bluuebunny/crossref_metadata_2025 huggingface dataset:
164-OR: Efficacy of New-Onset Type 1 Diabetes (T1D) Intervention Trials: Variation in 1-Year Outcomes
Authors: HALLER MICHAEL J. , GRECO MADISON N. , SCHATZ DESMOND , ATKINSON MARK A. , BRUSKO TODD M. , MATHEWS CLAYTON E. , JACOBSEN LAURA M. , HEROLD KEVAN C. , GITELMAN STEPHEN E. , KRISCHER JEFFREY , BUNDY BRIAN N.
Published: June 2019

Mean 2-hour area under the curve (AUC) C-peptide levels at 1 year remain the primary endpoint for most intervention trials in subjects with new onset T1D. Comparisons of efficacy across T1D intervention trials with positive outcomes remain limited. We performed a cross-trial comparison of the NIH TrialNet sponsored new-onset rituximab, abatacept, low-dose anti-thymocyte globulin (ATG) (2.5mg/kg), and ATG/GCSF trials and the NIH ITN sponsored high-dose ATG (6.5mg/kg), alefacept, and teplizumab trials. One-year study group mean AUC C-peptides were adjusted for baseline C-peptide and age and compared to their internal control to retain individual study effects. To further compare differences in AUC C-peptide across trials, rituximab was used as a reference and percent increase compared to rituximab effect was calculated. Using this methodology, low-dose ATG (164%) and teplizumab (171%) provided for the largest relative improvements in AUC C-peptide. Percent effects over rituximab of the other studies were: high-dose ATG (-43%), alefacept (33%), abatacept (37%) and ATG/GCSF (45%). Despite the limitations of meta-like analyses and the notable differences in control group AUC C-peptides, these data strongly support the notion that low-dose ATG and teplizumab provide for the greatest relative preservation of AUC C-peptide amongst recently completed new onset T1D interventions.

Disclosure

M.J. Haller: Advisory Panel; Self; Pancreum, SAB Biotherapeutics. M.N. Greco: None. D. Schatz: None. M.A. Atkinson: None. T.M. Brusko: Advisory Panel; Self; Caladrius Biosciences, Inc. Board Member; Self; OneVax, LLC. L.M. Jacobsen: None. K.C. Herold: Consultant; Self; Provention Bio, Roche Pharma. S.E. Gitelman: Advisory Panel; Self; Avortes, Intermountain Therapeutics, Lilly Diabetes, Tolerion, Inc. Research Support; Self; Caladrius Biosciences, Inc., Janssen Research & Development. Other Relationship; Self; Novo Nordisk Inc. J. Krischer: None. B.N. Bundy: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust; National Institutes of Health; JDRF; Sanofi; Amgen Inc.; McJunkin Family Charitable Foundation
1642-P: Glucose Control among Diabetes Cases Selected from a Representative National Survey in Brazil
Authors: DOS REIS RODRIGO C.P. , DUNCAN BRUCE B. , SCHMIDT MARIA I.
Published: June 2019

Background: A target of an HbA1c <7% is frequently the cornerstone of clinical guidelines for the care of diabetes globally. Yet, nationally representative NHANES surveys indicate that only 50 to 60% of those with diabetes meet this target. Our aim was to evaluate glucose control when assessed by HbA1c in a national sample of Brazilian adults with diabetes.

Methods: A sub-sample of adults (18 years or older) of the representative Brazilian National Health Survey (2014-2015) was randomly selected for the collection of biological samples. Of these, 8952 (52%) individuals provided samples, and 8541 (50%) have HbA1c results. HbA1c was measured at a NDPG-certified central laboratory. Diabetes was defined by self-report of a physician diagnosis. Given the complex sampling used to select participants and the response rate obtained, we used the rake method of post-stratification survey weights, calculated according to sex, age, and education, to estimate national rates.

Results: Among the 8541 adults, 573 (5.87%; 95% CI: 5.41%-6.33%) reported having received a previous diagnosis of diabetes outside of pregnancy. Of these, only 55.2% (51.1%-59.4%) had HbA1c less than 7%, and 69.5% (65.7%-73.4%) less than the more flexible HbA1c target of 8%. On the other hand, 19.8% (16.5%-23.1%) had HbA1c ≥9.0%, indicating very poor glucose control. Though small sample size limited statistical testing, we found no differences across socio-demographic characteristics except for educational achievement, those of lesser education more frequently presenting worse glucose control (p=0.004).

Conclusion: Our results, showing a glucose control similar to that observed in representative U.S. surveys, highlight the large fraction of cases with very poor control. New strategies are needed to improve glucose control in the entire population of persons living with diabetes.

Disclosure

R.C.P. dos Reis: None. B.B. Duncan: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company. M.I. Schmidt: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company.
1651-P: Diabetes Incidence among Medicare Beneficiaries, 2001-2014
Authors: ANDES LINDA J. , LI YANFENG , SRINIVASAN MEERA , ROLKA DEBORAH B. , GREGG EDWARD
Published: June 2019

Diabetes mellitus affects more than 12% of the U.S. adult population and has doubled in prevalence between 1990 and 2010. Older adults are particularly affected by the increasing prevalence, which doubles roughly every decade of life and then peaks in the mid-60s at more than 25%. However, there was no change in prevalence or incidence nationally between 2009 and 2012 based on data from the National Health Interview Survey. Increasing prevalence rates are due in part to a higher incidence among adults aged 65 and older. However, these estimates are based on survey research with relatively small numbers of geriatric adults. Administrative data sets built from Medicare claims contain millions of cases, affording an opportunity to explore both trends over time and heterogeneity within the geriatric population. Although most older adults in the U.S. are enrolled in Medicare, claims are only available for those beneficiaries who are enrolled in Fee-for-Service (FFS or Parts A and B). Because beneficiaries can switch between FFS and Medicare Advantage plans, the criteria for identifying prevalent and incident cases of diabetes in FFS claims must be defined carefully. To ensure we had all claims for our study population, we included the 50.4 million Medicare FFS beneficiaries (mean age 68.9 y) who were enrolled for all 60 months of each five-year window centered on index years 2001-2014. We identified prevalent cases as those with either one inpatient or two outpatient diabetes claims within two years. Incident cases were required to have a two year “clean” period with no diabetes diagnostic code. The overall national prevalence of diabetes among Medicare FFS beneficiaries increased from 23.3% in 2001 to a high of 32.2% in 2012, and then remained level through 2014. The overall incidence rate increased from 3.4% in 2001 to a high of 4.1% in 2006-7, then decreased to 3.2% in 2014. Diabetes prevalence and incidence varied considerably across states and were higher among blacks, Hispanics and Asians than among whites.

