Thus, inflammation and tissue fibrosis and remodeling seem to go hand in hand and are associated with adipocyte hypertrophy, rather than BMI or body fat, in FDRs of type 2 diabetic patients. Activation of the Wnt-signaling pathway is associated with adipocyte hypertrophy and insulin resistance, which was confirmed also in the present study. This finding is in agreement with our previous publications showing that hypertrophic obesity is associated with canonical Wnt activation in the stromal cells, inhibiting adipocyte precursor cell recruitment in the adipose tissue. It is well established that Nedaplatin impaired adipocyte differentiation is related to insulin resistance and type 2 diabetes. However, no differences were seen in the expression level of PPARgamma and other adipogenic genes between the groups, indicating that the preadipocytes that have been able to enter the differentiation process have differentiated well and that the mechanisms underlying adipocyte hypertrophy and adipose tissue dysfunction intervene at an earlier stage of precursor cell commitment and/or pre-adipocyte recruitment. We did, however, see a trend towards reduced circulating adiponectin levels, a marker of impaired adipose tissue function and reduced insulin sensitivity, among the FDRs. This finding is in line with previous publications by our group, although the difference was not significant for this small group of individuals. Taken together, the findings of the present study show that in spite of no differences in BMI or %BF, non-obese and glucosetolerant subjects with a genetic predisposition for type 2 diabetes display early changes of the GNE-9605 abdominal subcutaneous adipose tissue such as adipocyte hypertrophy with associated impaired glucose metabolism and an ����obese phenotype���� including increased markers of inflammation, remodeling and Wnt-signaling activation compared to healthy control subjects lacking a known genetic predisposition. The present study is limited by its small number of subjects and a relatively small range of adipocyte size. However, regardless of these limitations, the results provide important information in a high-risk cohort of first-degree relatives to type 2 diabetic patients.