The Regulation of Post‐prandial Cellular Cholesterol Metabolism in Type 2 Diabetic and Non‐diabetic Subjects

Abstract

The purpose of the study was to determine the effect of diabetes on the regulation of postprandial cholesterol metabolism. Four groups of patients (n = 8 for each group) were examined: Type 2 diabetic patients with and without hypercholesterolaemia and non-diabetic subjects with and without hypercholesterolaemia. Serum lipoproteins, lipoprotein composition, cellular cholesterol, and cellular cholesterol synthesis were measured before and 4 h after a high calorie meal. The BMI for the hypercholesterolaemic diabetic patients of 31.5 +/- 0.95 (SEM) was significantly higher than that for the control group of 26.2 +/- 1.0 (p < 0.01). Fasting triglyceride levels were significantly higher in the normocholesterolaemic and hypercholesterolaemic diabetic patients and in the hypercholesterolaemic non-diabetic subjects (1.45 +/- 0.22, 2.27 +/- 0.34, and 1.58 +/- 0.18 mmol l-1, respectively) compared with normocholesterolaemic non-diabetic subjects (0.75 +/- 0.12 mmol l-1: p < 0.01). The normocholesterolaemic and hypercholesterolaemic diabetic subjects had significantly lower fasting serum high density lipoprotein (HDL) (1.06 +/- 0.08 and 1.04 +/- 0.06 mmol l-1) compared to the corresponding non-diabetic groups (1.29 +/- 0.11 and 1.45 +/- 0.17 mmol l-1, p < 0.05). The esterified/free cholesterol ratio of very low density lipoprotein (including chylomicrons VLDL-C) decreased postprandially in all groups with an overall decrease of 1.33 to 0.83 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained postprandial decrease in plasma levels of LDL cholesterol in patients with type‐2 diabetes mellitus

“…Using either beta quantification [34,43] or gradient ultracentrifugation [25,[31][32][33], most previous studies likewise showed postprandial decreases in LDL-C levels. In 16, 10 and 43 patients with T2DM, previous studies, using gradient ultracentrifugation, reported a significant decrease [32], no significant difference (albeit a 0.4 to 0.7 mmol/L non-significant decrease) [30] and a significant increase (at 8 h) [10] in postprandial LDL-C levels, respectively. The latter studies used highcholesterol (490 and 600 mg) meals [10,30] as opposed to our medium-cholesterol (139 mg) meal (the per meal cholesterol intake in the Western diet averages 70 to 130 mg [1,44]).…”

“…For example, in the postprandial state, patients with T2DM show more pronounced changes in glucose, insulin, free fatty acids (FFAs) and triglycerides levels compared to non-diabetics [36][37][38][39]. However, in patients with T2DM, only three relatively small studies (including fewer than 45 patients) present data on postprandial LDL-C levels as measured by ultracentrifugation -and with conflicting results [10,30,32]. Despite this, in the daily routine, LDL-C levels are often measured in non-fasting samples and, at present, many patients with T2DM receive lipid lowering therapy with statins, for example.…”

“…The Center for Disease Control and Prevention (CDC) recommended method for measurement of LDL-C is ultracentrifugation precipitation, the so-called ''beta quantification'' [20][21][22]. In studies applying ultracentrifugation, each including fewer than 25 subjects, data for postprandial LDL-C levels indicate either no change [28][29][30] or suggest an approximately 5-10 % decrease compared to the fasting state in individuals without diabetes [25,[31][32][33][34] and in patients with type-1 diabetes [35]. Importantly, in patients with T2DM, lipid metabolism differs in several aspects from that in non-diabetics (and patients with type-1 diabetes).…”

Alterations in apolipoprotein B-48 in the postprandial state in NIDDM

“…TRL was composed of chylomicrons and VLDL, but apo B-48 is only contained in the intestinally-derived fraction. The plasma apolipoprotein changes in the TRL fraction of non-diabetic human subjects fed a fat-rich meal have previously been documented [10,17], but to our knowledge postprandial alterations in apo B-48 in the diabetic patient have not been reported.…”

“…Chylomicron remnants have been implicated as being potentially atherogenic [8] and apo B-48 has been proposed as a useful indicator of intestinally-derived lipoprotein particles [1,9]. Studies have examined postprandial alterations in lipoprotein metabolism in the diabetic state [10,11]; however, although postprandial changes in apo B-48 have been investigated in the non-diabetic population [12], the effect of diabetes on apo B-48 is unknown. Diabetic patients have a high incidence of atherosclerosis, a disease commonly associated with dyslipidaemia.…”