Amelioration of insulin resistance by rosiglitazone is associated with increased adipose cell size in obese type 2 diabetic patients

Abstract

Early studies reported that the size of adipose cells positively correlates with insulin resistance, but recent evidence suggests that the relationship between adipose cell size and insulin resistance is more complex. We previously reported that among BMI-matched moderately obese subjects who were either insulin sensitive or resistant insulin resistance correlated with the proportion of small adipose cells, rather than the size of the large adipose cells, whereas the size of large adipose cells was found to be a predictor of insulin resistance in the first-degree relatives of type 2 diabetic (T2D) patients. The relationship between adipose cellularity and insulin resistance thus appears to depend on the metabolic state of the individual. We did a longitudinal study with T2D patients treated with the insulin-sensitizer rosiglitazone to test the hypothesis that improved insulin sensitivity is associated with increased adipocyte size. Eleven T2D patients were recruited and treated with rosiglitazone for 90 days. Blood samples and needle biopsies of abdominal subcutaneous fat were taken at six time points and analyzed for cell size distributions. Rosiglitazone treatment ameliorated insulin resistance as evidenced by significantly decreased fasting plasma glucose and increased index of insulin sensitivity, QUICKI. In association with this, we found significantly increased size of the large adipose cells and, with a weaker effect, increased proportion of small adipose cells. We conclude rosiglitazone treatment both enlarges existing large adipose cells and recruits new small adipose cells in T2D patients, improving fat storage capacity in adipose tissue and thus systemic insulin sensitivity.

Keywords:

• adipose cell size
• insulin resistance
• type 2 diabetes
• rosiglitazone

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank Vipul Periwal (LBM, NIDDK) for insightful comments.

Funding

BE and US were supported by the Swedish Research Council, the Novo Nordisk Foundation, and the Swedish Diabetes Association. JY, SC, and AS were supported by the Intramural Research Program of NIDDK, NIH.

Supplemental data

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