مورد إلكتروني
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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| بيانات النشر: | Umeå universitet, Medicin Umeå universitet, Allmänmedicin 2014 |
| تفاصيل مُضافة: | Scott, Robert A. Fall, Tove Pasko, Dorota Barker, Adam Sharp, Stephen J. Arriola, Larraitz Balkau, Beverley Barricarte, Aurelio Barroso, Ines Boeing, Heiner Clavel-Chapelon, Francoise Crowe, Francesca L. Dekker, Jacqueline M. Fagherazzi, Guy Ferrannini, Ele Forouhi, Nita G. Franks, Paul Gavrila, Diana Giedraitis, Vilmantas Grioni, Sara Groop, Leif C. Kaaks, Rudolf Key, Timothy J. Kuehn, Tilman Lotta, Luca A. Nilsson, Peter M. Overvad, Kim Palli, Domenico Panico, Salvatore Quiros, J. Ramon Rolandsson, Olov Roswall, Nina Sacerdote, Carlotta Sala, Nuria Sanchez, Maria-Jose Schulze, Matthias B. Siddiq, Afshan Slimani, Nadia Sluijs, Ivonne Spijkerman, Annemieke M. W. Tjonneland, Anne Tumino, Rosario van der A, Daphne L. Yaghootkar, Hanieh McCarthy, Mark I. Semple, Robert K. Riboli, Elio Walker, Mark Ingelsson, Erik Frayling, Tim M. Savage, David B. Langenberg, Claudia Wareham, Nicholas J. |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | 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 (beta 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 = 1.4x10(-6) and with higher alanine transaminase (0.02 [0.01, 0.03]; P = 0.002) and gamma-glutamyl transferase (0.02 [0.01, 0.03]; P = 0.001). While the secretion score had a stronger association with T2D in leaner individuals (P-interaction = 0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI or waist strata (P-interaction > 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. |
| مصطلحات الفهرس: | FRONZO RA, 1979, AMERICAN JOURNAL OF PHYSIOLOGY, V237, PE214 thelius B, 2003, DIABETOLOGIA, V46, P20 ssenko Valeriya, 2007, JOURNAL OF CLINICAL INVESTIGATION, V117, P2155 vage David B., PHYSIOLOGICAL REVIEWS, V87, P507 iderman Allan D., INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, V36, P220 ms EAH, 2001, METABOLISM-CLINICAL AND EXPERIMENTAL, V50, P1499, Medical and Health Sciences, Medicin och hälsovetenskap, Article in journal, info:eu-repo/semantics/article, text |
| DOI: | 10.2337.db14-0319 |
| URL: | Diabetes, 0012-1797, 2014, 63:12, s. 4378-4387 |
| الإتاحة: | Open access content. Open access content |
| ملاحظة: | English |
| أرقام أخرى: | UPE oai:DiVA.org:umu-98557 doi:10.2337/db14-0319 PMID 24947364 ISI:000345335500046 Scopus 2-s2.0-84911949202 1233676647 |
| المصدر المساهم: | UPPSALA UNIV LIBR From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1233676647 |
| قاعدة البيانات: | OAIster |
| DOI: | 10.2337.db14-0319 |
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