 (4.0, 10.4)8.8 (5.1, 12.6)16.0 (10.7, 21.3)0.9 (0.6, 1.4)2.5 (1.5, 4.1)1.4 (1.0, 2.0)South AA345 (2.9)15.4 (9.6, 21.2)9.4 (4.9, 13.9)24.8 (17.5, 32.2)2.0 (1.4, 2.8)2.7 (1.5, 4.5)2.2 (1.6, 6.7)Southeast AA414 (3.5)14.1 (11.0, 17.3)9.2 (5.5, 12.9)23.3 (18.4, 28.2)1.8 (1.4, 2.3)2.6 (1.7, 3.9)2.0 (1.6, 2.6)Other AA164 (1.3)9.8 (4.6, 15.0)8.7 (1.9, 15.5)18.5 (11.8, 25.2)1.2 (0.7, 2.1)2.4 (1.1, 5.5)1.6 (1.1, 2.4)Non-Hispanic W4472 (148.4)7.9 (6.9, 8.8)3.6 (2.6, 4.5)11.5 (10.1, 12.8)1.0 (Ref.)1.0 (Ref.)1.0 (Ref.)Non-Hispanic B2594 (25.5)14.6 (13.3, 16.0)6.2 (4.4, 7.9)20.8 (18.4, 23.2)1.9 (1.6, 2.2)1.7 (1.2, 2.6)1.8 (1.5, 2.2)Mexican Am1296 (18.9)14.8 (12.4, 17.2)8.3 (6.4, 10.2)23.1 (19.8, 26.5)1.9 (1.6, 2.3)2.3 (1.7, 3.2)2.0 (1.7, 2.4)AA: Asian American; Non-Hispanic W: Non-Hispanic white; Non-Hispanic B: Non-Hispanic black; Mexican Am: Mexican American

Disclosure
Y.J. Cheng: None. A.M. Kanaya: None. S. Saydah: None. M. Araneta: None. H.S. Kahn: None. G. Imperatore: None.
Subclinical Microvascular Lesions among Normoglycemic and Prediabetic Subjects—The PROP-ABC Study
Authors: UMEKWE NKIRU A. , OWEI IBIYE , DAGOGO-JACK SAMUEL 
Published: June 2018

Background: We investigated the occurrence of microvascular lesions in nondiabetic offspring of parents with T2DM enrolled in the PROP-ABC (Pathobiology and Reversibility of Prediabetes in A Biracial Cohort)* study.
Design and Methods: We assessed albumin:creatinine ratio (MCR), vibration perception threshold (Vibratron II, Physitemp Instruments Inc, Clifton, NJ) and nonmydriatric retinal images (Zeiss digital camera, Carl Zeiss Meditec AG, Jena, Germany).
Results: There were 223 subjects (117 black, 106 white; 70% female), of whom 122 had prediabetes (impaired fasting glucose or impaired glucose tolerance) and 101 had normal glucose regulation (NGR; FPG &lt;100 mg/dl and 2hrPG&lt;140 mg/dl). The mean (± SD) age was 53.3 ± 9.1 years. Retinal lesions were found in 24 subjects (10.8% of the cohort), comprising macular changes (n=9), optic disc changes (n=8), epiretinal membrane (n=6), diabetic retinopathy (n=4), and vitreous opacities (n=2). The frequency of any retinal lesion was 12.3% vs. 8.9% among prediabetic vs. NGR subjects. The mean MCR was 9.95±2.1 ug/g among subjects with normal retina vs. 16.6 ±9.89ug/g among those with retinal lesions. There was a strong correlation between albuminuria and presence of retinal lesions (r=0.42, P&lt;0.0001). The index finger vibration amplitude was 0.56 ±0.31 microns in prediabetic subjects vs. 0.43±0.25 microns in NGT subjects (P=0.013).
Conclusions: We here demonstrate a significant association between albuminuria and diverse retinal lesions in a biracial cohort of nondiabetic subjects, and further show relative impairment of vibration perception in prediabetic subjects (NCT02027571).

Disclosure
N.A. Umekwe: None. I. Owei: None. S. Dagogo-Jack: None.
CMHX008, a Novel Thiazolidinedione-Like PPARγ Partial Agonist, Enhances Insulin Sensitivity with Minor Influences on Bone Loss
Authors: XIAO XIAOQIU , HOU YI , CAO XUEMEI , LI JIAYU 
Published: June 2018

Objective: Traditional thiazolidinediones (TZDs), rosiglitazone for instance, are peroxisome proliferator-activated receptor γ (PPARγ) potent agonists and can treat type 2 diabetes but carry unwanted effects including increased risk for fracture. Here we compared insulin-sensitizing efficacies and bone-loss side effects of CMHX008, a novel TZDs-like PPARγ partial agonist, with rosiglitazone.
Methods: TR-FRET PPARγ competitive binding assay was used to compare the binding affinity between CMHX0and rosiglitazone. High fat diet fed and ob/ob mice were administered with vehicle, CMHX0or rosiglitazone. Bone marrow mesenchymal stem cells (BMMSCs) were used to examine differences in differentiation into osteoblasts after treated with CMHX0and rosiglitazone.
Results: TR-FRET showed lower affinity to PPARγ by CMHX0compared with rosiglitazone. Mice treated with CMHX0for 16 weeks had the comparable effect of insulin sensitization as rosiglitazone, which was related to significant inhibition on PPARγ Ser 273 phosphorylation and improved insulin sensitivity by facilitating phosphorylation insulin receptor and AKT in adipose tissues. Micro-CT and histomorphometric analyses demonstrated that the degree of trabecular bone loss after treated with CMHX0was weaker than rosiglitazone as evidence by consistent changes in BV/TV, Tb.N, Tb.Th, Tb.Sp, and mineral apposition rate. BMMSCs treated with CMHX0showed higher ALP activity and mRNA levels of bone formation markers than those treated by rosiglitazone in osteoblast differentiation test.
Conclusion: PPARγ sparing eliminates the skeletal side effects of TZDs while maintaining their insulin-sensitizing properties. CMHX0shared the comparable insulin-sensitizing effects as rosiglitazone with lower risk of bone loss.

