Relationship Between Diurnal Blood Pressure, Renal Hemodynamic Function, and the Renin-Angiotensin System in Type 1 Diabetes

Abstract

In patients with diabetes, altered diurnal blood pressure (BP) regulation (high night-to-day [N/D] ratio, or "nondipping") is associated with increases in albumin excretion and a decline in the glomerular filtration rate (GFR) by an unknown mechanism. Because it is known that renin angiotensin system (RAS) activation and defective glucose control contribute to adverse renal outcomes, we examined renal responses to high glucose and to manipulation of the RAS in adolescents (mean age 14 ؎ 2 years) with uncomplicated type 1 diabetes, segregated into two groups on the basis of the presence or absence of normal N/D BP ratio. In the first experiment, renal hemodynamic comparisons were made during euglycemia (4 -6 mmol/l) and hyperglycemia (9 -11 mmol/l), maintained by modified clamp techniques. The induction of hyperglycemia resulted in a significant increase in GFR and filtration fraction (FF) in the high N/D ratio group. In the second experiment, we examined the renal response to graded angiotensin II (Ang II) infusion while subjects were euglycemic and salt replete. High N/D ratio was associated with an enhanced FF response to Ang II. In the third experiment, the N/D ratio and GFR were assessed after 3 weeks of ACE inhibition. This maneuver corrected the high N/D ratio, but it had no effect on glomerular hyperfiltration. These results suggest that RAS activation does not explain the hyperfiltration state, nor can it explain the poor outcomes, at least in this population. However, the observed deleterious hemodynamic responses to high glucose and Ang II and the insensitivity to ACE inhibition may, taken together, provide an explanation for the adverse renal outcomes in patients with type 1 diabetes and high N/D ratio. A mbulatory blood pressure monitoring (ABPM) has been used in the investigation and management of blood pressure (BP) problems for many years. Studies have shown that there is a normal diurnal pattern of BP variation that is characterized by an approximate 10% decrease in BP values during the night (1). Altered diurnal BP regulation, with a tendency for elevated nighttime BP (high night-to-day [N/D] ratio), is referred to as the "nondipping" pattern of BP, and it may be a risk factor for poor clinical outcome, possibly predicting the progression of renal disease (2), increased target organ damage (3-8), and increased cardiovascular morbidity (9 -11). Moreover, high N/D ratios are found more commonly in patients with diabetes (12), African Americans (13), and patients with renal disease (14).In type 1 diabetic patients, a high N/D ratio is associated with several undesirable outcomes, including early morphologic changes in the glomerulus (15), increased albumin excretion (16 -19), and an increased rate of decline of the glomerular filtration rate (GFR) in patients with overt diabetic nephropathy (20). Although the mechanism(s) responsible for these associations have not been fully elucidated, subjects with uncomplicated type 1 diabetes and high N/D ratio exhibit higher values for GFR in comparison to su...

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