Resolution Of Type 2 Diabetes Research Articles

Long-Term Weight Loss and Comorbidity Resolution of Laparoscopic Sleeve Gastrectomy and Laparoscopic Roux-en-Y Gastric Bypass and the Impact of Preoperative Weight Loss on Overall Outcome.

The impact of preoperative weight loss on long-term weight loss outcomes and comorbidity resolution in both laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) are poorly reported. Understanding this relationship is necessary to guide surgeons toward appropriate procedure and patient selection. The present study investigates long-term weight loss outcomes and comorbidity resolution following LSG and LRYGB and investigates the effect of preoperative variables on long-term outcomes. All patients who underwent LSG and LRYGB (2008-2022) in a tertiary referral centre were followed up prospectively. From 2010, a 12-week intensive preoperative information course (IPIC) became standard practice to optimize preoperative weight loss. Excess weight loss outcomes (EWL≥50% and ≥70%) were compared between LSG and LRYGB using multivariate logistic regression and the effect of preoperative weight loss on weight loss and comorbidity resolution, improvement, and exacerbation were reported. A total of 319 patients (median age: 49y; M:F, 75:244) were included (158 LSG: 161 LRYGB). During follow-up, 260 (81.5%) and 163 patients (51.1%) achieved EWL≥50% and ≥70%, respectively. Those with sustained EWL≥50% and EWL≥70% at the end of follow-up were more likely to have underwent a LRYGB versus a LSG (59.6% vs. 40.4%, P=0.002; 61.7% vs. 38.3%, P<0.001). IPIC and higher preoperative weight loss (HR: 2.59 to 3.72, P<0.001) increased rates of EWL≥50% and EWL70% for both procedures. Improvement or resolution of type-2 diabetes were significant (72.7%), but up to 27.3% of patients developed or suffered an exacerbation of a psychiatric illness. Excess weight loss outcomes are similar for LSG and LRYGB but LRYGB results in higher rates of sustained excess weight loss during long-term follow-up. Preoperative weight loss improves long-term weight loss. Comorbidity resolution is significant but rates of psychiatric illness exacerbation are high following metabolic and bariatric surgery.

One Anastomosis Gastric Bypass Compared with Sleeve Gastrectomy in Elderly Patients: Safety and Long-term Outcomes.

As life expectancy increases, more elderly patients are being considered for metabolic bariatric surgery. We aimed to assess the safety and long-term effectiveness of one anastomosis gastric bypass (OAGB) compared to sleeve gastrectomy (SG). Single-center retrospective comparative study of OAGB and SG (2012-2019) in patients aged ≥ 65years. In all, 124 patients underwent OAGB (n = 41) and SG (n = 83). Mean age was 67.6 ± 2.8 and 67.6 ± 2.6years (p = 0.89), respectively. Baseline characteristics were comparable, except lower rates of hypertension (HTN) and non-alcoholic fatty liver disease in OAGB than SG patients (43.9% vs. 74.6%; p < 0.001, and 39.0% vs. 89.1%; p < 0.001, respectively). Body mass index (BMI) of OAGB and SG patients decreased from 41.8 ± 7.8 and 43.3 ± 5.9kg/m2 (p = 0.25) to 28.6 ± 4.7 and 33.2 ± 5.3 (p < 0.001), at long-term follow-up, respectively. Excess weight loss (EWL) > 50% was achieved in 80.6% and 43.2% of OAGB and SG patients, with a mean EWL of 67.2% ± 22.3 and 45.8% ± 18.0 (p < 0.001) and a mean total weight loss (TWL) of 30.7% ± 10.4 and 21.9% ± 8.1 (p < 0.001), respectively. Resolution rates of obesity-associated medical problems were similar, except type 2 diabetes (T2D) and HTN, which were 86.6% and 73.3% in OAGB, compared with 29.7% and 36.3% in SG patients (p < 0.001 and p = 0.001), respectively. Major early complication rates were comparable (2.4% vs. 3.6%; p = 0.73, respectively). Revision for late complications was required in two OAGB patients. OAGB in the elderly is safe and results in better long-term weight reduction and resolution of T2D and HTN than SG.

