Effect of improved glycemic control on blood pressure and albuminuria of insulin-dependent diabetes without nephropathy

To assess the effect of glycemic control on blood pressure (BP) and albumin excretion rate (AER) in insulin-dependent diabetes, 35 patients (age 12.6 ñ 2.7 years) and 45 matched control subjects (11.9 ñ 1.8 years) were studied at an educational camp (Study I). They were evaluated at the beginning and at the end of a 9-day program of adequate diet and exercise twice daily, which induced statistically significant reductions in urinary glucose (18 ñ 21 to 5 ñ 7 g/12 h, P<0.01) and in insulin requirement (42 ñ 20 to 31 ñ 12 U/day, P<0.01) in the diabetic group. The mean BP and AER of the diabetic patients fell from 74 ñ 11 to 69ñ 11 mmHg,P<0.001, and from 4.9ñ 6.0 to 2.1 ñ 2.0 mug/min, P<0.01, and a correlation was found between AER and urinary glucose. In contrast, controls showed a lower reduction in BP and no change in AER. To evaluate the mechanisms involved in BP fall another group of 39 diabetics (age 12.7 ñ 2.1 years) was submitted to the same 9-day program and also to improved glycemic control (Study II). Changes in BP (79 ñ 11 to 76 ñ 11 mmHg, P<0.05) were slighter than in the previous study. Initial creatinine clearance was high and fell to the normal range at the end of the study (159 ñ 99 to 127 ñ 42 ml min(-1)(1.73 M2) (-1), P<0.05). Urinary aldosterone decreased from 5.3 ñ 3.9 to 3.4 ñ 2.4 mug/24 h (P<0.05), and fractional Na+ excretion tended to increase. Initial and final metanephrine values did not differ. Changes in mean BP did not correlate with changes in aldosterone, insulin requirement or urinary glucose. The decreases in hyperflltration and AER may have been due to the improved glycemic control induced by this educational program. Exercise may be responsible for BP reduction in diabetics and controls. BP changes particularly in diabetics could be attributed to the inhibition of the renin-angiotensin-aldosterone system and/or to decreased insulin requirement. The contribution of a negative Na+ balance consequent to decreased plasma insulin levels to the BP fall cannot be excluded.

Detection of insulin antibodies by radioassay and ELISA: interrelation and correlation with metabolic control in type I diabetes

1. The literature suggests that the radioassay (RA) and ELISA detect different types of insulin antibodies (IA) (Wilkin et al., 1989. Diabetes, 38: 172-181). 2. In the present study we evaluated the relationship between these two antibodies and their involvement in the metabolic control of Type I diabetic (DMI) patients. 3. IA were measured by RA and ELISA in sera obtained from 34 patients (age: 9-16 years, median = 12.5 years; clinical duration of DMI: 0.1-11.0 years, median = 1.7 years) treated with different types of insulin [purified (bovine + porcine) N = 18, and monocomponent (porcine or human) N = 16] and submitted to various degrees of metabolic control as assessed by glycosylated serum protein (GSP) levels: range, 3.4-13.5; median = 8.7; normal value, 0.8-2.4. 4. Insulin antibody levels measured by RA were: 3264 +/- 300 nU/ml (mean +/- SEM, normal value < 60 nU/ml) and by ELISA: 0.74 +/- 0.11 ELISA index (EI) (normal value, < 0.53). No correlation was found between IA levels measured by RA and ELISA, or between duration of the disease or insulin daily necessity and IA by either method. GSP was positively correlated with IA determined by ELISA (rS = 0.43, P < 0.01) but not with IA determined by RA. 5. The patients on purified bovine + porcine insulin had higher titers of IA by ELISA, compared to those of patients on monocomponent (0.96 +/- 0.15 vs 0.50 +/- 0.13 EI, P < 0.03, while IA levels measured by RA did not differ between groups. 6. These data show that RA or ELISA assays provide different serum titers of IA in insulin-treated diabetics and data obtained with ELISA correlated best with the metabolic control of Type I diabetic patients.

Microalbuminuria, arterial blood pressure and retinopathy in insulin dependent diabetes

In order to evaluate the relationship between urinary albumin excretion, arterial blood pressure and diabetic retinopathy in insulin dependent diabetics we examined 55 patients without clinical proteinuria and whose disease had started before the age of 30. Each patient was asked to collect at least one overnight timed urine sample for albumin analysis by an ELISA method. Normoalbuminuria was defined as urinary albumin excretion (UAE) of < 20 mug/min (n = 32) and microalbuminuria as 21-200 mug/min (n = 23). Patients with microalbuminuria showed higher levels of blood pressure, serum creatinine and glicosylated haemoglobin as compared to normoalbuminuric patients. Significant correlation was observed between diastolic blood pressure and UAE (r = 0.52; p < O.001).Preproliferative and proliferative diabetic retinopathy was detected in 9 patients (l6.4 per cent). All of them had diabetes for more than 10 years, elevated UAE and diastolic blood pressure equal or higher than 85 mmHg. In our population of insulin dependent diabetics we found a high prevalence of microalbuminuria which is considered to be predictive of the latter development of diabetic nephropathy. Microalbuminuria is associated with elevated blood pressure and diabetic retinal lesions. We conclude that urinary albumin excretion should be monitored in patients with insulin dependent diabetes to detect those who should be considered at risk of developing nephropathy and retinopathy.