Normal VLDL metabolism despite altered lipoprotein composition in type 1 diabetes mellitus.
OBJECTIVE
Patients with type 1 diabetes are at increased risk of cardiovascular disease, which may be related to abnormal lipid metabolism. Secretion and clearance of VLDL apolipoprotein B100 (apoB) are important determinants of plasma lipid concentrations and are known to be influenced by hormones, including insulin and growth hormone.


METHODS
This study examined overnight VLDL apoB metabolism and VLDL composition in six lean patients with type 1 diabetes during euglycaemia (controlled by a varying insulin infusion) and in six age-, sex- and BMI-matched control subjects.


METHODS
VLDL apoB kinetics were determined using a primed constant 1-13C leucine infusion, and VLDL apoB enrichment was measured by gas-chromatography mass-spectrometry. Fasting lipid profile, IGF-I, IGFBP-3, overnight GH profiles and free insulin concentrations were also assessed.


RESULTS
Fasting concentrations of triglycerides (TG), total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) were similar in both groups. The VLDL apoB secretion and metabolic clearance rates were not significantly different between the two groups, but the VLDL-TGNLDL apoB and the VLDL-CNLDL apoB ratios were significantly increased in those with diabetes (P < 0.02 and P < 0.03, respectively). Total IGF-I concentrations were similar between the two groups; however, the GH area under the curve and free insulin concentrations were increased in patients with type 1 diabetes (GH: diabetes: 94.8 +/- 15.1 vs. controls: 45.6 +/- 10-6, mU/L/h, P < 0.04; free insulin: diabetes: 78.4 +/- 5.0 vs. controls: 28.3 +/- 3.26, pmol/l, P < 0.001). IGFBP-3 concentrations were lower in diabetic patients (diabetes: 2,454.2 +/- 68.7 vs. controls: 3,219.4 +/- 76.4, ng/ml, P < 0.001). In the control group overnight GH secretion correlated negatively with fasting TC (P < 0.01) and LDL-C (P < 0.03) concentrations, whereas free insulin concentrations correlated positively with fasting TG concentrations (P < 0.009). No significant correlations were found in the patients with diabetes.


CONCLUSIONS
This study suggests that in euglycaemic conditions patients with type 1 diabetes mellitus have normal VLDL apoB kinetics but altered VLDL composition. The altered VLDL composition may be associated with accelerated atherogenesis. We speculate that the disrupted hormonal balance and, in particular, the increased GH secretion might be responsible for the compositional changes of VLDL particles in type 1 diabetes mellitus.
Christ
E R
ER
Department of Medicine, King's College London, St Thomas's Hospital, UK. Emanuel.Christ@insel.ch
Carroll
P V
PV
Albany
E
E
Umpleby
A M
AM
Lumb
P J
PJ
Wierzbicki
A S
AS
Simpson
H L
HL
Sönksen
P H
PH
Russell-Ones
D L
DL
D000328:Adult; D001055:Apolipoproteins B / Q000378:metabolism*; D019540:Area Under Curve; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008079:Lipoproteins, VLDL / Q000737:chemistry*; D008297:Male
D001055:Apolipoproteins B; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D008079:Lipoproteins, VLDL; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone