Effect of an acute hyperinsulinaemic clamp on post-prandial lipaemia in subjects with insulin resistance.
BACKGROUND
Obese, insulin-resistant individuals have raised levels of intestinal and hepatic lipoproteins. Insulin decreases the production of hepatic lipoproteins in vivo and so this study aimed to investigate whether an acute hyperinsulinaemic, euglycaemic clamp could correct fasting and post-prandial dyslipidaemia.


METHODS
In a randomized, cross-over design, post-prandial lipaemia was compared in subjects infused either with insulin to achieve a steady-state concentration of 100 mU L(-1) or with saline. Nine obese (Body Mass Index > 26 kg m(-2); waist : hip > 1.0) insulin-resistant (Homeostatic Model Assessment score > 2.0) male subjects were given an oral fat load 3 h after the infusions began, and sampling continued for 6 h. Plasma apoB-48, triglyceride and nonesterified fatty acid (NEFA) were measured hourly.


RESULTS
Average steady-state serum insulin levels during the hyperinsulinaemic clamp were 123 +/- 4.4 mU L(-1). A paired analysis showed no net effect of insulin on post-prandial chylomicron metabolism when calculated as the (apoB-48) incremental area under the curve (IAUC). However, there was a trend towards a delay in the apoB-48 peak, consistent with possible changes in the rates of chylomicron biogenesis, lipolysis and/or clearance. Similarly, post-prandial lipaemia (depicted as triglyceride IAUC) was similar for subjects infused with insulin or saline, but the peak post-prandial response was delayed during insulin infusion. The NEFA were rapidly decreased by 83% after 3 h of insulin infusion.


CONCLUSIONS
In obesity and insulin resistance, short-term changes in plasma insulin do not appreciably exert a regulatory effect on exogenously-derived post-prandial lipoproteins. The data suggest that hyperchylomicronaemia in insulin-resistant subjects is a result of chronic aberrations in insulin-mediated regulation of post-prandial lipid metabolism.
Allister
E M
EM
ATN Centre for Metabolic Fitness, Division of Health Sciences, Curtin University of Technology, Kent Street, Bentley, Western Australia 6102.
James
A P
AP
Watts
G F
GF
Barrett
P H R
PH
Mamo
J C L
JC
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002914:Chylomicrons / Q000097:blood; D018592:Cross-Over Studies; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000628:therapy*; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique / Q000379:methods*; D006801:Humans; D007263:Infusions, Parenteral; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000150:complications; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D001786:Blood Glucose; D002914:Chylomicrons; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides