Recently, increased human adipose tissue fibrosis has been Cyclophosphamide associated with obesity and insulin resistance. Most of the findings associating different aspects of adipose tissue dysfunction with type 2 diabetes have been demonstrated in subjects already affected by obesity and/or type 2 diabetes. In the present study, we investigated the presence of adipocyte hypertrophy and alteration of genes involved in adipose tissue dysfunction in subcutaneous adipose tissue from non-obese, glucose tolerant subjects with known genetic predisposition for type 2 diabetes compared to matched control subjects without known genetic predisposition. Our findings show that in spite of similar age, BMI and percent body fat, FDRs displayed adipocyte hypertrophy that was associated with impaired insulin sensitivity and other early signs of adipose tissue dysfunction. We have previously shown that genetic predisposition for type 2 diabetes, but not obesity, is associated with inappropriate expansion of the adipose cells for small increases in body fat and that this is associated with reduced insulin sensitivity. In line with these findings, the results of the present study show that although the groups were matched for BMI and, importantly, in spite of no Mogroside-IIA2 differences in FM and %FM, the adipose tissue of FDRs is characterized by cellular hypertrophy compared to matched control subjects without family history of type 2 diabetes. A previous publication from our laboratory has shown that increased adipocyte cell size in associated with reduced number of precursor cells able to differentiate into adipocytes. The finding of adipocyte hypertrophy in FDRs compared control subjects with similar BMI and %FM adds weight to the hypothesis that FDRs assume an ����obese phenotype���� before the conventional definition of obesity due to impaired ability to recruit and/or differentiate new pre-adipocytes. The adipocyte hypertrophy was associated with measures of impaired insulin sensitivity, suggesting that the adverse effects of adipocyte hypertrophy could be reflected within these associations. Not only adipocyte cell size is important for adipose tissue function-related traits.