ArticleDiabetes2011
Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 3 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 3 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- Pooled it
- Pooled it
- Multiple metabolic genetic risk scores and type 2 diabetes risk in three racial/ethnic groups.The Journal of clinical endocrinology and metabolism · 2014Pooled it
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- Impact of Remnant Cholesterol on Cardiovascular Risk in Diabetes.Current diabetes reports · 2024Review
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- Elevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity.Nature communications · 2024Article
- Age effect on the shared etiology of glycemic traits and serum lipids: evidence from a Chinese twin study.Journal of endocrinological investigation · 2024Article
- Fabrication and characterization of gold nanoparticles using alginate:Open life sciences · 2024Article
- Investigating sex-specific associations of lipid traits with type 2 diabetes, glycemic traits and sex hormones using Mendelian randomization.Cardiovascular diabetology · 2023Article
- Type 2 Diabetes Risk and Lipid Metabolism Related to the Pleiotropic Effects of anMetabolites · 2022Article
- Higher fasting triglyceride predicts higher risks of diabetes mortality in US adults.Lipids in health and disease · 2021Article
- Diminished 25-OH vitamin DJournal of clinical laboratory analysis · 2020Article
- Genetic contributions to NAFLD: leveraging shared genetics to uncover systems biology.Nature reviews. Gastroenterology & hepatology · 2020Review
- Causal relationships between lipid and glycemic levels in an Indian population: A bidirectional Mendelian randomization approach.PloS one · 2020Article
- Genetically Mediated Lipid Metabolism and Risk of Insulin Resistance: Insights from Mendelian Randomization Studies.Journal of lipid and atherosclerosis · 2019Review
- Association between the XKR6 rs7819412 SNP and serum lipid levels and the risk of coronary artery disease and ischemic stroke.BMC cardiovascular disorders · 2019Article
- Mendelian Randomization Analysis Support Causal Associations of HbA1c with Circulating Triglyceride, Total and Low-density Lipoprotein Cholesterol in a Chinese Population.Scientific reports · 2019Article
- Gene-Based Elevated Triglycerides and Type 2 Diabetes Mellitus Risk in the Women's Genome Health Study.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
Corrections and comments
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Authors and funding
22 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe 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
methodsWe 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.
resultsIndividuals 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).
conclusionsGenetically 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.