Serum sialic acid changes in type 2 diabetic patients on metformin or rosiglitazone treatment.

WHAT IS KNOWN AND OBJECTIVE: Serum sialic acid is a recently investigated potential risk-marker for cardiovascular complications. There is a known association between sialic acid and cardiovascular complications in diabetes mellitus. We aimed to investigate the effect of antidiabetic drugs on the serum concentration of sialic acid. METHODS: We investigated the effect of metformin and rosiglitazone on the concentration of sialic acid in 120 type 2 diabetic patients, divided into a group (n = 60) receiving metformin and a group (n = 60) receiving rosiglitazone treatment. RESULTS: Serum sialic acid was significantly higher in patients on rosiglitazone (66·90 ± 8·80 mg/dL vs. 57·6 ± 8·46 mg/dL, P < 0·01) and metformin (61·95 ± 10·49 mg/dL vs. 57·6 ± 8·46 mg/dL, P < 0·04) when compared with control subjects. In addition, rosiglitazone-treated patients showed a significant increase in cardiovascular risk factors, notably total cholesterol (246·45 ± 20·2 mg/dL vs. 170·6 ± 15·1 mg/dL, P = 0·01), triglyceride (178 ± 9·20 mg/dL vs. 149·35 ± 6·31 mg/dL, P < 0·04) and glycohemoglobin (HbA1-c) concentration (8·17 ± 1·43% vs. 4·38 ± 0·96%, P < 0·02) compared with normal control subjects. The patients on metformin also showed significantly higher levels of serum glucose (133·7 ± 9·63 mg/dL vs. 88·35 ± 6·31 mg/dL, P < 0·04) and glycohemoglobin (HbA1-c) (8·23 ± 1·75% vs. 4·38 ± 0·96%, P < 0·02) when compared with control subjects. Comparison of the two groups of patients revealed a significantly higher serum sialic acid (66·90 ± 8·80 mg/dL vs. 61·95 ± 10·49 mg/dL, P < 0·05), total cholesterol (246·45 ± 20·2 mg/dL vs. 192 ± 14·23 mg/dL, P < 0·02) and triglyceride (178 ± 9·20 mg/dL vs. 158 ± 14·51mg/dL, P < 0·05) concentrations in the rosiglitazone-treated patients. WHAT IS NEW AND CONCLUSIONS: This study suggests significantly higher levels of serum sialic acid and other cardiovascular risk factors in rosiglitazone-treated patients than in metformin-treated patients. The lower sialic acid concentration may explain a better metformin antidiabetic effect than with rosiglitazone.

Low density lipoprotein receptor-independent hepatic uptake of a synthetic, cholesterol-scavenging lipoprotein: implications for the treatment of receptor-deficient atherosclerosis.

The metabolism of infused 111In-labeled phospholipid liposomes was examined in Watanabe heritable hyperlipidemic (WHHL) rabbits, which lack low density lipoprotein (LDL) receptors, and in normal control rabbits. The half-times (t1/2) for clearance of 111In and excess phospholipid from plasma were 20.8 +/- 0.9 hr and 20.3 +/- 4.6 hr in WHHL and 20.0 +/- 0.8 hr and 19.6 +/- 2.2 hr in the normal rabbits (means +/- SEM; n = 4). By 6 hr postinfusion, the plasma concentration of unesterified cholesterol increased by 2.2 +/- 0.23 mmol/liter in WHHL and 2.1 +/- 0.04 mmol/liter in normal rabbits, presumably reflecting mobilization of tissue stores. Disappearance of excess plasma cholesterol was greater than 90% complete in both groups of rabbits by 70 hr postinfusion. By quantitative gamma camera imaging, hepatic trapping of 111In-labeled liposomes over time was indistinguishable between the two groups. At autopsy, the liver was the major organ of clearance, acquiring 22.0% +/- 1.7% (WHHL) and 16.8% +/- 1.0% (normal of total 111In. Aortic uptake of 111In was less than 0.02%. Thus, mobilization of cholesterol and hepatic uptake of phospholipid liposomes do not require LDL receptors. Because phospholipid infusions produce rapid substantial regression of atherosclerosis in genetically normal animals, our results suggest that phospholipid liposomes or triglyceride phospholipid emulsions (e.g., Intralipid) might reduce atherosclerosis in WHHL rabbits and in humans with familial hypercholesterolemia.