Lipoprotein metabolism in patients with type 1 diabetes under intensive insulin treatment

Abstract

BackgroundType 1 diabetes (T1DM) is frequently accompanied by dyslipidemia related with insulin-dependent steps of the intravascular lipoprotein metabolism. T1DM dyslipidemia may predispose to precocious cardiovascular disease and the lipid status in T1DM under intensive insulin treatment has not been sufficiently explored. The aim was to investigate the plasma lipids and the metabolism of LDL and HDL in insulin-treated T1DM patients with high glycemic levels.MethodsSixteen male patients with T1DM (26 ± 7 yrs) with glycated hemoglobin >7%, and 15 control subjects (28 ± 6 yrs) were injected with a lipid nanoemulsion (LDE) resembling LDL and labeled with 14C-cholesteryl ester and 3H-free-cholesterol for determination of fractional clearance rates (FCR, in h-1) and cholesterol esterification kinetics. Transfer of labeled lipids from LDE to HDL was assayed in vitro.ResultsLDL-cholesterol (83 ± 15 vs 100 ± 29 mg/dl, p=0.08) tended to be lower in T1DM than in controls; HDL-cholesterol and triglycerides were equal. LDE marker 14C-cholesteryl ester was removed faster from plasma in T1DM patients than in controls (FCR=0.059 ± 0.022 vs 0.039 ± 0.022h-1, p=0.019), which may account for their lower LDL-cholesterol levels. Cholesterol esterification kinetics and transfer of non-esterified and esterified cholesterol, phospholipids and triglycerides from LDE to HDL were also equal.ConclusionT1DM patients under intensive insulin treatment but with poor glycemic control had lower LDL-cholesterol with higher LDE plasma clearance, indicating that LDL plasma removal was even more efficient than in controls. Furthermore, HDL-cholesterol and triglycerides, cholesterol esterification and transfer of lipids to HDL, an important step in reverse cholesterol transport, were all normal. Coexistence of high glycemia levels with normal intravascular lipid metabolism may be related to differences in exogenous insulin bioavailabity and different insulin mechanisms of action on glucose and lipids. Those findings may have important implications for prevention of macrovascular disease by intensive insulin treatment.

Nuclear magnetic resonance-determined lipoprotein subclasses and carotid intima-media thickness in type 1 diabetes

“…HDL-C levels tend to be similar or increased in T1DM patients compared to non-diabetic subjects [39, 40], but may also exhibit qualitative differences, especially affecting large HDL particles, that might contribute to promotion of subclinical atherosclerosis in T1DM [39]. In the present study, we observed significant inverse associations of both large HDL particle concentrations and HDL particle diameter (at DCCT baseline) with carotid IMT (at EDIC Year 12); but again only in men and in univariate analysis.…”

Plasma triglycerides predict incident albuminuria and progression of coronary artery calcification in adults with type 1 diabetes: The Coronary Artery Calcification in Type 1 Diabetes Study

“…Lipoprotein subfraction cholesterol distribution has been proposed to be more atherogenic in those with type 1 diabetes [25]. Possible mechanisms include differences in lipoprotein particle size, LDL-C oxidation, COX2 expression, inflammatory response to lipids and increased transvascular and macrophage lipid transport in patients with type 1 diabetes [26]. …”

Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus

“…Our results are in accordance with previous studies which have shown that insulin treatment could account for normalizing the levels of total cholesterol, TG and LDL-cholesterol in type II diabetic patients under poor metabolic control 40 . Interestingly, the lipid-lowering action of insulin, independent of glycemic control in T2D patients, appeared to be beneficial because of the role of dyslipidemia in the development of diabetic macrovascular disease such as vasculopathy 41 .…”

“…protein lipase, resulting in increase of lipid metabolism and then decreased levels of lipids [39][40][41] . Our results are in accordance with previous studies which have shown that insulin treatment could account for normalizing the levels of total cholesterol, TG and LDL-cholesterol in type II diabetic patients under poor metabolic control 40 .…”