부산대학교 도서관

Objective: The underlying causes of type 2 diabetes (T2DM) remain poorly understood. Adipose tissue dysfunction with high leptin, inflammation, and increased oxidative stress may play a pivotal role in T2DM development in obese patients. Little is known about the changes in the adipose tissue after Roux-Y gastric bypass (RYGB) in non-severely obese patients (BMI < 35 kg/m) and since these patients have more T2DM-associated complications than obese patients ('obesity paradox'), we investigated changes in adipose tissue function in a cohort of BMI <35 kg/m with insulin-dependent T2DM after RYGB surgery which resolves T2DM. Methods: Twenty patients with insulin-dependent T2DM and BMI <35 kg/m underwent RYGB. Insulin-resistance, leptin, oxidative stress, and cytokines were determined over 24 months. Expression of cytokines and NF-kappaB pathway genes were measured in leukocytes (PBMC). Adipose tissue inflammation was examined histologically preoperatively and 24 months after RGYB in subcutaneous adipose tissue. Results: Insulin-resistance, leptin, oxidative stress as well as adipose tissue inflammation decreased significantly after RYGB. Similarly, systemic inflammation was reduced and peripheral blood mononuclear cells (PBMCs) were reprogrammed towards an M2-type inflammation. Loss of BMI correlated with leptin levels ( r = 0.891, p < 0.0001), insulin resistance ( r = 0.527, p = 0.003), and oxidative stress ( r = 0.592, p = 0.016). Leptin correlated with improved insulin resistance ( r = 0.449, p = 0.032) while reduced leptin showed a strong association with improved oxidative stress ( r = 0.809, p = 0.001). Lastly, reduced oxidative stress correlated strongly with improved insulin-resistance ( r = 0.776, p = 0.001). Conclusions: RYGB improves adipose tissue function and inflammation. Leptin as marker for adipose tissue dysfunction may be the mediating factor between insulin resistance and oxidative stress and thereby likely improving T2DM. [ABSTRACT FROM AUTHOR]