Low-grade inflammation characterizes obesity-associated type 2 diabetes mellitus. We have previously shown that greater reductions in circulating pro-inflammatory lymphocytes after bariatric surgery is closely associated with greater reductions in glucose in obese humans with type 2 diabetes. To further interrogate the nexus between cell-mediated immunity and weight and glycaemic responses, we examined adipose tissue gene expression of cytokines regulating systemic inflammation and responses after bariatric surgery.
Methods: Obese-subjects (n=36) undertaking gastric banding had measures of weight, HbA1c and fasting glucose at 6 and 12m. At surgery, subcutaneous (SAT) and visceral adipose tissue were collected and gene expression undertaken of molecules regulating inflammation. Adipose tissue gene expression data were analyzed against the 6 and 12m changes in weight, glucose and HbA1c.
Results- Weight loss and glucose responses after bariatric surgery are shown below.
N=36 |
Baseline (mean±SD) |
12 months (mean±SD) |
Age (years) |
50.3±12.3 |
|
Weight (kg) |
118.5±22.0 |
101.6 ±18.4† |
BMI (kg/m2) |
41.6±5.9 |
35.8 ±5.3† |
Waist (cm) |
122 17 |
112±16† |
F glucose (mmol/L) |
7.2±2.2 |
5.5±1.5† |
HbA1c (n=17) |
7.0±1.7 |
6.6±1.2* |
* Baseline vs 12n p=0.004; †p<0.0001
There were inverse associations between SAT gene expression of molecules promoting cell-mediated inflammation and the reduction in weight, glucose and HbA1c after bariatric surgery. ∆weight was inversely associated with expression of macrophage inflammatory protein-1 (MIP-1) (6m: ß=-0.34, p=0.017; 12m: ß=-0.33, p=0.03), and interferon-γ (6m: ß= -0.59, p=0.027; 12m: ß= -0.69, p=0.01). ∆FG was inversely associated with expression of MIP-1 (6m: ß= -0.92, p=0.002; 12m: ß= -0.86, p=0.007) and macrophage chemotactic protein-1 (MCP-1) (6m: ß= -0.69, p=0.018; 12m: ß= -0.65, p=0.039). ∆HbA1c was associated with M1P-1 expression (12m: ß= -0.88, p=0.006).
Conclusion: Lower SAT gene expression of molecules promoting cell-mediated inflammation is associated with greater reductions in weight, glucose and HbA1c after bariatric surgery. The interaction between cell-mediated immunity and glucose metabolism in obesity-associated type 2 diabetes requires further investigation for potential treatment opportunities.