c-peptide and Coronary-Disease

This study aims to investigate the effects of serum C-peptide levels on blood lipid and cardiovascular and cerebrovascular injury in patients with type 2 diabetes mellitus (T2DM).. China National Knowledge Infrastructure (CNKI), WanFang Data, PubMed, Web of Science, and Embase databases were searched for relevant studies published from January 2010 to June 2021. All retrieved randomized controlled trials that evaluated the effect of serum C-peptide levels on blood lipids or cardiovascular and cerebrovascular injuries in T2DM patients were included in our study. Patients in the included studies were divided into normal C-peptide group (control group) and low C-peptide group (treatment group) according to fasting C-peptide levels. Meta-analysis was performed using Stata16.0.. A total of 7 studies were included for the meta-analysis. Compared with the control group, the treatment group was associated with a higher incidence of coronary heart disease (OR = 4.89; 95% CI: 1.13, 21.24;. Low serum C-peptide level significantly increases the incidence of coronary heart disease and cerebral infarction. Additionally, low serum C-peptide increases blood lipid level and promotes lipid deposition. Collectively, low serum C-peptide has a negative impact on the occurrence and development of T2DM and therefore serum C-peptide level needs to be adjusted timely.

Topics: C-Peptide; Cerebral Infarction; Cholesterol; Coronary Disease; Diabetes Mellitus, Type 2; Humans; Lipids; Randomized Controlled Trials as Topic

Topics: Adolescent; Adult; Aged; C-Peptide; Child; Coronary Disease; Diabetes Complications; Glucose; Humans; Insulin; Insulin Resistance; Leptin; Middle Aged; Obesity; Potassium; Risk Factors; Vascular Resistance

The accumulation of Nxi-(carboxymethyl)lysine (CML), a product of glycoxidation and lipoxidation reactions, on tissue proteins is related to the formation and acceleration of diabetic and nondiabetic atherosclerotic lesions. Yet, little is known about the levels of circulating serum CML-containing protein in nondiabetic patients with clinical symptoms of advanced atherosclerosis. We measured the levels of immunoreactive CML in sera from non-diabetic patients with accelerated symptoms of coronary heart disease, from diabetic patients with no late complications, and from healthy individuals. Serum CML was significantly higher in non-diabetic patients with coronary heart disease than in healthy control subjects and was comparable to serum CML in patients with type 2 diabetes mellitus without late complications and coronary heart disease. In nondiabetic patients with coronary heart disease, a significant inverse correlation was found between serum levels of CML and proinsulin C-peptide, a marker of pancreatic beta cells activity that affects microvascular function. Serum levels of CML and high density lipoprotein (HDL) were positively correlated in this group. We conclude that glycoxidation and lipoxidation are associated with serum HDL levels and the secretive capacity of pancreatic beta cells in nondiabetic patients with coronary heart disease.

Topics: Arteriosclerosis; C-Peptide; Carbohydrate Metabolism; Cholesterol, HDL; Coronary Disease; Diabetes Mellitus; Enzyme-Linked Immunosorbent Assay; Female; Glucose; Humans; Islets of Langerhans; Lipid Metabolism; Lipoproteins, HDL; Lysine; Male; Middle Aged; Oxidation-Reduction

The acute effect of the anti-ischemic potassium channel opener nicorandil on glucose tolerance and post-challenge insulin levels was investigated in 11 subjects (6 males and 5 females, age 59 +/- 2 years) with borderline fasting blood glucose in a single blinded randomised study. All participants were submitted to two oral glucose tolerance tests in randomised order, once without any premedication and once 30 minutes after oral administration of 20 mg nicorandil. This single dose of nicorandil significantly increased blood glucose levels at 120 minutes (173 +/- 16 vs. 150 +/- 11 mg/dl, p < 0.05 by ANOVA) and 180 minutes (106 +/- 11 vs. 88 +/- 7 mg/dl, p < 0.05 by ANOVA) after ingestion of 75 mg of glucose. Serum insulin levels were not significantly altered. In conclusion we suggest that controlled studies in patients with coronary artery disease should be performed to investigate whether long term treatment with nicorandil increases progression rates from impaired glucose tolerance to type-II diabetes and/or from normal to impaired glucose tolerance with a possibly negative impact on the course of cardiovascular disease in comparison to conventional anti-anginal drugs.

Topics: Administration, Oral; Blood Glucose; C-Peptide; Coronary Disease; Fasting; Female; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Male; Middle Aged; Nicorandil; Radioimmunoassay; Time Factors; Vasodilator Agents

There are scarce data dealing with the degree of postprandial lipaemia after sulphonylurea administration. The aim of this study was to examine the effect of acute glibenclamide administration on postprandial lipaemia in Type 2 diabetic patients.. Eight randomly selected Type 2 diabetic individuals, aged 43-65 years (mean, 54 years), who had never received any anti-diabetic drug, were included in the study. Each patient was given a 485 kcal mixed meal (45% fat, 40% carbohydrate and 15% protein) twice on separate days after an overnight fast: once with placebo and once with 5 mg glibenclamide, per os, in a random order. The two tests were performed with an interval of 7 days. Venous blood samples were drawn just before and 2 h, 4 h and 6 h after meal consumption. Total triglyceride levels in plasma, in chylomicrons (CM), in CM-deficient plasma, in very low-density lipoprotein (VLDL) subfractions (VLDL-1, VLDL-2) and in intermediate-density lipoprotein (IDL) were determined. Free fatty acid (FFA) and total cholesterol levels in plasma, as well as high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol levels in CM-deficient plasma, were also measured. Finally, serum glucose, insulin and C-peptide concentrations were measured in each sample.. As expected there was a significant decrease in postprandial glycaemia after glibenclamide administration compared to placebo (mean area under the curve values: AUC = 53.3 +/- 18.2 and 69.1 +/- 21.6 mm/h, P = 0.00009). In addition, the mean AUC values of insulin and C-peptide were significantly greater after drug administration. The AUC values of total plasma triglyceride and of CM triglyceride following glibenclamide administration were significantly lower compared to placebo, while the AUC values of postprandial triglyceride in CM-deficient plasma and of postprandial triglyceride in VLDL-1, VLDL-2 and IDL were not different after drug administration compared to placebo. Finally, no significant differences were noted in the AUC values of total cholesterol, LDL cholesterol, HDL cholesterol and plasma FFA levels after glibenclamide administration.. These results demonstrate that glibenclamide administration improves postprandial hypertriglyceridaemia acutely by reducing postprandial triglycerides of intestinal origin.

