Effects of short-term modest weight loss on fasting and post-prandial lipoprotein sub-fractions in type 2 diabetes mellitus patients.

OBJECTIVE: We assessed the efficacy of a modest weight loss (1.5 +/- 0.3 kg) and simultaneous rapid improvement in glycemic control on fasting an post-prandial lipoprotein sub-fractions in nine overweight (BMI=28 +/- 1.7 kg/m(2)) well controlled Type 2 diabetic patients (HbA(1c)=7.3 +/- 0.1%). MATERIAL AND METHODS: They followed a non-drastical hypocaloric balanced diet (1 561 +/- 39 kcal/day) over ten days in hospital. The fat content of the diet was significantly lowered from 96 +/- 12 g/day to 62 +/- 4 g/day (p<0.03). Plasma lipid and lipoprotein levels were measured in fasting and four hours after standard breakfast and four hours after standard lunch twice before and after ten days of hospitalization. The sub-fractions of very low density and low density lipoprotein were obtained by cumulative flotation ultracentrifugation. RESULTS: This weight loss reduced two well known independent cardiovascular risk factors such as the post-prandial glycemic excursions (p<0.05) and the post-prandial lipemia (p<0.05). Multiple linear regression analyses identified weight loss as an independent variable accounting for the ability to predict post-prandial capillary triglyceride clearance (p<0.05). Improvements in post-prandial glycemic excursions which was also entered as a parameter did not appear as a variable being able to predict these changes (p=0.4). In addition to the 23% improvement in post-prandial capillary triglyceride clearance (p<0.02), a decrement in post-prandial VLDL-2 triglyceride enrichment was found (p<0.05). Finally, fasting and post-prandial LDL-3 cholesterol levels were diminished (p<0.05) and the LDL-2/LDL-3 mass ratio post-prandial kinetics were improved (p<0.05). CONCLUSIONS: Even a modest weight loss in overweight, average controlled type 2 diabetic patients can achieve a significant improvement in two cardiovascular risk factors, namely post-prandial triglyceride excursions and the LDL-2/LDL-3 mass ratio kinetics independently from glycemic control improvements.

Acute hyperinsulinemia and very-low-density and low-density lipoprotein subfractions in obese subjects.

BACKGROUND: The influence of hyperinsulinemia on concentrations of lipoprotein subfractions in obese, nondiabetic persons has not been clarified. OBJECTIVE: We analyzed VLDL and LDL subfractions before and after a euglycemic, hyperinsulinemic clamp. DESIGN: Lipoprotein subfractions were isolated from plasma samples obtained in the basal state and after a 4-h clamp from obese patients, obese patients with type 2 diabetes, and nonobese control subjects. RESULTS: Hyperinsulinemia tended to reduce concentrations (&xmacr;: 20%) of large, triacylglycerol-rich VLDL(1) in obese patients but had a minor effect on VLDL(2) and VLDL(3). Placing obese patients into insulin-sensitive and insulin-resistant subgroups revealed distinct effects of the degree of insulin sensitivity on VLDL. VLDL(1) concentrations decreased by a mean of 38% (P < 0.05) in insulin-sensitive patients after the clamp, similar to but less marked than the decrease observed in control subjects (&xmacr;: 62%; P < 0.01). VLDL(1) concentrations did not change significantly after the clamp in insulin-resistant patients (and patients with type 2 diabetes), whereas VLDL(3) concentrations decreased in both groups, in contrast with the changes seen in the insulin-sensitive patients and control subjects. Acute hyperinsulinemia modified the LDL subfraction profile toward a greater prevalence of small, dense LDLs in insulin-resistant patients and patients with type 2 diabetes. CONCLUSIONS: Insulin resistance appears to be the primary determinant of the modifications to VLDL subfraction concentrations. Our results suggest a continuum of impaired insulin action on VLDL, ranging from that in healthy persons to that in patients with type 2 diabetes, in which obese patients occupy a transition state. Insulin resistance may also play a role in detrimental modifications to the LDL profile by allowing the development of hypertriglyceridemia.

Apolipoprotein E polymorphism and the distribution profile of very low density lipoproteins; an influence of the E4 allele on large (Sf > 60) particles.

Very low density lipoprotein (VLDL) distribution and composition have been examined as a function of apo E genotype (E2/2 + E2/3 vs. E3/3 vs. E3/4 + E4/4) in healthy, normolipaemic subjects. Apo E genotype had a marked impact on plasma concentrations of apo E rich VLDL, but no influence on concentrations of apo E free particles. Thus, there was a trend to lower concentrations of apo E rich total VLDL in apo E4 carriers (mg/dl; E2, 49.1 +/- 35.2; E3, 52.5 +/- 30.9; E4 35.2 +/- 22.3; ANOVA P = 0.16; when comparing E4 with E2 + E3, P = 0.06). Consequently, there were highly significant differences between apo E-defined subgroups in terms of the percentage distribution of bound and non-bound fractions (% total VLDL non-bound to apo E: E2, 44.0 +/- 12.7%; E3, 39.7 +/- 8.7%; E4 51.0 +/- 12.2%; ANOVA P = 0.007). Subfractionation of VLDL into density subclasses revealed that genotype differences were restricted to large VLDL (Sf > 60). Significantly lower concentrations of apo E-rich particles were observed in E4 carriers for VLDL-1 Sf 400-100 (ANOVA P = 0.004) and VLDL-2 (P = 0.009) but not for small VLDL-3 Sf 60-20 (P = 0.34). No differences in plasma concentrations of apo E free VLDL were observed between genotype subclasses across the density spectrum. Compositional differences between the apo E defined VLDL were also evident for the core lipids. Apo E containing VLDL was enriched in esterified cholesterol and depleted in triglycerides compared to apo E poor VLDL: the difference became more marked with increasing density of the particles. Lipoprotein composition was not modulated to any great extent by apo E genotype. In patients with familial hypercholesterolaemia, relative concentrations of apo E rich, large VLDL were significantly higher than in controls. Treatment lowered concentrations of both apo E rich and apo E free VLDL but led to a greater relative enrichment of large VLDL in apo E containing particles. Apo E polymorphism appears to influence plasma concentrations of VLDL particles. The data are consistent with more pronounced receptor-mediated elimination of apo E4 containing VLDL. This may be a contributory factor to the down regulation of receptor activity which is suggested to be of major importance in provoking higher cholesterol levels associated with the apo E4 isoform.