scholarly journals Hormonal and Metabolic Mechanisms of Diabetes Remission after Gastrointestinal Surgery

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2518-2525 ◽  
Author(s):  
Joshua P. Thaler ◽  
David E. Cummings
Keyword(s):  
Weight Loss ◽  
Time Course ◽  
Gastrointestinal Surgery ◽  
Specific Weight ◽  
Diabetes Remission ◽  
Nutrient Sensing ◽  
Diabetic Patients ◽  
Intestinal Hormones ◽  
Glucagon Like Peptide 1 ◽  
Altered Physiology

Bariatric surgery is the most effective available treatment for obesity. The most frequently performed operation, Roux-en-Y gastric bypass (RYGB), causes profound weight loss and ameliorates obesity-related comorbid conditions, especially type 2 diabetes mellitus (T2DM). Approximately 84% of diabetic patients experience complete remission of T2DM after undergoing RYGB, often before significant weight reduction. The rapid time course and disproportional degree of T2DM improvement after RYGB compared with equivalent weight loss from other interventions suggest surgery-specific, weight-independent effects on glucose homeostasis. Potential mechanisms underlying the direct antidiabetic impact of RYGB include enhanced nutrient stimulation of lower intestinal hormones (e.g. glucagon-like peptide-1), altered physiology from excluding ingested nutrients from the upper intestine, compromised ghrelin secretion, modulations of intestinal nutrient sensing and regulation of insulin sensitivity, and other changes yet to be fully characterized. Research aimed at determining the relative importance of these effects and identifying additional mechanisms promises not only to improve surgical design but also to identify novel targets for diabetes medications.

scholarly journals Decrease of dipeptidyl peptidase 4 activity is associated with weight loss after bariatric surgery

2021 ◽  
Author(s):  
Carsten T. Herz ◽  
Johanna M. Brix ◽  
Bernhard Ludvik ◽  
Guntram Schernthaner ◽  
Gerit-Holger Schernthaner
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Hepatic Injury ◽  
Dipeptidyl Peptidase ◽  
Diabetic Patients ◽  
Metabolic Dysfunction ◽  
Dipeptidyl Peptidase 4 ◽  
Cholesterol Levels ◽  
Glucagon Like Peptide 1 ◽  
The Impact

Abstract Purpose Dipeptidyl peptidase 4 (DPP4) is expressed and secreted by adipocytes. DPP4 induces insulin resistance independently of its effect on glucagon-like peptide 1, thus it is conceivable that DPP4 directly contributes to metabolic dysfunction in patients with morbid obesity. The aim of this study was to investigate the impact of weight loss induced by bariatric surgery on DPP4 activity, and whether these changes are associated with improvements in markers of metabolic dysfunction and fatty liver disease. Materials and Methods We included 68 non-diabetic patients who underwent bariatric surgery. Serum DPP4 activity was measured using a fluorogenic substrate before and after surgery. Results Results: After a median follow-up period of 12 (IQR 11-17) months, median serum DPP4 activity decreased from 230 (IQR: 194-273) to 193 (164-252) pmol/min (p=0.012). The decrease in DPP4 activity was significantly correlated with decreases in BMI, improved cholesterol levels, reduced hepatic injury markers as well as improved post-prandial insulin sensitivity. After multivariable adjustment, ΔDPP4 activity remained significantly associated with Δcholesterol (beta=0.341, p=0.025), ΔLDL cholesterol (beta=0.350, p=0.019), Δgamma-glutamyltransferase (beta=0.323, p=0.040) and ΔMatsuda index (beta=-0.386, p=0.045). Conclusion We demonstrated that weight loss induced by bariatric surgery results in decreased circulating DPP4 activity beyond the initial phase of weight loss. The associations between decreased DPP4 activity and improved cholesterol levels as well as hepatic injury markers point towards pleiotropic effects of DPP4 beyond glucose metabolism which warrant further investigation.