One Anastomosis Gastric Bypass for Revision of Restrictive Procedures: Mid-Term Outcomes and Analysis of Possible Outcome Predictors.

Revisional one anastomosis gastric bypass (OAGB) for insufficient weight reduction following primary restrictive procedures is still investigated. We report mid-term outcomes and possible outcome predictors. Single-center retrospective comparative study of revisional OAGB outcomes (2015-2018) following laparoscopic adjustable gastric banding (LAGB) and sleeve gastrectomy (SG); silastic ring vertical gastroplasty (SRVG) is separately discussed. In all, 203 patients underwent revisional OAGB following LAGB (n = 125), SG (n = 64), and SRVG (n = 14). Comparing LAGB and SG, body mass index (BMI) at revision were 41.3 ± 6.6 and 42 ± 11.2kg/m2 (p = 0.64), reduced to 31.3 ± 8.3 and 31.9 ± 8.3 (p = 0.64) at mid-term follow-up, respectively. Excess weight loss (EWL) > 50% was achieved in ~ 50%, with EWL of 79.4 ± 20.4% (corresponding total weight loss 38.5 ± 10.4%). SRVG patients had comparable outcomes. Resolution rates of type 2 diabetes (T2D) and hypertension (HTN) were 93.3% and 84.6% in LAGB compared with 100% and 100% in SG patients (p = 0.47 and p = 0.46), respectively. In univariable analysis, EWL > 50% was associated with male gender (p < 0.001), higher weight (p < 0.001), and BMI (p = 0.007) at primary surgery, and higher BMI at revisional OAGB (p < 0.001). In multivariable analysis, independent predictors for EWL > 50% were male gender (OR = 2.8, 95% CI 1.27-6.18; p = 0.01) and higher BMI at revisional OAGB (OR = 1.11, 95% CI 1.03-1.19; p = 0.006). Revisional OAGB for insufficient restrictive procedures results in excellent weight reduction in nearly 50% of patients, with resolution of T2D and HTN at mid-term follow-up. Male gender and higher BMI at revision were associated with EWL > 50% following revisional OAGB. Identification of more predictors could aid judicious patient selection.

Baseline Metabolomic Profile as Potential Biomarker for Weight Change After Roux-en-Y Gastric Bypass Surgery

Introduction: Weight loss surgery (WLS) has emerged as an effective treatment for severe obesity (BMI ≥ 40 kg/m2 in adults) and Type 2 diabetes (T2D). There is a wide spectrum of long-term response, both in weight change and resolution of T2D after WLS. Younger age at surgery, white race and the extent of weight loss prior to surgery are the known traits associated with favorable outcomes. The aim of this study was to investigate untargeted metabolite profile prior to surgery as a potential biomarker for long-term weight change response to WLS. Methods: Latent class growth mixture modeling (LCGMM) was used to classify the longitudinal weight change trajectories in a cohort of individuals who underwent Roux-en-Y gastric bypass (RYGB). Untargeted metabolite profile was done on a 4-module Liquid Chromatography/ Mass Spectroscopy (LC-MS) platform on the pre-surgery fasting plasma samples from subjects with weight regain or sustained weight loss. Metabolite wide association studies followed by pathway analysis was undertaken using Mummichog and GSEA algorithms. Partial least-square discriminant analysis (PLS-DA), a supervised classification framework used for datasets with thousands of correlated variables and a small number of samples that performs variable selection and classification as a one-step procedure, was used to identify the informative features that defined the two groups. Results: LCGMM identified 3-classes of weight change in a cohort of 1589 subjects who had undergone RYGB – a) typical trajectory with significant weight loss by 12 months with plateau at ~80% weight loss (n= 1357, 85.4%), b) sustained weight loss without plateau (SWL, n=116, 7.3%) c) weight regain (RGN, 116, 7.3%). Samples from 80 subjects each with RGN or SWL (age 42.5 ± 10 years, 55% F, Excess body weight 221 ± 40 lbs) were used for untargeted profiling of 37,570 metabolite features (564 known). After QC and adjusting for age, sex, race and fasting time, 1920 features (37 known) were associated with the weight category at nominal significance (p <0.05). Amongst the known metabolites, the pathways represented in RGN were amino acid metabolism, branched chain and other essential amino acids that have been previously identified as markers of insulin resistance and T2D, while those with SWL were from sphingolipid metabolism. Dimethylguanidino valeric acid, a marker of liver fat and predictor of T2D was higher in individuals with SWL. Pathway analysis of the known and unknown metabolites together revealed pathways in urea cycle, pyrimidine, glutamate, essential amino acids, and butyrate metabolism. Features identified by PLS-DA overlapped with these pathways. Conclusions: Untargeted baseline metabolites may serve as predictive biomarkers for weight change after RYGB. Future work will focus on developing a metabolite risk score and replication in other cohorts.