Topics: Adult; Area Under Curve; Blood Glucose; C-Peptide; Cholesterol; Chylomicrons; Coronary Disease; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Glyburide; Humans; Hypertriglyceridemia; Hypoglycemic Agents; Insulin; Lipoproteins, VLDL; Middle Aged; Postprandial Period; Triglycerides

We investigated the influence of treatment with nicorandil, a K-channel opener currently used for angina, on glucose homeostasis in patients with non-insulin-dependent diabetes mellitus (NIDDM) and coronary artery disease (CAD). Adenosine triphosphate (ATP)-sensitive K (K-ATP) channels are present in various tissues, including pancreatic B cells and skeletal muscle, and are the putative targets of this agent. Nine NIDDM patients with CAD and five healthy subjects participated in the study. Fasting plasma levels (mean+/-SEM) of glucose (144+/-11 to 180+/-22 mg/dL, P<.05) and insulin (5.8+/-1.6 to 7.0+/-1.8 microU/mL, P<.05) and hemoglobin A1c (7.54+/-0.47 to 8.11+/-0.55%, P<.01) increased significantly in nine NIDDM patients after treatment with nicorandil at a dose of 5 mg three times daily for 2 to 8 months. Glucose tolerance as examined by an identical meal test deteriorated (P<.001), but the insulin response did not change significantly. A washout of nicorandil for 1 to 4 months restored glucose tolerance almost to pretreatment levels in four patients. A 5- to 7-day trial of nicorandil (5 mg three times daily) in five healthy subjects resulted in a marginal to twofold increase in fasting plasma insulin, reflecting the progression of insulin resistance. In addition, three healthy subjects showed a substantial reduction in the glucose infusion rate (GIR) required in the euglycemic-hyperinsulinemic clamp study. Since the therapeutic dose of nicorandil did not affect pancreatic B-cell function but caused insulin resistance in both healthy and NIDDM subjects, we conclude that K-ATP channels play a regulatory role in insulin-mediated glucose transport in humans.

Topics: Adenosine Triphosphate; Aged; ATP-Binding Cassette Transporters; Blood Glucose; C-Peptide; Coronary Disease; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; KATP Channels; Male; Middle Aged; Nicorandil; Potassium Channels; Potassium Channels, Inwardly Rectifying

The long-term metabolic effects of n-3 fatty acids were studied in patients with coronary artery disease. They were investigated before and 9 mo after bypass surgery. After postoperative randomization, 260 patients received 4 g fish-oil concentrate/d (approximately 3.4 g eicosapentaenoic and docosahexaenoic acids/d), whereas 251 patients comprised the control group. No group differences in the intake of energy and nutrients, apart from n-3 fatty acids, were discerned from dietary records. Compliance was affirmed by analyses of serum phospholipid fatty acids. Serum triglyceride concentrations were lowered by 19.1% in the fish-oil group, but no influence on the concentrations of cholesterol or apolipoproteins A-I and B-100 was seen. The concentrations of plasma glucose and serum insulin and C-peptide were not influenced by fish oil. The activity of liver enzymes increased slightly, but significantly, in the fish-oil group, whereas no group difference in the serum concentrations of thiobarbituric acid-reactive substances was observed. Thus, no adverse metabolic effects of long-term fish-oil supplementation assumed to be of clinical importance were seen.

Topics: Aged; Alanine Transaminase; Apolipoprotein A-I; Apolipoprotein B-100; Apolipoproteins B; Aspartate Aminotransferases; Blood Glucose; C-Peptide; Cholesterol; Coronary Disease; Fatty Acids, Omega-3; Female; Fish Oils; gamma-Glutamyltransferase; Humans; Insulin; Male; Middle Aged; Phospholipids; Prospective Studies; Thiobarbituric Acid Reactive Substances; Time Factors; Triglycerides

Diabetes and prediabetic conditions are growing cardiovascular risk factors. Better understanding and earlier recognition and treatment of dysglycemia-related risk are health priorities. We assessed the predictive value of 3 proposed new markers for diabetes and cardiovascular risk. We tested whether the plasma levels of (1) asymmetric dimethylarginine (ADMA), (2) cortisol/cortisone (Cl/Cn) ratio, and (3) C-peptide predicted glycemic status, coronary artery disease, and death or myocardial infarction (MI) in a nested case-control cohort (N = 850) with normal fasting glucose (< 110 mg/dL), impaired fasting glucose (110-125), or diabetic (> or = 126) status.. High-sensitivity C-reactive protein (hsCRP) served as a control risk marker. Follow-up averaged 2.6 +/- 1.4 years. High-pressure liquid chromatography with pre-column derivitization and fluorescence was used to assay ADMA, liquid chromatography/tandem mass spectrometry for Cl and Cn, and chemiluminescent immunoassay for C-peptide.. Asymmetric dimethylarginine levels were positively associated with glycemic category (P < .001). Quartiles 2 to 4 ADMA also conferred increased risk of death/MI independent of hsCRP and other risk factors (adjusted hazard ratio, 2.1; P = .002). Cortisol/Cortisone ratios (P = .013) and C-peptide (P = .047) were associated with glycemic categories but less strongly than ADMA. Quartiles 2 to 4 Cl/Cn were protective against incident death/MI (adjusted hazard ratio, 0.48; P < .001), whereas C-peptide did not predict outcomes.. Among a high coronary risk case-control cohort, ADMA (strongly), Cl/Cn (moderately), and C-peptide (weakly) predicted glycemic categories. Asymmetric dimethylarginine and Cl/Cn also predicted clinical outcome independent of and more strongly than hsCRP. Asymmetric dimethylarginine and Cl/Cn represent promising new candidate markers of dysglycemia and associated cardiovascular risk.

Topics: Arginine; Biomarkers; Blood Glucose; C-Peptide; Case-Control Studies; Coronary Disease; Cortisone; Diabetes Mellitus; Female; Humans; Hydrocortisone; Hyperinsulinism; Logistic Models; Male; Middle Aged; Myocardial Infarction; Nitric Oxide Synthase; Predictive Value of Tests; Risk Assessment

Coronary artery disease (CAD) is the most common cause of death in patients with type 1 diabetes. Asymptomatic CAD is common in uremic diabetic patients, but its prevalence in nonuremic type 1 diabetic patients is unknown. The prevalence of CAD was determined by coronary angiography and the performance of noninvasive cardiac investigation evaluated in type 1 diabetic islet transplant (ITX) candidates with preserved renal function.. A total of 60 consecutive type 1 diabetic ITX candidates (average age 46 years [mean 24-64], 23 men, and 47% ever smokers) underwent coronary angiography, electrocardiographic stress testing (EST), and myocardial perfusion imaging (MPI) in a prospective cohort study. CAD was indicated on angiography by the presence of stenoses >50%. Models to predict CAD were examined by logistic regression.. Most subjects (53 of 60) had no history or symptoms of CAD; 23 (43%) of these asymptomatic subjects had stenoses >50%. CAD was associated with age, duration of diabetes, hypertension, and smoking. Although specific, EST and MPI were not sensitive as predictors of CAD on angiography (specificity 0.97 and 0.93, sensitivity 0.17 and 0.04, respectively) but helped identify two of three subjects requiring revascularization. EST and MPI did not enhance logistic regression models. A clinical algorithm to identify low-risk subjects who may not require angiography was highly sensitive but was applicable only to a minority (n = 8, sensitivity 1.0, specificity 0.27, negative predictive value 1.0).. Nonuremic type 1 diabetic patients with hypoglycemic unawareness and/or metabolic lability referred for ITX are at high risk for asymptomatic CAD despite negative noninvasive investigations. Aggressive management of cardiovascular risk factors and further investigation into optimal cardiac risk stratification in type 1 diabetes are warranted.

