scholarly journals Galectin 3 as a new therapeutic target for fibrosis and metabolic disorders in type 2 diabetes

2021 ◽  
Author(s):  
Dayssem khelifi ◽  
Ibtissem Ben Nacef ◽  
Kahena Bouzid ◽  
Imen Rojbi ◽  
Youssef Lakhoua ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Therapeutic Target ◽  
Metabolic Disorders ◽  
Threshold Value ◽  
Lipid Lowering ◽  
Inverse Association ◽  
Type 2 Diabetics ◽  
Careful Clinical Examination ◽  
Galectin 3

Abstract Background: The objective of our research work was to identify the predictive factors of metabolic disorder and the pro-fibrotic factors which would be correlated with high levels of Galectin-3(Gal-3) in a population of patients with type 2 diabetes. Methods: We carried out an analytical cross-sectional study.We included 260 type 2 diabetics followed in our endocrinology department.For the purpose of determining a threshold value of Gal-3,we asked for a non-diabetic control group. The medical history interview included history of diabetes, use of antihypertensive medications, lipid-lowering medication, smoking habits and physical activity.A careful clinical examination was performed for all patients and all of them underwent a biological analysis with an assay of the plasma concentrations of Galectin-3. Results: Our study included 260 type 2 diabetics with an average age of 59.4±8.9years.The sex ratio was 0.78.We established a threshold for galectin-3 with the best sensitivity and specificity at 11.25ng/ml using the ROC curve.We found a significant positive correlation of Gal-3 with age (p<0.001),duration of diabetes (p=0.024),systolic blood pressure (p =0.032), diabetic retinopathy (p<0.001), body mass index (p=0.01), waist circumference(p<0.001), hypertension (p<0.001), dyslipidemia (p=0.023),triglyceridemia (p=0.029).An inverse association between Gal-3 level and physical activity(p=0.014),hypoplipemic treatment (p=0.040),metformin (p=0.028) and glomerular filtration rate (p<0.001) were observed. Conclusion: We established a threshold value of Gal-3 and we discovered the clinical and biological parameters correlated with the elevation of Gal-3 which would be pro-fibrosating factors.We have also demonstrated that this lectin is a key player as a new marker and therapeutic target for the control of metabolic disorders.

The Management of Dyslipidaemia in Patients with Type 2 Diabetes Mellitus Receiving Lipid-Lowering Drugs: A Sub-Analysis of the CEPHEUS Findings

2018 ◽  
Vol 16 (4) ◽  
pp. 368-375 ◽  
Author(s):  
Abdullah Shehab ◽  
Khalid Al-Rasadi ◽  
Mohamed Arafah ◽  
Ali T. Al-Hinai ◽  
Wael Al Mahmeed ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Lipid Lowering ◽  
Lipid Lowering Drugs

scholarly journals Multidisciplinary Pharmacotherapeutic Options for Nonalcoholic Fatty Liver Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Kei Nakajima
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Lipid Lowering ◽  
Nonalcoholic Fatty Liver ◽  
Ras Blockers

Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.

scholarly journals The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (7) ◽  
pp. 3566
Author(s):  
Chae Bin Lee ◽  
Soon Uk Chae ◽  
Seong Jun Jo ◽  
Ui Min Jerng ◽  
Soo Kyung Bae
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Metabolism ◽  
Gut Microbiome ◽  
Metabolic Disorders ◽  
Current Knowledge ◽  
Potential Target ◽  
The Relationship

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.

scholarly journals Therapies for the Treatment of Cardiovascular Disease Associated with Type 2 Diabetes and Dyslipidemia

2021 ◽  
Vol 22 (2) ◽  
pp. 660
Author(s):  
María Aguilar-Ballester ◽  
Gema Hurtado-Genovés ◽  
Alida Taberner-Cortés ◽  
Andrea Herrero-Cervera ◽  
Sergio Martínez-Hervás ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Leukocyte Adhesion ◽  
Experimental Studies ◽  
Lipid Lowering ◽  
Foam Cell Formation ◽  
Relevant Parameter

