scholarly journals NLRP3Inflammasome Polymorphism and Macrovascular Complications in Type 2 Diabetes Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Jasna Klen ◽  
Katja Goričar ◽  
Andrej Janež ◽  
Vita Dolžan
Keyword(s):  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Plasma Cholesterol ◽  
Microvascular Complications ◽  
Macrovascular Complications ◽  
Lipid Levels ◽  
Cholesterol Levels ◽  
Increased Risk

Background. It is generally accepted that poor glycemic control, arterial hypertension and/or hyperlipidemia, and the associated oxidative stress may contribute to the development of macro- and microvascular complications in type 2 diabetes (T2D). Such metabolic damage signals may activate inflammasome and trigger chronic inflammation. We investigated common polymorphisms in inflammasome coding genes and the risk for macro- and microvascular complications in T2D.Methods. In total 181 clinically well-characterised T2D patients were genotyped forNLRP3rs35829419 andCARD8rs2043211. Risk for diabetic complications was assessed using logistic regression.Results. Patients with median duration of T2D 11 (6–17) years had relatively well controlled blood glucose and lipid levels and blood pressure on the prescribed treatment regimen. Duration of T2D and plasma cholesterol levels were the most important clinical risk factors for macrovascular complications (P=0.007andP=0.031).NLRP3rs35829419 was associated with increased risk for macrovascular complications (P=0.004), with myocardial infarction in particular (P=0.052). No association was observed betweenCARD8polymorphism and any of T2D complications.Conclusions. Our preliminary data suggest the role ofNLRP3polymorphism in diabetic macrovascular complications, especially in myocardial infarction.

scholarly journals The Role of Combined SGLT1/SGLT2 Inhibition in Reducing the Incidence of Stroke and Myocardial Infarction in Patients with Type 2 Diabetes Mellitus

2021 ◽  
Author(s):  
Bertram Pitt ◽  
Gabriel Steg ◽  
Lawrence A. Leiter ◽  
Deepak L. Bhatt
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Relative Increase ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Sglt2 Inhibition

Abstract Purpose In patients with type 2 diabetes mellitus (T2DM), both sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide receptor agonists (GLP-1 RAs) have demonstrated significant improvements in cardiovascular and kidney outcomes independent of their glycemic benefits. This paper will briefly compare the effect of SGLT2is and GLP-1 RAs to that of the SGLT1/2 inhibitor sotagliflozin on the incidence of myocardial infarction (MI) and stroke in patients with T2DM and further postulate mechanisms to account for these findings. Methods and Results Thus far, the results from SCORED and SOLOIST (trials studying the SGLT1/2 inhibitor sotagliflozin) suggest that an increase in SGLT1 inhibition when added to SGLT2 inhibition may contribute to reductions in MI and stroke in patients with T2DM. This benefit is beyond what SGLT2is alone can accomplish and at least similar to GLP-1 RAs but with the added benefit of a reduction in hospitalizations and urgent visits for HF. Larger and longer studies are required to confirm the effectiveness of SGLT1/SGLT2 inhibition in reducing MI and stroke in patients with T2DM and elucidate the mechanisms associated with this finding. Conclusions The role of SGLT1/2 inhibition as an addition to GLP-1 RAs in patients with and without T2DM at increased risk for MI and stroke requires further study. Regardless, the finding that a relative increase in SGLT1/2 inhibition reduces the risk of MI and stroke as well as hospitalizations and urgent visits for heart failure could improve quality of life and reduce the healthcare burden associated with T2DM.

The GSTM1 and GSTT1 Null Genotypes Increase the Risk for Type 2 Diabetes Mellitus and the Subsequent Development of Diabetic Complications: A Meta-analysis

2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Meta Analysis ◽  
Subsequent Development ◽  
Asian Population ◽  
Gstm1 Null Genotype ◽  
Increased Risk

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.

Role of Circulating Microparticles in Type 2 Diabetes Mellitus: Implications for Pathological Clotting

2021 ◽  
Author(s):  
Siphosethu Cassandra Maphumulo ◽  
Etheresia Pretorius
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Systemic Inflammation ◽  
Blood Cells ◽  
Low Grade ◽  
Chronic Hyperglycemia ◽  
Increased Risk