Topics: Adult; Aged; Awareness; Blood Pressure; C-Peptide; Coronary Angiography; Coronary Disease; Coronary Stenosis; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Female; Humans; Hypoglycemia; Islets of Langerhans Transplantation; Male; Middle Aged; Postoperative Complications; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity; Smoking

IGFs and their binding proteins (IGFBPs) are produced both systemically and locally by cells of the cardiovascular system. As growth promoters, they may play a role in atherosclerosis.. Case-control, cross-sectional.. A total of 95 nondiabetic male patients with coronary heart disease (CHD) and 92 probands from the Prospective Cardiovascular Munster (PROCAM) who were below the age of 60 years and matched by age, body mass index (BMI) and smoking habits.. We analysed the strength and independence of associations of angiographically assessed presence of CHD with BMI, systolic and diastolic blood pressure, total, high-density lipoprotein (HDL) and LDL cholesterol, triglycerides, lipoprotein(a), apolipoproteins A-I and B, total and free IGF-I, IGF-II, IGFBP-1, IGFBP-3, IGFBP-5, acid-labile subunit (ALS), insulin, C-peptide, testosterone, DHEAS and sex hormone binding globulin.. Using multivariate statistical analysis, the presence of CHD had significant positive associations with total IGF-I, IGFBP-5, ALS and IGFBP-3. These associations were independent of each other as well as of traditional risk factors, insulin and sex hormones.. These observations may indicate a pathogenetic role of the GH/IGF axis in coronary atherosclerosis.

Topics: C-Peptide; Carrier Proteins; Case-Control Studies; Coronary Angiography; Coronary Disease; Cross-Sectional Studies; Dehydroepiandrosterone Sulfate; Glycoproteins; Health Surveys; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Protein 5; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Middle Aged; Multivariate Analysis; Sex Hormone-Binding Globulin; Somatomedins; Testosterone

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

To report the cardiac events in type 2 diabetic outpatients screened for unknown asymptomatic coronary heart disease (CHD) and followed for 5 years.. During 1993, 925 subjects aged 40-65 years underwent an exercise treadmill test (ETT). If it was abnormal, the subjects then underwent an exercise scintigraphy. Of the 925 subjects, 735 were followed for 5 years and cardiac events were recorded.. At the entry of the study, 638 of the 735 followed subjects had normal ETT, 45 had abnormal ETT with normal scintigraphy, and 52 had abnormal ETT and abnormal scintigraphy. The 52 subjects with abnormal scintigraphy and ETT underwent a cardiological and diabetological follow-up; the subjects with just abnormal ETT had a diabetological follow-up only. During the follow-ups, 42 cardiac events occurred: 1 fatal myocardial infarction (MI), 20 nonfatal MIs, and 10 cases of angina in the 638 subjects with normal ETT; 1 fatal MI in the 45 subjects with normal scintigraphy; and 1 fatal MI and 9 cases of angina in the 52 subjects with abnormal scintigraphy. In these 52 subjects all cardiac events were significantly more frequent (chi(2) = 21.40, P < 0.0001) but the ratio of major (cardiac death and MI) to minor (angina) cardiac events was significantly lower (P = 0.002). Scintigraphy abnormality (hazard ratio 5.47; P < 0.001; 95% CI 2.43-12.29), diabetes duration (1.06; P = 0.021; 1.008-1.106), and diabetic retinopathy (2.371; P = 0.036; 1.059-5.307) were independent predictors of cardiac events on multivariate analysis.. The low ratio of major to minor cardiac events in the positive scintigraphy group may suggest, although it does not prove, that the screening program followed by appropriate management was effective for the reduction of risk of major cardiac events.

Topics: Age Distribution; Aged; Blood Pressure; Body Mass Index; C-Peptide; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Exercise Test; Follow-Up Studies; Humans; Italy; Lipids; Mass Screening; Middle Aged; Proportional Hazards Models; Smoking

Insulin or insulin resistance is considered a coronary heart disease (CHD) risk factor, but proinsulin may have a stronger association with CHD than insulin. The role of sex differences in this association is unclear. We examined the cross-sectional association of proinsulin and insulin with CHD in older men and women without diabetes.. A cross-sectional study of community-dwelling men (n=554) and women (n=902), 50 to 97 years of age, without diabetes by history or oral glucose tolerance test, was done between 1992 and 1996; plasma levels of intact insulin, proinsulin, and C-peptide were measured by radioimmunoassay. Based on questionnaire, medical history, or ECG abnormalities, 25% of men (n=136) and 24% of women (n=214) had prevalent CHD. All insulin variables were positively correlated with CHD risk factors. Compared with those without CHD, men and women with CHD had significantly higher levels of proinsulin. Women but not men with CHD also had higher levels of C-peptide and fasting and postchallenge insulin. Only proinsulin was significantly and independently associated with prevalent CHD in both men (OR=2.41, 1.42 to 4.11) and women (OR=1.80, 1.22 to 2.64) (adjusted for age, body mass index, systolic blood pressure, and HDL cholesterol). Similar analyses for fasting and postchallenge intact insulin and for C-peptide showed that among these three variables, only postchallenge insulin was significantly associated with CHD, and only in women.. In older nondiabetic men and women, proinsulin was more strongly and consistently associated with CHD than was intact insulin.

Topics: Aged; Aged, 80 and over; Blood Pressure; Body Mass Index; C-Peptide; California; Cholesterol, HDL; Cohort Studies; Coronary Disease; Cross-Sectional Studies; Diabetes Mellitus; Electrocardiography; Female; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Odds Ratio; Proinsulin; Radioimmunoassay; Risk Factors; Sex Distribution; Sex Factors; Surveys and Questionnaires; White People

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

Insulin resistance is known as an important risk factor for coronary artery disease (CAD). However, CAD-related mortality in Japanese type 2 diabetics is lower than in Caucasians. To investigate whether insulin resistance is related to CAD in Japanese type 2 diabetics, we measured insulin sensitivity and several coronary risk factors in Japanese patients with type 2 diabetes with and without CAD. Thirty-three patients with definite CAD and 33 age- and sex-matched patients without CAD (control) were studied. Insulin sensitivity was assessed by the K index of insulin tolerance test (KITT). Clinical characteristics, classical risk factors, lipoprotein (a), and insulin sensitivity were compared between the two groups. Patients with CAD had a significantly longer duration of diabetes (9.0 +/- 1.4 vs. 5.5 +/- 0.9 years, P < 0.05, respectively), were mostly hypertensive (69.7 vs. 39.4%, P < 0.05), and more likely to be treated with insulin (45.5 vs. 18.2%, P < 0.05) compared with the control. Concerning the metabolic parameters, patients with CAD had a significantly higher insulin resistance than control (2.40 +/- 0.15 vs. 3.23 +/- 0.17%/min, P < 0.01, respectively), higher triglyceride (1.39 +/- 0.10 vs. 1.05 +/- 0.05 mmol/l, P < 0.05), lower HDL cholesterol (1.05 +/- 0.05 vs. 1.28 +/- 0.06 mmol/l, P < 0.05), and higher lipoprotein (a) (27.5 +/- 4.3 vs. 17.4 +/- 2.0 mg/dl, P < 0.05). Multiple logistic regression analysis indicated that hypertension, insulin resistance, high lipoprotein (a) and triglyceride, and low HDL cholesterol were independently related to CAD. Our results suggest that insulin resistance per se is a significant risk factor for CAD in Japanese patients with type 2 diabetes.

