Insulin resistance but not hypertriglyceridemia per se is associated with endothelial dysfunction in chronic hypertriglyceridemia.
OBJECTIVE
To infer the relative impact of elevated triglyceride levels and insulin resistance on endothelial dysfunction in patients with chronic hypertriglyceridemia (HTG).


METHODS
Endothelial function was studied in 11 HTG patients and 16 normolipidemic controls. Cumulative-dose infusions of 5-hydroxytryptamine (5HT) and sodium nitroprusside were infused locally into the brachial artery to study endothelium-dependent and endothelium-independent vasodilation, respectively. Data of the HTG patients were dichotomized around the median of insulin resistance, calculated as HOMA-index, forming HTG groups with mild (HTG-MIR) and severe insulin resistance (HTG-SIR).


RESULTS
HTG patients had higher triglyceride levels and smaller LDL particle size than controls (both P< or =0.001), whereas these parameters did not differ between both HTG groups. Insulin resistance was higher in both HTG groups than in controls (11.1 (7.0-14.5) and 4.9 (4.0-6.7) vs. 2.4 (4.9-5.2), respectively, both P<0.001). Similarly, free fatty acid levels, another indicator of insulin resistance, were highest in the HTG-SIR group, followed by those in the HTG-MIR and control group (0.7 (0.6-0.8), 0.5 (0.4-0.6) and 0.4 (0.3-0.4) mmol/l, respectively, all P<0.05). Endothelial-dependent vasodilation was similar in HTG-MIR and controls. In contrast, the response to 5HT was attenuated in the HTG-SIR group compared to controls (low and high dose by, respectively, -60 and -44%, both P<0.01), and tended to be lower than in the HTG-MIR group (-43%, P=0.068 and -41%, P=0.100, respectively). Endothelium-independent vasodilation did not differ between the three groups.


CONCLUSIONS
These findings indicate that chronic hypertriglyceridemia per se is not associated with endothelial dysfunction. In contrast, the presence of insulin resistance, characterized by hyperinsulinemia and FFA elevation, contributes to the induction of endothelial dysfunction in chronic HTG.
Jonkers
I J A M
IJ
Department of General Internal Medicine, Leiden Universiy Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
van de Ree
M A
MA
Smelt
A H M
AH
de Man
F H A F
FH
Jansen
H
H
Meinders
A E
AE
van der Laarse
A
A
Blauw
G J
GJ
D000328:Adult; D016022:Case-Control Studies; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000378:metabolism / Q000503:physiopathology*; D007333:Insulin Resistance; D008077:Lipoproteins, LDL; D008875:Middle Aged; D009599:Nitroprusside; D010316:Particle Size; D012701:Serotonin; D018709:Statistics, Nonparametric; D014665:Vasodilator Agents
D005230:Fatty Acids, Nonesterified; D008077:Lipoproteins, LDL; D014665:Vasodilator Agents; D009599:Nitroprusside; D012701:Serotonin