1904-P: Metabolomic Fingerprints after Metabolic Surgery: The STAMPEDE Trial

Introduction: Metabolic surgery (MS) results in durable resolution of hyperglycemia in ∼50% of patients with type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) account for more than 90% of all metabolic surgeries, and both have been demonstrated to have greater efficacy when compared to intensive medical and lifestyle therapy (IMT) to improve glycemic control. However, a subset of patients following MS exhibit inadequate weight loss, poor glycemic control, or both. Thus, the purpose of this study was to identify novel biomarkers of biochemical resolution of T2D following IMT and MS. Methods: Plasma samples from ninety patients (49.9±7.6 years, 57.7% female) randomly assigned to receive either IMT (n=30), RYGB (n=30) or SG (n=30) were retrospectively analyzed and quantified by untargeted metabolomic analysis using UPLC-tandem mass spectrometry at baseline (PRE) and 24 months (POST) of treatment. Results: We identified 384 metabolites altered by RYGB, SG and IMT treatment. 2-hydroxybutyrate was significantly decreased following all 3 interventions with a greater decrease in SG and RYGB at POST (p≤0.05). Pyruvate was significant lower in the IMT and RYGB group (p≤0.05), but not in SG at POST (vs. PRE). Markers of fatty acid metabolism, including acetylcarnitine and 3-hydroxybutyrate (BHBA), were also decreased following the SG intervention (p≤0.05). Several primary and secondary bile acid metabolites were significantly increased after RYGB compared to SG. Conclusion: We identified a novel metabolomic fingerprint characterizing the longer-term adaptations to IMT, RYGB, and SG. Notably, the metabolomic profile of both RYGB and SG procedures were distinct, suggesting that the roughly equivalent weight loss is achieved by divergent mechanisms. Disclosure W.S. Dantas: None. C.L. Axelrod: None. A. Hari: None. S. Kashyap: Other Relationship; Self; GI Dynamics Inc. P. Schauer: Advisory Panel; Self; GI Dynamics Inc. Consultant; Self; Ethicon US, LLC, Medtronic. Research Support; Self; Ethicon US, LLC, Medtronic. J.P. Kirwan: None. Funding Ethicon

Banded Sleeve Gastrectomy and One Anastomosis Gastric Bypass/Mini-gastric Bypass for Treatment of Obesity: a Retrospective Cohort Comparative Study with 6 years follow-up.

