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Review
. 2020 Mar;69(3):291-299.
doi: 10.2337/db19-0514.

Understanding Metabolic Memory: A Tale of Two Studies

Rachel G Miller  1 , Trevor J Orchard  2
Affiliations
Review

Understanding Metabolic Memory: A Tale of Two Studies

Rachel G Miller et al. Diabetes. 2020 Mar.

Abstract

The results of the Diabetes Control and Complications Trial (DCCT) have given rise to much encouragement in the battle to stave off the complications of type 1 diabetes, showing dramatic declines in the development of severe retinopathy, nephropathy, and neuropathy in those treated intensively compared with conventional therapy. Particularly encouraging has been the continuing difference between the two groups despite both having similar HbA1c (∼8%) since the end of DCCT, when 96% of participants entered the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. This continuing relative benefit has been termed "metabolic memory," which implies altered metabolic regulation. Based on evidence from both the Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset type 1 diabetes and DCCT/EDIC, we show that the metabolic memory effect can be largely explained by lower cumulative glycemic exposure in the intensive therapy group, and, on average, the development of complications increases with greater glycemic exposure, irrespective of whether this results from a high exposure for a short time or a lower exposure for a longer time. Thus, there is no need for a concept like "metabolic memory" to explain these observations. Potential mechanisms explaining the cumulative glycemic effect are also briefly discussed.

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Figures

Figure 1
Figure 1
Hazard ratios associated with each A1c Month quintile, compared with the reference group (<570 A1c Months). Error bars are 95% CI.
Figure 2
Figure 2
Predicted cumulative incidence of retinopathy (A), overt nephropathy (B), and CVD (C) by A1c Months in the DCCT-eligible subgroup of the EDC cohort (line) and the observed cumulative incidence in the DCCT/EDIC conventional (circle) and intensive (star) groups at 20 years’ duration (corresponding observed mean A1c Months 729 and 534, respectively). The inset panels provide a closer view of cumulative incidence curve at <1,000 A1c Months. T1D, type 1 diabetes.
See this image and copyright information in PMC

Comment in

References

    1. Nathan DM, Zinman B, Cleary PA, et al. .; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group . Modern-day clinical course of type 1 diabetes mellitus after 30 years’ duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983-2005). Arch Intern Med 2009;169:1307–1316 - PMC - PubMed
    1. Pambianco G, Costacou T, Ellis D, Becker DJ, Klein R, Orchard TJ. The 30-year natural history of type 1 diabetes complications: the Pittsburgh Epidemiology of Diabetes Complications Study experience. Diabetes 2006;55:1463–1469 - PubMed
    1. Costacou T, Orchard TJ. Cumulative kidney complication risk by 50 years of type 1 diabetes: the effects of sex, age, and calendar year at onset. Diabetes Care 2018;41:426–433 - PMC - PubMed
    1. Kahn R, Robertson RM, Smith R, Eddy D. The impact of prevention on reducing the burden of cardiovascular disease. Diabetes Care 2008;31:1686–1696 - PMC - PubMed
    1. Nathan DM, Genuth S, Lachin J, et al. .; Diabetes Control and Complications Trial Research Group . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–986 - PubMed

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