Development and validation of a predicting model of all-cause mortality in patients with type 2 diabetes

Salvatore De Cosmo, Massimiliano Copetti, Olga Lamacchia, Andrea Fontana, Michela Massa, Eleonora Morini, Antonio Pacilli, Stefania Fariello, Antonio Palena, Anna Rauseo, Rafaella Viti, Rosa Di Paola, Claudia Menzaghi, Mauro Cignarelli, Fabio Pellegrini, Vincenzo Trischitta, Salvatore De Cosmo, Massimiliano Copetti, Olga Lamacchia, Andrea Fontana, Michela Massa, Eleonora Morini, Antonio Pacilli, Stefania Fariello, Antonio Palena, Anna Rauseo, Rafaella Viti, Rosa Di Paola, Claudia Menzaghi, Mauro Cignarelli, Fabio Pellegrini, Vincenzo Trischitta

Abstract

Objective: To develop and validate a parsimonious model for predicting short-term all-cause mortality in patients with type 2 diabetes mellitus (T2DM).

Research design and methods: Two cohorts of patients with T2DM were investigated. The Gargano Mortality Study (GMS, n = 679 patients) was the training set and the Foggia Mortality Study (FMS, n = 936 patients) represented the validation sample. GMS and FMS cohorts were prospectively followed up for 7.40 ± 2.15 and 4.51 ± 1.69 years, respectively, and all-cause mortality was registered. A new forward variable selection within a multivariate Cox regression was implemented. Starting from the empty model, each step selected the predictor that, once included into the multivariate Cox model, yielded the maximum continuous net reclassification improvement (cNRI). The selection procedure stopped when no further statistically significant cNRI increase was detected.

Results: Nine variables (age, BMI, diastolic blood pressure, LDL cholesterol, triglycerides, HDL cholesterol, urine albumin-to-creatinine ratio, and antihypertensive and insulin therapy) were included in the final predictive model with a C statistic of 0.88 (95% CI 0.82-0.94) in the GMS and 0.82 (0.76-0.87) in the FMS. Finally, we used a recursive partition and amalgamation algorithm to identify patients at intermediate and high mortality risk (hazard ratio 7.0 and 24.4, respectively, as compared with those at low risk). A web-based risk calculator was also developed.

Conclusions: We developed and validated a parsimonious all-cause mortality equation in T2DM, providing also a user-friendly web-based risk calculator. Our model may help prioritize the use of available resources for targeting aggressive preventive and treatment strategies in a subset of very high-risk individuals.

Figures

Figure 1
Figure 1
Kaplan-Meier survival curves for 2-year mortality in the pooled sample according to the three risk score categories (low, medium, and high risk) obtained using an RECPAM analysis.

