C. Iovine

A controlled study on the effects of n-3 fatty acids on lipid and glucose metabolism in non-insulin-dependent diabetic patients.

Eight male non-insulin-dependent diabetic patients participated in a double-blind randomized cross-over study (2 weeks for each period) evaluating the effects of 10 g/day fish oil dietary supplementation on glucose and lipid metabolism. Fasting serum triglyceride concentrations were decreased by fish oil because of a reduction in VLDL (1.4 +/- 0.2 vs. 1.9 +/- 0.2 mmol/l, P less than 0.025). LDL cholesterol concentration was instead increased (3.4 +/- 0.3 vs. 2.8 +/- 0.3 mmol/l, P less than 0.025) and net changes in VLDL triglyceride and in LDL cholesterol were inversely correlated (r = -0.86, P less than 0.01). Plasma free fatty acids concentrations and turnover rate [( 3H]palmitate method) were similar after fish oil and placebo. Fish oil supplement did not induce significant changes in fasting blood glucose (8.1 +/- 1.1 vs. 8.5 +/- 1.2 mmol/l) and average daily blood glucose (BG) (9.4 +/- 3.2 vs. 9.3 +/- 3.5 mmol/l). Glucose stimulated plasma insulin response during a hyperglycemic clamp was not significantly influenced by fish oil both in the early phase and during steady state. Insulin sensitivity (M/I index) was also unchanged. In conclusion, this study shows that a dietary supplement of fish oil decreases plasma triglyceride levels in non-insulin-dependent diabetic patients, an increased conversion rate of VLDL to LDL playing a role in this change. With this dosage of fish oil no relevant variations in glycemic control, insulin secretion and insulin sensitivity occurred.

Insulin Resistance Is Independently Associated With Postprandial Alterations of Triglyceride-Rich Lipoproteins in Type 2 Diabetes Mellitus

Objective—To evaluate the role of insulin resistance in development of postprandial dyslipidemia in type 2 diabetic patients in an experimental setting in which these patients were compared with nondiabetic subjects at similar glucose and insulin blood levels. Methods and Results—Eight type 2 diabetic patients in optimal blood glucose control and 7 control subjects (aged 50.0±2.6 and 48.1±1.3 years; body mass index 28.3±1.2 and 25.6±1.1 kg/m2; fasting plasma triglycerides 1.12±0.13 and 0.87±0.08 mmol/L, respectively; mean±sem; NS) consumed a mixed meal during an 8-hour hyperinsulinemic glycemic clamp. Mean blood glucose during clamp was ≈7.8 mmol/L, and plasma insulin during the preprandial steady state was ≈480 pmol/L in both groups, that differed for insulin sensitivity (M/I value lower in diabetic subjects [1.65±0.30 and 3.42±0.60; P<0.05]). Subjects with diabetes had higher postprandial levels of lipids and apolipoprotein B (apoB) in large very low-density lipoprotein (incremental area for triglycerides 1814±421 versus 549±153 &mgr;mol/L×6 hours; P<0.05; cholesterol 694±167 versus 226±41 &mgr;mol/L×6 hours; P<0.05; apoB-48 6.3±1.0 versus 2.6±0.7 mg/L×6 hours; P<0.05; apoB-100 56.5±14.9 versus 26.2±11.0 mg/L×6 hours; NS). Basal lipoprotein lipase (LPL) activity before and after meal was higher in diabetic subjects, whereas postheparin LPL activity 6 hours after the meal was similar. Conclusions—Insulin resistance is also associated with postprandial lipoprotein abnormalities in type 2 diabetes after acute correction for hyperglycemia and hyperinsulinemia.

