scholarly journals Glycaemic control improves fibrin network characteristics in type 2 diabetes – A purified fibrinogen model

2008 ◽  
Vol 99 (04) ◽  
pp. 691-700 ◽  
Author(s):  
Namukolo Covic ◽  
Francois van der Westhuizen ◽  
Chandrasekaran Nagaswami ◽  
Yelena Baras ◽  
Du Loots ◽  
...  
Keyword(s):  
Glycaemic Control ◽  
Network Formation ◽  
Reference Group ◽  
Factor Xiiia ◽  
Network Structures ◽  
High Blood Glucose ◽  
Fibrin Network ◽  
Lysis Rate ◽  
Fibrin Clots

SummaryDiabetic subjects have been shown to have altered fibrin network structures. One proposed mechanism for this is non-enzymatic glycation of fibrinogen due to high blood glucose. We investigated whether glycaemic control would result in altered fibrin network structures due to decreased fibrinogen glycation. Twenty uncontrolled type 2 diabetic subjects were treated with insulin in order to achieve glycaemic control. Twenty age- and body mass index (BMI)-matched non-diabetic subjects were included as a reference group. Purified fibrinogen, isolated from plasma samples was used for analysis. There was a significant decrease in fibrinogen glycation (6.81 to 5.02 mol glucose/mol fibrinogen) with a corresponding decrease in rate of lateral aggregation (5.86 to 4.62) and increased permeability (2.45 to 2.85 × 10−8 cm2) and lysis rate (3.08 to 3.27 μm/min) in the diabetic subjects after glycaemic control. These variables correlated with markers of glycaemic control. Fibrin clots of non-diabetic subjects had a significantly higher ratio of inelastic to elastic deformation than the diabetic subjects (0.10 vs. 0.09). Although there was no difference in median fiber diameter between diabetic and non-diabetic subjects, there was a small increase in the proportion of thicker fibers in the diabetic samples after glycaemic control. Results from SDS-PAGE indicated no detectable difference in factor XIIIa-crosslinking of fibrin clots between uncontrolled and controlled diabetic samples. Diabetic subjects may have altered fibrin network formation kinetics which contributes to decreased pore size and lysis rate of fibrin clots. Achievement of glycaemic control and decreased fibrinogen glycation level improves permeability and lysis rates in a purified fibrinogen model

scholarly journals BβArg448Lys polymorphism is associated with altered fibrin clot structure and fibrinolysis in type 2 diabetes

2017 ◽  
Vol 117 (02) ◽  
pp. 295-302 ◽  
Author(s):  
Katie A. Greenhalgh ◽  
Mark W. Strachan ◽  
Saad Alzahrani ◽  
Paul D. Baxter ◽  
Kristina F. Standeven ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Plasma Clot ◽  
Lysis Time ◽  
Increased Risk ◽  
Fibrin Network ◽  
Clot Lysis Time ◽  
Fibrin Clots

SummaryBoth type 2 diabetes (T2DM) and Bß448Lys variant of fibrinogen are associated with dense fibrin clots, impaired fibrinolysis and increased cardiovascular risk. It was our objective to investigate whether BßArg448Lys adds to vascular risk by modulating fibrin network structure and/or fibrinolysis in diabetes. The primary aim was to study effects of BßArg448Lys on fibrin network characteristics in T2DM. Secondary aims investigated interactions between gender and BßArg448Lys substitution in relation to fibrin clot properties and vascular disease. Genotyping for BßArg448Lys and dynamic clot studies were carried out on 822 T2DM patients enrolled in the Edinburgh Type 2 Diabetes Study. Turbidimetric assays of individual plasma samples analysed fibrin clot characteristics with additional experiments conducted on clots made from purified fibrinogen, further examined by confocal and electron microscopy. Plasma clot lysis time in Bß448Lys was longer than Bß448Arg variant (mean ± SD; 763 ± 322 and 719 ± 351 seconds [s], respectively; p<0.05). Clots made from plasma-purified fibrinogen of individuals with Arg/Arg, Arg/Lys and Lys/Lys genotypes showed differences in fibre thickness (46.75 ± 8.07, 38.40 ± 6.04 and 25 ± 4.99 nm, respectively; p<0.001) and clot lysis time (419 ± 64, 442 ± 87 and 517 ± 65 s, respectively; p=0.02), directly implicating the polymorphism in the observed changes. Women with Bß448Lys genotype had increased risk of cerebrovascular events and were younger compared with Bß448Arg variant (67.2 ± 4.0 and 68.2 ± 4.4 years, respectively; p=0.035). In conclusion, fibrinogen Bβ448Lys variant is associated with thrombotic fibrin clots in diabetes independently of traditional risk factors. Prospective studies are warranted to fully understand the role of BβArg448Lys in predisposition to vascular ischaemia in T2DM with the potential to develop individualised antithrombotic management strategies.

The effect of glycaemic control on fibrin network structure of type 2 diabetic subjects

2006 ◽  
Vol 96 (11) ◽  
pp. 623-629 ◽  
Author(s):  
Namukolo Covic ◽  
Du Toit Loots ◽  
Francois van der Westhuizen ◽  
Danie van Zyl ◽  
Paul Rheeder ◽  
...  
Keyword(s):  
Glycaemic Control ◽  
Network Structure ◽  
Glucose Control ◽  
Clot Formation ◽  
Fibrinogen Concentration ◽  
Blood Samples ◽  
Fibrin Network ◽  
Kinetics Of ◽  
Fibrin Network Structure

SummaryDiabetic subjects have been shown to have altered fibrin network structures. One possible cause may be fibrinogen glycation resulting in altered structure/function properties. We investigated the effect of glucose control on fibrinogen glycation and fibrin network structure in type 2 diabetes. Blood samples were taken from twenty uncontrolled diabetic subjects at baseline to determine the levels of fibrinogen glycation and fibrin network structures. The subjects were then treated with insulin until blood glucose control was achieved before end blood samples were taken. Twenty age- and BMI-matched non-diabetic subjects were included as a reference group. The diabetic subjects had significantly higher mean fibrinogen glycation at baseline than the non-diabetic subjects (7.84 vs. 3.89 mol glucose / mol fibrinogen;p < 0.001).This was significantly reduced during the intervention (7.84 to 5.24 mol glucose / mol fibrinogen; p< 0.0002) in the diabetic group. Both groups had high mean fibrinogen concentrations (4.25 and 4.02 g/l, diabetic and non-diabetic subjects respectively). There was no difference in fibrinogen concentration, porosity, compaction and kinetics of clot formation between the diabetic subjects and non-diabetic subjects at baseline, nor were there any changes during the intervention despite the reduced fibrinogen glycation. Fibrin network characteristics correlated well with fibrinogen but not with any markers of glycaemic control. Improved glycaemic control resulted in decreased fibrinogen glycation but not fibrinogen concentration. It seems as though porosity, compaction and kinetics of clot formation are more related to fibrinogen concentration than fibrinogen glycation in this model.

Platelet Microtubules in Clot Structure Formation and Contractile Force Generation: Investigation of a Controversy

1986 ◽  
Vol 56 (01) ◽  
pp. 023-027 ◽  
Author(s):  
C J Jen ◽  
L V McIntire
Keyword(s):  
Network Formation ◽  
Contractile Force ◽  
Second Phase ◽  
Clot Retraction ◽  
Forming Process ◽  
Microtubule Organization ◽  
Physiological Processes ◽  
Fibrin Network ◽  
Two Parameters

SummaryWhether platelet microtubules are involved in clot retraction/ contraction has been controversial. To address this question we have simultaneously measured two clotting parameters, clot structural rigidity and isometric contractile force, using a rheological technique. For recalcified PRP clots these two parameters began rising together at about 15 min after CaCl2 addition. In the concentration range affecting microtubule organization in platelets, colchicine, vinca alkaloids and taxol demonstrated insignificant effects on both clotting parameters of a recalcified PRP clot. For PRP clots induced by adding small amounts of exogenous thrombin, the kinetic curves of clot rigidity were biphasic and without a lag time. The first phase corresponded to a platelet-independent network forming process, while the second phase corresponded to a platelet-dependent process. These PRP clots began generating contractile force at the onset of the second phase. For both rigidity and force parameters, only the second phase of clotting kinetics was retarded by microtubule affecting reagents. When PRP samples were clotted by adding a mixture of CaCl2 and thrombin, the second phase clotting was accelerated and became superimposed on the first phase. The inhibitory effects of micro tubule affecting reagents became less pronounced. Thrombin clotting of a two-component system (washed platelets/ purified fibrinogen) was also biphasic, with the second phase being microtubule-dependent. In conclusion, platelet microtubules are important in PRP clotted with low concentrations of thrombin, during which fibrin network formation precedes platelet-fibrin interactions. On the other hand they are unimportant if a PRP clot is induced by recalcification, during which the fibrin network is constructed in the presence of platelet-fibrin interactions. The latter is likely to be more analogous to physiological processes in vivo.

