Fasting Metabolomic Score Associated With Diabetes and Coronary Heart Disease Risk

Elevated 1-hour glucose during an oral glucose tolerance test predicts type 2 diabetes and cardiovascular disease. Researchers used untargeted fasting blood metabolomics and frequently sampled 75-g oral glucose tolerance tests in 162 OmniCarb trial participants to develop a metabolomic risk score (MRS). They then examined score changes during the POUNDS Lost dietary intervention and prospective associations with incident diabetes and coronary heart disease in the Nurses’ Health Study.

The MRS correlated with 1-hour glucose (Pearson r=0.80) and was associated with diurnal postprandial glucose excursions and insulin secretion after five-week controlled feeding interventions. In POUNDS Lost, diet-induced score changes were related to two-year glucose metabolism trajectories; circulating microRNAs were also implicated in these changes. In the Nurses’ Health Study, women in the highest versus lowest MRS quintile had adjusted relative risks of 3.80 (95% CI, 2.22–6.51) for diabetes and 1.48 (95% CI, 1.04–2.12) for coronary heart disease. Ten-year increases in metabolites related to 1-hour glucose were linearly associated with higher diabetes risk.

These findings identify a potential metabolic marker of future cardiometabolic risk, but do not establish that targeting the score prevents disease. The supplied abstract does not report sample sizes for POUNDS Lost or the Nurses’ Health Study analyses, absolute risks, or incremental predictive value over established clinical measures. Clinical implementation remains unestablished.