c-peptide and Cardiovascular-Diseases

The proinsulin connecting peptide, C-peptide, is a cleavage product of insulin synthesis that is co-secreted with insulin by pancreatic beta-cells following glucose stimulation. Recombinant insulin, used in the treatment of diabetes, lacks C-peptide and preclinical and clinical studies suggest that lack of C-peptide may exacerbate diabetes-associated complications. In accordance with this, several studies suggest that C-peptide has beneficial effects in a number of diabetes-associated complications. C-peptide has been shown to prevent diabetic neuropathy by improving endoneural blood flow, preventing neuronal apoptosis and by preventing axonal swelling. In the vascular system, C-peptide has been shown to prevent vascular dysfunction in diabetic rats, and to possess anti-proliferative effects on vascular smooth muscle cells, which may prevent atherosclerosis. However, C-peptide depositions have been found in arteriosclerotic lesions of patients with hyperinsulinemic diabetes and C-peptide has been shown to induce pro-inflammatory mediators, such as nuclear factor kappa B, inducible nitric oxide synthase, and cyclooxygenase-2, indicating that C-peptide treatment could be associated with side-effects that may accelerate the development of diabetes-associated complications. This review provides a brief summary of recent research in the field and discusses potential beneficial and detrimental effects of C-peptide supplementation.

Topics: Animals; Apoptosis; Blood Vessels; C-Peptide; Cardiovascular Diseases; Cell Proliferation; Diabetes Complications; Diabetes Mellitus; Humans; Immune System; Neovascularization, Physiologic; Neurons; Risk Assessment; Treatment Outcome

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

In contrast to earlier views, new data indicate that proinsulin C-peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. C-peptide in nanomolar concentrations binds specifically to cell membranes, probably to a G-protein coupled receptor. Ca(2+)- and MAP-kinase dependent signalling pathways are activated, resulting in stimulation of Na(+), K(+)-ATPase and endothelial nitric oxide (NO) synthase, two enzyme systems known to be deficient in diabetes. C-peptide may also interact synergistically with insulin signal transduction. Studies in intact animals and in patients with type 1 diabetes have demonstrated multifaceted effects. Thus, C-peptide administration in streptozotocin-diabetic animals results in normalization of diabetes-induced glomerular hyperfiltration, reduction of urinary albumin excretion and diminished glomerular expansion. The former two effects have also been observed in type 1 diabetes patients given C-peptide in replacement dose for up to 3 months. Peripheral nerve function and structure are likewise influenced by C-peptide administration; sensory and motor nerve conduction velocities increase and nerve structural changes are diminished or reversed in diabetic rats. In patients with type 1 diabetes, beneficial effects have been demonstrated on sensory nerve conduction velocity, vibration perception and autonomic nerve function. C-peptide also augments blood flow in several tissues in type 1 diabetes via its stimulation of endothelial NO release, emphasizing a role for C-peptide in maintaining vascular homeostasis. Continued research is needed to establish whether, among the hormones from the islets of Langerhans, C-peptide is the ugly duckling that--nearly 40 years after its discovery--may prove to be an endogenous peptide hormone of importance in the treatment of diabetic long-term complications.

Topics: Animals; C-Peptide; Cardiovascular Diseases; Cardiovascular System; Cell Membrane; Diabetes Mellitus; Humans; Nervous System; Nervous System Diseases; Signal Transduction

The diabetogenic action of statins remains a concern, particularly in patients at high risk for diabetes receiving intensive statin therapy. Despite the risk of diabetes with statin use being considered a potential class effect, recent studies have suggested that pitavastatin exerts neutral or favorable effects on diabetogenicity. However, no randomized trial has compared the long-term effects of pitavastatin with those of other statins on glycemic control in populations at high risk for diabetes. Hence, we aim to assess the long-term effects of pitavastatin in comparison with atorvastatin on glucose metabolism in patients with metabolic syndrome (MetS).. The Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM) trial is a prospective, randomized, open-label, active control clinical trial of patients with MetS. We plan to randomize 500 patients with MetS (1:1) to receive high-dose pitavastatin (4 mg) or atorvastatin (20 mg) daily for 24 months. The primary endpoint will be the change in hemoglobin A1c after statin treatment. Secondary endpoints will include the following: (1) changes in biochemical markers, including insulin, C-peptide, homeostasis model assessment of insulin resistance and insulin secretion, and adiponectin; (2) changes in imaging parameters, including carotid elasticity metrics and indices of cardiac function; and (3) the incidence of clinical events, including new-onset diabetes and cardiovascular disease.. In this trial, we will explore whether pitavastatin 4 mg does not disturb glucose metabolism in patients with MetS. It will also provide mechanistic information on statin type-dependent diabetogenic effects and surrogate data regarding vascular and cardiac changes achieved by intensive statin therapy.. ClinicalTrials.gov, NCT02940366 . Registered on 19 October 2016.

Topics: Atorvastatin; Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Clinical Protocols; Diabetes Mellitus; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Metabolic Syndrome; Prospective Studies; Quinolines; Republic of Korea; Research Design; Risk Factors; Time Factors; Treatment Outcome

Wholegrain (WG) consumption is associated with reduced risk of cardiovascular disease, but clinical data on inflammation and immune function is either conflicting or limited. The objective of this study was to assess the impact of increasing WG consumption to at least 80 g/day on markers of inflammation and glucose metabolism and on phenotypic and functional aspects of the immune system, in healthy, middle-aged adults with low habitual WG intake.. Subjects consumed a diet high in WG (>80 g/day) or low in WG (<16 g/day, refined grain diet) in a crossover study, with 6-week intervention periods, separated by a 4-week washout. Adherence to the dietary regimes was achieved by dietary advice and provision of a range of food products, with compliance verified by analysis of plasma alkylresorcinols (ARs).. On the WG intervention, WG consumption reached 168 g/day (P < 0.001), accompanied by an increase in plasma ARs (P < 0.001) and fibre intake (P < 0.001), without affecting other aspects of dietary intake. On the WG arm, there were trends for lower ex vivo activation of CD4(+) T cells and circulating concentrations of IL-10, C-reactive protein, C-peptide, insulin and plasminogen activator inhibitor-1. The percentage of CD4(+) central memory T cells and circulating levels of adipsin tended to increase during the WG intervention.. Despite the dramatic increase in WG consumption, there were no effects on phenotypic or functional immune parameters, markers of inflammation or metabolic markers.

Topics: Adult; Aged; Biomarkers; Body Mass Index; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Cross-Over Studies; Diet; Dietary Fiber; Feeding Behavior; Female; Humans; Insulin; Interleukin-10; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Treatment Outcome; Whole Grains

In patients with diabetes, intensive glycaemic control reduces microvascular complications. However, severe hypoglycaemia frequently complicates intensive glycaemic control. Blood biomarkers that predict successful intensification of glycaemic control in patients with type 2 diabetes without the development of severe hypoglycaemia would advance patient care. In patients who received intensive treatment for type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, we hypothesised that insulin deficiency and islet autoantibodies would be associated with severe hypoglycaemia and failure to achieve near-normal glycaemia (HbA1c <6.0% [42 mmol/mol]).. A nested case-control design was used. Cases (n = 326) were defined as participants having severe hypoglycaemia and failure to achieve an HbA1c level of <6.0% (42 mmol/mol) prior to the ACCORD transition or death. Controls (n = 1,075) were those who achieved an HbA1c level of <6.0% (42 mmol/mol) prior to the ACCORD transition or death without severe hypoglycaemia. Each case was matched (for race, age and BMI) by up to four controls. Baseline insulin deficiency (fasting C-peptide ≤0.15 nmol/l) and islet autoantibodies (glutamic acid decarboxylase [GAD], tyrosine phosphatase-related islet antigen 2 [IA2], insulin [IAA] and zinc transporter 8 [ZnT8]) were measured. Conditional logistic regression with and without adjustment for age, BMI and diabetes duration was used on the full cohort and after removal of patients who died and their respective controls.. Severe hypoglycaemia accompanied by an inability to achieve an HbA1c level of <6.0% (42 mmol/mol) was associated with insulin deficiency (adjusted OR 23.2 [95% CI 9.0, 59.5], p < 0.0001), the presence of IAA autoantibodies or baseline insulin use (adjusted OR 3.8 [95% CI 2.7, 5.3], p < 0.0001), GAD autoantibodies (OR 3.9 [95% CI 2.5, 6.0], p < 0.0001), IA2 autoantibodies (OR 16.7 [95% CI 3.9, 71.6], p = 0.0001) and ZnT8 autoantibodies (adjusted OR 3.9 [95% CI 1.2, 12.4], p = 0.02).. C-peptide and islet autoantibodies may serve as biomarkers to predict the risk of severe hypoglycaemia during intensification of type 2 diabetes treatment.. ClinicalTrials.gov NCT00000620 (original ACCORD study).

Topics: Aged; Autoantibodies; Biomarkers; Body Mass Index; C-Peptide; Cardiovascular Diseases; Case-Control Studies; Cation Transport Proteins; Cohort Studies; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; Humans; Hypoglycemia; Insulin; Islets of Langerhans; Male; Microcirculation; Middle Aged; Receptor-Like Protein Tyrosine Phosphatases, Class 8; Zinc Transporter 8

The effects of twice-daily GLP-1 analogue injections added on continuous subcutaneous insulin infusion (CSII) in patients with poorly controlled type 2 diabetes (T2DM) were unknown. After optimization of blood glucose in the first 3 days by CSII during hospitalization, patients with poorly controlled T2DM were randomized to receive CSII combined with injections of exenatide or placebo for another 3 days. A total of 51 patients (30 in exenatide and 21 in placebo groups) with mean A1C 11% were studied. There was no difference in mean glucose but a significant higher standard deviation of plasma glucose (SDPG) was found in the exenatide group (50.51 ± 2.43 vs. 41.49 ± 3.00 mg/dl, p = 0.027). The improvement of incremental area under the curve (AUC) of glucose and insulinogenic index (Insulin 0-peak/ Glucose 0-peak) in 75 g oral glucose tolerance test was prominent in the exenatide group (p < 0.01). The adiponectin level was significantly increased with exenatide added on (0.39 ± 0.32 vs. -1.62 ± 0.97 μg/mL, in exenatide and placebo groups, respectively, p = 0.045). In conclusion, the add-on of GLP-1 analogue to CSII increased glucose variability and the β - cell response in patients with poorly controlled T2DM.

Topics: Adiponectin; Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endpoint Determination; Exenatide; Female; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Injections, Subcutaneous; Insulin; Insulin Infusion Systems; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Peptides; Risk Factors; Venoms

Plasma calprotectin is a potential biomarker of cardiovascular disease (CVD), insulin resistance (IR), and obesity. We examined the relationship between plasma calprotectin concentrations, CVD manifestations and the metabolic syndrome (MetS) in patients with type 2 diabetes mellitus (T2DM) in order to evaluate plasma calprotectin as a risk assessor of CVD in diabetic patients without known CVD.. An automated immunoassay for determination of plasma calprotectin was developed based on a fecal Calprotectin ELIA, and a reference range was established from 120 healthy adults. Plasma calprotectin concentrations were measured in 305 T2DM patients without known CVD. They were screened for carotid arterial disease, peripheral arterial disease (PAD), and myocardial ischemia (MI) by means of carotid artery ultrasonography, peripheral ankle and toe systolic blood pressure measurements, and myocardial perfusion scintigraphy.. The reference population had a median plasma calprotectin concentration of 2437 ng/mL (2.5-97.5% reference range: 1040-4262 ng/mL). The T2DM patients had significantly higher concentrations (3754 ng/mL, p < 0.0001), and within this group plasma calprotectin was significantly higher in patients with MetS (p < 0.0001) and also in patients with autonomic neuropathy, PAD, and MI compared with patients without (p < 0.001, p = 0.021 and p = 0.043, respectively). Plasma calprotectin was by linear regression analysis found independently associated with BMI, C-reactive protein, and HDL cholesterol. However, plasma calprotectin did not predict autonomic neuropathy, PAD, MI or CVD when these variables entered the multivariable regression analysis as separate outcome variables.. T2DM patients had higher concentrations of plasma calprotectin, which were associated with obesity, MetS status, autonomic neuropathy, PAD, and MI. However, plasma calprotectin was not an independent predictor of CVD, MI, autonomic neuropathy or PAD.. NCT00298844.

Topics: Adult; Aged; Biomarkers; Body Mass Index; C-Peptide; Cardiovascular Diseases; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Leukocyte L1 Antigen Complex; Male; Metabolic Syndrome; Middle Aged; Obesity; Reference Values; Young Adult

This study was designed to compare glucose, lipids, and C-reactive protein (CRP) in women with gestational diabetes mellitus treated with metformin or insulin and in cord plasma of their offspring and to examine how these markers relate to infant size at birth.. Women with gestational diabetes mellitus were randomly assigned to metformin or insulin in the Metformin in Gestational Diabetes trial. Fasting maternal plasma glucose, lipids, and CRP were measured at randomization, 36 weeks' gestation, and 6-8 weeks postpartum as well as in cord plasma. Women with available cord blood samples (metformin n = 236, insulin n = 242) were included.. Maternal plasma triglycerides increased more from randomization to 36 weeks' gestation in women treated with metformin (21.93%) versus insulin (9.69%, P < 0.001). Maternal and cord plasma lipids, CRP, and neonatal anthropometry did not differ between treatments. In logistic regression analyses adjusted for confounders, the strongest associations with birth weight >90th centile were maternal triglycerides and measures of glucose control at 36 weeks.. There were few differences in circulating maternal and neonatal markers of metabolic status and no differences in measures of anthropometry between the offspring of women treated with metformin and the offspring of women treated with insulin. There may be subtle effects of metformin on maternal lipid function, but the findings suggest that treating gestational diabetes mellitus with metformin does not adversely affect lipids or CRP in cord plasma or neonatal anthropometric measures.

Topics: Adult; Blood Glucose; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Diabetes, Gestational; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Leptin; Metformin; Pregnancy; Risk Factors; Triglycerides

Chronic sub-acute inflammation contributes to the pathogenesis of type 2 diabetes mellitus and cardiovascular disease. High doses of salicylate reduce inflammation, glucose and triacylglycerols, and may improve insulin sensitivity, suggesting therapeutic potential in impaired fasting glucose and/or impaired glucose tolerance. This trial aimed to evaluate the effect of salsalate vs placebo on insulin resistance and glycaemia in impaired fasting glucose and/or impaired glucose tolerance.. We conducted a 12 week, two-centre, randomised, placebo-controlled study to evaluate the effect of salsalate (up to 4 g/day) vs placebo on systemic glucose disposal. Secondary objectives included treatment effects on glycaemia, inflammation and cardiovascular risk factors. Seventy-eight participants with impaired fasting glucose and/or impaired glucose tolerance from two VA healthcare systems were enrolled. Randomisation assignment was provided by the coordinating center directly to site pharmacists, and participants and research staff were blinded to treatment assignment.. Seventy-one individuals were randomised to placebo (n = 36) or salsalate (n = 35). Glucose disposal did not change in either group (salsalate 1% [95% CI -39%, 56%]; placebo 6% [95% CI -20%, 61%], p = 0.3 for placebo vs salsalate). Fasting glucose was reduced by 6% during the study by salsalate (p = 0.006) but did not change with placebo. Declines in glucose were accompanied by declines in fasting C-peptide with salsalate. Insulin clearance was reduced with salsalate. In the salsalate group, triacylglycerol levels were lower by 25% (p = 0.01) and adiponectin increased by 53% (p = 0.02) at the end of the study. Blood pressure, endothelial function and other inflammation markers did not differ between groups. Adipose tissue nuclear factor κB (NF-κB) activity declined in the salsalate group compared with placebo (-16% vs 42%, p = 0.005), but was not correlated with metabolic improvements. The frequency of tinnitus was low but tended to be higher with salsalate therapy (n = 4 vs n = 2).. In summary, salsalate therapy was well tolerated, lowered fasting glucose, increased adiponectin and reduced adipose tissue NF-κB activity. These changes were not related to changes in peripheral insulin sensitivity, suggesting additional mechanisms for metabolic improvement.. ClinicalTrials.gov NCT00330733.. Office of Research and Development, Medical Research Service, Department of Veterans Affairs and NIH K24 DK63214.

