scholarly journals GLP-1 Limits Adipocyte Inflammation and Its Low Circulating Pre-Operative Concentrations Predict Worse Type 2 Diabetes Remission after Bariatric Surgery in Obese Patients

2019 ◽  
Vol 8 (4) ◽  
pp. 479 ◽  
Author(s):  
Maitane Izaguirre ◽  
Javier Gómez-Ambrosi ◽  
Amaia Rodríguez ◽  
Beatriz Ramírez ◽  
Sara Becerril ◽  
...  

Objective: Glucagon-like peptide (GLP)-1 has been proposed as a key candidate in glucose improvements after bariatric surgery. Our aim was to explore the role of GLP-1 in surgically-induced type 2 diabetes (T2D) improvement and its capacity to regulate human adipocyte inflammation. Methods: Basal circulating concentrations of GLP-1 as well as during an oral glucose tolerance test (OGTT) were measured in lean and obese volunteers with and without T2D (n = 93). In addition, GLP-1 levels were determined before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 77). The impact of GLP-1 on inflammation signalling pathways was also evaluated. Results: We show that the reduced (p < 0.05) circulating levels of GLP-1 in obese T2D patients increased (p < 0.05) after RYGB. The area under the curve was significantly lower in obese patients with (p < 0.01) and without (p < 0.05) T2D compared to lean volunteers while obese patients with T2D exhibited decreased GLP-1 levels at baseline (p < 0.05) and 120 min (p < 0.01) after the OGTT. Importantly, higher (p < 0.05) pre-operative GLP-1 concentrations were found in patients with T2D remission after RYGB. We also revealed that exendin-4, a GLP-1 agonist, downregulated the expression of inflammation-related genes (IL1B, IL6, IL8, TNF) and, conversely, upregulated the mRNA levels of ADIPOQ in human visceral adipocytes. Furthermore, exendin-4 blocked (p < 0.05) LPS-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Conclusions: Our data indicate that GLP-1 may contribute to glycemic control and exert a role in T2D remission after RYGB. GLP-1 is also involved in limiting inflammation in human visceral adipocytes.

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1275-1275
Author(s):  
Magdalena Sevilla ◽  
Donaji Gomez-Velasco ◽  
Ivette Cruz-Bautista ◽  
Laura Lazaro-Carrera ◽  
Paloma Almeda-Valdes ◽  
...  

Abstract Objectives A haplotype in SLC16A11 is associated with decreased insulin action, and risk for type 2 diabetes (T2D) in Mexicans. We aim to determine the impact of the risk haplotype on SLC16A11 on early therapeutic responses in treatments to prevent T2D. Methods We recruited subjects with at least one prediabetes criteria according to the American Diabetes Association, and body mass index 25–45 kg/m2. Subjects were randomized in two groups: lifestyle intervention (LSI): hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids and 15% protein sources + physical activity (&gt;150 min medium intensity per week), or LSI + metformin (750 mg prolonged release twice a day). Interventions were prescribed by standardized dietitians. The goal was to achieve &gt;3% weight loss. We evaluated the early treatment response in a follow-up period of 12 weeks with intermediate visits each 3 weeks to reinforce knowledge and treatment goals. Evaluations (baseline and post-treatment) included an oral glucose tolerance test (OGTT), and dual-energy X-ray absorptiometry. Adherence to treatment was measured trough electronic recordings. Participants were genotyped for the risk allele rs13342232. Researchers remained blinded to the genotype results. The effects of the risk haplotype were evaluated with linear and logistic regressions adjusted by age, sex, and baseline body fat %. Results We evaluated 61 subjects, 30 carriers, and 31 non-carriers. Most of participants (57%) achieved ≥3% weight loss. The LSI + metformin treatment increased in carriers, 2 times OR 3 IC95% (1.07 – 8.6) (P = 0.04) the probability to reach the ≥3% weight loss goal compared with LSI and non-carriers. In the same treatment, carriers had a greater decrease in the total and incremental area under the curve of insulin in the OGTT IC95% (−1.75 −0.11) (P = 0.02) compared with non-carriers and LSI. Carriers also had higher decrease in postprandial glucose compared with non-carriers regardless of treatment −12.63 + 30.38 vs 0.71 30.24 (P = 0.02). Conclusions After 12 weeks of treatment, carriers with prediabetes showed a higher probability achieve weight loss and to improve insulin secretion with metformin. Regardless of the treatment, carriers were prone to improve postprandial glucose. Funding Sources Miguel Aleman Medical Research Award.


