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  • American Diabetes Association  (52)
  • 1
    Online Resource
    Online Resource
    18-OR: Efficacy and Safety of Chiglitazar vs. Sitagliptin in Patients with Type 2 Diabetes: A 24-Week, Randomized, Double-Blind, Noninferiority Phase 3 Trial (CMAS)
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Chiglitazar, a novel PPARα/γ/δ pan-agonist, showed favorable effects on glycemic control and lipid modulation with well tolerated safety profile in phase 2 trials. This trial aimed to compare the efficacy and safety of chiglitazar with DPP-4 inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled with diet and exercise (ClinicalTrials.gov NCT02173457). Patients were randomly assigned to receive chiglitazar 32 mg or 48 mg, or sitagliptin 100 mg once daily. The primary endpoint was change in HbA1c from baseline at week 24, with a non-inferiority of each chiglitazar dose versus sitagliptin. Analysis was done in all randomized patients who received at least one dose of study drug (n=739). Chiglitazar showed comparable HbA1c lowering effect compared with sitagliptin at 24 weeks (LS mean difference -0.04% [95% CI -0.22 to 0.15] and -0.08% [95% CI -0.27 to 0.10] for 32 mg and 48 mg, respectively), along with different trends in secondary endpoints. Overall adverse events were comparable across study groups. The incidences of weight gain and edema were generally low but relatively higher in chiglitazar 48 mg. In conclusion, chiglitazar showed non-inferior effect compared with sitagliptin on HbA1c reduction with well tolerated safety profile. Disclosure W. Jia: None. J. Ma: None. H. Miao: None. C. Wang: None. X. Wang: None. Q. Li: None. W. Lu: None. J. Yang: None. L. Zhang: None. J. Yang: None. G. Wang: None. X. Zhang: None. M. Zhang: None. L. Sun: None. X. Yu: None. J. Du: None. B. Shi: None. C. Xiao: None. D. Zhu: None. H. Liu: None. L. Zhong: None. C. Xu: None. Q. Xu: None. G. Liang: None. Y. Zhang: None. G. Li: None. M. Gu: None. J. Liu: None. Z. Ning: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi. Funding Ministry of Science and Technology of the People´s Republic of China (2013ZX09401301)
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-18-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1501252-9
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  • 2
    Online Resource
    Online Resource
    Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study
    American Diabetes Association ; 2017
    In:  Diabetes Vol. 66, No. 12 ( 2017-12-01), p. 3130-3141
    Details
    In: Diabetes, American Diabetes Association, Vol. 66, No. 12 ( 2017-12-01), p. 3130-3141
    Abstract: Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db17-0398
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2017
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  • 3
    Online Resource
    Online Resource
    Common Variants of Hepatocyte Nuclear Factor 1β Are Associated With Type 2 Diabetes in a Chinese Population
    American Diabetes Association ; 2009
    In:  Diabetes Vol. 58, No. 4 ( 2009-04-01), p. 1023-1027
    Details
    In: Diabetes, American Diabetes Association, Vol. 58, No. 4 ( 2009-04-01), p. 1023-1027
    Abstract: Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor that is critical for pancreatic cell formation and glucose homeostasis. Previous studies have reported that common variants of HNF1β were associated with type 2 diabetes in Caucasians and West Africans. However, analysis in the subjects from the Botnia study and Malmö Preventive Project produced conflicting results, and the role for HNF1β in type 2 diabetes susceptibility remains unclear. We therefore investigated common variants across the HNF1β gene in a Chinese population. RESEARCH DESIGN AND METHODS Fifteen tagging single nucleotide polymorphisms (SNPs) were analyzed for association with type 2 diabetes in subjects with type 2 diabetes (n = 1,859) and normal glucose regulation (n = 1,785). RESULTS Consistent with the initial study, we observed evidence that the risk G allele of rs4430796 in intron 2 was significantly associated with type 2 diabetes (odds ratio 1.16 [95% CI 1.05–1.29] , P = 0.0035, empirical P = 0.0475). Furthermore, the at-risk G allele was associated with earlier age at diagnosis in the type 2 diabetic subjects (P = 0.0228). CONCLUSIONS The result of this study provides evidence that variants in the HNF1β region contribute to susceptibility to type 2 diabetes in the Chinese population.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db08-1064
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2009
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  • 4
    Online Resource
    Online Resource
    Sodium Butyrate Stimulates Expression of Fibroblast Growth Factor 21 in Liver by Inhibition of Histone Deacetylase 3
    American Diabetes Association ; 2012
    In:  Diabetes Vol. 61, No. 4 ( 2012-04-01), p. 797-806
    Details
    In: Diabetes, American Diabetes Association, Vol. 61, No. 4 ( 2012-04-01), p. 797-806
