Variability in benefit from intensive insulin therapy on cardiovascular events in individuals with type 1 diabetes: A post hoc analysis of the DCCT/EDIC study.
cardiovascular diseases
insulin
randomized controlled trial
type 1 diabetes
Journal
Diabetic medicine : a journal of the British Diabetic Association
ISSN: 1464-5491
Titre abrégé: Diabet Med
Pays: England
ID NLM: 8500858
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
13
07
2023
received:
13
04
2023
accepted:
17
07
2023
medline:
23
10
2023
pubmed:
20
7
2023
entrez:
20
7
2023
Statut:
ppublish
Résumé
To evaluate presence of treatment effect heterogeneity of intensive insulin therapy (INT) on occurrence of major adverse cardiovascular events (MACE) in individuals with type 1 diabetes. In participants from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study, individual treatment effect of INT (≥3 daily insulin injections/insulin pump therapy) versus conventional therapy (once/twice daily insulin) on the risk of MACE was estimated using a penalized Cox regression model including treatment-by-covariate interaction terms. In 1441 participants, 120 first MACE events were observed and 1279 individuals (89%) were predicted to benefit from INT with regard to MACE risk reduction. The study population was divided into four groups based on predicted treatment effect: one group with no predicted benefit and three tertiles with predicted treatment benefit. The median absolute reduction in 30-year risk of MACE across groups of predicted treatment effect ranged from -0.2% (i.e. risk increase; interquartile range [IQR] -0.1% to -0.3%) in the group with no predicted benefit to 6.6% (i.e. risk reduction; IQR 3.8%-10.9%; number needed to treat 15) in the highest tertile of predicted benefit. The observed benefit of preventing microvascular complications was stable across all subgroups of predicted MACE benefit. Although INT reduces the risk of MACE in the majority of individuals with type 1 diabetes, benefit varies substantially. These individual differences in the effect of INT underline the necessity for a better understanding of the individual response to intensive treatment.
Substances chimiques
Insulin
0
Banques de données
ClinicalTrials.gov
['NCT00360893', 'NCT00360815']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e15183Informations de copyright
© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.
Références
Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41(2):255-323. doi:10.1093/eurheartj/ehz486
The DCCT Research Group. The diabetes control and complications trial (DCCT): design and methodologic considerations for the feasibility phase. Diabetes. 1986;35(5):530-545. doi:10.2337/diab.35.5.530
The DCCT 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.
Lachin JM, Genuth S, Cleary P, Davis MD, Nathan DM. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med. 2000;342(6):381-389. doi:10.1056/NEJM200002103420603
Gubitosi-Klug RA, Lachin JM, Backlund JYC, Lorenzi GM, Brillon DJ, Orchard TJ. Intensive diabetes treatment and cardiovascular outcomes in type 1 diabetes: the DCCT/EDIC study 30-year follow-up. Diabetes Care. 2016;39(5):686-693. doi:10.2337/dc15-1990
Gubitosi-Klug RA, Braffett BH, White NH, et al. Risk of severe hypoglycemia in type 1 diabetes over 30 years of follow-up in the DCCT/EDIC study. Diabetes Care. 2017;40:1010-1016. doi:10.2337//dc16-2723
Braffett BH, Bebu I, El ghormli L, et al. Cardiometabolic risk factors and incident cardiovascular disease events in women vs men with type 1 diabetes. JAMA Netw Open. 2022;5(9):e2230710. doi:10.1001/jamanetworkopen.2022.30710
The DCCT Research Group. Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: diabetes control and complications trial. J Pediatr. 1994;125(2):177-188. doi:10.1016/s0022-3476(94)70190-3
Kent DM, Steyerberg E, Van Klaveren D. Personalized evidence based medicine: predictive approaches to heterogeneous treatment effects. BMJ (Online). 2018;363:363. doi:10.1136/bmj.k4245
The EDIC Research Group. Epidemiology of diabetes interventions and complications (EDIC). Design, implementation, and preliminary results of a long-term follow-up of the diabetes control and complications trial cohort. Diabetes Care. 1999;22(1):99-111.
