OBJECTIVE -Dietary and nutritional supplements are modulators of HDL cholesterol levels and production of apolipoprotein (apo) AI. Previously, in vitro treatment of hepatocyte cell lines with glucosamine increased apoAI production by stabilization of apoAI mRNA. The hypothesis is that the neutraceutical glucosamine, when given in conventional doses (1,500 mg/day) may increase apoAI and HDL cholesterol levels in subjects with diabetes and low HDL cholesterol.RESEARCH DESIGN AND METHODS -Twelve subjects (three men and nine women) with type 1 (n ϭ 2) and type 2 (n ϭ 10) diabetes, aged 55 Ϯ 12 years (mean Ϯ SD), who had low HDL cholesterol (1.03 Ϯ 0.20 mmol/l), were randomly assigned to a double-blind, placebo-controlled, cross-over trial of 500 mg glucosamine or placebo orally three times daily for 2 weeks, followed by a 4-week washout phase and a 2-week cross-over to the alternate therapy.RESULTS -Fasting serum glucose, fructosamine, and total cholesterol remained stable during the drug and placebo phases. Glucosamine had no significant effect after therapy on serum levels of HDL cholesterol (from baseline of 1.02 Ϯ 0.15 to 1.05 Ϯ 0.16 mmol/l compared with placebo from 1.04 Ϯ 0.21 to 1.06 Ϯ 0.16 mmol/l) nor in changes in apoAI levels (from baseline of 147 Ϯ 15 to 140 Ϯ 126 mg/dl with glucosamine and from 146 Ϯ 25 to 142 Ϯ 17 mg/dl with placebo).CONCLUSIONS -These observations suggest that glucosamine at commonly consumed doses does not have significant effects on glycemic control, lipid profile, or levels of apoAI in diabetic subjects after 2 weeks of supplementation. Diabetes Care 30:2800-2803, 2007I t is generally accepted that the mechanism of the increased risk of cardiovascular disease in diabetes is multifactorial (1). One such factor is probably the reduced serum levels of HDL in obese type 2 diabetic individuals (1,2). Dietary composition and nutritional supplements are important modulators of the HDL cholesterol level and the production of its main apolipoprotein (apo), namely, AI (3). Glucosamine, a popular nutritional supplement for treating arthritis, has been shown to alter apoAI production in hepatocyte cultures (4).Endogenous glucosamine is synthesized by the amidation of glucose-6-phosphate via the hexosamine biosynthetic pathway (5). Approximately 5% of glucose-6-phosphate is metabolized to N-acetylglucosamine by glutamine: fructose-6-phosphate amidotransferase. In addition, the extracellular glucosamine is transported into tissues and is subsequently phosphorylated to enter the hexosamine biosynthetic pathway. This pathway has been implicated in insulin resistance that may contribute to diabetes and cardiovascular diseases (5).Commercially available products containing glucosamine are used extensively as neutraceuticals in the treatment of arthritis and have been shown in large clinical trials to be safe in conventional doses (1,500 mg/day) (6,7). Parenteral administration of high doses of glucosamine (i.e., 5-30 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) may cause diabetes in experimental animals (8). Studies in he...

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