Entero-Endocrine Changes After Gastric Bypass in Diabetic and Nondiabetic Patients: A Preliminary Study

doi:10.1016/j.jss.2007.02.022

Journal of Surgical Research

Volume 141, Issue 1, July 2007, Pages 31-39

https://doi.org/10.1016/j.jss.2007.02.022 Get rights and content

Introduction

Alterations in entero-endocrine signaling may play a role in improvements in satiety and glucose tolerance after Roux-en-Y gastric bypass (RYGB). We report our findings of gut hormone secretion in a cohort of diabetic and nondiabetic morbidly obese patients.

Materials and methods

Ten morbidly obese subjects who underwent uncomplicated RYGB were studied: 5 were diabetic and 9 were female. Nonfasting plasma levels of glucagon-like peptide-1 (GLP-1), insulin, desacyl ghrelin, active ghrelin, neuropeptide Y (NPY), and gastric inhibitory polypeptide (GIP) were determined preoperatively and 6 months postoperatively.

Results

Mean patient age was 42 ± 11 years, and the mean preoperative body mass index was 50 ± 6 kg/m². At 6 months mean BMI fell to 33 ± 5 kg/m² (P < 0.0001), and there were no differences between diabetics and nondiabetics with respect to amount of weight loss. In non-diabetics, compared to preoperative levels, there were significant increases in GLP-1 and desacyl-ghrelin in the nondiabetic patients (P = 0.046 and P = 0.016, respectively); no change in plasma insulin, active ghrelin, NPY, or GIP was demonstrated. In contrast, when compared to preoperative levels, there were no significant changes in entero-endocrine hormone levels in the diabetic cohort postoperatively.

Conclusions

At 6 months postoperation, RYGB significantly alters the hormone levels for GLP-1 and desacyl-ghrelin in morbidly obese nondiabetic patients. No significant change was noted in a matched cohort of diabetic patients. Weight loss was similar in diabetics and nondiabetics, suggesting that GLP-1 and ghrelin are not the only mechanisms producing weight loss after RYGB.

Introduction

Alterations in entero-endocrine signaling may play a role in improvements in appetite and glucose tolerance after Roux-en-Y gastric bypass (RYGB). The interaction of ghrelin (both active and desacyl), glucagon-like peptide-1 (GLP-1), gastric inhibitory peptide (GIP), neuropeptide Y (NPY), and insulin within the hormonal milieu is complex. These interactions contribute importantly to regulation of glucose and fat metabolism as well as satiety. RYGB has been noted to facilitate a more favorable hormonal profile. Whether or not the effects seen are consistent between diabetic and nondiabetic patients is unknown.

A marked improvement in type-2 diabetes mellitus (T2DM) after RYGB has been described: an 80% remission rate of T2DM has been observed and in many cases glucose tolerance is corrected within a few days of surgery [1, 2]. The mechanism for this improvement has not been elucidated. A small number of patients have been identified who develop a syndrome of hypoglycemic hyperinsulinemia after gastric bypass. Interestingly, to date, these patients have all been nondiabetics, suggesting a differential hormonal response in these patients compared to those with T2DM. The intent of this study was to characterize the entero-endocrine profiles of T2DM patients and nondiabetic patients before and after RYGB.

The focus of this study was to characterize the baseline preoperative and postoperative levels of the enterokine peptides. The concentration of plasma entero-endocrine gut hormone levels were measured in a cohort of T2DM (diabetic cohort) and nondiabetic morbidly obese patients undergoing RYGB to characterize differences in the entero-endocrine hormonal response among these two patient populations.

Section snippets

Materials and Methods

The Institutional Review Board at the University of Minnesota approved this study (0302M41801). A prospective nonrandomized observational study of patients undergoing primary RYGB was performed. Consecutive consenting patients were enrolled. Revision procedures were excluded. Five diabetic and five nondiabetic patients were included in the analysis.

