natriuretic-peptide--brain and Glucose-Intolerance

The metabolic disorders associated with chronic hypoxemia in adult patients with tetralogy of Fallot (TOF) have not been fully appreciated. We report a 53-year-old male patient with TOF who presented with fasting hypoglycemia, hypertriglyceridemia, increased blood levels of free fatty acids, adiponectin, B-type natriuretic peptide, and uric acid. The cluster of these metabolic derangements has not been previously reported, and the possible role of chronic hypoxia in the production of these disturbances is discussed with a review of pertinent literatures.

Topics: Adiponectin; Fatty Acids, Nonesterified; Glucose Intolerance; Humans; Hypertriglyceridemia; Hypoglycemia; Hypoxia; Male; Middle Aged; Natriuretic Peptide, Brain; Tetralogy of Fallot

Although impaired glucose tolerance (IGT) promotes cardiovascular events, our Alpha-glucosidase-inhibitor Blocks Cardiac Events in Patients with Myocardial Infarction and Impaired Glucose Tolerance (ABC) study showed that alpha-glucosidase inhibitors do not prevent cardiovascular events in patients with myocardial infarction (MI) and IGT. The aim of the present study was to identify potential clinical factors for cardiovascular events in patients with MI and IGT.. Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 385,391 combinations of fewer than four clinical parameters.. We identified 380 combinations predicting the occurrence of (1) all-cause hospitalization, (2) hospitalization due to worsening of heart failure (HF), (3) hospitalization due to non-fatal MI, and (4) hospitalization due to percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for stable angina among 385,391 combinations in 853 patients. Among these, either plasma BNP levels ≥ 200 pg/dl or diuretic use exclusively predicted (1) all-cause hospitalization, (2) hospitalization due to worsening of HF, and (3) hospitalization due to a non-fatal MI, with plasma BNP levels ≥ 200 pg/dl being the sole predictor of hospitalization due to PCI and CABG. Importantly, each finding was verified by independently drawn Kaplan-Meier curves, revealing the unexpected role of plasma BNP levels in the progression of coronary stenosis determined as the necessity of PCI and CABG for stable angina.. In patients with MI and IGT, high plasma BNP levels predicted the occurrence of coronary stenosis, recurrent MI, and worsening of HF, whereas diuretic use did not predict the progression of coronary stenosis but non-fatal MI and worsening of HF.

Topics: Aged; Artificial Intelligence; Biomarkers; Blood Glucose; Coronary Artery Bypass; Data Mining; Disease Progression; Diuretics; Female; Glucose Intolerance; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Patient Admission; Percutaneous Coronary Intervention; Prognosis; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors

Glucose intolerance (GI), defined as either prediabetes or diabetes, promotes cardiovascular events in patients with myocardial infarction (MI). Using the pooled clinical data from patients with MI and GI in the completed ABC and PPAR trials, we aimed to identify their clinical risk factors for cardiovascular events.. Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 415,328 combinations of < 4 clinical parameters.. We identified 242 combinations that predicted the occurrence of hospitalization for (1) percutaneous coronary intervention for stable angina, (2) non-fatal MI, (3) worsening of heart failure (HF), and (4) all causes, and we analyzed combinations in 1476 patients. Among these parameters, the use of proton pump inhibitors (PPIs) or plasma glucose levels > 200 mg/dl after 2 h of a 75 g oral glucose tolerance test were linked to the coronary events of (1, 2). Plasma BNP levels > 200 pg/dl were linked to coronary and cardiac events of (1, 2, 3). Diuretics use, advanced age, and lack of anti-dyslipidemia drugs were linked to cardiovascular events of (1, 3). All of these factors were linked to (4). Importantly, each finding was verified by independently drawn Kaplan-Meier curves, indicating that the determined factors accurately affected cardiovascular events.. In most previous MI patients with GI, progression of GI, PPI use, or high plasma BNP levels were linked to the occurrence of coronary stenosis or recurrent MI. We emphasize that use of AI may comprehensively uncover the hidden risk factors for cardiovascular events.

