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T2D is a complex disease with poorly understood mechanisms. In Asian Indians, it is associated with "thin fat" phenotype which resembles with partial lipodystrophy. We hypothesized that disturbed expression of lipodystrophy genes might play a role in T2D pathogenesis. Therefore, we attempted to establish a link between these two diseases by studying the overlap between the network of lipodystrophy genes and the differentially expressed genes (DEGs) in the peripheral subcutaneous adipose tissue of Asian Indians diabetics. We found that 16, out of 138 lipodystrophy genes were differentially regulated in diabetics and around 18% overlap between their network and the DEGs; the expression level of lipodystrophy genes showed an association with disease-related intermediate phenotypic traits among diabetics but not in the control group. We also attempted to individualize the diabetic patients based on ±2 fold altered expression of lipodystrophy genes as compared to their average expression in the control group. In conclusion, significant overlap exists between some of the lipodystrophy genes and their network with DEGs in the peripheral adipose tissue in diabetics. They possibly play a role in the pathogenesis of diabetes and individualization of diabetics is possible based on their altered expression in their peripheral adipose tissue. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a complex disease with an elusive link between its molecular aetiology and clinical presentation. Although, the role of visceral adipose tissue in insulin-resistance and T2D is known, limited information is available on the role of peripheral-subcutaneous adipose tissue especially in Asian Indians. In this microarray-based study of diabetic and normal glucose tolerant Asian Indians, we generated the transcriptome of their thigh adipose tissue and analyzed differentially expressed genes (DEGs) using weighted gene co-expression network analysis; further we identified perturbed pathways implicated by these DEGs in relevant co-expression modules. We also attempted to link these pathways with known aspects of T2D pathophysiology in terms of their association with some of their intermediate traits, namely; adipocyte size, HOMA-B, HOMA-R, Hb1Ac, insulin, glucose-level, TNF-α, IL-6, VLDLs, LDLs, HDLs, and NEFAs. It was observed that several modules of co-expressed genes show an association with diabetes and some of its intermediate phenotypic traits mentioned above. Therefore, these findings suggest a role of peripheral subcutaneous adipose tissue in the pathophsiology of T2D in Asian Indians. Additionally, our study indicated that the peripheral subcutaneous adipose tissue in diabetics shows pathologic changes characterized by adipocyte hypertrophy and up-regulation of inflammation-related pathways. [ABSTRACT FROM AUTHOR]