Abstract
BackgroundIdentifying the metabolite profile of individuals with prediabetes who turned to type 2 diabetes (T2D) may give novel insights into early T2D interception. The purpose of this study was to identify metabolic markers that predict the development of T2D from prediabetes in a Chinese population.MethodsWe used an untargeted metabolomics approach to investigate the associations between serum metabolites and risk of prediabetes who turned to overt T2D (n=153, mean follow up 5 years) in a Chinese population (REACTION study). Results were compared with matched controls who had prediabetes at baseline [age: 56 ± 7 years old, body mass index (BMI): 24.2 ± 2.8 kg/m2] and at a 5-year follow-up [age: 61 ± 7 years old, BMI: 24.5 ± 3.1 kg/m2]. Confounding factors were adjusted and the associations between metabolites and diabetes risk were evaluated with multivariate logistic regression analysis. A 10-fold cross-validation random forest classification (RFC) model was used to select the optimal metabolites panels for predicting the development of diabetes, and to internally validate the discriminatory capability of the selected metabolites beyond conventional clinical risk factors.FindingsMetabolic alterations, including those associated with amino acid and lipid metabolism, were associated with an increased risk of prediabetes progressing to diabetes. The most important metabolites were inosine [odds ratio (OR) = 19.00; 95% confidence interval (CI): 4.23-85.37] and carvacrol (OR = 17.63; 95% CI: 4.98-62.34). Thirteen metabolites were found to improve T2D risk prediction beyond eight conventional T2D risk factors [area under the curve (AUC) was 0.98 for risk factors + metabolites vs 0.72 for risk factors, P < 0.05].InterpretationsUse of the metabolites identified in this study may help determine patients with prediabetes who are at highest risk of progressing to diabetes.
Highlights
Prediabetes is an intermediate metabolic state of hyperglycemia in which the serum glucose level is higher than normal, but lower than the diagnostic threshold for diabetes
Patients who developed diabetes after the 5-year of follow-up had higher levels of body mass index (BMI), Waist circumference (WC), waist-hip ratio as well as hemoglobin A1c (HbA1c) comparing with prediabetes group
The combination risk prediction model provided an increased predictive value comparing to the metabolites panel alone, or the clinical features model alone. These results indicated that the metabolome profile was regulated in a complex manner during development from prediabetes to diabetes. In this prospective investigation using an untargeted highresolution metabolomics approach, we detected alterations in serum metabolites preceding the onset of diabetes from prediabetes by about 5 years
Summary
Prediabetes is an intermediate metabolic state of hyperglycemia in which the serum glucose level is higher than normal, but lower than the diagnostic threshold for diabetes. A number of traditional markers are used to estimate the risk of T2D in normal individuals, such as fasting plasma glucose and glycated hemoglobin A1c (HbA1c) [3]. Most of these markers fail to capture the complexity of the etiology of prediabetes, and are limited with respect to detecting early metabolic abnormalities that may occur years or even decades before the onset/diagnosis of overt diabetes. The purpose of this study was to identify metabolic markers that predict the development of T2D from prediabetes in a Chinese population
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