Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity
| العنوان: | Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity |
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| المؤلفون: | Núria Sala, Nina Roswall, Tilman Kühn, Larraitz Arriola, Dorota Pasko, Elio Riboli, Mark I. McCarthy, Afshan Siddiq, María José Sánchez, Luca A. Lotta, Francesca L. Crowe, Timothy J. Key, Peter M. Nilsson, Anne Tjønneland, Inês Barroso, Guy Fagherazzi, Nita G. Forouhi, Carlotta Sacerdote, Kim Overvad, Aurelio Barricarte, Nicholas J. Wareham, Sara Grioni, Tove Fall, Françoise Clavel-Chapelon, Olov Rolandsson, Heiner Boeing, Jacqueline M. Dekker, Mark Walker, Adam Barker, Vilmantas Giedraitis, Daphne L. van der A, Claudia Langenberg, Diana Gavrila, David B. Savage, Ele Ferrannini, Matthias B. Schulze, Hanieh Yaghootkar, Nadia Slimani, Paul W. Franks, Erik Ingelsson, Annemieke M.W. Spijkerman, Robert A. Scott, Ivonne Sluijs, Rosario Tumino, Stephen J. Sharp, Salvatore Panico, Robert K. Semple, Beverley Balkau, Leif Groop, Domenico Palli, Timothy M. Frayling, J. Ramón Quirós, Rudolf Kaaks |
| المساهمون: | Scott, Ra, Fall, T, Pasko, D, Barker, A, Sharp, Sj, Arriola, L, Balkau, B, Barricarte, A, Barroso, I, Boeing, H, Clavel Chapelon, F, Crowe, Fl, Dekker, Jm, Fagherazzi, G, Ferrannini, E, Forouhi, Ng, Franks, Pw, Gavrila, D, Giedraitis, V, Grioni, S, Groop, Lc, Kaaks, R, Key, Tj, K?hn, T, Lotta, La, Nilsson, Pm, Overvad, K, Palli, D, Panico, Salvatore, Quir?s, Jr, Rolandsson, O, Roswall, N, Sacerdote, C, Sala, N, S?nchez, Mj, Schulze, Mb, Siddiq, A, Slimani, N, Sluijs, I, Spijkerman, Am, Tjonneland, A, Tumino, R, van der A., Dl, Yaghootkar, H, Mccarthy, Mi, Semple, Rk, Riboli, E, Walker, M, Ingelsson, E, Frayling, Tm, Savage, Db, Langenberg, C, Wareham, Nj, The RISC The study group InterAct, Consortium, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes |
| المصدر: | Scott, R A, Fall, T, Pasko, D, Barker, A, Sharp, S J, Arriola, L, Balkau, B, Barricarte, A, Barroso, I, Boeing, H, Clavel-Chapelon, F, Crowe, F L, Dekker, J M, Fagherazzi, G, Ferrannini, E, Forouhi, N G, Franks, P W, Gavrila, D, Giedraitis, V, Grioni, S, Groop, L C, Kaaks, R, Key, T J, Kuhn, T, Lotta, L A, Nilsson, P M, Overvad, K, Palli, D, Panico, S, Quiros, J R, Rolandsson, O, Roswall, N, Sacerdote, C, Sala, N, Sanchez, MJ, Schulze, M B, Siddiq, A, Slimani, N, Sluijs, I, Spijkerman, A M W, Tjonneland, A, Tumino, R, van der A, D L, Yaghootkar, H, McCarthy, M I, Semple, R K, Riboli, E, Walker, M, Ingelsson, E, Frayling, T M, Savage, D B, Langenberg, C & Wareham, N J 2014, ' Common Genetic Variants Highlight the Role of Insulin Resistance and Body Fat Distribution in Type 2 Diabetes, Independent of Obesity ', Diabetes, vol. 63, no. 12, pp. 4378-4387 . https://doi.org/10.2337/db14-0319Test Scott, R A, Fall, T, Pasko, D, Barker, A, Sharp, S J, Arriola, L, Balkau, B, Barricarte, A, Barroso, I, Boeing, H, Clavel-Chapelon, F, Crowe, F L, Dekker, J M, Fagherazzi, G, Ferraninini, E, Forouhi, N G, Franks, P W, Gavrila, D, Giedraitis, V, Grioni, S, Groop, L C, Kaaks, R, Key, T J, Kühn, T, Lotta, L, Nilsson, P M, Overvad, K, Palli, D, Panico, S, Quirós, J R, Rolandsson, O, Roswall, N, Sacerdote, C, Sala, N, Sánchez, M-J, Schulze, M B, Siddiq, A, Slimani, N, Sluijs, I, Spijkerman, A M, Tjonneland, A, Tumino, R, van der A, D L, Yaghootkar, H, McCarthy, M I, Semple, R K, Riboli, E, Walker, M, Ingelsson, E, Frayling, T M & The RISC study group 2014, ' Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independently of obesity ', Diabetes, vol. 63, no. 12, pp. 4378-4387 . https://doi.org/10.2337/db14-0319Test Scott, R A, Fall, T, Pasko, D, Barker, A, Sharp, S J, Arriola, L, Balkau, B, Barricarte, A, Barroso, I, Boeing, H, Clavel-Chapelon, F, Crowe, F L, Dekker, J M, Fagherazzi, G, Ferraninini, E, Forouhi, N G, Franks, P W, Gavrila, D, Giedraitis, V, Grioni, S, Groop, L C, Kaaks, R, Key, T J, Kühn, T, Lotta, L, Nilsson, P M, Overvad, K, Palli, D, Panico, S, Quirós, J R, Rolandsson, O, Roswall, N, Sacerdote, C, Sala, N, Sánchez, M-J, Schulze, M B, Siddiq, A, Slimani, N, Sluijs, I, Spijkerman, A M, Tjonneland, A, Tumino, R, van der A, D L, Yaghootkar, H, McCarthy, M I, Semple, R K, Riboli, E, Walker, M, Ingelsson, E, Frayling, T M & The RISC study group 2014, ' Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independently of obesity ', Diabetes, vol. 63, no. 12, pp. 4378-87 . https://doi.org/10.2337/db14-0319Test Diabetes, 63(12), 4378-4387. American Diabetes Association Inc. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Type 2 diabetes, Overweight, Polymorphism, Single Nucleotide, Article, Body Mass Index, Cohort Studies, Insulin resistance, Diabetes mellitus, Internal medicine, Insulin Secretion, Internal Medicine, medicine, Body Fat Distribution, Humans, Insulin, Genetic Predisposition to Disease, Obesity, Aged, 2. Zero hunger, Glucose tolerance test, medicine.diagnostic_test, business.industry, nutritional and metabolic diseases, Genetic Variation, Alanine Transaminase, gamma-Glutamyltransferase, Glucose clamp technique, Glucose Tolerance Test, Middle Aged, medicine.disease, Endocrinology, Diabetes Mellitus, Type 2, Body Composition, Glucose Clamp Technique, Female, medicine.symptom, Insulin Resistance, Waist Circumference, business |
| الوصف: | We aimed to validate genetic variants as instruments for insulin resistance and secretion, to characterize their association with intermediate phenotypes, and to investigate their role in type 2 diabetes (T2D) risk among normal-weight, overweight, and obese individuals. We investigated the association of genetic scores with euglycemic-hyperinsulinemic clamp– and oral glucose tolerance test–based measures of insulin resistance and secretion and a range of metabolic measures in up to 18,565 individuals. We also studied their association with T2D risk among normal-weight, overweight, and obese individuals in up to 8,124 incident T2D cases. The insulin resistance score was associated with lower insulin sensitivity measured by M/I value (β in SDs per allele [95% CI], −0.03 [−0.04, −0.01]; P = 0.004). This score was associated with lower BMI (−0.01 [−0.01, −0.0]; P = 0.02) and gluteofemoral fat mass (−0.03 [−0.05, −0.02; P = 1.4 × 10−6) and with higher alanine transaminase (0.02 [0.01, 0.03]; P = 0.002) and γ-glutamyl transferase (0.02 [0.01, 0.03]; P = 0.001). While the secretion score had a stronger association with T2D in leaner individuals (Pinteraction = 0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI or waist strata (Pinteraction > 0.31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of body size. |
| اللغة: | English |
| تدمد: | 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c8ee2f66cc5ddfced99ae870e2bac31Test https://doi.org/10.2337/db14-0319Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3c8ee2f66cc5ddfced99ae870e2bac31 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00121797 |
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