Very
low calorie diets (VLCD) with and without exercise programs lead to major metabolic improvements in obese
type 2 diabetes patients. The mechanisms underlying these improvements have so far not been elucidated fully. To further investigate the mechanisms of a VLCD with or without exercise and to uncover possible
biomarkers associated with these interventions, blood samples were collected from 27 obese
type 2 diabetes patients before and after a 16-week VLCD (Modifast ∼ 450 kcal/day). Thirteen of these patients followed an exercise program in addition to the VCLD. Plasma was obtained from 27 lean and 27 obese controls as well. Proteomic analysis was performed using mass spectrometry (MS) and targeted multiple reaction monitoring (MRM) and a large scale isobaric tags for relative and absolute quantitation (iTRAQ) approach. After the 16-week VLCD, there was a significant decrease in
body weight and HbA1c in all patients, without differences between the two intervention groups. Targeted MRM analysis revealed differences in several
proteins, which could be divided in diabetes-associated (
fibrinogen,
transthyretin),
obesity-associated (
complement C3), and diet-associated markers (
apolipoproteins, especially
apolipoprotein A-IV). To further investigate the effects of exercise, large scale iTRAQ analysis was performed. However, no
proteins were found showing an exercise effect. Thus, in this study, specific
proteins were found to be differentially expressed in
type 2 diabetes patients versus controls and before and after a VLCD. These
proteins are potential disease state and intervention specific
biomarkers.
TRIAL REGISTRATION: Controlled-Trials.com ISRCTN76920690.