Topics: Adiponectin; Adipose Tissue; Aged; Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; C-Peptide; Cardiovascular Diseases; Female; Glucose Tolerance Test; Humans; Inflammation; Insulin; Insulin Resistance; Male; Middle Aged; NF-kappa B; Risk Factors; Salicylates; Triglycerides

Diabetic patients have a markedly increased risk of cardiovascular disease compared with non-diabetics. Two drug groups today target insulin resistance; biguanides and thiazolidinediones. In addition, these may have other effects on cardiovascular risk factors. The aim of this study was to evaluate the effects of metformin and rosiglitazone on non-traditional cardiovascular risk factors. Forty type 2 diabetic patients were randomized into metformin and rosiglitazone groups. After receiving the optimal doses, the patients were monitored for 12 weeks. Biochemical parameters, lipid parameters, CRP, insulin, c-peptide, and HbA1c levels were analyzed. VWF, PAI-1, ICAM-1, TNF-α, IL-6, E-selectin, and fibrinogen levels were measured in order to assess coagulation status and endothelial dysfunction. In the metformin group, body mass index, PPG, HbA1c, IL-6, ICAM-1, and TNF-α levels were significantly decreased after 12 weeks compared with the basal levels. IL-6 levels decreased from 75 pg/ml ± 20 to 42 pg/ml ± 9 (P 0.023) and TNF- α levels from 61 pg/ml ± 31 to 39 pg/ml ± 10 (P 0.018). In the rosiglitazone group, FPG, PPG, HbA1c, insulin, HOMA-IR, IL-6, and TNF-α levels decreased significantly after 12 weeks compared with the basal levels. IL-6 levels decreased from 78 pg/ml ± 21 to 41 pg/ml ± 9 (P 0.028) and TNF-α levels from 62 pg/ml ± 19 to 37 pg/ml ± 10 (P 0.012). At the end of the study, no significant differences were determined between groups. Insulin resistance and type 2 diabetes are strongly associated with low grade inflammation. Both metformin and rosiglitazone were effective in controlling inflammatory markers in addition to metabolic parameters.

Topics: Adult; C-Peptide; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelial Cells; Female; Humans; Interleukin-6; Male; Metformin; Middle Aged; Rosiglitazone; Thiazolidinediones; Tumor Necrosis Factor-alpha

The intake of wholemeal foods is consistently associated with reduced risk of type 2 diabetes and cardiovascular diseases in epidemiological studies, although the mechanisms of this association are unclear. Here we aim to compare in healthy subjects the metabolic effects of a diet rich in wholemeal wheat foods versus one based on the same products in refined form.. Fifteen healthy individuals (12 M/3 F), mean age 54.5+/-7.6 years, BMI 27.4+/-3.0 kg/m(2) (mean+/-SD), participated in a randomized sequential crossover study. After 2 weeks run-in, participants were randomly assigned to two isoenergetic diets with similar macronutrient composition, one rich in wholemeal wheat foods and the other with the same foods but in refined form (cereal fibre 23.1 vs. 9.8 g/day). After the two treatment periods (each lasting 3 weeks) plasma glucose and lipid metabolism, antioxidant activity, acetic acid, magnesium, adipokines, incretins and high-sensitivity C-reactive protein (hs-CRP) were measured at fasting and for 4h after a standard test meal (kcal 1103, protein 12%, CHO 53%, fat 35%) based on wholemeal or refined wheat foods, respectively. After the two diets there were no differences in fasting nor in postprandial plasma parameter responses; only glucose was slightly but significantly lower at 240 min after the refined wheat food meal compared to the wholemeal wheat food meal. Conversely, after the wholemeal diet both total (-4.3%; p<0.03) and LDL (-4.9%; p<0.04) cholesterol levels were lower than after the refined wheat diet at fasting.. Consumption of wholemeal wheat foods for 3 weeks reduces significantly fasting plasma cholesterol as well as LDL cholesterol levels in healthy individuals without major effects on glucose and insulin metabolism, antioxidant status and sub-clinical inflammation markers.

Topics: Blood Glucose; Blood Pressure; Body Weight; C-Peptide; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Cross-Over Studies; Diet; Fasting; Female; Food Handling; Gastric Inhibitory Polypeptide; Ghrelin; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Risk Factors; Triticum

Hormone treatment (HT) after the menopause affects lipid and carbohydrate metabolism and inflammation and may modify risk factors relevant for the clinical expression of the metabolic syndrome and cardiovascular disease. Tibolone has pharmacodynamic properties different from other hormone preparations. Here, we compare the effect of combined HT and tibolone on metabolic risk markers for the development of cardiovascular disease.. Postmenopausal women were randomly assigned to 1.25 or 2.5 mg/day of tibolone or oral continuous combined conjugated equine estrogen plus medroxyprogesterone acetate (CEE/MPA). Cardiovascular risk factors were determined at baseline and after 12 months of treatment.. Body mass index and blood pressure were unaffected by the HT. HOMA-IR decreased in the CEE/MPA group (3.69 vs. 3.38; p = 0.02). Treatment with tibolone increased tissue-type plasminogen activator activity (0.87 IU/ml vs. 1.21 IU/ml; p = 0.005) and C-reactive protein (0.83 mg/l vs. 1.88 mg/l; p < 0.001), and decreased plasminogen activator inhibitor activity (6.9 IU/ml vs. 2.0 IU/ml; p < 0.001) and triglycerides (0.99 vs. 0.87 mmol/l; p = 0.004). Both treatments decreased total cholesterol significantly.. CEE/MPA and tibolone have comparable effects on most metabolic risk factors investigated. The effect of tibolone on fibrinolysis and triglycerides suggests that tibolone has a favorable pharmacological profile on these risk factors when compared to CEE/MPA.

Topics: Blood Pressure; Body Composition; C-Peptide; Cardiovascular Diseases; Drug Therapy, Combination; Estrogen Receptor Modulators; Estrogens, Conjugated (USP); Female; Fibrinolysis; Humans; Medroxyprogesterone Acetate; Metabolic Syndrome; Middle Aged; Norpregnenes; Tissue Plasminogen Activator; Treatment Outcome; Triglycerides

Cardiovascular mortality and morbidity are major problems in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to determine whether islet transplantation can improve cardiovascular function in these patients.. We assessed various markers of cardiac function at baseline and 3 years later in a population of 42 type 1 diabetic patients with ESRD who received a kidney transplant. Seventeen patients then received an islet transplant that had persistent function as defined by long-term C-peptide secretion (kidney-islet group). Twenty-five patients did not receive a functioning islet transplant (kidney-only group).. GHb levels were similar in the two groups, whereas the exogenous insulin requirement was lower in the kidney-islet group with persistent C-peptide secretion. Overall, cardiovascular parameters improved in the kidney-islet group, but not in the kidney-only group, with an improvement of ejection fraction (from 68.2 +/- 3.5% at baseline to 74.9 +/- 2.1% at 3 years posttransplantation, P < 0.05) and peak filling rate in end-diastolic volume (EDV) per second (from 3.87 +/- 0.25 to 4.20 +/- 0.37 EDV/s, P < 0.05). Time to peak filling rate remained stable in the kidney-islet group but worsened in the kidney-only group (P < 0.05). The kidney-islet group also showed a reduction of both QT dispersion (53.5 +/- 4.9 to 44.6 +/- 2.9 ms, P < 0.05) and corrected QT (QTc) dispersion (67.3 +/- 8.3 to 57.2 +/- 4.6 ms, P < 0.05) with higher erythrocytes Na(+)-K(+)-ATPase activity. In the kidney-islet group only, both atrial natriuretic peptide and brain natriuretic peptide levels decreased during the follow-up, with a stabilization of intima-media thickness.. Our study showed that type 1 diabetic ESRD patients receiving a kidney transplant and a functioning islet transplant showed an improvement of cardiovascular function for up to 3 years of follow-up compared with the kidney-only group, who experienced an early failure of the islet graft or did not receive an islet graft.

Topics: Atrial Natriuretic Factor; C-Peptide; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Erythrocytes; Female; Graft Survival; Humans; Islets of Langerhans Transplantation; Kidney Transplantation; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Sodium-Potassium-Exchanging ATPase

To evaluate the influence of 2 continuous combined estrogen-progestin replacement products, compared with unopposed estrogen and placebo, on cardiovascular risk markers in postmenopausal women in a randomized, double-blind, placebo-controlled trial.. Two hundred seventy healthy postmenopausal women were randomly assigned to 1 of 4 treatment groups: placebo, unopposed 17-beta estradiol (1 mg), 1 mg of 17-beta estradiol with 0.25 mg of norethindrone acetate, or 1 mg of 17-beta estradiol with 0.5 mg of norethindrone acetate. The primary outcome variable was change from baseline in low-density lipoprotein cholesterol concentration. Additional outcome variables included changes in other serum lipid levels, hemostatic variables, and indicators of carbohydrate metabolism.. The low-density lipoprotein cholesterol level was reduced to a similar degree in all groups receiving active treatment (10%-14% from baseline; P =.001 for 17-beta estradiol with 0.5 mg of norethindrone acetate, P =.004 for 17-beta estradiol with 0.25 mg of norethindrone acetate, and P =. 001 for 1 mg of 17-beta estradiol vs placebo). Compared with unopposed 17-beta estradiol, 17-beta estradiol with 0.5 mg of norethindrone acetate enhanced the reductions in total cholesterol and apolipoprotein B levels (P<.01 vs 17-beta estradiol). 17-beta Estradiol plus norethindrone blunted or reversed the increases in levels of high-density lipoprotein cholesterol, apolipoprotein A-I, and triglycerides produced by 17-beta estradiol alone. Effects of 17-beta estradiol plus norethindrone on hemostatic variables were similar to those of 17-beta estradiol except for factor VII activity, which was significantly reduced with 17-beta estradiol combined with 0.25 mg (P<.01) and 0.5 mg (P<.05) of norethindrone acetate. 17-beta Estradiol plus norethindrone appeared to blunt reductions in C-peptide and insulin levels produced by unopposed 17-beta estradiol but did not elevate these values compared with placebo.. 17-beta Estradiol plus norethindrone produced favorable changes in most cardiovascular risk markers evaluated and has a profile distinct from that of unopposed 17-beta estradiol. The impact of these differences on cardiovascular events warrants investigation. Arch Intern Med. 2000;160:3315-3325.

Topics: Aged; Apolipoprotein A-I; Blood Coagulation Factors; Blood Glucose; C-Peptide; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Double-Blind Method; Drug Administration Schedule; Estradiol; Estrogen Replacement Therapy; Female; Glycated Hemoglobin; Humans; Insulin; Lipids; Lipoprotein(a); Middle Aged; Norethindrone; Norethindrone Acetate; Postmenopause; Risk Factors; Treatment Outcome; Triglycerides

The fundamental role of insulin resistance for metabolic changes linked to cardiovascular disease and type 2 diabetes is increasingly recognized. Oral contraceptives (OC) may affect insulin sensitivity, and a detailed characterization hereof, as well as the secondary effects on related metabolic systems, are relevant in the evaluation of the risk of developing vascular disorders or diabetes in OC users. We studied insulin sensitivity index (S(I)), glucose effectiveness (S(g)), and insulin response in young, healthy women by frequently sampled intravenous glucose tolerance tests before and after randomization to 6 months of treatment with ethinyl estradiol in triphasic combination with norgestimate (n = 17) or gestodene (n = 20). Measurements of fasting triglycerides and antigen concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were also included. Both compounds increased fasting plasma insulin and reduced S(i) but did not affect S(g). The relationships between S(i) and insulin response were unchanged. No consistent correlation between insulin sensitivity and triglycerides, t-PA, or PAI-1 were demonstrated before or during treatment. We conclude that the treatments were followed by a compensated decrease in insulin sensitivity that was unrelated to changes in triglycerides, t-PA, or PAI-1 antigen.

Topics: Adult; Antibodies, Monoclonal; Blood Glucose; C-Peptide; Cardiovascular Diseases; Contraceptives, Oral, Synthetic; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Ethinyl Estradiol; Female; Fibrinolysis; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Norgestrel; Plasminogen Activator Inhibitor 1; Prospective Studies; Tissue Plasminogen Activator; Triglycerides

To determine whether the lipoprotein response to weight loss in obese patients with type 2 diabetes can be improved by modifying the macronutrient composition of the commonly prescribed low-fat, high-carbohydrate (CHO) hypocaloric diet.. Nine obese patients with type 2 diabetes were treated with a monounsaturated fatty acid (MUFA)-enriched weight-reducing formula diet and compared with eight obese patients with type 2 diabetes treated with a low-fat, high-CHO weight-reducing formula diet. Weight loss ensued for 6 weeks, followed by 4 weeks of refeeding using isocaloric formulas enriched with MUFA or CHO, respectively. Fasting blood samples were obtained to measure plasma lipoproteins and LDL susceptibility to oxidation (measured as lag time: time required to induce in vitro formation of conjugated dienes).. At baseline, there were no differences between the groups in plasma lipids, lipoproteins, or LDL susceptibility to oxidation. Weight loss was similar between the groups. Dieting resulted in decreases in total plasma cholesterol, LDL, HDL, triglycerides, and apolipoproteins A and B (P < 0.05), but the MUFA group manifested a greater decrease in total cholesterol, triglycerides, and apolipoprotein B and a smaller decrease in HDL and apolipoprotein A than the CHO group (P < 0.05). Improvements in these parameters were sustained during refeeding. After dieting, lag time was prolonged in the MUFA group (208 +/- 10 min) compared with the CHO group (146 +/- 11 min; P < 0.05). Lag time was prolonged further during refeeding in the MUFA group (221 +/- 13 min, P = 0.10), while the CHO group remained unchanged (152 +/- 9 min, P < 0.05). Lag time correlated strongly with the oleic acid content of LDL after dieting and refeeding (r = 0.74 and r = 0.93, respectively; both P < 0.001).. Macronutrient content is an important determinant of the lipoprotein response to weight loss in obese patients with type 2 diabetes. MUFA-enriched hypocaloric diets potentiate the beneficial effects of weight loss to ameliorate cardiovascular risk factors in obese patients with type 2 diabetes.

Topics: Apolipoproteins; Blood Glucose; C-Peptide; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Dietary Carbohydrates; Dietary Fats, Unsaturated; Energy Intake; Fatty Acids, Monounsaturated; Female; Humans; Insulin; Lipids; Lipoproteins; Male; Middle Aged; Obesity; Regression Analysis; Risk Factors; Triglycerides; Weight Loss

To investigate the effects on serum lipids, plasma fibrinogen, plasma insulin, plasma C-peptide and blood glucose, of smoking cessation after 4 months. To develop a group-based smoking intervention programme in primary health care.. Twenty health centres in primary health care in southern Sweden.. Four hundred habitual smokers (> 10 cigarettes per day-1, > 10 years), recruited by advertisement in local papers.. The smokers were randomized, after stratification for age and sex, to one intervention group (n = 200) and one control group (n = 200). The intervention group was offered supportive group sessions and free nicotine supplementation (patches, chewing gum).. All participants were investigated at the start and after 4 months (medical history, physical examination, laboratory evaluation). Blood samples were drawn for determination of glucose, insulin and C-peptide, both in the fasting state and during an oral glucose tolerance test (OGTT), and for measurement of lipoproteins, fibrinogen, nicotine and cotinine.. In the intervention group 98 of the subjects (48%) had quit smoking after 4 months. They were compared with the 156 subjects in the control group (91%) who were still daily smokers during the whole period. There were no significant differences in any variable between the two (total) experimental groups at baseline. Plasma nicotine and cotinine decreased (P < 0.001) in the intervention group following smoking cessation, and weight increased by 2.7 kg. In the intervention group HDL-cholesterol increased by 11% (P < 0.001), whereas HbA1c increased by 2% (P < 0.05) only in the control group. No changes occurred in levels of glucose, insulin, C-peptide and fibrinogen.. The smoking cessation programme had a success rate of almost 50% over 4 months. Smoking cessation was associated with a marked increase in HDL-cholesterol levels but did not affect glucose tolerance. A concomitant weight increase may have blunted any independent beneficial effect of smoking cessation on glucose metabolism.

