The hypertriglyceridemic clamp technique. Studies using long-chain and structured triglyceride emulsions in healthy subjects.
In a randomized crossover study, plasma kinetics of 2 different types of fat emulsions were studied in 8 healthy volunteers by using a hypertriglyceridemic clamp technique. The method involves the stabilization of serum triglyceride (TG) concentration during 180 minutes at a predetermined level (4 mmol/L) by adjustment of TG infusion rate by repeated online measurements of serum TG concentration. The fat emulsions under study were a long-chain fatty acid triglyceride (LCT) emulsion (Intralipid 20%, Fresenius Kabi, Sweden) and a structured triglyceride (STG) emulsion (Structolipid 20%, Fresenius Kabi) where medium- and long-chain fatty acids have been interesterified within a TG molecule. The hypertriglyceridemic clamp was found to have acceptable reproducibility when tested in 3 healthy individuals on 2 different occasions, as similar steady-state TG levels were obtained by infusing similar amounts of fat. The average (+/-SEM) TG concentration during the 180-minute clamp was similar for STGs and LCTs (4.0 +/- 0.1 vs 3.9 +/- 0.1 mmol/L; not significant), but the amount of fat that had to be infused was significantly higher during STG than during LCT clamping (0.31 +/- 0.04 vs 0.21 +/- 0.02 g TG per minute; P < .05). Higher serum levels of free fatty acids (1.80 +/- 0.13 vs 0.96 +/- 0.09 mmol/L; P < .05), free glycerol (1.30 +/- 0.07 vs 0.76 +/- 0.08 mmol/L; P < .001), and beta-OH butyrate (1.61 +/- 0.44 vs 1.17 +/- 0.23 mmol/L; not significant) were obtained at the end of the clamp during infusion of STGs compared with LCTs. During infusion of STGs the medium-chain fatty acids octanoic (C:8) and decanoic acid (C:10) constituted approximately half of circulating fatty acids that correspond to the compositional ratio of the emulsion. Plasma lipoprotein lipase (LPL) concentration was higher during STG than during LCT clamping (6.06 +/- 0.62 vs 3.15 +/- 0.40 mU/mL; P < .05), and there was a positive correlation between the mean LPL concentration and the amount of infused TG during the steady-state period (r = 0.58; P < .05). In conclusion, the hypertriglyceridemic clamp method was found to give reproducible results and could be considered for comparison of metabolic clearance properties of different types of fat emulsions. The capacity of healthy subjects to eliminate STGs from blood was greater than for LCTs. An increased LPL activity induced by the higher TG infusion rate may have contributed to the increased metabolic clearance of STGs.
Nordenström
Jörgen
J
Department of Surgery, Karolinska University Hospital-Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden. jorgen.nordstrom@ki.se
Thörne
Anders
A
Aberg
Wiveca
W
Carneheim
Claes
C
Olivecrona
Thomas
T
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D005217:Fat Emulsions, Intravenous / Q000493:pharmacokinetics*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D008049:Lipase / Q000097:blood; D008071:Lipoprotein Lipase / Q000097:blood; D008297:Male; D015203:Reproducibility of Results; D014280:Triglycerides / Q000097:blood / Q000493:pharmacokinetics*
D001786:Blood Glucose; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; C504173:LIPC protein, human; D014280:Triglycerides; D002784:Cholesterol; D008049:Lipase; D008071:Lipoprotein Lipase