2018 ◽  
Vol 14 (3) ◽  
pp. 332-337 ◽  
Author(s):  
Kamyar Hariri ◽  
Daniela Guevara ◽  
Anusha Jayaram ◽  
Subhash U. Kini ◽  
Daniel M. Herron ◽  
...  

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 672-672
Author(s):  
Tiannan Wang ◽  
Guoxun Chen

Abstract Objectives We have shown that vitamin A (VA) status regulates obesity and fuel metabolism in rats. Here, we studied the effects of VA status on the development of obesity and type 2 diabetes in Zucker diabetic fat (ZDF) rats. Methods Zucker Lean (ZL) and ZDF rats at weaning were divided into 6 groups, VA deficient with basal fat (VAD-BF, 0 mg retinyl palmitate (RP)/kg and 22.1% fat energy), VA marginal with BF (VAM-BF, 0.35 mg RP/kg), VA sufficient with BF (VAS-BF, 4.0 mg RP/kg), VAD with high-fat (VAD-HF, 60% fat energy), VAM-HF and VAS-HF diets, and fed for 8 weeks (w). The body mass (BM), and peripheral blood glucose (PBG) were measured weekly. Insulin tolerance test (ITT) and oral glucose tolerance test (OGTT) were done at 6.5 and 7.5 w, respectively. At the end of the feeding, blood, liver and white adipose tissue (WTA) samples were collected. Results VAS-BF ZL and ZDF rats from 6 w had respectively higher BM than VAD/VAM-BF ZL and ZDF rats. VAS-HF ZL and ZDF rats from 4 w had respectively higher BM than VAD/VAM-HF ZL and ZDF rats. The liver/BM and WAT/BM ratios in VAD/VAM-BF/HF ZL and ZDF V rats were respectively lower than that of VAS-BF/HF groups. VAS-BF/HF ZDF rats from 6 w had respectively higher PBG levels than VAD/VAM-BF/HF ZDF rats. In ITT, PBG levels of VAD/VAM/VAS-BF ZL rats dropped until 15 mins. PBG levels of VAD-HF and VAM/VAS-HF ZL rats declined until 30 mins and 15 mins, respectively. PBG levels of VAM-BF and VAS-BF ZDF rats dropped until 15 mins and 5 mins, respectively. PBG levels of VAD-BF ZDF rats start to dropped after 10 mins and stopped after 20 mins. PBG levels of VAD/VAM-HF and VAS-HF ZDF rats dropped until 15 mins and 20 mins, respectively. The OGTT results showed that PBG levels of VAS-BF ZL rats peaked at 10 mins, and VAS-BF/HF ZL rats had respectively higher PBG levels than VAD/VAM-BF/HF ZL rats. PBG levels of all ZDF rats peaked at 60 mins (except for VAS-BF ZDF rats at 30) before dropped. TheOGTT area under the curve values of VAS-BF/HF ZL or ZDF rats were respectively higher than that of VAD/VAM-BF/HF ZL or ZDF rats, and that of VAM-HF ZL rats were higher than that of VAD-HF ZL rats. Conclusions VA statuses affect BM gain in ZL and ZDF rats in BF and HF diets. Reduced VA intake prevents obesity, and type 2 diabetes in ZDF rats. Funding Sources Diabetes Action Research and Education Foundation.


2020 ◽  
Author(s):  
Brenno Astiarraga ◽  
Laia Martínez ◽  
Victoria Ceperuelo-Mallafré ◽  
Gemma Llauradó ◽  
Margarida Terrón-Puig ◽  
...  

<div><b><i>Objective</i></b> To explore the meal response of circulating succinate in patients with obesity and type 2 diabetes undergoing bariatric surgery, and to examine the role of gastrointestinal glucose sensing in succinate dynamics in healthy subjects. <b><i><br></i></b></div><div><b><i>Research Design and</i></b> <b><i>Methods</i></b> Cohort I comprised 45 patients with morbid obesity and type 2 diabetes (BMI 39.4±1.9 kg/m<sup>2</sup>) undergoing metabolic surgery. Cohort II was a confirmatory cohort of 13 patients (BMI 39.3±1.4 kg/m<sup>2</sup>) undergoing gastric bypass surgery. Cohort III comprised 15 healthy subjects (BMI 26.4±0.5 kg/m<sup>2</sup>). Cohorts I and II completed a 2-hour meal tolerance test (MTT) before the intervention and at one-year of follow-up, and cohort II also completed a 3-hour lipid test (LT). Cohort III underwent a 3-hour oral glucose tolerance test (OGTT) and an isoglycemic variable glucose infusion (ISO) study. </div> <p><b><i>Results</i></b><i> </i>In cohort I, succinate response to MTT at follow-up was greater than before the intervention (p<0.0001). This response was confirmed in cohort II with a greater increase after one year of surgery (p=0.009). By contrast, LT did not elicit a succinate response. Changes in succinate response were associated with changes in the area under the curve of glucose (r=0.417, p<0.0001) and insulin (r=0.204, p=0.002). In cohort III, glycemia <i>per se</i> stimulated a plasma succinate response (p=0.0004), but its response was greater in the OGTT (p=0.02; OGTT <i>versus</i> ISO). </p> <p><b><i>Conclusions</i></b><b> </b>The<b> </b>meal-related response of circulating succinate in patients with obesity and type 2 diabetes is recovered after metabolic surgery.</p>