Disclosure

L.J. Andes: None. Y. Li: None. M. Srinivasan: None. D.B. Rolka: None. E. Gregg: None.
1664-P: Does “Healthy Diabetes” Exist? Long-Term Survival in Diabetes Heart Study Participants
Authors: BOWDEN DONALD W. , XU JIANZHAO , FREEDMAN BARRY I. , PALMER NICHOLETTE , HSU FANG-CHI
Published: June 2019

The Diabetes Heart Study, initiated in 1997, includes examination and follow-up of 1221 European Americans, 85% with type 2 diabetes (T2D). Baseline examination included extensive medical history, laboratory measures, and CT-imaging for coronary artery calcium (CAC). Through 2016, 451 participants had died. CVD-attributable deaths occurred over an age range of 39-93 years. In high-risk participants with T2D and CAC>1000, 52% died after mean 14.9 year follow-up; however, many are still alive. 64% of surviving T2D participants lived with diabetes for >20 years and 16.4% (31 male, 46 female) >30 years. Among deceased individuals, the average duration of diabetes was 20.8 years. Comparing long-term T2D-survivors to deceased, difference in CAC, a powerful predictor of mortality, was not significant (P=0.85) with mean CAC in survivors (male=4730, female=1147) and deceased (male=4085, female=1220). Conventional clinical measures did not differ significantly (glucose, HbA1c, BP; P>0.05) or were modestly different (cholesterol P=0.033; LDL P=0.035). There was a difference in the use of statins at baseline: 53% in survivors, 41% in deceased (P=0.05) and C-reactive protein (P=0.04). The strongest individual trait difference was in duration of T2D at baseline (P<0.0001) but mean T2D-duration at baseline in survivors was 20 vs. 12.5 years in deceased). Thus, a significant number of individuals with T2D have long-term survival even in the presence of a significant burden of subclinical CVD, but conventional clinical measures provide little Insight. Research into the characteristics of long-term survivors with T2D may prove beneficial to all T2D patients.

Disclosure

D.W. Bowden: None. J. Xu: None. B.I. Freedman: Consultant; Self; AstraZeneca, Ionis Pharmaceuticals, Inc. N. Palmer: None. F. Hsu: None.

Funding

National Institutes of Health
1669-P: Proinsulin: C-Peptide Ratios in Relatives of Persons with Type 1 Diabetes
Authors: TRIOLO TAYLOR M. , PYLE LAURA , SELIGOVA SONA , YU LIPING , SIMMONS KIMBER , GOTTLIEB PETER , EVANS-MOLINA CARMELLA , STECK ANDREA
Published: June 2019

Biomarkers are needed to characterize heterogeneity within populations at risk for type 1 diabetes (T1D). The ratio of proinsulin to C-peptide (PI:C ratio), a biomarker of beta cell dysfunction, has been associated with progression to T1D, but relationships between PI:C ratios and autoantibody (Ab) type and number have not been explored. We sought to characterize PI:C ratios in multiple islet Ab positive, single Ab positive and Ab negative relatives of individuals with T1D.

We measured PI:C ratios and Abs with both electrochemiluminescence (ECL) assays (ECL-IAA, ECL-GADA and ECL-IA2)and radio-binding (RBA) assays (mIAA, GADA, IA2A and ZnT8A) in 98 relatives of persons with T1D followed in the Pathway to Prevention Study at the Barbara Davis Center. Of these subjects, 31 were multiple Ab positive, 37 were single Ab positive and 22 were Ab negative at the most recent visit. Eight subjects progressed to T1D over a mean follow-up of 5.5±3.6 years. In cross-sectional analyses, there were no significant differences in PI:C ratios between T1D and/or multiple Ab positive subjects (4.16±4.06) compared to single Ab positive subjects (4.08±4.34) and negative Ab subjects (3.72±3.78) (p=0.92) overall or after adjusting for age, sex and BMI. Higher PI:C ratios were associated with ECL-IA2A (p=0.03) and ECL-IAA (p=0.03) levels, but not with mIAA, GADA, ECL-GADA, IA2A nor ZnT8A levels. In mixed-effects longitudinal models, the trajectories of PI:C ratio over time were not significantly different between the 4 groups, overall or after adjusting for sex, age, and BMI.

In conclusion, higher PI:C ratios were associated with ECL-IAA and ECL-IA2A levels, which have previously been associated with progression to T1D.

Disclosure

T.M. Triolo: None. L. Pyle: None. S. Seligova: None. L. Yu: None. K. Simmons: None. P. Gottlieb: Consultant; Self; Bristol-Myers Squibb Company, Eli Lilly and Company, Kamada, Tolerion, Inc. Research Support; Self; Intrexon, Janssen Pharmaceuticals, Inc., Mercia/NovaImmune, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc. Stock/Shareholder; Self; IM Therapeutics. Other Relationship; Self; Viacyte, Inc. C. Evans-Molina: None. A. Steck: None.