Results

There were five diabetic and five nondiabetic patients included in this investigation. Overall, the mean patient age was 42 ± 11 years, and the mean preoperative body mass index (BMI) was 50 ± 6 kg/m². There was no statistical difference between preoperative cohort age or BMI. The overall mean 6-month postoperative BMI decreased to 33 ± 5 kg/m² (P < 0.0001), and there were no differences between diabetics and nondiabetics with respect to amount of weight loss. Both the diabetic (P = 0.002) and

Discussion

Patients undergoing weight loss surgery for morbid obesity experience significant weight loss and improvement or resolution in comorbid diseases. These effects have generally been attributed to restriction of caloric intake or malabsorption. However, the rerouting of the intestinal flow in the RYGB and the biliopancreatic diversion (BPD) may have entero-endocrine metabolic advantages as well.

Interplay between the predominant incretins, GIP and GLP-1, is responsible for approximately 50% of

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Mucosal and hormonal adaptations after Roux-en-Y gastric bypass
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Citation Excerpt :
Following RYGB, fasting plasma GLP-1 level has been shown to be either normal or elevated in human models [24,45]. Human postprandial GLP-1 levels have been shown to be elevated up to 40 months after RYGB when compared with preoperative measurements [24,26,45–56]. A recent meta-analysis showed that peak postprandial GLP-1 level 30 minutes after a meal is the most consistent elevated measurement after RYGB [45].
The aim of this study was to perform a comprehensive literature review regarding the relevant hormonal and histologic changes observed after Roux-en-Y gastric bypass (RYGB). We aimed to describe the relevant hormonal (glucagon-like peptides 1 and 2 [GLP-1 and GLP-2], peptide YY [PYY], oxyntomodulin [OXM], bile acids [BA], cholecystokinin [CCK], ghrelin, glucagon, gastric inhibitory polypeptide [GIP], and amylin) profiles, as well as the histologic (mucosal cellular) adaptations happening after patients undergo RYGB. Our review compiles the current evidence and furthers the understanding of the rationale behind the food intake regulatory adaptations occurring after RYGB surgery. We identify gaps in the literature where the potential for future investigations and therapeutics may lie. We performed a comprehensive database search without language restrictions looking for RYGB bariatric surgery outcomes in patients with pre- and postoperative blood work hormonal profiling and/or gut mucosal biopsies. We gathered the relevant study results and describe them in this review. Where human findings were lacking, we included animal model studies. The amalgamation of physiologic, metabolic, and cellular adaptations following RYGB is yet to be fully characterized. This constitutes a fundamental aspiration for enhancing and individualizing obesity therapy.
Gastrointestinal peptides in eating-related disorders
2021, Physiology and Behavior
Food intake is tightly controlled by homeostatic signals sensitive to metabolic need for the regulation of body weight. This review focuses on the peripherally-secreted gastrointestinal peptides (i.e., ghrelin, cholecystokinin, glucagon-like peptide 1, and peptide tyrosine tyrosine) that contribute to the control of appetite and discusses how these peptides or the signals arising from their release are disrupted in eating-related disorders across the weight spectrum, namely anorexia nervosa, bulimia nervosa, and obesity, and whether they are normalized following weight restoration or weight loss treatment. Further, the role of gut peptides in the pathogenesis and treatment response in human weight conditions as identified by rodent models are discussed. Lastly, we review the incretin- and hormone-based pharmacotherapies available for the treatment of obesity and eating-related disorders.
Small intestinal physiology relevant to bariatric and metabolic endoscopic therapies: Incretins, bile acid signaling, and gut microbiome
2020, Techniques and Innovations in Gastrointestinal Endoscopy
