benefits of reduced A1c become smaller, and the intensive glycemic control required to reach this level leads to an increased rate of dangerous hypoglycemic episodes. A retrospective study of 47,970 type 2 diabetes patients, aged 50 years and older, found that patients with an HbA1c more than 48 mmol/mol (6.5 DCCT %) had an increased mortality rate, but a later international study contradicted these findings. A review of the UKPDS, Action to Control Cardiovascular Risk in Diabetes (ACCORD), Advance and Veterans Affairs Diabetes Trials (VADT) estimated that the risks of the main complications of diabetes (diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, and macrovascular disease) decreased by about 3% for every 1 mmol/mol decrease in HbA1c. However, a trial by ACCORD designed specifically to determine whether reducing HbA1c below 6.0% using increased amounts of medication would reduce the rate of cardiovascular events found higher mortality with this intensive therapy, so much so that the trial was terminated 17 months early. Practitioners must consider patients' health, their risk of hypoglycemia, and their specific health risks when setting a target HbA1c level. Because patients are responsible for averting or responding to their own hypoglycemic episodes, their input and the doctors' assessments of the patients' self-care skills are also important. Persistent elevations in blood sugar (and, therefore, HbA1c) increase the risk of long-term vascular complications of diabetes, such as coronary disease, heart attack, stroke, heart failure, kidney failure, blindness, erectile dysfunction, neuropathy (loss of sensation, especially in the feet), gangrene, and gastroparesis (slowed emptying of the stomach). Poor blood glucose control also increases the risk of short-term complications of surgery such as poor wound healing. Lower-than-expected levels of HbA1c can be seen in people with shortened red blood cell lifespans, such as with glucose-6-phosphate dehydrogenase deficiency, sickle-cell disease, or any other condition causing premature red blood cell death. Blood donation will result in rapid replacement of lost RBCs with newly formed red blood cells. Since these new RBCs will have only existed for a short period of time, their presence will lead HbA1c to underestimate the actual average levels. There may also be distortions resulting from blood donation during the preceding two months, due to an abnormal synchronization of the age of the RBCs, resulting in an older than normal average blood cell life (resulting in an overestimate of actual average blood glucose levels). Conversely, higher-than-expected levels can be seen in people with a