The ultimate goal of precision medicine is to deliver personalized disease risk assessment together with proactive and preventive care for citizens. Personalization is achieved by analyzing and using various data sources, such as clinical, genomic, environmental and lifestyle data. This task is challenging especially for the global public health challenges, such as cardiovascular diseases and type 2 diabetes mellitus (T2DM), due to the fact that the disease phenotype is a result of complex interaction between genes and environmental factors. This review focuses on the T2DM risk prediction.
T2DM is a common metabolic disorder characterized by insulin resistance and impaired pancreatic beta-cell function (1). There are many environmental, lifestyle and genetic factors known to be important in the development and progression of T2DM. A recent umbrella metareview (2) indicated that at least eleven associations presented convincing evidence for high risk of T2DM. Obesity stands out as a major risk factor, together with sedentary behavior and low adherence to a healthy diet. Association of several environmental factors and biomarkers to T2DM was also supported by convincing evidence. These include high levels of serum uric acid, low level of serum vitamin D, high level of serum alanine aminotransferase (ALT), and exposure to high level of ambient air pollution. Other convincing associations were found in the medical history of the patient (e.g., gestational diabetes, age at menarche) and a few psychosocial factors (2).
Quite many T2DM risk assessment tools have been developed worldwide in order to assess T2DM risk at an individual level, with the purpose of deploying preventive strategies early enough to prevent the progression of the disease from prediabetes stage to diabetes. Because of differences in the genetic and lifestyle characteristics, some scores developed for a certain population may not necessarily perform well in other populations (3). Therefore, a plethora of T2DM risk assessment tools have been created worldwide to get the best tool for each population.
The widely used T2DM risk scores were established during 2000 to 2010 and were based on various regression models (4-9). Recent advancements in the fields of artificial intelligence and machine learning have produced a renaissance of new studies aiming at developing better T2DM prediction models. This study aims to describe recent development in the T2DM risk prediction with machine learning algorithms and the new features applied in these studies. The specific research questions are: “Does deployment of machine learning algorithms provide more accurate prediction score for T2DM, as compared to the established regression methods?” “What kind of features have been added to T2DM risk prediction models to get a better accuracy?”
The inclusion criteria for the papers in this review were the following: (I) only published papers in refereed journals since 2003 (not conference papers or chapters in books); (II) dataset size was large enough (arbitrary limit was set to 700 persons); (III) results were validated with either an independent test data set or with 5-fold or 10-fold cross-validation and (IV) prediction performance has been reported with a standard measure, such as area under curve (AUC) or accuracy. AUC is the area under the ROC (receiver operating characteristics) curve, which has been proposed as a single-number measure for evaluating the predictive ability of learning algorithms (10). As all reviewed papers did not publish their results as AUC values, also research papers reporting their prediction performance with accuracy values were included in this review. Accuracy is defined as the number of correct predictions (true positives and true negatives) out of total number of predictions.
For machine learning papers with the commonly used Pima Indian diabetes dataset, only the papers with the highest accuracy or AUC for T2DM prediction were picked to this review from a vast number of research reports. For a compilation for T2DM prediction studies with the Pima Indian dataset, see e.g., Varma & Panda’s recent comprehensive survey (11).
A survey of regression models for T2DM prediction
Currently there are numerous logistic regression based T2DM risk scores, which are widely used in clinical settings or as web questionnaires (12). These share a common core set of predicting variables for T2DM [e.g., age, gender, body mass index (BMI) or other measure for obesity, family history of diabetes], but vary in the inclusion of clinical, genetic and lifestyle data (Table 1). The prediction performance values as measured by self-reported AUC values range from 0.64 to 0.85. Inclusion of more variables to the risk prediction model does not necessarily result in better AUC value, as the best AUC values (4,7) were achieved with only seven and eight features.
A survey of prediction models using machine learning
The number of machine learning based T2DM risk prediction studies has exploded during the last decade, largely because of the fertile co-operation of data analysts with medical experts. For clarity, Table 2 does not list all the research studies available, but a representative selection of the main studies with large datasets and the best T2DM prediction accuracies.