Topics: Adult; Blood Glucose; C-Peptide; Cardiovascular Diseases; Feasibility Studies; Female; Fibrinogen; Humans; Insulin; Lipids; Male; Middle Aged; Psychotherapy, Group; Risk Factors; Smoking; Smoking Cessation; Weight Gain

Altogether 86 patients with recently diagnosed NIDDM, aged 40-64 years were randomised after 3 months of basic education to intensified diet (Int. group, 21 men, 19 women) or conventional treatment groups (Conv. group, 28 men, 18 women). The aim was to examine whether an intensified diet education would result in a better metabolic control and greater reduction in cardiovascular risk factors than conventional treatment for obese patients with recently diagnosed type 2 diabetes mellitus. Furthermore, both groups were re-examined after a second year of observation period to find out the maintenance of the results after intervention. After basic education, Int. group participated in 12-months diet education, while Conv. group was treated in local health centres. During the intervention period, only Int. group showed further weight reduction. Only 20% of patients in Int. and 6% of patients in Conv. group had BMI < 27 kg/m2 at the end of the intervention, while 75% of patients in Int. and 52% of patients in Conv. group had achieved a good metabolic control (fasting blood glucose < 6.7 mmol/l; P = 0.005 between groups). Serum total cholesterol did not change significantly, but the changes in HDL-cholesterol, triglycerides and apolipoprotein B level were significant in Int. group only. The proposed acceptable values for serum lipids were achieved by 52 to 88% of patients without major differences between the two groups. During the second year of observation, weight gained in both groups and a deterioration was seen in metabolic control. Despite that a greater proportion of patients in the Int. group still was in good metabolic control (55.3% vs. 31.8%, P = 0.016), furthermore Int. group was receiving less frequently oral drugs for hyperglycaemia than Conv. group. No differences in serum lipids were observed between the groups after the observation period. HDL-cholesterol showed a persistent improvement in both groups.

Topics: Adult; Apolipoprotein A-I; Apolipoproteins B; Blood Glucose; Blood Pressure; C-Peptide; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diet, Diabetic; Female; Follow-Up Studies; Glucagon; Glycated Hemoglobin; Humans; Male; Middle Aged; Sex Factors; Triglycerides

To investigate the effects of metformin on glycemic control, insulin resistance, and risk factors for cardiovascular disease in NIDDM subjects from two ethnic groups (Caucasian and Asian) with different risks of cardiovascular disease.. A total of 27 subjects with NIDDM (17 Caucasian, 10 Asian) were given metformin and placebo each for a 12-wk period in a randomized, double-blind, placebo-controlled crossover study, and the dose was increased after 1 and 6 wk, up to a maximum of 850 mg three times a day. Insulin resistance, glycemic control, and cardiovascular risk factors were assessed before and after each treatment phase. The end of 12 wk of metformin treatment was compared with the end of 12 wk of placebo treatment.. Metformin treatment was associated with significant improvement in FPG at 6 and 12 wk (mean difference at 12 wk, -3.08 mM, 95% CI -4.12 to -2.04 mM, P < 0.0001) and MCR of glucose (median difference 0.40 ml.kg-1.min-1, interquartile range -0.10 to 1.30 ml.kg-1.min-1, P = 0.036). beta-cell function calculated by HOMA also improved significantly (median difference 14%, interquartile range 7 to 23%, P < 0.001). Total triglyceride (median difference -0.2 mM, interquartile range -0.6 to 0.1 mM, P = 0.034), total cholesterol (mean difference -0.52 mM, 95% CI -0.83 to -0.22 mM, P = 0.002), and LDL cholesterol (mean difference -0.40 mM, 95% CI -0.64 to -0.16 mM, P = 0.002) fell significantly on metformin treatment, whereas no significant changes were observed in HDL cholesterol. PAI-1 activity fell significantly (mean difference -5.3 AU/ml, 95% CI -8.2 to -2.4 AU/ml, P = 0.001), but plasma fibrinogen concentrations and platelet function, spontaneous or agonist induced, were unaffected. UAE was lower on metformin treatment (median difference -2.4 micrograms/min, interquartile range -4.4 to -0.2 micrograms/min, P = 0.004), but metformin had no significant effect on BP. The effects of metformin on glycemic control and cardiovascular risk factors were generally similar in the two ethnic groups.. These findings indicate that metformin treatment improves glycemic control, and lowers insulin resistance and risk factors for cardiovascular disease, including PAI-1, and may therefore be useful in the long-term management of NIDDM subjects who have a high risk of cardiovascular disease.

Topics: Albuminuria; Asia; Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Ethnicity; Fructosamine; Hexosamines; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Metabolic Clearance Rate; Metformin; Plasminogen Activator Inhibitor 1; Platelet Aggregation; Risk Factors; Triglycerides; United Kingdom; White People

Previous studies on the relationship between fructose intake and cardiometabolic biomarkers have yielded inconsistent results, and the metabolic effects of fructose are likely to vary across food sources such as fruit versus sugar-sweetened beverages (SSB).. We aimed to examine associations of fructose from 3 major sources (SSB, fruit juice, and fruit) with 14 insulinemic/glycemic, inflammatory, and lipid markers.. We utilized cross-sectional data from 6858 men in the Health Professionals Follow-up Study, 15,400 women in NHS, and 19,456 women in NHSII who were free of type 2 diabetes, CVDs, and cancer at blood draw. Fructose intake was assessed via a validated FFQ. Multivariable linear regression was used to estimate the percentage differences of biomarker concentrations according to fructose intake.. We found a 20 g/d increase in total fructose intake was associated with 1.5%- 1.9% higher concentrations of proinflammatory markers plus 3.5% lower adiponectin, as well as 5.9% higher TG/HDL cholesterol ratio. Unfavorable profiles of most biomarkers were only associated with fructose from SSB and juice. In contrast, fruit fructose was associated with lower concentrations of C-peptide, CRP, IL-6, leptin, and total cholesterol. Substituting 20 g/d fruit fructose for SSB fructose was associated with 10.1% lower C-peptide, 2.7%-14.5% lower proinflammatory markers and 1.8%-5.2% lower blood lipids.. Beverage fructose intake was associated with adverse profiles of multiple cardiometabolic biomarkers.

Topics: Beverages; Biomarkers; C-Peptide; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Fructose; Humans; Male

We investigated the relationship between hs-CRP, a marker of low-grade inflammation, alone or in combination with C-peptide, a marker of hyperinsulinemia/insulin resistance, and risk for cardiovascular events (CVEs) and mortality in patients recently diagnosed with type 2 diabetes (T2D).. In patients with recent-onset T2D, we measured serum hs-CRP (n = 7,301) and C-peptide (n = 5,765) in the prospective Danish Centre for Strategic Research in Type 2 Diabetes cohort study. Patients with no prior CVE (n = 6,407) were followed until first myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and all patients (n = 7,301) were followed for all-cause mortality. We computed adjusted hazard ratios (aHRs) by Cox regression and tested for the interaction between hs-CRP and C-peptide.. During follow-up (median 4.8 years), high (>3 mg/L) versus low (<1 mg/L) hs-CRP was associated with increased CVE risk (aHR 1.45 [95% CI 1.07-1.96]) and with even greater risk of all-cause mortality (2.47 [1.88-3.25]). Compared with patients with low hs-CRP (≤3 mg/L) and low C-peptide (<1,470 pmol/L), those with high levels of both biomarkers had the highest CVE (1.61 [1.10-2.34]) and all-cause mortality risk (2.36 [1.73-3.21]). Among patients with high C-peptide, risk of CVEs did not differ by low or high hs-CRP, whereas risk of all-cause mortality did.. The finding of high hs-CRP as a stronger prognostic biomarker of all-cause mortality than of CVEs may facilitate improved early detection and prevention of deadly diseases besides CVEs. Conversely, elevated C-peptide as a strong CVE biomarker supports the need to target hyperinsulinemia/insulin resistance in T2D CVE prevention.

Topics: Biomarkers; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Denmark; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Myocardial Infarction; Prospective Studies; Risk Factors

Metabolic syndrome (Syndrome X, insulin resistance syndrome) consists of a constellation of metabolic abnormalities that confer increased risk of cardiovascular disease and diabetes mellitus. Serum uric acid and end product of purine metabolism, has been shown to be associated with an increased risk of hypertension, cardiovascular disorder and chronic kidney disease. Excess of intra abdominal or visceral adipose and not the amount of subcutaneous abdominal fat which is the key correlate of the metabolic abnormalities observed in overweight/obese patients. It is well documented that high level of insulin are associated with elevated "connecting peptide"(c-peptide) levels as both are produced in equimolar Amounts since metabolic syndrome is a well established major risk factor preceding the onset of type 2 diabetes mellitus, pre and post prandial c peptide and itís correlation with serum uric acid further strengthens this understanding and may help take preventive measures to delay/reverse the onset of type 2 diabetes mellitus.. This is a cross sectional study conducted on 60 patients with metabolic syndrome satisfying inclusion and exclusion criteria admitted in hospitals attached to Bangalore Medical College & Research Institute. All necessary investigations were done. The patients with other co-morbid condition that could affect nutritional status (diabetes mellitus, sepis, congestive heart failure, cancer) and pregnant females were excluded. Anthropometric measures, biochemical parameters were used for correlation with fasting c-peptide and post prandial c-peptide with serum uric acid in metabolic syndrome.. Patients with metabolic syndrome We can observe that the Blood urea level showed positive correlation with uric acid level (p value 0.276), uric acid showed positive correlation with fasting c-peptide (p value 0.001) and post prandial c-peptide with (p value < 0.023), very low density lipoprotein showed positive correlation with post prandial c-peptide (p value < 0.022), very low density lipoprotein showed positive correlation with uric acid (p value< 0.002) triglyceride showed postive correlation with uric acid (p value < 0.001,) body mass index showed positive correlation with post prandial c peptide (p value < 0.002), body mass index showed positive correlation with uric acid (p value < 0.006).. Patients diagnosed as Metabolic syndrome after clinical, biochemical and anthropometric findings should be investigated for c-peptide in them which can be used as additional diagnosis factor in metabolic syndrome post prandial cpeptide being a better investigation when compared to fasting c-peptide. References Iliesiu A, Campeanu A, Dusceac D. Serum uric acid and cardiovascular disease. Maedica (Bucur) 2021;5(3):186-192. Abdullah A, Hasan H, Raigangar V, et al. C-Peptide versus insulin: relationships with risk biomarkers of cardiovascular disease in metabolic syndrome in young arab females. Int J Endocrinol 2012;2012:420792.

Topics: Body Mass Index; C-Peptide; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; India; Insulin; Metabolic Syndrome; Uric Acid

This study sought to examine the impacts of a high dietary fiber cereal meal in comparison to conventional dietary management for diabetes on body weight, distribution of adipose tissue, and cardiovascular risk among individuals diagnosed with type 2 diabetes (T2DM).. A cohort of 120 patients diagnosed with T2DM was enlisted as the study population and divided into two groups using a ratio of 2:1-namely, the W group (n=80) and the U group (n=40). The U group (control) received usual diet, while the W group (intervention) incorporated a high dietary fiber cereal meal in place of their regular staple food in addition to adhering to conventional diabetes dietary recommendations. The high dietary fiber cereal meal was based on whole grains, traditional Chinese medicinal foods, and prebiotics. A subsequent follow-up period of 3 months ensued, during which diverse parameters such as body mass index (BMI),waist-hip ratio (WHR), glycated hemoglobin (HbA1c),fasting blood glucose(FBG),C-peptide levels, blood pressure, blood lipids, high-sensitivity C-reactive protein (hsCRP),10-year cardiovascular disease (CVD) risk, and Lifetime CVD risk were assessed before and after the intervention.. Among the participants, a total of 107 successfully completed the intervention and follow-up, including 72 individuals from the W group and 35 from the U group. Following the intervention, both cohorts exhibited decrease in BMI, WHR, HbA1c, FBG, blood pressure, and blood lipid levels in contrast to their initial measurements. Remarkably, the improvements in BMI, WHR, HbA1c, FBG, total cholesterol (TC), triglycerides(TG), low-density lipoprotein cholesterol (LDL-C), the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C), and the ratio of 2-hour C-peptide (2hCP) to fasting C-peptide (FCP) were more marked within the W group, exhibiting statistically significant disparities (. The intervention centred on a cereal-based dietary approach showcased favourable outcomes with regard to body weight, adipose distribution, and cardiovascular risk in overweight individuals grappling with T2DM.

Topics: Body Weight; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Diabetes Mellitus, Type 2; Dietary Fiber; Edible Grain; Glycated Hemoglobin; Heart Disease Risk Factors; Humans; Lipids; Obesity; Risk Factors; Triglycerides

To determine the prognostic value of C-peptide in long-term nonalcoholic fatty liver disease (NAFLD) mortality.. A total of 4670 participants with NAFLD were enrolled in this study. Multivariable Cox regression models evaluated the links between C-peptide levels and all-cause and cardiovascular disease (CVD) mortality risk using adjusted hazard ratios (aHR). In addition, a two‑piecewise Cox model with penalized splines was adapted to investigate the nonlinear relationships between C-peptide and mortality.. After a mean follow‑up period of 20 years, 1714 deaths from all causes were recorded. In an adjusted Cox regression analysis, using the low C-peptide group as the reference (quartile 1), higher C-peptide (quartile 4) was notably associated with increased all-cause mortality (aHR =1.39; 95% CI: 1.18-1.65) and CVD death (aHR = 1.97; 95% CI: 1.41-2.76). Spline analyses demonstrated that the association between C-peptide levels and all-cause mortality was U-shaped, with a threshold value of 0.41 nmol/L. Below the threshold, every one-unit increment in C-peptide had a 70% reduced risk of all-cause death (aHR = 0.30, 95% CI: 0.1-0.7). Above the threshold, the C-peptide levels were associated with a higher probability of all-cause death (aHR = 1. 3, 95% CI:1.2-1.4).. In the US NAFLD population defined by ultrasound, a U-shaped association was detected between baseline serum C-peptide level and all-cause mortality.

Topics: C-Peptide; Cardiovascular Diseases; Humans; Non-alcoholic Fatty Liver Disease; Proportional Hazards Models; Regression Analysis; Risk Factors

Recent literature reported the biological role of C-peptide, but this role is still controversial and unclear. The primary aim of this study was to investigate associations between C-peptide and cardiovascular biomarkers as well as events.. A total of 55636 participants who had a health examination from 2017 to 2021 were included. Of them, 6727 participants visited the hospital at least twice. Cardiovascular biomarkers like high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured and their relationships with fasting C-peptide were evaluated for all participants. Cardiovascular events were obtained during the last visit and their associations with C-peptide were evaluated for those participants who visited the hospital at least twice.. Among the included participants, 11.1% had a previous type 2 diabetes mellitus (T2DM). In the participants without previous T2DM, the relationships between fasting C-peptide and hs-CRP and hs-cTnT were negative if the value of fasting C-peptide was < 1.4 ng/mL and positive if the value was ≥ 1.4 ng/mL. These relationships remained significant after adjusting for hemoglobin A1c, insulin resistance index, and its interaction with C-peptide, even if the participants were stratified by glucose metabolism status or levels of insulin resistance index. Hazard ratios of cardiovascular events were first decreased and then increased with the increasing of baseline C-peptide levels, though these associations became unsignificant using the multivariate Cox regression model. Unlike the participants without previous T2DM, the associations of C-peptide with cardiovascular biomarkers and events were not significant in the patients with previous T2DM.. The associations of C-peptide with cardiovascular biomarkers and events were different between the participants without previous T2DM and those with previous T2DM. The effect of C-peptide on cardiovascular risk may be bidirectional, play a benefit role at a low level, and play a harmful role at a high level in the nondiabetic adults and the patients with newly diagnosed T2DM.

Topics: Adult; Biomarkers; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucose; Glycated Hemoglobin; Heart Disease Risk Factors; Humans; Insulin Resistance; Retrospective Studies; Risk Factors; Troponin T

Low C-peptide levels, indicating beta-cell dysfunction, are associated with increased within-day glucose variation and hypoglycemia. In advanced type 2 diabetes, severe hypoglycemia and increased glucose variation predict cardiovascular (CVD) risk. The present study examined the association between C-peptide levels and CVD risk and whether it can be explained by visit-to-visit glucose variation and severe hypoglycemia.. Fasting C-peptide levels at baseline, composite CVD outcome, severe hypoglycemia, and visit-to-visit fasting glucose coefficient of variation (CV) and average real variability (ARV) were assessed in 1565 Veterans Affairs Diabetes Trial participants.. There was a U-shaped relationship between C-peptide and CVD risk with increased risk with declining levels in the low range (< 0.50 nmol/l, HR 1.30 [95%CI 1.05-1.60], p = 0.02) and with rising levels in the high range (> 1.23 nmol/l, 1.27 [1.00-1.63], p = 0.05). C-peptide levels were inversely associated with the risk of severe hypoglycemia (OR 0.68 [0.60-0.77]) and visit-to-visit glucose variation (CV, standardized beta-estimate - 0.12 [SE 0.01]; ARV, - 0.10 [0.01]) (p < 0.0001 all). The association of low C-peptide levels with CVD risk was independent of cardiometabolic risk factors (1.48 [1.17-1.87, p = 0.001) and remained associated with CVD when tested in the same model with severe hypoglycemia and glucose CV.. Low C-peptide levels were associated with increased CVD risk in advanced type 2 diabetes. The association was independent of increases in glucose variation or severe hypoglycemia. C-peptide levels may predict future glucose control patterns and CVD risk, and identify phenotypes influencing clinical decision making in advanced type 2 diabetes.

