c-peptide and Thrombosis

Twenty-four middle-aged healthy men were given a low-fat high-carbohydrate (5.5 g fat; L), or a moderately-fatty, (25.7 g fat; M) breakfast of similar energy contents for 28 d. Other meals were under less control. An oral glucose tolerance test (OGTT) was given at 09.00 hours on day 1 before treatment allocation and at 13.30 hours on day 29. There were no significant treatment differences in fasting serum values, either on day 1 or at the termination of treatments on day 29. The following was observed on day 29: (1) the M breakfast led to higher OGTT C-peptide responses and higher areas under the curves (AUC) of OGTT serum glucose and insulin responses compared with the OGTT responses to the L breakfast (P < 0.05); (2) treatment M failed to prevent OGTT glycosuria, eliminated with treatment L; (3) serum non-esterified fatty acid (NEFA) AUC was 59% lower with treatment L than with treatment M, between 09.00 and 13.20 hours (P < 0.0001), and lower with treatment L than with treatment M during the OGTT (P = 0.005); (4) serum triacylglycerol (TAG) concentrations were similar for both treatments, especially during the morning, but their origins were different during the afternoon OGTT when the Svedberg flotation unit 20-400 lipid fraction was higher with treatment L than with treatment M (P = 0.016); plasma apolipoprotein B-48 level with treatment M was not significantly greater than that with treatment L (P = 0.086); (5) plasma tissue plasminogen-activator activity increased after breakfast with treatment L (P = 0.0008), but not with treatment M (P = 0.80). Waist:hip circumference was positively correlated with serum insulin and glucose AUC and with fasting LDL-cholesterol. Waist:hip circumference and serum TAG and insulin AUC were correlated with factors of thrombus formation; and the OGTT NEFA and glucose AUC were correlated. A small difference in fat intake at breakfast has a large influence on circulating diurnal NEFA concentration, which it is concluded influences adversely glucose tolerance up to 6 h later.

Topics: Adult; Aged; Area Under Curve; Arteriosclerosis; Blood Glucose; Body Constitution; C-Peptide; Cholesterol, LDL; Dietary Fats; Fatty Acids, Nonesterified; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Risk Factors; Thrombosis; Time Factors; Tissue Plasminogen Activator; Triglycerides

Angiographic high thrombus burden (HTB) is associated with increased adverse cardiovascular events in patients with ST-elevation myocardial infarction (STEMI). HbA1c and C-peptide are two interrelated bioactive markers that affect many cardiovascular pathways. HbA1c exhibits prothrombogenic properties, while C-peptide, in contrast, exhibits antithrombogenic effects. In this study, we aimed to demonstrate the value of combining these two biomarkers in a single fraction in predicting HTB and short-term mortality in patients with STEMI.. 1202 patients who underwent primary percutaneous coronary intervention (pPCI) for STEMI were retrospectively included in this study. The study population was divided into thrombus burden (TB) groups and compared in terms of basic clinical demographics, laboratory parameters and HbA1c/C-peptide ratios (HCR). In addition, short-term mortality of the study population was compared according to HCR and TB categories.. HCR values were significantly higher in the HTB group than in the LTB group (3.5 ± 1.2 vs. 2.0 ± 1.1; P  < 0.001; respectively). In the multivariable regression analysis, HCR was determined as an independent predictor of HTB both as a continuous variable [odds ratio (OR): 2.377; confidence interval (CI): 2.090-2.704; P  < 0.001] and as a categorical variable (OR: 5.492; CI: 4.115-7.331; P  < 0.001). In the receiver operating characteristic (ROC) analysis, HCR predicted HTB with 73% sensitivity and 72% specificity, and furthermore, HCR's predictive value for HTB was superior to HbA1c and C-peptide. The Kaplan-Meier cumulative survival curve showed that short-term mortality increased at HTB. In addition, HCR strongly predicted short-term mortality in Cox regression analysis.. In conclusion, HCR is closely associated with HTB and short-term mortality in STEMI patients.