The reviewed T2DM prediction models based on machine learning showed higher classification accuracies than models based on logistic regression, as measured by the reported accuracy and AUC scores. With logistic regression methods, the AUCs were in the range between 65% and 85%, while machine learning methods gave AUCs between 80.8% and 99.36%—and accuracies in the range of 80.8–99.36%. However, the reported performance values are not directly comparable between the reviewed papers, because the validation strategies and datasets were not the same. Direct comparison for the algorithm’s and model’s prediction accuracy can be done only if the same dataset and validation dataset is used, as in several papers using Pima Indian dataset for benchmarking the prediction accuracies of different algorithms [e.g., in (23)].
Algorithm selection strategies
In summary, most of the known prediction algorithms have been employed in the reviewed studies. Note that Table 2 lists only the model which gave the best prediction accuracy for T2DM in each paper. Therefore, it seems that support vector machine (SVM) and random forest tend to be overrepresented among the best performers and give better prediction accuracies than the other tested algorithms. Both are known to be robust to data overfitting, but the resulting predicting model can be difficult to interpret (24)—often regarded as a limitation in medical context.
Deep learning neural networks have not yet been extensively used for T2DM prediction. Recently Ayon & Islam (21) published promising results in their paper describing the application of deep learning neural network for predicting T2DM in the Pima Indian dataset, with high accuracy (98.0%, Table 2). As Pima Indians have limited genetic and environmental variability (25), the prediction task is far easier than in other, genetically and environmentally more complex populations. It will be interesting to see how deep learning approach performs in future studies with larger datasets of mixed ethnicity.
Deep learning is widely used in the analysis of complex medical data, especially in medical imaging, as they have the benefit of using nonlinear activation functions instead of linear ones. In fact, in clinical health datasets the relationships between the dependent and independent variables are commonly not linear, such as gene-environment interactions or association between various physiological features, such as obesity and hypertension.
In addition to proper selection of the algorithm, accuracy of the disease prediction model can be improved by (I) increasing dataset size to capture enough variation of the population and (II) by careful selection of the most relevant features to the prediction model.
The core features for T2DM prediction were shared by majority of the reviewed papers, including age, BMI, waist circumference, hypertension and family history of diabetes. These features can be easily gathered in web surveys without any clinical data, thereby forming a general basis for T2DM prediction tools. Addition of clinical data (triglycerides, fasting plasma glucose, cholesterol data etc.) improved T2DM risk score performance (as measured by AUC) up to 85% for logistic regression models and up to 98% for machine learning based models.
Impact of genetic data
Genetic data can be included in the feature set for T2DM risk prediction either as a simple variable describing the family history of diabetes or as precise genetic markers associated with the disease, such as small nucleotide polymorphisms (SNPs). So far, SNPs have been included in the feature set for T2DM risk prediction in only few papers using machine learning approach. Lopez et al. (19) achieved an intermediate AUC of 0.85 for T2DM prediction by including SNP data to their predictive model together with only a few basic variables, but without clinical or biomarker data. The challenge with SNP data is a dimensionality problem: hundreds of subjects with thousands of SNPs per subject, resulting in complex models and high demands for computing capacity. Another challenge with SNPs is model overfitting (19), resulting in suboptimal generalizability of the prediction model to other datasets.
To date, over 400 genetic variants have been associated with the onset of T2DM, but even combined, they explain just 18% of the risk of T2DM, and the risk associated with individual variants is low, usually less than 1.2% (25,26). In a study with only genetic (SNP) data for T2DM risk prediction, different SNP combinations achieved prediction accuracy of 70.9% with Support Vector Machine algorithm for men in Korean subpopulations (27), emphasizing the inclusion of genetic markers to the disease prediction models.
Genetic heterogeneity within T2DM complicates the situation for T2DM risk prediction based on genetic data. A data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes in a Swedish cohort identified five replicable clusters of patients with diabetes, which had significantly different patient characteristics and risk of diabetic complications (28). When integrating SNP variant data to the T2DM risk prediction model, it might be interesting to first classify the different subgroups and look for the predicting variables and the best predicting model separately for each of these.
The authors thank the European Regional Development Fund, University of Oulu, Faculty of Medicine and the City of Oulu for their support in this study.
Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jmai-20-4). The author has no conflicts of interest to declare.
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Cite this article as: Riihimaa P. Impact of machine learning and feature selection on type 2 diabetes risk prediction. J Med Artif Intell 2020;3:10.