Reduced Fibrinogen Survival in Diabetes Mellitus

Fibrinogen survival and turnover were examined in 15 adult-onset diabetic patients. (125)I-labeled fibrinogen was prepared from each patient during the period of poor carbohydrate control, or hyperglycemic period, and fibrinogen survival determined. Improved control was established in each patient and during this euglycemic period, fibrinogen survival was determined simultaneously with (125)I-fibrinogen saved from the hyperglycemic period and (131)I-labeled fibrinogen prepared from the patient during the euglycemic period. The results confirm reduced fibrinogen survival in hyperglycemic diabetic patients and demonstrate reversal of the fibrinogen abnormality when euglycemia is achieved. The results of the double-label experiments in the euglycemic period suggest that the fibrinogen molecule is not altered functionally and that an abnormal plasma or vascular environment is a more likely basis for reduced fibrinogen survival during hyperglycemia. Electrophoretic and chromatographic experiments demonstrated no gross chemical differences between the fibrinogens prepared from the hyperglycemic and euglycemic periods and normal fibrinogen. Fibrinogen survival gave a better correlation with serial glucose measurements than with correction of hemoglobin A(Ic) levels indicating that the reduced fibrinogen survival noted in diabetics is a rapidly reversible phenomenon. During the hyperglycemic period, pharmacological intervention with aspirin and dipyrimadole was attempted to examine the role of platelets in reduced fibrinogen survival. No significant change in fibrinogen survival was observed. Heparin infusion during hyperglycemia normalized the fibrinogen kinetics of hyperglycemic diabetic patients, suggesting that reduced fibrinogen survival during hyperglycemia is secondary to an effect on thrombin or one of its antagonists.