Reversible abnormalities in postheparin lipolytic activity during the late phase of release in diabetes mellitus (postheparin lipolytic activity in diabetes).

To test whether abnormalities in multiphasic release of lipoprotein lipase are associated with hypertriglyceridemia in diabetes mellitus, postheparin lipolytic activity (PHLA) was measured during a high-dose, constant heparin infusion in 20 diabetic subjects with hypertriglyceridemia, 25 nondiabetic hypertriglyceridemic subjects and 7 normal subjects. The standard low heparin dose PHLA and the PHLa during the early phase of the heparin infusion were the same in all groups. In constrast, the PHLA during the late phase of the heparin infusion was lower in the 12 untreated diabetic subjects than in the 25 nondiabetic hypertriglyceridemic and the 7 normal subjects (p less than 0.001). An abnormality in late phase PHLA in the untreated diabetic subjects was more apparent when it was compared to the level of PHLA attained during the early phase of the heparin infusion (Equilibrium PHLA/60 min PHLA). The relative PHLA in the late phase of the infusion was lower in the untreated diabetic subjects (0.671 +/- 0.147) than in the nondiabetic hypertriglyceridemic subjects (0.847 +/- 0.019, p less than 0.001), or in the chronically treated diabetic subjects (0.823 +/- 0.108, p less than 0.05). Among the untreated diabetic subjects, increasing fasting glucose levels were associated with both decreasing absolute PHLA levels at the late phase of the infusion (r = 0.61, p less than 0.02) and greater decreases in relative PHLA during the infusion (r = -0.80, p less than 0.001). Treatment of the diabetes with long-term oral sulfonylurea or insulin therapy corrected the abnormality in the late phase PHLA with an associated decrease in plasma triglyceride levels (p less than 0.001). In five subjects with a deficient PHLA response to a standard, low dose of heparin, the PHLA response was low throughout the heparin infusion. With treatment, the PHLA response to the low heparin dose corrected rapidly toward normal in those two diabetic subjects with PHLa deficiency, and the early PHLA response during the heparin infusion increased. However, the late phase abnormality in all untreated diabetic subjects did not correct to normal until after several months of antihyperglycemic therapy. In the untreated diabetic subjects the degree of elevation of the plasma triglyceride level appeared to result from the interaction of the abnormality in PHLA with the presence or absence of an inherited familial lipid disorder.