    Abstract: Fibroblast growth factor 21 (FGF21) stimulates fatty acid oxidation and ketone body production in animals. In this study, we investigated the role of FGF21 in the metabolic activity of sodium butyrate, a dietary histone deacetylase (HDAC) inhibitor. FGF21 expression was examined in serum and liver after injection of sodium butyrate into dietary obese C57BL/6J mice. The role of FGF21 was determined using antibody neutralization or knockout mice. FGF21 transcription was investigated in liver and HepG2 hepatocytes. Trichostatin A (TSA) was used in the control as an HDAC inhibitor. Butyrate was compared with bezafibrate and fenofibrate in the induction of FGF21 expression. Butyrate induced FGF21 in the serum, enhanced fatty acid oxidation in mice, and stimulated ketone body production in liver. The butyrate activity was significantly reduced by the FGF21 antibody or gene knockout. Butyrate induced FGF21 gene expression in liver and hepatocytes by inhibiting HDAC3, which suppresses peroxisome proliferator–activated receptor-α function. Butyrate enhanced bezafibrate activity in the induction of FGF21. TSA exhibited a similar set of activities to butyrate. FGF21 mediates the butyrate activity to increase fatty acid use and ketogenesis. Butyrate induces FGF21 transcription by inhibition of HDAC3.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db11-0846
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2012
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  • 5
    Online Resource
    Online Resource
    Frequency, Immunogenetics, and Clinical Characteristics of Latent Autoimmune Diabetes in China (LADA China Study)
    American Diabetes Association ; 2013
    In:  Diabetes Vol. 62, No. 2 ( 2013-02-01), p. 543-550
    Details
    In: Diabetes, American Diabetes Association, Vol. 62, No. 2 ( 2013-02-01), p. 543-550
    Abstract: Adult non–insulin requiring diabetes includes latent autoimmune diabetes of adults (LADA), distinguished from type 2 diabetes by the presence of islet autoantibodies. LADA China determined the characteristics of Chinese LADA. This nationwide, multicenter, clinic-based cross-sectional study was conducted in 46 university-affiliated hospitals in 25 Chinese cities. All 4,880 ketosis-free diabetic patients ( & lt;1 year postdiagnosis, without insulin therapy for & gt;6 months, aged ≥30 years) had GAD antibody (GADA) and HLA-DQ genotype measured centrally with clinical data collected locally. GADA-positive subjects were classified as LADA. Of the patients, 5.9% were GADA positive with LADA. LADA showed a north-south gradient. Compared with GADA-negative type 2 diabetes, LADA patients were leaner, with lower fasting C-peptide and less metabolic syndrome. Patients with high GADA titers are phenotypically different from those with low GADA titers, while only a higher HDL distinguished the latter from those with type 2 diabetes. HLA diabetes–susceptible haplotypes were more frequent in LADA, even in those with low-titer GADA. HLA diabetes-protective haplotypes were less frequent in LADA. Our study implicates universal immunogenetic effects, with some ethnic differences, in adult-onset autoimmune diabetes. Autoantibody positivity and titer could be important for LADA risk stratification and accurate therapeutic choice in clinical practice.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db12-0207
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2013
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  • 6
    Online Resource
    Online Resource
    The Family Coriobacteriaceae Is a Potential Contributor to the Beneficial Effects of Roux-en-Y Gastric Bypass on Type 2 Diabetes
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Background: Changes in gut microbiota induced by bariatric surgery have been associated with metabolic benefits. Objectives: Our aim was to identify specific gut microbiota that may contribute to the improvement of type 2 diabetes (T2D) after RYGB.Setting: Laboratories of Shanghai Diabetes Institute and Shanghai Sixth People’s Hospital. Methods: Diabetic rats induced via a high-fat diet and low-dose streptozotocin administration were randomized to RYGB or sham surgery (SHAM), and stool samples were collected at baseline and at postoperative week 8. The faecal microbiota was profiled using 16S ribosomal RNA (rRNA) gene sequencing. Additionally, we performed a case-control study of the gut microbial community profiles of T2DM patients compared to those of healthy individuals (CONT) via 16S rRNA gene sequencing of mucosal-luminal interface samples collected from the ascending colon during colonoscopy. Results: RYGB significantly reduced the body weight and improved glucose tolerance and insulin sensitivity in diabetic rats. Principal coordinate analysis showed that RYGB caused marked alterations in the gut microbiota. The RYGB group was postoperatively enriched for Bacteroidetes, Proteobacteria, Fusobacteria and Actinobacteria; whereas the SHAM group was enriched for Firmicutes and Verrucomicrobia. Based on the gut microbial patterns in the T2D patients, we found that the family Coriobacteriaceae within Actinobacteria might contribute to the beneficial effects of RYGB on T2D. Conclusions: RYGB significantly improves glucose metabolism and alters the gut microbiota. Moreover, the family Coriobacteriaceae may partly mediate the beneficial effects of RYGB on T2D and thus possibly contribute to the development of novel bacteria-based therapeutic approaches. Disclosure C. Hu: None. W. Jia: None. H. Liu: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-1977-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 7
