natriuretic-peptide--brain and Diabetes-Mellitus--Type-1

Our aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF).. We pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF. Stroke occurred in 165 patients (4.7%) with AF and in 206 patients (3.4%) without AF (rates 16.8/1000 patient-years and 11.1/1000 patient-years, respectively). Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74). N-terminal pro B-type natriuretic peptide (available in 2632 patients) was also an independent predictor of stroke (hazard ratio, 1.31; 1.11-1.57 per log unit) when added to this model. With the use of a risk score formulated from these predictors, we found that patients in the upper third of risk had a rate of stroke that approximated the risk in patients with AF.. A small number of demographic and clinical variables identified a subset of patients who have heart failure without AF at a high risk of stroke.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Benzimidazoles; Biomarkers; Biphenyl Compounds; Cardiovascular Agents; Diabetes Mellitus, Type 1; Fatty Acids, Omega-3; Female; Fluorobenzenes; Follow-Up Studies; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Pyrimidines; Randomized Controlled Trials as Topic; Risk Factors; Rosuvastatin Calcium; Stroke; Stroke Volume; Sulfonamides; Tetrazoles

To evaluate the effects of therapy with the vitamin D analogue paricalcitol on markers of cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy.. In a double-blind, randomized placebo-controlled, crossover trial, 48 participants on stable renin angiotensin aldosterone system blockade and diuretics were assigned, in random order, to 12 weeks of paricalcitol and 12 weeks of placebo therapy, separated by a 4-week washout period. Primary and secondary endpoints were changes in plasma N-terminal probrain natriuretic peptide and urinary albumin excretion rate obtained before and after each intervention. Glomerular filtration rates were estimated and measured ((51) Cr-EDTA plasma clearance glomerular filtration rate) after each intervention.. The mean (sd) age of the participants was 57 (9) years, the baseline geometric mean (95% CI) urinary albumin excretion rate was 148 (85-259) mg/24 h, the mean (sd) HbA1c was 70 (9) mmol/mol [8.6 (3)%], the mean (sd) estimated glomerular filtration rate was 47 (15) ml/min/1.73 m(2) and the mean (sd) 24-h blood pressure was 135 (17)/74 (10) mmHg. Compared with placebo therapy, vitamin D analogue therapy had no significant effect on plasma N-terminal probrain natriuretic peptide concentration (P = 0.6), urinary albumin excretion rate was reduced by 18% (P = 0.03 for comparison), estimated glomerular filtration rate was reduced by 5 ml/min/1.73 m(2) (P < 0.001) and measured glomerular filtration rate was reduced by 1.5 ml/min/1.73 m(2) (P = 0.2).. Paricalcitol therapy did not affect plasma N-terminal probrain natriuretic peptide concentration in people with Type 1 diabetes and diabetic nephropathy; however, the urinary albumin excretion rate was significantly lowered.

Topics: Adult; Aged; Albuminuria; Biomarkers; Cardiovascular Diseases; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Disease Progression; Double-Blind Method; Ergocalciferols; Female; Glomerular Filtration Rate; Glycopeptides; Humans; Incidence; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Vitamin D

Renin-angiotensin-aldosterone system (RAAS) blockade may reduce levels of biomarkers of chronic low-grade inflammation and endothelial dysfunction. We investigated the effect of spironolactone added to standard RAAS blockade on these biomarkers in an analysis of four original studies.. The studies were double-blind, randomised, placebo-controlled studies in 46 type 1 and 23 type 2 diabetic patients with micro- or macroalbuminuria treated with angiotensin-converting enzyme inhibitor (ACE inhibitor) or angiotensin receptor blocker (ARB), and randomised to additional treatment with spironolactone 25 mg and placebo daily for 60 days.. Changes in inflammatory (hsCRP, s-ICAM, TNFα, IL-6, IL-8, Serum amyloid A, IL1β), endothelial dysfunction (sE-selectin, s-ICAM1, s-VCAM1, VWF, p-selectin, s-thrombomodulin) and NT-proBNP after each treatment period.. During spironolactone treatment, u-albumin excretion rate was reduced from 605 (411-890) to 433 (295-636) mg/24 h, as previously reported. Markers of inflammation and endothelial dysfunction did not change; only changes in NT-proBNP (reduced by 14%, p=0.05) and serum amyloid A (reduced by 62%, p=0.10) were borderline significant.. Our results indicate that the renoprotective effect of spironolactone when added to RAAS blockade is not mediated through anti-inflammatory pathways since markers of inflammation and endothelial dysfunction are not affected during treatment.