Topics: C-Peptide; Coronary Angiography; Glycated Hemoglobin; Humans; Percutaneous Coronary Intervention; Retrospective Studies; ST Elevation Myocardial Infarction; Thrombosis; Treatment Outcome

Since the beginning of our pancreas transplant programme, plasma C-peptide was routinely measured daily during the postoperative period. We aimed to evaluate the clinical interest of the C-peptide in the follow-up of pancreas transplantation with a particular look on early graft failure. From 2000 to 2016, 384 pancreas transplantations were evaluated. We collected and compared C-peptide, glycaemia and adjusted C-peptide (aCP; calculated based on C-peptide, glycaemia and creatininaemia) in patients with and without pancreas failure within 30 days after surgery. Variations of glycaemia, C-peptide and aCP between the day before and the day of failure were also recorded. The difference of aCP was significant during the first week after transplantation between patients with thrombosis and those with functional allograft: 63.2 vs. 26.7 on day 1, P = 0.0003; 61.4 vs. 26.7 on day 3, P < 0.0001; 64.8 vs. 5.7 on day 7, P < 0.0001, respectively. Glycaemia had a median increase of 8% on the day of failure, whereas C-peptide and aCP had, respectively, a median decrease of 88% and 83%. C-peptide monitoring after pancreas transplantation may help to identify graft function and early failure. This sensitive biomarker could allow pre-emptive diagnosis of an early thrombotic event allowing the possibility of rescue interventions.

Topics: C-Peptide; Graft Survival; Humans; Pancreas Transplantation; Postoperative Period; Retrospective Studies; Thrombosis; Transplantation, Homologous

Diabetic macro- and microangiopathy are associated with a high risk of vascular complications. The diabetic patient exhibits a pathological coagulation state, with an increased synthesis of coagulation factors and plasminogen activator inhibitor 1 (PAI-1) as well as an enhanced aggregation of platelets. Previous studies have shown that C-peptide can reduce leucocyte-endothelial cell interaction and improve microvascular blood flow in patients with type 1 diabetes. In the present study, we examined in vivo whether C-peptide is able to reduce platelet activation and through that microvascular thrombus formation.. In the microvessels of cremaster muscle preparations taken from normal and diabetic mice, ferric chloride-induced thrombus formation was analysed using intravital fluorescence microscopy.. I.V. administration of C-peptide in high dose (70 nmol/kg), but not in low dose (7 nmol/kg), caused a significant delay in arteriolar and venular thrombus growth in normal and diabetic mice. This effect was repressed by cremaster muscle superfusion with insulin (100 microU/ml) in diabetic animals, but particularly in normal animals. In parallel, immunohistochemistry demonstrated a higher number of PAI-1-expressing vessels in cremaster muscle tissue from control animals and from animals treated with C-peptide and insulin compared with tissue from animals with C-peptide treatment application alone.. We conclude that C-peptide possesses antithrombotic actions in vivo. A causal role of PAI-1 in this scenario needs to be further addressed. However, the reversal of C-peptide action by insulin may invalidate the use of this peptide as a treatment option to improve rheology and microcirculation in diabetic patients.

Topics: Animals; C-Peptide; Diabetes Mellitus; Disease Models, Animal; Dose-Response Relationship, Drug; Flow Cytometry; Humans; Immunohistochemistry; Insulin; Mice; Microcirculation; P-Selectin; Plasminogen Activator Inhibitor 1; Platelet Glycoprotein GPIIb-IIIa Complex; Thrombosis

Insulin degradation was measured by the C-peptide/insulin ratio in 19 patients with portal vein block with extensive spontaneous portal-systemic shunting but minimal liver cell damage: 13 patients with biopsy-proved cirrhosis and 12 controls. Blood obtained fasting and for 3 hr after oral glucose was assayed for glucose, insulin, and C-peptide. Fasting C-peptide and insulin levels in patients with portal vein block and those in controls did not differ. Eight of 13 cirrhotic patients had fasting hyperinsulinemia with a significantly reduced C-peptide/insulin ratio. After glucose administration, the C-peptide/insulin ratio in portal vein block patients with normal aspartate transaminase levels did not differ from control values. In portal vein block patients with elevated asparatate transaminase levels, the C-peptide/insulin ratio was significantly reduced only from 60 min onwards. All the cirrhotic patients showed a significantly reduced C-peptide/insulin ratio after glucose administration. It is suggested that portal-systemic shunting of blood in the presence of a normal liver does not influence hepatic insulin metabolism and that the hyperinsulinemia of cirrhosis is a feature of parenchymal liver damage. In addition, insulin degradation was abnormal in all cirrhotic patients at high insulin secretion rates, even when fasting insulin levels were normal.

Topics: Adolescent; Adult; Aged; Aspartate Aminotransferases; Blood Glucose; C-Peptide; Constriction, Pathologic; Female; Glucose Tolerance Test; Humans; Insulin; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Thrombosis