Topics: Aged; Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fasting; Female; Glycemic Control; Heart Disease Risk Factors; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Middle Aged; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Time Factors; United States; United States Department of Veterans Affairs

The urinary C-peptide/creatinine ratio (UCPCR) is low in patients with type 1 diabetes mellitus, but it has not been well characterized in patients with type 2 diabetes mellitus (T2DM). We aimed to measure the UCPCRs in patients with T2DM and explore the relationships among UCPCR, insulin resistance (IR), and chronic vascular complications of diabetes.. A cross-sectional study was performed of 1299 Chinese hospitalized patients with T2DM. Binary logistic regression was used to evaluate the relationships between the chronic vascular complications of diabetes and UCPCR. K-means analysis was used to allocate participants to subgroups with five to six variables (age at diagnosis, body mass index [BMI], glycosylated hemoglobin, homoeostasis model assessment 2-estimated beta-cell function (HOMA2-B), and HOMA2-insulin resistance (HOMA2-IR), with or without UCPCR).. UCPCR positively correlated with HOMA2-IR (r = 0.448, P < .001). After adjustment for sex, age, duration of diabetes, and other cardiovascular risk factors, UCPCR was positively associated with diabetic kidney disease (DKD) (odds ratio [OR] = 1.198, 95% CI 1.019-1.408, P = .029) and coronary heart disease (CHD) (OR = 1.312, 95% CI 1.079-1.594, P = .006). When UCPCR was added, cluster analysis using the six variables identified five subgroups of T2DM, characterized by differing age at diagnosis, BMI, beta-cell function, IR, and prevalence of vascular complications.. UCPCR is positively associated with IR, DKD, and CHD and represents a promising biomarker that could refine the classification of T2DM.. 背景: 1型糖尿病患者尿C肽/肌酐比值水平低。但尿C肽/肌酐比值在2型糖尿病患者中并没有被充分评估, 本研究拟测定2型糖尿病患者的尿C肽/肌酐比值水平, 探讨尿C肽/肌酐比值与胰岛素抵抗及糖尿病慢性血管并发症的相关性, 并评估尿C肽/肌酐比值改善2型糖尿病精准分型的可能性。 方法: 本研究共纳入北京大学人民医院内分泌科住院2型糖尿病患者1299名。采集所有患者的临床资料, 测定其空腹尿C肽/肌酐比, 通过二元Logistic回归分析尿C肽/肌酐比值与糖尿病血管并发症的相关性。并分别用传统的五个变量[诊断年龄, 体重指数, 糖化血红蛋白, 改良稳态模型计算的β细胞功能指数(HOMA2-B)及胰岛素抵抗指数(HOMR2-IR)]和加入尿C肽/肌酐比值后的六个变量, 通过相同的k-means聚类算法对2型糖尿病患者进行聚类分组, 比较不同亚组的临床特点。 结果: 尿C肽/肌酐比值与HOMA2-IR水平 (r=0.448, P<0.001)正相关。在调整了性别, 年龄, 病程及其他心血管疾病危险因素后, 尿C肽/肌酐比值水平与糖尿病肾病 [比值比(OR) =1.198, 95%CI (1.019, 1.408), P=0.029]及冠状动脉粥样硬化性心脏病的发生风险呈正相关 [OR=1.312, 95%CI (1.079, 1.594), P=0.006]。在五个传统临床变量基础上, 加入尿C肽/肌酐比值后再进行聚类分型, 可以清晰地将患者分为五组:两组具有早发糖尿病特征[早发胰岛素缺乏型糖尿病(n=350)和早发胰岛素抵抗型糖尿病(n=176)], 两组具有晚发糖尿病特征[晚发胰岛素缺乏型糖尿病(n=318)和晚发胰岛素抵抗型糖尿病(n=133)]及轻型糖尿病(n=299)。各组间诊断年龄, 体重指数, 胰岛β细胞功能, 胰岛素抵抗水平以及糖尿病血管并发症比例显著不同。 结论: 尿C肽/肌酐比值与胰岛素抵抗水平及糖尿病肾病, 冠状动脉粥样硬化性心脏病发生风险正相关。在传统临床变量基础上引入尿C肽/肌酐比值, 可以改善2型糖尿病的精准分型。.

Topics: Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Creatinine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucose Intolerance; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Middle Aged; Prognosis

It remains widely perceived that early-onset Type 2 Diabetes (T2D) in children and adolescents is rare and clinically distinct from Type 1 Diabetes (T1D). We studied the challenges of classifying subtypes of early-onset diabetes using clinical features and biomarkers, and management of these patients. We reviewed retrospectively the record of patients < 25 years old who attended the diabetes clinic in Penang General Hospital, Malaysia between 1st December 2012 and 30th June 2015. We examined their clinical features, C-peptide and pancreatic autoantibodies. Comparisons were made between T1D and T2D for magnitude, demographics, metabolic status and complications. We studied 176 patients with a mean age of 20 ± 3.7 years, 43.2% had T1D, 13.6% had T2D, and 13.6% had mixed features of both. When tested, pancreatic autoantibodies were positive in 59.4% of the T1D. T2D presented two years later than T1D at 14.3 years, 20% were asymptomatic at presentation, and 50% required insulin supplementation despite fasting c-peptide of > 250 pmol/L. HbA1C of ≤ 8.0% (64 mmol/mol) was achieved in 30.3% of T1D, 58.3% of T2D on OAD and 16.7% of T2D on insulin. The T2D had greater cardiovascular risk with higher body mass index, more dyslipidaemia, higher blood pressure and earlier onset of nephropathy. The overlapping clinical features, variable autoimmunity, and beta-cell loss complicate classification of young diabetes. Pancreatic autoantibodies and C-peptide did not always predict diabetes subtypes nor respond to insulin. The poor metabolic control and high cardiovascular risk burden among the T2D highlight the need for population-based study and focused intervention.

Topics: Adolescent; Age of Onset; Autoantibodies; C-Peptide; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Malaysia; Male; Pancreas; Retrospective Studies; Young Adult

To study the association between baseline level of C-peptide and all-cause death, cardiovascular death and cardiovascular complications among persons with newly diagnosed type 2 diabetes.. The Skaraborg Diabetes Register contains data on baseline C-peptide concentrations among 398 persons <65 years with newly diagnosed type 2 diabetes 1996-1998. National registries were used to determine all-cause death, cardiovascular death and incidence of myocardial infarction and ischemic stroke until 31 December 2014. The association between baseline C-peptide and outcomes were evaluated with adjustment for multiple confounders by Cox regression analysis. Missing data were handled by multiple imputation.. In the imputed and fully adjusted model there was a significant association between 1 nmol/l increase in C-peptide concentration and all-cause death (HR 2.20, 95% CI 1.49-3.25, p < 0.001, number of events = 104), underlying cardiovascular death (HR 2.69, 1.49-4.85, p = 0.001, n = 35) and the composite outcome of underlying cardiovascular death, myocardial infarction or ischemic stroke (HR 1.61, 1.06-2.45, p = 0.027, n = 90).. Elevated C-peptide levels at baseline in persons with newly diagnosed type 2 diabetes are associated with increased risk of all-cause and cardiovascular mortality. C-peptide might be used to identify persons at high risk of cardiovascular complications and premature death.

Topics: Biomarkers; C-Peptide; Cardiovascular Diseases; Cause of Death; Cohort Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Registries; Stroke; Sweden; Time Factors

Soda intake is associated with an increased risk of cardiovascular disease. Consumption of diet sodas, often considered healthy alternatives to sodas, could also increase the likelihood of cardiovascular outcomes.. This study aims to evaluate the relation between soda and diet soda and biomarkers of cardiovascular risk.. We conducted a cross-sectional analysis among 825 Mexican women free of diabetes, cardiovascular disease, and cancer, and for whom serum concentrations of C-reactive protein (CRP), C-peptide, adiponectin, and leptin were available. Mean ± SD age was 45.9 ± 6.6 y, the majority of women were premenopausal (60.4%), and the prevalence of obesity was 35%. We estimated the adjusted percentage differences in biomarkers and 95% CIs by performing multiple linear regression models comparing categories of consumption for soda and diet soda adjusting for age, family history of heart disease, menopause, menopausal hormone therapy, socioeconomic status, region, smoking, physical activity, alcohol intake, and dietary patterns.. In the entire study sample we observed a 50% higher serum CRP concentration in women in the highest soda intake quartile (median intake: 202.9 mL/d, IQR: 101.4, 304.3 mL/d) compared to those in the lowest (median intake: 11.8 mL/d, IQR: 0.0, 152.1 mL/d). After stratification by menopausal status, results remained significant only for premenopausal women. Premenopausal women in the highest quartile of soda intake had 56% higher CRP concentration relative to women in the lowest quartile. We observed no significant association with the other biomarkers. After further adjustment for body mass index, a potential mediator, results remained significant only for CRP. Diet soda consumption was not associated with any of the biomarkers.. Consumption of soda was associated with adverse levels in a biomarker of inflammation and cardiovascular risk, serum CRP, in Mexican women. These results add to the accumulating evidence on soda and cardiovascular risk. More research is necessary to understand the potential impact of artificially sweetened sodas.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; C-Peptide; C-Reactive Protein; Carbonated Beverages; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Exercise; Female; Humans; Inflammation; Leptin; Mexico; Middle Aged; Nutritive Sweeteners; Obesity; Risk Factors; Socioeconomic Factors

Proinsulin connecting peptide (C-Peptide) is a marker of the beta-cell function and has been considered a marker of insulin resistance whose evidence suggests were associated with cardiovascular mortality. Our study aims to evaluate the association of C-Peptide with metabolic cardiovascular risk factors among young adults followed since birth in southern Brazil.. In 1982, maternity hospital in Pelotas, a southern Brazilian city, were visited daily and all births were identified. Live births whose family lived in the urban area of the city were identified, their mothers interviewed, and these subjects have been prospectively followed. Casual hyperglycemia patients were excluded from analysis. C-Peptide was assessed at 23 years, when transversely analyzed its association with cardiometabolic and hemodynamic risk factors, and longitudinally 30 years of age.. At age 23, 4297 individuals were evaluated, and C-Peptide was measured in 3.807. In a cross-sectional analysis at 23 years of age, C-Peptide was positively associated with waist circumference, body mass index, glycaemia, triglycerides, and C-reactive protein. The association with HDL cholesterol was negative. In the longitudinal analysis at 30 years, C-Peptide remained associated with BMI, waist circumference, glycated hemoglobin, triglycerides, and C-reactive protein, whereas the association was negative for HDL.. In the Pelotas birth cohort, the C-Peptide was associated with obesity indicators (waist circumference and BMI) cross-sectional (23 years) and longitudinal (30 years). We also observed cross-sectional and longitudinal associations of C-Peptide with cardiometabolic and inflammatory risk factors.

Topics: Adult; Biomarkers; Body Mass Index; Brazil; C-Peptide; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Female; Humans; Longitudinal Studies; Male; Obesity; Prospective Studies; Risk Factors; Waist Circumference; Young Adult

Type 2 diabetes is associated with cardiovascular complications. It is largely unknown which patients have poor treatment response and high complication risk; biomarkers are studied for this purpose. The aim of the study was to investigate the association between clinical factors such as HbA1c, level of biomarkers (C-peptide, copeptin) at diagnosis and changes in HbA1c, blood pressure or body mass index (BMI) after five years.. Clinical data and blood samples from 460 newly diagnosed type 2 diabetes patients from the Skaraborg diabetes register (SDR) at diagnosis and after 5years and were analyzed with linear and logistic regressions.. High BMI at diagnosis and smoking were associated with less reduction of HbA1c i.e. poorer treatment outcome after 5years. A high HbA1c at baseline predicted a greater reduction of HbA1c and need for insulin treatment. High systolic blood pressure and BMI at baseline were associated with greater reduction. The biomarkers were not associated with increase of blood pressure, HbA1c, BMI or need for insulin treatment.. Smokers and patients with high HbA1c at diagnosis respond poorer to treatment over 5years. This highlights the importance of advice for non-smoking and weight reduction and more intensive treatment over time.

Topics: Biomarkers; Body Mass Index; C-Peptide; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Female; Follow-Up Studies; Glycated Hemoglobin; Glycopeptides; Humans; Male; Middle Aged; Obesity; Overweight; Prognosis; Registries; Risk Factors; Sweden; Tobacco Smoking

Although physical activity is an established risk factor for chronic disease prevention, the specific mechanisms underlying these relationships are poorly understood. We examined the associations between total activity counts and moderate-vigorous physical activity (MVPA) measured by accelerometer, and physical activity energy expenditure measured by doubly labeled water, with plasma levels of proinsulin, insulin, c-peptide, insulin growth factor binding protein-3, insulin growth factor-1, adiponectin, leptin, and leptin-sR.. We conducted a cross-sectional analysis of 526 healthy US women in the Women's Lifestyle Validation Study, 2010 to 2012. We performed multiple linear regression models adjusting for potential lifestyle and health-related confounders to assess the associations between physical activity, measured in quartiles (Q) and biomarkers.. Participants in Q4 versus Q1 of total activity counts had lower proinsulin (-20%), c-peptide (-7%), insulin (-31%), and leptin (-46%) levels, and higher adiponectin (55%), leptin-sR (25%), and insulin growth factor-1 (9.6%) levels (all P trend ≤ 0.05). Participants in Q4 versus Q1 of MVPA had lower proinsulin (-26%), c-peptide (-7%), insulin (-32%), and leptin (-40%) levels, and higher adiponectin (31%) and leptin-sR (22%) levels (all P trend ≤ 0.05). Further adjustment for body mass index (BMI) attenuated these associations, but the associations with adipokines remained significant. Those in Q4 versus Q1 of physical activity energy expenditure had lower leptin (-21%) and higher leptin-sR (10%) levels (all P trend ≤ 0.05), after additional adjustment for BMI. In the sensitivity analysis, the associations were similar but attenuated when physical activity was measured using the subjective physical activity questionnaire.. Our data suggest that greater physical activity is modestly associated with favorable levels of cardiometabolic and endocrine biomarkers, where the strongest associations were found with accelerometer-measured physical activity. These associations may be only partially mediated through BMI, further supporting the role of physical activity in the reduction of cardiometabolic and endocrine disease risk, independent of adiposity.

Topics: Accelerometry; Adiponectin; Aged; Biomarkers; Body Mass Index; C-Peptide; Cardiovascular Diseases; Cross-Sectional Studies; Endocrine System Diseases; Energy Metabolism; Exercise; Female; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Middle Aged; Proinsulin; Risk Factors

The serum levels of C-peptide, an important risk factor for cardiovascular disease (CVD), increase with age. This study aimed to investigate the association between serum C-peptide and increased risk for CVD with altered lipid metabolism in the elderly.. This was a population-based cross-sectional study that included 3091 elderly participants aged ≥65 years. Serum C-peptide and lipid levels were measured according to standard protocols. Sampling weights were used to estimate the characteristics of study participants. Stratified analysis of covariance was used to evaluate the changes in the serum lipid levels according to quartiles of serum C-peptide levels, and the linear trend was assessed using a linear model. The logistic regression model was carried out to determine the association between the serum C-peptide levels and serum lipid levels.. The results of the analysis of covariance stratified by sex and serum insulin level showed that the serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels were significantly associated with changes in the serum C-peptide levels, independent of the serum insulin level. The logistic regression analyses indicated that the serum C-peptide levels were positively associated with the serum TG levels, and negatively associated with the serum HDL-C levels. A significant dose-response association was obtained in both men and women.. Serum C-peptide levels were strongly associated with increased serum TG and reduced HDL-C levels in the elderly. Our results suggest that serum C-peptide increases the risk of CVD via a pathway that increases TG or decreases HDL-C levels.

Topics: Aged; Aged, 80 and over; C-Peptide; Cardiovascular Diseases; Cholesterol, HDL; Cross-Sectional Studies; Female; Humans; Insulin; Linear Models; Lipids; Logistic Models; Male; Nutrition Surveys; Risk Factors; Triglycerides

Healthful dietary patterns have been associated with lower risks of type 2 diabetes and coronary artery disease, but their relations with intermediate markers of cardiometabolic and endocrine health are less established.. We evaluated the Dietary Approaches to Stop Hypertension (DASH), the alternate Mediterranean diet (aMED), and the Alternate Healthy Eating Index (aHEI) diet-quality scores with cardiometabolic and endocrine plasma biomarkers in US women.. The trial was a cross-sectional analysis of 775 healthy women in the Women's Lifestyle Validation Study that was conducted within the NHS (Nurses' Health Study) and NHS II longitudinal cohorts. Multiple linear regression models adjusted for potential confounders were used to estimate associations between quartiles of dietary pattern-adherence scores that were derived from a food-frequency questionnaire and plasma biomarker concentrations that were collected simultaneously.. In multivariable models in which highest and lowest quartiles of dietary pattern scores were compared, 1) DASH was significantly associated with higher concentrations of high-density lipoprotein (9%) and sex-hormone binding globulin (SHBG) (21%), and lower concentrations of leptin (28%), triglycerides (19%), and C-peptide (4%) (all P-trend ≤ 0.04); 2) the aMED was associated with 19% higher SHBG and 16% lower triglycerides (P-trend = 0.02 and 0.003, respectively); and 3) the aHEI was associated with significantly higher concentrations of insulin (16%) and SHBG (19%) and lower concentrations of leptin (18%) (all P-trend ≤ 0.02). Further adjustment for body mass index (BMI) attenuated these associations but remained significant for 1) DASH with leptin and triglycerides and 2) the aMED with triglycerides (all P-trend ≤ 0.03).. Adherence to healthful dietary patterns is associated with favorable concentrations of many cardiometabolic and endocrine biomarkers. These relations are mediated in part by BMI.

Topics: Adiponectin; Aged; Biomarkers; Body Mass Index; C-Peptide; Cardiovascular Diseases; Cholesterol, HDL; Cross-Sectional Studies; Diet, Mediterranean; Female; Folic Acid; Follow-Up Studies; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Metabolic Syndrome; Middle Aged; Receptors, Leptin; Reproducibility of Results; Risk Factors; Sex Hormone-Binding Globulin; Surveys and Questionnaires; Triglycerides; United States

Bardet-Biedl syndrome is a rare ciliopathy characterized by retinal dystrophy, obesity, intellectual disability, polydactyly, hypogonadism and renal impairment. Patients are at high risk of cardiovascular disease. Mutations in BBS1 and BBS10 account for more than half of those with molecular confirmation of the diagnosis. To elucidate genotype-phenotype correlations with respect to cardiovascular risk indicators 50 patients with mutations in BBS1 were compared with 19 patients harbouring BBS10 mutations. All patients had truncating, missense or compound missense/truncating mutations. The effect of genotype and mutation type was analysed. C-reactive protein was higher in those with mutations in BBS10 and homozygous truncating mutations (p = 0.013 and p = 0.002, respectively). Patients with mutations in BBS10 had higher levels of C peptide than those with mutations in BBS1 (p = 0.043). Triglyceride levels were significantly elevated in patients with homozygous truncating mutations (p = 0.048). Gamma glutamyl transferase was higher in patients with homozygous truncating mutations (p = 0.007) and heterozygous missense and truncating mutations (p = 0.002) than those with homozygous missense mutations. The results are compared with clinical cardiovascular risk factors. Patients with missense mutations in BBS1 have lower biochemical cardiovascular disease markers compared with patients with BBS10 and other BBS1 mutations. This could contribute to stratification of the clinical service.

Topics: Bardet-Biedl Syndrome; C-Peptide; Cardiovascular Diseases; Chaperonins; gamma-Glutamylcyclotransferase; Genetic Testing; Group II Chaperonins; Humans; Microtubule-Associated Proteins; Mutation; Phenotype; Risk Factors; Statistics, Nonparametric; Triglycerides

To study the prognosis of patients with newly diagnosed Type 2 diabetes in primary care in relation to their baseline C-peptide concentration.. C-peptide concentrations were determined in 399 patients aged < 65 years with newly diagnosed Type 2 diabetes using the Skaraborg Diabetes Register, Sweden. Data on cardiovascular complications and death were extracted from national registers and a local study of retinopathy. Statistical analyses were performed using Cox regression.. An analysis of C-peptide concentrations in quartiles, after adjusting for confounders, showed that patients in the highest quartile had a 2.75-fold higher risk of death from all causes compared with those in the lowest quartile (CI 1.17-6.47). By contrast, C-peptide concentration was not associated with the incidence of cardiovascular events or the development of retinopathy.. Measurement of C-peptide concentration at diagnosis could help identify patients who are at high risk and who presumably would benefit from more intensive treatment.

Topics: Aging; Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Incidence; Male; Middle Aged; Patient Selection; Prognosis; Proportional Hazards Models; Registries; Risk Factors; Sweden; Time Factors

In this study, we compared predialysis and dialysis patients with the controls in terms of insulin resistance and evaluated the association with inflammation that is a risk factor for cardiovascular disease.. A total of 134 non-diabetic patients with controls (n=33), predialysis (n=29) and dialysis patient group (n=72) were included in the study. Fasting blood glucose, insulin, C-peptide, albumin, CRP (C-reactive protein) and homocysteine plasma levels were simultaneously analyzed in all the patients. HOMA-IR index was calculated to show existence of insulin resistance.. Mean insulin and HOMA-IR index values were found to be higher in the predialysis and dialysis patient groups than in the control group (p=0.019, p=0.014; respectively). When three groups were compared in terms of C-peptide levels; these values were found to be statistically significantly higher in the predialysis patients than in controls (p=0.017) and in the dialysis group than in the predialysis patients and controls (p=0.0001, p=0.0001; respectively). CRP and homocysteine levels were found to be statistically higher (p=0.0001, p=0.0001; respectively), while albumin levels were significantly lower (p=0.0001) in the dialysis patient group.. In our study, we demonstrated that insulin resistance was higher in patients in the various stages of chronic kidney disease compared to healthy population. We found that insulin resistance, C-peptid and inflammation related cardiovascular risk factors increased.

Topics: Adult; Biomarkers; Blood Glucose; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Female; Homocysteine; Humans; Inflammation; Insulin; Insulin Resistance; Kidney Function Tests; Male; Middle Aged; Renal Insufficiency, Chronic; Risk Factors; Statistics as Topic; Turkey

Objective: Although serum C-peptide has increasingly received attention as a new and important risk factor for cardiovascular disease (CVD), the potential mechanisms remain unclear. This study aimed to investigate the association between serum C-peptide as a risk factor for CVD and high-density lipoprotein cholesterol (HDL-C) levels.. The present study included 13,185 participants aged ≥20 years. Serum C-peptide and HDL-C levels were measured according to a standard protocol. Stratified analysis of covariance was used to compare serum HDL-C levels between different quartiles of serum C-peptide levels. Logistic regression analysis was used to determine the association between serum C-peptide and HDL-C levels. Cox proportional hazard regression analysis was conducted to determine the hazard ratio of serum HDL-C for CVD-related mortality.. The results of the ANCOVA analysis showed a significant linear trend between the mean serum HDL-C level and the different quartiles of serum C-peptide. Compared to the first quartile (25th percentile), the second, third, and fourth quartiles had gradual reduction in serum HDL-C levels. Logistic regression analyses showed a strong negative association between serum C-peptide levels and HDL-C levels; the p value for the linear trend was <0.001. In men, compared with the lowest quartile of the serum C-peptide level, the relative risk was 1.75, 2.79, and 3.07 for the upper three quartiles of the serum C-peptide level. The relative risk was 1.60, 2.61, and 3.67 for women. The results of the survival analysis showed that serum HDL-C levels were negatively associated with CVD-related death in both men and women.. Serum C-peptide as a risk factor for CVD was significantly and negatively associated with serum HDL-C levels in individuals without diabetes. These findings suggest that serum C-peptide levels association with CVD death can be caused, at least in part, by the low serum HDL-C level.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; C-Peptide; Cardiovascular Diseases; Cholesterol, HDL; Female; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Proportional Hazards Models; Risk Assessment; Risk Factors; Survival Analysis; Young Adult

Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear.. Fifty nondiabetic (fasting plasma glucose ≤ 7.0 mmol/L), antipsychotic-treated male patients (ICD-10 diagnosis code F20, F21, F22, F25, F28, or F60; mean ± SD age = 33.0 ± 6.7 years; body mass index [BMI; kg/m²] = 26.0 ± 4.7; waist circumference = 95.9 ± 13.3 cm; glycated hemoglobin A1c [HbA1c] = 5.7% ± 0.3%) and 93 age- and waist circumference-matched healthy male controls (age = 33 ± 7.3 years; BMI = 26.1 ± 3.9; waist circumference = 94.6 ± 11.9 cm; HbA1c = 5.7% ± 0.3%) participated in this cross-sectional study. Blood was sampled in the fasting state and 90 minutes after ingestion of a standardized liquid meal (2,268 kJ). The primary outcomes were glucometabolic hormones and cardiovascular risk markers. Data were collected between March 2008 and February 2010.. Compared to healthy controls, patients were characterized by elevated fasting levels of proinsulin, C-peptide, and glucose-dependent insulinotropic polypeptide (GIP) (P < .05) and higher postprandial levels of insulin, proinsulin, C-peptide, and GIP (P ≤ .02). Also, patients exhibited elevated plasma levels of C-reactive protein and signs of dyslipidemia. Fasting plasma levels of insulin, glucagon, glucagon-like peptide-1 (GLP-1), ghrelin, leptin, adiponectin, tumor necrosis factor-α, plasminogen activator inhibitor-1, and interleukin-6 and postprandial levels of glucagon, GLP-1, ghrelin, leptin, and adiponectin did not differ between groups.. Presenting with an insulin resistant-like pattern, including beta cell hypersecretion and elevated GIP levels, nondiabetic antipsychotic-treated patients display emerging signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite-regulating hormones GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight into the pathophysiology associated with metabolic side effects of antipsychotic treatment and put emphasis on the importance of implementing metabolic screening into psychiatric practice.. ClinicalTrials.gov identifier NCT00627757.

Topics: Adiponectin; Adolescent; Adult; Antipsychotic Agents; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Cross-Sectional Studies; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Ghrelin; Glucagon; Glucose Metabolism Disorders; Humans; Insulin; Interleukin-6; Leptin; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Proinsulin; Risk Factors; Tumor Necrosis Factor-alpha; Young Adult

The aim of the present study was to investigate the relationship of C-peptide levels with insulin, resistance; components of metabolic syndrome and cardiovascular disease in patients with diabetes mellitus type 2. The study included 98 patients with diabetes mellitus type 2, who were divided into two groups by the level of C-peptide. The first group consisted of 54 patients with elevated levels of C-peptide; the second group consisted of 44 patients with normal levels of C-peptide. Our study has shown a positive correlation between C-peptide levels and a body mass index (BMI), triglyceride levels and the triglyceride/high-density lipoprotein ratio. Correlation analysis also allowed identifying a statistically significant association of the HOMA-2-IR-C-peptide with a BMI, triglycerides and the triglyceride/high-density lipoprotein ratio. In the group of patients with elevated levels of C-peptide found in practically all components of metabolic syndrome, as well as a high incidence of arterial hypertension and ischemic heart disease. The study shows that the detection of the C-peptide level is preferred in comparison with insulin for assessment of insulin resistance, presence of metabolic syndrome and can be used in type 2 diabetic patients for early detection of cardiovascular risk.

Topics: Adult; Aged; C-Peptide; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Risk Factors

Connecting peptide (C-peptide) plays a role in early atherogenesis in patients with diabetes mellitus and may be a marker for cardiovascular morbidity and mortality in patients without diabetes. We investigated whether serum C-peptide levels are associated with all-cause, cardiovascular-related and coronary artery disease-related mortality in adults without diabetes.. We used data from the Third Nutrition and Health Examination Survey (NHANES III) and the NHANES III Linked Mortality File in the United States. We analyzed mortality data for 5902 participants aged 40 years and older with no history of diabetes and who had available serum C-peptide levels from the baseline examination. We grouped the participants by C-peptide quartile, and we performed Cox proportional hazards regression analysis. The primary outcome was all-cause, cardiovascular-related and coronary artery disease-related mortality.. The mean serum C-peptide level in the study sample was 0.78 (± standard deviation 0.47) nmol/L. The adjusted hazards ratio comparing the highest quartile with the lowest quartile was 1.80 (95% confidence interval [CI] 1.33-2.43) for all-cause mortality, 3.20 (95% CI 2.07-4.93) for cardiovascular-related mortality, and 2.73 (95% CI 1.55-4.82) for coronary artery disease-related mortality. Higher C-peptide levels were associated with increased mortality among strata of glycated hemoglobin and fasting serum glucose.. We found an association between serum C-peptide levels and all-cause and cause-specific mortality among adults without diabetes at baseline. Our finding suggests that elevated C-peptide levels may be a predictor of death.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Coronary Artery Disease; Female; Glycated Hemoglobin; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Nutrition Surveys; Proportional Hazards Models; Regression Analysis; Risk Factors; Sex Factors

C-peptide is a proinsulin cleavage product released from the pancreas in amounts equimolar to insulin, and elevated levels of C-peptide have been found in patients with insulin resistance and early type 2 diabetes mellitus. Recent data suggest that C-peptide could play a causal role in the pathophysiology of vascular disease, but nothing is known about the prognostic value of C-peptide concentrations in the circulation.. We examined whether C-peptide is associated with cardiovascular and total mortality in 2,306 patients from the Ludwigshafen Risk and Cardiovascular Health Study who underwent coronary angiography at baseline (1997-2000).. During a mean follow-up of 7.6 years, 440 deaths (19.1%) occurred, 252 (10.9%) of which were due to cardiovascular causes. Age- and sex-adjusted hazard ratios (HRs) in the third compared with the first tertile of C-peptide were 1.46 (95% CI 1.15-1.85; P = 0.002) for all cause and 1.58 (1.15-2.18; P = 0.005) for cardiovascular mortality. After further adjustment for common risk factors as well as markers of glucose metabolism, these HRs remained significant at 1.46 (1.10-1.93; P = 0.008) and 1.55 (1.07-2.24; P = 0.022), respectively. Moreover, patients in higher tertiles of C-peptide exhibited higher levels of markers of endothelial dysfunction and atherosclerosis as well as a more severe extent of coronary lesions.. In patients undergoing coronary angiography, C-peptide levels are independently associated with all cause and cardiovascular mortality as well as presence and severity of coronary artery disease. Further studies are needed to examine a potential causal role of C-peptide in atherogenesis in humans.

Topics: Aged; Arteriosclerosis; C-Peptide; Cardiovascular Diseases; Coronary Angiography; Female; Humans; Male; Middle Aged; Mortality

Indices of overall dietary patterns are used in epidemiologic research to examine the relationship between nutrition and health. The objective of this study was to develop and validate an interpretable summary measure of dietary intake of whole plant foods (WPF; whole grains, vegetables, whole fruit, legumes, nuts, seeds) because of their similar nutritional characteristics and health effects. Six candidate WPF measures were calculated using data from subjects (age ≥ 6 years) participating in the 1999-2000 and 2001-2002 National Health and Nutrition Examination Survey. Measures differed by the inclusion or exclusion of potatoes and whether they were expressed as total intake or as a proportion of energy (4180 kJ) or mass (kg) consumed. Both standard and nontruncated (allowed to vary proportionally with intake) Healthy Eating Index-2005 (HEI-2005) scores were calculated. Regression analysis examined the associations between WPF and HEI-2005 measures, and between all diet measures and serum carotenoid concentration, serum lipids, fasting glucose, insulin, C-peptide, and C-reactive protein. Mean total WPF intake was 3.6 cup/oz equivalents, or 1.7 cup/oz equivalents per 4180 kJ and per kg. The largest R² between WPF and HEI-2005 measures was found for energy-adjusted WPF including potatoes and nontruncated HEI-2005 (R² = 0.50). All diet measures were positively related to serum carotenoids (P <.001) and were similarly related to health indicators (R² range from 0.003 to 0.16, P <.045 for regressions, indicating significant associations between WPF measures and health indicators). Whole plant food measures are interpretable indicators of dietary intake that are significantly related to nutrition and health biomarkers and may be of public health use.

Topics: Adult; Biomarkers; Blood Glucose; Body Mass Index; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Carotenoids; Cholesterol; Cross-Sectional Studies; Diet; Edible Grain; Energy Intake; Feeding Behavior; Female; Food, Organic; Fruit; Humans; Inflammation; Insulin; Male; Middle Aged; Nutrition Surveys; Nutritional Status; Reproducibility of Results; United States; Vegetables

To ascertain to which extent the use of HbA(1c) and oral glucose tolerance test (OGTT) for diagnosis of glucose tolerance could identify individuals with different pathogenetic mechanisms and cardiovascular risk profile.. A total of 844 subjects (44% men; age 49.5 ± 11 years; BMI 29 ± 5 kg/m(2)) participated in this study. Parameters of β-cell function were derived from deconvolution of the plasma C-peptide concentration after a 75-g OGTT and insulin sensitivity assessed by homeostasis model assessment of insulin resistance (IR). Cardiovascular risk profile was based on determination of plasma lipids and measurements of body weight, waist circumference, and blood pressure. Glucose regulation categories by OGTT and HbA(1c) were compared with respect to insulin action, insulin secretion, and cardiovascular risk profile.. OGTT results showed 42% of the subjects had prediabetes and 15% had type 2 diabetes mellitus (T2DM), whereas the corresponding figures based on HbA(1c) were 38 and 11%, with a respective concordance rate of 54 and 44%. Subjects meeting both diagnostic criteria for prediabetes presented greater IR and impairment of insulin secretion and had a worse cardiovascular risk profile than those with normal glucose tolerance at both diagnostic methods. In a logistic regression analyses adjusted for age, sex, and BMI, prediabetic subjects, and even more T2DM subjects by OGTT, had greater chance to have IR and impaired insulin secretion.. HbA(1c) identifies a smaller proportion of prediabetic individuals and even a smaller proportion of T2DM individuals than OGTT, with no difference in IR, insulin secretion, and cardiovascular risk profile. Subjects fulfilling both diagnostic methods for prediabetes or T2DM are characterized by a worse metabolic profile.

Topics: Adult; C-Peptide; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Middle Aged; Prediabetic State

Insulin resistance, characterized by hyperinsulinemia and normal or elevated serum glucose, is an established precursor to diabetes and cardiovascular disease. Despite fasting serum C-peptide levels being an accurate and stable marker of endogenous insulin production used in patients with diabetes, it is unknown whether C-peptide could serve as a marker of insulin resistance and predict outcomes in patients without diabetes.. This is a retrospective cohort study using data from the NHANES-3 (1988-1994) survey with mortality follow-up through December 31, 2006. Participants included 5153 subjects, 40 to 74 years of age with fasting glucose ≥ 70 mg/dL, without diabetes by history or laboratory testing. Receiver-operating-curve analysis compared fasting C-peptide against known insulin resistance measures such as fasting plasma glucose, serum insulin, HOMA-IR, quantitative-insulin-sensitivity-check-index, and metabolic syndrome for the prediction of cardiovascular and overall death. Subjects were then stratified by quartiles of C-peptide levels. Cox proportional-hazards modeling compared hazards of cardiovascular and overall death amongst C-peptide quartiles and adjusted for potential confounders of cardiovascular and diabetes risk. Fasting serum C-peptide levels predicted cardiovascular and overall death better than other studied measures (AUC=0.62 and 0.60 respectively vs the rest, with AUC ≤ 0.58 and ≤ 0.57 respectively, P<0.001). When compared with the lowest C-peptide quartile, subjects in the highest quartile had significantly higher adjusted hazard ratios (HR) of cardiovascular death (HR=1.60, 95%CI 1.07 to 2.39) and overall mortality (HR=1.72, 95%CI 1.34 to 2.21) after controlling for confounders.. C-peptide levels significantly related to hazards of cardiovascular and overall death in nondiabetic adults and was a better predictor of these outcomes than serum insulin and/or glucose derived measures.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus; Fasting; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Mortality; Nutrition Surveys; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Factors; ROC Curve

In the postprandial state, insulin regulates metabolic and cardiovascular responses. In insulin resistance, the insulin action is impaired at both levels. However, postprandial hemodynamic responses are poorly characterized in this setting.. We investigated fasting and postprandial cardiac and vascular hemodynamic responses in subjects with and without insulin resistance.. Sixty-six atherosclerosis-free, healthy volunteers were studied in a fasted state and ≤180 min after ingestion of a mixed meal. The insulin sensitivity index was determined by using a minimal model analysis; hemodynamic response was monitored by using continuous impedance cardiography that allowed a reliable beat-to-beat noninvasive evaluation of stroke volume, cardiac contractility, and several derived variables.. Subjects were divided into insulin-resistant (IR; n = 33) and insulin-sensitive (IS; n = 33) groups. After fasting, IR subjects had significantly higher values of systolic and diastolic blood pressures and the systemic vascular resistance index (SVRI) than did IS subjects. In the postprandial state, acute vasodilatation was comparable and synchronous (at 30 min) in IR and IS subjects (P = 0.209), but subsequent vascular tone recovery (30-180 min) was significantly impaired in IR subjects (P = 0.018), even after adjustment for age and sex (P = 0.031). Hemodynamic dysregulation was directly correlated with metabolic disturbances in the postprandial state. In basal and postprandial states, hemodynamic variables related to cardiac function were not significantly different in IR and IS subjects.. IR subjects had a worse fasting vascular performance than did IS subjects. In the postprandial phase, insulin resistance was associated with a shorter duration of vasodilatation in the absence of an altered cardiac performance. Peripheral hemodynamic alterations in fasting and postprandial states may have a negative effect on cardiovascular performance in IR patients.

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Cardiography, Impedance; Cardiovascular Diseases; Cross-Sectional Studies; Eating; Female; Hemodynamics; Humans; Insulin; Insulin Resistance; Kinetics; Male; Middle Aged; Postprandial Period; Vascular Resistance; Vasodilation

A protective effect of residual beta-cell function on microvascular complications of type 1 diabetes has been suggested. Our aim was to retrospectively evaluate the association of fasting plasma C-peptide values with micro- and macrovascular complications.. We recruited a clinic-based cohort of 471 type 1 diabetic patients born after 1945 and cared for in the period 1994-2004. Centralized measurements and standardized procedures of ascertainment of micro- and macrovascular complications were employed. Individual cumulative averages of A1C up to 2007 were calculated.. Residual beta-cell secretion was detected even many years after diabetes diagnosis. In multivariate linear regression analysis, fasting plasma C-peptide values were positively associated with age at diagnosis (beta = 0.02; P < 0.0001) and triglycerides (beta = 0.20; P = 0.05) and inversely associated with diabetes duration (beta = -0.03; P < 0.0001) and HDL cholesterol (beta = -0.006; P = 0.03). The final model explained 21% of fasting C-peptide variability. With respect to fasting C-peptide values in the lowest tertile (<0.06 nmol/l), higher values were associated with lower prevalence of microvascular complications (odds ratio [OR] 0.59 [95% CI 0.37-0.94]) independently of age, sex, diabetes duration, individual cumulative A1C average during the study period, hypertension, and cardiovascular diseases. No association was evident with macrovascular complications (0.77 [0.38-1.58]).. Our study shows an independent protective effect of residual beta-cell function on the development of microvascular complications in type 1 diabetes, suggesting the potential beneficial effect of treatment that allows the preservation of even modest beta-cell function over time.

Topics: Adult; Age of Onset; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Fasting; Female; Humans; Hypertension; Insulin-Secreting Cells; Italy; Male; Multivariate Analysis; Odds Ratio; Regression Analysis

Several intervention studies have convincingly demonstrated the importance of good glycemic control to avoid long-term diabetic complications, but the importance of other risk factors remains controversial. We previously reported a markedly reduced incidence of severe retinopathy and nephropathy during the past decades in an unselected population of type 1 diabetes mellitus diagnosed in childhood. The aim of the present study was to analyze possible risk factors, which could explain the improved prognosis.. In this longitudinal population-based cohort study, we followed all 269 patients in whom type 1 diabetes mellitus was diagnosed in childhood 1961-1985 in a well-defined geographical area in Sweden. The patients were followed until the end of 1990 s. Multivariable regression models were used to analyze the importance of hemoglobin A1c (HbA(1c)), diabetes duration, blood pressure, cardiovascular risk factors and persisting C-peptide secretion for the development of diabetic retinopathy and nephropathy.. Beside longer duration and higher HbA(1c), blood pressure and lipid values were higher and cardiovascular disease and smoking were more common in patients with severe complications. However, multivariable analysis abolished these associations. Diabetes duration and long-term HbA(1c) were the only significant independent risk factors for both retinopathy and nephropathy. The risk of overt nephropathy increased substantially when HbA(1c) was above 9.6% [Diabetes Control and Complications Trial (DCCT) corrected value], while the risk of severe retinopathy increased already when HbA(1c) exceeded 8.6%.. In this unselected population, glycemic control was the only significant risk factor for the development of long-term complications.

Topics: Age of Onset; Albuminuria; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Child; Cholesterol; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Glycated Hemoglobin; Homeostasis; Humans; Triglycerides

Chronic iodine deficiency (ID) increases thyrotropin (TSH) concentrations and produces a thyroid hormone pattern consistent with subclinical hypothyroidism (ScH). ScH may be associated with cardiovascular disease risk factors. Thus, the study aim was to determine if iodine treatment of children with elevated TSH concentrations due to ID would affect their lipid profile, insulin (C-peptide) levels, and/or subclinical inflammation.. In controlled intervention trials of oral iodized oil or iodized salt, 5-14-year-old children from Morocco, Albania, and South Africa with TSH concentrations > or = 2.5 mU/L (n = 262) received 400 mg iodine as oral iodized oil or household distribution of iodized salt containing 25 microg iodine/g salt. At baseline and after 5 or 6 months, urinary iodine (UI) and blood concentrations of total thyroxine, TSH, C-reactive protein (CRP), C-peptide, and lipids were measured.. Median (range) UI at baseline was 46 (2-601) microg/L. Compared to the control group, iodine treatment significantly increased UI and total thyroxine and decreased TSH, C-peptide, and total and low-density lipoprotein cholesterol. The mean low-density lipoprotein/high-density lipoprotein cholesterol ratio fell from 3.3 to 2.4 after iodine treatment (p < 0.001). Iodine treatment had no significant effect on concentrations of high-density lipoprotein cholesterol, triglycerides, or C-reactive protein.. Correction of ID-associated ScH improves the insulin and lipid profile and may thereby reduce risk for cardiovascular disease. This previously unrecognized benefit of iodine prophylaxis may be important because ID remains common in rapidly developing countries with increasing rates of obesity and cardiovascular disease.

Topics: Adolescent; C-Peptide; Cardiovascular Diseases; Child; Child, Preschool; Female; Humans; Hypothyroidism; Inflammation; Insulin; Iodine; Lipids; Male; Risk Factors; Thyrotropin; Thyroxine

Waist circumference (WC) was measured in 200 Japanese patients with type 2 diabetes mellitus (T2DM: male 106, female 94, mean age 61 years old) who had been admitted in our hospital, and relationship with various risk factors to predict future cardiovascular disease (CVD) was analyzed. There was a positive and statistically significant trend in WC levels with an increasing number of CVD risk factors in male patients, whereas no significant trend of WC was observed in female patients. The receiver operator characteristic (ROC) curve for WC to predict the presence of two or more risk factors of CVD depicted greater area under the curve in male patients (0.732) than that in female patients (0.571). Apart from positive correlation with fasting serum C-peptide (S-CPR) and log-transformed high-sensitivity C-reactive protein (log HS-CRP) in both genders, WC was positively correlated with log-transformed triglyceride (log TG), systolic and diastolic blood pressure (SBP and DBP) and negatively with HDL-cholesterol (HDL-C) in male patients, whereas it was negatively correlated with HbA1c and fasting plasma glucose (FPG) in female patients. The change of WC after administration (DeltaWC) was correlated with DeltaS-CPR, DeltaLDL-C, DeltaSBP and DeltaDBP in male patients, while no relationship was observed in female patients. In conclusion, WC is a reliable marker to predict future CVD events at least in Japanese male, but not female patients with T2DM.

Topics: Aged; Asian People; Blood Pressure; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Risk Factors; Triglycerides; Waist Circumference

The aim of this study was to establish the reference values of the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check (QUICKI) indexes, as well as those of insulin and C-peptide levels in healthy children and adolescents with a view to determining reference percentiles to detect those at cardiovascular risk.. A total of 372 children boys and girls of different ages and at distinct pubertal stages with normal body mass index participated in the study. Fasting glucose, insulin and C-peptide values were measured by chemiluminescence and the HOMA and QUICKI indexes were calculated.. Fasting glucose levels were normal in all children. The mean values obtained for each variable were (mean (SD)): fasting glucose 87(7.75) mg/dL, insulin 7.74 (5.35) microU/mL, C-peptide: 1.76 (0.79) ng/mL, HOMA index 1.72 (1.27) and QUICKI index 0.72 (0.29). All the variables progressively increased with age, with statistically significant differences between prepubertal and pubertal children. The QUICKI index showed an inverse relationship. In addition, significant differences were found between sexes. The 90th percentile for all the variables was as follows: insulin 15.05 microU/mL, C-peptide: 2.85 ng/mL, HOMA index 3.43 and QUICKI index 1.10.. Values of fasting glucose, insulin, C-peptide and the HOMA index significantly increased with age and pubertal stage, while the QUICKI index decreased. We defined the 90th percentile for all the parameters studied as the cut-off point to identify children at cardiovascular risk in our population.

Topics: Adolescent; C-Peptide; Cardiovascular Diseases; Child; Child, Preschool; Female; Homeostasis; Humans; Infant; Insulin; Male; Metabolic Syndrome; Reference Values; Risk Factors

Our study was designed to assess the impact on nitrogen and glucose metabolism when it is administered either as discontinuous or as continuous infusion.. We assessed the nutritional efficacy (nitrogen balance) and hyperinsulinism risk (urine C peptide excretion) of enteral nutrition in 23 patients hospitalized because of acute stroke.. The feeding tolerance of our enteral nutrition protocol (nasoenteric catheter) was full in every patient. The nitrogen balance was positive in both patterns, but the balance in the continuous feeding pattern was better than in the bolus feeding one. On the contrary, the urine C peptide excretion was increased when enteral nutrition was administered intermittently as compared with continuous feeding. Calciuria was greater in the continuous fed pattern than in the bolus feeding.. Continuous feeding is associated with better nitrogen balance and less urine C peptide excretion than intermittent feeding. These results suggest that continuous feeding would be an interesting choice to improve glucose control in diabetic patients with enteral nutrition.

Topics: Aged; C-Peptide; Cardiovascular Diseases; Enteral Nutrition; Female; Humans; Male; Nitrogen

Impaired glucose tolerance (IGT) is associated with an increased cardiovascular disease risk. Less is known about cardiovascular disease risk among subjects with impaired fasting glucose (IFG) or with combined IFG and IGT.. To compare body composition, body fat distribution, plasma glucose-insulin homeostasis and plasma lipid-lipoprotein profile between pre-menopausal women having either a normal glucose tolerance (NGT), isolated IFG, isolated IGT or combined IFG and IGT.. Three hundred and thirty-four women with NGT, 11 women with IFG, 35 women with IGT and 10 women with both IFG and IGT were studied.. Women with IFG were characterized by a higher visceral adipose tissue (AT) accumulation than women with NGT (P < 0.05). Also, they were characterized by a higher subcutaneous AT area and by higher body fat mass than NGT and IGT women (P < 0.05). However, their lipid-lipoprotein profile was comparable with that of NGT women, except for reduced HDL-cholesterol concentrations (P < 0.05). After adjustment for visceral AT, women with IFG had lower total cholesterol, LDL-cholesterol and apolipoprotein B (apoB) levels than the three other groups. They also had lower HDL(2)-cholesterol than NGT women and lower total cholesterol/HDL-cholesterol ratio than IGT women. Women with IGT showed higher triglyceride and apoB concentrations and a higher total cholesterol/HDL-cholesterol ratio than women with NGT (P < 0.05). Overall, women with combined IFG and IGT showed body fatness characteristics and alterations in their metabolic risk profile which were essentially similar to women with isolated IGT.. These results indicate that there are significant differences in anthropometric and metabolic variables between pre-menopausal women with IFG vs. IGT and that the association between body fatness-body fat distribution indices and the metabolic profile may differ between IFG and IGT women.

Topics: Adolescent; Adult; Anthropometry; Blood Glucose; C-Peptide; Cardiovascular Diseases; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Middle Aged; Premenopause; Risk Factors

To compare brain perfusion in hypertensive patients with diabetes mellitus type 2 (DM2) or metabolic (MS) syndrome and hypertensive patients without clinicobiochemical signs of DM2 or MS; to study enoxaparin effects on brain perfusion in DM2 and arterial hypertension (AH).. Seventy patients included in the study were divided into three groups: 30 patients with DM2 and AH (group 1), 30 patients with MS and AH (group 2) and 10 AH patients without manifestations of MS or DM2 (group 3). All the patients have undergone single-photon emission computed tomography (SPECT) of the brain, carbohydrate and lipid metabolism were examined.. Deterioration of brain perfusion was more prominent in DM2 and MS patients with AH than in hypertensive patients with normal metabolism. Stress test with acetasolamide revealed defective autoregulation of cerebral blood flow in hypertensive patients with DM2. A 6-week therapy with enoxaparin significantly improved brain perfusion in hypertensive patients with DM2.. Enoxaparin treatment of hypertensive DM2 and MS patients with abnormal perfusion of the brain can be used for prevention of cerebrovascular complications.

Topics: Adult; Anticoagulants; Blood Glucose; Blood Pressure; Body Mass Index; Brain; C-Peptide; Cardiovascular Diseases; Cerebrovascular Circulation; Diabetes Mellitus, Type 2; Enoxaparin; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin Resistance; Lipids; Male; Metabolic Syndrome; Postprandial Period; Radionuclide Imaging; Risk

Our aim was to evaluate the long-term effects of transplanted islets on diabetic macro-/microangiopathy in type 1 diabetic kidney-transplanted patients.. A total of 34 type 1 diabetic kidney-transplanted patients underwent islet transplantation and were divided into two groups: successful islet-kidney transplantation (SI-K; 21 patients, fasting C-peptide serum concentration >0.5 ng/ml for >1 year) and unsuccessful islet-kidney transplantation (UI-K; 13 patients, fasting C-peptide serum concentration <0.5 ng/ml). Patients cumulative survival, cardiovascular death rate, and atherosclerosis progression were compared in the two groups. Skin biopsies, endothelial dependent dilation (EDD), nitric oxide (NO) levels, and atherothrombotic risk factors [von Willebrand factor (vWF) and D-dimer fragment (DDF)] were studied cross-sectionally.. The SI-K group showed a significant better patient survival rate (SI-K 100, 100, and 90% vs. UI-K 84, 74, and 51% at 1, 4, and 7 years, respectively, P = 0.04), lower cardiovascular death rate (SI-K 1/21 vs. UI-K 4/13, chi(2) = 3.9, P = 0.04), and lower intima-media thickness progression than the UI-K group (SI-K group: delta1-3 years -13 +/- 30 micro m vs. UI-K group: delta1-3 years 245 +/- 20 micro m, P = 0.03) with decreased signs of endothelial injuring at skin biopsy. Furthermore, the SI-K group showed a higher EDD than the UI-K group (EDD: SI-K 7.8 +/- 4.5% vs. UI-K 0.5 +/- 2.7%, P = 0.02), higher basal NO (SI-K 42.9 +/- 6.5 vs. UI-K 20.2 +/- 6.8 micro mol/l, P = 0.02), and lower levels of vWF (SI-K 138.6 +/- 15.3 vs. UI-K 180.6 +/- 7.0%, P = 0.02) and DDF (SI-K 0.61 +/- 0.22 vs. UI-K 3.07 +/- 0.68 micro g/ml, P < 0.01). C-peptide-to-creatinine ratio correlated positively with EDD and NO and negatively with vWF and DDF.. Successful islet transplantation improves survival, cardiovascular, and endothelial function in type 1 diabetic kidney-transplanted patients.

Topics: Adult; C-Peptide; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Female; Follow-Up Studies; Humans; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Male; Survival Rate; Time Factors; Treatment Failure; Treatment Outcome

To assess the occurrence and development of new peripheral arterial occlusive disease (PAOD), its risk factors, and the outcome in patients with type 2 diabetes.. A total of 130 type 2 diabetic patients (mean age 58 years) were examined at baseline and after a mean follow-up of 11 years (range 7-14). The ankle-brachial index (ABI) and toe-brachial index were used to detect PAOD. Blood and urine samples were taken at baseline, and a history of cardiovascular events was recorded during follow-up.. PAOD was diagnosed in 21 (16%) patients at baseline. During follow-up, 21 of 89 (24%) patients developed new PAOD. There were 29 patients who died, 21 (72%) of them from cardiovascular disease. Patients with PAOD suffered an excess mortality compared with patients without PAOD (58 vs. 16%; P < 0.001). Logistic regression analysis showed that PAOD at baseline was associated with age, duration of diabetes, smoking, and urinary albumin excretion rate. Patients who developed new PAOD during follow-up had higher serum LDL cholesterol concentrations and lower HDL cholesterol concentrations and were older than the patients who remained free of PAOD.. Objectively measured PAOD is frequent in type 2 diabetic patients. It presents the early clinical signs of atherosclerosis and is strongly associated with cardiovascular death. The risk factor pattern for PAOD was different at baseline and after a mean follow-up of 11 years. We consider routine ABI measurements and modification of risk factors necessary also in patients with asymptomatic PAOD.

Topics: Age of Onset; Arterial Occlusive Diseases; Brachial Artery; C-Peptide; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Disease Progression; Electrocardiography; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Peripheral Vascular Diseases; Smoking; Survival Rate; Time Factors; Triglycerides

To evaluate the role of lipoprotein abnormalities as risk factors for macroangiopathy in Type 2 diabetes.. This prospective nine-year follow-up study involved 113 Type 2 diabetic patients (50 men and 63 women, mean age 66.9 +/- 9.9 years), 37 of whom had clinical signs of coronary heart disease (CHD) and cerebrovascular disease (CVD) at baseline. During the follow-up, 32 patients died: 17 of CHD, five of CVD, and 10 of non-vascular causes. The patients who died because of vascular disease were more frequently smokers, and had baseline symptoms of vascular disease; they were also significantly different from the other patients insofar as they were older, and had higher fasting plasma glucose levels, lower fasting C-peptide levels, and lower apoprotein (apo) AII, apo CII, apo CIII and apo E levels. Univariate analysis showed that baseline symptoms of vascular disease, current smoking, age, high fasting plasma glucose levels, low fasting C-peptide levels, and low apo AII, apo CII, apo CIII and apo E levels [but not cholesterol, triglyceride, high-density lipoprotein (HDL)-cholesterol or qualitative low-density lipoprotein or HDL abnormalities] were associated with cardiovascular mortality. Multivariate analysis showed that only age, smoking, glycated hemoglobin (HbA1c) and fasting C-peptide levels were significant independent determinants of macrovascular death.. In Type 2 normolipidemic diabetic patients, only age, smoking, HbA1c and fasting C-peptide levels are independent vascular risk factors. The differences in apo concentrations between patients with and without vascular disease may reflect qualitative abnormalities in plasma lipoproteins related to vascular disease.

Topics: Age Factors; Aged; Apolipoprotein A-II; Apolipoprotein C-II; Apolipoprotein C-III; Apolipoproteins C; Apolipoproteins E; Apoproteins; C-Peptide; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Diabetes Mellitus, Type 2; Fasting; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Lipoproteins; Male; Middle Aged; Prospective Studies; Risk Factors; Smoking

Insulin resistance with increased insulin and C-peptide levels is the basis of the metabolic X-syndrome, so it is reasonable to expect them to be a good predictor of associated cardiovascular risk factors.. A total of 29 patients (21 postmenopausal women and 8 men) with type 2 diabetes mellitus (mean duration 14.6 years, 95% CI 11.9 to 17.3 years), all older than 50, were studied for possible links between fasting serum C-peptide levels and other vascular risk factors. The mean value of the C-peptide in the group was 0.627 nmol/l (95% CI: 0.464 to 0.789 nmol/l).. We found statistically significant correlations between C-peptide and triacylglycerols (TG; r=0.474; p=0.009), HDL-cholesterol (inverse; r = -0.567; p = 0.001) and various lipoprotein ratios: atherogenic index (= total/HDL cholesterol: r = 0.599; p = 0.0006) or TG/HDL (r = 0.587; p = 0.0008). C-peptide also correlated with the body mass index (BMI: r = 0.519; p= 0.004) and leptin (r = 0.492; p = 0.007). After the coefficient CpG (C-peptide x fasting glycemia) was introduced, the correlations with lipoproteins became even stronger.. We suggest that elevated (fasting) serum C-peptide levels constitute a clinically important marker of the cardiovascular risks associated with the metabolic X-syndrome. It can be used as an effective tool for the early detection of diabetic patients at particular risk for atherosclerotic cardiovascular diseases and needing early preventive measures or aggressive treatment.

Topics: Aged; C-Peptide; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Hyperlipoproteinemias; Insulin; Insulin Resistance; Lipoproteins; Male; Metabolic Syndrome; Middle Aged; Peptides; Postmenopause; Risk Factors

To compare the American Diabetes Association (ADA) fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD).. Study subjects were 596 Japanese-Americans. Fasting insulin, lipids, and C-peptide levels; systolic and diastolic blood pressures (BPs); BMI (kg/m2); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria as having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75-g OGTT as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT).. Of 503 patients with NFG, 176 had IGT and 20 had DGT These patients had worse CVD risk factors than those with NGT . The mean values for NGT, IGT, and DGT, respectively, and analysis of covariance P values, adjusted for age and sex, are as follows; intra-abdominal fat area by CT 69.7, 95.0, and 101.1 cm2 (P < 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm2 (P < 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80, 0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P = 0.01).. NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles.

Topics: Adult; Aged; Asian; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Japan; Lipids; Male; Middle Aged; Risk Factors; Sensitivity and Specificity

To determine whether the impaired glucose tolerance (IGT) state contributes to the deterioration of the metabolic profile in women after taking into account the contribution of visceral adipose tissue (AT) accumulation, as measured by computed tomography.. We studied 203 women with normal glucose tolerance (NGT) and 46 women with IGT, defined as a glycemia between 7.8 and 11.1 mmol/l measured 2 h after a 75-g oral glucose load.. Women with IGT were characterized by a higher visceral AT accumulation and by higher concentrations of fasting plasma glucose, insulin, and C-peptide as well as by higher plasma concentrations of cholesterol, triglycerides, and apolipoprotein B (apoB) and by greater cholesterol-to-HDL-cholesterol ratio, reduced LDL peak particle size, lower HDL-cholesterol and HDL2-cholesterol concentrations, and higher blood pressure (P < 0.01) than women with NGT. When we matched 27 pairs of women for visceral AT and fat mass as well as for menopausal status, differences previously found in LDL-cholesterol, LDL peak particle size, HDL-cholesterol, and HDL2-cholesterol concentrations as well as in the cholesterol-to-HDL-cholesterol ratio and blood pressure were eliminated, whereas triglyceride concentrations remained significantly higher in women with IGT.. A high visceral AT accumulation is a major factor involved in the deterioration of many metabolic variables in women with IGT, with the notable exception of triglyceride concentrations, which remained significantly different between women with NGT and women with IGT after adjustment for visceral fat.

Topics: Adipose Tissue; Adult; Aged; Apolipoproteins; Blood Glucose; Blood Pressure; C-Peptide; Cardiovascular Diseases; Cholesterol; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Lipoproteins; Middle Aged; Quebec; Risk Assessment; Risk Factors; Tomography, X-Ray Computed; Triglycerides; Viscera

To examine cross-sectional and prospective associations between proinsulin and cardiovascular disease risk factors using data from a population-based study of type 2 diabetes among Native Canadians.. Between 1993 and 1995, 72% of eligible members of a Native Canadian community participated in a baseline diabetes prevalence survey. Fasting samples were collected for glucose, C-peptide, proinsulin, lipids, and apolipoproteins. A 75-g oral glucose tolerance test was administered, and a second sample for glucose was drawn after 120 min. Blood pressure and waist circumference were determined. In the present study, subjects with normal glucose tolerance (NGT) (n = 505) and impaired glucose tolerance (IGT) (n = 74) were included in cross-sectional analyses. In 1998, 95 individuals who had IGT or NGT at baseline with an elevated 2-h glucose concentration (> or = 7.0 mmol/l) participated in a follow-up evaluation using the protocol used at baseline. Cross-sectional and prospective associations between proinsulin and cardiovascular risk factors were assessed using correlation and multiple linear regression analyses.. After adjustment for covariates including age, sex, C-peptide, waist circumference, and glucose tolerance status, fasting proinsulin concentration was significantly associated with concurrently measured lipid and apolipoprotein concentrations (triglycerides: r = 0.18, P < 0.0001; total cholesterol: r = 0.10, P = 0.02; LDL cholesterol: r = 0.11, P = 0.01; HDL cholesterol: r = -0.16, P = 0.0002; apolipoprotein (apo) B: r = 0.17, P < 0.0001; apoAI: r = -0.11, P = 0.008). In the adjusted prospective analysis, baseline triglycerides, HDL cholesterol, and apoB were associated with changes over time in proinsulin (r = 0.23, P = 0.04; r = -0.30, P = 0.01; r = 0.23, P = 0.04; respectively).. These results confirm previously reported cross-sectional associations between proinsulin and lipid concentrations. In addition, an unexpected association between baseline lipids and proinsulin change was documented.

Topics: Adult; Apolipoproteins; Apolipoproteins B; Blood Pressure; C-Peptide; Canada; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Cross-Sectional Studies; Female; Humans; Indians, North American; Lipids; Male; Proinsulin; Prospective Studies; Risk Factors; Triglycerides

To investigate whether fasting hyperinsulinemia is associated with a clustering of cardiovascular disease (CVD) risk factors, manifesting as the insulin resistance syndrome (IRS), in a population of native Hawaiians.. A total of 574 native Hawaiians > or = 30 years of age were examined for blood pressure, waist-to-hip ratio (WHR), BMI, oral glucose tolerance, and fasting lipid, insulin, and C-peptide concentrations. All statistical analyses (n = 384) excluded 190 individuals who had NIDDM or who were taking hypertension medication. Using logistic regression analysis, fasting insulin and C-peptide levels were compared with CVD risk factors (glucose intolerance, hypertension, central adiposity, elevated triglyceride levels, and low HDL cholesterol levels) after adjusting for age and obesity.. Sixty-six percent of native Hawaiians were overweight or obese, and 70% were found to have central adiposity. Fasting insulin concentrations were correlated with BMI, WHR, blood pressure, and triglyceride, HDL cholesterol, and glucose concentrations. Fasting insulin was also significantly associated with an increasing number of CVD risk factors in each participant (P < 0.001). Fasting insulin and C-peptide concentrations were independently associated with glucose intolerance, high triglyceride levels, and low HDL cholesterol levels. However, only fasting C-peptide concentrations were independently associated with hypertension and central adiposity. Apparent differences in the correlates of fasting insulin and C-peptide may be related to multiple factors and warrant further evaluation.. This study provides cross-sectional data confirming the existence of the IRS in native Hawaiians. However, further longitudinal studies are needed to examine the relationship of insulin resistance and/or surrogate markers to increased rates of NIDDM and CVD mortality in native Hawaiians.

Topics: Adult; Asian; Body Constitution; C-Peptide; Cardiovascular Diseases; Cross-Sectional Studies; Fasting; Female; Hawaii; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Logistic Models; Male; Middle Aged; Obesity; Odds Ratio; Prevalence; Risk Factors; Sex Characteristics; Syndrome

To evaluate the relationships of total and differential white blood cell (WBC) count to the components of the so-called insulin resistance syndrome.. The study population consisted of a random sample of 90 38-year-old healthy men with normal glucose tolerance.. A 75 g oral glucose tolerance test was performed in all participants.. Total and differential WBC count, lipids, blood pressure, plasma glucose, C-peptide and insulin (at fasting and 2 h after glucose load).. Total WBC count correlated consistently with plasma 2-h glucose (r = 0.38; P < 0.001), fasting and 2-h postload insulin (r = 0.26 and r = 0.33; P < 0.01-0.001, respectively) and C-peptide (r = 0.28 and r = 0.32; P < 0.01-0.001) concentrations. Smokers had significantly higher total leukocytes (P < 0.01), neutrophils and lymphocytes than nonsmokers. Furthermore, total WBC count correlated positively with body mass index, blood pressure, plasma triglycerides, fibrinogen, and negatively with HDL cholesterol concentration. As differential WBC count, most variables correlated essentially to neutrophils and/or lymphocytes, whereas plasma insulin and C-peptide concentrations correlated essentially to lymphocytes and monocytes, but not to neutrophils. In a multiple linear regression analysis, only 2-h plasma glucose (P < 0.01) and fibrinogen (P < 0.05) were positive predictors of total WBC count after adjusting for all potentially confounding variables.. The results indicate that increased, albeit normal, WBC count associates with the cluster of metabolic and haemodynamic disorders typical of the insulin resistance syndrome, and suggest that increased WBC count may be yet another component of this syndrome.

Topics: Adult; C-Peptide; Cardiovascular Diseases; Glucose Tolerance Test; Hemodynamics; Humans; Insulin; Insulin Resistance; Leukocyte Count; Male; Predictive Value of Tests; Regression Analysis; Risk Factors; Smoking

To investigate the acute effect of cigarette smoking on glucose tolerance, insulin sensitivity, serum lipids, blood pressure, and heart rate.. This nonrandomized experimental control trial in a tertiary care center included 20 healthy chronic smokers and 20 age-, sex-, and BMI-matched healthy volunteers. Two oral glucose tolerance tests (OGTTs) were performed on each subject. Three cigarettes were smoked during the first 30 min in one of the tests. Serum glucose, insulin, and C-peptide levels were measured every 30 min; the area under the curve (AUC) and the insulin sensitivity index (ISI) were calculated; serum total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels were measured at 0 and 180 min; and blood pressure and heart rate were recorded every 5 min throughout 180 min.. Smoking acutely impaired glucose tolerance: the AUC for glucose in smokers was 25.5 +/- 1.03 mmol/l (mean +/- SE) (95% CI 22.9-28) during the smoking OGTT and 21.8 +/- 0.85 mmol/l (CI 19.2-24.3) in the control OGTT (P < 0.01); in nonsmokers, it was 19.7 +/- 0.3 mmol/l (CI 18.8-20.5) in the smoking OGTT and 18.7 +/- 0.35 mmol/l (CI 17.8-19.5) in the control OGTT (P < 0.05). Smoking acutely increased serum insulin and C-peptide levels and decreased ISI only in smokers: ISI in smokers was 55 +/- 2.8 (CI 47.4-62.6) in the control OGTT and 43 +/- 2.7 (CI 35.4-50.6) in the smoking OGTT (P < 0.05). Smoking acutely caused a rise of serum total cholesterol levels in both groups and increased LDL cholesterol and triglyceride serum levels significantly only in smokers (P < 0.05). A significant rise of blood pressure and heart rate while smoking was present in all the subjects.. Smoking acutely impaired glucose tolerance and insulin sensitivity, enhanced serum cholesterol and triglyceride levels, and raised blood pressure and heart rate. These findings support the pathogenetic role of cigarette smoking on cardiovascular risk factors.

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Cardiovascular Diseases; Case-Control Studies; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Glucose Tolerance Test; Heart Rate; Humans; Insulin; Male; Middle Aged; Reference Values; Risk Factors; Smoking; Time Factors; Triglycerides

To evaluate the relationship between islet cell antibodies (ICAs) and the cardiovascular risk profile 5 years after clinical diagnosis of NIDDM.. Five years after clinical diagnosis, we evaluated blood pressure (BP) and lipids in 17 NIDDM patients with ICA at diagnosis (age 60 +/- 4 years) and 133 NIDDM patients without ICA at diagnosis (age 61 +/- 1 year). Urinary albumin excretion was evaluated in a subset of 12 NIDDM patients with ICA at diagnosis (age 60 +/- 4 years) and 82 NIDDM patients without ICA at diagnosis (age 61 +/- 1 year).. NIDDM patients without ICA showed higher BP (140/86 +/- 2/1 mmHg vs. 128/79 +/- 3/2 mmHg; P < 0.05), total cholesterol (6.10 +/- 0.11 vs. 5.09 +/- 0.29 mmol/l; P < 0.01), LDL-to-HDL ratio (3.85 +/- 0.14 vs. 2.49 +/- 0.18; P < 0.001), and triglycerides (2.58 +/- 0.24 vs. 0.90 +/- 0.06 mmol/l; P < 0.001), lower HDL cholesterol (1.08 +/- 0.03 vs. 1.40 +/- 0.08 mmol/l; P < 0.001), and higher urinary albumin excretion (0.16 +/- 0.06 vs. 0.01 +/- 0.01 g/24 h; P < 0.05) than NIDDM patients with ICA. Among NIDDM patients without ICA, no differences concerning BP or lipids were found between obese and nonobese patients.. ICA at diagnosis of NIDDM is a marker of more favorable cardiovascular risk profile 5 years after clinical diagnosis.

Topics: Adult; Autoantibodies; Biomarkers; Blood Glucose; Blood Pressure; C-Peptide; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Follow-Up Studies; Humans; Hypertension; Islets of Langerhans; Middle Aged; Predictive Value of Tests; Risk Factors; Time Factors; Triglycerides

To test the hypothesis that hyperinsulinemia and glucose intolerance are present at an early age in australian aborigines and can be used to predict the eventual development of NIDDM.. Baseline anthropometric, pubertal stage, and blood pressure data were collected for 100 Australian aboriginal children and adolescents in 1989. Plasma concentrations of glucose, insulin, C-peptide, triglycerides, and LDL, HDL, and total cholesterol were measured before and during an oral glucose tolerance test. All measurements were repeated in 74 individuals from the original study population in 1994. Results were compared among hyperinsulinemic and normoinsulinemic subjects, and subjects with normal or abnormal glucose tolerance.. The percentage of subjects who were overweight increased from 2.7% at baseline to 17.6% 5 years later. At a mean age of 18.5 years, 8.1% of the population had impaired glucose tolerance (IGT), 2.7% had diabetes, and 21.6% had elevated cholesterol concentrations in plasma. Dyslipidemia was particularly prevalent among male subjects in the population: 34.4% had elevated plasma cholesterol and 21.9% had elevated LDL cholesterol values. Of the eight subjects who had diabetes or IGT in 1994, four were classified as hyperinsulinemic in 1989 and four were not.. The major finding of this study is the high prevalence of risk factors for NIDDM and cardiovascular disease in this population of aboriginal children and adolescents. Abnormalities of carbohydrate and lipid metabolism were well established by late in the second decade of life. Although many subjects had high insulin levels and there was evidence of insulin resistance in the population, hyperinsulinemia did not predict the development of abnormal glucose tolerance 5 years later.

Topics: Adolescent; Anthropometry; Australia; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Child; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperinsulinism; Hyperlipidemias; Insulin; Male; Native Hawaiian or Other Pacific Islander; Obesity; Risk Factors; Sex Characteristics; Sex Factors; Time Factors; Triglycerides

% of type I diabetics are not administering insulin according to the intensified conventional therapy schedules, only 16.8% of all type II diabetics are treated with diet only. Type II diabetics are much too often treated with pre-mixed insulins of too high dosage (26.2%) or with oral hypoglycemics (46.2%) of which 90% were sulphonylureas and nearly exclusively glibenclamide. Oral hypoglycemics with extrapancreatic activity or combined therapies were not common among the patients.

Topics: Adult; C-Peptide; Cardiovascular Diseases; Creatinine; Diabetes Complications; Diabetes Mellitus; Employment; Female; Germany; Glycated Hemoglobin; Government Agencies; Humans; Hypoglycemic Agents; Inpatients; Insurance, Health; Lipids; Male; Middle Aged; Serum Albumin

To compare clinical and biochemical features in non-diabetic persons with a family history of non-insulin dependent diabetes mellitus (NIDDM) to non-diabetic persons without a family history of diabetes.. Cross-sectional study.. Population-based survey in Fredericia, Denmark.. Seven hundred and forty subjects, the second generation of an earlier defined cohort was examined. The median age was 48 (range 26-65) years. Of the 740 subjects 696 were non-diabetic.. The subjects had a clinical examination.. Known risk factors for development of diabetes and cardiovascular disease.. More offspring of diabetic persons had NIDDM (chi 2 = 6.36, P < 0.05). Non-diabetic males with a family history of diabetes had a higher BMI fasting blood glucose, and triglycerides compared to males without a family history of diabetes. Non-diabetic females with a family history of diabetes had a higher BMI, fasting blood glucose. HbA1C, diastolic blood pressure, and lower HDL-cholesterol than female offspring of non-diabetics. In a multiple regression model we found that non-diabetic off-spring of diabetic persons had higher fasting blood glucose and HbA1C compared to offspring of non-diabetic persons when adjusted for the independent variables age, BMI, WHR, and sex.. Our results may indicate that the only inherited factors from NIDDM patients are plasma blood glucose. HbA1C and increased BMI which may be an indication for later diabetes, whereas other cardiovascular risk factors may be inherited independently of diabetes but associated with BMI.

Topics: Adult; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Case-Control Studies; Cross-Sectional Studies; Denmark; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Lipids; Male; Microvascular Angina; Middle Aged; Multivariate Analysis; Regression Analysis; Risk Factors

The examination of 40 patients with generalized lipodystrophy elucidated the dependence of the severity of cardiovascular disorders in these patients on the immunoreactive insulin/C-peptide index. In high values of the latter cardiovascular disorders occur more frequently. The role of insulin in pathogenesis of essential hypertension, chronic IHD is assessed.

Topics: Adolescent; Adult; C-Peptide; Cardiovascular Diseases; Coronary Disease; Humans; Hypertension; Insulin; Lipodystrophy; Middle Aged; Risk Factors; Syndrome

Data from a previous study, designed to compare metabolic risk markers for cardiovascular disease in non-users and oral contraceptive (OC) users, were analysed to evaluate the influence of OC composition on blood pressure. Healthy, female volunteers (1189 women) either not using OC (non-users) or currently using one of six different combined formulations (users) were compared. Combinations studied contained 30-40 micrograms ethinyl estradiol combined with the progestins levonorgestrel, norethindrone (at two and three different doses, respectively) or desogestrel. After statistical standardisation to account for the significantly greater age of the non-users and longer duration of OC use amongst the levonorgestrel combination users, mean blood pressure was higher, compared with non-users, in users of monophasic or triphasic levonorgestrel combinations (systolic: +4.3 mmHg (p < 0.001) and +2.7 mmHg (p < 0.001), respectively; diastolic: +2.6 mmHg (p < 0.001) and +2.3 mmHg (p < 0.05), respectively). Blood pressures in users of monophasic norethindrone and desogestrel combinations were not significantly raised and there was no increase in the proportion of women with abnormal values. Diastolic and systolic blood pressures were positively associated with oral glucose tolerance test insulin response (r = 0.11 (p < 0.01) and r = 0.15 (p < 0.001), respectively) in users but not in non-users. Currently used OC containing norethindrone or desogestrel progestins have little impact on blood pressure. Their correlated reduction in impact on insulin concentrations, though small, suggests common mechanisms through which OC affect blood pressure and insulin.. The influence of oral contraceptive (OC) composition on blood pressure was investigated in 1189 healthy volunteers recruited from centers in London and southeast England. The mean age of the non-users was 32.5 years compared with 28.0 years among OC users. The OC users were currently taking one of six types of combined OCs containing 30-40 mcg of ethinyl estradiol combined with the progestins levonorgestrel (150 mcg or a 50-125 mcg triphasic), norethindrone (500 mcg, 1000 mcg, or a 500-1000 mcg triphasic), and desogestrel (150 mcg). After adjustment for age and duration of OC use, mean blood pressure was significantly higher compared to non-users in users of monophasic or triphasic levonorgestrel combinations (systolic, +4.3 and +2.7 mm Hg, respectively; diastolic, +2.6 and +2.3 mm Hg, respectively). There was no significant increase in blood pressure levels in users of monophasic norethindrone and desogestrel combinations. Diastolic and systolic blood pressures were significantly positively associated with oral glucose tolerance test insulin responses (r = 0.11 and -0.15, respectively) in OC users but not in non-users. These findings suggest that currently used low-estrogen dose OCs containing norethindrone or desogestrel have little effect on blood pressure. They further indicate that the typical profile recorded in OC users--elevated blood pressure, increased triglycerides, decreased high density lipoprotein cholesterol, increased insulin concentrations, and reduced insulin sensitivity--mainly reflect the independent effects of the contraceptive steroids rather than a single coordinated disturbance.

Topics: Adolescent; Adult; Biomarkers; Blood Glucose; Blood Pressure; C-Peptide; Cardiovascular Diseases; Cholesterol, HDL; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Desogestrel; Ethinyl Estradiol; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin; Levonorgestrel; Middle Aged; Norethindrone; Risk Factors

An increased risk of ischemic heart disease in men with the Lewis blood group phenotype Le(a-b-) has been reported. It has been suggested that the Le(a-b-) phenotype is a genetic marker of the insulin resistance syndrome. To examine whether Le(a-b-) confers the insulin resistance syndrome, we studied a random sample of unrelated healthy young white men and women living in Copenhagen (n = 380, 18 to 32 years). All individuals had their insulin sensitivity estimated using Bergman's minimal model (intravenous glucose in combination with tolbutamide) and systolic blood pressure (SBP) was measured with a London School of Hygiene Sphygmomanometer. A number of anthropometric measurements including body mass index (BMI, kilograms/meters squared) and biochemical characteristics were performed. The Lewis blood group typing was carried out on erythrocytes. Twenty-one men had the Le(a-b-) phenotype. Compared to all other men (N = 165), the Le(a-b-) men had a significantly higher SBP (6 mm Hg, P = .0024). They also had higher values of BMI (8%, P = .016), total body fat mass (25%, P = .015), fasting values of serum insulin (32%, P = .006), serum C-peptide (20%, P = .029), and plasma glucose (8%, P = .003). The fasting values of serum lipids, plasminogen activator inhibitor (PAI-1) activity, tissue plasminogen activator (t-PA) antigen, and insulin sensitivity did not differ between Le(a-b-) men and men with other Lewis phenotypes. Altogether 194 women participated in the study of which 21 women had the Le(a-b-) phenotype. Except for a lower PAI-1 activity (45%, P = .044), no values differed between Le(a-b-) women and women with other Lewis phenotypes. The women were also stratified according to use of oral contraceptives. Le(a-b-) women using oral contraceptives (N = 8) had a significantly lower plasma level of fasting PAI-1 activity (P = .029) and t-PA antigen (P = .004) compared to women using oral contraceptives without the Le(a-b-) phenotype (N = 42). Our data support the hypothesis that Le(a-b-) men exhibit features of the insulin resistance syndrome, including higher levels of BMI, SBP, and fasting levels of serum insulin and plasma glucose. In young women no signs of the insulin resistance syndrome were found in subjects with the Le(a-b-) phenotype.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Cardiovascular Diseases; Female; Genetic Markers; Humans; Insulin; Insulin Resistance; Lewis Blood Group Antigens; Life Style; Male; Risk Factors; Sex Factors; Syndrome

Topics: Age Factors; Aged; Analysis of Variance; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Creatinine; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Follow-Up Studies; Glucagon; Humans; Insulin; Insulin Secretion; Male; Morbidity; Myocardial Ischemia; Obesity; Risk Factors; Sex Factors

Insulin treatment of patients with type 2 diabetes causes hyperinsulinaemia and improves glycaemic control. We have studied how this affects risk factors for cardiovascular disease.. Patients with secondary failure to oral hypoglycaemic agents were studied whilst still taking oral agents and after insulin treatment for 8 weeks in an open study.. Department of Internal Medicine, University Hospital, Linköping.. Ten consecutive patients with type 2 diabetes and secondary failure to oral hypoglycaemic agents.. Switching oral treatment to insulin treatment.. Effect on several cardiovascular risk factors.. Fasting and postprandial plasma insulin concentrations were increased by insulin treatment whereas C-peptide concentrations were lowered. HbA1c was reduced from 8.9 +/- 0.3% (mean +/- SEM) to 6.3 +/- 0.2% after 8 weeks. There was a weight gain of 2.8 +/- 0.7 kg. Plasma concentrations of total- and very-low-density-lipoprotein (VLDL) cholesterol, VLDL-, low density lipoprotein and high-density-lipoprotein triglycerides were all reduced. The plasma concentration of apolipoprotein B was also lowered. Tissue plasminogen activator antigen measured after venous occlusion showed a significant reduction whilst plasminogen activator inhibitor 1 activity was 26.0 +/- 9.8 IU ml-1 on oral treatment and 18.2 +/- 4.7 IU ml-1 on insulin treatment (NS). Albumin excretion in the urine was reduced and the percentage reduction correlated with the percentage lowering of the tissue plasminogen activator antigen concentration after venous occlusion but not with the percentage change of basal tissue plasminogen activator antigen concentration.. Insulin treatment of patients with type 2 diabetes and secondary failure to oral hypoglycaemic agents causes hyperinsulinaemia and improves or has no unfavourable effect on several cardiovascular risk factors.

Topics: Adult; Aged; Albuminuria; Analysis of Variance; Blood Coagulation; Blood Glucose; Blood Pressure; C-Peptide; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Lipoproteins; Male; Middle Aged; Risk Factors