AbstractType 2 diabetes mellitus (T2DM) is a multifactorial chronic metabolic disease characterized by chronic hyperglycemia due to insulin resistance and a deficiency in insulin secretion. The global diabetes pandemic relates primarily to T2DM, which is the most prevalent form of diabetes, accounting for over 90% of all cases. Chronic low-grade inflammation, triggered by numerous risk factors, and the chronic activation of the immune system are prominent features of T2DM. Here we highlight the role of blood cells (platelets, and red and white blood cells) and vascular endothelial cells as drivers of systemic inflammation in T2DM. In addition, we discuss the role of microparticles (MPs) in systemic inflammation and hypercoagulation. Although once seen as inert by-products of cell activation or destruction, MPs are now considered to be a disseminated storage pool of bioactive effectors of thrombosis, inflammation, and vascular function. They have been identified to circulate at elevated levels in the bloodstream of individuals with increased risk of atherothrombosis or cardiovascular disease, two significant hallmark conditions of T2DM. There is also general evidence that MPs activate blood cells, express proinflammatory and coagulant effects, interact directly with cell receptors, and transfer biological material. MPs are considered major players in the pathogenesis of many systemic inflammatory diseases and may be potentially useful biomarkers of disease activity and may not only be of prognostic value but may act as novel therapeutic targets.

The Old and the New in the Treatment of Type 2 Diabetes: Focus on the Combination Therapy with Dipeptidyl Peptidase-4 Inhibitors and Metformin

2010 ◽  
Vol 2 ◽  
pp. CMT.S3420 ◽  
Author(s):  
Giovanni Anfossi ◽  
Isabella Russo ◽  
Katia Bonomo ◽  
Mariella Trovati
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Microvascular Complications ◽  
Chronic Complications ◽  
Dipeptidyl Peptidase 4 ◽  
Chronic Hyperglycemia ◽  
Oral Agents ◽  
Dipeptidyl Peptidase 4 Inhibitors

Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease which affects the length and quality of life by severe chronic complications. Chronic hyperglycemia, which is the main alteration in T2DM, is strictly related to microvascular complications (such as retinopathy and nephropathy) and neuropathy, whereas large vessel atherosclerosis is also dependent on lipid and hemostasis abnormalities, arterial hypertension and other known cardiovascular risk factors. An early intervention to control hyperglycemia and to prevent deterioration of β-cell function is considered mandatory in patients with T2DM to minimize the risk of chronic complications. Recently, the availability of new pharmacological agents with different targets, including the activation of the incretin system has allowed the proposal of more effective strategies for early treatment of metabolic alterations in patients with T2DM. This commentary will focus on the role of new oral agents influencing the incretin system and the putative advantages of their co-administration with metformin, an old, effective anti-hyperglycemic agent also able to exert beneficial actions on arterial vessels, reducing the risk of macrovascular-related events. The vasoprotective role of metformin is largely independent of its hypoglycemic action, and has been ascribed to pleiotropic effects.

scholarly journals Role of Sodium-Glucose Cotransporter 2 (SGLT 2) Inhibitors in the Treatment of Type 2 Diabetes

2011 ◽  
Vol 32 (4) ◽  
pp. 515-531 ◽  
Author(s):  
Muhammad A. Abdul-Ghani ◽  
Luke Norton ◽  
Ralph A. DeFronzo
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Microvascular Complications ◽  
Tight Glycemic Control ◽  
Β Cell ◽  
Oral Antidiabetic Agents ◽  
Oral Antidiabetic ◽  
Sodium Glucose Cotransporter

Hyperglycemia plays an important role in the pathogenesis of type 2 diabetes mellitus, i.e., glucotoxicity, and it also is the major risk factor for microvascular complications. Thus, effective glycemic control will not only reduce the incidence of microvascular complications but also correct some of the metabolic abnormalities that contribute to the progression of the disease. Achieving durable tight glycemic control is challenging because of progressive β-cell failure and is hampered by increased frequency of side effects, e.g., hypoglycemia and weight gain. Most recently, inhibitors of the renal sodium-glucose cotransporter have been developed to produce glucosuria and reduce the plasma glucose concentration. These oral antidiabetic agents have the potential to improve glycemic control while avoiding hypoglycemia, to correct the glucotoxicity, and to promote weight loss. In this review, we will summarize the available data concerning the mechanism of action, efficacy, and safety of this novel antidiabetic therapeutic approach.

scholarly journals Low Adiponectin Levels and Increased Risk of Type 2 Diabetes in Patients With Myocardial Infarction

Diabetes Care ◽  
2014 ◽  
Vol 37 (11) ◽  
pp. 3003-3008 ◽  
Author(s):  
Søren Lindberg ◽  
Jan S. Jensen ◽  
Sune H. Pedersen ◽  
Søren Galatius ◽  
Jan Frystyk ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Increased Risk

scholarly journals Genetic basis underlying connection between hyperglycemia and dyslipidemia in Apoe-deficient mice

