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.

Standard

Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.. / De Silva, N. Maneka G.; Freathy, Rachel M.; Palmer, Tom M.; Donnelly, Louise A.; Luan, Jian'an; Gaunt, Tom; Langenberg, Claudia; Weedon, Michael N.; Shields, Beverley; Knight, Beatrice A.; Ward, Kirsten J.; Sandhu, Manjinder S.; Harbord, Roger M.; McCarthy, Mark I.; Smith, George Davey; Ebrahim, Shah; Hattersley, Andrew T.; Wareham, Nicholas; Lawlor, Debbie A.; Morris, Andrew D.; Palmer, Colin N. A.; Frayling, Timothy M.

In: Diabetes, Vol. 60, No. 3, 03.2011, p. 1008-1018.

Research output: Contribution to journalArticle

Harvard

De Silva, NMG, Freathy, RM, Palmer, TM, Donnelly, LA, Luan, J, Gaunt, T, Langenberg, C, Weedon, MN, Shields, B, Knight, BA, Ward, KJ, Sandhu, MS, Harbord, RM, McCarthy, MI, Smith, GD, Ebrahim, S, Hattersley, AT, Wareham, N, Lawlor, DA, Morris, AD, Palmer, CNA & Frayling, TM 2011, 'Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.' Diabetes, vol 60, no. 3, pp. 1008-1018., 10.2337/db10-1317

APA

De Silva, N. M. G., Freathy, R. M., Palmer, T. M., Donnelly, L. A., Luan, J., Gaunt, T., ... Frayling, T. M. (2011). Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.Diabetes, 60(3), 1008-1018. 10.2337/db10-1317

Vancouver

De Silva NMG, Freathy RM, Palmer TM, Donnelly LA, Luan J, Gaunt T et al. Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance. Diabetes. 2011 Mar;60(3):1008-1018. Available from: 10.2337/db10-1317

Author

De Silva, N. Maneka G.; Freathy, Rachel M.; Palmer, Tom M.; Donnelly, Louise A.; Luan, Jian'an; Gaunt, Tom; Langenberg, Claudia; Weedon, Michael N.; Shields, Beverley; Knight, Beatrice A.; Ward, Kirsten J.; Sandhu, Manjinder S.; Harbord, Roger M.; McCarthy, Mark I.; Smith, George Davey; Ebrahim, Shah; Hattersley, Andrew T.; Wareham, Nicholas; Lawlor, Debbie A.; Morris, Andrew D.; Palmer, Colin N. A.; Frayling, Timothy M. / Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance..

In: Diabetes, Vol. 60, No. 3, 03.2011, p. 1008-1018.

Research output: Contribution to journalArticle

Bibtex - Download

@article{407d22097c9f4814a0c738ef57cb61e3,
title = "Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.",
keywords = "PANCREATIC BETA-CELL, CORONARY-ARTERY-DISEASE, LIPOPROTEIN-LIPASE, FASTING GLUCOSE, BLOOD-PRESSURE, PLASMA TRIGLYCERIDES, RISK-FACTORS, FATTY LIVER, MELLITUS, BEZAFIBRATE",
author = "{De Silva}, {N. Maneka G.} and Freathy, {Rachel M.} and Palmer, {Tom M.} and Donnelly, {Louise A.} and Jian'an Luan and Tom Gaunt and Claudia Langenberg and Weedon, {Michael N.} and Beverley Shields and Knight, {Beatrice A.} and Ward, {Kirsten J.} and Sandhu, {Manjinder S.} and Harbord, {Roger M.} and McCarthy, {Mark I.} and Smith, {George Davey} and Shah Ebrahim and Hattersley, {Andrew T.} and Nicholas Wareham and Lawlor, {Debbie A.} and Morris, {Andrew D.} and Palmer, {Colin N. A.} and Frayling, {Timothy M.}",
year = "2011",
doi = "10.2337/db10-1317",
volume = "60",
number = "3",
pages = "1008--1018",
journal = "Diabetes",
issn = "0012-1797",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.

A1 - De Silva,N. Maneka G.

A1 - Freathy,Rachel M.

A1 - Palmer,Tom M.

A1 - Donnelly,Louise A.

A1 - Luan,Jian'an

A1 - Gaunt,Tom

A1 - Langenberg,Claudia

A1 - Weedon,Michael N.

A1 - Shields,Beverley

A1 - Knight,Beatrice A.

A1 - Ward,Kirsten J.

A1 - Sandhu,Manjinder S.

A1 - Harbord,Roger M.

A1 - McCarthy,Mark I.

A1 - Smith,George Davey

A1 - Ebrahim,Shah

A1 - Hattersley,Andrew T.

A1 - Wareham,Nicholas

A1 - Lawlor,Debbie A.

A1 - Morris,Andrew D.

A1 - Palmer,Colin N. A.

A1 - Frayling,Timothy M.

AU - De Silva,N. Maneka G.

AU - Freathy,Rachel M.

AU - Palmer,Tom M.

AU - Donnelly,Louise A.

AU - Luan,Jian'an

AU - Gaunt,Tom

AU - Langenberg,Claudia

AU - Weedon,Michael N.

AU - Shields,Beverley

AU - Knight,Beatrice A.

AU - Ward,Kirsten J.

AU - Sandhu,Manjinder S.

AU - Harbord,Roger M.

AU - McCarthy,Mark I.

AU - Smith,George Davey

AU - Ebrahim,Shah

AU - Hattersley,Andrew T.

AU - Wareham,Nicholas

AU - Lawlor,Debbie A.

AU - Morris,Andrew D.

AU - Palmer,Colin N. A.

AU - Frayling,Timothy M.

PY - 2011/3

Y1 - 2011/3

N2 - <p>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.</p><p>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.</p><p>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).</p><p>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</p>

AB - <p>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.</p><p>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.</p><p>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).</p><p>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</p>

KW - PANCREATIC BETA-CELL

KW - CORONARY-ARTERY-DISEASE

KW - LIPOPROTEIN-LIPASE

KW - FASTING GLUCOSE

KW - BLOOD-PRESSURE

KW - PLASMA TRIGLYCERIDES

KW - RISK-FACTORS

KW - FATTY LIVER

KW - MELLITUS

KW - BEZAFIBRATE

U2 - 10.2337/db10-1317

DO - 10.2337/db10-1317

M1 - Article

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 3

VL - 60

SP - 1008

EP - 1018

ER -

Documents

Library & Learning Centre

Contact | Accessibility | Policy