Banded sleeve gastrectomy (BSG), a modification of the laparoscopic sleeve gastrectomy (SG), and one anastomotic gastric bypass/mini-gastric bypass (OAGB/MGB), a modification to the Roux-en-Y gastric bypass (RYGB), have been reported to enhance weight loss and minimize significant weight regain when compared with the SG and RYGB respectively. However, there has not been any report or study comparing these two operations. We did a retrospective cohort study comparing these two operations and present a review and analysis with follow-up for 6years. A review of all the operations performed at MBRSC in 2011 from a prospectively maintained database was done. Patients who had either a BSG or OAGB/MGB were identified. Data on the patients' profile, co-morbid conditions, perioperative complications, late complications, weight loss, resolution of comorbidities, and changes in quality of life (QLF) were collected reviewed and analyzed. Sixty-eight patients were identified who had a primary BSG and 55 who had an OAGB/MGB in 2011. The follow-up rate, the age, BMI, and gender composition were similar in both groups. There were more patients with type 2 diabetes (T2D) in the BSG group than in the OAGB/MGB group (44.1% vs. 27.2%). The incidences of hypertension (HTN) and obstructive sleep apnea (OSA) were higher in the OAGB/MGB group (62% vs. 36% and 96.3% vs. 2.9% respectively). The weight loss was faster in the OAGB/MGB group in the first year, but by the sixth year, the weight loss was slightly higher in the BSG group (84% vs. 79%). Resolution rate of T2D and HTN was higher after the OAGB/MGB group, 86.6% vs. 75.7% and 85.3% vs. 64.0% respectively. There was a 20% incidence of nutrient deficiencies in OAGB/MGB group and none in the BSG group. Both operations produced excellent weight loss and maintenance in the short to intermediate term. There was better resolution of T2D and HTN after OAGB/MGB at the expense of a higher incidence of nutrient deficiency and some protein caloric malnutrition. There is need for prospective and larger series studies to confirm these findings.

Mechanism of diabetes control after metabolic surgery

Gastrointestinal metabolic surgery is becoming the most effective therapy for type 2 diabetes (T2D) in obese patients. Mechanism underlying the glycemic control of metabolic surgery is intriguing and has been heavily investigated but still not well defined. Multiple plausible mechanisms, rather than a single predominant mechanism, likely mediate the early and long-term glycemic control after metabolic surgery. This paper examines the proposed mechanism from published research findings. Bariatric surgery consisted of three parts of anatomical changes: (I) gastric restriction; (II) exclusion of duodenum and upper intestine; (III) rapid delivery of food to distal intestine or short common channel. These anatomical changes may induce a lot of physiologic and molecular changes helping in the resolution of T2D. The proposed mechanisms included calories restriction and weight loss, ghrelin, duodenum exclusion effect with gastro-intestinal (GI) tract nutrient sensing, rapid distal nutrient delivery with gut hormone response, changes in bile acid metabolism, and intestinal microbiome. These changes, acting through peripheral and central pathway, result in reduced hepatic glucose, increased tissue glucose uptake, improved insulin sensitivity, and enhanced B-cell function. Different procedures may provide different mechanism and help in identifying novel therapeutic targets.

Mechanism of diabetes control after metabolic surgery

Gastrointestinal metabolic surgery is becoming the most effective therapy for type 2 diabetes (T2D) in obese patients. Mechanism underlying the glycemic control of metabolic surgery is intriguing and has been heavily investigated but still not well defined. Multiple plausible mechanisms, rather than a single predominant mechanism, likely mediate the early and long-term glycemic control after metabolic surgery. This paper examines the proposed mechanism from published research findings. Bariatric surgery consisted of three parts of anatomical changes: (I) gastric restriction; (II) exclusion of duodenum and upper intestine; (III) rapid delivery of food to distal intestine or short common channel. These anatomical changes may induce a lot of physiologic and molecular changes helping in the resolution of T2D. The proposed mechanisms included calories restriction and weight loss, ghrelin, duodenum exclusion effect with gastro-intestinal (GI) tract nutrient sensing, rapid distal nutrient delivery with gut hormone response, changes in bile acid metabolism, and intestinal microbiome. These changes, acting through peripheral and central pathway, result in reduced hepatic glucose, increased tissue glucose uptake, improved insulin sensitivity, and enhanced B-cell function. Different procedures may provide different mechanism and help in identifying novel therapeutic targets.

