scholarly journals Thromboxane-Dependent Platelet Activation in Obese Subjects with Prediabetes or Early Type 2 Diabetes: Effects of Liraglutide- or Lifestyle Changes-Induced Weight Loss

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1872 ◽  
Author(s):  
Paola Simeone ◽  
Rossella Liani ◽  
Romina Tripaldi ◽  
Augusto Di Castelnuovo ◽  
Maria Guagnano ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lipid Peroxidation ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Glycemic Control ◽  
Platelet Activation ◽  
Glycosylated Hemoglobin ◽  
Lifestyle Changes ◽  
Obese Subjects

Thromboxane (TX)-dependent platelet activation and lipid peroxidation, as reflected in vivo by the urinary excretion of 11-dehydro-TXB2 and 8-iso-prostaglandin (PG)F2α, play a key role in atherothrombosis in obesity and type 2 diabetes mellitus (T2DM) since the earlier stages. Thirty-five metformin-treated obese subjects with prediabetes or newly-diagnosed T2DM were randomized to the glucagon-like peptide receptor agonist (GLP-RA) liraglutide (1.8 mg/day) or lifestyle counseling until achieving a comparable weight loss (−7% of initial body weight), to assess whether changes in subcutaneous (SAT) and visceral (VAT) adipose tissue distribution (MRI), insulin sensitivity (Matsuda Index) and beta-cell performance (multiple sampling OGTT beta-index), with either intervention, might affect TX-dependent platelet activation, lipid peroxidation and inflammation. At baseline, Ln-8-iso-PGF2α (Beta = 0.31, p = 0.0088), glycosylated hemoglobin (HbA1c) (Beta = 2.64, p = 0.0011) Ln-TNF-α (Beta = 0.58, p = 0.0075) and SAT (Beta = 0.14, p = 0.044) were significant independent predictors of 11-dehydro-TXB2. After achievement of the weight loss target, a comparable reduction in U-11-dehydro-TXB2 (between-group p = 0.679) and 8-iso-PGF-2α (p = 0.985) was observed in both arms in parallel with a comparable improvement in glycemic control, insulin sensitivity, SAT, high-sensitivity C-reactive protein (hs-CRP). In obese patients with initial impairment of glucose metabolism, the extent of platelet activation is related to systemic inflammation, isoprostane formation and degree of glycemic control and abdominal SAT. Successful weight loss, achieved with either lifestyle changes or an incretin-based therapy, is associated with a significant reduction in lipid peroxidation and platelet activation.

1014-P: Relationship between Glycemic Control and Weight Loss with Once-Weekly Efpeglenatide in Uncontrolled Type 2 Diabetes: A Subanalysis of EXCEED 203

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1014-P
Author(s):  
JULIO ROSENSTOCK ◽  
CRISTOBAL MORALES ◽  
ULRICH WENDISCH ◽  
GEORGE E. DAILEY ◽  
MICHAEL E. TRAUTMANN ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Glycemic Control

Abstract 018: Two-year Changes of Adiponectin after Bariatric Surgery and Their Association with Incident Type 2 Diabetes, Cardiovascular Disease, Cancer and Mortality: Results from the Swedish Obese Subjects Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Christian Herder ◽  
Markku Peltonen ◽  
Per-Arne Svensson ◽  
Maren Carstensen ◽  
Peter Jacobson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Control Group ◽  
Incident Type ◽  
Surgery Group ◽  
Obese Subjects