Clinical Experience with Insulin Detemir: Results from the Bangladesh Cohort of Global A1chieve Study

2013 ◽  
Vol 3 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Zafar Ahmed Latif ◽  
Md. Faruque Pathan ◽  
Md. Nazrul Islam Siddiqui ◽  
MA Mannan ◽  
SM Ashrafuzzaman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Glycaemic Control ◽  
Insulin Therapy ◽  
Hba1c Level ◽  
Insulin Detemir ◽  
Entire Cohort ◽  
Baseline Visit ◽  
Effective Option

Objective: To present results from the Bangladesh cohort of the A1chieve study receiving insulin detemir (Levemir) ± oral anti diabetic drugs. Methods: Out of 1093 patients recruited from 49 sites in Bangladesh, 370 were initiated on insulin detemir (Levemir).Study visits were defined as baseline, interim (around 12 weeks from baseline) and final (around 24 weeks from baseline) visit. Results: Glycaemic control was poor in all the groups at baseline. In the entire cohort at 24 weeks, significant reductions from baseline were observed in mean HbA1c (from 10.0 % to 7.2%, p<0.001), FPG (from 10.5 to 6.7 mmol/L, p<0.001) and PPPG (from 15.3 to 8.9 mmol/L, p<0.001) levels. Overall 45.5% of the participants achieved target HbA1c level of < 7% after 24 weeks. The rate of all hypoglycaemic events in the entire cohort reduced from 1.34 (baseline) to 0.12 events/person year after 24 weeks of insulin detemir therapy (p<0.0001). There was no clinically relevant change in body weight in insulin naïve or prior insulin users groups after 24 weeks of insulin detemir therapy. Conclusions: The current study suggests that insulin detemir may be considered as a safe and effective option for initiating insulin therapy for type 2 diabetes in Bangladesh. Birdem Med J 2013; 3(1): 11-18 DOI: http://dx.doi.org/10.3329/birdem.v3i1.17121

INCRETIN AND DIABETES

2011 ◽  
pp. 5-10
Author(s):  
Huu Dang Tran
Keyword(s):  
Type 2 Diabetes ◽  
Cell Proliferation ◽  
Glycaemic Control ◽  
Animal Studies ◽  
Dipeptidyl Peptidase ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Glucose Sensitivity ◽  
Cell Glucose

The incretins are peptide hormones secreted from the gut in response to food. They increase the secretion of insulin. The incretin response is reduced in patients with type 2 diabetes so drugs acting on incretins may improve glycaemic control. Incretins are metabolised by dipeptidyl peptidase, so selectively inhibiting this enzyme increases the concentration of circulating incretins. A similar effect results from giving an incretin analogue that cannot be cleaved by dipeptidyl peptidase. Studies have identified other actions including improvement in pancreatic β cell glucose sensitivity and, in animal studies, promotion of pancreatic β cell proliferation and reduction in β cell apoptosis.

Phytogenic Polyphenols as Glycogen Phosphorylase Inhibitors: The Potential of Triterpenes and Flavonoids for Glycaemic Control in Type 2 Diabetes

2017 ◽  
Vol 24 (4) ◽  
pp. 384-403 ◽  
Author(s):  
Demetres Leonidas ◽  
Joseph Hayes ◽  
Atsushi Kato ◽  
Vassiliki Skamnaki ◽  
Demetra Chatzileontiadou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycaemic Control ◽  
Glycogen Phosphorylase ◽  
Glycogen Phosphorylase Inhibitors

Proportion of type 2 diabetic patients achieving treatment goals and the survey of patient’s attitude towards insulin initiation in patients with inadequate glycaemic control with oral anti-diabetic drugs

2020 ◽  
Vol 16 ◽  
Author(s):  
Shivashankara Bhat ◽  
Mukta Chowta ◽  
Nithyananda Chowta ◽  
Rajeshwari Shastry ◽  
Priyanka Kamath
Keyword(s):  
Glycaemic Control ◽  
Diabetic Patients ◽  
Treatment Goals ◽  
Insulin Initiation ◽  
Type 2 Diabetic Patients ◽  
Number Of Patients ◽  
Patient’S Perception ◽  
Hba1c Target ◽  
Type 2 Diabetic

Background: Type 2 diabetic patients often require insulin therapy for better glycaemic control. However, many of these patients do not receive insulin or do not receive it in a timely manner. Objective: The study was planned to assess the proportion of type 2 diabetic patients attaining treatment goals as per the ADA 2018 guidelines. In addition, patient’s perception on insulin therapy assessed and compared between insulin naïve and insulin initiated type 2 diabetic patients. Methods: The study was conducted in type 2 diabetic patients. Data on their demographics, medical history, duration of diabetes, history of diabetes related complications, the current antidiabetic medication received, most recent glycaemic parameters were noted. Patient’s perception on insulin initiation was recorded through structured interview. Results: A total of 129 patients were included in the study. Around 76.7% patients achieved HbA1c target (<7%). Duration of the disease is much higher in patients who did not meet the HBA1c target. A good number of patients felt that insulin injection would be physically painful (56.5%). Majority of the patients also felt that insulin will make their life less flexible (64.8%). Many patients are having the opinion that insulin is required for life long (73.2%). More number of patients on insulin agreed with the statement ‘Leads to good short-term outcomes as well as long-term benefits’ compared to insulin naïve patients. Conclusion: The results highlight that the proportion of patients achieving recommended glycaemic target is not satisfactory. Many patients who are inadequately controlled with oral antidiabetic drugs were reluctant to initiate insulin.

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