Plasma ghrelin concentrations in different clinical stages of diabetic complications and glycemic control in Japanese diabetics

Ghrelin is an acylated 28-amino-acid peptide that stimulates food intake, GH secretion, and gastric motility. Experimental studies have suggested that ghrelin plays roles in glucose homeostasis, atherosclerosis, and microangiopathy. We investigated possible involvement of ghrelin in micro- and macro-vascular diabetic complications and glycemic control in diabetic patients. Fasting and postprandial plasma ghrelin concentrations after a test meal were measured in 108 and 61 Japanese diabetic patients, respectively. Plasma ghrelin concentrations were negatively correlated with body mass index (BMI) (r=-0.309, P=0.002) or HbA(1c) (r=-0.264, P=0.0065). Plasma ghrelin levels in patients with diabetic nephropathy who showed high serum creatinine levels (s-Cre) were significantly higher than those in patients who showed normal s-Cre (P<0.02). In patients with diabetic triopathy, plasma ghrelin concentrations were significantly lower than those in patients without diabetic complications (P<0.05). Stepwise multiple regression analyses revealed that s-Cre, BMI, and HbA(1c) were independently associated with plasma ghrelin levels. A postprandial decrease of ghrelin was observed in patients with normal CVR-R values or those with normal body weight, whereas it was not seen in obese patients or in patients with low CVR-R values. Suppression rates of ghrelin 30-60 min after a test meal in obese patients were significantly lower than those in normal-weight patients. These Findings suggest that ghrelin secretion is suppressed by long-term hyperglycemia and that obesity influences the regulation of ghrelin secretion.