Background: Type 2 diabetes (T2D) accounts for ~90% of all cases of diabetes, resulting in an estimated 6.7 million deaths in 2021, according to the International Diabetes Federation (IDF). Early detection of patients with high risk of developing T2D can reduce the incidence of the disease through a change in lifestyle, diet, or medication. Since populations of lower socio-demographic status are more susceptible to T2D and might have limited resources or access to sophisticated computational resources, there is a need for accurate yet accessible prediction models.

Methods: In this study, we analyzed data from 44,709 non-diabetic U.K. Biobank participants aged 40-69, predicting the risk of T2D onset within a selected timeframe (mean of 7.3 years with a standard deviation of 2.3 years). We started with 798 features that we identified as potential predictors for T2D onset. We first analyzed the data using gradient boosting decision trees, survival analysis, and logistic regression methods. We devised one non-laboratory model accessible to the general population and one more precise yet simple model that utilizes laboratory tests. We simplified both models to an accessible scorecard form, tested the models on normoglycemic and prediabetes sub cohorts, and compared the results to the results of the general cohort. We established the non-laboratory model using the following covariates: sex, age, weight, height, waist size, hip circumference, waist-to-hip Ratio (WHR), and Body-Mass Index (BMI). For the laboratory model, we used age and sex together with four common blood tests: HDL (high-density lipoprotein), gamma-glutamyl transferase, glycated hemoglobin, and triglycerides. As an external validation dataset, we used the electronic medical record database of Clalit Health Services.

Results: The non-laboratory scorecard model achieved an Area Under the Receiver Operating Curve (auROC) of 0.81 (0.77-0.84 95% Confidence Interval (CI)) and an odds ratio (OR) between the upper and fifth prevalence deciles of 17.2 (5-66 95% CI). Using this model, we classified three risk groups, a group with 1% (0.8-1%), 5% (3-6%), and the third group with a 9% (7-12%) risk of developing T2D. We further analyzed the contribution of the laboratory-based model and devised a blood-test model based on age, sex and the four common blood tests noted above. In this scorecard model, we included age, sex, glycated hemoglobin (HbA1c%), gamma glutamyl-transferase, triglycerides, and HDL cholesterol. Using this model, we achieved an auROC of 0.87 (0.85-0.90 95% CI) and a deciles' OR of x48 (12-109 95% CI). Using this model, we classified the cohort into four risk groups with the following risks: 0.5% (0.4%-7%); 3% (2-4%); 10% (8-12%) and a high-risk group of 23% (10-37%) of developing T2D. When applying the blood tests model using the external validation cohort (Clalit), we achieved an auROC of 0.75 (0.74-0.75 95% CI). We analyzed several additional comprehensive models, which included genotyping data and other environmental factors. We found that these models did not provide cost-efficient benefits over the four blood test model. The commonly used German Diabetes Risk Score (GDRS) and Finnish Diabetes Risk Score (FINDRISC) models, trained using our data, achieved an auROC of 0.73 (0.69-0.76) and 0.66 (0.62-0.70), respectively, inferior to the results achieved by the four blood test model and by the Anthropometry models.

Conclusions: The four blood tests and anthropometric models outperformed the commonly used non-laboratory models, the FINDRISC and the GDRS. We suggest that our models be used as tools for decision-makers to assess populations at elevated T2D risk and thus improve medical strategies. These models might also provide a personal catalyst for changing lifestyle, diet, or medication modifications to lower the risk of T2D onset.

Funding: No Funders. The funders had no role in study design, data collection, interpretation, or the decision to submit the work for publication.