Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes mellitus

Hiukka, A.; Leinonen, E.; Jauhiainen, M.; Sundvall, J.; Ehnholm, C.; Keech, A. C.; Taskinen, M. R.

doi:10.1007/s00125-007-0751-8

Cited by 68Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsLipid metabolism and disorders

Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes mellitus

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Hiukka, A., Leinonen, E., Jauhiainen, M., Sundvall, J., Ehnholm, C., Keech, A. C., Taskinen, M. R.·2007·Diabetologia

DOI 10.1007/s00125-007-0751-8

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Abstract

Aims/hypothesis Low HDL-cholesterol (HDL-C) is frequently accompanied by high triacylglycerol levels in diabetic dyslipidaemia, increasing the risk of CHD. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, fenofibrate treatment lowered triacylglycerol levels, but the initial 5% increase in HDL-C attenuated over 5 years. We explored the changes in VLDL and HDL subspecies during fenofibrate treatment in a statin-free FIELD cohort. Methods We randomised 171 participants with type 2 diabetes mellitus, who had been recruited to the FIELD study in Helsinki, to micronised fenofibrate (200 mg/day) or placebo in double-blind study design. VLDL and HDL subspecies were separated by ultracentrifugation at baseline and at the second and fifth year. Apolipoprotein (apo)A-I and apoA-II were measured by immunoturbidometric methods and lipoprotein (Lp)A-I and LpAI-AII particles by differential immunoassay. Results Fenofibrate reduced plasma triacylglycerol levels by 26%, resulting from a marked reduction in VLDL1 triacylglycerol (0.62 vs 0.29 mmol/l, p < 0.001). Fenofibrate caused an increase in LDL size (Delta 0.80 nm, p < 0.001). HDL-C was similar between the groups. HDL2-C was decreased by fenofibrate (-27.5% at 5th year, p < 0.001) and HDL3-C increased (13.0% at 5th year, p < 0.001). Fenofibrate had no effect on apoA-I, whereas apoA-II increased. Thus, LpA-I decreased while LpAI-AII increased. Activities of cholesteryl ester transfer protein, phospholipids transfer protein and lecithin:cholesterylacyl transferase were unchanged by fenofibrate. High homocysteine levels were associated with a slight decrease in HDL-C and apoA-I. Conclusions/interpretation Fenofibrate markedly reduced large VLDL particles and produced a clear shift in HDL subspecies towards smaller particles. The HDL3-C increase in conjunction with unchanged apoA-I [corrected] levels is a dilemma with regard to cardiovascular disease.

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Fenofibrate treatment typically reduces serum triglycerides by a mean change of −93.7 mg/dL (−39.3%), increases high density lipoprotein cholesterol by +5.5 mg/dL (+12.4%), and reduces low density lipoprotein cholesterol by −17.9 mg/dL (−12.3%).
“Typical changes in serum lipids as a result of FF treatment include clinically important mean reductions of serum triglycerides (TG) by a mean change of −93.7 mg/dL (−39.3%), increases of high density lipoprotein cholesterol (HDLC) by +5.5 mg/dL (+12.4%), and reductions in low density lipoprotein cholesterol (LDLC) by −17.9 mg/dL (−12.3%).”
From Fenofibrate and metabolic syndrome (2010) · cites this paper as [40]

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Long-term effects of fenofibrate on lipoproteins and surrogate markers of macrovascular and microvascular disease in people with type 2 diabetes
Hiukka, A. (2009) · Työväentutkimus Vuosikirja
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Authors: Hiukka, A., Leinonen, E., Jauhiainen, M., Sundvall, J., Ehnholm, C., Keech, A. C., & Taskinen, M. R.
Affiliations: Helsinki University Hospital (FI)
The University of Sydney (AU)
Corresponding author: Taskinen, M. R.
ORCID: Jauhiainen, M.
Keech, A. C.
Taskinen, M. R.
Venue: Diabetologia
Publisher: Springer Science and Business Media LLC
Published: 2007-07-26
Volume: 50
Issue: 10
Pages: 2067-2075
ISSN: 0012-186X (ISSN-L)
1432-0428
DOI: 10.1007/s00125-007-0751-8
OpenAlex: W2049360498
Cited by: 68
References: 42
Citations by year: 2026: 1 · 2025: 5 · 2023: 2 · 2022: 4 · 2020: 2 · 2019: 4 · 2017: 1 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 4
FWCI: 9.96
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Diabetologia (publishedVersion)
PubMed (publishedVersion)
Griffith Research Online (submittedVersion)
Funders: Eli Lilly and Company
Helsingin ja Uudenmaan Sairaanhoitopiiri
Aarne Koskelon Säätiö
Biomedicum Helsinki-säätiö
Diabetesliitto
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords: fenofibrate, type 2 diabetes, HDL subfractions, HDL3 cholesterol, apolipoprotein A-II, LDL particle size, diabetic dyslipidemia, homocysteine, cholesteryl ester transfer protein
MeSH terms: Aged, Hypolipidemic Agents, Cholesterol, Diabetes Mellitus, Type 2, Female, Homocysteine, Humans, Lipoproteins, HDL, Cholesterol, HDL, Cholesterol, LDL, Lipoproteins, VLDL, Male, Middle Aged, Placebos, Fenofibrate

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Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes mellitus

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