References

    1. The Emerging Risk Factors Collaboration , Seshasai SR, Kaptoge S, Thompson A, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific deaths. N Engl J Med 2011;364:829–841
    1. Roglic G, Unwin N, Bennett PH, et al. The burden of mortality attributable to diabetes: realistic estimates for the year 2000. Diabetes Care 2005;28:2130–2135
    1. International Diabetes Federation (IDF). Diabetes atlas (e-Atlas) [Internet]. Available from Accessed 2 September 2012
    1. Yang X, So WY, Tong PC, et al. Hong Kong Diabetes Registry Development and validation of an all-cause mortality risk score in type 2 diabetes. Arch Intern Med 2008;168:451–457
    1. Wells BJ, Jain A, Arrigain S, Yu C, Rosenkrans WA, Jr, Kattan MW. Predicting 6-year mortality risk in patients with type 2 diabetes. Diabetes Care 2008;31:2301–2306
    1. McEwen LN, Karter AJ, Waitzfelder BE, et al. Predictors of mortality over 8 years in type 2 diabetic patients: Translating Research Into Action for Diabetes (TRIAD). Diabetes Care 2012;35:1301–1309
    1. Pencina MJ, D’Agostino RB. Overall C as a measure of discrimination in survival analysis: model specific population value and confidence interval estimation. Stat Med 2004;23:2109–2123
    1. D’Agostino RB, Nam BH. Evaluation of the Performance of Survival Analysis Models: Discrimination and Calibration Measures. Handbook of Statistics. Vol 23 Amsterdam, the Netherlands, Elsevier Science B.V., 2004
    1. Steyerberg EW, Vickers AJ, Cook NR, et al. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology 2010;21:128–138
    1. Steyerberg EW, Pencina MJ. Reclassification calculations for persons with incomplete follow-up. Ann Intern Med 2010;152:195–196
    1. Pencina MJ, D’Agostino RB, Sr, Steyerberg EW. Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med 2011;30:11–21
    1. Pencina MJ, D’Agostino RB, Sr, Demler OV. Novel metrics for evaluating improvement in discrimination: net reclassification and integrated discrimination improvement for normal variables and nested models. Stat Med 2012;31:101–113
    1. Levey AS, Greene T, Kusek JW, et al. A simplified equation to predict glomerular filtration rate from serum creatinine (Abstract). J Am Soc Nephrol 2000;11:155A
    1. Pencina MJ, D’Agostino RB, Sr, D’Agostino RB, Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008;27:157–172; discussion 207–212
    1. Lin DY, Wei LJ. The robust inference for the Cox proportional hazards model. J Am Stat Ass 1989;84:1074–1078
    1. Ciampi A. Generalized regression trees. Comput Stat Data Anal 1991;12:57–78
    1. Addante F, Sancarlo D, Copetti M, et al. Effect of obesity, serum lipoproteins, and apolipoprotein E genotypes on mortality in hospitalized elderly patients. Rejuvenation Res 2011;14:111–118
    1. Mehran R, Pocock SJ, Nikolsky E, et al. A risk score to predict bleeding in patients with acute coronary syndromes. J Am Coll Cardiol 2010;55:2556–2566
    1. Collins GS, Altman DG. Predicting the 10 year risk of cardiovascular disease in the United Kingdom: independent and external validation of an updated version of QRISK2. BMJ 2012;344:e4181.
    1. Stevens RJ, Kothari V, Adler AI, Stratton IM, United Kingdom Prospective Diabetes Study (UKPDS) Group The UKPDS risk engine: a model for the risk of coronary heart disease in Type II diabetes (UKPDS 56). Clin Sci (Lond) 2001;101:671–679
    1. Skol AD, Scott LJ, Abecasis GR, Boehnke M. Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet 2006;38:209–213
    1. Weedon MN, McCarthy MI, Hitman G, et al. Combining information from common type 2 diabetes risk polymorphisms improves disease prediction. PLoS Med 2006;3:e374.
    1. Barzi F, Woodward M. Imputations of missing values in practice: results from imputations of serum cholesterol in 28 cohort studies. Am J Epidemiol 2004;160:34–45
    1. Miettinen H, Lehto S, Salomaa VV, et al. The FINMONICA Myocardial Infarction Register Study Group Impact of diabetes on mortality after the first myocardial infarction. Diabetes Care 1998;21:69–75
    1. Valmadrid CT, Klein R, Moss SE, Klein BE. The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus. Arch Intern Med 2000;160:1093–1100
    1. Solomon SD, Lin J, Solomon CG, et al. Prevention of Events With ACE Inhibition (PEACE) Investigators Influence of albuminuria on cardiovascular risk in patients with stable coronary artery disease. Circulation 2007;116:2687–2693
    1. Khaw KT, Barrett-Connor E, Suarez L, Criqui MH. Predictors of stroke-associated mortality in the elderly. Stroke 1984;15:244–248
    1. Smooke S, Horwich TB, Fonarow GC. Insulin-treated diabetes is associated with a marked increase in mortality in patients with advanced heart failure. Am Heart J 2005;149:168–174
    1. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143–3421
    1. Carnethon MR, De Chavez PJ, Biggs ML, et al. Association of weight status with mortality in adults with incident diabetes. JAMA 2012;308:581–590
    1. Anderson RJ, Bahn GD, Moritz TE, Kaufman D, Abraira C, Duckworth W, VADT Study Group Blood pressure and cardiovascular disease risk in the Veterans Affairs Diabetes Trial. Diabetes Care 2011;34:34–38

Source: PubMed

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