Topics: Aged; Asian People; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Cholesterol, HDL; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Japan; Lipoprotein(a); Male; Middle Aged; Myocardial Infarction; Risk Factors; Smoking; Triglycerides; White People

The major concern about percutaneous transluminal coronary angioplasty (PTCA) is the high incidence of restenosis.. Demographic, clinical and biochemical data were recorded 2 weeks prior to PTCA in 388 patients fulfilling the criteria for initial stenosis, successful PTCA, and angiographic follow-up after 6 months. Restenosis was evaluated by quantitative coronary angiography.. Variables predictive of restenosis in univariate analysis were diabetes mellitus, male gender, and the levels of high density lipoprotein (HDL) cholesterol, apolipoprotein A1 (Apo A1) and thio-barbituric acid-reactive substances (TBARS). In trend analysis through quartiles TBARS and fasting glucose levels were significantly associated with restenosis (p = 0.016 and 0.044, respectively), whereas the negative predictivity of Apo A1 and HDL-cholesterol were of borderline significance. In multivariate analysis male gender and diabetes mellitus showed predictivity of significance, and a negative predictivity was also apparent for HDL-cholesterol.. We conclude that diabetes mellitus, male gender, and low HDL-cholesterol are predictors of restenosis 6 months after PTCA. In addition, TBARS may be a marker for the development of restenosis after PTCA.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Biomarkers; Blood Glucose; C-Peptide; Cohort Studies; Coronary Angiography; Coronary Disease; Diabetes Complications; Female; Follow-Up Studies; Humans; Hypertension; Insulin; Lipids; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Recurrence; Risk Factors; Smoking

Low serum levels of high-density lipoprotein (HDL) cholesterol or apolipoprotein A-I and high serum levels of insulin increase the risk of coronary heart disease (CHD) and can indicate insulin resistance. We tested the strength, independence, and interactions of associations between HDL cholesterol (or apolipoprotein A-I), insulin (or C-peptide), glucose, and CHD in 95 male nondiabetic patients with CHD who were <60 years old, in 92 probands from the PROCAM study, and in 61 non-cardiologic patients; all subjects were matched by age, body mass index, and smoking habits. Systemic hypertension (odds radio [OR] 2.8, 95% confidence intervals [CI] 1.6 to 4.8), high serum levels of glucose (OR 2.3, 95% CI 1.6 to 4.8), insulin (OR 2.1, 95% CI 1.3 to 3.6), and C-peptide (OR 4.1, 95% CI 2.2 to 7.5) as well as low serum levels of HDL cholesterol (OR 2.0, 95% CI 1.1 to 3.5) or apolipoprotein A-I (OR 3.9, 95% CI 2.1 to 7.1) had significant associations with CHD. At multivariate analysis, systolic blood pressure, glucose, apolipoprotein A-I, and C-peptide, but not HDL cholesterol and insulin, had consistent independent associations with CHD. Thus, the combined measurement of apolipoprotein A-I and C-peptide may improve the identification of nondiabetic patients at increased risk for CHD.

Topics: Adult; Apolipoprotein A-I; C-Peptide; Case-Control Studies; Cholesterol, HDL; Coronary Disease; Humans; Insulin; Male; Middle Aged; Myocardial Infarction; Regression Analysis; Risk Factors

Our study was aimed at determining whether beneficial modification of carbohydrate metabolism can be obtained after a short-term training program and whether it is associated with an increase in binding and degradation of (125)I-insulin by erythrocyte receptors that suggests a decrease in insulin resistance.. The study was conducted in a group of 20 patients aged 56 +/- 1.9 years (mean +/- SEM), within 1 to 6 months after coronary bypass surgery. All patients completed 15 training sessions based on 30 min of cycling with a constant load. Before and after a 3-week training program, glucose, insulin, and C-peptide blood levels, as well as binding and degradation of (125)I-insulin by erythrocyte receptors, were determined.. A statistically significant decrease was found in the blood glucose level, from 111.2 +/- 4.2 to 97.8 +/- 3.5 mg/dL (p < 0.01); this decrease was not accompanied by significant insulin concentration changes. There was also a significant increase in insulin binding, from 0.535 +/- 0.059 to 0.668 +/- 0.042 pg (125)I/10(11) RBCs (p < 0.01), and degradation from 7.64 +/- 0.54 to 9.49 +/- 0.58 pg (125)I/10(11) RBCs (p < 0.05).. The results indicated that even short-term endurance training in patients rehabilitated after coronary bypass surgery induced favorable modification of glucose metabolism, presumably caused by a decrease in insulin resistance.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Coronary Artery Bypass; Coronary Disease; Exercise; Exercise Therapy; Humans; Insulin; Insulin Resistance; Lipids; Male; Middle Aged; Treatment Outcome

Syndrome X is used to describe a constellation of factors that lead to coronary heart disease (CHD): hypertension, hyperinsulinemia, impaired glucose tolerance, and an abnormality in lipid metabolism. We investigated the relationship between serum levels of C-peptide immunoreactivity (CPR) and diabetic complications in 256 patients with type-2 diabetes mellitus. The serum level of CPR was measured by radioimmunoassay (RIA). Diabetic patients were divided into 3 groups according to the serum level of CPR as follows: low CPR (n = 19, <0.7 ng/ml), normal CPR (n = 174, 0.7 to 2.2 ng/ml) and high CPR (n = 63, >2.2 ng/ml). The body mass index (BMI) and the serum level of triglycerides were significantly higher in the high CPR group (P < 0.05, respectively) compared with normal CPR group. The prevalence of hypertension was significantly higher in the high CPR group than in the other 2 groups (low CPR: 16%, normal CPR: 28%, high CPR: 38%). The frequency of the number of patients receiving insulin therapy was greater in the low CPR group than in the other 2 groups, (low CPR: 58%, normal CPR: 15%, high CPR: 11%). The serum CPR level was significantly lower in patients with than without proliferative retinopathy or macroalbuminuria. Our conclusion is that the present data suggest that an increased serum level of CPR is associated with obesity, elevated serum triglycerides, and hypertension in patients with type-2 diabetes mellitus. A low CPR level leading to hyperglycemia is associated with the progression of diabetic microangiopathies, such as retinopathy and nephropathy.

Topics: Albuminuria; Body Mass Index; C-Peptide; Coronary Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Female; Humans; Hypertension; Hypertriglyceridemia; Insulin; Male; Middle Aged; Obesity; Risk Factors

Hyperinsulinaemia and dyslipoproteinaemia are markers and risk factors for coronary artery disease (CAD) and non-insulin-dependent diabetes mellitus (NIDDM). We investigated the influence of a tumour necrosis factor beta (TNF-beta) gene polymorphism on serum parameters related to these metabolic disorders in patients with CAD.. A total of 199 patients with CAD and 81 control subjects with angiographically normal coronary arteries were studied. A digestion of amplified DNA with NcoI revealed three fragment patterns: homozygosity for TNF-beta *1 or TNF-beta *2 and heterozygosity (TNF-beta *1/*2).. Patients with CAD who had increased serum insulin or C-peptide (fasting and after glucose load) were predominantly heterozygous for TNF-beta (72% vs. 47%) and less frequently homozygous for TNF-beta *2 (22% vs. 43%, P = 0 x 0.03).. This study demonstrates an association of TNF-beta alleles with the risk factor hyperinsulinaemia in CAD. Genomic variants of TNF-beta may therefore contribute to the complex susceptibility for the metabolic syndrome in patients with CAD.

