Benefits in routinely measured liver function tests following bariatric surgery: a retrospective cohort study.

Background: Bariatric surgery is well-established to support long-term metabolic health benefits associated with considerable weight loss. Here, we aim to determine the longer-term impact of bariatric surgery on liver enzymes and associations with other metabolic improvements. Methods: One hundred patients who underwent bariatric surgery between 2007 and 2014 were included, and changes in liver enzymes, anthropometric measures and other parameters were observed over a mean 9.8 years. Results: At the time of surgery, the mean age was 45.4 ± 9.6 years, weight 141.2 ± 31.6 kg, and body mass index (BMI) 50.2 ± 10.1 kg/m2. Most patients underwent sleeve gastrectomy [n = 71] with a mean follow-up duration 9.8 ± 2.3 years. From baseline, alanine transaminase (ALT) reduced by 41.3% within 12 months post-operatively (36.6 ± 29.2 U/L to 21.5 ± 14.9 U/L, p < 0.001), which was sustained at recent follow-up (20.2 ± 10.7 U/L, p < 0.001). There were associated reductions in body weight, BMI, HbA1c, blood pressure and triglycerides. Patients with greater baseline ALT had the greatest reduction in ALT over follow-up. Conclusions: Bariatric surgery is associated with rapid and sustained improvements in routine liver enzymes at 10 years, and sustained improvements in features of the metabolic syndrome. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01311-4.

The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials.

Glucagon-like peptide 1 (GLP-1) based therapy is an established treatment option for the management of type 2 diabetes mellitus (T2DM) and is recommended early in the treatment algorithm owing to glycaemic efficacy, weight reduction and favourable cardiovascular outcomes. Glucose-dependent insulinotropic polypeptide (GIP), on the other hand, was thought to have no potential as a glucose-lowering therapy because of observations showing no insulinotropic effect from supraphysiological infusion in people with T2DM. However, emerging evidence has illustrated that co-infusion of GLP-1 and GIP has a synergetic effect, resulting in significantly increased insulin response and glucagonostatic response, compared with separate administration of each hormone. These observations have led to the development of a dual GIP/GLP-1 receptor agonist, known as a 'twincretin'. Tirzepatide is a novel dual GIP/GLP-1 receptor agonist formulated as a synthetic peptide containing 39 amino acids, based on the native GIP sequence. Pre-clinical trials and phase 1 and 2 clinical trials indicate that tirzepatide has potent glucose lowering and weight loss with adverse effects comparable to those of established GLP-1 receptor agonists. The long-term efficacy, safety and cardiovascular outcomes of tirzepatide will be investigated in the SURPASS phase 3 clinical trial programme. In this paper, we will review the pre-clinical and phase 1 and 2 trials for tirzepatide in the management of T2DM and give an overview of the SURPASS clinical trials.

Temporal Effects of Bariatric Surgery on Adipokines, Inflammation and Oxidative Stress in Subjects with Impaired Glucose Homeostasis at 4 Years of Follow-up.

BACKGROUND: Previous studies have examined changes in plasma markers of inflammation and oxidative stress up to 24 months following bariatric surgery, but there is limited evidence on the long-term effects of bariatric surgery. OBJECTIVES: To examine the effects of bariatric surgery on adipokines (adiponectin, leptin), inflammatory cytokines [C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10(IL-10)] and global plasma measures of oxidative stress [thiobarbituric acid reactive substances (TBARS) and total antioxidant status (TAOS) 1 and 6 months, and 4 years post-surgery in subjects with obesity and impaired glucose regulation. METHODS: A prospective study comprising of 19 participants (13 females, mean age 50.4 ± 6.2 years, mean body mass index (BMI) 54 ± 14 kg/m2, 17 type 2 diabetes) undergoing bariatric surgery (10 sleeve gastrectomy, 6 biliopancreatic diversion, 2 Roux-en-Y gastric bypass and 1 laparoscopic adjustable gastric banding). Serial measurements of the above markers were made pre-operatively, 1 and 6 months and 4 years post-operatively. RESULTS: Compared to pre-operative levels, significant decreases were seen 4 years post-operatively in CRP (11.4 vs 2.8 ng/mL, p < 0.001), IL-6 (8.0 vs 2.1 pg/mL, p < 0.001) and leptin (60.7 vs 32.1 pg/mL, p = 0.001). At 4 years, both fasting and 120 min TAOS significantly increased by 35% and 19% respectively. However, fasting and 120 min TBARS did not show any significant changes. CONCLUSION: To our knowledge, no other studies have described changes in inflammation and oxidative stress at 4 years following bariatric surgery. This study contributes to the current literature supporting the longer-term beneficial effect of bariatric surgery on chronic inflammation and oxidative stress.

Effect of Laparoscopic Sleeve Gastrectomy on Static and Dynamic Measures of Glucose Homeostasis and Incretin Hormone Response 4-Years Post-Operatively.

