Evaluating variations in metabolic profiles during the dry period related to the time of hyperketonemia onset in dairy cows

Hyperketonemia (HYK) in early lactation can have a different impact on health and productivity depending on the timing of HYK onset. While specific metabolites measured during the dry period may serve as biomarkers of HYK, the correlations between metabolites represent a challenge for the use of metabolic profiles dataset, and little has been explored on HYK. This exploratory cohort study aimed a) to characterize the correlations among metabolites measured during the late dry period in dairy cows, and b) to identify biomarkers in the late dry period associated with the onset of HYK at the first (wk1) and second (wk2) week of lactation. Individual blood samples from 440 Holstein dairy cows were collected at 21 ± 3 days before expected parturition. From each sample, 36 different metabolites were measured in serum and plasma. Hyperketonemia was diagnosed in wk1 and wk2 of lactation based on the blood concentration of beta-hydroxybutyrate (BHB > 1.2 mmol/L). Principal component analysis (PCA) was performed to reduce metabolites to a smaller number of uncorrelated components. Multivariable logistic regression models were applied to assess the associations between principal components (PC) and HYK at wk1 only (HYK+ wk1), wk2 only (HYK + wk2), or both weeks (HYK+ wk1-2). The incidence of HYK was 16.2% in the first week, 13.0% in the second week, and 21.2% within the first two weeks of lactation. The results of PCA highlighted 10 PCs from which two were associated with HYK+ wk1 as compared with cows without HYK during the first two weeks of lactation (non-HYK); the PC a2 led by bilirubin and non-esterified fatty acids (OR = 1.29; 95%CI: 1.02–1.68), and the PC a5 led by alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) (OR = 2.77; 95%CI: 1.61–4.97). There was no evidence of an association between any PC and HYK+ wk2 (vs. non-HYK cows). Cows with elevated PC a5 (led by ALP and GGT) in the dry period were 3.18 times more likely to be HYK+ wk1 than HYK+ wk2 (OR: 3.18, 95%CI: 1.34–8.73; P = 0.013). Overall, the main hypothesis generated by our exploratory study suggests that cows with biomarkers of liver dysfunction (ALP, GGT, bilirubin) assessed by PCA at 3 weeks before calving are more likely to develop HYK during the first week of lactation compared to the second week. In addition, results suggest that cows with HYK in both of the first two weeks of lactation had an overall metabolic disbalance during the onset of the late dry period, which based on PCs, encompass biomarkers related to glucogenic and ketogenic metabolic pathways as well as liver dysfunction and fatty liver. Further research is needed to determine the underlying mechanisms associated with the different adaptations between cows that develop HYK during the first and second week of lactation.