Introduction: Adiponectin has anti-inflammatory, insulin-sensitising and atheroprotective effects in rodents. Although serum adiponectin is uniformly downregulated in obesity, its clinical relevance in humans seems more complex. It is not known whether changes in circulating adiponectin predict type 2 diabetes, cardiovascular disease, cancer and mortality in an obese population. Hypothesis: We hypothesised that adiponectin levels are upregulated substantially after weight loss following bariatric surgery and that pronounced increases of adiponectin should offer better protection for individuals against type 2 diabetes. In addition, findings for type 2 diabetes should be compared to associations with cardiovascular disease, myocardial infarction, stroke, cancer and mortality. Methods: Serum concentrations of total adiponectin were measured in 3,223 participants of the Swedish Obese Subjects (SOS) Study (1,533 in the bariatric surgery group: 229 with gastric bypass, 1056 with vertical banded gastroplasty, 248 with adjustable gastric banding; 1,690 in the control group without surgery) at study baseline and after 2 years. Hazard ratios (HR) and 95% confidence intervals (CI) per 1 standard deviation (SD) of 2-year changes (concentration at year 2 - concentration at baseline) in adiponectin were calculated for incident type 2 diabetes, cardiovascular disease, myocardial infarction, stroke, cancer and mortality in the combined surgery group. Numbers of cases were 93, 122, 78, 55, 82 and 179, respectively. Median follow-up times ranged from 10 years for diabetes up to 16 years for mortality. Results: Mean (SD) levels of adiponectin at baseline were 7,453 (4,150) ng/ml in the combined surgery group and 8,247 (4,846) ng/ml in the control group. During the first 2 years of follow-up, adiponectin levels increased in the surgery group by 4,850 (5,387) ng/ml (parallel to a loss of 24% of body weight) and decreased slightly by 270 (2,650) ng/ml in the control group (parallel to a slight gain of 0.1% body weight). The degree of correlation between changes in adiponectin and weight loss in kg was more pronounced in the surgery groups compared with the control group (p=0.001 for interaction). Two-year increases in adiponectin in the surgery group were associated with decreased risk of type 2 diabetes (HR [95% CI] 0.61 [0.38-0.98], adjusted for baseline data for age, sex, BMI, lipids, blood pressure, alcohol consumption, smoking, anti-hypertensive drugs, glucose, insulin), but not with cardiovascular disease, myocardial infarction, stroke, cancer and mortality (adjusted HR between 0.89 and 1.05). Conclusions: Weight loss after bariatric surgery is paralleled by a substantial increase in circulating adiponectin. The degree of upregulation of adiponectin is associated with protection against future type 2 diabetes, but not with the incidence of cardiovascular outcomes, cancer or mortality.

scholarly journals Incretin-Based Therapies in Type 2 Diabetes Mellitus

2008 ◽  
Vol 93 (10) ◽  
pp. 3703-3716 ◽  
Author(s):  
Chee W. Chia ◽  
Josephine M. Egan
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Type 2 Diabetes Mellitus ◽  
Evidence Synthesis ◽  
Glycosylated Hemoglobin ◽  
Cell Mass ◽  
New Drugs ◽  
Medline Search

Context: Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide are incretins secreted from enteroendocrine cells postprandially in part to regulate glucose homeostasis. Dysregulation of these hormones is evident in type 2 diabetes mellitus (T2DM). Two new drugs, exenatide (GLP-1 mimetic) and sitagliptin [dipeptidyl peptidase (DPP) 4 inhibitor], have been approved by regulatory agencies for treating T2DM. Liraglutide (GLP-1 mimetic) and vildagliptin (DPP 4 inhibitor) are expected to arrive on the market soon. Evidence Acquisition: The background of incretin-based therapy and selected clinical trials of these four drugs are reviewed. A MEDLINE search was conducted for published articles using the key words incretin, glucose-dependent insulinotropic polypeptide, GLP-1, exendin-4, exenatide, DPP 4, liraglutide, sitagliptin, and vildagliptin. Evidence Synthesis: Exenatide and liraglutide are injection based. Three-year follow-up data on exenatide showed a sustained weight loss and glycosylated hemoglobin (HbA1c) reduction of 1%. Nausea and vomiting are common. Results from phase 3 studies are pending on liraglutide. Sitagliptin and vildagliptin are orally active. In 24-wk studies, sitagliptin reduces HbA1c by 0.6–0.8% as monotherapy, 1.8% as initial combination therapy with metformin, and 0.7% as add-on therapy to metformin. Vildagliptin monotherapy lowered HbA1c by 1.0–1.4% after 24 wk. Their major side effects are urinary tract and nasopharyngeal infections and headaches. Exenatide and liraglutide cause weight loss, whereas sitagliptin and vildagliptin do not. Conclusions: The availability of GLP-1 mimetics and DPP 4 inhibitors has increased our armamentarium for treating T2DM. Unresolved issues such as the effects of GLP-1 mimetics and DPP 4 inhibitors on β-cell mass, the mechanism by which GLP-1 mimetics lowers glucagon levels, and exactly how DPP 4 inhibitors lead to a decline in plasma glucose levels without an increase in insulin secretion, need further research.

