Evaluation of Polypeptide YY and Ghrelin in Complicated Type 2 Diabetic Patients

The gut peptides polypeptide YY (PYY), (a potent satiety agent) and ghrelin (a potent hunger signal) are suggested to play a role in obesity. Obesity is commonly associated or complicated with hypertension (HT) and type 2 diabetes (T2D). Thus, the current study aimed to: (i) estimate the fasting plasma levels of PYY and ghrelin in lean versus overweight subjects as well as overweight HT and T2D subjects, (ii) assess if PYY and ghrelin are affected by the glycemic state; and (iii) intercorrelate the levels of PYY and ghrelin considering insulin sensitivity, blood pressure values, and lipid profile in HT and/or T2D subjects.Twelve lean healthy male subjects (group I) and fifty eight overweight, age and sex matched subjects (group II) were included in the present study. Group II (overweight group) was further sub-classified into: (i) group Ha: normoglycemic normotensive subjects (n=14); (ii) group lib: T2D normotensive patients (n=18); (iii) group lie: normoglycemic HT patients (n=14). Fasting plasma lipid profile, glucose (FG), insulin (FI), PYY, ghrelin and blood glycated hemoglobin Ajc (HbA1c) were estimated. Insulin sensitivity was evaluated according to the homeostatic model assessment (HOMA) index. In the present study significantly lower mean plasma levels of both ghrelin and PYY were observed in all overweight groups versus the lean control group. The hypertensive and T2D groups, also, showed lower PYY and ghrelin levels compared to the overweight normotensive normoglycemic group. Furthermore, in hypertension T2D group both present, both PYY and ghrelin levels showed further decrease. Ghrelin correlated positively with high density lipoprotein cholesterol, HDL-c (r=0.43, p 0.01). Both ghrelin and PYY correlated negatively with BMI, FG, FI, HbAlc, HOMA index, low density lipoprotein cholesterol (LDL-c) and mean arterial blood pressure (r=-0.52, r=-0.62, r=-0.73, r—0.71, r=-0.76, r=-0.42, and r=-0.5, p 0.01 respectively for ghrelin; and r=-0.51, r=-0.62, r=-0.61, r=-0.62, r=-0.39, and r=-0.48, p 0.05 respectively for PYY). In controls, PYY and ghrelin were negatively correlated (r=-0.76, p 0.001). However, in all groups of patients studied, they were positively correlated (r=0.64, p 0.001). Multiple regression analysis revealed that low ghrelin and PYY concentration were independently correlated to BMI (p=0.002, and p=0.009 respectively).Low ghrelin was, also, independently correlated to FI (i.e., hyperinsulinemia) (p=0.04). In the diabetic groups both PYY and ghrelin levels were lower in patients with poor glycemic control versus controlled diabetics, as assessed by HbA]c. Thus, from the current study it could be concluded that low PYY and ghrelin levels may play a role in the pathogenesis of obesity, hypertension and T2D. Combination of a ghrelin antagonist (a hunger signal antagonist) and PYY (a satiety signal) is potentially and attractive therapeutic strategy for treatment of obesity and its complications.