Topics: Alleles; C-Peptide; Coronary Disease; Gene Frequency; Glucose Tolerance Test; Heart Valve Diseases; Heterozygote; Homozygote; Humans; Hyperinsulinism; Insulin; Lymphotoxin-alpha; Male; Middle Aged; Polymorphism, Genetic

Increasing attention is being paid to disturbances in glucose metabolism as key explanatory factors for the development of coronary artery disease. We studied the prevalence of impaired glucose tolerance and non-insulin-dependent diabetes and the levels of plasma insulin after an oral glucose tolerance test in 99 men with heart disease but without a history of diabetes referred to coronary arteriography; we also compared the outcome with a matched control group (n = 116). The severity of atherosclerosis in coronary angiograms was evaluated according to glucose tolerance status. Among the 99 patients with coronary artery disease, 37.4% had an abnormal oral glucose tolerance test result, whereas only 18.1% of the control group had an abnormal result (p < 0.01). Moreover, patients with heart disease and normal glucose tolerance were hyperinsulinemic compared with the control group (p < 0.01). By analysis of variance no statistically significant difference in severity of coronary atherosclerosis on coronary angiograms was found. In conclusion, we demonstrated frequent disturbances in glucose metabolism indicating insulin resistance in patients with ischemic heart disease without a history of diabetes, but we could not demonstrate a relation between these disturbances and degree of coronary atherosclerosis.

Topics: Adult; Aged; Albuminuria; Analysis of Variance; Blood Glucose; C-Peptide; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Coronary Disease; Diabetes Mellitus, Type 1; Glucose; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male; Middle Aged; Myocardial Ischemia; Prevalence; Proinsulin

Prolongation of heart rate-adjusted QT length (corrected QT interval [QTc]) is associated with elevated risk of coronary heart disease and sudden death. This may have to do with autonomic cardiac control. Because insulin is known to stimulate sympathetic activity, we studied the association of insulin level and glucose tolerance with QTc. In 1990, 383 elderly men 70-89 years of age without previous myocardial infarctions or known diabetes had a 12-lead electrocardiogram recorded and glucose tolerance determined in the frame of an ongoing follow-up study. QTc was significantly associated with fasting glucose, insulin, and C-peptide and glucose levels 60 and 120 min after an oral glucose load. For fasting C-peptide and the area under the glucose curve (AUGC), this association could not be explained by the concomitant occurrence of other risk factors of coronary heart disease. Furthermore, fasting C-peptide and the AUGC were independently additive predictors of QTc duration. The difference in QTc between men in the extreme quintiles of both variables was 22 ms. QTc prolongation seems to be part of the insulin resistance syndrome. The association may be explained by increased sympathetic activity induced by high insulin levels. An additional explanation could be an effect of high insulin, impaired glucose utilization, or both on membrane activity of myocardial cells.

Topics: Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Coronary Disease; Electrocardiography; Fasting; Glucose Tolerance Test; Humans; Insulin; Male; Netherlands; Risk Factors

Controversy persists about whether hyperinsulinemia and hyperproinsulinemia are independent risk markers for coronary atherosclerosis. A common limitation of most previous studies has been imprecise categorization of disease status in normal and coronary artery disease (CAD) groups. We assessed the relationship of pancreatic beta-cell secretory products and premature CAD in a case-control study of 134 nondiabetic subjects, aged < or = 55 years old, carefully defined for CAD status by catheterization and/or thallium stress studies. Case patients comprised 66 patients with premature CAD, and control subjects (non-CAD group) included 68 patients without CAD but with traditional CAD risk factors and chest pain and/or abnormal electrocardiograms but normal catheterization and/or thallium stress studies. In addition to the CAD and non-CAD group comparison, both groups were compared with a reference group of 27 mixed lean and obese control volunteers. All CAD and non-CAD patients had a 3-h 75-g oral glucose tolerance test with measurement of fasting and post-glucose load immunoreactive insulin (IRI), specific insulin (INS), proinsulin-like material (PI), and C-peptide. Increased fasting insulin and fasting proinsulin levels both were statistically significantly associated with higher odds of being in either the premature CAD and the non-CAD groups when compared with the reference group in a polychotomous logistic regression model (odds ratio of at least 1.20 for a 20% increase in each beta-cell secretory product in both comparisons, P < 0.05). However, increased pancreatic beta-cell secretory hormone levels did not show a statistically significant relative risk for being in the premature CAD group when compared with the non-CAD group. After adjustment for BMI, all statistically significant associations disappeared for IRI, INS, and PI when the odds favoring being in the CAD and non-CAD groups were compared versus the reference group. Furthermore, the odds of being in the premature CAD and non-CAD groups when compared with the reference group were not significantly associated to the ratio of PI to insulin and C-peptide. Thus, although there is a statistically significant association between the odds of having premature CAD with elevated insulin and proinsulin levels compared with the reference group, these findings are equally common in subjects with traditional CAD risk factors without detectable CAD. Furthermore, the association of higher insulin and proinsulin

Topics: Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Chest Pain; Coronary Disease; Diabetes Mellitus; Ethnicity; Female; Glucose Intolerance; Humans; Insulin; Male; Middle Aged; Odds Ratio; Proinsulin; Reference Values; Regression Analysis; Risk Factors; Sex Factors; Smoking

The authors examined the correlations of Type A behavior and vital exhaustion with the metabolic hormonal variables of the hypothalamic-pituitary-adrenal axis (ACTH and cortisol), as well as with the ensuing parameters (insulin, glucose, and C-peptide). The participants were 64 healthy middle-aged men with stressful work. The authors found that Type A behavior and vital exhaustion were not correlated but made independent contributions to the single metabolic hormonal variables. The central finding was that when the whole HPA axis, Type A behavior, and exhaustion were all analyzed at the same time, Type A behavior per se had different, even opposite, hormonal correlates from Type A behavior associated with vital exhaustion. Type A behavior by itself was not related to a metabolic hormonal dysfunction. However, the Type A by vital exhaustion interaction was statistically significant. This finding suggests that the quality or components of Type A behavior, particularly the presence of vital exhaustion, may be more important than the intensity of Type A behavior considered alone.

Topics: Adrenocorticotropic Hormone; Adult; Blood Glucose; C-Peptide; Coronary Disease; Energy Metabolism; Hormones; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Male; Mental Fatigue; Middle Aged; Pituitary-Adrenal System; Risk Factors; Type A Personality

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

The association between psychological coronary risk factors and serum insulin, and C-peptide and blood glucose concentrations, [the latter measured while fasting and during the oral glucose tolerance test (OGTT)], was examined in healthy middle-aged men (n = 64). The results indicate that among the evaluated psychological risk factors, high levels of hostile paranoia and vital exhaustion were most consistently associated with an enhanced insulin/glucose ratio, and enhanced insulin, C-peptide and glucose responses during OGTT. The associations persisted after controlling for age, smoking, alcohol consumption and visceral fat distribution. Thus, in addition to age, life-style factors and obesity, psychological factors may have an effect on insulin and glucose metabolism.

