scholarly journals Plasma non-esterified fatty acids contribute to increased coagulability in type-2 diabetes through altered plasma zinc speciation

2019 ◽  
Author(s):  
Amélie I. S. Sobczak ◽  
Kondwani G. H. Katundu ◽  
Fladia A. Phoenix ◽  
Siavash Khazaipoul ◽  
Ruitao Yu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Platelet Rich Plasma ◽  
Fibrin Clot ◽  
Plasma Zinc ◽  
Thrombotic Risk ◽  
Esterified Fatty Acids ◽  
Increased Risk ◽  
Zinc Speciation

AbstractZn2+ is an essential regulator of coagulation and its availability in plasma is fine-tuned through buffering by human serum albumin (HSA). Non-esterified fatty acids (NEFAs) transported by HSA reduce its ability to bind/buffer Zn2+. This is important as plasma NEFA levels are elevated in type-2 diabetes mellitus (T2DM) and other diseases with an increased risk of developing thrombotic complications. The presence of 5 mol. eq. of myristate, palmitate, stearate, palmitoleate and palmitelaidate reduced Zn2+ binding to HSA. Addition of myristate and Zn2+ increased thrombin-induced platelet aggregation in platelet-rich plasma and increased fibrin clot density and clot time in a purified protein system. The concentrations of key saturated (myristate, palmitate, stearate) and monounsaturated (oleate, vaccinate) NEFAs positively correlated with clot density in subjects with T2DM (and controls). Collectively, these data strongly support the concept that elevated NEFA levels contribute to an increased thrombotic risk in T2DM through dysregulation of plasma zinc speciation.

scholarly journals The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its Influence on Thrombotic Risk in Obesity and Type 2 Diabetes

2021 ◽  
Vol 22 (18) ◽  
pp. 10140
Author(s):  
Stephen J. Hierons ◽  
Jordan S. Marsh ◽  
Dongmei Wu ◽  
Claudia A. Blindauer ◽  
Alan J. Stewart
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Plasma Zinc ◽  
Disease Mechanism ◽  
Plasma Nefa ◽  
Thrombotic Risk ◽  
Esterified Fatty Acids ◽  
Coagulation Proteins ◽  
Thrombotic Complications

Thrombosis is a major comorbidity of obesity and type-2 diabetes mellitus (T2DM). Despite the development of numerous effective treatments and preventative strategies to address thrombotic disease in such individuals, the incidence of thrombotic complications remains high. This suggests that not all the pathophysiological mechanisms underlying these events have been identified or targeted. Non-esterified fatty acids (NEFAs) are increasingly regarded as a nexus between obesity, insulin resistance, and vascular disease. Notably, plasma NEFA levels are consistently elevated in obesity and T2DM and may impact hemostasis in several ways. A potentially unrecognized route of NEFA-mediated thrombotic activity is their ability to disturb Zn2+ speciation in the plasma. Zn2+ is a potent regulator of coagulation and its availability in the plasma is monitored carefully through buffering by human serum albumin (HSA). The binding of long-chain NEFAs such as palmitate and stearate, however, trigger a conformational change in HSA that reduces its ability to bind Zn2+, thus increasing the ion’s availability to bind and activate coagulation proteins. NEFA-mediated perturbation of HSA-Zn2+ binding is thus predicted to contribute to the prothrombotic milieu in obesity and T2DM, representing a novel targetable disease mechanism in these disorders.

scholarly journals Albumin-mediated alteration of plasma zinc speciation by fatty acids modulates blood clotting in type-2 diabetes

2021 ◽  
Author(s):  
Amélie I. S. Sobczak ◽  
Kondwani G. H. Katundu ◽  
Fladia A. Phoenix ◽  
Siavash Khazaipoul ◽  
Ruitao Yu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Blood Clotting ◽  
Plasma Zinc ◽  
Zinc Speciation

Zn2+ is an essential regulator of coagulation. In plasma, Zn2+ availability is fine-tuned by human serum albumin (HSA). Here we show that elevated fatty acid levels contribute to altered coagulation in type-2 diabetes through Zn2+ mishandling by HSA.

scholarly journals Local Non-Esterified Fatty Acids Correlate With Inflammation in Atheroma Plaques of Patients With Type 2 Diabetes

Diabetes ◽  
2010 ◽  
Vol 59 (6) ◽  
pp. 1292-1301 ◽  
Author(s):  
S. Mas ◽  
R. Martinez-Pinna ◽  
J. L. Martin-Ventura ◽  
R. Perez ◽  
D. Gomez-Garre ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Esterified Fatty Acids

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.

scholarly journals Type 2 Diabetes Associated Changes in the Plasma Non-Esterified Fatty Acids, Oxylipins and Endocannabinoids

