4. Discussion
T2DM
ADVERSE EVENTS, HYPERGLYCEMIA, DISEASE, DIABETIC COMPLICATIONS
In this randomized placebo-controlled trial, the overall beneficial effects of a 12-week endurance exercise training program with and without VD intervention on fasting glucose in participants with T2DM were observed, accompanied by notable alterations in the plasma lipidome. Although VD intervention failed to provide additional benefits to the HOMA-IR index and other glycemic indicators beyond EX intervention, we observed a regulatory effect of EX + VD intervention on the plasma lipidome and noted that such effects lasted until the 12-week follow-up. Some specific lipid changes were associated with changes in obesity-related traits. Importantly, we found high inter-individual variability in glycemic control indicators, i.e., HOMA-IR, HbA1c level, and glucose tolerance, as a result of our interventions, which to a great extent may explain the lack of synergistic improvement in glycemic control upon intervention. We thereafter identified several lipid species alone or in combination with clinical indices that largely improved the prediction of changes in glycemic control, with an AROC value over 0.9.Recently, a systematic review reported that combined exercise training (endurance and resistance exercises) was the most effective exercise intervention for cardiometabolic outcomes in participants with overweight and obesity [Hyperglycemia is a key risk factor for the development of diabetic complications [Recent advances in lipidomics have greatly expanded the associations between lipid species and metabolic pathways with disease onset and progression, such as T2DM [Moreover, maintaining appropriate levels of exercise as an effective strategy for keeping healthy can produce vast changes in multiple lipid species [Glycerophospholipids, in particular PCs and LPCs, play important roles in regulating glucose homeostasis and chronic inflammatory status [Apart from the observed effects of EX and VD interventions on glycemic control and the plasma lipidome, we found that the individual responsiveness of glycemic control indicator changes varied greatly among those undergoing interventions. For participants allocated in each intervention group, only about half were responders for HOMA-IR, HbA1c level, and glucose tolerance (i.e., participants who had lower glycemic indicators after intervention compared with baseline). These results corroborate and expand existing evidence that there are inter-individual differences in responses to diet or exercise treatments [Our findings explore the use of metabolomics in the fields of exercise metabolism and sports nutrition, promoting personalized exercise and/or nutrition strategies to maximize exercise performance and provide additional exercise-related health benefits, such as glycemic control. Additionally, no intervention-related adverse events were reported. These results indicated progressive and individual tailored programming may be effective in controlling body weight in participants with T2DM in a gym setting. Notably, although the frequency of attendance at exercise sessions did not differ between the EX and EX + VD groups, lower levels of adherence of some participants to the exercise program in the present study may have underestimated the effect of exercise on glycemic indicators, resulting in the inability to achieve significant results for blood indicators. Further comprehensive interventions targeting lifestyle, using novel approaches such as mHealth, are warranted to address this issues.Our study had several limitations. First, the study duration was relatively short, although it has been demonstrated that body fat and blood metabolic profile changes can be detected within 12 weeks [