Objective: To examine the effect of different patterns of durable glycemic control on the development of comorbidities among youth with type 2 diabetes and to assess the impact of fasting glucose variability on the clinical course of type 2 diabetes. Research Design and Methods: 457 TODAY participants, mean age 14 years and diabetes duration Results: Higher baseline HbA1c concentration, lower beta-cell function, and maternal history of diabetes were strongly associated with loss of glycemic control in youth with type 2 diabetes. Higher cumulative HbA1c concentration over 4 years and greater fasting glucose variability over a year’s time within 3 years of diagnosis were related to higher prevalence of dyslipidemia, nephropathy, and retinopathy progression over the subsequent 10 years. A coefficient of variability in fasting glucose at or above 8.3% predicted future loss of glycemic control and development of comorbidities. Conclusions: Higher baseline HbA1c concentration and fasting glucose variability during year 1 accurately predicted youth with type 2 diabetes who will experience metabolic decompensation and comorbidities and may be useful tools for clinicians when considering early intensification of therapy.