Cardiovascular disease (CVD) is the leading cause of death worldwide and is the clinical manifestation of the atherosclerosis. Elevated LDL-cholesterol levels are the first line of therapy but the increasing prevalence in type 2 diabetes mellitus (T2DM) has positioned the cardiometabolic risk as the most relevant parameter for treatment. Therefore, the control of this risk, characterized by dyslipidemia, hypertension, obesity, and insulin resistance, has become a major goal in many experimental and clinical studies in the context of CVD. In the present review, we summarized experimental studies and clinical trials of recent anti-diabetic and lipid-lowering therapies targeted to reduce CVD. Specifically, incretin-based therapies, sodium-glucose co-transporter 2 inhibitors, and proprotein convertase subtilisin kexin 9 inactivating therapies are described. Moreover, the novel molecular mechanisms explaining the CVD protection of the drugs reviewed here indicate major effects on vascular cells, inflammatory cells, and cardiomyocytes, beyond their expected anti-diabetic and lipid-lowering control. The revealed key mechanism is a prevention of acute cardiovascular events by restraining atherosclerosis at early stages, with decreased leukocyte adhesion, recruitment, and foam cell formation, and increased plaque stability and diminished necrotic core in advanced plaques. These emergent cardiometabolic therapies have a promising future to reduce CVD burden.

scholarly journals Associations of markers of arterial stiffness and remodeling with new-onset type 2 diabetes mellitus

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
F Ahmadizar ◽  
K Wang ◽  
F Mattace Raso ◽  
MA Ikram ◽  
M Kavousi
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Arterial Stiffness ◽  
Wall Stress ◽  
Lipid Lowering ◽  
Circumferential Wall Stress ◽  
Increased Risk

Abstract Funding Acknowledgements Type of funding sources: None. Background. Arterial stiffness/remodeling results in impaired blood flow and, eventually, decreased glucose disposal in peripheral tissues and increased blood glucose. Besides, increased arterial stiffness/remodeling may lead to hypertension, as a potential reciprocal risk factor for type 2 diabetes mellitus (T2D). We, therefore, hypothesized that increased arterial stiffness/remodeling is associated with an increased risk of T2D. Purpose. To study the associations between arterial stiffness/remodeling and incident T2D. Methods. We used the prospective population-based Rotterdam Study. Common carotid arterial properties were ultrasonically determined in plaque-free areas. Aortic stiffness was estimated by carotid-femoral pulse wave velocity (cf_PWV), carotid stiffness was estimated by the carotid distensibility coefficient (carDC). Arterial remodeling was estimated by carotid artery lumen diameter (carDi), carotid intima-media thickness (cIMT), mean circumferential wall stress (CWSmean), and pulsatile circumferential wall stress (CWSpuls). Cox proportional hazard regression analysis was used to estimate the associations between arterial stiffness/remodeling and the risk of incident T2D, adjusted for age, sex, cohort, mean arterial pressure (MAP), antihypertensive medications, heart rate, non- high-density lipoprotein (HDL)-cholesterol, lipid-lowering medications, and smoking. We included interaction terms in the fully adjusted models to study whether any significant associations were modified by sex, age, blood glucose, or MAP. Spearman correlation analyses were applied to examine the correlations between measurements of arterial stiffness/remodeling and glycemic traits. Results. We included 3,055 individuals free of T2D at baseline (mean (SD) age, 67.2 (7.9) years). During a median follow-up of 14.0 years, 395 (12.9%) T2D occurred. After adjustments, higher cf_PWV (hazard ratio (HR),1.18; 95%CI:1.04-1.35), carDi (1.17; 1.04-1.32), cIMT (1.15; 1.01-1.32), and CWSpuls (1.28; 1.12-1.47) were associated with increased risk of incident T2D. After further adjustment for the baseline glucose, the associations attenuated but remained statistically significant. Sex, age, blood glucose, or MAP did not modify the associations between measurements of arterial stiffness/remodeling, and incident T2D. Among the population with prediabetes at baseline (n = 513) compared to the general population, larger cIMT was associated with a greater increase in the risk of T2D. Most measurements of arterial stiffness/remodeling significantly but weakly correlated with baseline glycemic traits, particularly with blood glucose.  Conclusions. Our study suggests that greater arterial stiffness/remodeling is independently associated with an increased risk of T2D development. Blood glucose and hypertension do not seem to play significant roles in these associations. Further studies should disentangle the underlying mechanism that links arterial stiffness/remodeling and T2D.

