Glycemic goals in diabetes: trade-off between glycemic control and iatrogenic hypoglycemia

The selection of a glycemic goal in a person with diabetes is a compromise between the documented upside of glycemic control-the partial prevention or delay of microvascular complications-and the documented downside of glycemic control-the recurrent morbidity and potential mortality of iatrogenic hypoglycemia. The latter is not an issue if glycemic control is accomplished with drugs that do not cause hypoglycemia or with substantial weight loss. However, hypoglycemia becomes an issue if glycemic control is accomplished with a sulfonylurea, a glinide, or insulin, particularly in the setting of absolute endogenous insulin deficiency with loss of the normal decrease in circulating insulin and increase in glucagon secretion and attenuation of the sympathoadrenal response as plasma glucose concentrations fall. Then the selection of a glycemic goal should be linked to the risk of hypoglycemia. A reasonable individualized glycemic goal is the lowest A1C that does not cause severe hypoglycemia and preserves awareness of hypoglycemia, preferably with little or no symptomatic or even asymptomatic hypoglycemia, at a given stage in the evolution of the individual's diabetes.