Near normal HbA1c with stable glucose homeostasis: the ultimate target/aim of diabetes therapy

Achieving near normal glucose homeostasis implies that all components of dysglycemia that are present in diabetes states be eliminated. Reducing ambient/overall hyperglycemia is a pre-requisite to eliminate the risk of development and progression of diabetes complications. More controversially however, are the relative and related contributions of postprandial glucose excursions, glucose variability, hypoglycemia and the dawn phenomenon across the spectrum of dysglycemia. For instance, it is likely that the dawn phenomenon contributes to ambient hyperglycemia and that postprandial glucose excursions are at the cross road of ambient hyperglycemia and glucose variability with glucose fluctuations as causative risk factors for hypoglycemia. Proof-of-concept trials such as the ongoing FLAT-SUGAR study are necessary for gaining further insight into the possible harmful effects of some of these features such as excessive glycemic variability and glucose excursions, still considered to be of minor relevance by several diabetologists. Whether their role will be more thoroughly proven through further intervention trials with "hard" endpoints, remains to be seen. In the meantime more consideration should be given to medications aimed at concomitantly reducing ambient/overall hyperglycemia and those additional abnormal glycemic features of dysglycemia.