INTRODUCTION: There is limited literature available on the long-term effect of bariatric surgery especially laparoscopic sleeve gastrectomy (LSG) on the incretin hormone response. AIM: Our primary aim was to investigate changes in glucose metabolism and incretin hormone responses in participants with impaired glucose regulation approximately 4 years after LSG. The secondary aim was to examine the long-term incretin hormone changes of biliopancreatic diversion (BPD). METHOD: A non-randomised prospective study comprising of 10 participants undergoing LSG and 6 participants undergoing BPD. Serial measurements of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were performed during an oral glucose tolerance test pre-operatively and 1 month, 6 months and at approximately 4-7 years post-operatively. Area under the curve (AUC) was examined at 60 and 120 min. RESULTS: In the LSG group, a significant reduction in 2-h plasma glucose (2 h PG), HbA1c and HOMA-IR was observed at 4 years. Compared with pre-operative levels, significant increases in post-glucose GLP-1 secretion were observed at 1 and 6 months, but not maintained at 4 years. A linear increase was seen in post-glucose GIP response at 1 month and 6 months and 4 years. Within the BPD group, a reduction in HbA1c along with an increase GLP-1 response was observed at 7 years. CONCLUSION: An increase in GLP-1 response was not preserved at 4 years, but a significant increase in GIP response was observed along with improved glycaemic control following LSG.

Temporal effects of laparoscopic sleeve gastrectomy on adipokines, inflammation, and oxidative stress in patients with impaired glucose homeostasis.

BACKGROUND: Bariatric surgery is an effective treatment for morbid obesity and metabolic dysfunction. OBJECTIVES: The aim of this work was to examine the early temporal effects of laparoscopic sleeve gastrectomy (LSG) on adipokines (adiponectin, leptin), inflammatory cytokines (interleukin-6, C-reactive protein, interleukin-10), and global plasma measures of oxidative stress (thiobarbituric acid reactive substances and total antioxidant status) in a sample of 55 participants preoperatively, and 1 and 6 months postoperatively. The focus was on a sample of patients with impaired glucose tolerance and type 2 diabetes, which is associated with increased low-grade systemic inflammation and oxidative stress. SETTING: University hospital, United Kingdom. METHODS: This was a prospective study comprising 55 participants with impaired glucose homeostasis and type 2 diabetes undergoing LSG (mean body mass index 50.4 kg/m2, mean glycated hemoglobin 7.4%). Serial measurements of the above markers were made preoperatively, 1 and 6 months postoperatively (43 had measurable cytokines and oxidative stress at 1- and 6-mo follow-up). RESULTS: We observed a significant reduction in interleukin-6, C-reactive protein, leptin, and thiobarbituric acid reactive substances, along with an increase in adiponectin 6 months postoperatively. CONCLUSIONS: To our knowledge the effects of LSG on inflammatory cytokines and plasma markers of oxidative stress have not been examined temporally in a sizeable sample of participants who have undergone LSG. This present study supports the role of LSG for the treatment of the proinflammatory and pro-oxidant status associated with obesity-related glucose dysregulation.

Bariatric Surgery Is Accompanied by Changes in Extracellular Vesicle-Associated and Plasma Fatty Acid Binding Protein 4.

BACKGROUND: Bariatric surgery markedly reduces fat mass with beneficial effects on cardiometabolic health but the mechanisms involved are not fully understood. Extracellular vesicles (EVs) are secreted by a variety of cells, including adipocytes, and may mediate some of these benefits. However, the effects of bariatric surgery on circulating EVs are unclear. METHODS: Concentration of plasma EVs isolated by ultracentrifugation at baseline, 1 and 6 months post-bariatric surgery (n = 20) was established using Nanoparticle Tracking Analysis. EV origin (CD9: exosome; CD41: platelet; CD235a: erythrocyte; CD11b: leukocyte; CD144: endothelial), cytokine (interferon γ, interleukin-6, TNF-α) and adipocyte marker (adiponectin, FABP4, PPARγ) expression was measured by time-resolved fluorescence immunoassay. RESULTS: EV concentration and cell-of-origin markers (CD41, CD235a, CD11b, CD144) did not alter in response to surgery, neither did EV-expressed interferon γ, IL-6, TNF-α, adiponectin, PPARγ or CD9. EV-derived fatty acid binding protein 4 (FABP4) increased at 1 month (+ 49%) before returning to baseline by 6 months (- 51%, p < 0.05), corresponding to similar changes in circulating plasma FABP4 (+ 22 and - 24% at 1 and 6 months, respectively; p < 0.001). Patients who underwent biliopancreatic diversion had lower FABP4-expressing EVs at 6 months compared to those who underwent sleeve gastrectomy/gastric banding (p < 0.05), despite similar percentage weight reduction (- 19 vs - 20%, respectively). CD9 expression correlated with EV-expressed FABP4, adiponectin, TNF-α and interferon γ (r = 0.5, r = 0.59, r = 0.53, r = 0.41, respectively, p < 0.005), suggesting transport by an EV population of exosomal rather than microvesicular origin. CONCLUSIONS: Bariatric surgery leads to a transient change in circulating EV- and plasma-derived FABP4, reflecting alterations in adipose tissue homeostasis.

