PLASMA SIALIC-ACID IN ANIMAL-MODELS OF DIABETES-MELLITUS - EVIDENCE FOR MODULATION OF SIALIC-ACID CONCENTRATIONS BY INSULIN DEFICIENCY

An elevated circulating sialic acid concentration is a risk factor for cardiovascular disease. Serum sialic acid levels are elevated in NIDD M but not in uncomplicated IDDM. To study why sialic acid is increased in some types of diabetes, we assayed plasma sialic acid in Various a nimal models of diabetes: obese (ob/ob) mice, before and after strepto zotocin treatment, neonatal streptozotocin-treated (nSTZ) rats, and di abetic BE rats during and after insulin treatment. In obese mice, whic h exhibit moderate hyperglycemia and marked hyperinsulinemia, plasma s ialic acid was decreased by 45% (fed) and 42% (fasted), compared to le an controls. Fasting reduced plasma glucose and insulin but increased sialic acid in the obese and lean mice. There was a negative correlati on (r = -0.84, P < 0.001) between log plasma insulin and sialic acid i n the lean and obese mice. The plasma sialic acid:globulin ratio was r educed by 35% in obese mice vs. lean controls, indicating that there m ay be altered sialylation of glycoproteins in obese mice. Streptozotoc in treatment of obese and lean mice reduced plasma insulin but increas ed sialic acid. In nSTZ rats, hyperglycemia was associated with mild h ypoinsulinemia, but not significantly different from control animals, and sialic acid was not altered. In diabetic BE rats, plasma glucose r ose from a mean of 4.9 to 23.5 mM 48 hr after insulin withdrawal but s ialic acid did not change. We conclude that an elevated plasma sialic acid level is associated with marked insulin deficiency, rather than h yperglycemia per se. The magnitude and speed of this change in sialic acid varies between species.