The Use of Machine Learning Techniques to Determine the Predictive Value of Inflammatory Biomarkers in the Development of Type 2 Diabetes Mellitus

Abstract

Background: Certain inflammatory biomarkers, such as interleukin-6, interleukin-1, C-reactive protein (CRP), and fibrinogen, are prototypical acute-phase parameters that can also be predictors of cardiovascular disease. However, this inflammatory response can also be linked to the development of type 2 diabetes mellitus (T2DM). Methods: We performed a cross-sectional, retrospective study of hypertensive patients in an outpatient setting. Demographic, clinical, and laboratory parameters, such as the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), CRP, and fibrinogen, were recorded. The outcome was progression to overt T2DM over the 12-year observation period. Results: A total of 3,472 hypertensive patients were screened, but 1,576 individuals without T2DM were ultimately included in the analyses. Patients with elevated fibrinogen, CRP, and insulin resistance had a significantly greater incidence of progression to T2DM. During follow-up, 199 patients progressed to T2DM. Multivariate logistic regression analyses showed that body mass index [odds ratio (OR) 1.04, 95% confidence interval (CI): 1.01–1.07], HOMA-IR (OR 1.13, 95% CI: 1.08–1.16), age (OR 1.05, 95% CI: 1.03–1.07), log(CRP) (OR 1.37, 95% CI: 1.14–1.55), and fibrinogen (OR 1.44, 95% CI: 1.23–1.66) were the most important predictors of progression to T2DM. The area under the receiver operating characteristic curve (AUC) of this model was 0.76. Using machine learning methods, we built a model that included HOMA-IR, fibrinogen, and log(CRP) that was more accurate than the logistic regression model, with an AUC of 0.9. Conclusion: Our results suggest that inflammatory biomarkers and HOMA-IR have a strong prognostic value in predicting progression to T2DM. Machine learning methods can provide more accurate results to better understand the implications of these features in terms of progression to T2DM. A successful therapeutic approach based on these features can avoid progression to T2DM and thus improve long-term survival.