Chylomicron remnant metabolism studied with a new breath test in postmenopausal women with and without type 2 diabetes mellitus.
OBJECTIVE
The kinetic basis for the effect of type 2 diabetes mellitus (DM) on postprandial lipoproteins has not been fully established. We investigated chylomicron remnant metabolism using a stable isotope breath test and fasting measurements of plasma apolipoprotein (apo) B-48 and apoC-III concentrations in postmenopausal women with and without type 2 DM.


METHODS
Twenty-four postmenopausal women without DM and 14 postmenopausal women with diet-controlled DM of similar age and body mass index (BMI) were studied in the postabsorptive state.


METHODS
The fractional catabolic rate (FCR) of an intravenously injected chylomicron remnant-like emulsion was determined from the appearance of 13CO2 in the breath using isotope-ratio mass spectrometry and multicompartmental modelling. apoB-48, a marker of particle number of intestinal lipoproteins, was determined immunoelectrophoretically. apoC-III was measured by immunoturbidimetric assay.


RESULTS
Compared with the nondiabetic women, the women with DM had significantly higher plasma apoB-48 concentration (16.40 +/- 1.18 mg/l vs. 13.0 +/- 0.9 mg/l; mean +/- standard error mean; P = 0.021), higher plasma apoC-III concentration (204.24 +/- 15.18 mg/l vs. 170.74 +/- 10.75 mg/l; P = 0.042) and lower FCR of the chylomicron remnant-like emulsion (0.06 +/- 0.05 pools/h vs. 0.12 +/- 0.02 pools/h; P < 0.001). In the diabetic patients, the FCR of the emulsion was correlated significantly with plasma apoB-48 levels (r = -0.641, P = 0.007) but not with apoC-III levels.


CONCLUSIONS
In postmenopausal women, diabetes mellitus appears to decrease the catabolism of chylomicron remnants and result in an accumulation of these particles in plasma. This may chiefly be due to decreased clearance by hepatic receptors related to an effect of insulin resistance. Impairment in the catabolism of chylomicron remnants may contribute to increased risk of atherosclerosis in postmenopausal women with type 2 diabetes mellitus.
Dane-Stewart
C A
CA
University Department of Medicine, Royal Perth Hospital, University of Western Australia and Western Australian Institute for Medical Research, Perth, Australia.
Watts
G F
GF
Barrett
P H R
PH
Stuckey
B G A
BG
Mamo
J C L
JC
Martins
I J
IJ
Redgrave
T G
TG
D053283:Apolipoprotein B-48; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B / Q000032:analysis; D001056:Apolipoproteins C / Q000032:analysis; D001161:Arteriosclerosis / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D001944:Breath Tests; D002247:Carbon Isotopes; D016022:Case-Control Studies; D002914:Chylomicrons / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007122:Immunoelectrophoresis / Q000379:methods; D007553:Isotope Labeling; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood / Q000378:metabolism*; D012306:Risk; D018709:Statistics, Nonparametric
D053283:Apolipoprotein B-48; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D015415:Biomarkers; D002247:Carbon Isotopes; D002914:Chylomicrons