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    Online Resource
    Collaborative Formative Evaluation for Implementation of Primary Care–Based Peer Support in the Shanghai Integration Model
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Peer support (PS) is effective in promoting diabetes self-management, but pragmatic models are needed for specific cultural contexts and healthcare systems. Although rare in China, recent government priorities have created opportunities for PS by encouraging the integration of specialty/hospital with primary/community care. In particular, the Shanghai Integration Model coordinates specialty/hospital care with primary care in Community Health Centers (CHCs), providing an organizational base for implementation of PS. This study reports formative evaluation for PS within the Shanghai model, emphasizing collaboration with CHCs. Intervention refinement was guided by structured interviews with 15 CHC staff and patients and a focus group with as well as monthly feedback from CHC staff. Based on these, the intervention emphasizes education on medication use, healthy diet, and sustaining physical activity among older adults, and addresses diabetes distress and barriers to insulin treatment. Results of this collaborative formative evaluation include focus on group as opposed to individual PS with theme-based, interactive activities co-led by CHC staff along with peer leaders. In addition, peer leaders follow-up with individuals and organize neighborhood activities for physical activity, healthy diet, and feelings of comradery. To date, PS has been implemented in 9 CHCs, involving 74 trained peer leaders, reaching 885 adults. Mean age is 68.24, years with diabetes is 12.52, and HbA1c lower than expected at 7.36%. Counter to common difficulties in reaching men, 41.1% are male. Only 14.2% are taking insulin but 75.9% take oral medications. Important implementation benchmarks include clinician buy-in, high retention, positive participant and peer leader feedback, and extension of programs through engagement with neighborhood residential committees. Collaboration with CHC staff in program refinement have been important in implementation success. Disclosure M.M. Coufal: Research Support; Self; Sanofi, Merck Foundation, Novo Nordisk Inc. P.Y. Tang: Research Support; Self; Sanofi, Merck Foundation, Novo Nordisk A/S. E.B. Fisher: Research Support; Self; Sanofi, Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Merck Foundation. W. Jia: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-718-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 8
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    Online Resource
    International Consensus on Use of Continuous Glucose Monitoring
    American Diabetes Association ; 2017
    In:  Diabetes Care Vol. 40, No. 12 ( 2017-12-01), p. 1631-1640
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 40, No. 12 ( 2017-12-01), p. 1631-1640
    Abstract: Measurement of glycated hemoglobin (HbA1c) has been the traditional method for assessing glycemic control. However, it does not reflect intra- and interday glycemic excursions that may lead to acute events (such as hypoglycemia) or postprandial hyperglycemia, which have been linked to both microvascular and macrovascular complications. Continuous glucose monitoring (CGM), either from real-time use (rtCGM) or intermittently viewed (iCGM), addresses many of the limitations inherent in HbA1c testing and self-monitoring of blood glucose. Although both provide the means to move beyond the HbA1c measurement as the sole marker of glycemic control, standardized metrics for analyzing CGM data are lacking. Moreover, clear criteria for matching people with diabetes to the most appropriate glucose monitoring methodologies, as well as standardized advice about how best to use the new information they provide, have yet to be established. In February 2017, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address these issues. This article summarizes the ATTD consensus recommendations and represents the current understanding of how CGM results can affect outcomes.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc17-1600
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2017
    detail.hit.zdb_id: 1490520-6
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  • 9
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    Online Resource
    Serum Fibroblast Growth Factor-21 Is Related to Atherosclerosis Independent of Nonalcoholic Fatty Liver Disease and Predicts Incident Atherosclerotic Cardiovascular Diseases
    American Diabetes Association ; 2018
