RELATIONSHIP OF PROGRESSIVELY INCREASING ALBUMINURIA TO APOPROTEIN(A) AND BLOOD-PRESSURE IN TYPE-2 (NON-INSULIN-DEPENDENT) AND TYPE-1 (INSULIN-DEPENDENT) DIABETIC-PATIENTS

This study has explored the temporal relationship between apoprotein(a), blood pressure and albuminuria over a mean interval of 11 years in a cohort of 107 diabetic patients of whom 26 (14 Type 2 (non-insulin-dependent), 12 Type 1 (insulin-dependent) had progressively increasing albuminuria ('progressors'). In Type 2 diabetic patients, no significant differences were noted for HbA1, blood pressure, creatinine clearance or serum lipids between progressors and non-progressors. In Type 1 diabetic patients, final systolic and diastolic blood pressures were higher in progressors compared with non-progressors and progressors showed impairment of renal function in association with a rise in blood pressure at the macroalbuminuric stage. Initial apoprotein(a) levels were similar in progressors and non-progressors of either diabetes type. Apoprotein(a) levels increased exponentially with time in 12 of 14 Type 2 progressors but only in 5 of 12 Type 1 progressors (p < 0.01). In Type 2 diabetic patients, the annual increase in apoprotein(a) levels was 9.1 +/- 2.4 %, which was significantly greater than in non-progressors, 2.0 +/- 1.2 % (p < 0.01) and also exceeded the rates of increase of apoprotein (a) in progressors with Type 1 diabetes, 4.0 +/- 1.4 %, (p < 0.05). Apoprotein(a) levels correlated significantly with albuminuria in 8 of, 14 Type 2 progressors but only in 3 of 12 Type 1 progressors (p < 0.05). The rate of increase of apoprotein (a) levels was not related to mean HbA1, creatinine or creatinine clearance levels, or to albuminuria. The rate of rise of apoprotein(a) was not influenced by initial apoprotein(a) levels, suggesting that specific apoprotein(a) isoforms do not influence albuminuria-related increases in apoprotein(a). The data are consistent with the hypothesis that apoprotein (a) levels increase in response to albuminuria and may be part of a self-perpetuating process. This study also suggests that increases in apoprotein(a) levels commence during the microalbuminuria stage in diabetic patients, which is earlier than has been documented in non-diabetic proteinuria.