Screening for Prediabetes Using Machine Learning Models

The global prevalence of diabetes is rapidly increasing. Studies support the necessity of screening and interventions for prediabetes, which could result in serious complications and diabetes. This study aimed at developing an intelligence-based screening model for prediabetes. Data from the Korean National Health and Nutrition Examination Survey (KNHANES) were used, excluding subjects with diabetes. The KNHANES 2010 data (n = 4685) were used for training and internal validation, while data from KNHANES 2011 (n = 4566) were used for external validation. We developed two models to screen for prediabetes using an artificial neural network (ANN) and support vector machine (SVM) and performed a systematic evaluation of the models using internal and external validation. We compared the performance of our models with that of a screening score model based on logistic regression analysis for prediabetes that had been developed previously. The SVM model showed the areas under the curve of 0.731 in the external datasets, which is higher than those of the ANN model (0.729) and the screening score model (0.712), respectively. The prescreening methods developed in this study performed better than the screening score model that had been developed previously and may be more effective method for prediabetes screening.ope

Utilizing Temporal Information in The EHR for Developing a Novel Continuous Prediction Model

Type 2 diabetes mellitus (T2DM) is a nation-wide prevalent chronic condition, which includes direct and indirect healthcare costs. T2DM, however, is a preventable chronic condition based on previous clinical research. Many prediction models were based on the risk factors identified by clinical trials. One of the major tasks of the T2DM prediction models is to estimate the risks for further testing by HbA1c or fasting plasma glucose to determine whether the patient has or does not have T2DM because nation-wide screening is not cost-effective. Those models had substantial limitations on data quality, such as missing values. In this dissertation, I tested the conventional models which were based on the most widely used risk factors to predict the possibility of developing T2DM. The AUC was an average of 0.5, which implies the conventional model cannot be used to screen for T2DM risks. Based on this result, I further implemented three types of temporal representations, including non-temporal representation, interval-temporal representation, and continuous-temporal representation for building the T2DM prediction model. According to the results, continuous-temporal representation had the best performance. Continuous-temporal representation was based on deep learning methods. The result implied that the deep learning method could overcome the data quality issue and could achieve better performance. This dissertation also contributes to a continuous risk output model based on the seq2seq model. This model can generate a monotonic increasing function for a given patient to predict the future probability of developing T2DM. The model is workable but still has many limitations to overcome. Finally, this dissertation demonstrates some risks factors which are underestimated and are worthy for further research to revise the current T2DM screening guideline. The results were still preliminary. I need to collaborate with an epidemiologist and other fields to verify the findings. In the future, the methods for building a T2DM prediction model can also be used for other prediction models of chronic conditions

Feasibility study of constructing a screening tool for adolescent diabetes detection applying machine learning methods

Prediabetes and diabetes are becoming alarmingly prevalent among adolescents over the past decade. However, an effective screening tool that can assess diabetes risks smoothly is still in its infancy. In order to contribute to such significant gaps, this research proposes a machine learning-based predictive model to detect adolescent diabetes. The model applies supervised machine learning and a novel feature selection method to the National Health and Nutritional Examination Survey datasets after an exhaustive search to select reliable and accurate data. The best model achieved an area under the curve (AUC) score of 71%. This research proves that a screening tool based on supervised machine learning models can assist in the automated detection of youth diabetes. It also identifies some critical predictors to such detection using Lasso Regression, Random Forest Importance and Gradient Boosted Tree Importance feature selection methods. The most contributing features to Youth diabetes detection are physical characteristics (e.g., waist, leg length, gender), dietary information (e.g., water, protein, sodium) and demographics. These predictors can be further utilised in other areas of medical research, such as electronic medical history

