Adipose tissue and immune cell predictors of the weight and glucose responses at 12 months after bariatric surgery

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 695-707-Obesity Treatment
Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-699
Katherine Samaras*1, Alexander Viardot2, Elizabeth Blanchard3 and Reginald V Lord4
1Garvan Institute of Medical Research, Sydney NSW, Australia, 2Garvan Institute of Medical Research, Sydney-Darlinghurst NSW, Australia, 3Garvan Institute of Medical Research, Sydney, Australia, 4St Vincent's Hospital, Sydneu, Australia
Obesity-associated type 2 diabetes mellitus (T2D) is characterized by  low-grade circulating and adipose tissue inflammation. The aim of this study was to interrogate the nexus between the cell-mediated immune system (circulating and in adipose tissue) and the weight and glucose responses after bariatric surgery.

Methods: Obese-subjects (n=36, 113.4 ± 19.1 kg, BMI 39.5 ± 5.5 kg/m2) undertaking gastric banding had measures of weight, HbA1c and fasting glucose (FG) at 6 and 12m. Subcutaneous (SAT) and visceral adipose tissue were collected at surgery and gene expression of molecules regulating inflammation undertaken. A subset of 15 subjects also underwent measures of glucose tolerance, glucose AUC, insulin resistance [HOMA-B], circulating immune cell phenotypes and activation status at baseline and 3m. Gene expression data were analyzed against 3, 6 and 12m changes in weight, glucose and HbA1c using general linear modelling, with age, sex and baseline measures as covariates. Changes in glucose metabolism were also examined against changes in immune cell measures.

Results- As expected, at 6 and 12 months there were significant falls in weight (10.5±2.1 and 13.0±2.3 kg, respectively, P<0.0001).  HbA1c fell (7.2 ± 1.8 at baseline, by 0.7% at 6, maintained at 12m, p=0.01), as did  FG (6.2 ± 2.2 at baseline, by 0.7 mmol/L at 6 and 12m, respectively).

There were inverse associations between SAT gene expression of molecules promoting cell-mediated inflammation and metabolic improvement after bariatric surgery. Dweight was inversely associated with SAT expression of macrophage inflammatory protein-1 (MIP-1) (6m: ß=-0.34, p=0.017; 12m: ß=-0.33, p=0.03), and interferon-g (6m: ß=-0.59, p=0.027; 12m: ß=-0.69, p=0.01). DFG 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 (6m: ß=0.69, p=0.018; 12m: ß=0.65, p=0.039). DHbA1c at 12 months was associated with SAT M1P-1 expression (ß=-0.88, p=0.006).

In the subgroup, 80% of T2D participants had reverted to normal or IGT at 3 m. DFG at 3m was associated with decreased lymphocytes and T lymphocyte numbers, as well as increased (anti-inflammatory) T helper-2 lymphocytes.

Conclusion: Lower SAT gene expression of molecules promoting cell-mediated inflammation predict greater reduction in weight, glucose and HbA1c after bariatric surgery. Early improvements in FG are related to the degree of attenuation of circulating lymphocyte-mediated inflammation after weight loss. The interaction between cell-mediated immunity and its regulation and glucose metabolism in obesity-associated diabetes requires further investigation.

Nothing to Disclose: KS, AV, EB, RVL

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: The Ladies Committee-Sister Bernice Award of the St Vincent’s Clinic Foundation