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e48852 ◽  
Author(s):  
Dmitry Grapov ◽  
Sean H. Adams ◽  
Theresa L. Pedersen ◽  
W. Timothy Garvey ◽  
John W. Newman
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Esterified Fatty Acids

Non-esterified fatty acids are related with hypofibrinolysis in type 2 diabetes mellitus

1994 ◽  
Vol 8 ◽  
pp. 25-27 ◽  
Author(s):  
H.E. Brussaard ◽  
J.A. Gevers Leuven ◽  
H.M.J. Krans ◽  
P. Meijer ◽  
R. Buytenhek ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Type 2 Diabetes Mellitus ◽  
Esterified Fatty Acids

scholarly journals MICRONUTRIENT DEFICIENCY IN THE PATHOGENESIS OF INSULIN RESISTANCE AND WAYS TO CORRECT IT

2021 ◽  
Vol 78 (4) ◽  
pp. 135-145
Author(s):  
Myroslava Mykytyuk
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Mediterranean Diet ◽  
Micronutrient Deficiency ◽  
The Body ◽  
Omega 3 ◽  
Increased Risk

The review discusses modern views on the pathogenesis of insulin resistance (IR), in particular the role of micronutrient deficiency. The spread of IR in various somatic pathologies indicates an adaptive IR value not only for glucose homeostasis disorders, but also for metabolism in the body as a whole. A promising area of therapy for IR and cardiovascular diseases closely related to obesity and metabolic syndrome (MS) is the use of modulators of products by the human body of endogenous regulatory factors based on omega-3 polyunsaturated fatty acids. The American Diabetic Association supports adherence to a Mediterranean diet enriched with omega-3 polyunsaturated fatty acids. A meta-analysis of 50 clinical, prospective and cross-examination studies has proven the positive protection effect of the Mediterranean diet on MS components. The development of IR can be associated with a deficiency of chromium and magnesium, and the additional intake of these trace elements with nutritional supplements reduces the severity of IR. Pancreatic β-cell dysfunction, IR, increased risk of MS and type 2 diabetes associated with hypomagnemia. It has been shown that the combination of oral food additives chromium (160 icg/day) and magnesium (200 mg/day) reduces IR more effectively than their use separately, which may be associated with increased induction and repression, respectively, the expression of glucose transporter 4 and glycogen-synthase kinase 3. Thus, micronutrients can be used in complex therapy of patients with IR and associated pathological conditions, such as excess body weight/obesity, type 2 diabetes and MS.

scholarly journals Diet, nutrition and the prevention of type 2 diabetes

2004 ◽  
Vol 7 (1a) ◽  
pp. 147-165 ◽  
Author(s):  
NP Steyn ◽  
J Mann ◽  
PH Bennett ◽  
N Temple ◽  
P Zimmet ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Cohort Studies ◽  
Abdominal Obesity ◽  
Diabetes Prevention ◽  
Overweight And Obesity ◽  
Fat Intake ◽  
Increased Risk ◽  
Diet And Lifestyle

AbstractObjectives:The overall objective of this study was to evaluate and provide evidence and recommendations on current published literature about diet and lifestyle in the prevention of type 2 diabetes.Design:Epidemiological and experimental studies, focusing on nutritional intervention in the prevention of type 2 diabetes are used to make disease-specific recommendations. Long-term cohort studies are given the most weight as to strength of evidence available.Setting and subjects:Numerous clinical trials and cohort studies in low, middle and high income countries are evaluated regarding recommendations for dietary prevention of type 2 diabetes. These include, among others, the Finnish Diabetes Prevention Study, US Diabetes Prevention Program, Da Qing Study; Pima Indian Study; Iowa Women's Health Study; and the study of the US Male Physicians.Results:There is convincing evidence for a decreased risk of diabetes in adults who are physically active and maintain a normal body mass index (BMI) throughout adulthood, and in overweight adults with impaired glucose tolerance who lose weight voluntarily. An increased risk for developing type 2 diabetes is associated with overweight and obesity; abdominal obesity; physical inactivity; and maternal diabetes. It is probable that a high intake of saturated fats and intrauterine growth retardation also contribute to an increased risk, while non-starch polysaccharides are likely to be associated with a decreased risk. From existing evidence it is also possible that omega-3 fatty acids, low glycaemic index foods and exclusive breastfeeding may play a protective role, and that total fat intake and trans fatty acids may contribute to the risk. However, insufficient evidence is currently available to provide convincing proof.Conclusions:Based on the strength of available evidence regarding diet and lifestyle in the prevention of type 2 diabetes, it is recommended that a normal weight status in the lower BMI range (BMI 21–23) and regular physical activity be maintained throughout adulthood; abdominal obesity be prevented; and saturated fat intake be less than 7% of the total energy intake.

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