Trace element dynamics following low-calorie formula diet and their association with glycaemic traits

Formula diets (FD) lead to weight loss and may result in remission of type 2 diabetes mellitus (T2D). Macronutrient compositions for FD are well studied, however it is not established whether common FD lead to alterations in trace element status, and whether these changes are associated with HbA1c or other glycaemic traits.

The FAsting-induced Immune-metabolic Remission of type 2 diabetes (FAIR) study is a monocentric, stratified, randomized, non-blinded clinical nutritional intervention study that enrols participants with T2D. Participants were assigned to one of two different FD (HEPAFAST® or OPTIFAST®; the former particularly rich in protein and fibre) for 12 weeks. The present study on trace elements is a subset (n = 44) of FAIR. Weight, BMI and HbA1c were assessed before and after the intervention. As trace element biomarkers, total serum copper, zinc, and selenium were quantified using total reflection X-ray fluorescence, ceruloplasmin and selenoprotein P concentrations were measured with a sandwich chemiluminescent immunoassay (CLIA) and glutathione peroxidase 3 activity was assessed using an enzymatic test.

Body weight and HbA1c decreased in both groups after FD. At baseline, there was a positive correlation of copper and ceruloplasmin, and between all three selenium biomarkers (p < 0.001). In the HEPAFAST® group, selenoprotein P (p = 0.049) and ceruloplasmin (p = 0.020) increased after FD compared to baseline. In the OPTIFAST® group, copper (p = 0.046), selenium (p = 0.002), selenoprotein P (p = 0.002) and ceruloplasmin (p = 0.001) increased during the intervention. The proportion of subjects displaying trace elements within the reference range increased during the study. Changes in trace elements were mostly unrelated to the FD-induced decline in HbA1c, except for selenoprotein P, which was positively associated with HbA1c in the OPTIFAST® group (β = 0.21, p = 0.025).

This study demonstrates that weight loss and remission of T2D can be achieved through a balanced FD without significant risk of trace element deficiency or excess. The trial was registered at ClinicalTrials.gov (No. NCT05295160).