Discovery - University of Dundee - Online Publications

Library & Learning Centre

Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.

Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.

Research output: Contribution to journalArticle

View graph of relations

Authors

  • N. Maneka G. De Silva
  • Rachel M. Freathy
  • Tom M. Palmer
  • Louise A. Donnelly
  • Jian'an Luan
  • Tom Gaunt
  • Claudia Langenberg
  • Michael N. Weedon
  • Beverley Shields
  • Beatrice A. Knight
  • Kirsten J. Ward
  • Manjinder S. Sandhu
  • Roger M. Harbord
  • Mark I. McCarthy
  • George Davey Smith
  • Shah Ebrahim
  • Andrew T. Hattersley
  • Nicholas Wareham
  • Debbie A. Lawlor
  • Colin N. A. Palmer
  • Timothy M. Frayling

Research units

Info

Original languageEnglish
Pages1008-1018
Number of pages11
JournalDiabetes
Journal publication dateMar 2011
Journal number3
Volume60
DOIs
StatePublished

Abstract

OBJECTIVE-The causal nature of associations between circulating triglycerides, insulin resistance, and type 2 diabetes is unclear. We aimed to use Mendelian randomization to test the hypothesis that raised circulating triglyceride levels causally influence the risk of type 2 diabetes and raise normal fasting glucose levels and hepatic insulin resistance.

RESEARCH DESIGN AND METHODS-We tested 10 common genetic variants robustly associated with circulating triglyceride levels against the type 2 diabetes status in 5,637 case and 6,860 control subjects and four continuous outcomes (reflecting glycemia and hepatic insulin resistance) in 8,271 nondiabetic individuals from four studies.

RESULTS-Individuals carrying greater numbers of triglyceride-raising alleles had increased circulating triglyceride levels (SD 0.59 [95% CI 0.52-0.65] difference between the 20% of individuals with the most alleles and the 20% with the fewest alleles). There was no evidence that the carriers of greater numbers of triglyceride-raising alleles were at increased risk of type 2 diabetes (per weighted allele odds ratio [OR] 0.99 [95% CI 0.97-1.01]; P = 0.26). In nondiabetic individuals, there was no evidence that carriers of greater numbers of triglyceride-raising alleles had increased fasting insulin levels (SD 0.00 per weighted allele [95% CI -0.01 to 0.02]; P = 0.72) or increased fasting glucose levels (0.00 [-0.01 to 0.01]; P = 0.88). Instrumental variable analyses confirmed that genetically raised circulating triglyceride levels were not associated with increased diabetes risk, fasting glucose, or fasting insulin and, for diabetes, showed a trend toward a protective association (OR per 1-SD increase in log(10) triglycerides: 0.61 [95% CI 0.45-0.83]; P = 0.002).

CONCLUSIONS-Genetically raised circulating triglyceride levels do not increase the risk of type 2 diabetes or raise fasting glucose or fasting insulin levels in nondiabetic individuals. One explanation for our results is that raised circulating triglycerides are predominantly secondary to the diabetes disease process rather than causal. Diabetes 60:1008-1018, 2011

Documents

Library & Learning Centre

Contact | Accessibility | Policy