The purpose of this study was to evaluate the effect of physical inactivity on adipose tissue (AT) metabolism in first-degree relative (FDR) of subjects with type 2 diabetes. The study sample included 13 FDR and 20 control (CON) subjects who underwent glucose clamp and microdialysis techniques before and after 10 days of bed rest. Results showed that prior to bed rest, FDR had a significantly higher glucose uptake in subcutaneous abdominal AT (SCAAT) and decreased SCAAT mRNA expression of lipases compared with CON. No differences were observed between groups for subcutaneous femoral AT (SCFAT) glucose uptake. After bed rest, SCAAT glucose uptake was increased in CON subjects to the same level as in FDR subjects. However, in SCFAT, but not in SCAAT, lipolysis decreased in response to physical inactivity in both FDR and CON subjects. These results suggest that the abnormalities of whole-body and AT metabolism seen in FDR subjects are comparable to the metabolic abnormalities induced by 10 days of bed rest in healthy CON subjects without any family history of type 2 diabetes. Therefore, FDR subjects are not more sensitive to the deleterious effects of physical inactivity on AT metabolism when compared to healthy controls. In his editorial comment, Franks PW discussed the findings of the study by Højbjerre et al. and underlined the interest of having studied normal weight individuals in this context in order to highlight obesity-independent mechanisms linking FDR and type 2 diabetes risk. He also emphasized the complexity of determining which factor between genetic predisposition and diabetogenic behaviours contributes the most to diabetes risk.
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