Diabetes and obesity are the main metabolic drivers of peripheral neuropathy

ObjectiveTo determine the associations between individual metabolic syndrome (MetS) components and peripheral neuropathy in a large populationâ based cohort from Pinggu, China.MethodsA crossâ sectional, randomly selected, populationâ based survey of participants from Pinggu, China was performed. Metabolic phenotyping and neuropathy outcomes were performed by trained personnel. Glycemic status was defined according to the American Diabetes Association criteria, and the MetS using modified consensus criteria (body mass index instead of waist circumference). The primary peripheral neuropathy outcome was the Michigan Neuropathy Screening Instrument (MNSI) examination. Secondary outcomes were the MNSI questionnaire and monofilament testing. Multivariable models were used to assess for associations between individual MetS components and peripheral neuropathy. Treeâ based methods were used to construct a classifier for peripheral neuropathy using demographics and MetS components.ResultsThe mean (SD) age of the 4002 participants was 51.6 (11.8) and 51.0% were male; 37.2% of the population had normoglycemia, 44.0% prediabetes, and 18.9% diabetes. The prevalence of peripheral neuropathy increased with worsening glycemic status (3.25% in normoglycemia, 6.29% in prediabetes, and 15.12% in diabetes, P < 0.0001). Diabetes (odds ratio [OR] 2.60, 95% CI 1.77â 3.80) and weight (OR 1.09, 95% CI 1.02â 1.18) were significantly associated with peripheral neuropathy. Age, diabetes, and weight were the primary splitters in the classification tree for peripheral neuropathy.InterpretationSimilar to previous studies, diabetes and obesity are the main metabolic drivers of peripheral neuropathy. The consistency of these results reinforces the urgent need for effective interventions that target these metabolic factors to prevent and/or treat peripheral neuropathy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143679/1/acn3531_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143679/2/acn3531.pd

Elucidating causal relationships between energy homeostasis and cardiometabolic outcomes

Energy metabolism dyshomeostasis is associated with multiple health problems. For example, abundant epidemiological data show that obesity and overweight increase the risk of cardiometabolic diseases and early mortality. Type 2 diabetes (T2D), characterized by chronically elevated blood glucose, is also associated with debilitating complications, high healthcare costs and mortality, with cardiovascular complications accounting for more than half of T2D-related deaths. Prediabetes, which is defined as elevated blood glucose below the diagnostic threshold for T2D, affects approximately 350M people worldwide, with about 35-50% developing T2D within 5 years. Further, non-alcoholic fatty liver disease, a form of ectopic fat deposition as a result of energy imbalance, is associated with increased risk of T2D, CVD and hepatocellular carcinoma. Determination of causal relationships between phenotypes related to positive energy balance and disease outcomes, as well as elucidation of the nature of these relationships, may help inform public health intervention policies. In addition, utilizing big data and machine learning (ML) approaches can improve prediction of outcomes related to excess adiposity both for research purposes and eventual validation and clinical translation. AimsIn paper 1, I set out to summarize observational evidence and further determine the causal relationships between prediabetes and common vascular complications associated with T2D i.e., coronary artery disease (CAD), stroke and renal disease. In paper 2, I studied the association between LRIG1 genetic variants and BMI, T2D and lipid biomarkers. In paper 3, we used ML to identify novel molecular features associated with non-alcoholic fatty liver disease (NAFLD). In paper 4, I elucidate the nature of causal relationships between BMI and cardiometabolic traits and investigate sex differences within the causal framework.ResultsPrediabetes was associated with CAD and stroke but not renal disease in observational analyses, whilst in the causal inference analyses, prediabetes was only associated with CAD. Common LRIG1 variant (rs4856886) was associated with increased BMI and lipid hyperplasia but a decreased risk of T2D. In paper 3, models using common clinical variables showed strong NAFLD prediction ability (ROCAUC = 0.73, p < 0.001); addition of hepatic and glycemic biomarkers and omics data to these models strengthened predictive power (ROCAUC = 0.84, p < 0.001). Finally, there was evidence of non-linearity in the causal effect of BMI on T2D and CAD, biomarkers and blood pressure. The causal effects BMI on CAD were different in men and women, though this difference did no hold after Bonferroni correction. ConclusionWe show that derangements in energy homeostasis are causally associated with increased risk of cardiometabolic outcomes and that early intervention on perturbed glucose control and excess adiposity may help prevent these adverse health outcomes. In addition, effects of novel LRIG1 genetic variants on BMI and T2D might enrich our understanding of lipid metabolism and T2D and thus warrant further investigations. Finally, application of ML to multidimensional data improves prediction of NAFLD; similar approaches could be used in other disease research

Automated Machine Learning (AutoML)-Derived Preconception Predictive Risk Model to Guide Early Intervention for Gestational Diabetes Mellitus