Mechanisms of Action of Surgical Interventions on Weight-Related Diseases: the Potential Role of Bile Acids.

Surgical interventions for weight-related diseases (SWRD) may have substantial and sustainable effect on weight reduction, also leading to a higher remission rate of type 2 diabetes (T2D) mellitus than any other medical treatment or lifestyle intervention. The resolution of T2D after Roux-en-Y gastric bypass (RYGB) typically occurs too quickly to be accounted for by weight loss alone, suggesting that these operations have a direct impact on glucose homeostasis. The mechanisms underlying these beneficial effects however remain unclear. Recent research suggests that changes in the concentrations of plasma bile acids might contribute to these metabolic changes after surgery. In this review, we aimed to outline the potential role of bile acids in SWRD. We systematically reviewed MEDLINE, SCOPUS, and Web of Science for articles reporting the effect of SWRD on outcomes published between 1969 and 2016. We found that changes in circulating bile acids after surgery may play a major role through activation of the farnesoid X receptor A (FXRA), the fibroblast growth factor 19 (FGF19), and the G protein-coupled bile acid receptor (TGR5). Bile acid concentration increased significantly after RYGB. Some studies suggest that a transitory decrease occurs at 1week post-surgery, followed by a gradual increase. Most studies have shown the increase to be proportionate by all bile acid subtypes. Bile acids can regulate glucose metabolism through the expression of TGR5 receptor in L cells, resulting in a release of glucagon-like peptide 1 (GLP-1). It may also induce the synthesis and secretion of FGF19 in ileal cells, thereby improving insulin sensitivity and regulating glucose metabolism. All the present SWRD are involved with changes in food stimulation to the stomach. This implies that discovering and developing the antagonists to TGR5 and FXRA may effectively control metabolic syndrome and the elucidation of the mechanisms underlying the physiological effects related to weight loss and T2D remission after surgery may help to identify new drug targets.

Is There a Role for Visceral Adiposity in Inducing Type 2 Diabetes Remission in Severely Obese Patients Following Biliopancreatic Diversion with Duodenal Switch Surgery?

Severe obesity is often characterized by ectopic fat deposition, which is related to development of type 2 diabetes (T2D). Thus, resolution of T2D may not be linearly associated with weight loss. The importance of ectopic fat reduction after bariatric surgery and T2D resolution is uncertain. The aim of this pilot study is to compare body composition and body fat distribution in severely obese patients with or without T2D after biliopancreatic diversion with duodenal switch (BPD-DS) surgery in relation to diabetes resolution. Sixty-two severely obese patients were evaluated at baseline, 6, and 12months. Of these, 40 patients underwent BPD-DS surgery. Anthropometric measurements and abdominal and mid-thigh computed tomography scans were performed at each visit. Before BPD-DS surgery, obese patients with T2D had higher weight as well as greater ectopic fat deposition in the abdomen and mid-thigh level than obese patients without T2D (p < 0.05). Resolution of T2D was 65 and 90% at 6 and 12months, respectively. No difference in body composition changes at 6 and 12months could be found between patients without T2D, patients with T2D resolution, and patients who remained T2D. Resolution of T2D was associated with a greater absolute loss of visceral adipose tissue (VAT) in comparison to patients without T2D (-1175 ± 570cm(3) vs. -729 ± 394cm(3) at 6months and -1647 ± 816cm(3) vs. -1103 ± 422cm(3) at 12months; all p ≤ 0.05). Ectopic fat mobilization, particularly the absolute loss of VAT, may play a major role in T2D resolution following BPD-DS surgery, regardless of the amount of weight loss.

Intestinal sweet-sensing pathways and metabolic changes after Roux-en-Y gastric bypass surgery.

