**6. Hormonal effect of sleeve-plus procedures**

When food is ingested, there are changes in the entero-insular axis which involve the gastrointestinal, endocrine and pancreatic secretions that contribute to insulin production. The main hormones in this mechanism includes ghrelin, glucagon-like polypeptide (GLP-1), peptide YY (PYY), gastric inhibitory peptide, oxyntomodulin, and cholecystokinin. Anatomical alterations of the food passageway can affect these entero-hormones which can both influence the central regulation of body weight homeostasis, and make glycemic control more efficient. The hormones affect the hypothalamic-appetite regulation and suppress food intake. The enhanced glucose homeostasis can be explained by "foregut" and "hindgut" theories. The foregut theory hypothesizes that exclusion of food contact with the

duodenum prevents secretion of "anti-incretin" substances. Incretins are metabolic hormones that promote a decrease in blood glucose by making the pancreas more efficient. On the other hand, the hindgut theory explains that contact of undigested food immediately into the distal bowel stimulates production of incretins. The more relevant incretins involved are the GLP-1 and the PYY. These are produced from the L-cells in the distal ileum and colon after immediate contact with nutrients. The postprandial GLP-1 levels are significantly increased after both RYGB and LSG [27–29].

The sleeve-plus procedures are comprised of a sleeve gastrectomy and an intestinal bypass component. Sleeve gastrectomy has been shown to significantly decrease ghrelin, an orexigenic hormone predominantly secreted in the stomach. Ghrelin is also known to suppress insulin and have a modulating effect on glucose homeostasis, hence the decreased levels after SG also helps improve blood sugar control [30]. The SGPJB and SGDJB both have additional glycemic control effect by allowing food to be in early contact to the distal jejunum, stimulating earlier incretin production. The SGDJB has the added benefit of bypassing the duodenum and averts secretion of anti-incretin substances [31].

#### **6.1 Hormonal study**

A prospective observational study was conducted by Dr. Chih-Kun Huang on the incretin effect of SGDJB in type II diabetic patients with BMI <35 kg/m2 from May 2013 to March 2014. The study included 27 patients, 23 females and four males, mean age of 51, mean weight at 74.5 kg and mean BMI 28.4 kg/m2 . All patients have T2DM for a mean duration of 10 years and underwent SGDJB with an afferent limb of 200 cm. The C-peptide, ghrelin, GLP-1, PYY were measured over time together with an oral glucose tolerance test (OGTT).

Hormone levels were analyzed by time courses, area under the plasma concentration time profile (AUC) and maximum plasma concentration (Cmax). Follow-up hormone levels were compared using the paired t-test. The fisher exact test was used when 20% of the cells had expected values of less than 5. A p-value of less than 0.05 denoted statistical significance. All statistical tests were 2-tailed and calculated using the SPSS statistical software (version 15.0; SPSS Inc., Chicago Il.)

The surgery resulted in substantial weight loss with good glycemic control. At six months, the mean BMI had decreased to 22 (p < 0.01), fasting glucose from 160 to 111 gm/dL, and mean glycosylated hemoglobin levels from 9.3 to 6.28% (p < 0.01). Fasting ghrelin assays over time alongside OGTT was significantly lower with an AUC-120 of 82.13 ± 49.36 pg./mL/min dropping down to 17.90 ± 9.01 pg./ mL/min (p < 0.05). The GLP-1 showed an exaggerated response with an AUC-120 increase from 139.37 ± 109.93 pg./mL/min preoperatively to 349.10 ± 187.35 pg./ mL/min at one month (p < 0.05) and to 185.75 ± 118.81 pg./mL/min at six months (p = 0.06). The PYY also showed significant postprandial response at one month postoperatively with and AUC-120 change from 137.10 ± 93.20 pg./ mL/min to 454.50 ± 134.85 pg./mL/min (p < 0.05). However, this dropped to 136.57 ± 134.53 pg./mL/min at six months (p = 0.987) postoperatively (**Figure 2**).

The results in this hormonal study can infer that SGDJB leads to the immediate decrease in hunger, increase in satiety and better glycemic control. However, the decrease in PYY levels after six months is different from that of other hormonal studies where GLP-1 and PYY were shown to be elevated up to one year after bariatric surgery [32, 33]. Further research is needed to confirm how long the elevated incretin levels can persist postoperatively and how the body eventually adapts to it.

*Sleeve-Plus Procedures in Asia: Duodenojejunal Bypass and Proximal Jejunal Bypass DOI: http://dx.doi.org/10.5772/intechopen.96042*

**Figure 2.**

*C-peptide and hormone assays at zero, one and six months after SGDJB against time in minutes alongside an oral glucose tolerance test.*
