Multistate Models to Predict Development of Late Complications of Type 2 Diabetes in an Open Cohort Study

Abstract

Background: Increase in the prevalence of type 2 diabetic mellitus (T2DM) as a complex disease, its complications, and spread has become a dominant global health threat in recent decades. Objective: The aim of the current study was to investigate the impact of risk factors and transition probability on the development and progression of the late complications of T2DM. Methods: This study was an open cohort one which was conducted at Isfahan Endocrine and Metabolism Research Center (IEMRC). The data were collected from 1993 to 2018. The sample size consisted of 2519 adults diagnosed with type 2 diabetes. We applied the homogeneous multistate models including no complication, retinopathy alone, coronary artery disease (CAD), microalbuminuria, retinopathy and CAD, and the final absorbing mortality states. Results: Based on our results, time-varying hypertension strongly intensified the hazard of transition to mortality in CAD, no complication, CAD and retinopathy, and retinopathy patients by 4.99, 4.09, 3.42, and 2.65 times, respectively. Hypertension seemed to be a potential factor for the transition of microalbuminuria to no complication in diabetic patients. One-unit increase in LDL increased the hazard ratio of transition from CAD, and retinopathy and CAD to mortality by 1.8 and 2.4, respectively. Moreover, one level increase in time-varying HbA1c increased the hazard ratio of transition to retinopathy and mortality among no complication diabetic patients by 30 and 67, respectively. One level increase in time-varying HbA1c also intensified the hazard ratio of transition from retinopathy to mortality by 45. The same level of increase in time-varying HbA1c also intensified the hazard ratio of transition from CAD alone to CAD and retinopathy, and microalbuminuria to retinopathy by 26 and 50, respectively. Conclusion: In addition to glycemic control, our study indicates that controlling hypertension and hyperlipidemia is more effective in reducing mortality and the diabetic macro- and microvascular complications.