scholarly journals Baseline interleukin1beta expression in peripheral blood monocytes predicts the extent of weight loss and nonalcoholic fatty liver improvement in obese subjects with prediabetes or type 2 diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P.G Simeone ◽  
S Costantino ◽  
R Tripaldi ◽  
R Liani ◽  
S Ciotti ◽  
...  
Keyword(s):  
Weight Loss ◽  
Peripheral Blood ◽  
Receptor Agonist ◽  
Mononuclear Cells ◽  
Lifestyle Changes ◽  
Funding Source ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Obese Subjects

Abstract Background Non-alcoholic fatty liver disease (NAFLD) represents a hallmark of metabolic syndrome. Interleukin-1β (IL-1β), a well-studied cytokine involved in obesity-related systemic inflammation as well as in the pathogenesis of type 2 diabetes (T2D), promotes hepatic steatosis by stimulating triglycerides and cholesterol accumulation in primary liver hepatocytes and lipid droplets formation. The most compelling evidence for a major role for IL-1β in metabolic imbalance and inflammation comes from the recent Canakinumab Anti-inflammatory Thrombosis Outcome (CANTOs)trial, where inhibition of IL-1β pathway was associated with a reduction of cardiovascular events in high-risk patients. Purpose The present study was designed to determine: i)whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on NAFLD extent and IL-1β expression in peripheral blood mononuclear cells from obese subjects with prediabetes or early T2D; ii)whether baseline IL-1β levels may predict the extent of weight loss and related metabolic changes. Methods Thirty-two metformin-treated obese subjects with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n=16)] or newly diagnosed T2D (n=16), were randomized to the glucagon-like peptide receptor agonist (GLP-RA) liraglutide (1.8 mg/d) or lifestyle counselling until achieving a modest and comparable weight loss (−7% of initial body weight). Visceral (VAT) and adipose tissue distribution were assessed by magnetic resonance. Gene expression of IL-1β in peripheral blood mononuclear cells was assessed by real time PCR. Results At baseline, IL-1β positively correlated to body mass index (BMI) (rho=0.421, p=0.016), fasting plasma glucose (rho=0.415, p=0.018), HbA1c (rho=0.349, p=0.050), VAT (rho=0.388, p=0.028), NAFLD (rho=0.454, p=0.009), platelet count (rho=0.510, p=0.003), chemerin (rho=0.455, p=0.009) and interleukin-1 receptor agonist (IL1-RA) (rho=0.519, p=0.002). After achievement of the weight loss target in the two groups, a comparable reduction of IL-1 β (p<0.001 lifestyle changes; p=0.029 liraglutide treatment) was observed in both arms, in parallel with a comparable improvement in glycaemic control, C-reactive protein (CRP),BMI and NAFLD. Furthermore, basal levels of IL-1β correlated directly with delta BMI (p=0.015) and delta NAFLD (p=0.002) (Figure 1). Conclusion In obese patients with initial impairment of glucose metabolism, IL-β-driven inflammation correlates with glycaemic control, adipose tissue distribution and platelet count. Successful weight loss, achieved with either lifestyle changes or an incretin-based therapy, is associated with a significant reduction of both IL-1β levels and NAFLD degree. Of interest, basal levels of IL-1β predicts the extent of weight loss and NAFLD improvement, regardless of the intervention. Our results may set the stage for ad-hoc studies investigating the usefulness of baseline IL-1β a levels as a drug-response biomarker. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): This study was supported by a grant from the Italian Ministry of University and Research (PRIN no. 2010JS3PMZ to F.S.).

P-72: Intermittent vagal blockade with an implantable device improves glycemic control in obese subjects with type 2 diabetes

2009 ◽  
Vol 5 (3) ◽  
pp. S48-S49
Author(s):  
Miguel F. Herrera ◽  
Roy Brancatisano ◽  
Ulrich Keller ◽  
Baard Kulseng ◽  
James Toouli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Implantable Device ◽  
Vagal Blockade ◽  
Obese Subjects
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