Topics: Adult; Anger; Blood Glucose; C-Peptide; Coronary Disease; Glucose Tolerance Test; Hostility; Humans; Insulin; Life Style; Male; Middle Aged; Obesity; Paranoid Disorders; Psychiatric Status Rating Scales; Risk Factors; Type A Personality

Since second-generation (Nisei) Japanese Americans are prone to develop the insulin resistance syndrome, younger third-generation (Sansei) Japanese Americans from a cross-sectional 10% volunteer sample of Sansei men (n = 115) and women (n = 115) 34 years or older in King County, Washington with normal glucose tolerance or IGT were examined for metabolic and adipose risk factors associated with this syndrome. After an overnight 10-h fast, blood samples were taken for measurement of glucose, insulin, C-peptide, lipids, and lipoproteins, followed by a 3-h 75-g oral glucose tolerance test with blood samples taken for glucose, insulin, and C-peptide measurement. BMI (kg/m2), skinfolds, and body fat areas (by computed tomography) were measured. IGT was diagnosed in 19% of the men and 31% of the women. Men with IGT had more adiposity, both overall and in thoracic and visceral sites, had higher fasting plasma insulin and C-peptide, and tended to have higher fasting triglyceride and lower HDL cholesterol than men with normal glucose tolerance. Women with IGT had more thoracic subcutaneous fat and intra-abdominal fat and lower fasting HDL cholesterol than women with normal glucose tolerance, and tended to have higher fasting triglyceride and LDL cholesterol. Women with IGT also had higher fasting plasma insulin than women with normal glucose tolerance but tended to be less hyperinsulinaemic than men. Differences in fasting insulin, C-peptide, and lipids were best predicted by intra-abdominal fat.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue; Adult; Blood Glucose; Body Mass Index; C-Peptide; Coronary Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Japan; Lipids; Lipoproteins; Male; Middle Aged; Risk Factors; Sex Characteristics; Sex Factors; Skinfold Thickness; Washington

This study was conducted to compare the insulin responses to an oral glucose load in healthy volunteers and patients with syndrome X and patients with coronary artery disease.. An abnormal coronary flow reserve has been reported in syndrome X by several investigators. However, its cause is not known. Recently, it has been suggested that elevated insulin levels in syndrome X may contribute to microvascular dysfunction.. Insulin responses to an oral glucose load (75 g) were compared in 17 patients with coronary artery disease, 17 patients with chest pain, positive exercise test findings, normal coronary arteries and impaired coronary flow reserve (syndrome X) and 17 healthy volunteers (control subjects). All were matched for age, gender and body weight. Patients with overt diabetes mellitus or hypertension were excluded. Venous blood samples were taken during fasting and at 30, 60, 90 and 120 min after the glucose load. Samples were analyzed for glucose, immunoreactive insulin and C peptides.. There was no significant difference in the glucose levels at all sampling points among the three groups. The C peptide and immunoreactive insulin levels were significantly higher than values in the control group at 60, 90 and 120 min in the groups with syndrome X and coronary artery disease. The peak responses and the areas under the curve were also significantly greater in the latter two groups. There was no significant difference at all sampling points between the group with syndrome X and the group with coronary artery disease.. Patients with syndrome X have stimulated hyperinsulinemia, which may contribute to the pathophysiology of syndrome X.

Topics: Blood Flow Velocity; Blood Glucose; C-Peptide; Cardiac Catheterization; Coronary Circulation; Coronary Disease; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Lipids; Male; Microvascular Angina; Middle Aged

Plasma insulin, C-peptide and plasminogen activator inhibitor-1 (PAI-1) levels were measured in 64 men with coronary artery disease (CAD) documented by angiography. Coronary arteriograms were analyzed, and the severity and diffusion of coronary lesions were quantified by score systems. C-peptide and PAI-1 levels in patients with CAD were significantly higher than in 30 control subjects. Insulin, C-peptide and PAI-1 showed a highly significant correlation with the severity scores for coronary lesions (C-peptide more than insulin), but only a weak correlation with diffusion scores. Highly significant correlations were found between insulin and PAI-1, and even greater ones between C-peptide and PAI-1. It has been proposed that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease by dysregulating lipoprotein metabolism and blood pressure. These findings support that hypothesis and suggest that insulin secretion may be an index of the severity of CAD. Because a direct effect of insulin on the cells that synthesize PAI-1 has been shown, the present data further indicate that the effect of insulin on fibrinolysis may be another way by which hyperinsulinemia accelerates atherogenesis.

Topics: Body Mass Index; C-Peptide; Cholesterol, HDL; Coronary Angiography; Coronary Disease; Fibrinogen; Humans; Insulin; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Reference Values; Triglycerides

Topics: Albuminuria; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Glycated Hemoglobin; Humans; Hyperinsulinism; Triglycerides

The contribution from lipoproteins, blood pressure, albuminuria and demographic variables to coronary heart disease in 90 adult subjects with and 172 without Type 1 diabetes mellitus was examined in order to investigate whether risk factors were of equivalent importance in diabetic and non-diabetic coronary heart disease. Coronary heart disease (CHD) was present in roughly 25% of subjects in each group. In Type 1 diabetes those with CHD had significantly higher levels of systolic blood pressure, albumin excretion, serum creatinine, triglycerides, VLDL cholesterol and C-peptide, and reductions in serum concentrations of HDL and HDL2 cholesterol, in comparison to those without. However, the prevalence of smokers, and concentrations of Lp(a), ApoB and fibrinogen were comparable. Blood pressure and HDL cholesterol were higher in the CHD group with Type 1 diabetes in comparison to the nondiabetic group with CHD, although LDL concentrations and the prevalence of Lp(a) concentrations > 200 mg/l were lower. Logistic regression analysis revealed the strongest independent predictors of CHD in Type 1 diabetes were serum triglycerides, systolic blood pressure, age, serum LDL cholesterol, and the daily insulin dosage, whereas in the non-diabetic control group HDL2 cholesterol, Lp(a), ApoA1 and ApoB, total serum cholesterol and body mass index were additional predictors. CHD in Type 1 diabetes appears to be most closely associated with increasing age and levels of blood pressure and total serum lipids. Apolipoproteins and albuminuria did not seem to be important independent predictors of CHD in Type 1 diabetes, whereas the former were more clearly associated with CHD in non-diabetic controls.

Topics: Adult; Albuminuria; Alcohol Drinking; Apolipoproteins A; Apolipoproteins B; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol, HDL; Cholesterol, VLDL; Coronary Disease; Creatinine; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Fibrinogen; Humans; Lipoprotein(a); Lipoproteins, HDL; Lipoproteins, LDL; Middle Aged; Regression Analysis; Risk Factors; Smoking; Triglycerides

The influence of albuminuria and proliferative retinopathy on concentration of serum lipoprotein (a) was examined cross-sectionally in 90 Type 1 diabetic patients. Concentrations of lipoprotein (a) were less in those with normoalbuminuria (90 (8-882) (median (range] U l-1) than in those with micro- or macro-albuminuria (137 (19-1722) U l-1, p less than 0.05). The prevalence of patients whose lipoprotein (a) concentrations were greater than 200 U l-1 was also greater (45% vs 24%, p = 0.03) among patients with albuminuria, but no difference was found between the microalbuminuric and macroalbuminuric groups (53 and 41%, respectively), or between those with or without proliferative retinopathy. The present finding that lipoprotein (a) concentrations may be increased at an early stage of diabetic renal disease may in part account for the excess ischaemic heart disease associated with diabetic nephropathy.