2015 ◽  
Author(s):  
Qian Wang ◽  
Andrew Grainger ◽  
Ani Manichaikul ◽  
Emily Farber ◽  
Suna Onengut-Gumuscu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Fasting Glucose ◽  
Hdl Cholesterol ◽  
Western Diet ◽  
Chromosome 9 ◽  
Lipid Levels ◽  
Glucose Levels ◽  
Cholesterol Levels

Individuals with dyslipidemia often develop type 2 diabetes, and diabetic patients often have dyslipidemia. It remains to be determined whether there are genetic connections between the 2 disorders. A female F2 cohort, generated from BALB/cJ (BALB) and SM/J (SM) Apoe-deficient (Apoe−/−) strains, was fed a Western diet for 12 weeks. Fasting plasma glucose and lipid levels were measured before and after Western diet feeding. 144 genetic markers across the entire genome were used for analysis. One significant QTL on chromosome 9, named Bglu17 [26.4 cM, logarithm of odds ratio (LOD): 5.4], and 3 suggestive QTLs were identified for fasting glucose levels. The suggestive QTL near the proximal end of chromosome 9 (2.4 cM, LOD: 3.12) was detected when mice were fed chow or Western diet and named Bglu16. Bglu17 coincided with a significant QTL for HDL and a suggestive QTL for non-HDL cholesterol levels. Plasma glucose levels were inversely correlated with HDL but positively correlated with non-HDL cholesterol levels in F2 mice fed either diet. A significant correlation between fasting glucose and triglyceride levels was observed on the Western but not chow diet. Haplotype analysis revealed that ???lipid genes??? Sik3 and Apoc3 were probable candidates for Bglu17. We have identified multiple QTLs for fasting glucose and lipid levels. The colocalization of QTLs for both phenotypes and the sharing of potential causal genes suggest that dyslipidemia and type 2 diabetes are genetically connected.

scholarly journals PROLANIS IMPLEMENTATION EFFECTIVE TO CONTROL FASTING BLOOD SUGAR, HbA1c AND TOTAL CHOLESTEROL LEVELS IN PATIENTS WITH TYPE 2 DIABETES

Jurnal NERS ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 88
Author(s):  
Musfirah Ahmad ◽  
Rini Rachmawaty ◽  
Elly L. Sjattar ◽  
Saldy Yusuf
Keyword(s):  
Type 2 Diabetes ◽  
Total Cholesterol ◽  
Blood Sugar ◽  
Microvascular Complications ◽  
Sampling Technique ◽  
Fasting Blood Sugar ◽  
Cross Sectional ◽  
Cholesterol Levels ◽  
The Mean

Introduction: Diabetes mellitus (DM) is a global disease endemic and causing of 4.6 million deaths in the world. The Indonesian government and health insurance [BPJS Kesehatan] formulate a Chronic Disease Care Program [Program Pengelolaan Penyakit Kronis (PROLANIS)] for type 2 diabetes that aimed at controlling the glycemic status and the risk factors of macro and microvascular complications. The purpose of this study was to analyze the correlation between the implementation of PROLANIS and fasting blood sugar, HbA1c, and total cholesterol levels in patients diagnosed with type 2 diabetes at Antang and Pampang community health centers, Makassar, Indonesia. Methods: This study used descriptive correlation design with cross sectional study approach. Subjects were 40 patients diagnosed with type 2 diabetes who joined PROLANIS at PUSKESMAS Antang and Pampang, Makassar, with sampling technique used was total sampling. The data were analyzed using correlation test to assess the significance (p), the direction (+/-), and the strength of the correlation (r). The implementation of PROLANIS was measured by using the observation sheets developed based on BPJS Kesehatan criteria, while the fasting blood sugar, HbA1c, and total cholesterol levels were checked by laboratory. Results: The mean of the implementation of PROLANIS was 15.05 (SD ± 5.62), while the mean levels of fasting blood sugar, HbA1c, and total cholesterolwere as followed: 191.80 mg/dL (SD ± 85.15); 8.4% (SD ± 2.08); and 192.87 mg/dL (SD ± 45.07). Using the Spearman's rho test, the study result showed that there was a significant and negative correlation between the implementation of PROLANIS and the levels of fasting blood sugar (p= 0.001; r= -0.724), HbA1c (p= 0.001; r= -0.870), and total cholesterol (p= 0.029; r= -0.35) in patients diagnosed with type 2 diabetes at Puskemas Antang and Pampang, Makassar. Conclusions: The optimal implementation of the PROLANIS is very effective to control the levels of fasting blood sugar, HbA1c, and total cholesterol in patients type 2 diabetes. 

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