c-peptide and Atherosclerosis

C-peptide is a cleavage product of proinsulin that acts on different type of cells, such as blood and endothelial cells. C-peptide biological effects may be different in type 1 and type 2 diabetes. Besides, there are further evidence for a functional interaction between C-peptide and insulin. In this way, C-peptide has ambiguous effects, acting as an antithrombotic or thrombotic molecule, depending on the physiological environment and disease conditions. Moreover, C-peptide regulates interaction of leucocytes, erythrocytes, and platelets with the endothelium. The beneficial effects include stimulation of nitric oxide production with its subsequent release by platelets and endothelium, the interaction with erythrocytes leading to the generation of adenosine triphosphate, and inhibition of atherogenic cytokine release. The undesirable action of C-peptide includes the chemotaxis of monocytes, lymphocytes, and smooth muscle cells. Also, C-peptide was related with increased lipid deposits and elevated smooth muscle cells proliferation in the vessel wall, contributing to atherosclerosis. Purpose of this review is to explore these dual roles of C-peptide on the blood, contributing at one side to haemostasis and the other to atherosclerotic process.

Topics: Animals; Atherosclerosis; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Endothelium, Vascular; Erythrocytes; Humans; Nitric Oxide

The incidence and prevalence of diabetes are increasing worldwide. According to the International Diabetes Federation, more than 55 million people in the European region have diabetes, and this number is expected to rise to 64 million in 2030, with most of the cases being due to type 2 diabetes. Diabetes is associated with potentially serious microvascular and macrovascular complications such as nephropathy, neuropathy, and retinopathy as well as coronary artery disease. The pathophysiological mechanism behind this phenomenon is complex. In recent years the impact of proinsulin C-peptide in the development of vascular disease has been highlighted, but it displays differential function in type 1 and type 2 diabetes. In type 1 diabetes, which is characterized by a lack of insulin and C-peptide, supplementation of C-peptide has been shown to improve microvascular complications. In type 2 diabetes, however, C-peptide levels are increased above normal levels and correlate with the occurrence of macrovascular complications and cardiovascular deaths. This review focuses on the impact of C-peptide in the atherogenic process.

Topics: Animals; Atherosclerosis; C-Peptide; Diabetic Angiopathies; Disease Models, Animal; Endothelium, Vascular; Humans; Hyperglycemia; Inflammation; NF-kappa B

Proinsulin C-peptide, released in equimolar amounts with insulin by pancreatic β cells, since its discovery in 1967 has been thought to be devoid of biological functions apart from correct insulin processing and formation of disulfide bonds between A and B chains. However, in the last two decades research has brought a substantial amount of data indicating a crucial role of C-peptide in regulating various processes in different types of cells and organs. C-peptide acts presumably via either G-protein-coupled receptor or directly inside the cell, after being internalized. However, a receptor binding this peptide has not been identified yet. This peptide ameliorates pathological changes induced by type 1 diabetes mellitus, including glomerular hyperfiltration, vessel endothelium inflammation and neuron demyelinization. In diabetic patients and diabetic animal models, C-peptide substitution in physiological doses improves the functional and structural properties of peripheral neurons and protects against hyperglycemia-induced apoptosis, promoting neuronal development, regeneration and cell survival. Moreover, it affects glycogen synthesis in skeletal muscles. In vitro C-peptide promotes disaggregation of insulin oligomers, thus enhancing its bioavailability and effects on metabolism. There are controversies concerning the biological action of C-peptide, particularly with respect to its effect on Na⁺/K⁺-ATPase activity. Surprisingly, the excess of circulating peptide associated with diabetes type 2 contributes to atherosclerosis development. In view of these observations, long-term, large-scale clinical investigations using C-peptide physiological doses need to be conducted in order to determine safety and health outcomes of long-term administration of C-peptide to diabetic patients.