Topics: Albuminuria; Apolipoproteins B; Biomarkers; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Lipoprotein(a); Lipoproteins; Male; Middle Aged; Triglycerides; Vascular Diseases

Phenytoin is known to induce hyperglycaemia. The mechanism has generally been considered primarily an inhibition of insulin release. We have recently treated a patient who became hyperglycaemic on phenytoin and whose markedly increased insulin requirements suggested an insulin resistant state. Reduction of the phenytoin dose resulted in amelioration of the hyperglycaemia. In vitro studies of phenytoin in a primary culture system of adipocytes that allowed assessment of both insulin receptor binding and post-binding function showed a 57% reduction in maximum [14C]3-0-methylglucose transport in the presence of phenytoin while having no effect on maximum insulin binding. These results suggest that phenytoin administration can result in insulin insensitivity by inducing a post-binding defect in insulin action.

Topics: Aged; Aged, 80 and over; C-Peptide; Coronary Artery Bypass; Coronary Disease; Epilepsies, Partial; Humans; Hyperglycemia; Insulin; Male; Phenytoin

Several clinical and epidemiological evidences support the increased risk of cardiovascular disease (CVD) in pathological conditions as obesity, hypertension, non-insulin-dependent diabetes mellitus, which have hyperinsulinemia as a common feature. In this study, we assessed basal plasma insulin (IRI) and C-peptide (CPR) concentrations in 297 volunteers who participated in a survey concerning risk factors of CVD. We found a stepwise increase in fasting insulin and C-peptide levels in normal subjects (IRI 9.10 +/- 0.41 microU/ml; CPR 1.79 +/- 0.08 ng/ml), in obese subjects (IRI 11.31 +/- 0.38 microU/ml; CPR 2.54 +/- 0.07 ng/ml) in obese hypertensive subjects (IRI 14.17 +/- 0.72 microU/ml; CPR 2.64 +/- 0.09 ng/ml), in obese hypertensive diabetic subjects (IRI 22.57 +/- 2.62 microU/ml; CPR 3.33 +/- 0.27 ng/ml). Thus, we found increasing levels of IRI and CPR as normal conditions changed towards progressively more severe pathological conditions. Although several other factors contribute to determine CVD, we conclude that increasing levels of insulin and C-peptide could play an important role in causing CVD.

Topics: Adult; Biomarkers; Blood Pressure; C-Peptide; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hypertension; Insulin; Male; Medical History Taking; Middle Aged; Obesity; Risk Factors; Surveys and Questionnaires

Coronary heart disease has been described to be increased with both glucose intolerance and cigarette smoking. All three of these have also been reported to be associated with central adiposity (disproportionate deposition of fat on the trunk compared to the extremities). The purpose of this analysis was to determine the relationship of cigarette smoking to glucose intolerance and coronary heart disease, the relationship of cigarette smoking to risk factors such as adiposity, body fat distribution, and plasma lipoprotein and insulin levels, the relationship of cigarette smoking to these risk factors independent of disease status, and whether these risk factors could account for any of the relationship between cigarette smoking and disease status.. The study design was cross-sectional. The study sample contained 219 middle-aged and elderly Japanese-American men: 77 with normal and 74 with impaired glucose tolerance and 68 with type II diabetes. There were 54 men with coronary heart disease. A detailed smoking history was obtained. Glucose tolerance status was established by medical history and a 75-g oral glucose tolerance test. Coronary heart disease was determined by medical history and a resting electrocardiogram. Adiposity and fat distribution measurements were body mass index (kg/m2), skinfold thicknesses, body circumferences, and cross-sectional fat areas by computed tomography. Levels of insulin, C-peptide, cholesterol (total, low-density lipoprotein [LDL], high-density lipoprotein [HDL], HDL2, HDL3, very-low-density lipoprotein [VLDL]), and triglyceride (total, VLDL) were measured in fasting blood specimens.. A central pattern of body fat was associated with both non-insulin-dependent diabetes mellitus and coronary heart disease. Smoking history was related to both adiposity and body fat distribution, and was strongly related to coronary heart disease but not to diabetes. Past smokers who had smoked up to a month ago were the heaviest while present smokers who were currently smoking or had smoked within the past month were the leanest. However, although present smokers had reduced amounts of fat, this was attributable to those present smokers without heart disease. Present smokers with heart disease were not as lean and had increased amounts of intra-abdominal fat. Past smokers had the greatest amount of central fat and this was attributable to those with heart disease. By two-way (smoking history and coronary heart disease status) analysis of covariance, smoking history was significantly related only to subcutaneous fat disposition on the chest and abdomen independent of coronary heart disease, while coronary heart disease status was strongly related to plasma levels of insulin C-peptide, VLDL, HDL, HDL2, and HDL3 cholesterol, and total and VLDL triglyceride, independent of smoking history. Further analysis showed that none of the body fat variables could account for the risk of coronary heart disease associated with smoking history. Higher fasting plasma C-peptide levels in past smokers accounted statistically for part of the risk of coronary heart disease associated with cigarette smoking. However, this effect was not mediated by any of the body fat measurements.. Disproportionately increased intra-abdominal fat is related to coronary heart disease but not to smoking history. Smoking history is related to coronary heart disease but not to diabetes. Weight gain is associated with smoking cessation and appears to be concentrated in the central subcutaneous regions, especially for those who have coronary heart disease. Weight gain associated with cessation of smoking appears to be unrelated to atherogenic changes in lipids, lipoproteins, or insulin. Other pathogenic processes must be considered in the association between smoking and coronary heart disease.

Topics: Adipose Tissue; Adrenergic beta-Antagonists; Analysis of Variance; Body Mass Index; Body Weight; C-Peptide; Cholesterol, HDL; Cholesterol, VLDL; Coronary Disease; Diabetes Mellitus, Type 2; Humans; Insulin; Japan; Male; Middle Aged; Regression Analysis; Skinfold Thickness; Smoking; United States

The concentration of C peptide which is an indicator of the secretory capacity of the beta-cells of the pancreas was assessed in 109 patients with type II diabetes, hospitalized on account of prolonged difficulties as regards compensation. The values on fasting, the maximal values after stimulation following an experimental meal and increments were greater than in age- and weight-matched controls. In diabetic patients some highly significant relationships were revealed between the C peptide concentration on fasting and indicators of the risk of ischaemic heart disease [IHD]. They included HDL cholesterol, the body mass index and uric acid. The relationship between the maximal C peptide concentration and serum sodium may be associated with a greater disposition for hypertension. Thirty-one patients with symptoms of an ischaemic myocardial lesion had a significantly elevated C peptide concentration on fasting. The increments of C peptide concentration after an alimentary stimulus correlated indirectly with indicators of the actual and long-term compensation of diabetes. In relation to the reduced increments also the need of insulin therapy was reflected. Data obtained by examination of the C peptide concentration in the blood of type II diabetics can contribute to the objectivization of needs of insulin treatment and to the detection of the link between cardiovascular risk and hyperinulinaemia.

