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Objective: It is currently suggested that chronic hyperinsulinemia is a causal factor for the increased production rate of very-low-density lipoproteins (VLDL) associated with metabolic syndrome. However, the involvement of hyperinsulinemia independently of the other abnormalities also observed in metabolic syndrome has never been proven in humans., Design: We used patients with insulinoma showing hyperinsulinemia but no insulin resistance as a model and conducted an apolipoprotein B (apoB) kinetic study in seven patients with insulinoma, seven insulin-resistant (IR) obese patients, and 12 controls., Results: Insulinemia was higher in patients with insulinoma or IR than in controls both in the fasting state [2.4-fold (P = 0.039) and 3.1-fold (P = 0.003), respectively] and in the fed state [3.5-fold (P = 0.006) and 2.6-fold (P = 0.05), respectively]. Patients with insulinoma were not IR (steady state plasma glucose = 80 ± 46 mg/dl, a value lower than in IR subjects (231 ± 75, P = 0.0013). In the fed state, triglyceridemia and VLDL apoB pool size were higher in IR subjects compared with controls and patients with insulinoma [208 ± 56 vs. 89 ± 30 mg/dl (P < 0.0001) and 96 ± 42 mg/dl (P < 0.0001), respectively, for triglyceridemia and 3.56 ± 0.60 vs. 1.85 ± 0.88 mg/kg (P = 0.004) and 2.32 ± 1.79 (P = 0.052) mg/kg for VLDL apoB pool size]. The production rate of VLDL apoB in subjects with insulinoma was not significantly different from that in controls (14.56 ± 7.43 vs. 16.40 ± 7.70 mg/kg · d) but was higher in IR subjects compared with these two groups [25.66 ± 12.84 mg/kg · d (P = 0.046 and 0.035, respectively)]., Conclusion: Chronic endogenous hyperinsulinemia is not directly responsible for any increase in the production rate of VLDL apoB in humans.

Aims/hypothesis: In addition to its efficacy in reducing LDL-cholesterol, rosuvastatin has been shown to significantly decrease plasma triacylglycerol. The use of rosuvastatin may be beneficial in patients with type 2 diabetes, who usually have increased triacylglycerol levels. However, its effects on the metabolism of triacylglycerol-rich lipoproteins in type 2 diabetic patients remains unknown., Methods: We performed a randomised double-blind crossover trial of 6-week treatment with placebo or rosuvastatin 20 mg in eight patients with type 2 diabetes who were being treated with oral glucose-lowering agents. In each patient, an in vivo kinetic study of apolipoprotein B (ApoB)-containing lipoproteins with [13C]leucine was performed at the end of each treatment period. A central randomisation centre used computer-generated tables to allocate treatments. Participants, caregivers and those assessing the outcomes were blinded to group assignment., Results: Rosuvastatin 20 mg significantly reduced plasma LDL-cholesterol, triacylglycerol and total ApoB. It also significantly reduced ApoB pool sizes of larger triacylglycerol-rich VLDL particles (VLDL1; p = 0.011), smaller VLDL particles (VLDL2; p = 0.011), intermediate density lipoprotein (IDL; p = 0.011) and LDL (p = 0.011). This reduction was associated with a significant increase in the total fractional catabolic rate of VLDL1-ApoB (6.70 +/- 3.24 vs 4.52 +/- 2.34 pool/day, p = 0.049), VLDL2-ApoB (8.72 +/- 3.37 vs 5.36 +/- 2.64, p = 0.011), IDL-ApoB (7.06 +/- 1.68 vs 4.21 +/- 1.51, p = 0.011) and LDL-ApoB (1.02 +/- 0.27 vs 0.59 +/- 0.13, p = 0.011). Rosuvastatin did not change the production rates of VLDL2-, IDL- or LDL-, but did reduce VLDL1-ApoB production rate (12.4 +/- 4.5 vs 19.5 +/- 8.4 mg kg(-1) day(-1), p = 0.035). No side effects of rosuvastatin were observed during the study., Conclusions/interpretation: In type 2 diabetic patients rosuvastatin 20 mg not only induces a significant increase of LDL-ApoB catabolism (73%), but also has favourable effects on the catabolism of triacylglycerol-rich lipoproteins, e.g. a significant increase in the catabolism of VLDL1-ApoB (48%), VLDL2-ApoB (63%) and IDL-ApoB (68%), and a reduction in the production rate of VLDL1-ApoB (-36%). The effects of rosuvastatin on the metabolism of triacylglycerol-rich lipoproteins may be beneficial for prevention of atherosclerosis in type 2 diabetic patients.

