Basal and insulin-regulated VLDL1 and VLDL2 kinetics in men with type 2 diabetes

Abstract

Aims/hypothesis Hypertriacylglycerolaemia is a hallmark of diabetic dyslipidaemia with increased concentrations of triacylglycerol (TG)-rich VLDL 1 particles. However, whether VLDL 1 secretion or removal is abnormal in type 2 diabetes remains unclear. The aim of this study was to compare basal and insulin-mediated VLDL 1 -and VLDL 2 -TG kinetics in men with type 2 diabetes and healthy men using a novel direct VLDL 1 -and VLDL 2 -TG labelling method. Methods Twelve men with type 2 diabetes and 12 healthy men matched for age and BMI were recruited. VLDL 1 -and VLDL 2 -TG turnover were measured during a 4 h basal period and a 3.5 h hyperinsulinaemic clamp period using a primed-constant infusion of ex vivo labelled VLDL 1 -TG and VLDL 2 -TG. Results Basal VLDL 1 -TG and VLDL 2 -TG secretion rates were similar in men with diabetes and healthy men. During hyperinsulinaemia, VLDL 1 -TG secretion rates were suppressed significantly in both groups, whereas no suppression of VLDL 2 -TG secretion rate was observed. VLDL 1 -TG to VLDL 2 -TG transfer rate was not significantly different from zero in both groups, while VLDL 1 -TG fatty acid oxidation rate was substantial, with a contribution to total energy expenditure of approximately 15% during postabsorptive conditions. VLDL 1 and VLDL 2 particle size (TG/apolipoprotein B [apoB] ratio) and apoB-100 concentration were unaltered by hyperinsulinaemia in men with type 2 diabetes, but significantly reduced in healthy men. Conclusions/interpretation Insulin inhibits VLDL 1 -TG secretion rate similarly in age-and BMI-matched men with type 2 diabetes and healthy men, while VLDL 2 -TG secretion is unaltered by hyperinsulinaemia. However, VLDL 1 -and VLDL 2 -apoB levels are not lowered by hyperinsulinaemia in men with type 2 diabetes, which is indicative of a diminished hepatic response to insulin. Trial registration ClinicalTrials.gov NCT01564550

Metformin does not affect postabsorptive hepatic free fatty acid uptake, oxidation or resecretion in humans: A 3‐month placebo‐controlled clinical trial in patients with type 2 diabetes and healthy controls

“…As in most, but not all, previous studies of VLDL‐TG secretion, patients with T2D had greater VLDL‐TG secretion and consequently elevated levels of TGs when compared with healthy controls. Our control subjects did not significantly differ from patients with T2D in terms of body composition (visceral fat, total fat mass or BMI) at inclusion and it is therefore likely that the increased VLDL‐TG secretion and VLDL‐TG levels were a consequence of decreased insulin sensitivity.…”

Familial Combined Hyperlipidemia: Current Knowledge, Perspectives, and Controversies

“…FCHL comprises both hyperapobetalipoproteinemia and normal or elevated apoB synthesis 27,28 . Alterations in both secretion and degradation of apoB particles have been encountered in FCHL patients and have been linked to IR, decreased apoB clearance rate, and increased expression of molecules that downregulate the LDL receptor 2,12,30 . Imbalance between de novo lipogenesis and β-oxidation is a hallmark of FCHL, resulting in hepatic fat accumulation and very low-density lipoprotein (VLDL) overproduction 31 .…”

Unexplained reciprocal regulation of diabetes and lipoproteins

“…Nielsen et al assessed VLDL kinetics in male type 2 diabetes patients and healthy controls [59▪,60,61]. In contrast to prior studies, the two groups were matched for body mass index.…”

“…In contrast to prior studies, the two groups were matched for body mass index. Surprisingly, VLDL-triglyceride secretion, clearance, and oxidation were the same between the two groups [59▪,60]. The effects of insulin or a mixed meal to suppress VLDL-triglyceride secretion were also comparable.…”

“…These findings suggest that VLDL-triglyceride kinetics may be affected more strongly by obesity or insulin resistance than by diabetes per se. One of the only differences observed in diabetes patients was impaired suppression of apoB-100 secretion by insulin [59▪]. Perhaps this suggests a contributor to the accumulation of small, dense LDL particles.…”