LOW-DENSITY-LIPOPROTEIN RICH IN TRIGLYCER IDES AND HEPATIC LIPASE ACTIVITY IN INSULIN-DEPENDENT DIABETES-MELLITUS PATIENTS

Genetic hepatic lipase (HL) deficiency is associated with low density lipoprotein (LDL) rich in triglycerides (TG), whose affinity for B:E r eceptors is decreased. In rats, experimental hypoinsulinemia produces HL deficiency. However, the relation between human insulin-dependent D iabetes Mellitus (IDDM), HL activity and the characteristics of LDL ha ve not been studied. The objective of our study is to evaluate the rel ation between HL activity and the chemical composition of LDL in treat ed IDDM patients. Subjects were 15 IDDM patients and 15 controls (C), matched for sex and body mass index (BMI). The IDDM patients were clas sified by the WHO criteria, were free of nephropathy and hypothyroidis m, and received no medication except insulin. Controls were clinically healthy and normolipidemic with no family history of diabetes. The ID DM group was divided into two subgroups: subgroup IDDM-A (n = 9) with HL values greater than or equal to 4.3 and IDDM-B (n = 6) with HL less than or equal to than 4.2 mu moles glycerol/ml h. The HL in IDDM was lower than in C (p < 0.001). Table 1 shows clinical data. Blood sample s were drawn after 12 h fasting. Percentage of HbA1c and plasma concen trations of glucose, total cholesterol, LDL-cholesterol, HDL-cholester ol and TG were assayed. LDL was separated by sequential ultracentrifug ation at densities of 1.019-1.063 g/ml and its chemical composition wa s analyzed. The most relevant results were: plasma TG concentration wa s higher in IDDM than in C (p < 0.05) (Table 2), although average valu es 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, m edia +/- 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 co ntained a higher percentage of TG than C: 8.5 +/- 0.7 vs 6.8 +/- 0.3% (p < 0.051, 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 correlatio ns 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 tow HL activity. Anomalies in the chemical compositi on of LDL like those described decrease the uptake of this particle by its physiological B:E receptors. It has recently been demonstrated th at LDL is an indisoluble association of lipids and apoproteins, and th at both act simultaneously to hold the apoB in a spatial position that expresses normal epitopes. It has been described that particles of LD L rich in TG and poor in cholesterol, shows low affinity for LDL recep tors 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 .