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To determine effects of diabetic gestation on plasma concentration of the coagulation regulatory protein, protein C, pregnant ewes were given glucose infusions to raise plasma glucose to twice baseline concentration or insulin infusions to lower glucose concentration to half baseline value. Control animals received no infusions. Concentrations of protein S, factor X, and antithrombin III were determined for comparison. Concentrations of glucose, insulin, and those above were determined thrice weekly for 2-9 wk. Short-term (8-12 h) infusions of glucose or insulin were performed to isolate their effect on concentration of protein C. Results were analyzed using a two-tailed t test, and protein C concentrations were further analyzed using a full linear mixed-effects model. In long-term infusions, hyperglycemia-induced hyperinsulinemia (mean insulin concentration 141 microU/L) exerted negative effects on maternal concentrations of protein C [0.69 U/mL, n (number of samples) = 32, experimental versus 0.97 U/mL, n = 157, control], protein S (0.86 U/mL, n = 31, experimental versus 1.04 U/mL, n = 109, control), and factor X (0.89 U/mL, n = 31, experimental versus 1.04 U/mL, n = 109, control); it exerted no effects on antithrombin III (1.05 U/mL, n = 23, experimental versus 1.04 U/mL, n = 32, control). The fetal lamb did not respond to chronic moderate hyperglycemia (mean 33 mg/dL) with a consistent change in insulin concentration (mean 10 versus 9 microU/mL): no coagulation protein changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperglycemia-Induced Hyperinsulinemia Decreases Maternal and Fetal Plasma Protein C Concentration during Ovine Gestation