Current guidelines for treating patients with type 2 diabetes mellitus are based on glycemic standards derived from epidemiologic data; however, the course of the disease, from prediabetes to end-stage complications, is not the same in all patients. Microvascular complications, including nephropathy, retinopathy, and neuropathy, are strongly related to hemoglobin A1c (HbA1c). However, vascular complications may progress in patients who have HbA1c <7.0% and may appear even in undiagnosed patients owing to transient increases in plasma glucose concentrations. Concomitant atherosclerosis and occult macrovascular disease may follow an accelerated course in type 2 diabetes. Macrovascular complications may develop early, and, like microvascular complications, do not correlate linearly with HbA1c. Managing hyperglycemia in the later stages of type 2 diabetes does not appear to be associated with improved cardiovascular outcomes. The glucotoxicity and lipotoxicity that may precede prolonged hyperglycemia and beta-cell dysfunction are early, reversible pathophysiologic events. This suggests that prompt management may modify the course of hyperglycemia and prevent or delay long-term complications. The challenge remains to identify patients with early type 2 diabetes who are at risk for rapid progression of beta-cell decline and premature development of microvascular complications. Ongoing research into the mechanisms responsible for diabetic complications may provide new markers to help identify patients with type 2 diabetes who can benefit from earlier antidiabetes treatments.
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