Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

Abstract

OBJECTIVEAcylcarnitines were suggested as early biomarkers even prior to insulin resistance in animal studies, but their roles in predicting type 2 diabetes were unknown. Therefore, we aimed to determine whether acylcarnitines could independently predict type 2 diabetes by using a targeted metabolic profiling approach. RESEARCH DESIGN AND METHODSA population-based prospective study was conducted among 2,103 communityliving Chinese individuals aged 50-70 years from Beijing and Shanghai with a mean follow-up duration of 6 years. Fasting glucose, glycohemoglobin, and insulin were determined at baseline and in a follow-up survey. Baseline plasma acylcarnitines were profiled by liquid chromatography-tandem mass spectrometry. RESULTSOver the 6-year period, 507 participants developed diabetes. A panel of acylcanitines, especially with long chain, was significantly associated with increased risk of type 2 diabetes. The relative risks of type 2 diabetes per SD increase of the predictive model score were 2.48 (95% CI 2.20-2.78) for the conventional and 9.41 (95% CI 7.62-11.62) for the full model including acylcarnitines, respectively. Moreover, adding selected acylcarnitines substantially improved predictive ability for incident diabetes, as area under the receiver operator characteristic curve improved to 0.89 in the full model compared with 0.73 in the conventional model. Similar associations were obtained when the predictive models were established separately among Beijing or Shanghai residents. CONCLUSIONSA panel of acylcarnitines, mainly involving mitochondrial lipid dysregulation, significantly improved predictive ability for type 2 diabetes beyond conventional risk factors. These findings need to be replicated in other populations, and the underlying mechanisms should be elucidated.The escalating global epidemic of type 2 diabetes has contributed considerably to socioeconomic burdens in both developed and developing countries (1). To understand biological mechanisms and improve clinical predictions, it is essential to identify novel biomarkers to enhance the capability to predict early pathophysiological changes (2). As a largely preventable disease, early prediction is the key to control the epidemic trend of type 2 diabetes, particularly in those countries with

Metabolomic analysis of obesity, metabolic syndrome, and type 2 diabetes: amino acid and acylcarnitine levels change along a spectrum of metabolic wellness

“…Few studies have reported changes in these metabolites. One study noted elevated levels of malonylcarnitine in incident T2D (Sun et al, 2016) and Mai et al (2013) reported that the sum of malonylcarnitine and 3-OHbutyrylcarnitine increased in T2D subjects compared to subjects with normal glucose tolerance, impaired fasting glucose, and impaired glucose tolerance.…”

Distinct developmental trajectories of body mass index and diabetes risk: A 5‐year longitudinal study of Chinese adults

“…The intra‐assay coefficients of variation for blood glucose were <2.5%. Diabetes was defined by the presence of any of the following: (i) self‐reported doctor‐diagnosed diabetes; (ii) current use of insulin or oral hypoglycemic agents; and (iii) fasting blood glucose ≥7.0 mmol/L.…”

Linking of metabolomic biomarkers with cardiometabolic health in Chinese population

“…By using a targeted metabolomic approach, we detected a total of 34 plasma acylcarnitines among 2103 subjects that completed the 6-year follow-up in the NHAPC study. 49 It was shown, for the first time, that a panel of acylcarnitines, especially with long chains, could substantially improve predictive ability for incident T2D, because the AUC improved to 0.89 in the full model (vs 0.73 in the conventional model including lifestyle factors, family history of diabetes, body mass index, fasting glucose, and HbA1c). Nonetheless, the roles of different acylcarnitines in cardiometabolic health need to be elucidated in further studies.…”