Topics: Aged; Angina, Stable; Artificial Intelligence; Biomarkers; Blood Glucose; Coronary Artery Disease; Data Mining; Databases, Factual; Female; Glucose Intolerance; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Percutaneous Coronary Intervention; Prognosis; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Retrospective Studies; Risk Factors

Circulating B-type natriuretic peptide, as measured by the N-terminal fragment of its prohormone (NT-proBNP), is inversely associated with incident type 2 diabetes (T2DM) but positively related to future cardiovascular disease (CVD). Recognizing that gestational diabetes (GDM) identifies women at future risk for both T2DM and CVD, we sought to determine whether gestational glucose tolerance relates to NT-proBNP in the years after delivery.. Three hundred and forty women underwent a glucose challenge test (GCT) and an oral glucose tolerance test (OGTT) in pregnancy, yielding 4 gestational glucose tolerance groups: GDM (n = 105); gestational impaired glucose tolerance (n = 59); abnormal GCT with a normal OGTT (n = 98); and normal GCT with normal OGTT (n = 75). At 3-year postpartum, they underwent cardiometabolic characterization (including measurement of estimated glomerular filtration rate (eGFR), adiponectin and NT-proBNP) and repeated the OGTT, revealing 69 women with glucose intolerance (prediabetes/diabetes).. At 3-year postpartum, serum NT-proBNP did not differ between the 4 original gestational glucose tolerance groups (P = .44), but instead progressively decreased across current glucose tolerance strata, from normal to prediabetes to diabetes (P = .006). Indeed, on logistic regression analysis, NT-proBNP emerged as a negative predictor of prediabetes/diabetes (OR = 0.903, 95% CI 0.825-0.988, P = .026). On multiple linear regression analyses of NT-proBNP, the significant association with current glucose intolerance was ultimately attenuated in a fully adjusted model, revealing two independent determinants of NT-proBNP: eGFR (t = -2.71, P = .007) and adiponectin (t = 2.44, P = .015).. Serum NT-proBNP relates to current glucose intolerance, rather than preceding gestational dysglycaemia. Thus, the diabetic (rather than vascular) risk implications of NT-proBNP predominate in young women.

Topics: Adult; Blood Glucose; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Postpartum Period; Pregnancy; Prospective Studies

The cardiac hormones atrial (ANP) and B-type natriuretic peptides (BNP) moderate arterial blood pressure and improve energy metabolism as well as insulin sensitivity via their shared cGMP-producing guanylyl cyclase-A (GC-A) receptor. Obesity is associated with impaired NP/GC-A/cGMP signaling, which possibly contributes to the development of type 2 diabetes and its cardiometabolic complications. In vitro, synthetic ANP, via GC-A, stimulates glucose-dependent insulin release from cultured pancreatic islets and β-cell proliferation. However, the relevance for systemic glucose homeostasis in vivo is not known. To dissect whether the endogenous cardiac hormones modulate the secretory function and/or proliferation of β-cells under (patho)physiological conditions in vivo, here we generated a novel genetic mouse model with selective disruption of the GC-A receptor in β-cells.. Mice with a floxed GC-A gene were bred to Rip-Cre. In vitro, the insulinotropic and proliferative actions of ANP were abolished in islets isolated from β GC-A KO mice. Concordantly, in vivo, infusion of BNP mildly enhanced baseline plasma insulin levels and glucose-induced insulin secretion in control mice. This effect of exogenous BNP was abolished in β GC-A KO mice, corroborating the efficient inactivation of the GC-A receptor in β-cells. Despite this under physiological, ND conditions, fasted and fed insulin levels, glucose-induced insulin secretion, glucose tolerance and β-cell morphology were similar in β GC-A KO mice and control littermates. However, HFD-fed β GC-A KO animals had accelerated glucose intolerance and diminished adaptative β-cell proliferation.. Our studies of β GC-A KO mice demonstrate that the cardiac hormones ANP and BNP do not modulate β-cell's growth and secretory functions under physiological, normal dietary conditions. However, endogenous NP/GC-A signaling improves the initial adaptative response of β-cells to HFD-induced obesity. Impaired β-cell NP/GC-A signaling in obese individuals might contribute to the development of type 2 diabetes.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Cell Proliferation; Disease Models, Animal; Disease Progression; Gene Deletion; Genetic Predisposition to Disease; Glucose Intolerance; Insulin; Insulin-Secreting Cells; Mice, Knockout; Natriuretic Peptide, Brain; Obesity; Phenotype; Receptors, Atrial Natriuretic Factor; Signal Transduction; Tissue Culture Techniques

