Overnight Albumin Excretion Rate And Arterial Blood Pressure

The normal range for diastolic blood pressure in diabetic boys (Figure 3) and girls (Figure 4) aged 8 to 18 years with normoalbuminuria was determined in a study of the relationship between blood pressure and urinary albumin excretion in young Danish Type 1 diabetic patients [69]. Figures 3 and 4 also include data from patients diagnosed with micro- and macroalbuminuria [69]. Ten out of 16 boys with microalbuminuria had diastolic blood pressure above the upper quartile while eight out of 14 girls with microalbuminuria had diastolic blood pressure above this quartile [69]. Three of four boys with macroalbuminuria had diastolic blood pressure below the upper quartile while two of three girls with macroalbuminuria had values above [69]. Overall, 60% of adolescents with microalbuminuria had diastolic blood pressure in the upper quartile for normoalbuminuria [69]. In keeping with this, Kordonouri et al. [70] reported a relationship between diastolic blood pressure and albumin excretion rate in juvenile Type 1 diabetic patients. This excess prevalence of raised blood pressure in Type 1 diabetic patients could, therefore, be explained by the presence of elevated blood pressure in adolescents with micro- and macroalbuminuria [32]

Re-examination of 15 of the adolescents with microalbuminuria, 2 years after identification, revealed that two of these (13%) had developed overt proteinuria during this period. They had initially an overnight albumin excretion rate of

62.0 and 115.7 ^g.min-1, respectively, increasing to 184.4 and 448.3 ^g.min-1, respectively (unpublished data). Gorman et al. [71] showed that microalbuminuria detected in the first decade of disease will persist or progress in the second decade in around two-thirds of patients, while a third of those initially normoalbuminuric will develop microalbuminuria. Thus, without treatment, a marked increase in the progression to overt diabetic nephropathy is seen in many individuals. In a study of young diabetic patients all diagnosed before 15 years of age, Bojestig et al. [72] found no relationship between the level of microalbuminuria at the initial investigation and the development of nephropathy. They conclude that, even in the upper range of AER, excellent glycaemic control seems to be effective in preventing macroalbuminuria and reversing AER to normal.

Altered glomerular haemodynamics with increased glomerular plasma flow and transcapillary pressures are considered key factors in the initiation and progression of diabetic nephropathy [73,74,75,76]. Therapy with an angiotensin converting enzyme (ACE) inhibitor has been shown to lower albumin excretion rate and mean arterial blood pressure in normotensive adolescents [77,78] and adults [79] with Type 1 diabetes and microalbuminuria, in the short term at least. Recently, long-term studies have demonstrated that ACE-inhibition delays progression to diabetic nephropathy in normotensive Type 1 diabetic patients with persistent microalbuminuria [80,81,82,83]. Rudberg et al. [84] found less progression of early diabetic glomerulopathy in Type 1 diabetic young microalbuminuric patients who were treated with either ACE-inhibitors or beta blockers (for an average of 3 years) than in patients who did not receive antihypertensive treatment and that this effect possibly was due to maintenance of a normal or low blood pressure. Thus, ACE inhibitors have beneficial effects in nephropathy [85], a microvascular complication of Type 1 diabetes that shares many of the risk factors of retinopathy. Interestingly, The EUCLID Study Group [86] recently reported that the ACE inhibitor, lisinopril, both reduced the progression and incidence of retinopathy and that this is not fully accounted for by effects on blood pressure. The EUCLID study investigators suggest that ACE inhibitor therapy should be considered for all patients with Type 1 diabetes who have some degree of retinopathy.

Previous investigations in adults with Type 1 diabetes have shown that, at the time of recognition of microalbuminuria, blood pressure is often within the normal range [87] and tends to increase in parallel with the extent of albuminuria. However some studies have shown a progressive elevation of blood pressure, even in the normotensive range, before the occurrence of persistent microalbuminuria (105). This was particularly true for patients with a family history of hypertension (106). However, in a recent matched case-control study it was reported that a rise in systemic blood pressure could not be detected before the first appearance of microalbuminuria in children. Blood pressure rose concurrently with the onset of microalbuminuria and was also closely related to BMI (107). However, higher levels of albumin-to-creatinine ratio within the first 2 years after diagnosis and a significantly higher rate of increase of the albumin-to-creatinine ratio within the first 5 years from diagnosis could be detected in subjects who subsequently developed microalbuminuria (103).

Only two out of five adolescents with macroalbuminuria had elevated blood pressure in our study of blood pressure and AER (Figures 3 and 4) [69]. This may be a selection bias because two patients with macroalbuminuria were excluded due to antihypertensive treatment. However, shorter duration of diabetes and lower body mass index compared to an adult population could explain the observed discrepancies.

Diastotic BP (mmHg)

100-

Diastotic BP (mmHg)

100-

Age (years)

Age (years)

Figure 3. Percentile distribution of diastolic blood pressure in 487 boys aged 8 to 18 years with type 1 diabetes. The dots represent diastolic blood pressure for the 16 boys with microalbuminuria, the squares the three boys with macroalbuminuria [ref. 69, with permission].

Diastotic BP (mmHg)

100-

Diastotic BP (mmHg)

100-

Age (years)

Age (years)

Figure 4. Percentile distribution of diastolic blood pressure in 425 girls aged 8 to 18 years with type 1 diabetes. The dots represent diastolic blood pressure of the 14 girls with microalbuminuria, the squares the two girls with macroalbuminuria [69, with permission].

These findings suggest that elevated arterial blood pressure may be related to the increased prevalence of elevated albumin excretion rate observed in adolescents with Type 1 diabetes and it suggests that hypertension plays an important role for the initiation and the progression of diabetic nephropathy in keeping with previous reports [4,7,10]

Supplements For Diabetics

Supplements For Diabetics

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