Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity

OBJECTIVES: Insulin-resistance syndrome and hyperinsulinaemia are linked wi th cardiovascular disease (CVD) in the obese population, In particular, car diovascular risk is more frequent in central obesity and is associated with microalbuminuria (MA). MA and changes of glomerular permeability to protei ns in obesity might be related with renal haemodynamic modifications (that is glomerular hyperfiltration). Since glucagon is physiologically involved in renal haemodynamic regulation, the purpose of this study was to examine whether changes of circulating glucagon levels might haemodynamically induc e MA and proteinuria in patients with central obesity, SUBJECTS: Forty normotensive obese out-patients, 22 with central (CO group) and 18 with peripheral (PO group) body fat distribution and 11 healthy sub jects. MEASUREMENTS: Serum insulin and glucagon concentrations (fasting and after oral glucose tolerance test (OGTT)) by radio immune assay (RIA); glomerular filtration rate (GFR, isotopic); total clearances and urinary excretion ra tes of albumin (AER), IgG (IgGER) and alpha 1 microglobulin (computerized i mmunonephelometry). RESULTS: GFR and insulin concentrations (fasting and during OGTT) were high er in the CO than the PO group. Fasting glucagon concentrations were increa sed, and not physiologically suppressed during OGTT in patients with CO (fa sting, P < 0.05; OGTT 60 and 120 min, P < 0.001 vs PO group). Moreover, glu cagon concentrations were significantly correlated with GFR in the CO group (fasting, r = 0.49, P < 0.05; 60 min after OGTT, r = 0.58, P < 0.01); wher eas no correlations were found in the PO group. Higher AER (P < 0.001), IgG ER (P < 0.001) and alpha 1 microglobulin (P < 0.05) urinary concentrations were found in patients with CO than in the PO group. CONCLUSIONS: The increase of serum glucagon concentrations may be associate d with the enhancement of GFR in patients with central obesity. Glomerular hyperfiltration might influence the development of MA and of proteinuria by means of a haemodynamic mechanism so contributing to increase the risk of renal microvascular complications and of CVD in central obesity.