title: Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity.
abstract: OBJECTIVE
  Insulin-resistance syndrome and hyperinsulinaemia are linked with cardiovascular disease (CVD) in the obese population. In particular, cardiovascular risk is more frequent in central obesity and is associated with microalbuminuria (MA). MA and changes of glomerular permeability to proteins 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 induce MA and proteinuria in patients with central obesity.
  
  
  METHODS
  Forty normotensive obese out-patients, 22 with central (CO group) and 18 with peripheral (PO group) body fat distribution and 11 healthy subjects.
  
  
  METHODS
  Serum insulin and glucagon concentrations (fasting and after oral glucose tolerance test (OGTT)) by radio immuno assay (RIA); glomerular filtration rate (GFR, isotopic); total clearances and urinary excretion rates of albumin (AER), IgG (IgGER) and alpha1 microglobulin (computerized immunonephelometry).
  
  
  RESULTS
  GFR and insulin concentrations (fasting and during OGTT) were higher in the CO than the PO group. Fasting glucagon concentrations were increased, and not physiologically suppressed during OGTT in patients with CO (fasting, P<0.05; OGTT 60 and 120 min, P<0.001 vs PO group). Moreover, glucagon 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); whereas no correlations were found in the PO group. Higher AER (P<0.001), IgGER (P<0.001) and alpha1 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 associated 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.
authors.affiliation: Department of Internal Medicine, School of Endocrinology and Metabolism and Chair of Geriatrics, University of Pavia, Piazza Borromeo 2, 27100 Pavia, Italy. ferrari@unipv.it
authors.forename: S B
authors.initials: SB
authors.lastname: Solerte
authors.forename: M
authors.initials: M
authors.lastname: Rondanelli
authors.forename: R
authors.initials: R
authors.lastname: Giacchero
authors.forename: M
authors.initials: M
authors.lastname: Stabile
authors.forename: E
authors.initials: E
authors.lastname: Lovati
authors.forename: L
authors.initials: L
authors.lastname: Cravello
authors.forename: B
authors.initials: B
authors.lastname: Pontiggia
authors.forename: G
authors.initials: G
authors.lastname: Vignati
authors.forename: E
authors.initials: E
authors.lastname: Ferrari
authors.forename: M
authors.initials: M
authors.lastname: Fioravanti
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology; D016022:Case-Control Studies; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D005934:Glucagon / Q000097:blood*; D005951:Glucose Tolerance Test; D006023:Glycoproteins / Q000652:urine; D006439:Hemodynamics; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000652:urine; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D011507:Proteinuria / Q000209:etiology / Q000652:urine; D012307:Risk Factors; D014360:Trypsin Inhibitor, Kunitz Soybean
chemical_list: D005230:Fatty Acids, Nonesterified; D006023:Glycoproteins; D007074:Immunoglobulin G; D007328:Insulin; D008562:Membrane Glycoproteins; C109148:SPINT2 protein, human; D005934:Glucagon; D014360:Trypsin Inhibitor, Kunitz Soybean