Lingering Effects of Hyperglycemia in Recently Diagnosed Diabetes During Long-term Follow-up of the DCCT/EDIC and UKPDS Cohorts: More Evidence That Early Control Matters

The Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS) have given us fundamental insights into the natural history and management of diabetes (1,2). These include strong evidence that 1 ) enhanced glycemic management can limit some of the complications of diabetes, 2 ) there is a dose-response relationship between HbA1c levels and the risk of complications, and 3 ) a treatment target of <7.0% (<53 mmol/mol) HbA1c is realistic and appropriate. Continued observation of the randomized cohorts after the planned end of study has further shown that cardiovascular events and mortality, which could not be shown to be improved during the randomized treatment phases, were significantly reduced long after glucose control equalized in the two arms (3–5). In both studies glycemic control as assessed by HbA1c accounted statistically for most of the difference in outcomes. In three articles in this issue of Diabetes Care the DCCT and UKPDS investigators provide more information on the long-term effects of enhanced glycemic control early in the natural history of diabetes (6–8). In the first of two articles based on more than 20 years of additional observation of the DCCT cohorts in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, Lachin and Nathan (6) report new analyses of data on microvascular complications. These add to previously reported evidence for persistence of lower rates of progression of microvascular disease in the originally intensively managed cohort, despite convergence of HbA1c values in the two groups soon after cessation of the randomized comparison of treatments. The investigators have previously termed this phenomenon “metabolic memory.” Here they further report a gradual waning of outcome differences after ∼10 years. They emphasize a distinction between the incremental effect on microvascular complications, which slowly declines, and the cumulative …