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Diabetologia
Published in: Diabetologia 6/2010

01-06-2010

The shape of the metabolic memory of HbA1c: re-analysing the DCCT with respect to time-dependent effects

Authors: M. Lind, A. Odén, M. Fahlén, B. Eliasson

Published in: Diabetologia | Issue 6/2010

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Abstract

Aims/hypothesis

We determined the shape of the metabolic memory of HbA1c and its contribution to retinopathy, as well as the importance of reducing HbA1c to prevent progression of retinopathy.

Methods

The relative risk contribution of HbA1c values at different points in time to current progression of retinopathy was determined in the DCCT patients.

Results

HbA1c 2 to 3 years earlier had the greatest relative risk contribution to current progression of retinopathy. HbA1c up to 5 years earlier made a greater contribution than current values, while values from 8 years earlier still had an important impact. When HbA1c had been at 8% for a long period and was subsequently lowered to 7%, the salutary effects did not begin to appear until 2 to 3 years after lowering. The hazard function for a constant level of HbA1c increased with time. The numbers needed to treat when reducing HbA1c from 8.3% to 8% from diagnosis was estimated to be 1,688 for the first 3 years and 13 for the period 9 to 12 years. Survival functions when reducing HbA1c from 8% to 7% show that pre-study glycaemic control dominates the effect on progression of retinopathy during the first years of a trial.

Conclusions/interpretation

The most harmful effect of hyperglycaemia on progression of retinopathy in type 1 diabetes initially increases, but declines after roughly 5 years. The salutary effect of reducing HbA1c accelerates with time and becomes greater in clinical practice than has been previously understood. Clinical trials should preferably be designed for long periods or include patients with low previous glycaemic exposure to distinguish trial effects from those of the metabolic memory.
Appendix
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Literature
1.
Lind M, Odén A, Fahlén M, Eliasson B (2008) A systematic review of HbA1c variables used in the Study of Diabetic Complications, Diabetes and Metabolic Syndrome. Clin Res Rev 2:282–293
2.
Lind M, Odén A, Fahlén M, Eliasson B (2009) The true value of HbA1c as a predictor of diabetic complications: simulations of HbA1c variables. PLoS ONE 4:e4412CrossRefPubMed
3.
DCCT Study Group (1993) 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 329:977–986CrossRef
4.
The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group (2000) Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med 342:381–389CrossRef
5.
Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group (2003) Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. J Am Med Assoc 290:2159–2167CrossRef
6.
Nathan DM, Cleary PA, Backlund JY et al (2005) Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 353:2643–2653CrossRefPubMed
7.
Martin CL, Albers J, Herman WH et al (2006) Neuropathy among the diabetes control and complications trial cohort 8 years after trial completion. Diabetes Care 29:340–344CrossRefPubMed
8.
Ceriello A, Ihnat MA, Thorpe JE (2009) Clinical review 2: The “metabolic memory”: is more than just tight glucose control necessary to prevent diabetic complications? J Clin Endocrinol Metab 94:410–415CrossRefPubMed
9.
Zhang L, Krzentowski G, Albert A, Lefebvre PJ (2001) Risk of developing retinopathy in Diabetes Control and Complications Trial type 1 diabetic patients with good or poor metabolic control. Diabetes Care 24:1275–1279CrossRefPubMed
10.
Skyler JS, Bergenstal R, Bonow RO et al (2009) Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA Diabetes Trials: a position statement of the American Diabetes Association and a Scientific Statement of the American College of Cardiology Foundation and the American Heart Association. J Am Coll Cardiol 53:298–304CrossRefPubMed
11.
12.
No authors listed (1991) Grading diabetic retinopathy from stereoscopic color fundus photographs-an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 98(Suppl 5):786–806
13.
No authors listed (1991) Fundus photographic risk factors for progression of diabetic retinopathy: ETDRS report number 12. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 98(Suppl):823–833
14.
Breslow NE, Day NE (1987) Statistical methods in cancer research, vol 2. IARC Scientific Publications, Lyon, pp 131–135
15.
DCCT Study Group (1995) The relationship of glycaemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial. Diabetes 44:968–983CrossRef
16.
Yoshida Y, Hagura R, Hara Y, Sugasawa G, Akanuma Y (2001) Risk factors for the development of diabetic retinopathy in Japanese type 2 diabetic patients. Diabetes Res Clin Pract 51:195–203CrossRefPubMed
17.
Reichard P, Pihl M, Rosenqvist U, Sule J (1996) Complications in IDDM are caused by elevated blood glucose level: the Stockholm Diabetes Intervention Study (SDIS) at 10-year follow up. Diabetologia 39:1483–1488CrossRefPubMed
18.
Reichard P, Nilsson BY, Rosenqvist U (1993) The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 329:304–309CrossRefPubMed
19.
Kilpatrick ES, Rigby AS, Atkin SL (2008) A1C variability and the risk of microvascular complications in type 1 diabetes: data from the Diabetes Control and Complications Trial. Diabetes Care 31:2198–2202CrossRefPubMed
20.
Lauritzen T, Frost-Larsen K, Larsen HW, Deckert T (1983) Effect of 1 year of near-normal blood glucose levels on retinopathy in insulin-dependent diabetics. Lancet 1:200–204CrossRefPubMed
21.
Dahl-Jorgensen K, Brinchmann-Hansen O, Hanssen KF, Sandvik L, Aagenaes O (1985) Rapid tightening of blood glucose control leads to transient deterioration of retinopathy in insulin dependent diabetes mellitus: the Oslo Study. BMJ 290:811–815CrossRefPubMed
22.
Chantelau E (1998) Evidence that upregulation of serum IGF-1 concentration can trigger acceleration of diabetic retinopathy. Br J Ophthalmol 82:725–730CrossRefPubMed
23.
Fioretto P, Mauer SM, Bilous RW, Goetz FC, Sutherland DE, Steffes MW (1993) Effects of pancreas transplantation on glomerular structure in insulin-dependent diabetic patients with their own kidneys. Lancet 342:1193–1196CrossRefPubMed
24.
Fioretto P, Steffes MW, Sutherland DE, Goetz FC, Mauer M (1998) Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 339:69–75CrossRefPubMed
25.
Fioretto P, Bruseghin M, Berto I, Gallina P, Manzato E, Mussap M (2006) Renal protection in diabetes: role of glycemic control. J Am Soc Nephrol 17(Suppl 2):S86–S89CrossRefPubMed
26.
Selvin E, Marinopoulos S, Berkenblit G et al (2004) Meta-analysis: glycosylated haemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med 141:421–431PubMed
27.
Stevens R, Kothari V, Adler A, Stratton I, Holman R (2001) The UKPDS risk engine: a model for the risk of coronary heart disease in type II diabetes (UKPDS 56). Clin Sci 101:671–679CrossRefPubMed
Metadata
Title
The shape of the metabolic memory of HbA1c: re-analysing the DCCT with respect to time-dependent effects
Authors
M. Lind
A. Odén
M. Fahlén
B. Eliasson
Publication date
01-06-2010
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 6/2010
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-010-1706-z

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