Incretins, bile acids and the gut microbiome are involved in the pathophysiology of obesity and type 2 diabetes. The incretins glucagon-like peptide-1 and glucose-dependent-insulinetrophic polypeptide, both influence beta-cell function, insulin and glucose sensitivity, and food intake. Studies have shown that concentrations of both incretins change after bariatric surgery and nowadays glucagon-like peptide-1 agonists are administered as glucose and body weight regulating agents. Bile acids also play an important role in glycemic and metabolic regulation via multiple signaling pathways. After bariatric surgical interventions increase in bile acid concentrations have been observed combined with improvement of metabolic health. It is not clear though, whether this is a direct effect of the altered concentration of bile acids or an epiphenomenon. In addition, alterations in the microbiome are seen in patients with type 2 diabetes and people with obesity. The gut microbiome, probably together with incretins and bile acids, is essential in digestion and nutrient metabolism. After bariatric procedures several alterations in bacterial abundance have been demonstrated with specific bacterial species having different effects on glycemic and metabolic conditions
Fasting ghrelin levels after gastric bypass and vertical sleeve gastrectomy: An analytic cohort study
2020, Endocrinologia, Diabetes y Nutricion
En el hipotálamo existen poblaciones neuronales involucradas en la regulación de la ingesta, destacando la ghrelina como hormona orexígena (estimula el apetito). Después de los diferentes procedimientos de cirugía bariátrica se han observado cambios en los niveles plasmáticos de ghrelina, siendo los resultados de los estudios contradictorios. Existen muchas lagunas en cuanto al papel que desempeña la ghrelina en el proceso de pérdida de peso después de cirugía bariátrica.
Nuestro objetivo es describir el comportamiento de ghrelina en ayunas, comparando los cambios acontecidos en 2 técnicas quirúrgicas (bypass gástrico versus gastrectomía vertical) y su correlación con la pérdida ponderal.
Estudio observacional de cohortes analíticas prospectivo, donde se incluyen 54 pacientes (27 por cada técnica quirúrgica) y un período de seguimiento de 12 meses. Se analizaron datos demográficos, datos antropométricos, comorbilidades, pérdida ponderal y evolución del comportamiento de ghrelina en ayunas.
Con ambas técnicas quirúrgicas el comportamiento de ghrelina acilada fue similar, sin diferencias significativas entre bypass gástrico y gastrectomía vertical. Con ambos procedimientos se produce un ascenso de ghrelina acilada al 5.^o día y caída posterior, para luego ir ascendiendo hasta alcanzar valores superiores a los preoperatorios a los 12 meses. Este aumento en los niveles de ghrelina no afecta a la pérdida ponderal, ya que al año de la cirugía con las 2 técnicas quirúrgicas se alcanza un 30% de pérdida de peso.
Observamos un incremento de los niveles de ghrelina acilada en ayunas al año de seguimiento con ambas técnicas quirúrgicas, cuando existe una pérdida ponderal del 30%.
Neuronal populations involved in the regulation of food intake, particularly the orexigenic (appetite-stimulating) hormone ghrelin, are found in the hypothalamus. Changes in plasma ghrelin levels have been observed following different bariatric surgery procedures, but the results from different studies are contradictory. Much remains unknown regarding the role of ghrelin in the weight loss process following bariatric surgery.
Our objective was to describe the behaviour of fasting ghrelin levels, comparing the changes occurring between 2 different surgical techniques (gastric bypass versus vertical sleeve gastrectomy) and their correlation with weight loss.
A prospective, observational, analytic cohort study of 54 patients (27 for each surgical technique) with a 12-month follow-up period. We analysed demographic data, anthropometric data, comorbidities, weight loss and evolution of fasting ghrelin.
The behaviour of acylated ghrelin was similar with the 2 surgical techniques, with no significant differences between gastric bypass and vertical sleeve gastrectomy. With both procedures, there was an increase in acylated ghrelin on day 5 and a subsequent decrease, and levels then gradually increased to reach values at 12 months that were higher than those reported preoperatively. This increase in ghrelin levels did not affect weight loss, since one year post-surgery, 30% weight loss was achieved with both types of surgery.
We observed an increase in fasting acylated ghrelin levels at one year of follow-up with both surgical techniques, with 30% weight loss.
Unacylated ghrelin is correlated with the decline of bone mineral density after Roux-en-Y gastric bypass in obese Chinese with type 2 diabetes
2019, Surgery for Obesity and Related Diseases
Bariatric surgery is an effective and therapeutic way for different metabolic diseases. It has become a focus of attention about the effects and molecular mechanisms to bone metabolism.