In spite of accumulating evidences suggesting an inverse association between insulin resistance and plasma B-type natriuretic peptide (BNP) levels, the effect of daily physical activity on plasma BNP in individuals with glucose intolerance remains unknown. We investigated the association of physical activity level (PAL) with plasma BNP in patients with impaired fasting glucose, impaired glucose tolerance and type 2 diabetes.. Cross-sectional study.. Outpatients visiting the National Center for Global Health and Medicine Kohnodai Hospital.. A total of 60 patients with glucose intolerance who did not take any hypoglycaemic agents, cholesterol-lowering agents and antihypertensive agents were recruited. Patients who were diagnosed as having heart failure and renal impairment, engaged in sports-like exercise and resistance training were excluded.. PAL was objectively measured by a triaxial accelerometer. The association between PAL and plasma BNP levels was assessed by multiple regression analysis.. PAL was positively correlated with plasma BNP levels (r=0.296, p=0.021). PAL was still significantly correlated with plasma BNP levels after adjustment for age (β=0.290, p=0.014), and adjustment for age and body mass index (β=0.282, p=0.018). Plasma BNP levels were inversely correlated with serum insulin levels (r=-0.350, p=0.006) and homeostasis model assessment-estimated insulin resistance (HOMA-IR; r=-0.363, p=0.004). Serum insulin levels (mean±SD, 8.1±6.4 μU/mL) and HOMA-IR (2.4±1.9) in the high-BNP group were significantly lower than those (11.2±7.4 μU/mL and 3.7±3.0, respectively) in the low-BNP group.. Our findings propose the possibility that plasma BNP may be increased by daily physical activity and BNP is associated with insulin resistance.

Topics: Adult; Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Exercise; Female; Glucose Intolerance; Humans; Insulin; Male; Middle Aged; Natriuretic Peptide, Brain; Time Factors

Adiponectin is produced by adipose tissue and regarded as protective hormone for diabetes and coronary heart disease (CHD). Its role in heart failure is discussed controversially.. In this study, 1015 consecutive patients admitted for acute (n = 149) or elective (n = 866) coronary angiography were enrolled. Patients with known diabetes mellitus (DM) were excluded. All patients were classified by oral glucose tolerance test (oGTT) according to World Health Organization (WHO) criteria and by the results of coronary angiography as no/minor coronary heart disease (CHD), single-vessel disease (1-VD), double-vessel disease (2-VD) or triple-vessel disease (3-VD), by New York Heart Association (NYHA) criteria and by echocardiography for heart failure. Adiponectin and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured in all patients.. Adiponectin was higher in patients with normal glucose tolerance (NGT) (13.65 ± 10.31 mg/l) compared to impaired glucose tolerance (IGT) (11.12 ± 7.5, p < 0.001) or diabetes (11.22 ± 7.63, p < 0.001). There was a stepwise decrease in adiponectin from no CHD (18.16 ± 12.49 mg/L) to minor CHD (16.01 ± 11.42) to 1-VD (12.18 ± 8.8, p < 0.001 to no/minor CHD) to 2- and 3-VD (10.68 ± 7.5, p < 0.001 to no/minor CHD, p = 0.004 to 1-VD). Patients with heart failure NYHA III (17.4 ± 10.27) had higher adiponectin levels compared to NYHA II (12.94 ± 9.41, p < 0.001 to NYHA III) and NYHA I (10.3 ± 7.75, p < 0.001 to NYHA III/II). In this line, adiponectin levels were positively correlated to NT-proBNP levels (r = 0.303), and patients with ejection fraction (EF) < 50% had higher adiponectin levels than those with EF > 50% (14.96 ± 4.35 to 11.78 ± 3.71, p = 0.006).. Adiponectin levels are inversely correlated to progressing CHD and glucose intolerance but positively correlated to increasing heart failure.

