Recent evidence suggests the rise in urinary albumin excretion preceding diabetic nephropathy may represent a continuum. We therefore studied factors relating to albumin excretion rate in children with insulin-dependent diabetes. Normal overnight albumin excretion rate was determined in 690 healthy schoolchildren. The 95th centile was 7.2 micrograms min-1. Patients included 169 children with IDDM aged 12.4 +/- 3.1 years who performed 4.8 +/- 0.4 overnight collections during 15 +/- 0.5 months and were analysed cross sectionally. They were stratified accordingly to mean albumin excretion rate: normal < 7.2 micrograms min-1, borderline 7.2-20 micrograms min-1, microalbuminuria 20-200 micrograms min-1; 96/169 patients performed 6.4 +/- 0.2 overnight collections during 24 months follow-up and were analysed longitudinally. Cigarette smoking was determined by history and urine cotinine levels. Smoking correlated with albumin excretion rate, independent of age and other variables, in cross-sectional and longitudinal analysis (p < 0.003). Smoking was more prevalent in the borderline albuminuria and microalbuminuria groups (p < 0.004, p < 0.001). Mean HbA1c during follow-up and mean HbA1c since diagnosis were significantly higher in the microalbuminuric group, compared with the normal patient group. HbA1c since diagnosis, mean blood pressure, lipoprotein(a), and apolipoprotein B did not correlate with albumin excretion rate, after controlling for other variables. Our findings highlight the continuing need for strategies to prevent smoking in this age group.
Pubertal and postpubertal IDDM patients have higher serum lipoprotein(a) than Caucasian control subjects. Our findings suggest a rise in lipoprotein(a) may occur during puberty in IDDM. Longitudinal studies are required to clarify the relationship between lipoprotein(a), albumin excretion rate, and puberty.
We aimed to examine the longitudinal relationship between lipoprotein(a) and haemoglobin A1c, albumin excretion rate, and puberty in peripubertal children with insulin-dependent diabetes. A total of 114 patients aged 11.5 +/- 3.6 years (mean (SD)) were followed prospectively for 15.2 +/- 2.8 months. Lipoprotein(a), apolipoproteinB-100, haemoglobin A1c, mean overnight albumin excretion rate and Tanner stage were determined at the beginning and end of the study period. Lipoprotein(a) and apolipoproteinB-100 were measured using nephelometry. This method was correlated with radioimmunoassay and there was no significant change in mean bias during the study. Lipoprotein(a) fell significantly over time (214, (152, 276); 160 (84, 236) mg l-1 geometric mean (0.95 confidence intervals), p < 0.001); apolipoproteinB-100 did not change. Lipoprotein(a) and apolipoproteinB-100 did not differ in 233 cross-sectional controls of similar age. The change in lipoprotein(a) did not correlate with a small fall in haemoglobin A1c or with overnight albumin excretion rate, Tanner stage or insulin dose. Separate analysis of male and female patients and prepubertal and pubertal patients continued to show a significant fall in lipoprotein(a) independent of change in haemoglobin A1c or albumin excretion rate. Likewise, 53 patients with a change in haemoglobin A1c of greater than 1%, and 20 patients who progressed from normal albumin excretion rate to albumin excretion rate above the 95th centile, showed no relationship between lipoprotein(a) and haemoglobin A1c or albumin excretion rate. In conclusion, longitudinal changes in lipoprotein(a) do not relate to metabolic control or early changes in albuminuria in young patients with insulin-dependent diabetes.
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