Topics: Animals; Apoptosis; Atherosclerosis; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Disease Models, Animal; Glycogen; Humans; Hyperglycemia; Muscle, Skeletal; Peripheral Nervous System

Diabetes type 2 and insulin resistance are the risk factors for cardiovascular disease. It is already known that atherosclerosis is an inflammatory disease, and a lot of different factors are involved in its onset. C-peptide is a cleavage product of proinsulin, an active substance with a number of effects within different complications of diabetes. In this paper we discuss the role of C-peptide and its effects in the development of atherosclerosis in type 2 diabetic patients.

Topics: Animals; Atherosclerosis; C-Peptide; Diabetes Complications; Diabetes Mellitus; Humans; Inflammation; Insulin; Insulin Resistance; Models, Biological; Proinsulin; Signal Transduction

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Diabetic subjects show a remarkable increase in vascular complications, including myocardial infarction and strokes. The accelerated atherosclerosis in these patients is likely to be multifactorial. In this review, we focus on the advanced glycation end product (AGE)-receptor for AGE (RAGE) axis and the role of C-peptide as a mediator of lesion development. AGEs are proteins or lipids that become glycated after exposure to sugars. By engaging the RAGEs, AGEs induce the expression of proinflammatory mediators in various vascular cell types and are involved in a variety of microvascular and macrovascular complications. In animal models, interruption of the AGE-RAGE interaction reduces lesion size and plaque development and RAGE deficiency in a RAGE(-/-)/apolipoprotein E(-/-) double knockout mouse attenuates the development of atherosclerosis in diabetes. On the other side, patients with type 2 diabetes show increased levels of C-peptide and over the last years various groups examined the effect of C-peptide in vascular cells as well as its potential role in lesion development. Recent data suggest that the proinsulin cleavage product C-peptide could play a causal role in atherogenesis by promoting monocyte and CD4-positive lymphocyte recruitment in early arteriosclerotic lesions and by inducing the proliferation of vascular smooth muscle cells. The following review will summarize these two pathophysiological aspects and discuss on the one hand the potential role of the activated AGE-RAGE axis in diabetes-accelerated atherogenesis and on the other hand the role of C-peptide as a mediator in lesion development in patients with type 2 diabetes.

Topics: Animals; Apolipoproteins E; Atherosclerosis; C-Peptide; CD4-Positive T-Lymphocytes; Cell Proliferation; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Gene Expression Regulation; Glycation End Products, Advanced; Humans; Inflammation Mediators; Mice; Mice, Knockout; Mitogen-Activated Protein Kinases; Monocytes; Myocardial Infarction; Myocytes, Smooth Muscle; Receptor for Advanced Glycation End Products; Stroke

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Various risk factors such as hypertension, dyslipidemia, and a proinflammatory and prothrombotic state contribute to atherogenesis in this high-risk population, but the pathophysiologic mechanisms leading to this characteristic pattern remain largely unexplored. Recent data suggest that the proinsulin cleavage product C-peptide could play a causal role in atherogenesis by promoting monocyte and CD4-positive lymphocyte recruitment in early arteriosclerotic lesions and by inducing the proliferation of vascular smooth muscle cells. The following review will summarize the effects of C-peptide in vascular cells and discuss the potential relevance of such C-peptide effects on atherogenesis in diabetic patients.

Topics: Atherosclerosis; C-Peptide; Diabetic Angiopathies; Humans; Insulin Resistance

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Typically, these patients show increased levels of C-peptide and over the last years various groups examined the effect of C-peptide in vascular cells as well as its potential role in lesion development. While some studies demonstrated beneficial effects of C-peptide, for example, by showing an inhibition of smooth muscle cell proliferation, others suggested proatherogenic mechanisms in patients with type 2 diabetes. Among them, C-peptide may facilitate the recruitment of inflammatory cells into early lesions and promote lesion progression by inducing smooth muscle cell proliferation. The following review will summarize the effects of C-peptide in vascular cells and discuss the potential role of C-peptide in atherogenesis in patients with type 2 diabetes.