Topics: Adiponectin; Aged; Aged, 80 and over; Coronary Disease; Diabetes Mellitus; Female; Glucose; Glucose Intolerance; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain

In this study, we aimed to evaluate myocardial functions in patients with diabetes mellitus (DM) and impaired glucose tolerance (IGT). We also aimed to investigate the relationship between B-type natriuretic peptide (BNP) levels and myocardial performance index (Tei index) in these patients.. A total of 38 patients with DM, 34 patients with IGT, and 40 healthy volunteers were recruited to the study. Basal clinical and laboratory findings were recorded. BNP levels of all individuals were measured. Both conventional transthoracic and tissue Doppler echocardiogaphy were performed to all study participants.. B-type natriuretic peptide levels of the diabetic group were greater than in patients with IGT and the control group. BNP levels of the IGT group were also higher than the control group. Myocardial performance index values, measured by both the conventional method and tissue Doppler echocardiography, were significantly higher in the diabetic group than in the control group. There was a significant relationship between myocardial performance index and BNP levels.. Myocardial functions are disturbed in patients with DM and also in patients with IGT. BNP and myocardial performance index can be used in diabetic patients and in patients with IGT to define myocardial dysfunction.

Topics: Age Factors; Blood Glucose; Diabetes Mellitus, Type 2; Echocardiography; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; ROC Curve; Ventricular Dysfunction, Left

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Humans; Male; Myocardium; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

We studied the influence of abnormal glucose metabolism on left ventricular (LV) function and prognosis in 203 patients with acute myocardial infarction.. Abnormal glucose metabolism is associated with increased mortality after acute myocardial infarction. This appears to be particularly attributable to an increased incidence of post-infarction congestive heart failure. A relationship between glucose metabolism and LV function could potentially explain this excess mortality.. In patients without known diabetes, glucose metabolism was determined using an oral glucose tolerance test before discharge. LV function was assessed using echocardiographic measurements (LV end-diastolic volume, LV end-systolic volume, LV ejection fraction, restrictive diastolic filling pattern, early transmitral flow velocity to early diastolic mitral annular velocity ratio [E/e'], and left atrial volume index) and by measuring plasma N-terminal pro-B-type natriuretic peptide levels.. After adjustment for age and gender, a linear relationship between the degree of abnormal glucose metabolism was observed for each marker of LV dysfunction (p(trend) < 0.05) with the exception of left atrial volume index (p = 0.10). During a median follow-up of 21 months, 32 patients died, and 39 patients met the secondary end point of death or hospitalization for heart failure. After adjustment for differences in LV function, as well as other relevant characteristics, newly detected, as well as known diabetes were independent predictors of both all-cause mortality (hazard ratios [HR]: 4.2 [95% confidence interval (CI): 1.1 to 17.1] and HR: 5.7 [95% CI: 1.3 to 25.2], respectively), and the composite of death or hospitalization for heart failure (HR: 4.3 [95% CI: 1.2 to 15.6] and HR: 5.8 [95% CI: 1.5 to 22.3], respectively). Comparable nonsignificant trends were observed for patients with impaired glucose tolerance.. Although perturbations in glucose metabolism were linearly associated with impairment of LV function in the early phase of acute myocardial infarction, this relationship alone did not explain the excess mortality in patients with newly detected or known diabetes.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Diabetes Mellitus; Echocardiography, Doppler; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Heart Failure; Hospitalization; Humans; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prognosis; Proportional Hazards Models; Risk Assessment; Risk Factors; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

