The objective was to study the natural history and the predictive value of glomerular filtration rate, albumin excretion rate, blood pressure, and hemoglobin A1c for diabetic nephropathy. A cohort of 75 type-1 diabetic adolescents with a diabetes duration of 8 years was studied. Thirty-one females, 33 males, mean age 16.9 +/- 0.3 (SEM) participated in the follow-up study. Glomerular filtration rate, albumin excretion rate, blood pressure, and hemoglobin A1c were measured every second year during 8 years to determine the predictive value of glomerular filtration rate for future nephropathy. Initial differences and patterns of changes in glomerular filtration rate, albumin excretion rate, and hemoglobin A1c were examined in patients who did (group 1) and did not (group 2) develop incipient or overt nephropathy. Five of 64 patients developed overt nephropathy. They had an initial glomerular filtration rate of greater than 125 ml/min/1.73 m2. Fifteen of 53 initially normoalbuminuric patients developed incipient and three of 53 overt nephropathy. Age, age at onset, diabetes duration, initial albumin excretion rate, initial blood pressure, and hemoglobin A1c were similar in groups 1 and 2. Glomerular filtration rate was initially higher in group 1 than in group 2 (P = 0.01). The positive predictive value for combined incipient and overt nephropathy of an initial glomerular filtration rate greater than 125 ml/min was 53%. The negative predictive value of glomerular filtration rate less than 125 ml/min was 95%. In initially normoalbuminuric patients multiple regression revealed initial glomerular filtration rate as the only significant independent predictor for nephropathy when also corrected for hemoglobin A1c (P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term treatment with angiotensin converting enzyme inhibitors (ACEI) has a beneficial effect on the progression of microalbuminuria in patients with Type I (insulin-dependent) diabetes mellitus [1,2]. In addition, some clinical studies but not all [3±5] have suggested a superior effect of ACE-inhibitors over beta-blockers on the progressive decline in glomerular filtration rate (GFR) in Type I diabetic patients with nephropathy.Microalbuminuria predicts overt diabetic renal disease [6]. Still around 30 % of patients with low- Diabetologia (1999) Abstract Aims/hypothesis. To investigate the influence of angiotensin converting enzyme inhibitors and beta blockers on the progression of early diabetic glomerulopathy.Methods. Thirteen patients with Type I (insulin-dependent) diabetes mellitus (mean age 18.8 years) with microalbuminuria 31 (19±160) mg/min were randomised to treatment with enalapril (group 1, n = 7) or metoprolol (group 2, n = 6). Renal biopsies were taken before and after 38 (36±48) months of treatment. Albumin excretion rate, blood pressure and HbA 1 c were measured every third month. A reference group without antihypertensive treatment (group 3, n = 9), with similar age, diabetes duration and degree of microalbuminuria as group 1 and 2, had baseline and follow-up renal biopsies taken previously with an interval of 26±34 months, analysed at the same laboratory. Glomerular structures were measured by stereological methods.

The albumin excretion rate (AER) was studied in two groups of diabetic children and adolescents. Twenty-four-hour AER was studied in 75 children with diabetes for 5 years, in 49 children with diabetes for 10 years, in 55 children with diabetes for 10-20 years and in 21 age matched healthy controls. Overnight AER was studied in 129 diabetic children and adolescents with a duration of diabetes varying from 1-14 years. Diabetics exhibited a wide range of AER-values and when expressed per body surface area, diabetic children had significantly higher AER compared to controls. Log transformed AER-values were significantly correlated to age and body surface area in diabetics but not in controls. In the diabetics, log AER was also correlated to systolic and diastolic blood pressure but not to HbA1c. 20% of the diabetics had AER values exceeding the upper value for healthy controls which was 18.5 micrograms/min. 31/35 of them were older than 12 years. In both groups of diabetics, 5% had AER-values exceeding those reported to be predictive for later development of overt nephropathy, the youngest being 16 years old. When comparing diabetic children 0-12 years (i.e. before the maximal growth spurt of puberty) to those older than 12 years, at the same duration of diabetes, the latter group had significantly higher AER-values. No sex difference was found in either age group. It is concluded that after puberty diabetic patients also show evidence of incipient diabetic nephropathy. Thus, routine screening for microalbuminuria is recommended also in pediatric diabetes care after 12 years of age.

At a mean diabetes duration of 29 years the cumulative incidence of macroalbuminuria was 12%; however, another 20% had persistent microalbuminuria. A screening value of 24-h AER >15 mg/min was a strong predictor, whereas increased GFR was a weaker but significant predictor for micro and macroalbuminuria.

In the very early stage of microalbuminuria in IDDM adolescents, a high percentage of the variation in BMT and overall severity of glomerulopathy is explained by prolonged hyperglycemia and diabetes duration. Previous glomerular hyperfiltration may also add to the prediction of these morphological changes.