Topics: Atherosclerosis; C-Peptide; Cell Division; Chemotaxis, Leukocyte; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Muscle, Smooth, Vascular

To evaluate the lipoprotein profiles, triglycerides and glycemia along with the abdominal fat to explore the risk factors associated with non-diabetic state to IGF, IGT and Type-2 diabetes in Canadian population.. We examined 780 subjects using the ADA and WHO criteria to classify them into groups based on (1) normal glucose tolerance with FBS <6.0 and 2hBS <7.0 mmol/l), (2) IFG; FPG > or =6.1 mmol/l but 2hBS >7.8-11.1 mmol/l; (3) combined IFG/IGT (FPG > or =7.0 mmol/l and 2hBS >11.1 mmol/l). We compared the three groups for glycemia, insulin secretion and insulin sensitivity based on their WHR, abdominal and visceral fat measurements.. The subjects with higher 2 hrs glucose levels 5.2 for NGT vs. 9.1 for IGT and 13.4 mmol/l for NIDDM, p<0.001, apo C-III level (12.8 (DM) vs. 8.9 mg/dl (normal), p<0.001), waist to hip ratio (0.91 (IGT) vs. 0.89 (Normal), p<0.01) and abdominal fat and were found to be highly insulin resistant.. The higher apolipoproteins levels, BMI and abdominal and visceral fat accompanied by poor glycemia were shown to be associated strongly with the metabolic abnormalities. These factors led to the worsening of insulin secretory dysfunction and insulin resistance and were strong predictors of diabetes.

Topics: Adipose Tissue; Atherosclerosis; Biomarkers; Blood Glucose; C-Peptide; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Diabetic Angiopathies; Fatty Acids, Nonesterified; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Metabolic Syndrome; Risk Factors; Triglycerides

Topics: Atherosclerosis; C-Peptide; Cardiovascular Diseases; Cell Proliferation; Diabetic Angiopathies; Humans; Hyperinsulinism; Insulin Resistance; Mitogens; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle

Diabetes is associated with increased oxidative stress and atherosclerosis development. In the present study, we investigated the effects of pomegranate juice (PJ; which contains sugars and potent anti-oxidants) consumption by diabetic patients on blood diabetic parameters, and on oxidative stress in their serum and macrophages. Ten healthy subjects (controls) and 10 non-insulin dependent diabetes mellitus (NIDDM) patients who consumed PJ (50ml per day for 3 months) participated in the study. In the patients versus controls serum levels of lipid peroxides and thiobarbituric acid reactive substances (TBARS) were both increased, by 350% and 51%, respectively, whereas serum SH groups content and paraoxonase 1 (PON1) activity, were both decreased (by 23%). PJ consumption did not affect serum glucose, cholesterol and triglyceride levels, but it resulted in a significant reduction in serum lipid peroxides and TBARS levels by 56% and 28%, whereas serum SH groups and PON1 activity significantly increased by 12% and 24%, respectively. In the patients versus controls monocytes-derived macrophages (HMDM), we observed increased level of cellular peroxides (by 36%), and decreased glutathione content (by 64%). PJ consumption significantly reduced cellular peroxides (by 71%), and increased glutathione levels (by 141%) in the patients' HMDM. The patients' versus control HMDM took up oxidized LDL (Ox-LDL) at enhanced rate (by 37%) and PJ consumption significantly decreased the extent of Ox-LDL cellular uptake (by 39%). We thus conclude that PJ consumption by diabetic patients did not worsen the diabetic parameters, but rather resulted in anti-oxidative effects on serum and macrophages, which could contribute to attenuation of atherosclerosis development in these patients.