Funding

American Diabetes Association (1-14-CD-17 to A.S.)
168-LB: Burden of Cardiovascular Comorbidity in U.S. Adults with T1D
Authors: EDELMAN STEVEN V. , ZHOU FANG L. , PREBLICK RON , VERMA SUMIT , PARANJAPE SACHIN A. , DAVIES MICHAEL J. , JOISH VIJAY N.
Published: June 2019

Around 75% of adults with T1D do not achieve glycemic control, putting them at risk of macrovascular complications. This observational study evaluated prevalence of CVD and cardiovascular risk factors (CVRF) in T1D and the economic impact on U.S. payers. Adults with T1D were identified using previously published criteria and a large health plan claims dataset. Descriptive and multivariate analyses were performed to compare economic outcomes between those with/without CVD/CVRF. A total of 12687 adults with T1D met the study criteria; prevalence of CVD and CVRF were 23% and 42%, respectively. Patients with CVD/CVRF had significantly (P<0.05) greater healthcare utilization compared with those without CVD/CVRF. Percentage of hospitalized patients (CVD: 11%; CVRF: 27%; none: 8%) and mean number of outpatient physician visits (CVD: 8.1±7.6; CVRF: 5.0±5.1; none: 3.5±3.6) were higher among CVD comorbid patients vs. those without comorbidity. Significantly higher overall costs, as well as higher inpatient, outpatient, ED, and prescription costs, were observed for the CVD and CVRF cohorts vs. the No CVD/CVRF cohort (Figure). The results were consistent for all-cause and diabetes-related parameters after adjusting for confounding factors. Over 1 in 5 adults with T1D have CVD and 2 in 5 have a CVRF, with higher healthcare expenditures vs. those without. Better management of CVD in T1D could significantly reduce the economic burden and improve patient outcomes.

Disclosure

S.V. Edelman: Advisory Panel; Self; BrightSight, InPen, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Board Member; Self; Senseonics. Speaker’s Bureau; Self; AstraZeneca, Lilly Diabetes, MannKind Corporation, Merck Foundation, Sanofi-Aventis. F.L. Zhou: Employee; Spouse/Partner; Lexicon Pharmaceuticals, Inc. Employee; Self; Sanofi. Stock/Shareholder; Spouse/Partner; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Sanofi. R. Preblick: Employee; Self; Sanofi-Aventis. S. Verma: None. S.A. Paranjape: Employee; Self; Sanofi US. M.J. Davies: Employee; Self; Lexicon Pharmaceuticals, Inc. V.N. Joish: Employee; Self; Lexicon Pharmaceuticals, Inc.

Funding

Sanofi US
1683-P: Analysis of Type 1 Diabetes Genetic Risk Score Shows 1 in 8 People with Clinically Diagnosed Adult-Onset T1D Are Misdiagnosed, and Presenting Features at Diagnosis Do Not Identify Those Misdiagnosed
Authors: PATEL KASHYAP A. , THOMAS NICHOLAS , WEEDON MICHAEL N. , WALKEY HELEN C. , KAUR AKAAL , WILLIAMS ALISTAIR J. , MISRA SHIVANI , OLIVER NICK , JOHNSTON DESMOND G. , HATTERSLEY ANDREW T. ,   ADDRESS-2 CONSORTIUM
Published: June 2019

Aims: Accurate initial diagnosis of adult-onset type 1 diabetes (T1D) is important. We aimed to estimate the rate of misdiagnosis in clinically-diagnosed adult T1D. We also assessed the utility of Islet autoantibodies and presenting features to identify misdiagnosed-T1D.

Methods: We used a T1D-genetic risk score (T1D-GRS) to estimate misdiagnosed-T1D in 1112 white-Europeans adults clinically-diagnosed with T1D (age diagnosis >18y) from the ADDRESS-2 study. We used 1924 gold-standard T2D as a non-T1D control. All patients were recruited <6m from diagnosis and insulin treated. We assessed clinical features and autoantibodies (GADA, IA-2A, ZNT8A) in misdiagnosed and true-T1D.

Results: People with one (n=309), two (n=285) or three (n=300) autoantibodies had a similar T1D-GRS suggesting people with ≥1 antibody positive had true-T1D (mean GRS 0.270 vs. 0.269 vs. 0.273, p=0.13). People without antibody had T1D-GRS (0.243, n=218) between true-T1D (0.271, n=894, ≥1ab+ve) and T2D (0.229, n=1924, p<0.0001) suggesting presence of non-T1D in antibody negative group. The estimated proportion of non-T1D in antibody negative group was 67% (n=146/218) which was 13% of the whole cohort (95% CI 11-15%). Misdiagnosis was higher in people diagnosed 30-75y (21%) vs. 18-30y (6%, p<0.001). Misdiagnosed-T1D and true-T1D had similar rates of polyuria (91% vs. 95%), weight loss (85% vs. 88%) and DKA (38% vs. 43%) (all p>0.05). Misdiagnosed-T1D were more likely to be male (81% vs. 59%), older (40y vs. 32y), had higher BMI (28 vs. 24) and HbA1c (105 vs. 91 mmol/mol) compared to true-T1D (all p<0.001).

Conclusion: Initial misdiagnosis of T1D is common in people diagnosed >30y (21%). When clinically-diagnosed with T1D at diagnosis, negative islet autoantibodies but not severe hyperglycaemia/DKA identify misdiagnosed people.

Disclosure

K.A. Patel: None. N. Thomas: None. M.N. Weedon: None. H.C. Walkey: None. A. Kaur: None. A.J. Williams: None. S. Misra: None. N. Oliver: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Self; Dexcom, Inc., Sanofi. D.G. Johnston: None. A.T. Hattersley: None.

Funding

Diabetes UK; JDRF; Diabetes Research & Wellness Foundation
169-LB: A Randomized Encouragement Trial to Increase Mail Order Pharmacy Use and Medication Adherence
Authors: SCHMITTDIEL JULIE , TRINACTY CONNIE M. , WHARAM J. FRANK , DURU O. KENRIK , NEUGEBAUER ROMAIN , BROWN SUSAN D. , ROSS-DEGNAN DENNIS , KARTER ANDREW J. , DYER WENDY T. , RAMACHANDRAN BHARATHI
Published: June 2019

Medication non-adherence is a major contributor to poor diabetes outcomes. Observational studies show positive associations between mail order pharmacy (MOP) use and adherence, and suggest that mail order is cost-saving to patients. However, no prospective trials have examined the effect of encouraging MOP use on medication adherence. We conducted a randomized encouragement trial in 2017 in three health plans: Kaiser Permanente (KP) Northern California, KP Hawaii, and Harvard Pilgrim Health Care (HPHC). Patients were eligible if they had diabetes, poor adherence (Proportion of Days Covered <80%) to at least one class of cardiometabolic medications, and had not used MOP in the prior 12 months. Patients were randomized to receive either no intervention (controls) or outreach encouraging MOP use consisting of a mailed letter, secure email message, and automated telephone call outlining the potential benefits of MOP use for diabetes patients; HPHC intervention patients received the letter only. We compared the percentages of patients in both arms that began using mail order and that became adherent to cardiometabolic medication classes during the 12-month follow-up. A total of 63,012 patients were included: mean age was 60; 45% were female; 41% were non-Hispanic white; 12% were black; 25% were Hispanic/Latino, and 22% were Asian/Native Hawaiian/Pacific Islander. During follow-up, 12% of intervention patients used the mail order pharmacy vs. 10% of controls (p<.001); the percent of cardiometabolic medications delivered via mail was 42% vs. 39% (p<.01). Metformin adherence improved in the intervention group relative to controls at the two KP sites (52% vs. 49%, p<.01). This randomized trial shows that simple outreach to encourage MOP use modestly improved its use, and improved adherence to a key class of diabetes medications in some settings. Clinicians and health systems should consider such low-cost interventions to actively promote MOP among diabetes patients.

