| Autor: |
Pedro Ferreira, João, Lamiral, Zohra, Xhaard, Constance, Duarte, Kévin, Bresso, Emmanuel, Devignes, Marie-Dominique, Le Floch, Edith, Dandine Roulland, Claire, Deleuze, Jean-François, Wagner, Sandra, Guerci, Bruno, Girerd, Nicolas, Zannad, Faiez, Boivin, Jean-Marc, Rossignol, Patrick |
| Předmět: |
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| Zdroj: |
European Journal of Endocrinology; Sep2020, Vol. 183 Issue 3, p285-295, 11p |
| Abstrakt: |
Objective: Determining the factors associated with new-onset pre-diabetes and type 2 diabetes mellitus (T2D) is important for improving the current prevention strategies and f or a better understanding of the disease. Design: To study the factors (clinical, circulating protein and geneti c) associated with new onset pre-diabetes and T2D in an initially healthy (without diabetes) populational familia l cohort with a long follow-up (STANISLAS cohort). Methods: A total of 1506 participants attended both the visit 1 and vis it 4, separated by ≈20 years. Over 400 proteins, GWAS and genetic associations were studied using models adjuste d for potential confounders. Both prospective (V1 to V4) and cross-sectional (V4) analyses were performed. Results: People who developed pre-diabetes (n = 555) and/or T2D (n = 73) were older, had higher BMI, blood pressure, glucose, LDL cholesterol, and lower eGFR. After multivariable s election, PAPP-A (pappalysin-1) was the only circulating protein associated with the onset of both pre-diabetes and T2D with associations persisting at visit 4 (i.e. ≈20 years later). FGF-21 (fibroblast growth factor 21) was a strong prognosticator for incident T2D in the longitudinal analysis, but not in the cross-sectional analysis. The heritability of the ci rculating PAPP-A was estimated at 44%. In GWAS analysis, the SNP rs634737 was associated with PAPP-A both at V1 and V4. External replication also showed lower levels of PAPP-A in patients with T2D. Conclusions: The risk of developing pre-diabetes and T2D increases with age and with features of the metabolic syndrome. Circulating PAPP-A, which has an important genetic co mponent, was associated with both the development and presence of pre-diabetes and T2D. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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