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Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity
- Source :
- 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/db14-0319, 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/db14-0319, 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/db14-0319, Diabetes, 63(12), 4378-4387. American Diabetes Association Inc.
- Publication Year :
- 2016
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 00121797
- Database :
- OpenAIRE
- Journal :
- 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/db14-0319, 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/db14-0319, 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/db14-0319, Diabetes, 63(12), 4378-4387. American Diabetes Association Inc.
- Accession number :
- edsair.doi.dedup.....3c8ee2f66cc5ddfced99ae870e2bac31
- Full Text :
- https://doi.org/10.2337/db14-0319