The influence of fenofibrate on lipid profile, endothelial dysfunction, and inflammatory markers in type 2 diabetes mellitus patients with typical and mixed dyslipidemia

Rohana Abdul Ghani, Ismail Bin Yaakob, Norasyikin A. Wahab @ A. Rahman, Suehazlyn Zainudin, Norlaila Mustafa, Norlela Sukor, Wan Nazaimoon Wan Mohamud, Khalid Abdul Kadir, Nor Azmi Kamaruddin

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Type 2 diabetes is associated with early development of endothelial dysfunction. Patients present with typical dyslipidemia (predominantly high levels of triglycerides [TG] and low levels of high-density lipoprotein cholesterol [HDL-C]) or mixed hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C] and TG with low HDL-C). Normal levels include LDL-C < 100 mg/dL, TG < 135 mg/dL, and HDL-C > 40 mg/dL for men and >50 mg/dL for women. Objective: To determine the effects of 8 weeks' administration of fenofibrate on inflammatory markers, metabolic parameters, and endothelial dysfunction. Methods: We administered micronized fenofibrate (Laboratories Fourneir S.A Dijon, France) daily for 8 weeks to 40 dyslipidemic, type 2 diabetes patients with equal numbers in each arm of the typical or mixed dyslipidemia groups. Noninvasive endothelial function assessments were performed and serum inflammatory markers obtained before and after treatment. Results: The typical group demonstrated significantly greater TG reduction and HDL-C increment, ie, 56% vs, 21.3% (P <.005) and 21% vs. 7.6% (P =.001), respectively, compared with the mixed group. There was greater LDL-C reduction within the mixed group compared with the typical group 21.0% vs. 2.2% (P <.05). Endothelial dysfunction was present in both groups at baseline. After treatment, the typical group demonstrated significant improvement in resting brachial diameter (3.9 mm [interquartile range {IQR} 3.3-4.7] to 4.2 mm [IQR 3.4-4.8], P =.001) compared with no change within the mixed group (3.6 mm [IQR 3.1-5.4] to 3.7 mm [IQR 3.1-5.3], P =.26). Flow-mediated diameter improved significantly in both groups. The mixed group had significantly greater levels of hs-CRP at baseline but no changes throughout the study. The mixed group demonstrated an increase in vascular adhesion molecule-1 from 706 ng/mL (IQR 566-1195) to 845 ng/mL (637-1653; P =.01), a reduction of tumor necrosis factor-α from 7.0 pg/mL (IQR 1.0-43.5) to 2.5 pg/mL (IQR 1.5-13.5; P =.04) throughout the study. Conclusions: We effectively compared 8 weeks of fenofibrate therapy in type 2 diabetics with contrasting lipid abnormalities. The typical dyslipidemia group showed significantly greater lipid improvements compared with the mixed dyslipidemia group. Both groups had improvements in endothelial functions that were independent of the lipid levels. We concluded that fibrate therapy in type 2 diabetics is beneficial, especially those with typical dyslipidemia and extends beyond its lipid lowering properties.

Original languageEnglish
Pages (from-to)446-453
Number of pages8
JournalJournal of Clinical Lipidology
Volume7
Issue number5
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Fenofibrate
Dyslipidemias
Type 2 Diabetes Mellitus
LDL Cholesterol
Lipids
HDL Cholesterol
Triglycerides
Fibric Acids
Therapeutics
Hypercholesterolemia
France
Blood Vessels
Arm
Tumor Necrosis Factor-alpha
Biomarkers

Keywords

  • Endothelial dysfunction
  • Fenofibrate
  • High-density lipoprotein cholesterol
  • hsCRP
  • Low density lipoprotein
  • Noninvasive endothelial function assessments
  • Triglyceride
  • Vascular cell adhesion molecule-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine
  • Nutrition and Dietetics

Cite this

The influence of fenofibrate on lipid profile, endothelial dysfunction, and inflammatory markers in type 2 diabetes mellitus patients with typical and mixed dyslipidemia. / Ghani, Rohana Abdul; Yaakob, Ismail Bin; A. Wahab @ A. Rahman, Norasyikin; Zainudin, Suehazlyn; Mustafa, Norlaila; Sukor, Norlela; Wan Mohamud, Wan Nazaimoon; Kadir, Khalid Abdul; Kamaruddin, Nor Azmi.

In: Journal of Clinical Lipidology, Vol. 7, No. 5, 09.2013, p. 446-453.