Disclosure

J. Schmittdiel: None. C.M. Trinacty: None. J. Wharam: None. O. Duru: Advisory Panel; Self; Healthwise. R. Neugebauer: None. S.D. Brown: None. D. Ross-Degnan: None. A.J. Karter: None. W.T. Dyer: None. B. Ramachandran: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases
1704-P: SIRT1 rs7896005 SNP and Incidence of Major Vascular Events in Type 2 Diabetes: A 13-Year, Single-Centre, Follow-Up Study
Authors: PENNO GIUSEPPE , GAROFOLO MONIA , GUALDANI ELISA , LUCCHESI DANIELA , GIUSTI LAURA , SANCHO-BORNEZ VERONICA , DARDANO ANGELA , FRANCESCONI PAOLO , PRATO STEFANO DEL
Published: June 2019

Genetic variants of SIRT1, in particular the G allele of the rs7896005 SNP, are associated with increased risk for T2DM. We recently reported that this SNP was not associated with all-cause mortality over a 13-year follow-up. We are now exploring the association of this SNP with incidence of major CV events in 917 T2DM (98.6% of the original cohort). Incidence data were obtained by interrogating hospital discharge registers. Genotypes distribution was: AA, n. 83 (9.1%), AG, n. 397 (43.3%), GG, n. 437 (47.7%). MAF was 0.307 and Hardy-Weinberg equilibrium met (chi-square 0.2809, p=0.596). There was no difference across genotypes for major CV risk factors and treatments. Over 11.25±4.40 years, 261 major CV events occurred (28.5%): AA/AG n. 121, 25.2%; GG n. 140, 32.0% (K-M logrank 5.798, p=0.016). After adjustment for age, sex, DD, BMI, HbA1c, A/C ratio, eGFR (CKD-EPI), smoking, hypertension, dyslipidemia, retinopathy, peripheral neuropathy and prior CV events, HR of GG vs. AA/AG was 1.28 (95% CI 1.00-1.65, p=0.047). Over 11.81±4.06 years, 176 coronary events occurred (19.2%): AA/AG n. 77, 16.0%; GG n. 99, 22.7% (K-M logrank 7.093, p=0.008). After adjustment, HR vs. AA/AG was 1.47 (1.09-2.00, p=0.013). A total of 81 (8.8%) hospitalization for heart failure (HF) occurred over a follow-up of 12.75±3.11 years: AA/AG n. 33, 6.9%; GG n. 48, 11.0% (K-M logrank 4.999, p=0.025). After correction, HR vs. AA/AG was 1.54 (0.98-2.42, p=0.063). Finally, over 12.92±2.95 years, 36 peripheral vascular events occurred (3.9%): AA/AG n. 11, 2.3%; GG n. 25, 5.7% (K-M logrank 7.320, p=0.007). After adjustment, HR vs. AA/AG was 2.15 (1.02-4.50, p=0.043). No association was found with cerebrovascular events and ESRD. With the limitations of the relatively small sample size, but the strength of the long-term observation, we suggest that in T2DM rs7896005 A/G SNP of SIRT1 is independently associated with incidence of major CV, coronary and peripheral vascular events and also with hospitalization for heart failure.

Disclosure

G. Penno: None. M. Garofolo: None. E. Gualdani: None. D. Lucchesi: None. L. Giusti: None. V. Sancho-Bornez: None. A. Dardano: None. P. Francesconi: None. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Board Member; Self; AstraZeneca. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited.
1706-P: A Promoter Variant of TYK2, a Putative Virus-Induced Susceptibility Gene, Is Associated with Impaired Insulin Secretion and Nonobese Type 2 Diabetes
Authors: MORI HITOE , TAKAHASHI HIROKAZU , MINE KEIICHIRO , INOUE KANAKO , KOJIMA MOTOYASU , KUROKI SHIGETAKA , ONO YASUHIRO , INUZUKA SADATAKA , NAGAFUCHI SEIHO , ANZAI KEIZO
Published: June 2019

Background: Type 2 diabetes mellitus is typically associated with obesity and insulin resistance. It is well known that viral infection triggers type 1 diabetes, but a potential link with type 2 diabetes has not been fully established. We have reported that a natural mutation in the tyrosine kinase 2 (TYK2) gene, which encodes an interferon receptor signaling molecule, is responsible for encephalomyocarditis (EMC) virus-induced diabetes in mice (Nat Commun 2015). Moreover, a human TYK2 promoter variant (TYK2PV) (NCBI ClinVer ID:440728) is associated with higher risks of not only type 1, but also type 2 diabetes (EBioMedicine 2015). Therefore, we hypothesized that impaired insulin secretion associated with TYK2PV causes type 2 diabetes. Here, we studied the relationships between TYK2PV, and insulin secretion and obesity in patients with type 2 diabetes.

Methods: The presence of TYK2PV was determined using direct sequencing, and insulin secretion was evaluated, in type 2 diabetes patients who were not administering either sulfonylureas or insulin.

Results: Of the 173 patients assessed, 18 (10.4%) were TYK2PV-positive, and their median BMI was significantly lower than those without the variant (25.3 vs. 23.4 kg/m2, p=0.029). Moreover, the HOMA-β (19.1 vs. 30.0, p=0.027) and fasting serum insulin (3.91 vs. 6.16 μIU/mL, p=0.007) were lower in patients with TYK2PV than in those without. Multivariable analysis showed that TYK2PV was significantly associated with fasting insulin <5μIU/ml (odds ratio 4.14, 95% confidence interval 1.404-12.21, p=0.021).

Conclusions: TYK2PV is associated with lower insulin secretion in type 2 diabetes, consistent with it being a virus-induced diabetes susceptibility gene. Therefore, type 2 diabetes patients with TYK2PV should be carefully followed, so that they receive the most appropriate treatment, including insulin.

Disclosure

H. Mori: None. H. Takahashi: None. K. Mine: None. K. Inoue: None. M. Kojima: None. S. Kuroki: None. Y. Ono: None. S. Inuzuka: None. S. Nagafuchi: None. K. Anzai: None.
1710-P: A Case with Monogenic Diabetes Caused by RFX6 Mutation in a 14-Year-Old-Girl
Authors: YU JEESUK , KWAK SOO HEON
Published: June 2019

Introduction: It is worthwhile to find new causes of monogenic diabetes to understand glycemic regulation as well as the management of diabetes mellitus. In previous times, diabetes mellitus in children and adolescents was usually type 1 diabetes which was caused by autoimmune beta cell destruction, but due to the increased prevalence of obesity, the incidence of type 2 diabetes was explosively increased in children and adolescents. The underlying mechanism of childhood-onset type 2 diabetes mellitus may be different to the adult-onset type 2 diabetes. Therefore, it is useful to conduct genetic study in children with type 2 feature.

Case: A 14 year-old-girl was diagnosed as having type 2 diabetes mellitus. Initially, she was presented with glycosuria, polydipsia, and polyuria. Initial HbA1c was 11.7%. She had no specific past medical problems. Her mother was already diagnosed as diabetes mellitus and on medication. her weight was 66.3kg (95 pecentile) and height was 148.3cm (3 percentile). Acanthosis nigricans was detected in neck and axillary areas. Blood glucose was 345 mg/dL, insulin was 27.2 uIU/mL, and C-peptide was 8.7 ug/dL, implying the presence of insulin resistance. There was neither ketonuria nor acidosis. Blood lipid profile showed 200 mg/dL of cholesterol, 45 mg/dL of HDL cholesterol, and 144 mg/dL of triglyceride. Thyroid function was normal. She was managed with long-acting insulin and oral hypoglycemic agent (MetforminTM) and her HbA1c level became 9.3% at one year after the diagnosis. To find the candidate gene, targeted exome sequencing was performed which included 29 genes associated with monogenic diabetes. Nonsense mutation of the gene RFX6 was found (Tyr887*). The RFX6 gene mutation is known to contribute to beta-cell dysfunction and is associated with lower fasting and stimulated gastric inhibitory polypeptide (GIP) levels.

Conclusion: It may be recommended to perform the genetic test in childhood-onset type 2 diabetes mellitus to find the candidate gene of type 2 diabetes mellitus.

Disclosure

J. Yu: None. S. Kwak: None.
1715-P: Identifying Potentially Functional Variants in Regulatory Regions in KCNQ1 that Associate with Type 2 Diabetes in American Indians
Authors: MULLER YUNHUA L. , DAY SAMANTHA E. , KOBES SAYUKO , KNOWLER WILLIAM C. , HANSON ROBERT L. , BOGARDUS CLIFTON , BAIER LESLIE J.
Published: June 2019

A prior genome-wide association study in 7701 Pima Indians utilized a custom Axiom array (Affymetrix) which contained 474,196 SNPs. These SNPs tagged 92% of common variants (R2≥0.85, minor allele frequency ≥0.05) identified in the Pima Indian genome. SNP rs79788804, which tags 38 additional SNPs in intron 15 of KCNQ1, achieved genome-wide significance in its association with type 2 diabetes (T2D; OR=1.31, p=2 x10-8). A 3 SNP haplotype (rs79788804, rs2237892 and rs2299620) with >1 maternally-derived alleles strongly associated with T2D (ORM=2.05, p=2x10-12). ENCODE and Islet regulome databases mapped putative strong enhancers to 4 regions in intron 15 with multiple epigenetic marks and transcription factor binding sites. To validate these regulatory regions, we tested gene activation from the putative enhancers using CRISPR-CAS9-based acetyltransferase (dCas9p300) in human pancreatic beta cells (EndoC-βH3). Guide RNA specific acetylation by dCas9p300 at a 341 bp region spanning rs2299620, rs2237896, rs2237897 and rs74046911 resulted in a 1.5 fold gene activation for KCNQ1 and nearby gene TRPM5 (both p=0.001). A chromatin immunoprecipitation-qPCR assay confirmed that dCas9P300 acetylated chromatin at this targeted region. We further assessed the effects of 5 transcription factors (NKX2.2, MAFB, NKX6.1, FOXA2, PDX1) on transcriptional activity under control of these 4 enhancer regions. Mouse pancreatic β-cells (NIT1) were co-transfected with a vector expressing each transcription factor and a luciferase reporter construct containing the KCNQ1 SNPs. NKX2.2 had a 5.5 fold activation for the construct containing the same 341 bp KCNQ1 region, as compared to a 4.1 fold activation for the construct containing KCNQ1 promoter alone (p=0.02). Our data suggested that a 341 bp region containing rs2299620, rs2237896, rs2237897 and rs74046911 may harbor functional variant(s) which affect expression of KCNQ1 and TRPM5.

Disclosure

Y.L. Muller: None. S.E. Day: None. S. Kobes: None. W.C. Knowler: None. R.L. Hanson: None. C. Bogardus: None. L.J. Baier: None.