Author(s):  
Amrandra Prasad Singh

Background: Type 2 Diabetes mellitus (T2DM) is the most common non-communicable chronic diseases in developed and developing countries around the world. The study reported the prevalence of diabetes association with rheumatoid arthritis (RA) among different obese and non-obese populations of Patna, India.Methods: This clinic based descriptive study was conducted in Patna city from 1st August 2017 to 30th September 2018. A total 250 patients with diagnosed RA were enrolled. DM was defined according to the ADA recommendations as FBS ≥126mg/dl or oral glucose tolerance test OGTT2 ≥200mg/dl and HbA1c≥6.5. On the basis of the BMI calculated, patients were categorized either as obese or non-obese. Random diabetic detection was done to detect T2DM and followed by proper investigation at clinical laboratories. Patients also asked for hyperglycemic events during initial counselling.Results: Mean BMI in obese was found to be 29.22±3.22 and in non-obese it was 22.99±1.38 (p<0.001). Most of the patients had been type 2 diabetes for more than 5 years duration. In both genders, an increasing trend was observed in the prevalence of type 2 diabetes with increasing BMI. Among these, a total of 198 (79.2%) were found to have diabetes, 115 (58.08%) of these were obese and 83 (41.91%) non-obese (p=0.003).Conclusions: BMI is directly correlated to type 2 diabetes, as T2DM was significantly more common in obese patients with RA compared to non-obese patients with RA. Obese patients with RA had significantly more frequent diabetes.


2010 ◽  
Vol 77 (7) ◽  
pp. 468-476 ◽  
Author(s):  
Sangeeta R. Kashyap ◽  
Patrick Gatmaitan ◽  
Stacy Brethauer ◽  
Philip Schauer

2020 ◽  
Author(s):  
Brenno Astiarraga ◽  
Laia Martínez ◽  
Victoria Ceperuelo-Mallafré ◽  
Gemma Llauradó ◽  
Margarida Terrón-Puig ◽  
...  

<div><b><i>Objective</i></b> To explore the meal response of circulating succinate in patients with obesity and type 2 diabetes undergoing bariatric surgery, and to examine the role of gastrointestinal glucose sensing in succinate dynamics in healthy subjects. <b><i><br></i></b></div><div><b><i>Research Design and</i></b> <b><i>Methods</i></b> Cohort I comprised 45 patients with morbid obesity and type 2 diabetes (BMI 39.4±1.9 kg/m<sup>2</sup>) undergoing metabolic surgery. Cohort II was a confirmatory cohort of 13 patients (BMI 39.3±1.4 kg/m<sup>2</sup>) undergoing gastric bypass surgery. Cohort III comprised 15 healthy subjects (BMI 26.4±0.5 kg/m<sup>2</sup>). Cohorts I and II completed a 2-hour meal tolerance test (MTT) before the intervention and at one-year of follow-up, and cohort II also completed a 3-hour lipid test (LT). Cohort III underwent a 3-hour oral glucose tolerance test (OGTT) and an isoglycemic variable glucose infusion (ISO) study. </div> <p><b><i>Results</i></b><i> </i>In cohort I, succinate response to MTT at follow-up was greater than before the intervention (p<0.0001). This response was confirmed in cohort II with a greater increase after one year of surgery (p=0.009). By contrast, LT did not elicit a succinate response. Changes in succinate response were associated with changes in the area under the curve of glucose (r=0.417, p<0.0001) and insulin (r=0.204, p=0.002). In cohort III, glycemia <i>per se</i> stimulated a plasma succinate response (p=0.0004), but its response was greater in the OGTT (p=0.02; OGTT <i>versus</i> ISO). </p> <p><b><i>Conclusions</i></b><b> </b>The<b> </b>meal-related response of circulating succinate in patients with obesity and type 2 diabetes is recovered after metabolic surgery.</p>


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