Genetic hepatic
lipase (HL) deficiency is associated with
low density lipoprotein (
LDL) rich in
triglycerides (TG), whose affinity for B:E receptors is decreased. In rats, experimental hypoinsulinemia produces HL deficiency. However, the relation between human
insulin-dependent Diabetes Mellitus (
IDDM), HL activity and the characteristics of
LDL have not been studied. The objective of our study is to evaluate the relation between HL activity and the chemical composition of
LDL in treated
IDDM patients. Subjects were 15
IDDM patients and 15 controls (C), matched for sex and body mass index (BMI). The
IDDM patients were classified by the WHO criteria, were free of nephropathy and
hypothyroidism, and received no medication except
insulin. Controls were clinically healthy and normolipidemic with no family history of diabetes. The
IDDM group was divided into two subgroups: subgroup
IDDM-A (n = 9) with HL values > or = 4.3 and
IDDM-B (n = 6) with HL < or = than 4.2 mumoles
glycerol/ml h. the HL in
IDDM was lower than in C (p < 0.001). Table 1 shows clinical data. Blood samples were drawn after 12 h fasting. Percentage of HbA1c and plasma concentrations of
glucose, total
cholesterol, LDL-
cholesterol, HDL-
cholesterol and TG were assayed.
LDL was separated by sequential ultracentrifugation at densities of 1.019-1.063 g/ml and its chemical composition was analyzed. The most relevant results were: plasma TG concentration was higher in
IDDM than in C (p < 0.05) (Table 2), although average values
DMID not exceed the reference values of 200 mg/dl. The TG-
LDL were higher in
IDDM than in C: 24.8 +/- 2.7 vs 17.5 +/- 1.1 mg/dl plasma, media +/- SE, (p < 0.02). This difference reflected the values of
IDDM-B, whose plasma concentrations of TG-
LDL were higher than in C: 32.3 +/- 3.6 vs 17.5 +/- 1.1 mg/dl (p < 0.001), and also higher than in
IDDM-A (p < 0.02). (Table 3). The chemical composition of
LDL in IDDM-B contained a higher percentage of TG than C: 8.5 +/- 0.7 vs 6.8 +/- 0.3% (p < 0.05), a lower percentage of
cholesterol than
IDDM-A: 39.0 +/- 1.7 vs 45.2 +/- 2.2% (p < 0.05) and also a larger percentage of
proteins than
IDDM-A: 28.9 +/- 1.9 vs 20.8 +/- 1.0% (p < 0.01). The correlations between TG/
cholesterol and HL activity in
IDDM were r = -0.53 (p < 0.05) and in
IDDM-B, r = -0.81 (p = 0.05). The noteworthy result of this study is the modification of the
LDL particle in
IDDM, rich in TG in patients with low HL activity. Anomalies in the chemical composition of
LDL like those described decrease the uptake of this particle by its physiological B:E receptors. It has recently been demonstrated that
LDL is an indisoluble association of
lipids and
apoproteins, and that both act simultaneously to hold the
apoB in a spatial position that expresses normal
epitopes. It has been described that particles of
LDL rich in TG and poor in
cholesterol, shows low affinity for
LDL receptors in human fibroblasts. Also in
IDDM the interaction of
LDL rich in TG with B:E receptors is decreased. This might be one more mechanism contributing to the accelerated
atherosclerosis of these patients. Our results suggest that there may be a threshold of HL activity for the complete hydrolysis of the TG of
LDL, for the normalization of the TG/
cholesterol relation and for the conformation of typical
LDL particles.