Topics: Adult; Aged; Antioxidants; Atherosclerosis; C-Peptide; Carbohydrates; Cells, Cultured; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Flavonoids; Humans; Lipid Peroxidation; Lipoproteins, LDL; Lythraceae; Macrophages; Male; Middle Aged; Monocytes; Oxidative Stress; Phenols; Plant Extracts; Polyphenols; Triglycerides

A literature search was conducted to identify publications addressing the early phases of lipid phenotypes in children and adults with either type 1 diabetes or type 2 diabetes. Medline, EMBASE, and Ovid were searched using the following search terms:

Topics: Adolescent; Atherosclerosis; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin; Lipids; Remission Induction

Coronary artery ectasia (CAE) is an entity frequently associated with atherosclerotic coronary artery disease (CAD) in clinical practice. Although it has common risk factors with atherosclerotic CAD in its development, the pathophysiology of CAE is not fully known and it is not seen in every CAD suggesting that different determinants may play a pivotal role in the development of CAD. This study aimed to reveal the impact of C-peptide and diabetes mellitus (DM) on CAE and the effect of C-peptide and coronary ectasia on long-term outcomes in patients who underwent coronary angiography.. A total of 6611 patients who underwent coronary angiography were followed up retrospectively, and their major adverse cardiovascular event (MACE) status of an average of sixty months was recorded. According to their angiographic features, the patients were divided into two groups those with and without CAE. MACE development was accepted as the primary endpoint.. A total of 552 patients had CAE and MACE developed in 573 patients. Patients with CAE and higher C-peptide levels (Q4 + Q3) showed higher rates of MACE as compared to those without CAE and lower C-peptide levels (Q1 + Q2) (20.8% vs 7.6%; 70.1% vs 29.1%;. Our study revealed that a high C-peptide level is an independent risk factor for CAE and that CAE and C-peptide are independent predictors for the development of MACE.

Topics: Atherosclerosis; C-Peptide; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Diabetes Mellitus; Dilatation, Pathologic; Humans; Retrospective Studies

Introduction: Atherosclerosis is a trigger in the development of cardiovascular disease. Complications of atherosclerosis give reason to search for new criteria, diagnostic concepts, treatment methods and active preventive measures. The aim of our work is to study of the structural changes in the intima-media complex of the common carotid artery, pro-inflammatory cytokines (TNF-α, IL-6) secreted by mononuclear cells; the level of the intercellular adhesion molecule (according to sICAM-1), the level of the C-peptide of the blood, as well as the study of the relationship between these factors affecting the development of atherosclerosis.. Materials and methods: In the group of 110 patients are studied the levels of secretion of TNF-α, IL-6, the soluble intercellular adhesion molecule-1, the level of blood C-peptide, performed of duplex scanning of the brachiocephalic vessels, studied of biopsy of the skin.. Results and conclusions: In the group of patients with atherosclerosis and the accompanying metabolic syndrome, endothelial activation is noted under the influence of risk factors (hyperinsulinemia, arterial hypertension, hypercholesterolemia), accompanied with the activation of mononuclear cells (with marked hyperproduction of proinflammatory cytokines (IL-6) and thickening of the intima-media complex of the common carotid artery with an increase in body weight. Patients with metabolic syndrome develop microangiopathy (edema of endothelial cells, thickening and reduplication of the basement membranes, focal reaction of the pericytes).

Topics: Atherosclerosis; Biomarkers; C-Peptide; Carotid Arteries; Carotid Intima-Media Thickness; Cytokines; Humans; Intercellular Adhesion Molecule-1; Leukocytes, Mononuclear; Tunica Intima

Insulin resistance and type 2 diabetes are independent risk factors for cardiovascular diseases. Levels of C-peptide are increased in these patients and its role in the atherosclerosis progression was studied in vitro and in vivo over the past years. To evaluate the possible use of C-peptide as cardiovascular biomarkers, we designed an observational study in which we enrolled patients with mono- or poly-vascular atherosclerotic disease.. We recruited 431 patients with stable atherosclerosis and performed a yearly follow-up to estimate the cardiovascular and total mortality and cardiovascular events.. We performed a mean follow-up of 56 months on 268 patients. A multivariate Cox analysis showed that C-peptide significantly increased the risk of cardiovascular mortality [Hazard Ratio: 1.29 (95% confidence interval: 1.02-1.65, p < 0.03513)] after adjustment for age, sex, diabetes treatment, estimated glomerular filtration rate and known diabetes status. Furthermore, levels of C-peptide were significantly correlated with metabolic parameters and atherogenic factors.. C-peptide was associated with cardiovascular mortality independently of known diabetes status in a cohort of patients with chronic atherosclerotic disease. Future studies using C-peptide into a reclassification approach might be undertaken to consider its potential as a cardiovascular disease biomarker.

Topics: Aged; Atherosclerosis; Biomarkers; C-Peptide; Cause of Death; Chronic Disease; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Linear Models; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Proportional Hazards Models; Registries; Risk Factors; Time Factors

Postprandial hyperlipidemia and hyperinsulinemia have been thought to play an important role in the development of atherosclerosis. Diabetes mellitus (DM) has an impact on lipid metabolism, however, little is known about the relationship between the postprandial lipid and glucose metabolism in normoglycemic patients with coronary artery disease (CAD).. To compare the postprandial lipid and glucose metabolism in normoglycemic patients with and without CAD, a total of 36 normoglycemic patients: 19 patients with stable CAD (CAD group, age 60.2±11.3 years) and 17 patients without CAD (Non-CAD group, age 60.4±9.6 years) were loaded with a high-fat and high-glucose test meal, and the changes in serum level of the lipid and glucose parameters were monitored before and 0, 2, 4, and 6h later.. In the Non-CAD group, postprandial serum levels of triglycerides (TG) and remnant-like particle cholesterol increased significantly and reached peak levels at the 4th hour and decreased significantly at the 6th hour of observation, whereas those levels in CAD group kept rising during 6h of observation. Although there was no significant difference in the area under the curves (AUCs) for the postprandial plasma glucose levels between CAD and Non-CAD group, the AUCs for the postprandial plasma insulin and C-peptide levels were significantly higher in the CAD group than in the Non-CAD group. The AUCs for postprandial TG levels showed good correlation with those for postprandial plasma insulin and C-peptide levels (insulin: r=0.455, p<0.005; C-peptide: r=0.462, p<0.05).. These findings suggest that postprandial hyperlipidemia and hyperinsulinemia may have a close relationship in CAD patients without DM and might play an important role in the development of atherosclerosis even before the onset of diabetes.

Topics: Aged; Area Under Curve; Atherosclerosis; Blood Glucose; C-Peptide; Cholesterol; Coronary Artery Disease; Diet, High-Fat; Female; Glucose; Humans; Hyperinsulinism; Hyperlipidemias; Insulin; Insulin Resistance; Lipid Metabolism; Lipids; Lipoproteins; Male; Middle Aged; Postprandial Period; Sweetening Agents; Time Factors; Triglycerides

Previous research on the association between fish consumption and incident type 2 diabetes has been inconclusive. In addition, few studies have investigated how fish consumption may be related to the metabolic abnormalities underlying diabetes. Therefore, we examined the association of fish consumption with measures of insulin sensitivity and beta-cell function in a multi-ethnic population.. We examined the cross-sectional association between fish consumption and measures of insulin sensitivity and secretion in 951 non-diabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS). Fish consumption, categorized as <2 vs. ≥2 portions/week, was measured using a validated food frequency questionnaire. Insulin sensitivity (S(I)) and acute insulin response (AIR) were determined from frequently sampled intravenous glucose tolerance tests. Higher fish consumption was independently associated with lower S(I)-adjusted AIR (β = -0.13 [-0.25, -0.016], p = 0.03, comparing ≥2 vs. <2 portions/week). Fish consumption was positively associated with intact and split proinsulin/C-peptide ratios, however, these associations were confounded by ethnicity (multivariable-adjusted β = 0.073 [-0.014, 0.16] for intact proinsulin/C-peptide ratio, β = 0.031 [-0.065, 0.13] for split proinsulin/C-peptide ratio). We also observed a significant positive association between fish consumption and fasting blood glucose (multivariable-adjusted β = 2.27 [0.68, 3.86], p = 0.005). We found no association between fish consumption and S(I) (multivariable-adjusted β = -0.015 [-0.083, 0.053]) or fasting insulin (multivariable-adjusted β = 0.016 [-0.066, 0.10]).. Fish consumption was not associated with measures of insulin sensitivity in the multi-ethnic IRAS cohort. However, higher fish consumption may be associated with pancreatic beta-cell dysfunction.

Topics: Adult; Aged; Animals; Atherosclerosis; Blood Glucose; C-Peptide; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet; Female; Fishes; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Linear Models; Male; Meat; Middle Aged; Multivariate Analysis; Surveys and Questionnaires

Large for gestational age (LAG) neonates who had been exposed to an intrauterine environment of either diabetes or maternal obesity are at increased risk of developing the metabolic syndrome. This can be explained by exposure to high glucose and insulin levels in utero which alter fetal adaptation and programming.. The aim of the study was to evaluate the onset of preclinical atherosclerosis in utero.. We measured umbilical artery wall thickness (ruWT) in the third trimester by obstetric ultrasound and umbilical artery intima-media thickness (uIMT) in pathologic specimens of umbilical cords obtained shortly after delivery and investigated the relation between these measurements and serum insulin level and C-peptide level in cord blood and assessed insulin resistance with the homeostasis model assessment of insulin resistance (HOMA-IR) in infants of diabetic mothers (IDMs), i.e. the study group, which was divided into a large for gestational age group (LGA)-IDM group and an appropriate for gestational age group (AGA)-IDM group and compared with a control group.. The LGA-IDM group had significantly higher insulin (p < 0.001), C-peptide (p = 0.018) and HOMA-IR levels (p < 0.001) compared with the AGA-IDM and control groups. The LGA-IDM group had significantly larger ruWT (p = 0.013) and uIMT (p < 0.001) compared with the AGA-IDM and the control groups. The LGA-IDM group had increased uIMT and ruWT that correlated with the severity of maternal hyperglycemia.. Measurement of ruWT in the third trimester is feasible, reproducible and strongly correlated with pathological serum insulin, C-peptide in cord blood and HOMA-IR levels.

Topics: Adult; Atherosclerosis; C-Peptide; Case-Control Studies; Chi-Square Distribution; Diabetes, Gestational; Diabetic Angiopathies; Female; Fetal Blood; Gestational Age; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, Third; Prospective Studies; Tunica Intima; Tunica Media; Turkey; Ultrasonography; Umbilical Arteries

Infants of diabetic mothers (IDM) are considered as a risk group for atherosclerosis. Increased aortic intima-media thickness has been reported in IDM. The purpose of this study was to assess carotid artery intima-media thickness (CA-IMT), left ventricular mass index (LVMI) and atherosclerotic risk factors in IDM.. Thirty IDM and 25 healthy controls were included in the study. Of these infants, 14 were appropriate-for-gestational age (AGA) and 16 were large-for-gestational age (LGA). CA-IMT and LVMI were obtained by M-mode echocardiographic examination. The relationship between parameters of atherosclerosis and echocardiographic measurements was assessed by Pearson's correlation analysis.. LVMI was higher in LGA IDM when compared to AGA IDM and controls. CA-IMT was not significantly different between the groups and was also not related to atherosclerotic risk factors. Serum lipid and insulin levels were higher in LGA IDM when compared with AGA IDM and controls. There were no correlations between CA-IMT, LVMI and atherosclerotic risk factors.. In contrast to previous reports indicating an increase in CA-IMT in IDM, no differences were found between IDM and controls in this study. Our results indicate that macrosomic IDM are prone to hypertrophic cardiomyopathy but not to atherosclerotic changes in the blood vessels.

Topics: Atherosclerosis; Birth Weight; Blood Glucose; C-Peptide; Carotid Intima-Media Thickness; Case-Control Studies; Cholesterol; Female; Fetal Blood; Heart; Heart Ventricles; Humans; Infant, Newborn; Insulin; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy in Diabetics; Prospective Studies; Statistics, Nonparametric; Triglycerides; Ultrasonography, Doppler

Associations of proinsulin-to-insulin ratios with incident type 2 diabetes have been inconsistent. The use of C-peptide as the denominator in the ratio may allow for better prediction because C-peptide concentration is not affected by hepatic insulin clearance. The objective of this paper was to compare fasting intact and split proinsulin-to-insulin ratios (PI/I, SPI/I) with intact and split proinsulin-to-C-peptide ratios (PI/C-pep, SPI/C-pep) in the prediction of type 2 diabetes.. Prospective data on 818 multi-ethnic adults without diabetes at baseline from the Insulin Resistance Atherosclerosis Study (IRAS) were used. Insulin sensitivity (S(I)) and acute insulin response (AIR) were determined from frequently sampled intravenous glucose tolerance tests, and fasting intact and split proinsulin were measured using specific two-site monoclonal antibody-based immunoradiometric assays. Associations of proinsulin ratios with type 2 diabetes were determined using logistic regression and differences in prediction were assessed by comparing areas under the receiver operating characteristic curve (AROCs).. In logistic regression analyses, PI/C-pep and SPI/C-pep were more strongly associated with incident type 2 diabetes (n = 128) than PI/I and SPI/I, and were significantly better predictors of diabetes in AROC analyses (PI/C-pep = 0.662 vs PI/I = 0.603, p = 0.02; SPI/C-pep = 0.690 vs SPI/I = 0.631, p = 0.01). Both PI/C-pep and SPI/C-pep were associated with type 2 diabetes after adjustment for age, sex, ethnicity, waist circumference, impaired glucose tolerance, lipids and S(I). Both PI/C-pep and SPI/C-pep were significantly associated with incident type 2 diabetes in models that included AIR.. Proinsulin-to-C-peptide ratios were stronger predictors of diabetes in comparison with proinsulin-to-insulin ratios. These findings support the use of C-peptide as the denominator for proinsulin ratios, to more accurately reflect the degree of disproportional hyperproinsulinaemia.

Topics: Atherosclerosis; C-Peptide; Fasting; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Prediabetic State; Predictive Value of Tests; Proinsulin; Prospective Studies; ROC Curve; Waist Circumference

Several studies have shown an association between psoriasis and atherosclerotic risk factors. In this study, we aimed to evaluate endothelial function by flow-mediated dilation (FMD) and insulin resistance by Homeostasis model assessment-insulin resistance (HOMA-IR).. We examined 75 consecutive psoriasis patients and 50 healthy controls. All subjects underwent transthoracic echocardiography and brachial artery imaging for detecting FMD. Fasting blood samples were drawn from all subjects for measuring insulin, C-peptide, fasting blood glucose. HOMA-IR was calculated.. Baseline characteristics of both groups were similar. Twenty-four psoriatic patients had arthritis. Insulin [9.3 (4.0-208.1) vs. 8.2 (2.3-16.5) mcIU/ml, P = 0.016] and C-peptide [2.5 (0.9-20.0) vs. 2.0 (0.9-3.7) ng/ml, P = 0.009] levels were significantly higher in patients with psoriasis than in controls. HOMA-IR [2.1 (0.8-68.9) vs. 1.8 (0.6-8.6), P = 0.036] was significantly higher in patients with psoriasis than in controls. FMD was reduced in patients with psoriasis compared with healthy controls (5.6 +/- 1.9% vs. 10.9 +/- 1.9%, P < 0.001).. This study demonstrated a significant impairment in endothelial function and increased insulin resistance in patients with psoriasis. This is a comprehensive study for identifying atherosclerotic risk factors in psoriasis. We suggest that psoriatic patients should be paid attention for atherosclerosis and its risk factors.

Topics: Adult; Atherosclerosis; Blood Glucose; Brachial Artery; C-Peptide; Echocardiography; Endothelium, Vascular; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Lipids; Male; Middle Aged; Psoriasis; Regional Blood Flow; Risk Factors