The influence of fenofibrate on lipid profile, endothelial dysfunction, and inflammatory markers in type 2 diabetes mellitus patients with typical and mixed dyslipidemia.
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.
Department of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. Electronic address: agrohana@gmail.com.
Rohana Abdul
RA
Ghani
Ismail
I
Bin Yaakob
Norasyikin Abdul
NA
Wahab
Suehazlyn
S
Zainudin
Norlaila
N
Mustafa
Norlela
N
Sukor
Wan Nazaimoon
WN
Wan Mohamud
Khalid Abdul
KA
Kadir
Nor Azmi
NA
Kamaruddin
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D050171:Dyslipidemias / Q000097:blood* / Q000150:complications / Q000473:pathology*; D004727:Endothelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000378:metabolism; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D000960:Hypolipidemic Agents; D008055:Lipids; D011345:Fenofibrate
Endothelial dysfunction; Fenofibrate; High-density lipoprotein cholesterol; Low density lipoprotein; Noninvasive endothelial function assessments; Triglyceride; Vascular cell adhesion molecule-1; hsCRP