GCG and Hyperglycemia: Given the facts that serum DPP-4 activity is largely associated with circulating DPP-4 levels [10,32] and that 20% of incretins derived from gastrointestinal tract are still alive in the blood pool [33,34], cumulative hyperglycemia and resultant AGE accumulation might impair the incretins’ effects via elevation of circulating DPP-4 levels, further deteriorating glycemic control and thereby forming a vicious cycle in diabetic subjects.