Practical Use of Exenatide and Pramlintide for the Treatment of Type 2 Diabetes

2009 ◽  
Vol 22 (6) ◽  
pp. 540-545 ◽  
Author(s):  
Lisa T. Meade
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Case Reports ◽  
Common Side Effect ◽  
Diabetic Patients ◽  
Patient Counseling ◽  
Antihyperglycemic Therapy ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Type 2 diabetes is a progressive disease that affects more than 20.8 million Americans. Traditional antihyperglycemic therapy can cause weight gain and hypoglycemia in this population. Research shows that type 2 diabetic patients have low levels of glucagon-like peptide-1 and amylin. This discovery led to the creation of 2 newer agents, exenatide and pramlintide. Exenatide, a glucagon-like peptide-1 agonist, stimulates insulin secretion, suppresses glucagon secretion, and slows gastric motility. Transient nausea is the most common side effect, which can be minimized with slow titration. Weight loss associated with exenatide is between 0.9 and 2.8 kg. Hypoglycemia occurs more frequently when exenatide is used with a sulfonylurea. There are some case reports of pancreatitis in patients taking exenatide. Pramlintide, a synthetic form of amylin, inhibits the postmeal rise in glucagon, slows gastric emptying, and promotes satiety. Common side effects of pramlintide include transient nausea, headache, and modest weight loss (1.6 kg). Exenatide and pramlintide are contraindicated in patients with gastroparesis. The success of therapy with both agents is enhanced with slow titration to minimize nausea and patient counseling. Exenatide and pramlintide offer improved postprandial control with the potential for weight loss in patients with type 2 diabetes.

Metabolic surgery in the treatment of type 2 diabetes mellitus

2011 ◽  
pp. 1818-1825
Author(s):  
David E. Cummings
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Type 2 Diabetes Mellitus ◽  
Glycaemic Control ◽  
Gastrointestinal Surgery ◽  
Diabetes Remission ◽  
Obese Patients

Faced with the dual pandemics of obesity and type 2 diabetes mellitus, heath care providers require a broad array of treatment options. Diet, exercise, and medications remain the cornerstones of type 2 diabetes therapy, but long-term results with lifestyle modifications can be disappointing, and, despite an ever-increasing armamentarium of pharmacotherapeutics, adequate glycaemic control often remains elusive. Moreover, most diabetes medications promote weight gain, and using them to achieve tight glycaemic control introduces a proportionate risk of hypoglycaemia. In cases where behavioural/pharmacological strategies prove insufficient, gastrointestinal surgery offers powerful alternatives for obesity and type 2 diabetes treatment (Fig. 13.4.5.1). Among severely obese patients, bariatric operations cause profound, sustained weight loss, ameliorating obesity-related comorbidities and reducing long-term mortality (1–4). Operations involving intestinal bypasses exert particularly dramatic antidiabetes effects. For example, approximately 84% of obese patients with type 2 diabetes experience diabetes remission after a Roux-en-Y gastric bypass (RYGB), maintaining euglycaemia off diabetes medications for at least 14 years (1, 5–8). Mounting evidence indicates that these effects result not only from weight loss, but also from weight-independent antidiabetic mechanisms (9). Whereas diabetes is traditionally viewed as a relentless disease in which delay of end-organ complications is the major treatment goal, gastrointestinal surgery offers a novel endpoint: complete disease remission. Consequently, conventional bariatric procedures and experimental gastrointestinal manipulations are being used worldwide to treat type 2 diabetes in association with obesity, and, increasingly, among less obese or merely overweight patients (8). Gastrointestinal surgery also offers valuable research opportunities to improve knowledge of diabetes pathogenesis and help develop less invasive procedures and novel pharmaceuticals. This chapter discusses the effects of gastrointestinal operations on type 2 diabetes, and focuses on potential antidiabetic mechanisms that mediate those effects.

scholarly journals Genetic Testing to Predict Weight Loss and Diabetes Remission and Long-Term Sustainability after Bariatric Surgery: A Pilot Study