Natriuretic peptides (NPs) have been characterized as vascular hormones that regulate vascular tone via guanylyl cyclase (GC), cyclic GMP (cGMP), and cGMP-dependent protein kinase (cGK). Recent clinical studies have shown that plasma NP levels were lower in subjects with the metabolic syndrome. The present study was conducted to elucidate the roles for NP/cGK cascades in energy metabolism.. We used three types of genetically engineered mice: brain NP (BNP) transgenic (BNP-Tg), cGK-Tg, and guanylyl cyclase-A (GCA) heterozygous knockout (GCA(+/-)) mice and analyzed the metabolic consequences of chronic activation of NP/cGK cascades in vivo. We also examined the effect of NPs in cultured myocytes.. BNP-Tg mice fed on high-fat diet were protected against diet-induced obesity and insulin resistance, and cGK-Tg mice had reduced body weight even on standard diet; surprisingly, giant mitochondria were densely packed in the skeletal muscle. Both mice showed an increase in muscle mitochondrial content and fat oxidation through upregulation of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1alpha and PPARdelta. The functional NP receptors, GCA and guanylyl cyclase-B, were downregulated by feeding a high-fat diet, while GCA(+/-) mice showed increases in body weight and glucose intolerance when fed a high-fat diet. NPs directly increased the expression of PGC-1alpha and PPARdelta and mitochondrial content in cultured myocytes.. The findings together suggest that NP/cGK cascades can promote muscle mitochondrial biogenesis and fat oxidation, as to prevent obesity and glucose intolerance. The vascular hormone, NP, would contribute to coordinated regulation of oxygen supply and consumption.

Topics: Animals; Blood Glucose; Cells, Cultured; Cyclic GMP; Dietary Fats; Down-Regulation; Genetic Engineering; Glucose Intolerance; Insulin Resistance; Lipid Peroxidation; Mice; Mice, Knockout; Mitochondria; Molecular Sequence Data; Muscle Cells; Muscle, Skeletal; Natriuretic Peptide, Brain; Natriuretic Peptides; Obesity; Oxygen Consumption; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; PPAR delta; PPAR gamma; Protein Kinases; Receptors, Atrial Natriuretic Factor; Trans-Activators; Transcription Factors; Up-Regulation

Since 1) dilated cardiomyopathy (DCM) causes chronic heart failure (CHF), and 2) augmentation of neurohumoral factors such as angiotensin II impairs glucose metabolism, we examined the rate of abnormal glucose metabolism in patients having both DCM and CHF and whether correction of the impairment of glucose metabolism would improve the pathophysiology of CHF in DCM patients. A 75-g oral glucose tolerance test (OGTT) was performed in 56 patients with DCM-induced CHF and 168 age- and sex-matched control subjects. Among the CHF patients, 26.8% and 50.0% suffered from diabetes mellitus (DM) and impaired glucose tolerance (IGT), respectively, showing that abnormal glucose tolerance was more prevalent in DCM patients than in the control subjects (7.7% and 14.3%, respectively). In the patients with DCM-induced CHF, a correlation was observed between the brain natriuretic peptide (BNP) levels and the difference between the plasma glucose levels at the time of fasting and at 2 h of OGTT. Since neither DM nor IGT are thought to cause DCM, the abnormalities of glucose metabolism may be attributed to the progression of CHF. Furthermore, we tested whether correction of the abnormal glucose tolerance using voglibose (an alpha-glucosidase inhibitor) would improve the severity of CHF in another group of 30 patients with DCM-induced CHF and IGT. The patients treated with voglibose for 24 weeks showed decreases in left ventricular dimension, NYHA functional classification values, and plasma BNP levels, and an improvement in cardiac function. In conclusion, abnormal glucose tolerance was more prevalent among patients with DCM-induced CHF than controls, and the correction of IGT improved the pathophysiology of CHF.

Topics: Cardiomyopathy, Dilated; Chronic Disease; Disease Progression; Echocardiography; Female; Glucose Intolerance; Glucose Tolerance Test; Heart Failure; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Severity of Illness Index