scholarly journals Age- and Gender-Related Differences in LDL-Cholesterol Management in Outpatients with Type 2 Diabetes Mellitus

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Giuseppina Russo ◽  
Basilio Pintaudi ◽  
Carlo Giorda ◽  
Giuseppe Lucisano ◽  
Antonio Nicolucci ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Diabetes Duration ◽  
Lipid Lowering ◽  
Age And Gender ◽  
Chd Risk ◽  
And Gender

Background. Dyslipidemia contribute to the excess of coronary heart disease (CHD) risk observed in women with type 2 diabetes (T2DM). Low density lipoprotein-cholesterol (LDL-C) is the major target for CHD prevention, and T2DM women seem to reach LDL-C targets less frequently than men.Aim. To explore age- and gender-related differences in LDL-C management in a large sample of outpatients with T2DM.Results. Overall, 415.294 patients (45.3% women) from 236 diabetes centers in Italy were included. Women were older and more obese, with longer diabetes duration, higher total-cholesterol, LDL-C, and HDL-C serum levels compared to men (P<0.0001). Lipid profile was monitored in ~75% of subjects, women being monitored less frequently than men, irrespective of age. More women did not reach the LDL-C target as compared to men, particularly in the subgroup treated with lipid-lowering medications. The between-genders gap in reaching LDL-C targets increased with age and diabetes duration, favouring men in all groups.Conclusions. LDL-C management is worst in women with T2DM, who are monitored and reach targets less frequently than T2DM men. Similarly to men, they do not receive medications despite high LDL-C. These gender discrepancies increase with age and diabetes duration, exposing older women to higher CHD risk.

Galectin-3 predicts cardiovascular events in patients with type-2 diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Lorenzo-Almoros ◽  
A Pello ◽  
A Acena ◽  
J Martinez-Milla ◽  
N Tarin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Plasma Levels ◽  
Cardiovascular Events ◽  
Primary Outcome ◽  
Funding Source ◽  
Increased Risk ◽  
Galectin 3 ◽  
Secondary Outcomes

Abstract Introduction Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. Methods We followed 964 patients with coronary artery disease (CAD), assessing at baseline galectin-3, monocyte chemoattractant protein-1 (MCP-1) and N-terminal fragment of brain natriuretic peptide (NT-proBNP) plasma levels. Secondary outcomes were acute ischemia and heart failure or death. Primary outcome was the combination of the secondary outcomes. Results Male patients were 75.0% in T2DM and 76.6% in the non-T2DM subgroup (p=0.609). Age was 61.0 (54–72) and 60.0 (51–71) years, respectively (p=0.092). 232 patients had T2DM. Patients with T2DM showed higher MCP-1 [144 (113–195) vs. 133 (105–173) pg/ml, p=0.006] and galectin-3 [8.3 (6.5–10.5) vs. 7.8 (5.9–9.8) ng/ml, p=0.049] levels. Median follow-up was 5.39 years (2.81- 6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients [HR 1.57 (1.07–2.30); p=0.022], along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in non-diabetic patients [HR 1.21 (1.04–1.42); p=0.017 and HR 1.23 (1.05–1.44); p=0.012, respectively], along with male sex and age. Galectin-3 was also the only biomarker that predicted the development of acute ischemic events and heart failure or death in T2DM patients, while in non-diabetics MCP-1 and NT-proBNP, respectively, predicted these events. Conclusion In CAD patients, cardiovascular events are predicted by galectin-3 plasma levels in patients with T2DM, and by MCP-1 and NT-proBNP in those without T2DM. Effect of Gal-3 on the primary endpoint Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Insituto de Salud Carlos III

Sign in / Sign up

Export Citation Format

Share Document