Research output: Contribution to journalArticle

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title = "The influence of fenofibrate on lipid profile, endothelial dysfunction, and inflammatory markers in type 2 diabetes mellitus patients with typical and mixed dyslipidemia",
abstract = "Background: Type 2 diabetes is associated with early development of endothelial dysfunction. Patients present with typical dyslipidemia (predominantly high levels of triglycerides [TG] and low levels of high-density lipoprotein cholesterol [HDL-C]) or mixed hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C] and TG with low HDL-C). Normal levels include LDL-C < 100 mg/dL, TG < 135 mg/dL, and HDL-C > 40 mg/dL for men and >50 mg/dL for women. Objective: To determine the effects of 8 weeks' administration of fenofibrate on inflammatory markers, metabolic parameters, and endothelial dysfunction. Methods: We administered micronized fenofibrate (Laboratories Fourneir S.A Dijon, France) daily for 8 weeks to 40 dyslipidemic, type 2 diabetes patients with equal numbers in each arm of the typical or mixed dyslipidemia groups. Noninvasive endothelial function assessments were performed and serum inflammatory markers obtained before and after treatment. Results: The typical group demonstrated significantly greater TG reduction and HDL-C increment, ie, 56{\%} vs, 21.3{\%} (P <.005) and 21{\%} vs. 7.6{\%} (P =.001), respectively, compared with the mixed group. There was greater LDL-C reduction within the mixed group compared with the typical group 21.0{\%} vs. 2.2{\%} (P <.05). Endothelial dysfunction was present in both groups at baseline. After treatment, the typical group demonstrated significant improvement in resting brachial diameter (3.9 mm [interquartile range {IQR} 3.3-4.7] to 4.2 mm [IQR 3.4-4.8], P =.001) compared with no change within the mixed group (3.6 mm [IQR 3.1-5.4] to 3.7 mm [IQR 3.1-5.3], P =.26). Flow-mediated diameter improved significantly in both groups. The mixed group had significantly greater levels of hs-CRP at baseline but no changes throughout the study. The mixed group demonstrated an increase in vascular adhesion molecule-1 from 706 ng/mL (IQR 566-1195) to 845 ng/mL (637-1653; P =.01), a reduction of tumor necrosis factor-α from 7.0 pg/mL (IQR 1.0-43.5) to 2.5 pg/mL (IQR 1.5-13.5; P =.04) throughout the study. Conclusions: We effectively compared 8 weeks of fenofibrate therapy in type 2 diabetics with contrasting lipid abnormalities. The typical dyslipidemia group showed significantly greater lipid improvements compared with the mixed dyslipidemia group. Both groups had improvements in endothelial functions that were independent of the lipid levels. We concluded that fibrate therapy in type 2 diabetics is beneficial, especially those with typical dyslipidemia and extends beyond its lipid lowering properties.",
keywords = "Endothelial dysfunction, Fenofibrate, High-density lipoprotein cholesterol, hsCRP, Low density lipoprotein, Noninvasive endothelial function assessments, Triglyceride, Vascular cell adhesion molecule-1",
author = "Ghani, {Rohana Abdul} and Yaakob, {Ismail Bin} and {A. Wahab @ A. Rahman}, Norasyikin and Suehazlyn Zainudin and Norlaila Mustafa and Norlela Sukor and {Wan Mohamud}, {Wan Nazaimoon} and Kadir, {Khalid Abdul} and Kamaruddin, {Nor Azmi}",
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TY - JOUR

T1 - The influence of fenofibrate on lipid profile, endothelial dysfunction, and inflammatory markers in type 2 diabetes mellitus patients with typical and mixed dyslipidemia