2019 ◽  
Vol 8 (7) ◽  
pp. 964 ◽  
Author(s):  
Andreea Ciudin ◽  
Enzamaria Fidilio ◽  
Angel Ortiz ◽  
Sara Pich ◽  
Eduardo Salas ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Genetic Testing ◽  
Pilot Study ◽  
Diabetes Remission ◽  
Risk Scores ◽  
Diabetic Patients ◽  
Type 2 Diabetic

Introduction: The aim of this pilot study was to assess genetic predisposition risk scores (GPS) in type 2 diabetic and non-diabetic patients in order to predict the better response to bariatric surgery (BS) in terms of either weight loss or diabetes remission. Research Design and Methods: A case-control study in which 96 females (47 with type 2 diabetes) underwent Roux-en-Y gastric by-pass were included. The DNA was extracted from saliva samples and SNPs were examined and grouped into 3 GPS. ROC curves were used to calculate sensitivity and specificity. Results: A highly sensitive and specific predictive model of response to BS was obtained by combining the GPS in non-diabetic subjects. This combination was different in diabetic subjects and highly predictive of diabetes remission. Additionally, the model was able to predict the weight regain and type 2 diabetes relapse after 5 years’ follow-up. Conclusions: Genetic testing is a simple, reliable and useful tool for implementing personalized medicine in type 2 diabetic patients requiring BS.

scholarly journals Time Course of Normalization of Functional β-Cell Capacity in the Diabetes Remission Clinical Trial After Weight Loss in Type 2 Diabetes

Diabetes Care ◽  
2020 ◽  
Vol 43 (4) ◽  
pp. 813-820 ◽  
Author(s):  
Sviatlana V. Zhyzhneuskaya ◽  
Ahmad Al-Mrabeh ◽  
Carl Peters ◽  
Alison Barnes ◽  
Benjamin Aribisala ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Weight Loss ◽  
Time Course ◽  
Diabetes Remission ◽  
Β Cell ◽  
Cell Capacity

scholarly journals A Review on the Role of Food-Derived Bioactive Molecules and the Microbiota–Gut–Brain Axis in Satiety Regulation

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 632
Author(s):  
Nuria A. Pizarroso ◽  
Pablo Fuciños ◽  
Catarina Gonçalves ◽  
Lorenzo Pastrana ◽  
Isabel R. Amado
Keyword(s):  
Metabolic Diseases ◽  
Environmental Changes ◽  
Peptide Yy ◽  
Brain Regions ◽  
Nutrient Sensing ◽  
Bioactive Molecules ◽  
Intestinal Hormones ◽  
Signaling Systems ◽  
Chip Technology ◽  
Glucagon Like Peptide 1

Obesity is a chronic disease resulting from an imbalance between energy intake and expenditure. The growing relevance of this metabolic disease lies in its association with other comorbidities. Obesity is a multifaceted disease where intestinal hormones such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), produced by enteroendocrine cells (EECs), have a pivotal role as signaling systems. Receptors for these hormones have been identified in the gut and different brain regions, highlighting the interconnection between gut and brain in satiation mechanisms. The intestinal microbiota (IM), directly interacting with EECs, can be modulated by the diet by providing specific nutrients that induce environmental changes in the gut ecosystem. Therefore, macronutrients may trigger the microbiota–gut–brain axis (MGBA) through mechanisms including specific nutrient-sensing receptors in EECs, inducing the secretion of specific hormones that lead to decreased appetite or increased energy expenditure. Designing drugs/functional foods based in bioactive compounds exploiting these nutrient-sensing mechanisms may offer an alternative treatment for obesity and/or associated metabolic diseases. Organ-on-a-chip technology represents a suitable approach to model multi-organ communication that can provide a robust platform for studying the potential of these compounds as modulators of the MGBA.