Studies suggest that improvements in type 2 diabetes (T2D) post- Roux-en-Y gastric bypass (RYGB) surgery are attributable to decreased intestinal glucose absorption capacity mediated by exclusion of sweet taste-sensing pathways in isolated proximal bowel. We probed these pathways in rat models that had undergone RYGB with catheter placement in the biliopancreatic (BP) limb to permit post-RYGB exposure of isolated bowel to sweet taste stimulants. Lean Sprague Dawley (n = 13) and obese Zucker diabetic fatty rats (n = 15) underwent RYGB with BP catheter placement. On postoperative day 11 (POD 11), rats received catheter infusions of saccharin [sweet taste receptor (T1R2/3) agonist] or saline (control). Jejunum was analyzed for changes in glucose transporter/sensor mRNA expression and functional sodium-glucose transporter 1 (SGLT1)-mediated glucose uptake. Saccharin infusion did not alter glucose uptake in the Roux limb of RYGB rats. Intestinal expression of the glucose sensor T1R2 and transporters (SGLT1, glucose transporter 2) was similar in saccharin- vs. saline-infused rats of both strains. However, the abundance of SGLT3b mRNA, a putative glucose sensor, was higher in the common limb vs. BP/Roux limb in both strains of bypassed rats and was significantly decreased in the Roux limb after saccharin infusion. We concluded that failure of BP limb exposure to saccharin to increase Roux limb glucose uptake suggests that isolation of T1R2/3 is unlikely to be involved in metabolic benefits of RYGB, as restimulation failed to reverse changes in intestinal glucose absorption capacity. The altered expression pattern of SGLT3 after RYGB warrants further investigation of its potential involvement in resolution of T2D after RYGB.

Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: understanding weight loss and improvements in type 2 diabetes after bariatric surgery

Obesity increases the likelihood of diseases like type 2 diabetes (T2D), heart disease, and cancer, and is one of the most serious public health problems of this century. In contrast to ineffectual prevention strategies, lifestyle modifications, and pharmacological therapies, bariatric surgery is a very effective treatment for morbid obesity and also markedly improves associated comorbidities like T2D. However, weight loss and resolution of T2D after bariatric surgery is heterogeneous and specific to type of bariatric procedure performed. Conventional mechanisms like intestinal malabsorption and gastric restriction do not fully explain this, and potent changes in appetite and the enteroinsular axis, as a result of anatomical reorganization and altered hormonal, neuronal, and nutrient signaling, are the portended cause. Uniquely these signaling changes appear to override vigorous homeostatic defenses of stable body weight and compelling self-gratifying motivations to eat and to reverse defects in beta-cell function and insulin sensitivity. Here we review mechanisms of weight loss and T2D resolution after Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy bariatric surgery, two markedly different procedures with robust clinical outcomes.

Surgical treatment of morbid obesity

Patients with morbid obesity are prone to weight-related disease, reduced quality of life and shortened life expectancy. Long-term weight loss is unsatisfactory with conservative treatment and weight-reducing surgery is increasingly performed in all Norwegian health regions.This review is based on electronic database searches. We describe the two procedures most commonly performed in Norway, i.e. gastric bypass and biliopancreatic diversion with duodenal switch, including preoperative workup and expected results after surgery. The domestic use of different surgical techniques is also outlined.In Norway, around 750 bariatric procedures were planned in 2006. Gastric bypass yields a weight reduction of 30% two years after the operative. Resolution of type 2-diabetes, hypertension, hyperlipidemia, and obstructive sleep apnea has been demonstrated in most patients. A majority of patients report improved quality of life. Procedure-related mortality is less than 1% and surgical complications occur in approximately 20%. Nutritional deficiencies are frequent. Weight loss is somewhat greater after biliopancreatic diversion with duodenal switch, but the procedure is more complex. Life-long follow-up is recommended after bariatric surgery.In selected patients with morbid obesity, bariatric surgery is a viable treatment. However, prospective long- term studies are needed.