The effect of sensitisation to insulin with pioglitazone on fasting and postprandial lipid metabolism, lipoprotein modification by lipases, and lipid transfer activities in type 2 diabetic patients

Abstract

Aims/hypothesis: Insulin resistance is thought to be central to the pathogenesis of diabetic dyslipidaemia. We hypothesised that improving insulin sensitivity would improve fasting and postprandial triglyceride metabolism in patients with type 2 diabetes. To this aim we studied fasting and postprandial lipaemia in type 2 diabetic patients before and after sensitisation to insulin with pioglitazone, compared with that observed in patients on an insulinproviding regime. Methods: In a double-blind placebo-controlled protocol, 22 patients with type 2 diabetes were randomly allocated to receive either pioglitazone (45 mg/day) or glibenclamide (5 mg/day), for a 20-week period. Fasting and postprandial lipid metabolism were investigated at baseline and at the end of the treatment period. A group of non-diabetic subjects was also studied. Results: Compared with glibenclamide treatment, pioglitazone treatment decreased fasting triglyceride, glucose and insulin levels and the homeostasis model assessment score of insulin resistance. Decreased fasting triglyceride after pioglitazone treatment was due to reduced VLDL triglyceride, particularly VLDL-2. Lipoprotein lipase activity was unchanged by pioglitazone treatment but hepatic lipase showed a significant decrease. Pioglitazone treatment lowered total postprandial triglyceride, as well as chylomicron-and chylomicron-remnant retinyl palmitate levels to normal. Glucose disposal improved but remained abnormal. Conclusions/interpretation: Insulin sensitisation with pioglitazone has major effects in restoring postprandial lipaemia to normal, while also correcting fasting hypertriglyceridaemia; both factors may have consequences for atherogenic risk in diabetes.

Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study

“…The present results of unchanged LPL activity following PGZ and RGZ therapy suggest that divergent effects on VLDL elimination are not involved in explaining the difference in TG concentrations. This finding is consistent with a recent study [26]. It is, therefore, conceivable that different effects of RGZ and PGZ on hepatic VLDL production are involved.…”

“…Insulin resistance is associated with increased activity of HL [30]. The comparable reduction in HL activity after RGZ and PGZ indicates that this result is most likely due to the observed comparable improvement of insulin sensitivity after treatment with either of the glitazones, and is consistent with a recent observation after PGZ therapy [26]. ApoC-II stimulates LPL activity while apoC-III inhibits it, and both are found on VLDL particles [31,32].…”

“…This result further substantiates the hypothesis that a factor, which is independent from insulin sensitivity, is involved in the differential impact of RGZ and PGZ on lipid metabolism. Following a standardized fat load, a decrease in postprandial TG concentrations after PGZ therapy has recently been reported [26]. In contrast, the increase in postprandial TG after RGZ is a new finding.…”

Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes

“…Thiazolidinediones have been reported to exert beneficial effects on postprandial TG metabolism [17][18][19][20], but these are unlikely to be mediated by reduced NEFA flux to the liver, a mechanism that is largely independent of improved glycaemia. Both metformin [21,22] and glipizide [23] can improve postprandial lipaemia in poorly controlled patients with type 2 diabetes.…”

Remnant-like lipoprotein particles impair endothelial function: direct and indirect effects on nitric oxide synthase

“…Pioglitazone, a peroxisome proliferator-activated receptorg agonist, lowers total postprandial triglyceride, as well as chylomicron-and chylomicron-remnant retinyl palmitate levels to normal (68). Moreover, pioglitazone treatment can improve FMD and reduce CRP concentrations in patients with type 2 diabetes (69,70).…”