The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials.

Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)60401-2.pdf

Bariatric surgery for type 2 diabetes

To identify factors contributing to the variation in weight loss after Roux-en-Y gastric bypass (RYGB). Cross-sectional study of patients with good (excess body mass index lost (EBL) >60%) and poor weight loss response (EBL 12 months after RYGB and a lean control group matched for age and gender. Sixteen patients with good weight loss response, 17 patients with poor weight loss response, and eight control subjects were included in the study. Participants underwent dual energy X-ray absorptiometry scan, indirect calorimetry and a 9 h multiple-meal test with measurements of glucose, insulin, total bile acids (TBA), glucagon-like peptide (GLP)-1, peptide YY3–36 (PYY), cholecystokinin (CCK), ghrelin, neurotensin and pancreatic polypeptide (PP) as well as assessment of early dumping and appetite. Suppression of hunger was more pronounced in the good than the poor responders in response to the multiple-meal test (P=0.006). In addition, the good responders had a larger release of GLP-1 (P=0.009) and a greater suppression of ghrelin (P=0.037) during the test, whereas the postprandial secretion of CCK was highest in the poor responders (P=0.005). PYY, neurotensin, PP and TBA release did not differ between the RYGB-operated groups. Compared with control subjects, patients had exaggerated release of GLP-1 (P<0.001), PYY (P=0.008), CCK (P=0.010) and neurotensin (P<0.001). Early dumping was comparable in the good and poor responders, but more pronounced than in controlled subjects. Differences in resting energy expenditure between the three groups were entirely explained by differences in body composition. Favorable meal-induced changes in hunger and gut hormone release in patients with good compared with poor weight loss response support the role of gut hormones in the weight loss after RYGB.

Gut hormones, early dumping and resting energy expenditure in patients with good and poor weight loss response after Roux-en-Y gastric bypass.

SummaryBackground
Obesity surgery is acknowledged as a highly effective therapy for morbidly obese patients. Beneficial short-term effects on common comorbidities are practically undisputed, but a growing data pool from long-term follow-up reveals increasing evidence of potentially severe nutritional and pharmacological consequences.

Aims
To assess the prevalence, causes and symptoms of complications after obesity surgery, to elucidate and compare therapy recommendations for macro- and micronutrient deficiencies, and to explore surgically-induced effects on drug absorption and bioavailability, discussing ramifications for long-term therapy and prophylaxis.

Methods
PubMed, Embase and MEDLINE were searched using terms including, but not limited to, bariatric surgery, gastric bypass, obesity surgery and Roux-en-Y, coupled with secondary search terms, e.g. anaemia, micronutrients, vitamin deficiency, bacterial overgrowth, drug absorption, pharmacokinetics, undernutrition. All studies in English, French or German published January 1980 through March 2014 were included.

Results
Macro- and micronutrient deficiencies are common after obesity surgery. The most critical, depending on surgical technique, are hypoalbuminemia (3–18%) and deficiencies of vitamins B1 (≤49%), B12 (19–35%) and D (25–73%), iron (17–45%) and zinc (12–91%). Many drugs commonly administered to obese patients (e.g. anti-depressants, anti-microbials, metformin) are subject to post-operative and/or PPI-associated changes affecting bioavailability and absorption.

Conclusions
Complications are associated with pre-operative and/or post-operative malnutrition or procedure-related changes in intake, absorption and drug bioavailability. The high prevalence of nutrient deficiencies after obesity surgery makes life-long nutritional monitoring and supplementation essential. Post-operative changes to drug absorption and bioavailability in bariatric patients cast doubt on the validity of standard drug dosage and administration recommendations.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/apt.12872

Review article: the nutritional and pharmacological consequences of obesity surgery

Neural Control of Energy Balance: Translating Circuits to Therapies

Little is known about eating behaviour and meal pattern subsequent to Roux-en-Y gastric bypass (RYGB), knowledge important for the nutritional care process. The objective of the study was to obtain basic information of how meal size, eating rate, meal frequency and eating behaviour change upon the RYGB surgery. Voluntary chosen meal size and eating rate were measured in a longitudinal, within subject, cohort study of 43 patients, 31 women and 12 men, age 42.6 (s.d. 9.7) years, body mass index (BMI) 44.5 (4.9) kg m−2. Thirty-one non-obese subjects, 37.8 (13.6) years, BMI 23.7 (2.7) kg m−2 served as a reference group. All subjects completed a meal pattern questionnaire and the Three-Factor Eating Questionnaire (TFEQ-R21). Six weeks postoperatively meal size was 42% of the preoperative meal size, (P<0.001). After 1 and 2 years, meal size increased but was still lower than preoperative size 57% (P<0.001) and 66% (P<0.001), respectively. Mean meal duration was constant before and after surgery. Mean eating rate measured as amount consumed food per minute was 45% of preoperative eating rate 6 weeks postoperatively (P<0.001). After 1 and 2 years, eating rate increased to 65% (P<0.001) and 72% (P<0.001), respectively, of preoperative rate. Number of meals per day increased from 4.9 (95% confidence interval, 4.4,5.4) preoperatively to 6 weeks: 5.2 (4.9,5.6), (not significant), 1 year 5.8 (5.5,6.1), (P=0.003), and 2 years 5.4 (5.1,5.7), (not significant). Emotional and uncontrolled eating were significantly decreased postoperatively, (both P<0.001 at all-time points), while cognitive restraint was only transiently increased 6 weeks postoperatively (P=0.011). Subsequent to RYGB, patients display markedly changed eating behaviour and meal patterns, which may lead to sustained weight loss.

I Bosaeus

Papers

Changes in eating behaviour and meal pattern following Roux-en-Y gastric bypass.