Objective: Our objective was to delineate the potential role of adipogenesis in insulin resistance and type 2 diabetes. Obesity is characterized by an increase in adipose tissue mass resulting from enlargement of existing fat cells (hypertrophy) and/or from increased number of adipocytes (hyperplasia). The inability of the adipose tissue to recruit new fat cells may cause ectopic fat deposition and insulin resistance.

Research Methods and Procedures: We examined the expression of candidate genes involved in adipocyte proliferation and/or differentiation [CCAAT/enhancer‐binding protein (C/EBP) α, C/EBPδ, GATA domain‐binding protein 3 (GATA3), C/EBPβ, peroxisome proliferator‐activated receptor (PPAR) γ2, signal transducer and activator of transcription 5A (STAT5A), Wnt‐10b, tumor necrosis factor α, sterol regulatory element‐binding protein 1c (SREBP1c), 11 beta‐hydroxysteroid dehydrogenase, PPARG angiopoietin‐related protein (PGAR), insulin‐like growth factor 1, PPARγ coactivator 1α, PPARγ coactivator 1β, and PPARδ] in subcutaneous adipose tissue from 42 obese individuals with type 2 diabetes and 25 non‐diabetic subjects matched for age and obesity.

Results: Insulin sensitivity was measured by a 3‐hour 80 mU/m² per minute hyperinsulinemic glucose clamp (100 mg/dL). As expected, subjects with type 2 diabetes had lower glucose disposal (4.9 ± 1.9 vs. 7.5 ± 2.8 mg/min per kilogram fat‐free mass; p < 0.001) and larger fat cells (0.90 ± 0.26 vs. 0.78 ± 0.17 μm; p = 0.04) as compared with obese control subjects. Three genes (SREBP1c, p < 0.01; STAT5A, p = 0.02; and PPARγ2, p = 0.02) had significantly lower expression in obese type 2 diabetics, whereas C/EBPβ only tended to be lower (p = 0.07).

Discussion: This cross‐sectional study supports the hypothesis that impaired expression of adipogenic genes may result in impaired adipogenesis, potentially leading to larger fat cells in subcutaneous adipose tissue and insulin resistance.