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Insulin resistance-related lipoproteins linked to diabetes risk
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A lipoprotein-based insulin resistance index, very low density lipoprotein particle concentration and size, triglycerides and their ratio with HDL cholesterol were associated with incident diabetes across a range of ages and ethnicities, according to research published in Diabetes Care.
“Insulin resistance is associated with changes in levels of lipids and lipoproteins, which may occur independently and precede insulin resistance-related changes in levels of glucose, insulin, and homeostasis model assessment of insulin resistance,” Rachel H. Mackey, PhD, MPH, of the University of Pittsburgh Graduate School of Public Health, told Endocrine Today.
Rachel H. Mackey
These relationships demonstrated in participants from the prospective Multi-Ethnic Study of Atherosclerosis were independent of established risk factors, glucose, insulin or homeostasis model assessment of insulin resistance (HOMA-IR), and the use of lipid-lowering medications or hormone therapy.
“Our study found that higher baseline levels of lipoprotein-based insulin resistance index, an insulin-resistance index calculated from lipoprotein particles and size, higher levels of large very low density lipoprotein particles, triglycerides, the triglyceride:HDL cholesterol ratio and larger mean very low density lipoprotein size add to glucose, insulin and HOMA-IR in predicting risk of incident diabetes among adults not using or using lipid-lowering medications or hormone therapy at baseline,” Mackey said.
Mackey and colleagues from other institutions examined data from 5,314 men and women from the multicenter study.
Participants were aged 45 to 84 years, of black, Hispanic, white or Chinese ethnicities with no diabetes or cardiovascular disease at baseline. During a mean follow-up of 7.7 years, 656 cases of diabetes were identified.
Through nuclear magnetic resonance spectroscopy of stored baseline plasma, the researchers determined lipoprotein particle concentrations and size and the lipoprotein-based insulin resistance (LP-IR) index.
The researchers also assessed potential effect modification by race/ethnicity, sex, baseline use of lipid-lowering medications or HT, and glucose strata (< 90 mg/dL, 90-99 mg/dL and ≥ 100 mg/dL).
Significant associations existed between higher levels of LP-IR, large very low density lipoprotein (VLDL) particles, small LDL particles, triglycerides (TG) and TG:HDL cholesterol ratio and lower levels of large HDL particles, smaller HDL and LDL size.
Larger VLDL particle size significantly correlated with incident diabetes, after adjusting for confounders and glucose or insulin. Similar results were seen across race/ethnicity, sex and treatment group.
The relationships were similar for LP-IR, large VLDL particles, mean VLDL size, TG and TG:HDL ratio and persisted for LP-IR, large VLDL particles, or mean VLDL size, with adjustments for HOMA-IR or TG:HDL-C ratio and glucose; this was not the case for the TG-to-HDL-C ratio, when adjusted for LP-IR or for HOMA-IR or insulin adjusted for LP-IR and glucose.
“These results suggest that lipids and lipoproteins may provide information about risk of diabetes even among individuals using some common lipid-altering medications,” Mackey said. “This hypothesis should be tested in clinical trials.” - by Allegra Tiver
For more information:
Rachel H. Mackey, PhD, MPH, can be reached at the University of Pittsburgh Graduate School of Public Health, 542 Bellefield Professional Building, 130 N. Bellefield Ave, University of Pittsburgh, Pittsburgh PA 15213; email: mackey@edc.pitt.edu.
Disclosure:
Mackey was funded by an unrestricted research grant from LipoScience Inc. and reports speaker honoraria from the National Lipid Association for educational activities. Other researchers report relationships with Abbott, AstraZeneca, Atherotec Diagnostics, Genzyme, Merck, the National Heart, Lung, and Blood Institute, National Lipid Association, Pfizer and Quest Diagnostics.
Perspective
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Kavita Sharma, MD
Mackey and colleagues raise the question of whether the LP-IR index, large VLDL particles, large VLDL size, TG and TG:HDL-C better predict the onset of diabetes than established risk factors, glucose, insulin or HOMA-IR. Although these variables may prove to be superior in the prediction of diabetes, this is not to say that traditional, readily available factors are not useful. Models combining age, family history of diabetes, body mass index, metabolic syndrome traits, and standard lipid profile levels have been shown to be beneficial in estimation of risk of diabetes. Perhaps a direct comparison of the different models may define an answer. The researchers also found that the LP-IR score is predictive of diabetes in patients on lipid-lowering therapy. The confirmation that an LP-IR score relates to diabetes risk among those on lipid-lowering therapy (primarily statins) does reinforce prior findings in clinical trials of statins that high triglycerides and high glucose concentration relate to increased diabetes risk, supporting the notion that characteristics of patients on statin therapy may contribute to their risk of the development of future diabetes.
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