Topics: C-Peptide; Coronary Disease; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Male; Middle Aged; Prognosis

Topics: C-Peptide; Coronary Disease; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Humans; Insulin

In a community-based study of second-generation Japanese-American men known to have a high prevalence of both Type 2 (non-insulin-dependent) diabetes and impaired glucose tolerance, there was a highly significant association of coronary heart disease with glucose intolerance in a study sample of 219 men. Intra-abdominal cross sectional fat area determined by computed tomography was significantly elevated in men with coronary heart disease even after adjustment for glucose intolerance and body mass index (p = 0.026). Other differences that were significantly related to coronary heart disease after adjustment for glucose intolerance were lower high density lipoprotein cholesterol levels (p = 0.001), elevated total triglyceride and very low density lipoprotein triglyceride (p less than 0.001), and elevated fasting insulin and C-peptide levels p = 0.001. When these variables were tested in a stepwise multiple logistic regression model, significant independent associations with coronary heart disease were found only for total triglyceride and fasting C-peptide after adjustment for glucose tolerance status. Variables identified to be associated with coronary heart disease were interpreted as representing or manifesting an insulin resistant state. Thus, insulin resistance may be the underlying risk factor aetiologically linking glucose intolerance with coronary heart disease.

Topics: Alcohol Drinking; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Coronary Disease; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Humans; Japan; Male; Multivariate Analysis; Prevalence; Regression Analysis; Smoking; Triglycerides; United States

The effect of residual C-peptide secretion in longer standing IDDM on glycaemic control and the prevalence and evolution of complications over 2 years was evaluated. Thirty-one subjects with IDDM of 15.4 (1.5) years duration (mean SEM)) and residual C-peptide secretion, were matched for age, duration of diabetes and body mass index with 31 subjects without detectable C-peptide secretion. At trial entry and over 2 years, levels of HbA1, fructosamine and mean blood glucose were essentially similar in both groups. Levels of glycated albumin (GSA) were significantly higher in the C-peptide negative group after 3 and 9 months (P less than 0.05). An increased prevalence of proliferative retinopathy in the C-peptide negative group and of peripheral vascular disease in the C-peptide secretor group was apparent at entry to the study (both P less than 0.05), although no significant differences were observed after 1 or 2 years. There was no difference in the prevalence of peripheral or autonomic neuropathy, hypertension, nephropathy or ischaemic heart disease. Subjects with C-peptide concentrations greater than 0.100 pmol/ml at entry to this study had lower daily insulin requirements after 1 and 2 years, but behaved like the larger group with any detectable C-peptide secretion in all other respects. Residual C-peptide secretion was lost after 1 year in 7 patients, in whom glycaemic control during the year had been particularly poor. Insulin antibody titres were no different in the 2 groups at any time point. This study suggests that residual C-peptide secretion in longer standing IDDM confers the potential for limited improvements in glycaemic control. This effect appears to be insufficient to prevent the evolution of microvascular complications over a 2-year period. Residual C-peptide secretion and relative hyperinsulinaemia may be associated with an excess of peripheral vascular disease.

Topics: Adult; Albuminuria; Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Blood Pressure; C-Peptide; Coronary Disease; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Follow-Up Studies; Fructosamine; Glycated Hemoglobin; Hexosamines; Humans; Hypertension; Middle Aged

Topics: Asia; C-Peptide; Coronary Disease; England; Humans; Insulin; Male

Variation in insulin and C peptide levels was examined in patients with angina of new onset and chronic coronary heart disease. Insulin secretion was increased in all coronary patients, as compared to the controls, and hormonal response to additional stress was abnormal in postmyocardial infarction patients. It is demonstrated that insulin secretion is already changed at early stages of coronary disease, and the pattern of change is presented.

Topics: Adult; Angina Pectoris; C-Peptide; Chronic Disease; Coronary Disease; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Physical Exertion; Rest

Topics: Adult; Aged; C-Peptide; Coronary Disease; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged

There is a large amount of epidemiological and clinical evidence for associations among obesity, impaired glucose tolerance, and arterial hypertension; nevertheless, the pathophysiological mechanisms underlying these associations have not yet been elucidated. In this article, some working hypotheses are discussed, and original data are presented from two studies focusing on these pathophysiological interrelations. A case-control study of obese normotensive and hypertensive patients, matched for sex, age, and degree of overweight, has shown that obese patients with associated arterial hypertension have higher fasting serum insulin levels and reduced glucose tolerance compared with their normotensive peers. A second study compared subjects with impaired glucose tolerance with a control group of clinically healthy individuals of comparable sex, age, and body mass index, and it revealed that impaired glucose tolerance is associated with significantly higher blood pressure levels, independent of body weight. The results of the two studies together suggest that the association between hypertension and impaired glucose tolerance is independent of overweight; they also give some support to the hypothesis that hyperinsulinemia may contribute to the development of high blood pressure in obese patients.

Topics: Adult; Blood Glucose; Blood Pressure; C-Peptide; Coronary Disease; Diabetes Mellitus, Type 1; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin; Male; Middle Aged; Obesity; Risk

Secretions of hormones responsible for carbohydrate metabolism, STH, insulin, S-peptide and somatostatin, were measured in coronary patients in order to investigate hormonal mechanisms involved in disordered carbohydrate metabolism. A persistent hyperinsulinemia was found in patients with disordered carbohydrate metabolism, both in cases of glucose stimulation and insulin inhibition, where glandular function was assessed on the basis of S-peptide concentration as opposed to the control level. Baseline somatostatin concentrations were beyond the method's sensitivity limit in most of the patients. There was a tendency to elevated hormonal levels in the insulin test, whereas glucose administration produced an opposite response. Blood basal STH levels did not differ significantly in the study groups, however the increase in hormonal secretion following insulin administration was less pronounced in patients with disordered carbohydrate metabolism as compared to other groups.

Topics: Adult; C-Peptide; Coronary Disease; Glucose Tolerance Test; Growth Hormone; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Somatostatin

Fasting insulin secretion was assessed by measuring fasting serum C-peptide levels in 529 women and 399 men aged 18-90 years, to study the relationship between insulin secretion, insulin resistance and risk factors for coronary heart disease. Subjects with low serum high density lipoprotein (HDL) cholesterol levels showed higher mean serum insulin and C-peptide levels than subjects with normal HDL cholesterol levels. In male subjects these differences were significant for both serum insulin and serum C-peptide results (P less than 0.005). In female subjects serum insulin results differed significantly (P less than 0.0005) but for the difference in mean serum C-peptide levels P was equal to 0.012. Fasting serum C-peptide correlated negatively with serum HDL cholesterol. However, serum C-peptide also correlated with serum triglyceride and serum triglyceride correlated negatively with serum HDL cholesterol. Each correlation was statistically significant (P less than 0.001). Multiple regression analysis suggested that the apparent association of C-peptide with HDL cholesterol was a consequence of the interrelated association between C-peptide, triglyceride and HDL cholesterol. The analysis was consistent with the hypothesis that obesity and increased insulin resistance were associated with increased insulin secretion and in turn with high serum triglyceride levels and consequentially low levels of serum HDL cholesterol. The data were compatible with the suggestion that insulin resistance rather than fasting insulin concentration per se could be a risk factor for coronary heart disease.

Topics: Adolescent; Adult; Aged; Body Weight; C-Peptide; Cholesterol; Cholesterol, HDL; Coronary Disease; Fasting; Female; Humans; Insulin; Insulin Resistance; Lipoproteins, HDL; Male; Middle Aged; Risk; Triglycerides

Topics: Adult; C-Peptide; Coronary Disease; Glucose Tolerance Test; Growth Hormone; Humans; Male; Middle Aged; Peptides; Somatostatin