Temporal changes in plasma markers of oxidative stress following laparoscopic sleeve gastrectomy in subjects with impaired glucose regulation.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity and associated metabolic complications. Obesity and type 2 diabetes are associated with increased oxidative stress. Previous studies have examined changes in plasma oxidative stress after laparoscopic Roux-en-Y gastric bypass, but there is limited evidence of the effects of LSG. OBJECTIVES: To examine the effects of LSG on plasma thiobarbituric acid reactive substances (TBARS) and total antioxidant status (TAOS) at 1 and 6 months after LSG in patients with obesity and impaired glucose regulation. SETTING: University hospital, United Kingdom. METHODS: Twenty-two participants with impaired glucose homeostasis undergoing LSG (body mass index 50.1 kg/m2, glycated hemoglobin 53 mmol/mol) were studied. Measurements of fasting and 120-minute TBARS and TAOS were performed during an oral glucose tolerance test preoperatively and postoperatively. RESULTS: Compared with preoperative levels, significant decreases were seen 6 months postoperatively in fasting TBARS (61.0±17.9 versus 39.4±13.8 ng/mL, P = .04) and 120-minute TBARS (76.0±29.5 versus 46.5±16.3 ng/mL, P = .02). No significant changes were observed in plasma TAOS. No significant association was observed between changes in TBARS and other clinical or biochemical measures. CONCLUSION: We observed a significant reduction in TBARS, a global measure of lipid peroxidation 6 months after LSG in participants with obesity and impaired glucose regulation.

Temporal Effect of Bariatric Surgery on Predicted 10-Year and Lifetime Cardiovascular Risk at 1 Month, 6 Months, and 5 Years Following Surgery: A Pilot Study.

BACKGROUND AND AIMS: Cardiovascular (CV) risk equations are routinely used to predict risk in nonbariatric populations, but have not been studied in depth in patients undergoing bariatric surgery and specifically those with impaired glucose regulation. The aim of this pilot study was to investigate changes in the 10-year and lifetime predicted CV risk in subjects with impaired glucose regulation before, 1 month, 6 months, and 5 years after bariatric surgery. METHOD AND RESULTS: A nonrandomized prospective study was conducted of 45 participants with impaired glucose regulation undergoing temporal assessments during follow-up. Body weight, body mass index (BMI), blood pressure, lipid profile, and HbA1c were recorded preoperatively, 1 month, 6 months, and 5 years postoperatively. Preoperative and postoperative predicted CV risk was calculated using the QRISK2, QRISK lifetime, and JBS3 calculators. Follow-up rates were 93%, 91%, and 71% at 1 month, 6 months, and 5 years, respectively. The sample had a mean age of 48.8 ± 7.0 years, a mean BMI of 53.9 ± 11.1 kg/m2, and a mean HbA1c of 7.5% ± 1.7%. The predicted 10-year QRISK2 score decreased by 35%, 54%, and 24% at 1 month, 6 months, and 5 years, respectively (P < 0.001). The predicted lifetime risk also decreased with the greatest reduction (24.5% with QRISK lifetime and 26.7% with JBS3 lifetime score) observed at 5 years even though the subjects were 5 years older. CONCLUSION: Bariatric surgery in patients with impaired glucose regulation is associated with a significant reduction in predicted 10-year and lifetime CV risk in a population that was 5 years older compared to baseline.

Association between the preoperative fasting and postprandial C-peptide AUC with resolution of type 2 diabetes 6 months following bariatric surgery.

BACKGROUND AND AIMS: Bariatric surgery results in the remission of type 2 diabetes mellitus (T2DM) in morbidly obese subjects. The aim of the study was to investigate the predictive value of both static and dynamic measures of C-peptide in relation to T2DM resolution 6 months after bariatric surgery regardless of the operation type. METHODS AND RESULTS: A non-randomized prospective study of 24 participants with T2DM undergoing bariatric surgery. Measurements of fasting and 2-hour plasma glucose, insulin, C-peptide and measures of insulin sensitivity were recorded temporally during an oral glucose tolerance test pre-operatively and 6 months post-operatively. A responder was defined with a fasting glucose <5.6 mmol/L and HbA1c <6.0% postoperatively. Within the sample there were 11 responders and 13 non-responders at 6 months. There was a significant difference in the duration of diabetes between the groups. Fasting C-peptide (P≤0.05) and 2-hour C-peptide (P≤0.05) were higher in responders compared to non-responders. Significantly higher C-peptide levels were observed preoperatively at all time points for responders, with significantly higher area under the curve (AUC0-60 and AUC0-120). Using the lower quartiles for C-peptide levels, both fasting C-peptide (>2.5 ng/mL [0.83 nmol/L]) and 2-hour C-peptide (>5.2 ng/mL [1.73 nmol/L]) had a sensitivity and negative predictive value of 100% to predict T2DM remission. Logistic regression showed that C-peptide, duration of diabetes and BMI were associated with response. The area under the ROC curve was 0.94 and a regression model predicted diabetes remission with a sensitivity of 85.7% and a specificity of 88.9%. CONCLUSIONS: This study demonstrated that static (fasting) and dynamic (AUC, 2-hour) C-peptide measurements predict T2DM resolution 6 months following bariatric surgery. This work provides insight into C-peptide dynamics as a predictor of response to bariatric surgery.