The increasing prevalence of gestational diabetes mellitus (GDM) is contributing to the rising global burden of type 2 diabetes (T2D) and intergenerational cycle of chronic metabolic disorders. Primary lifestyle interventions to manage GDM, including second trimester dietary and exercise guidance, have met with limited success due to late implementation, poor adherence and generic guidelines. In this study, we aimed to build a preconception-based GDM predictor to enable early intervention. We also assessed the associations of top predictors with GDM and adverse birth outcomes. Our evolutionary algorithm-based automated machine learning (AutoML) model was implemented with data from 222 Asian multi-ethnic women in a preconception cohort study, Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO). A stacked ensemble model with a gradient boosting classifier and linear support vector machine classifier (stochastic gradient descent training) was derived using genetic programming, achieving an excellent AUC of 0.93 based on four features (glycated hemoglobin A(1c) (HbA(1c)), mean arterial blood pressure, fasting insulin, triglycerides/HDL ratio). The results of multivariate logistic regression model showed that each 1 mmol/mol increase in preconception HbA(1c) was positively associated with increased risks of GDM (p = 0.001, odds ratio (95% CI) 1.34 (1.13-1.60)) and preterm birth (p = 0.011, odds ratio 1.63 (1.12-2.38)). Optimal control of preconception HbA(1c) may aid in preventing GDM and reducing the incidence of preterm birth. Our trained predictor has been deployed as a web application that can be easily employed in GDM intervention programs, prior to conception.Peer reviewe

Proteomic signatures for identification of impaired glucose tolerance

The implementation of recommendations for type 2 diabetes (T2D) screening and diagnosis focuses on the measurement of glycated hemoglobin (HbA1c) and fasting glucose. This approach leaves a large number of individuals with isolated impaired glucose tolerance (iIGT), who are only detectable through oral glucose tolerance tests (OGTTs), at risk of diabetes and its severe complications. We applied machine learning to the proteomic profiles of a single fasted sample from 11,546 participants of the Fenland study to test discrimination of iIGT defined using the gold-standard OGTTs. We observed significantly improved discriminative performance by adding only three proteins (RTN4R, CBPM and GHR) to the best clinical model (AUROC = 0.80 (95% confidence interval: 0.79–0.86), P = 0.004), which we validated in an external cohort. Increased plasma levels of these candidate proteins were associated with an increased risk for future T2D in an independent cohort and were also increased in individuals genetically susceptible to impaired glucose homeostasis and T2D. Assessment of a limited number of proteins can identify individuals likely to be missed by current diagnostic strategies and at high risk of T2D and its complications

Risk factor patterns in type 2 diabetes and cardiovascular disease : exploring methods for precision medicine in public health

Non-communicable diseases, including type 2 diabetes and cardiovascular disease, are leading contributors to the global burden of disease and an important public health challenge. At an individual level, there is important variability in the risk of these conditions. However, public health interventions often adopt a generalized one-size-fits-all approach. The overall aim of this thesis was to explore the utility of a precision medicine approach to public health and epidemiology, by applying different analytical methods to classify individuals into similar sub-populations based on their individual level characteristics. In study I, I investigated the patterns of weight changes from childhood to early adulthood and how they relate to the occurrence of type 2 diabetes later in life. The results indicate that exposure to overweight/obesity during early adulthood explains a large proportion of the cases of type 2 diabetes, highlighting the importance of public health interventions during this period. In study II, I used different methods for mediation analysis to study the importance of different mechanisms linking low socioeconomic status and type 2 diabetes. The findings show that around 50% of the association between socioeconomic status and type 2 diabetes could be reduced if unhealthy behaviors and metabolic exposures were removed. Interestingly, the results were similar across the different mediation methods. Finally, in studies III and IV, I used data-driven methods to identify sub-groups of healthy adults based on simple clinical characteristics and laboratory values. The findings show that this method was equally effective, or even better, than those commonly used in clinical practice, and could improve the way we define who is at high risk of type 2 diabetes or cardiovascular disease. In conclusion, these studies provide evidence that precision medicine can be a useful approach to guide development and implementation of public health interventions

Artificial intelligence methodologies and their application to diabetes

In the past decade diabetes management has been transformed by the addition of continuous glucose monitoring and insulin pump data. More recently, a wide variety of functions and physiologic variables, such as heart rate, hours of sleep, number of steps walked and movement, have been available through wristbands or watches. New data, hydration, geolocation, and barometric pressure, among others, will be incorporated in the future. All these parameters, when analyzed, can be helpful for patients and doctors' decision support. Similar new scenarios have appeared in most medical fields, in such a way that in recent years, there has been an increased interest in the development and application of the methods of artificial intelligence (AI) to decision support and knowledge acquisition. Multidisciplinary research teams integrated by computer engineers and doctors are more and more frequent, mirroring the need of cooperation in this new topic. AI, as a science, can be defined as the ability to make computers do things that would require intelligence if done by humans. Increasingly, diabetes-related journals have been incorporating publications focused on AI tools applied to diabetes. In summary, diabetes management scenarios have suffered a deep transformation that forces diabetologists to incorporate skills from new areas. This recently needed knowledge includes AI tools, which have become part of the diabetes health care. The aim of this article is to explain in an easy and plane way the most used AI methodologies to promote the implication of health care providers?doctors and nurses?in this field