    In:  Diabetes Vol. 67, No. Supplement_1 ( 2018-07-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Fibroblast growth factor 21 (FGF-21), a key hepatokine regulating lipid metabolism, is related to several atherosclerotic diseases. But whether this relationship is mediated by nonalcoholic fatty liver disease (NAFLD) is not clear. Here we assessed the association of serum FGF-21 with atherosclerosis in non-NAFLD subjects and further investigated prospectively whether baseline FGF-21 could predict incident atherosclerotic cardiovascular disease (ASCVD) in a 7-year community study.Serum FGF-21 were measured in a cross-sectional cohort of 371 type 2 diabetic patients without NAFLD as determined by hepatic magnetic resonance spectroscopy, and a population-based prospective cohort of 7subjects from the Shanghai Diabetes Study. In the cross-sectional study, serum FGF-21 was significantly higher in those with subclinical carotid atherosclerosis (268.8 [139.0-415.2] vs. 188.3 [100.2-376.4] pg/ml, P=0.005). Multiple logistic regression analysis showed that serum FGF-21 was independently associated with atherosclerosis. In the prospective study, baseline serum FGF-21 was significantly higher in those who developed ischemic heart disease (479.5 [302.4-627.0] pg/ml, P=0.004) or cerebral infarction (401.6 [238.3-616.4] pg/ml, P=0.021) than those who did not (325.2 [189.0-498.9] pg/ml) during the follow-up. In multivariable Cox regression analysis, baseline serum FGF-21 independently predicted incident ASCVD events and significantly improved discriminatory and reclassifying abilities of the prediction model after adjustment for established cardiovascular risk factors.This study provides the first evidence that FGF-21 is elevated, independent of NAFLD, in subjects with subclinical atherosclerosis. Baseline FGF-21 is an independent predictor of incident ASCVD and could be utilized as a novel biomarker for primary prevention in general population. Disclosure L. Wu: None. L. Qian: None. H. Li: None. W. Jia: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db18-166-OR
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 10
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    729-P: Metabolic Surgery for the Treatment of Type 2 Diabetes Mellitus in China—Five-Year Outcomes from a Prospective Multicenter Study
    American Diabetes Association ; 2023
    In:  Diabetes Vol. 72, No. Supplement_1 ( 2023-06-20)
    Details
    In: Diabetes, American Diabetes Association, Vol. 72, No. Supplement_1 ( 2023-06-20)
    Abstract: The prevalence of type 2 diabetes (T2D) among adults in China is 10.9%-13.2%. Multicenter, long-term, prospective studies evaluating bariatric/metabolic surgery in obese patients with T2D in China are limited. This prospective study evaluated the 5-year impact of laparoscopic Roux-en-Y gastric bypass (RYGB; n=76 subjects, mean [SD] age 36.4 [9.5] , 52.6% women, mean [SD] BMI 34.6 [4.9] kg/m2, mean [SD] glycosylated hemoglobin A1c [HbA1c] 8.3% [1.7%], mean [SD] duration diabetes 3.7 [2.7]) and sleeve gastrectomy (SG; n=25 subjects, mean [SD] age 41.1 [10.8] , 44.0% women, mean [SD] BMI 36.4 [6.0] kg/m2, mean [SD] HbA1c 7.5% [1.5%] , mean [SD] duration diabetes 2.4 [2.4] ) on T2D at six centers in China from August 2014-April 2021. According to the composite measure of glycemic control for metabolic surgeries as suggested by the American Society for Metabolic and Bariatric Surgery, among 62 subjects evaluable at five years (50 RYGB, 12 SG), complete remission occurred in 28.6% (27.5% RYGB, 33.3% SG), partial remission in 27.0% (29.4% RYGB, 16.7% SG), improvement in 30.2% (29.4% RYBG, 33.3% SG), no change in 9.5% (7.8% RYBG, 16.7% SG), and recurrence in 4.8% (5.9% RYGB). Significant 5-year reductions in HbA1c (RYGB -1.7±2.1%, SG -1.8±1.1%), body weight (RYGB -19.8±8.4 kg, SG -21.2±6.0 kg), and BMI (RYGB -7.1±3.1 kg/m2, SG -7.7±2.1 kg/m2) were observed (all p & lt;0.001). Five-year improvements in triglycerides and high-density lipoprotein cholesterol were also observed. Procedure-related serious adverse events occurred in 8 RYGB subjects (7.9%). To our knowledge, this is the first prospective, multicenter, 5-year study of bariatric/metabolic surgery in subjects with T2D in China. These data demonstrate that RYGB and SG achieved clinically meaningful, sustained impacts on T2D remission in many subjects for up to five years. Bariatric/metabolic surgery has enormous potential to provide a safe and effective option for appropriately selected subjects with T2D in China. Disclosure Y.Bao: None. Y.Tu: None. S.Lin: None. H.Zhang: None. W.Yang: None. J.Yang: None. S.Chen: None. Q.Fan: None. Y.Ma: None. C.Ma: None. J.Waggoner: Employee; Ethicon, Inc., Janssen Research & Development, LLC, Stock/Shareholder; Johnson & Johnson. H.Liang: None. A.Tokarski: Employee; Ethicon, Inc. N.Edwards: Consultant; Boston Scientific Corporation, EMD Serono, Inc., Ethicon, Inc., Johnson & Johnson, Becton, Dickinson and Company. T.Yang: None. R.Zhang: None. W.Jia: None. P.Zhang: None. C.Wang: None. T.Jiang: None. N.Zhang: None. J.Zhu: None. H.Yu: None. J.Han: None. Funding Ethicon, Inc.; Johnson & Johnson
    Type of Medium: Online Resource
    ISSN: 0012-1797
    URL: Article
    DOI: 10.2337/db23-729-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2023
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