Type 2 diabetes, obesity, and the renal response to blocking the renin system with irbesartan.
OBJECTIVE
Our recent studies revealed a striking but variable enhancement of renal vasodilator responses to blockers of the renin-angiotensin system in subjects with diabetes mellitus, possibly reflecting the level of intrarenal activation of the renin-angiotensin system, and thus a risk of nephropathy. As obesity is a common finding in diabetic individuals, and obesity has been linked to an increase in plasma angiotensinogen levels, we enrolled diabetic subjects with a wide range of body mass index (BMI) for this study.


METHODS
Twelve Type 2 diabetic subjects in balance on a low sodium diet participated after baseline renal plasma flow and glomerular filtration measurements were made. Each subject then received 150 mg irbesartan, and renal function was measured every 45 min for 4 h.


RESULTS
The average vasodilator response to irbesartan was 174 +/- 33 ml/min. No correlation was found between renal plasma flow response to irbesartan and duration of diabetes, baseline glucose, or HbA1c level. BMI, our measure of obesity, was highly correlated to the renal response to irbesartan (r = 0.7; P = 0.01).


CONCLUSIONS
Our findings suggest an important role for obesity in activating the intrarenal renin system, perhaps via production of angiotensinogen. BMI may be an indicator of risk of nephropathy.
D000328:Adult; D000803:Angiotensin I; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D000077405:Irbesartan; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012307:Risk Factors; D013777:Tetrazoles; D014665:Vasodilator Agents
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D013777:Tetrazoles; D014665:Vasodilator Agents; D000803:Angiotensin I; D000077405:Irbesartan