Effectiveness of Dulaglutide in the Real World and in Special Populations of Type 2 Diabetic Patients

2020 ◽  
Vol 105 (7) ◽  
pp. e2617-e2625 ◽  
Author(s):  
Mario Luca Morieri ◽  
Vera Frison ◽  
Mauro Rigato ◽  
Michele D’Ambrosio ◽  
Federica Tadiotto ◽  
...  
Keyword(s):  
Body Weight ◽  
Real World ◽  
Disease Duration ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Body Weight Reduction ◽  
Background Population ◽  
Glucagon Like Peptide 1

Abstract Context In randomized controlled trials (RCTs) on type 2 diabetes (T2D) patients, the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-RA) dulaglutide reduced HbA1c and body weight, but generalizability of such findings to real-world T2D patients is challenging. Objective We evaluated effectiveness of dulaglutide in routine clinical practice, especially in subgroups of patient that are underrepresented in RCTs. Design Retrospective multicenter study. Setting Diabetes outpatient clinics. Patients and intervention All consecutive patients who initiated dulaglutide between 2015 and 2018. Main outcome measures Changes in HbA1c and body weight were assessed up to 30 months after baseline. Effectiveness was analyzed in patient subgroups according to: prior use of GLP-1RA, persistence on treatment and dose, age, sex, disease duration, renal function, obesity, cardiovascular disease, or concomitant use of insulin or sulphonylurea. Results From a background population of 83,116 patients, 2084 initiated dulaglutide (15.3% switching from another GLP-1RA), 1307 of whom had at least 1 follow-up visit. Overall, dulaglutide reduced HbA1c by 1.0% and body weight by 2.9 kg at the end of observation. These effects were more pronounced in GLP-1RA-naïve patients and in those with shorter disease duration. Improvement in HbA1c was highly significant and consistent across all subgroups, including those aged ≥ 75 years, nonobese, or with chronic kidney disease. Body weight declined in all subgroups and significantly more with the 1.5-mg versus 0.75-mg dose. Conclusions In real-world T2D patients, effectiveness of dulaglutide on HbA1c and body weight reduction was highly consistent and significant even in subgroups of patients poorly represented in RCTs.

scholarly journals Bariatric Surgery vs Lifestyle Intervention for Diabetes Treatment: 5-Year Outcomes From a Randomized Trial

2020 ◽  
Vol 105 (3) ◽  
pp. 866-876 ◽  
Author(s):  
Anita P Courcoulas ◽  
James W Gallagher ◽  
Rebecca H Neiberg ◽  
Emily B Eagleton ◽  
James P DeLany ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Lifestyle Intervention ◽  
Controlled Trial ◽  
The United States ◽  
Diabetes Remission ◽  
University Of Pittsburgh ◽  
Lifestyle Treatment ◽  
Surgical Treatments ◽  
The University

Abstract Context Questions remain about bariatric surgery for type 2 diabetes mellitus (T2DM) treatment. Objective Compare the remission of T2DM following surgical or nonsurgical treatments. Design, setting, and participants Randomized controlled trial at the University of Pittsburgh, in the United States. Five-year follow-up from February 2015 until June 2016. Interventions 61 participants with obesity and T2DM who were initially randomized to either bariatric surgical treatments (Roux-en-Y gastric bypass [RYGB] or laparoscopic adjustable gastric banding [LAGB]) or an intensive lifestyle weight loss intervention (LWLI) program for 1 year. Lower level lifestyle weight loss interventions (LLLIs) were then delivered for 4 years. Main Outcomes and Measures Diabetes remission assessed at 5 years. Results The mean age of the patients was 47 ± 6.6 years, 82% were women, and 21% African American. Mean hemoglobin A1c level 7.8% ± 1.9%, body mass index (BMI) 35.7 ± 3.1 kg/m2, and 26 participants (43%) had BMI < 35 kg/m2. Partial or complete T2DM remission was achieved by 30% (n = 6) of RYGB, 19% (n = 4) of LAGB, and no LWLI participants (P = .0208). At 5 years those in the RYGB group had the largest percentage of individuals (56%) not requiring any medications for T2DM compared with those in the LAGB (45%) and LWLI (0%) groups (P = .0065). Mean reductions in percent body weight at 5 years was the greatest after RYGB 25.2% ± 2.1%, followed by LAGB 12.7% ± 2.0% and lifestyle treatment 5.1% ± 2.5% (all pairwise P < .01). Conclusions Surgical treatments are more effective than lifestyle intervention alone for T2DM treatment.

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