Solerte S B, Rondanelli M, Giacchero R, Stabile M, Lovati E, Cravello L, Pontiggia B, Vignati G, Ferrari E, Fioravanti M
Department of Internal Medicine, School of Endocrinology and Metabolism and Chair of Geriatrics, University of Pavia, Piazza Borromeo 2, 27100 Pavia, Italy.
Int J Obes Relat Metab Disord. 1999 Sep;23(9):997-1003. doi: 10.1038/sj.ijo.0801032.
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.
Forty normotensive obese out-patients, 22 with central (CO group) and 18 with peripheral (PO group) body fat distribution and 11 healthy subjects.
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).
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.
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.
胰岛素抵抗综合征和高胰岛素血症与肥胖人群的心血管疾病（CVD）相关。特别是，中心性肥胖患者心血管风险更高，且与微量白蛋白尿（MA）有关。肥胖患者的MA和肾小球对蛋白质通透性的变化可能与肾脏血流动力学改变（即肾小球高滤过）有关。由于胰高血糖素在生理上参与肾脏血流动力学调节，本研究旨在探讨循环胰高血糖素水平的变化是否会在血流动力学上导致中心性肥胖患者出现MA和蛋白尿。
40名血压正常的肥胖门诊患者，其中22名中心性肥胖（CO组），18名外周性肥胖（PO组），以及11名健康受试者。
通过放射免疫分析（RIA）测定血清胰岛素和胰高血糖素浓度（空腹及口服葡萄糖耐量试验（OGTT）后）；肾小球滤过率（GFR，同位素法）；白蛋白（AER）、IgG（IgGER）和α1微球蛋白的总清除率及尿排泄率（计算机化免疫比浊法）。
CO组的GFR和胰岛素浓度（空腹及OGTT期间）高于PO组。CO组患者空腹胰高血糖素浓度升高，且在OGTT期间未出现生理性抑制（空腹时，P<0.05；OGTT 60分钟和120分钟时，与PO组相比P<0.001）。此外，CO组中胰高血糖素浓度与GFR显著相关（空腹时，r=0.49，P<0.05；OGTT 60分钟后，r=0.58，P<0.01）；而PO组未发现相关性。CO组患者的尿AER（P<0.001）、IgGER（P<0.001）和α1微球蛋白浓度（P<0.05）高于PO组。
血清胰高血糖素浓度升高可能与中心性肥胖患者GFR升高有关。肾小球高滤过可能通过血流动力学机制影响MA和蛋白尿的发生，从而增加中心性肥胖患者发生肾脏微血管并发症和CVD的风险。