Objective: In type 1 diabetic patients, the replacement of s.c. insulin infusion with i.p. insulin infusion restores the normal physiological gradient between the portal vein and the peripheral circulation, which is likely to modify lipoprotein metabolism., Design: To check this hypothesis, we performed two apolipoprotein (apo) B100 kinetic studies in seven type 1 diabetic patients, first under s.c. insulin infusion and then 3 months after the beginning of i.p. insulin infusion., Results: Glycemic control was similar under s.c. insulin infusion and i.p. insulin infusion, as assessed by glycated hemoglobin A1c and the capillary glycemic curve determined during the kinetic study. Very low-density and intermediate-density lipoprotein apoB100 pool size, production rate, and fractional catabolic rate (FCR) were similar under s.c. insulin infusion and i.p. insulin infusion. The low-density lipoprotein apoB100 FCR tended to decrease under ip insulin (0.45 +/- 0.06 vs. 0.55 +/- 0.11 pool/d), but the difference did not reach statistical significance (95% confidence interval for the difference, -0.33, 0.11). The low-density lipoprotein apoB100 pool size and production rate remained unchanged under i.p. insulin infusion compared with s.c. insulin infusion., Conclusion: In type 1 diabetic patients, the replacement of s.c. insulin infusion with i.p. insulin infusion does not induce profound modifications of apoB100-containing lipoprotein production and FCRs.

Aims/hypothesis: Type 1 diabetic subjects are at increased risk of cardiovascular disease and exhibit multiple qualitative abnormalities of apolipoprotein (apo) B100-containing lipoproteins. This stable isotope kinetic experiment was designed to study whether these abnormalities are associated with changes in the synthesis and fractional catabolic rates of VLDL-, IDL- and LDL-apoB100., Methods: Using a bolus followed by a 16-h constant infusion of 13C-leucine, we performed a kinetic study in eight men with type 1 diabetes treated with a continuous subcutaneous insulin infusion administered by an external pump and in seven healthy men, in the fed state., Results: The mean HbA1c level in the type 1 diabetic patients was 8.00+/-1.48%. Plasma triglyceride, and total, LDL and HDL cholesterol levels were similar in patients and control subjects. VLDL were less triglyceride rich in type 1 diabetic patients than in control subjects (VLDL triglyceride : apoB 6.91+/-0.81 vs 8.29+/-1.24 mmol/g, p=0.05). Conversely, the IDL and LDL of the type 1 diabetic patients contained relatively higher levels of triglycerides (IDL triglycerides : apoB 2.16+/-0.36 vs 1.57+/-0.30 mmol/g, p<0.01; LDL triglycerides : apoB 0.27+/-0.06 vs 0.16+/-0.04 mmol/g, p<0.05). The apoB100 pool size, production and fractional catabolic rates in the two groups of subjects were similar for all lipoprotein fractions., Conclusions/interpretation: Despite qualitative abnormalities, especially abnormalities of triglyceride content, the metabolism of apoB100-containing lipoproteins is not altered in type 1 diabetic men with fair glycaemic control with continuous subcutaneous insulin infusion. The high risk of atherosclerosis in these patients cannot be explained by kinetic abnormalities of apoB100-containing lipoproteins.