Disclosure
X. Xiao: None. Y. Hou: None. X. Cao: None. J. Li: None.
Intestinal Epigenetic Reprogramming Relates to Glycemic Improvement after Roux-en-Y Gastric Bypass Surgery
Authors: STEFATER MARGARET A. , PANCIOTTI COURTNEY , FELDMAN HENRY A. , GOURASH WILLIAM F. , SHIRLEY ELEANOR , COURCOULAS ANITA , STYLOPOULOS NICHOLAS 
Published: June 2018

Despite the remarkable, early remission of T2D after RYGB, the surgery’s key mechanisms have yet to be defined in a way that can be translated to less invasive therapies. Recently, we demonstrated that improved glucose homeostasis after RYGB in rodents is associated with intestinal metabolic reprogramming: the Roux Limb (RL) exhibits dramatic morphologic and metabolic remodeling, leading to augmented utilization of metabolic fuels to support the increased bioenergetic demand. To address whether this phenomenon is important for T2D remission in human patients after RYGB, RL biopsies were obtained at the time of surgery and at 1 and 6 months postoperatively. Differentially expressed genes (DEG) were determined using Affymetrix HTA 2.0 microarrays; morphology was examined via electron microscopy, revealing a significant increase in microvillus length over time (P&lt;0.01). Enrichment analysis showed robust changes cellular proliferation, cell cycle regulation, and cytoskeletal remodeling pathways at both timepoints. DEG suggest a metabolic shift away from fatty acid oxidation, toward utilization of glucose and amino acids. Common DEG (FDR&lt;0.05) at 1 and 6 months were strongly correlated (R2=0.899, P&lt;0.0001), suggesting that RL signatures are established early and persist. Interestingly, 91% of the top 100 DEG at 6 months were downregulated; GSEA revealed significant enrichment of genes regulating epigenetic reprogramming (P&lt;0.01), e.g., DNMT1 and DNMT3B at 1 and 6 months. Remarkably, change in DNMT1 expression at 1 month, controlling for baseline body weight, predicted 6-month HbA1c change (R2=0.744, P=0.002). This suggests a mechanistic role for methylation to underlie glycemic improvement, and points to a potential predictive role for early RL DEG. We hypothesize that post-RYGB T2D improvement may relate to RL remodeling including increased energy utilization, and that the stimulus may be epigenetic reprogramming as a result of altered intestinal nutrient flow.

Disclosure
M.A. Stefater: None. C. Panciotti: None. H.A. Feldman: None. W.F. Gourash: Research Support; Self; Coviden, Ethicon US, LLC., National Institute of Diabetes and Digestive and Kidney Diseases. E. Shirley: None. A. Courcoulas: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, National Institutes of Health, Coviden. N. Stylopoulos: None.
IDegAsp Improves Glycemic Control with Minimal Hypoglycemia—An Indian Real-World Study in T2D Subjects
Authors: KESAVADEV JOTHYDEV , SABOO BANSHI D. , SHANKAR ARUN , DAVID ASHWIN , WARRIER ROHIT , KRISHNAN GOPIKA , RAMACHANDRAN LAKSHMY , JOTHYDEV SUNITHA 
Published: June 2018

Background: IDegAsp is the first insulin co-formulation constituting 70% insulin degludec and 30% insulin aspart. In contrast to conventional premix analogues, degludec component of IDegAsp lowers variability, fasting glucose with comparable glycemic control and fewer hypoglycemic events. Re-suspension errors inherent to premix analogues also does not occur with IDegAsp. In routine diabetes practice, patients have customised A1c goals depending on the associated comorbidities and risk factors.
Aim: To assess the safety and efficacy of IDegAsp in Indian T2D subjects in a real-world setting.
Methods: T2D initiated on IDegAsp and on regular follow-up were de-identified from EMR. Clinical outcomes and hypoglycemic events were captured. n= 152, age= 52.9±11.9y, diabetes duration= 11.5±13.8y, 78.57% males, treatment duration= 10.3±6.5mths.
Results: 92% of the patients achieved customised A1c targets.Reduction from baseline: 0.91% in A1c(p=0.0004), 41.4 mg/dL in FBS(p&lt;0.0001), 0.80 kg in body weight(p=0.0083).Five hypoglycemic episodes were reported (none severe). There were no reported episodes of nocturnal hypos.
Conclusion: In this real-world study involving T2D subjects in India, IDegAsp improved HbA1c and FBS significantly,with less hypoglycemia and no weight gain. Some of these outcomes are contrary to those reported in clinical trials and could have resulted from the new combination oral therapies.

Disclosure
J. Kesavadev: Advisory Panel; Self; Novo Nordisk India Private Limited. Speaker's Bureau; Self; Novo Nordisk India Private Limited. Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; MSD. Speaker's Bureau; Self; MSD. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. B.D. Saboo: None. A. Shankar: None. A. David: None. R. Warrier: None. G. Krishnan: None. L. Ramachandran: None. S. Jothydev: None.