The objective of this study was to examine total exchangeable sodium, plasma-blood volume, and the status of the renin-angiotensin system in hypertensive diabetic patients with established nephropathy. We also evaluated hypertensive patients with diabetes who were free of clinically apparent nephropathy or other diabetic complications. Total exchangeable sodium (by 24Na dilution) was expressed as percentage predicted. Subjects were studied as inpatients receiving unrestricted sodium intake and in stable metabolic control. Total exchangeable sodium was 100 +/- 2% in controls (n = 42), higher (p less than 0.01) at 108 +/- 2% in normotensive patients with diabetes (n = 30), and higher still (p less than 0.005) in hypertensive patients with diabetic nephropathy (n = 16) 118 +/- 4% (p less than 0.05 vs normotensive diabetics). The value correlated with blood pressure only in diabetics with nephropathy (r = 0.61, p less than 0.01). Plasma renin activity, and blood and plasma volumes were similar in nephropathic diabetics and controls. Hypertensive patients with maturity-onset (type II) diabetes free of nephropathy (n = 18) were compared with nondiabetic controls (n = 16) and normotensive patients with type II diabetes (n = 18) of similar age. Total exchangeable sodium in the controls was 100 +/- 3%, higher (p less than 0.01) in normotensive diabetics at 109 +/- 2%, but not significantly elevated in hypertensive diabetics at 106 +/- 2%. Again, blood and plasma volumes did not differ among the groups. Plasma renin activity was suppressed (p less than 0.01) to a comparable degree in both normotensive and hypertensive patients with type II diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Available evidence indicates that poor metabolic control and raised blood pressure each accelerate the development of diabetic microangiopathy. Microangiopathy is associated with excess albumin deposition in capillary basement membranes and it has been suggested that increased extravasation of plasma constituents may lead to basement membrane thickening. We measured the transcapillary escape rate of albumin, an indicator of the rate of extravasation of intravascular albumin from the circulation per unit time, following intravenous injection of 125I-human serum albumin. We examined the independent effects on the transcapillary escape rate of albumin of non-ketotic poor metabolic control, hypertension and microangiopathy. We studied non-diabetic control subjects and diabetic patients, initially when in non-ketotic poor metabolic control and again when control had been improved. We also studied normotensive well-controlled diabetic patients without microangiopathy, normotensive well-controlled diabetic patients with microangiopathy, hypertensive well-controlled diabetic patients without microangiopathy and hypertensive well-controlled diabetic patients with microangiopathy. The transcapillary escape rate of albumin was similar in non-diabetic control subjects (5.5 +/- 0.7%/h) and in both Type 1 (5.3 +/- 1.2%/h) and Type 2 (5.1 +/- 0.6%/h) normotensive diabetic patients without long-term complications. During poor metabolic control the transcapillary escape rate of albumin was significantly higher than in non-diabetic subjects (8.8 +/- 0.8%/h and 5.5 +/- 0.7%/h respectively, p less than 0.01). With improved control values fell significantly to 6.3 +/- 0.9%/h (p less than 0.02), not significantly different from control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

1.We studied 12 normotensive non-ketotic diabetic patients during poor metabolic control, with sustained hyperglycaemia, and again, after an interval of 3 weeks, when metabolic control was improved. On each occasion we measured blood pressure, total exchangeable sodium, plasma volume, transcapillary escape rate of albumin, and plasma concentrations of angiotensin 11 and aldosterone.2. With improved diabetic control there was a small but significant fall in arterial pressure. Total exchangeable sodium was normal when control was poor but rose significantly to above normal with improved control.3. Plasma volume also rose significantly with improved control, and the transcapillary escape rate of albumin fell and the intravascular mass of albumin rose. 4. Plasma angiotensin I1 and aldosterone concentrations were significantly above normal during poor metabolic control, but fell to normal with improved control. 5. These findings indicate a resetting of the relationship between blood pressure and exchangeable sodium when diabetic control improves. The association between exchangeable sodium and concentrations of angiotensin I1 and aldosterone also appears altered in diabetic patients. These changes associated with varying metabolic control must be considered when studying cardiovascular disease in diabetic patients.

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