We aim to assess the changes of bone mineral density (BMD) among Chinese obese individuals with type 2 diabetes who have undergone Roux-en-Y gastric bypass surgery (RYGB). Two ghrelin gene products, namely unacylated ghrelin (UAG) and obestatin, were evaluated the roles in this pathologic process.
University-affiliated hospital, China.
Thirty patients who had received RYGB were enrolled in the study. Changes in anthropometric parameters, metabolic indexes, and serum UAG and obestatin were assessed preoperatively, 6, 12, and 24 months postoperatively. BMD at lumbar spine (LS), femoral neck (FN), and total hip (TH) were identified.
RYGB resulted in statistical reductions of BMD in 3 different skeletal parts. After the first 6 months, BMD began to reduce and maintained a declining trend until 24 months postoperatively. Comparing to baseline, the maximal reduction of BMD was as high as 10.28% in total hip. The plasma concentration of UAG increased after 6 months (51.61 ± 55.21 versus 71.95 ± 64.91 pg/mL; P < .01), as well as the serum obestatin level (1.65 ± 0.88 versus 1.71 ± 0.99 ng/mL; P > .05). Although there was a slight drop of both peptides in the first year, they were still above the baseline. Notably, in the second year, UAG and obestatin rose to their peak values, respectively (91.90 ± 77.11 pg/mL and 1.74 ± 1.09 ng/mL). There was a negative correlation between UAG and BMD in all sites. Multiple linear regression analysis showed that the UAG level was the independent parameter associated with BMD at baseline (FN: β = -.407, P = .012 and TH: β = -0.396, P = .030 respectively), as well as the changes of UAG that were independently related with reduction percentage of LS BMD after 24 months (β = - .379, P = .046).
The reduction of BMD in obese Chinese with type 2 diabetes was observed after RYGB. The pronounced increase of serum UAG acts as an independent risk factor for the decrease of BMD.
The influence of high fat diet on plasma incretins and insulin concentrations in Sprague-Dawley rats with diet-induced obesity and glucose intolerance undergoing ileal transposition
2019, Peptides
The benefits of IT surgery are based on incretin effects. In this study we show the influence of high fat diet (HFD) used both before and after surgery, on ileal transposition (IT) effects.
Forty-eight male rats were assigned to two groups: HFD and control diet (CD) fed rats. After eight weeks, HFD and CD fed rats were randomly assigned to two types of surgery: IT and SHAM, then for 50% of animals of each group the diet was changed, whereas the other 50% received the same type of diet. Eight weeks after surgery the incretin level, glucose tolerance as well as body mass and insulin level were assessed.
GLP-1 plasma concentration was significantly higher in the IT operated CD/CD group compared to fasting state and did not differ significantly from the SHAM operated CD/CD animals. IT influenced the glucose stimulated PYY plasma level when compared with SHAM operated animals in the CD/HFD group, where the PYY plasma level was higher than in the SHAM operated animals. The effect of IT as well as of pre and postoperative diet on GIP plasma levels were insignificant. The IT group members maintained on the CD were characterised by a lower fasting glucose level, both pre and postoperatively, compared with the SHAM operated animals. The effect of IT on the fasting glucose level in groups preoperatively maintained on an HFD was insignificant.
IT surgery itself seems to have rather limited incretin effects in rats, whose obesity is the result of HFD.

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View full text

GastrointestinalEntero-Endocrine Changes After Gastric Bypass in Diabetic and Nondiabetic Patients: A Preliminary Study

Introduction

Materials and methods

Results

Conclusions

Introduction

Section snippets

Materials and Methods

Results

Discussion

Surg Obes Relat Dis

Lancet

Surg Obes Relat Dis

Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus

Ann Surg

Outcomes after laparoscopic Roux-en-Y gastric bypass for morbid obesity

Ann Surg

Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery

Diabetes

Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters

Ann Surg

The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism

Ann Surg

Hormonal changes after Roux-en Y gastric bypass for morbid obesity and the control of type-II diabetes mellitus

Am Surg

Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery

N Engl J Med

Gastrointestinal
Entero-Endocrine Changes After Gastric Bypass in Diabetic and Nondiabetic Patients: A Preliminary Study