Plasma Angiotensin II, Renin Activity and Serum Angiotensin-Converting Enzyme Activity in Non-Insulin Dependent Diabetes Mellitus Patients with Diabetic Nephropathy.

Abstract

Abstract.The renin-angiotensin system (RAS) has been unequivocally implicated as a mediator of diabetic complications. The present study was designed to evaluate the RAS in non-insulin dependent diabetic patients with diabetic nephropathy.Plasma renin activity, plasma angiotensin II and serum angiotensin-converting enzyme (ACE) activity were measured in 45 non-insulin dependent diabetes mellitus (NIDDM) patients and 15 healthy non-diabetic controls. Diabetics were subdivided into 15 normoalbuminuric NIDDM subjects, 15 NIDDM patients with microalbuminuria and 15 diabetics with macroalbuminuria. Mean plasma renin activity for macroalbuminuric diabetics (0.65 ±0. 10 ng/ml/hr) was significantly reduced than the controls (1.28 ±0.37 ng/ml/hr) (P < 0.001), the diabetic group with microalbuminuria (1.08 ±0.48 ng/ml/hr) (P < 0.05) and normoalbuminuric patients (1 .56 ±0.82 ng/ml/hr) (P<0.001). A significant negative correlation was obtained between serum creatinine and plasma renin activity (r=-0.842, p<0.001) in macroalbuminuric NIDDM patients. Plasma angiotensin II was significantly decreased in non-complicated diabetics compared to healthy controls (4.36± 1.49 pg/ml vs 14.87 ± 3.48 pg/ml respectively, p < 0.001). Non-insulin dependent diabetic patients with nephropathy had significantly higher plasma angiotensin II levels (28.99 ± 5.88 pg/ml) than non-complicated diabetics (p < 0.001). Serum ACE activity was increased in 53.3% of NIDDM patients. All diabetic groups showed increased serum ACE activity (normoalbuminuric NIDDM 114.9 ± 28.3 nmol/min/ml, microalbuminuric NIDDM 127.9 ± 31.2 nmol/min/ml and macroalbuminuric NIDDM 127.0±29.3 nmol/min/ml) when compared to the normal control group (76.3±16.5 nmol/min/ml) (p<0.001). No significant difference in serum ACE activity was obtained between normoalbuminuric and nephropathic diabetics or between diabetics with and without retinopathy.No significant correlation was obtained between serum ACE activity and blood pressure, blood glucose level and duration of diabetes. Thus plasma renin activity is decreased in diabetic nephropathy and negatively correlates with serum creatinine. Plasma angiotensin II is decreased in normoalbuminuric diabetics and elevated in diabetic nephropathy. Serum ACE activity is raised in NIDDM patients with no relation to albumin excretion rate. The role of increased ACE activity in NIDDM remains to be established.

Cardiovascular dysfunction in Zucker obese and Zucker diabetic fatty rats: role of hydronephrosis

“…A decrease in renin production is the likely cause of lower ANG II levels in ZO and ZDFO rats; this may be a reflection of a greater loss of renal parenchyma with the more severe levels of hydronephrosis in ZO and ZDFO rats than that seen in ZL rats. Nevertheless, the lower plasma ANG II levels are not consistent with previous reports in diabetic rats with renal dysfunction (16). Importantly, the lower ANG II levels in ZDFO rats in the face of LV dysfunction and increased plasma norepinephrine levels suggest a blunted renin-angiotensin system.…”

Pioglitazone Decreases Plasma Angiotensin II Concentration inType 2 Diabetes

“…Nicola et al 31) have reported that plasma A is lower in non-complicated T2Ds compared to healthy controls, and higher in T2Ds with nephropathy compared to non-complicated T2Ds. In this study, although pioglitazone decreased HbA1c significantly, the decrease in HbA1c did not correlate with the decrease in plasma A ; therefore, the effect of pioglitazone on decreasing plasma A may be independent of its glucose-lowering effect.…”

Renal ACE and ACE2 Expression in Early Diabetic Rats

“…Previous studies have reported suppressed, normal, or elevated levels of renal and plasma Ang II in diabetes [24,25,26]. Kikkawa et al [27] reported biphasic alteration of the RAS that included higher plasma renin activity and higher levels of Ang II and aldosterone in the plasma in early diabetes, while lower levels were observed 4 weeks after STZ injection.…”