AU - Ghani, Rohana Abdul

AU - Yaakob, Ismail Bin

AU - A. Wahab @ A. Rahman, Norasyikin

AU - Zainudin, Suehazlyn

AU - Mustafa, Norlaila

AU - Sukor, Norlela

AU - Wan Mohamud, Wan Nazaimoon

AU - Kadir, Khalid Abdul

AU - Kamaruddin, Nor Azmi

PY - 2013/9

Y1 - 2013/9

N2 - Background: Type 2 diabetes is associated with early development of endothelial dysfunction. Patients present with typical dyslipidemia (predominantly high levels of triglycerides [TG] and low levels of high-density lipoprotein cholesterol [HDL-C]) or mixed hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C] and TG with low HDL-C). Normal levels include LDL-C < 100 mg/dL, TG < 135 mg/dL, and HDL-C > 40 mg/dL for men and >50 mg/dL for women. Objective: To determine the effects of 8 weeks' administration of fenofibrate on inflammatory markers, metabolic parameters, and endothelial dysfunction. Methods: We administered micronized fenofibrate (Laboratories Fourneir S.A Dijon, France) daily for 8 weeks to 40 dyslipidemic, type 2 diabetes patients with equal numbers in each arm of the typical or mixed dyslipidemia groups. Noninvasive endothelial function assessments were performed and serum inflammatory markers obtained before and after treatment. Results: The typical group demonstrated significantly greater TG reduction and HDL-C increment, ie, 56% vs, 21.3% (P <.005) and 21% vs. 7.6% (P =.001), respectively, compared with the mixed group. There was greater LDL-C reduction within the mixed group compared with the typical group 21.0% vs. 2.2% (P <.05). Endothelial dysfunction was present in both groups at baseline. After treatment, the typical group demonstrated significant improvement in resting brachial diameter (3.9 mm [interquartile range {IQR} 3.3-4.7] to 4.2 mm [IQR 3.4-4.8], P =.001) compared with no change within the mixed group (3.6 mm [IQR 3.1-5.4] to 3.7 mm [IQR 3.1-5.3], P =.26). Flow-mediated diameter improved significantly in both groups. The mixed group had significantly greater levels of hs-CRP at baseline but no changes throughout the study. The mixed group demonstrated an increase in vascular adhesion molecule-1 from 706 ng/mL (IQR 566-1195) to 845 ng/mL (637-1653; P =.01), a reduction of tumor necrosis factor-α from 7.0 pg/mL (IQR 1.0-43.5) to 2.5 pg/mL (IQR 1.5-13.5; P =.04) throughout the study. Conclusions: We effectively compared 8 weeks of fenofibrate therapy in type 2 diabetics with contrasting lipid abnormalities. The typical dyslipidemia group showed significantly greater lipid improvements compared with the mixed dyslipidemia group. Both groups had improvements in endothelial functions that were independent of the lipid levels. We concluded that fibrate therapy in type 2 diabetics is beneficial, especially those with typical dyslipidemia and extends beyond its lipid lowering properties.

AB - Background: Type 2 diabetes is associated with early development of endothelial dysfunction. Patients present with typical dyslipidemia (predominantly high levels of triglycerides [TG] and low levels of high-density lipoprotein cholesterol [HDL-C]) or mixed hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C] and TG with low HDL-C). Normal levels include LDL-C < 100 mg/dL, TG < 135 mg/dL, and HDL-C > 40 mg/dL for men and >50 mg/dL for women. Objective: To determine the effects of 8 weeks' administration of fenofibrate on inflammatory markers, metabolic parameters, and endothelial dysfunction. Methods: We administered micronized fenofibrate (Laboratories Fourneir S.A Dijon, France) daily for 8 weeks to 40 dyslipidemic, type 2 diabetes patients with equal numbers in each arm of the typical or mixed dyslipidemia groups. Noninvasive endothelial function assessments were performed and serum inflammatory markers obtained before and after treatment. Results: The typical group demonstrated significantly greater TG reduction and HDL-C increment, ie, 56% vs, 21.3% (P <.005) and 21% vs. 7.6% (P =.001), respectively, compared with the mixed group. There was greater LDL-C reduction within the mixed group compared with the typical group 21.0% vs. 2.2% (P <.05). Endothelial dysfunction was present in both groups at baseline. After treatment, the typical group demonstrated significant improvement in resting brachial diameter (3.9 mm [interquartile range {IQR} 3.3-4.7] to 4.2 mm [IQR 3.4-4.8], P =.001) compared with no change within the mixed group (3.6 mm [IQR 3.1-5.4] to 3.7 mm [IQR 3.1-5.3], P =.26). Flow-mediated diameter improved significantly in both groups. The mixed group had significantly greater levels of hs-CRP at baseline but no changes throughout the study. The mixed group demonstrated an increase in vascular adhesion molecule-1 from 706 ng/mL (IQR 566-1195) to 845 ng/mL (637-1653; P =.01), a reduction of tumor necrosis factor-α from 7.0 pg/mL (IQR 1.0-43.5) to 2.5 pg/mL (IQR 1.5-13.5; P =.04) throughout the study. Conclusions: We effectively compared 8 weeks of fenofibrate therapy in type 2 diabetics with contrasting lipid abnormalities. The typical dyslipidemia group showed significantly greater lipid improvements compared with the mixed dyslipidemia group. Both groups had improvements in endothelial functions that were independent of the lipid levels. We concluded that fibrate therapy in type 2 diabetics is beneficial, especially those with typical dyslipidemia and extends beyond its lipid lowering properties.

KW - Endothelial dysfunction

KW - Fenofibrate

KW - High-density lipoprotein cholesterol

KW - hsCRP

KW - Low density lipoprotein

KW - Noninvasive endothelial function assessments

KW - Triglyceride

KW - Vascular cell adhesion molecule-1

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