Suchergebnisse

Chenghui Zhang,1,2,* Qing Ou,1,* Yan Gu,1,* Gaiping Cheng,3 Rong Du,1,2 Li Yuan,1 Ruth LM Cordiner,4 Deying Kang,5 Jiaying Zhang,6 Qiaorong Huang,7 Chuan Yu,8 Li Kang,9 Xuan Wang,4,10 Xin Sun,5 Xianming Mo,7 Haoming Tian,1 Ewan R Pearson,4 Wentong Meng,7 Sheyu Li1,4 1Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China; 2Department of Endocrinology and Metabolism, Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, Chengdu 610041, People's Republic of China; 3Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China; 4Division of Population Health and Genomics, Ninewells Hospital and School of Medicine, University of Dundee, Dundee DD1 9SY, Scotland, UK; 5Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China; 6Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China; 7Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China; 8Department of Health-Related Social and Behavioral Science, West China School of Public Health, Sichuan University, Chengdu 610041, People's Republic of China; 9Division of Systems Medicine, Ninewells Hospital and School of Medicine, University of Dundee, Dundee DD1 9SY, Scotland, UK; 10Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Uppsala 75123, Sweden*These authors contributed equally to this workCorrespondence: Sheyu LiDepartment of Endocrinology and Metabolism, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu 610041, ChinaTel +86-13194874843Fax +86-28-85422982Email lisheyu@gmail.comWentong MengLaboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, Sichuan 610041, People's Republic of ChinaTel +86-18980601256Fax +86-28-85422982Email mwentong@sina.comAim: To investigate the count of circulating tissue factor-positive (TF+) procoagulant microparticles (MPs) in patients with type 1 diabetes mellitus (T1DM).Methods: This case-control study included patients with T1DM and age and sex-matched healthy volunteers. The counts of phosphatidylserine-positive (PS+) MPs and TF+PS+MPs and the subgroups derived from different cell types were measured in the peripheral blood sample of the two groups using multicolor flow cytometric assay. We compared the counts of each MP between groups as well as the ratio of the TF+PS+MPs and PS+MPs (TF+PS+MPs/PS+MPs).Results: We recruited 36 patients with T1DM and 36 matched healthy controls. Compared with healthy volunteers, PS+MPs, TF+PS+MPs and TF+PS+MPs/PS+MPs were elevated in patients with T1DM (PS+MPs: 1078.5 ± 158.08 vs 686.84 ± 122.04/μL, P <0.001; TF+PS+MPs: 202.10 ± 47.47 vs 108.33 ± 29.42/μL, P <0.001; and TF+PS+MPs/PS+MPs: 0.16 ± 0.04 vs 0.19 ± 0.05, P = 0.004), mostly derived from platelet, lymphocytes and endothelial cells. In the subgroup analysis, the counts of total and platelet TF+PS+MPs were increased in patients with diabetic retinopathy (DR) and with higher HbA1c, respectively.Conclusion: Circulating TF+PS+MPs and those derived from platelet, lymphocytes and endothelial cells were elevated in patients with T1DM.Keywords: type 1 diabetes mellitus, microparticles, tissue factor, diabetic retinopathy

Aims/hypothesis The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT. Methods Prediabetic participants (target sample size 2,200-2,700) and patients with newly diagnosed type 2 diabetes (target sample size similar to 1,000) are undergoing detailed metabolic phenotyping at baseline and 18 months and 36 months later. Abdominal, pancreatic and liver fat is assessed using MRI. Insulin secretion and action are assessed using frequently sampled OGTTs in non-diabetic participants, and frequently sampled mixed-meal tolerance tests in patients with type 2 diabetes. Biosamples include venous blood, faeces, urine and nail clippings, which, among other biochemical analyses, will be characterised at genetic, transcriptomic, metabolomic, proteomic and metagenomic levels. Lifestyle is assessed using high-resolution triaxial accelerometry, 24 h diet record, and food habit questionnaires. Conclusinos/interpretation DIRECT will yield an unprecedented array of biomaterials and data. This resource, available through managed access to scientists within and outside the Consortium, will facilitate the development of new treatments and therapeutic strategies for the prevention and management of type 2 diabetes.

The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT.

Aims/hypothesis The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT. Methods Prediabetic participants (target sample size 2,200–2,700) and patients with newly diagnosed type 2 diabetes (target sample size ~1,000) are undergoing detailed metabolic phenotyping at baseline and 18 months and 36 months later. Abdominal, pancreatic and liver fat is assessed using MRI. Insulin secretion and action are assessed using frequently sampled OGTTs in non-diabetic participants, and frequently sampled mixed-meal tolerance tests in patients with type 2 diabetes. Biosamples include venous blood, faeces, urine and nail clippings, which, among other biochemical analyses, will be characterised at genetic, transcriptomic, metabolomic, proteomic and metagenomic levels. Lifestyle is assessed using high-resolution triaxial accelerometry, 24 h diet record, and food habit questionnaires. Conclusions/interpretation DIRECT will yield an unprecedented array of biomaterials and data. This resource, available through managed access to scientists within and outside the Consortium, will facilitate the development of new treatments and therapeutic strategies for the prevention and management of type 2 diabetes.

Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (T pred ) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous T pred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models. Findings: A higher T pred score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=–0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher T pred score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the T pred score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) and insulin (β=-11.0 pmol/mol, 95% CI -19.5, -2.6). Longitudinal analysis showed at 18-month follow up a higher T pred score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, 95% CI -0.3, -0.01) and insulin (β=-9.2 pmol/mol, 95% CI -17.9, -0.4) concentrations in cohort 2. Interpretation: Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health. Funding: This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115,317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013) and EFPIA companies.