Funding

National Institutes of Health
1720-P: The rs10423928 GIP Receptor “A” Allele Contributes to an Improved ß-Cell Response in Prediabetes Patients
Authors: BARBOSA-YAÑEZ RENATE LUZÍA , DAMBECK ULRIKE , HONSEK CAROLINE , KABISCH STEFAN , PFEIFFER ANDREAS F.
Published: June 2019

The gut hormone GIP has become a novel target for T2DM and obesity research due to its glucose-dependent insulinotropic effect. GIP-receptor is therefore a biologically plausible candidate for T2DM treatment. A meta-analysis of genome-wide association studies identified a genetic variant in intron 12 of GIPR (rs10423928, A-allele) that is linked to impaired glucose metabolism. The aim of this study was to investigate the relationship between “A” allele carriers and T2DM susceptibility. Glucose challenge data of 424 prediabetes subjects was analyzed. Genotyping was performed using TaqMan™ SNP Genotyping Assay rs10423928. We extended previous data by showing that carriers of the A allele displayed increased fasting glucose. Unexpectedly, A carriers showed lower glucose levels 2 h after an oral glucose challenge and higher insulin sensitivity (assessed by Cederholm Index) compared to homozygous subjects for the T allele, indicating an enhanced ß-cell response. Furthermore, we found no link between rs10423928 variant and liver fat, total adipose tissue and visceral adipose tissue determined by MRI. Longitudinally, the SNP did not determine responses to dietary supplementation of oat fibers or low-fat vs. low-carb diets. The results suggest a partially advantageous effect of the minor allele A. Further investigation of the role of this gene, along with other SNPs in linkage with rs10423928 is required in larger study groups.

Disclosure

R. Barbosa-Yañez: None. U. Dambeck: None. C. Honsek: None. S. Kabisch: Research Support; Self; California Walnut Commission, Institute for Grain Processing, Nuthetal, J. Rettenmaier Söhne, Südzucker / Beneo. Other Relationship; Self; Berlin-Chemie AG, Sanofi. A.F. Pfeiffer: Advisory Panel; Self; Abbott, Berlin-Chemie AG, Novo Nordisk A/S. Speaker's Bureau; Self; Lilly Diabetes, Novartis AG, Sanofi-Aventis Deutschland GmbH.

Funding

German Center for Diabetes Research
174-LB: Impact of Quality Improvement (QI) Program on 5-Year Risk of Diabetes-Related Complications
Authors: SHAO HUI , SHI LIZHENG , FURMAN ROY E. , MENEGHINI LUIGI , HARLAN TIMOTHY S. , FONSECA VIVIAN
Published: June 2019

We have successfully implemented the ADA’s Diabetes INSIDE® QI program at a University hospital and safety-net health system (Tulane and Parkland), focused on system-wide improvement in poorly controlled type 2 diabetes (A1c>8.0%). We extrapolated clinical outcomes of the QI program on a 5-year risk of complications, utilizing a validated risk prediction model: Building, Relating, Assessing, Validating of Outcomes (BRAVO) simulation model. We measured the differences between the baseline and post-intervention values of risk factors in 2,429 individuals with A1c >8% at baseline and used the BRAVO model to project the 5-year risk reduction of diabetes-related complications under the assumption that intervention benefits diminished with time. The intervention period was defined as one year and the post-intervention period as the subsequent six months. The QI program was associated with reductions in A1c (-0.84%) and LDL-C (-5.94 mg/dl) among individuals with A1c level >8.0%, with greater reduction in A1c (-1.67%) and LDL-C (-6.81 mg/dl) among those with A1c level > 9.5% at baseline (all p<0.05). The potential outcome of the QI program on 5-year risk of complications are presented in Fig 1. Our outcomes model suggests that the observed risk factor reduction is projected to lead to clinically significant 5-year risk of events - benefiting patients and population health as it relates to future complications burden."

Disclosure

H. Shao: None. L. Shi: None. R.E. Furman: None. L. Meneghini: Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Sanofi-Aventis. Consultant; Self; Sanofi-Aventis. Other Relationship; Self; American Diabetes Association. T.S. Harlan: None. V. Fonseca: Board Member; Self; American Association of Clinical Endocrinologists. Consultant; Self; Abbott, Asahi Kasei Corporation, Novo Nordisk Inc., Sanofi US, Takeda Pharmaceutical Company Limited. Research Support; Self; Bayer US. Stock/Shareholder; Self; Amgen Inc., Bravo4health, Mellitus Health.

Funding

Lilly USA, LLC; Novo Nordisk; Sanofi
1743-P: Engineering Erythrocytes with the SQZ Cell Therapy Platform to Enhance Immunotolerance
Authors: RAMAKRISHNAN AMRITHA , LEE THOMAS , MOORE LINDSAY J. , SUAREZ ALFONSO VICENTE , MOORE FINOLA , BERNSTEIN HOWARD
Published: June 2019

Current treatments for autoimmune disorders typically rely on the use of broadly immunosuppressive agents that increase the risk of adverse events in patients, such as cancer and opportunistic infections. Antigen (Ag)-specific immunotherapies have the potential to minimize these risks and improve efficacy by generating Ag-specific suppression to maintain immunohomeostasis. Several studies have established Ag-specific tolerance using red blood cells (RBCs) as a platform for delivery and Ag presentation in the context of eryptosis, a mechanism of RBC clearance. Here, we used the SQZ cell therapy platform to create Agloaded, pro-eryptotic RBCs to induce tolerance. In this approach, cells pass through constricted channels that cause transient permeation of the cell membrane and permit diffusion of cargo before the membrane reseals. In mice, we demonstrated that these highly delivered RBCs are rapidly cleared from circulation by splenic and liver-resident macrophages. The administration of ovalbumin (OVA)-SQZ’d RBCs led to a reduction of OVA-specific T cell proliferation and cytokine production in an OVA immunization model. In an autoimmune diabetes BDC2.5 T cell transfer model, mice treated with RBCs SQZ’d with 1040-p31 peptide mimetope delayed the onset of hyperglycemia in 80% of mice. Additionally, we developed mouse models for adenoassociated virus (AAV)-gene therapy and anti-drug antibody (ADA) to examine immunemediated clearance of exogenous Ag. In the AAV vector-specific model, mice treated with RBCs loaded with AAV-derived peptides abrogated the effector responses of AAV-specific CD8+ T cells upon restimulation. In a model of ADA responses, RBCs SQZ’d with a model drug also led to potent inhibition of ADA responses and preserved drug levels in circulation.

In summary, SQZ’d RBCs are a potentially exciting allogeneic cell therapy strategy to induce Ag-specific tolerance across a range of disease mechanisms and indications.

Disclosure

A. Ramakrishnan: None. T. Lee: None. L.J. Moore: None. A. Vicente Suarez: None. F. Moore: None. H. Bernstein: Employee; Self; SQZ Biotechnologies.