Orchard TJ, Nathan DM, Zinman B, et al. Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality. JAMA. 2015;313(1):45-53. doi:10.1001/jama.2014.16107
Cederholm J, Eeg-Olofsson K, Eliasson B, Zethelius B, Gudbjörnsdottir S. A new model for 5-year risk of cardiovascular disease in type 1 diabetes; from the Swedish National Diabetes Register (NDR). Diabetes Med. 2011;28(10):1213-1220. doi:10.1111/j.1464-5491.2011.03342.x
McGurnaghan SJ, McKeigue PM, Read SH, et al. Development and validation of a cardiovascular risk prediction model in type 1 diabetes. Diabetologia. 2021;64(9):2001-2011. doi:10.1007/s00125-021-05478-4
Soedamah-Muthu SS, Vergouwe Y, Costacou T, et al. Predicting major outcomes in type 1 diabetes: a model development and validation study. Diabetologia. 2014;57(11):2304-2314. doi:10.1007/s00125-014-3358-x
Vistisen D, Andersen GS, Hansen CS, et al. Prediction of first cardiovascular disease event in type 1 diabetes mellitus-the steno type 1 risk engine. Circulation. 2016;133(11):1058-1066. doi:10.1161/CIRCULATIONAHA.115.018844
Hansen GM, Jørgensen PG, Andersen HU, Rossing P, Jensen MT. Relationship between peripheral neuropathy, diastolic function and adverse cardiovascular outcome in individuals with type 1 diabetes mellitus without known cardiovascular disease: results from the thousand & 1 study. Diabetes Obes Metab. 2021;23(1):158-165. doi:10.1111/dom.14209
Shah VN, Bailey R, Wu M, et al. Risk factors for cardiovascular disease (CVD) in adults with type 1 diabetes: findings from prospective real-life T1D exchange registry. J Clin Endocrinol Metabol. 2020;105(5):2032-2038. doi:10.1210/clinem/dgaa015
De Ferranti SD, De Boer IH, Fonseca V, et al. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Circulation. 2014;130(13):1110-1130. doi:10.1161/CIR.0000000000000034
Hoerl AE, Kennard RW. Ridge regression: biased estimation for nonorthogonal problems. Dent Tech. 2000;42(1):80-86. doi:10.1080/00401706.2000.10485983
van Klaveren D, Steyerberg EW, Serruys PW, Kent DM. The proposed ‘concordance-statistic for benefit’ provided a useful metric when modeling heterogeneous treatment effects. J Clin Epidemiol. 2018;94:59-68. doi:10.1016/j.jclinepi.2017.10.021
De Vries TI, Dorresteijn JAN, Van Der Graaf Y, Visseren FLJ, Westerink J. Heterogeneity of treatment effects from an intensive lifestyle weight loss intervention on cardiovascular events in patients with type 2 diabetes: data from the look AHEAD trial. Diabetes Care. 2019;42(10):1988-1994. doi:10.2337/dc19-0776
Koopal C, Visseren FLJ, Westerink J, Van Der Graaf Y, Ginsberg HN, Keech AC. Predicting the effect of fenofibrate on cardiovascular risk for individual patients with type 2 diabetes. Diabetes Care. 2018;41(6):1244-1250. doi:10.2337/dc17-0968
Nathan DM. Realising the long-term promise of insulin therapy: the DCCT / EDIC study diabetes control and complications trial. Diabetologia. 2021;64:1049-1058.
Nathan DM, Bebu I, Braffett BH, et al. Risk factors for cardiovascular disease in type 1 diabetes. Diabetes. 2016;65(5):1370-1379. doi:10.2337/db15-1517
The Writing Group for the DCCT/EDIC Research Group. Coprogression of cardiovascular risk factors in type 1 diabetes during 30 years of follow-up in the DCCT/EDIC study. Diabetes Care. 2016;39(9):1621-1630. doi:10.2337/dc16-0502
Bebu I, Schade D, Braffett B, et al. Risk factors for first and subsequent CVD events in type 1 diabetes: the DCCT/EDIC study. Diabetes Care. 2020;43(4):867-874. doi:10.2337/dc19-2292
Bebu I, Braffett BH, Orchard TJ, Lorenzi GM, Lachin JM, the DCCT/EDIC Research Group. Mediation of the effect of Glycemia on the risk of CVD outcomes in type 1 diabetes: the DCCT/EDIC study. Diabetes Care. 2019;42(7):1284-1289. doi:10.2337/dc18-1613
Orchard TJ, Backlund JYC, Costacou T, et al. Haptoglobin 2-2 genotype and the risk of coronary artery disease in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study (DCCT/EDIC). J Diabetes Complications. 2016;30(8):1577-1584. doi:10.1016/j.jdiacomp.2016.07.014
Kaptoge S, Pennells L, De Bacquer D, et al. World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions. Lancet Glob Health. 2019;7(10):e1332-e1345. doi:10.1016/S2214-109X(19)30318-3
Xu Z, Arnold M, Stevens D, et al. Prediction of cardiovascular disease risk accounting for future initiation of statin treatment. Am J Epidemiol. 2021;190(10):2000-2014. doi:10.1093/aje/kwab031