Elevated triglyceride-rich lipoproteins in diabetes

Abstract

The role of the intestine in cholesterol metabolism in human diabetes is unclear, although abnormalities have been demonstrated in cholesterol synthesis and absorption in diabetic animals. This study examines the relationship between fasting and post-prandial apolipoprotein B-48 in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Eight type 2 diabetic patients and ten healthy non-diabetic control subjects were given a high-fat meal (1300 kcal), and the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (d < 1.006 g/ml) from fasting and post-prandial plasma. Apolipoprotein B-48 and apo B-100 were separated on 4%-15% gradient gels and quantified by densitometric scanning with reference to a purified low-density lipoprotein (LDL) apo B-100 preparation. Diabetic patients had significantly higher concentrations of apo B-48 and apo B-100 in both the fasting (P < 0.05) and post-prandial (P < 0.001) triglyceride-rich lipoprotein samples compared with non-diabetic subjects. The diabetic patients also exhibited a significantly different post-prandial profile for apo B-48 and apo B-100, with a prolonged increase and a later post-prandial peak, than the non-diabetic subjects (P < 0.01). These results suggest that the raised fasting triglyceride-rich lipoproteins, often found in diabetes, are associated with apo B-48 and may be derived from increased intestinal chylomicron production. The post-prandial pattern suggests an abnormality in intestinal production as well as hepatic clearance of apo B-48 in type 2 diabetes.

Dietary unsaturated fatty acids in type 2 diabetes: higher levels of postprandial lipoprotein on a linoleic acid-rich sunflower oil diet compared with an oleic acid-rich olive oil diet.

“…The other postprandial particle is the apo B100-containing VLDL, which is produced by the liver. We and others (11, [13][14][15] have shown very considerable disturbance in both the amount and the size of these particles in diabetes. We have demonstrated in the experimental animal that clearance and synthesis of these particles account for the abnormalities found in diabetes (16,17).…”

Hyperinsulinemia Is Associated With Increased Production Rate of Intestinal Apolipoprotein B-48–Containing Lipoproteins in Humans

“…However, there is evidence to suggest that the intestine constitutively synthesizes smaller TRL particles 48 and maintains a basal level of apoB-48, even in the fasting state. 2 The current thinking is that chylomicron formation involves the formation of small, phospholipidrich, TG-poor primordial particles in the membrane of the smooth endoplasmic reticulum, with subsequent core lipid expansion and particle transfer from the smooth endoplasmic reticulum to the golgi for secretion. 49 We have shown previously that hamster enterocytes have the capacity to secrete small, lipid-poor (HDL size) apoB-48 -containing particles, and that in hamsters made insulin-resistant with fructose or high-fat feeding, there is a marked increase in TRL apoB-48 secretion not only in the fed but also in the fasted state.…”

“…1 It is also now well established that insulin-resistant and type 2 diabetic individuals have elevated levels of TG-rich lipoprotein (TRL) particles and remnants, including intestinally derived apolipoprotein B-48 (apoB-48)-containing TRL, in both the fasted and postprandial states. [2][3][4][5][6] The latter is of particular clinical importance because these remnant lipoprotein particles may impair endothelial function and may enter and be retained in the subendothelial space of the vascular wall, thus potentially accelerating the development of atherosclerotic lesions. [7][8][9] Indeed, elevated intestinally derived remnant lipoproteins have been associated with increased cardiovascular disease.…”

“…Indeed, in humans, insulin resistance is associated with postprandial elevation of apoB-48 -containing TRL particles, and fasting hypertriglyceridemia predicts this abnormal postprandial response. 2,12 However, the precise mechanisms underlying this overaccumulation of intestinal lipoproteins in insulin-resistant states are not yet fully understood. To date, studies have focused on the delayed clearance of TRL remnants, attributed to: (1) impaired lipolysis attrib-utable to decreased lipoprotein lipase activity, (2) modified lipoprotein composition, (3) reduced remnant recognition by hepatic receptors, or (4) an expanded pool of VLDL leading to competition for removal between VLDL and chylomicrons.…”

Isolation and Characterization of Apolipoprotein B48-Containing Lipoproteins with a Monoclonal Antibody Against Apolipoprotein B48

“…This indicated that the isolated lipoproteins were very similar to CM. Diabetes mellitus is a typical disease associated with lipid abnormalities, such as hypertriglyceridemia and low HDL-cholesterol, as well as an increase of remnant lipoproteins 26) . It was shown by the JDCS 27) , a Japanese study, that the incidence of coronary artery disease is higher in patients with type 2 diabetes.…”