Funding

JDRF
1753-P: Foot Ulceration in the Immunosuppressed Population: Surgeon Beware!
Authors: WALTERS ELLIOT , TERMANINI KAREEM M. , JACKSON BRANDON T. , CHADAB TARA M. , WANG JESSICA , KIM PAUL J. , EVANS KAREN
Published: June 2019

Background: Over the past 3 decades, advances in transplant surgery have allowed life-saving renewal of solid organ function. Many of these patients are predisposed to the development of lower extremity wounds. There is a paucity of data describing treatment and outcomes of this complex patient population. The purpose of this study is to examine the surgical outcomes of these patients and overall limb salvage rates in a tertiary care center with a multi-disciplinary team focused on limb salvage.

Methods: Medical records were reviewed for all patients with a foot wound and functioning solid organ transplant who received surgery (including debridement or toe/foot/limb amputation) at our institution from 2010-2017.

Results: We identified 59 patients with lower extremity wounds and a prior transplant, 40 with a kidney transplant, 13 with combined kidney-pancreas transplant, and 6 with a liver transplant. The average solid organ transplant patient received 6.5 (±4.8) procedures during the follow-up period (46mos, 6.8-149.4). There were 32 patients (54.2%) who required toe amputations, 15/32 (46.9%) of these healed, 14 (43.8%) required a midfoot amputation, and 8 (25%) progressed to a below-knee amputation (BKA). Of patients with hind foot wounds 11/15 (73.3%) required calcanectomy, of these 7/11 (63.6%) progressed to a BKA. Overall, there were 19/59 (32.2%) patients who required below knee amputations, including the 15 which progressed from lesser procedures; two of the patients requiring BKA progressed to an above knee amputation.

Conclusions: This retrospective study highlights the morbidity associated with foot ulceration in the immunosuppressed patient with an overall BKA rate of 32.2%. Solid organ transplant patients who develop lower extremity wounds require a high level of surgical care. A large proportion of these patients will eventually require a major lower extremity amputation. Further investigation is needed to develop better strategies for lower extremity salvage in the immunosuppressed patient.

Disclosure

E. Walters: None. K.M. Termanini: None. B.T. Jackson: None. T.M. Chadab: None. J. Wang: None. P.J. Kim: Consultant; Self; Acelity, Integra LifeSciences. K. Evans: None.
176-OR: ApoC3 Related with Postprandial Hyperlipidemia Independently of ANGPTL3 and ANGPTL4 in Type 2 Diabetes
Authors: GOTO SATOSHI , HAYASHI TOSHIYUKI , NAGAIKE HIROE , KUSHIMA HIDEKI , HIROMURA MUNENORI , OHARA MAKOTO , YAMAMOTO TAKESHI , MORI YUSAKU , FUKUI TOMOYASU , HIRANO TSUTOMU
Published: June 2019

Aims: While the angiopoietin-like protein (ANGPTL) has attracted recent attention for its causative role in hypertriglyceridemia, the relationship between postprandial hyperlipidemia and ANGPTL has yet to clarified. In this study we sought to investigate how the pre-heparin lipoprotein lipase mass (LPL), ANGPTL3 and ANGPTL4 relates to postprandial hyperlipidemia in patients with type 2 diabetes.

Methods: Thirty-eight type 2 diabetics (M/F: 15/23) were enrolled. Blood samples were drawn from the patients just before and at 2h after every meal and measured the triglyceride (TG) levels. LPL, ANGPTL3 and ANGPTL4 were determined by the enzyme-linked immunosorbent assay method in the fasting samples. The TG incremental area under the curve (TG-iAUC) and area under the curve (TG-AUC) were calculated to investigate how they related to the lipid parameters.

Results: The findings were as follows: mean age, 65.9±12.3 years; BMI, 24.5±4.5 kg/m2; HbA1c, 8.4±1.0 %; LPL, 55.1±23.5 ng/mL; ApoCII, 5.6±1.6 mg/dL; ApoCIII, 10.4±3.1 mg/dL; ANGPTL3 409.5±114.8 ng/mL; ANGPTL4, 254.1±120.2 pg/mL; circadian variation of TG just before every meal/2h after every meal, 141.1±78.5/148.4±86.4-160.7±93.6/172.9±94.5-153.9±80.1/149.5±74.3 mg/dL; TG-AUC, 1889.2±1011.2 mg•h/dL; TG- iAUC, 196.6 ± 241.9 mg•h/dL. The TG-AUC was significantly correlated with LPL (r=-0.44, p<0.05), ApoCIII(r=0.83, p<0.0001), and logANGPTL3 (r=-0.45, p<0.05). There was confirmed to be no significant correlation, however, between the TG-AUC and logANGPTL4. The TG-iAUC was confirmed not to be significantly correlated with either LPL, logANGPTL3, or logANGPTL4. The TG-iAUC was significantly correlated with ApoCIII(r=0.41, p<0.05).

Conclusions: ApoCIII related with Postprandial hyperlipidemia independently of ANGPTL3 and ANGPTL4 in T2DM.

Disclosure

S. Goto: Research Support; Spouse/Partner; DENKA SEIKEN CO., LTD. T. Hayashi: Research Support; Spouse/Partner; DENKA SEIKEN CO., LTD. H. Nagaike: None. H. Kushima: None. M. Hiromura: None. M. Ohara: None. T. Yamamoto: None. Y. Mori: None. T. Fukui: None. T. Hirano: None.

Funding

Denka Seiken Co., Ltd.
177-LB: Use of Online Diabetes Management Programs among Patients with a New Diabetes Diagnosis
Authors: HUANG JIE , GRAETZ ILANA , REED MARY
Published: June 2019

Objective: Online wellness programs offer a convenient way for newly diagnosed patients to engage with targeted health education and self-management tools, but there is limited evidence on use rates and user characteristics. We examined patient characteristics associated with use of an online diabetes self-management program among patients with a new diabetes diagnosis in a large integrated health system.

Research Design and Methods: A diabetes self-management program was introduced on the health system's patient portal website in 2010 without formal clinician promotion. Using the health system clinical diabetes registry, we identified patients newly diagnosed with diabetes in 2010-2018 and examined the use of diabetes care tool in the same year they joined the registry. We examined use of the online diabetes program and used multivariable logistic regression model to examine the association between use and patient characteristics including age, gender, race/ethnicity, neighborhood socioeconomic status (SES) and baseline HbA1c.