Long-term effects of fish oil on lipoprotein subfractions and low density lipoprotein size in non-insulin-dependent diabetic patients with hypertriglyceridemia

The effects of fish oil on lipoprotein subfractions and low density lipoprotein (LDL) size in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertriglyceridemia are unknown. To elucidate this, 16 NIDDM hypertriglyceridemic patients (plasma triglyceride 2.25- 5.65 mmol/l, plasma cholesterol < or = 7.75 mmol/l) were randomly assigned to a 6-month period with either moderate amounts of fish oil (n = 8) or placebo (n = 8) after 4 weeks of wash-out and 3 weeks of run-in. Diet and hypoglycemic treatment were unchanged throughout the experiment. LDL size were evaluated at baseline and after 6 months. Three VLDL and LDL subfractions were measured at the end of the two periods. The total lipid concentration of all very low density lipoprotein (VLDL) subfractions was lower at the end of fish oil treatment compared with placebo (large VLDL 124.3 +/- 19.7 mg/dl vs 156.7 +/- 45.5 mg/dl; intermediate VLDL 88.5 +/- 9.5 mg/dl vs 113.9 +/- 23.2 mg/dl; small VLDL 105.9 +/- 9.7 mg/dl vs 128.9 +/- 40.7 mg/dl) (mean +/- SEM), although the difference was not statistically significant. Moreover, at the end of the two treatments, the percentage distribution of VLDL subfractions was very similar (large 37.5 +/- 3.3% vs 37.6 +/- 2.6%, intermediate 27.6 +/- 0.9% vs 31.0 +/- 2.4%; small 34.9 +/- 3.7% vs 31.4 +/- 2.1%). Concerning LDL, no significant change in LDL size was observed after the two treatments (255.4 +/- 2.2 A vs 254.2 +/- 1.7 A, fish oil; 253.7 +/- 2.0 A vs 253.3 +/- 1.7 A, placebo). LDL subfraction distribution was also very similar (large 17 +/- 3% vs 17 +/- 2%; intermediate 62 +/- 3% vs 65 +/- 3%; small 21 +/- 3% vs 18 +/- 2%), at the end of the two periods, confirming the lack of effects on LDL size. In conclusion, our study indicates that in NIDDM patients with hypertriglyceridemia, fish oil does not induce any improvement in LDL distribution and LDL size despite its positive effects on plasma triglycerides.

Assay of erythrocyte membrane fatty acids. Effects of storage time at low temperature

The study of the stability of saturated mono-, or polyunsaturated fatty acids, both esterified and not esterified, in plasma, circulating cells, and tissues is extremely important to validate the use of biological samples stored at low temperature in “biological banks”, which are used for experimental, observational, dietary, or pharmacological studies. Since red blood cells are easily accessible cells, they are used as a marker of less-accessible tissues, especially in large-scale epidemiological studies. Data from the literature suggest that the addition of an antioxidant and the freezing of red blood cells do not cause any variation in the fatty acid composition for a period of 2–6 months up to 1 year. We evaluated the fatty acid concentration in red blood cells isolated from venous blood samples of one subject, preserved with butylated hydroxytoluene and N2 and stored at −80°C for up to 2 years. Erythrocytes of venous samples of six subjects stored at −20°C for 6 months without butylated hydroxytoluene and in the presence of air were used for comparison purposes. Our data demonstrate that a long storage time (2 years) does not significantly influence the erythrocyte fatty acid concentration when using very low temperatures (−80°C) and antioxidants (butylated hydroxytoluene) in the presence of N2.

Effect of acute exogenous hyperinsulinaemia on very low density lipoprotein subfraction composition in normal subjects

Subtle abnormalities of very‐low‐density lipoprotein (VLDL) composition and distribution seem to be associated with increased cardiovascular risk. The aims of this study were first, to evaluate whether hyperinsulinaemia per se is able to produce VLDL abnormalities and second, whether this occurs through a stimulation of lipolytic enzymes.

Atorvastatin or fenofibrate on post‐prandial lipaemia in type 2 diabetic patients with hyperlipidaemia

Background  Post‐prandial lipid abnormalities might contribute to the excess of cardiovascular risk typical of type 2 diabetic patients. The study evaluated the effects of atorvastatin (20 mg d−1) vs. fenofibrate (200 mg d−1) on post‐prandial lipids in type 2 diabetic patients with mixed hyperlipidaemia.