Results: Among 277,032 total patients diagnosed with diabetes 2010-2018, 1,734 (0.63%) patients used the diabetes management program in that same year. Patients of older age (OR=0.34, 95% CI: 0.27-0.43 for age 75+ vs. <45), male (OR=0.48, 95% CI:0.44-0.53), non-white (e.g., OR=0.32, 95% CI: 0.28-0.37 for Asian vs. white), living in a low SES neighborhood (OR=0.71, 95% CI: 0.63-0.81) were less likely to use the online diabetes wellness program. Patients with higher baseline HbA1c were more likely to use the program (OR=1.29, 95% CI: 1.04-1.59 for A1c 9+ vs. A1c <7).

Conclusions: Few newly diagnosed diabetes patients used the diabetes management program on their own, with evidence of a digital divide in use. It is encouraging, however, that patients with higher baseline A1c were more likely to use the program. Efforts to promote patient-facing online tools use in clinical care delivery from providers may increase use, and research is needed on clinical impacts.

Disclosure

J. Huang: None. I. Graetz: None. M. Reed: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases
1770-P: Further Evidence Supporting a Potential Role for ADH1B in Obesity
Authors: JENKINSON CHRIS , MORALES LIZA D. , TRIPATHY DEVJIT , HU SHIRLEY L. , LOPEZ-ALVARENGA JUAN C. , DUGGIRALA RAVINDRANATH , DEFRONZO RALPH A. , MUMMIDI SRINIVAS , ARYA RECTOR , NORTON LUKE , BLANGERO JOHN , DIAZ-BADILLO ALVARO
Published: June 2019

We previously showed that expression of the human cytosolic enzyme, alcohol dehydrogenase 1B (ADH1B), was inversely correlated with measures of obesity and insulin resistance in subcutaneous adipose tissue in Mexican Americans. Here, we sought to determine the relationship between ADH1B RNA, protein expression, adipogenesis and insulin action in human subcutaneous primary adipocytes in culture, derived from lean (BMI < 28 kg.m-2) and obese (BMI ≥ 30 kg.m-2) donors. ADH1B expression increased ∼160-fold during adipogenesis as preadipocytes differentiated into mature adipocytes, reaching maximal levels at 14 days whereas the expression of two homologous genes, ADH1A and ADH1C was relatively unchanged. This indicates that ADH1B may play a role in adipocyte differentiation and proliferation. Adipocytes from lean donors expressed ADH1B at higher levels compared with those from obese donors. Given the multiple passaging of these cells, this indicates likely epigenetic regulation of expression. We performed a meta-analysis of the relationship between ADH1B expression and obesity using data from four populations (Mexican Americans, African Americans, Europeans and Pima Indians). The results showed that BMI was increased by 0.56 standard deviations for each standard deviation of decreased ADH1B expression. This finding illustrates the global relevance of the inverse correlation of ADH1B expression with obesity. Insulin stimulated ADH1B expression dose dependently, with higher levels in the “lean adipocytes.” Phosphorylation of AKT, an important mediator of insulin signaling, was lower in “obese adipocytes” compared with “lean adipocytes” (p<0.01) demonstrating that the “obese adipocytes” were relatively insulin resistant. Knockdown of ADH1B expression resulted in a decrease in insulin-stimulated glucose uptake of 35% (p<0.05). Taken together, these findings show that ADH1B is involved in insulin signaling and action in human subcutaneous adipocytes and that this activity is suppressed in obesity.

Disclosure

C. Jenkinson: None. L.D. Morales: None. D. Tripathy: None. S.L. Hu: None. J.C. Lopez-Alvarenga: None. R. Duggirala: None. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. S. Mummidi: None. R. Arya: None. L. Norton: None. J. Blangero: None. A. Diaz-Badillo: None.

Funding

National Institutes of Health
1776-P: Gut Microbiota Remodeling and Intestinal FXR Inhibition Mediate the Antimetabolic Syndrome Properties of Gynostemma Pentaphyllum
Authors: XIE ZHIFU , HU LIHONG , LI JINGYA , LI JIA
Published: June 2019

Gynostemma pentaphyllum (G. pentaphyllum) is widely used as a traditonal chinese medicine with anti-metabolic syndrome properties in Asian countries, however, the critical mechanism with the metabolic benefits of G. pentaphyllum remained unclarified. Herein, we performed metabolomic analysis (LC-MS/MS) of samples from obese mice treated with G. pentaphyllum, and identified 2α-OH-PPD (GP2) may be the principal bioactive constituent responsible for the anti-metabolic syndrome effect of G. pentaphyllum. In mouse model of high fat diet-induced obesity, GP2 prevented diet-induced obesity, along with hepatic steatosis and insulin resistance after 5 weeks treatment. The metabolic benefits of GP2 treatment were abrogated in the antibiotic treated DIO mice, which indicated GP2 improves metabolic syndrome dependent on gut microbiota remodeling. Mechanically, GP2, play as an inhibitor of bile salt hydrolase (BSH) in the gut microbiota, increased the bile acid tauro-α/β-muricholic acid (Tα/βMCA) and tauroursodeoxycholic acid (TUDCA) in the gut through decrease in level of the genus Clostridium, but not the genus Lactobacillus (LefSe Analysis for gut microbiota composition). The expression of FGF-15 and shp gene were dramatically decreased in the ileum, and the expression of pro-glucagon in the L cell and glucose induced GLP-1 secretion were markedly increased in the GP2 treated mice, which were accompanied by farnesoid X receptor (FXR) signaling inhibition in the intestine. Finally, after transplanted the fecal microbiota of mice treated by GP2 into recipient mice pretreated with antibiotics, the mice reflected much more GLP-1 secretion after glucose stimulated and high Tα/βMCA level in the gut than the mice received control microbiota. These results indicated that GP2 as well as G. pentaphyllum improved metabolic syndrome in part through intestinal FXR inhibition induced by gut microbiota remodeling.

Disclosure

Z. Xie: None. L. Hu: None. J. Li: None. J. Li: None.

Funding

National Natural Science Foundation of China