Topics: Albuminuria; Biomarkers; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Double-Blind Method; Endothelium; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Spironolactone

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

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

This study sought to determine if the severity of autonomic perturbations in patients with heart failure are affected by the presence of diabetes. Decreased HRV is frequent in diabetic patients free of clinically apparent heart disease and has been invoked as a risk factor for sudden cardiac death. However, reduced HRV is also commonly present in patients with left ventricular dysfunction. The effect of diabetes on autonomic dysfunction in this setting is not known. Holter ECGs from 69 diabetic patients and 85 nondiabetic control subjects with heart failure were analyzed. The severity of autonomic dysfunction was assessed using 24-hour time- and frequency-domain HRV analysis. Prognostically important time- and frequency-domain HRV measures (SDNN, SDANN5, total power, and ultra-low frequency power) were not different between the two groups. Time- and frequency-domain parameters modulated by parasympathetic tone (pNN50, RMSSD, and HF power) were depressed to a similar degree in the diabetic and the nondiabetic groups. The low frequency power was significantly lower in diabetic patients (5.8 +/- 0.7 vs 5.3 +/- 1.0, P = 0.02). The ratio of low to high frequency power was substantially lower in the diabetic group (2.2 +/- 0.2 vs 1.4 +/- 0.2, P < 0.0001). These differences were more apparent in insulin-treated diabetics. In the presence of heart failure, HRV parameters that are most predictive of adverse outcome are similar in diabetic and nondiabetic patients. Furthermore, during increased sympathetic stimulation in the setting of heart failure, diabetes does not worsen parasympathetic withdrawal but may mitigate sympathetic activation.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dobutamine; Electrocardiography, Ambulatory; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Signal Processing, Computer-Assisted

Atrial natriuretic peptide (ANP) increases urinary albumin excretion in Type 1 diabetes mellitus (DM). Brain natriuretic peptide (BNP) is structurally and functionally related to ANP, but its effect on urine albumin excretion rate (UAER) is unknown.. To compare the albuminuric effects of intravenous infusion of ANP and BNP, and to assess the effect of both peptides on tubular protein excretion.. Eight subjects with Type 1 DM were randomised to a three leg, double blind, and placebo controlled study. On each study day, subjects were euglycaemic clamped and subsequently water loaded (20 mL/kg orally, plus urine losses) to steady state diuresis. When in steady state, creatinine clearance was estimated in three separate 1 hour periods. At the end of the first period, a 1 hour intravenous infusion of either placebo, ANP 0.025 microg/kg/min, or BNP 0.025 microg/kg/min was administered. There followed a 1 hour recovery period. Urine was collected at 15 min intervals for estimation of urine albumin (ACR) and alpha1 microglobulin creatinine ratio (MCR). Results were analysed by anova.. Creatinine clearance was similar on the three study days, and was unaltered by any infusion. ACR was unaltered by placebo (1.3 +/- 0.5-1.2 +/- 0.4 mg/mmol, mean +/- SD, p = 0.81), but increased compared to placebo with infusion of both ANP (1.2 +/- 0.4-9.8 +/- 8.4 mg/mmol, P = 0.0004), and BNP (1.1 +/- 0.4-13.4 +/- 8.6 mg/mmol, P = 0.0001). The MCR was unaltered by placebo infusion (P = 0.89), but increased compared with placebo after infusion of ANP (5.4 +/- 0.9-12.3 +/- 4.2 mg/mmol, P < 0.0001), and BNP (5.4 +/- 0.8-12.1 +/- 2.5 mg/mmol, P < 0.0001).. Intravenous infusion of BNP and ANP both increase the urine excretion of albumin and the tubular protein alpha1 microglobulin, independent of creatinine clearance.

Topics: Adult; Albuminuria; Alpha-Globulins; Atrial Natriuretic Factor; Creatinine; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Natriuretic Peptide, Brain; Placebos

To examine the effect of acute hyperglycaemia on atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations in Type 1 diabetes.. The study was two limb, randomized, and single-blind. Eight Type 1 diabetes subjects were clamped at euglycaemia by intravenous infusion of insulin. When euglycaemia was established, the insulin infusion rate was left unaltered for the remainder of the protocol, and an intravenous infusion of either 500 ml 0.9% saline or 500 ml 10% dextrose was administered over 1 h. Blood was collected for estimation of plasma glucose, ANP and BNP concentrations at 30 min intervals for 2 h from the start of the infusion period. One week later, each subject received the alternate infusion. Results are expressed as mean +/- standard deviation, and were analysed by ANOVA.. Baseline plasma glucose (P = 0.8), ANP (P = 0.8) and BNP (P = 0.8) concentrations were similar on the study days. Plasma glucose rose with dextrose (6.1 + 0.5-15.1 + 2.8 mmol/l, P = 0.9). Plasma ANP concentrations were unaltered by saline infusion (76.5 +/- 14.7-77.7 +/- 15.2 pg/ml, P = 0.9), but increased with dextrose infusion (79 +/- 14-134 +/- 17.1 pg/ml, P < 0.0001), and were higher with dextrose than saline infusion (P < 0.0001). Plasma concentrations of BNP were not significantly altered by infusion of either dextrose (5.1 +/- 3.9-9.3 +/- 5.4 pg/ml, P = 0.63) or saline (4.3 +/- 3.5-6 +/- 5.2 pg/ml, P = 0.84).. Plasma concentrations of ANP, but not BNP, rise in response to acute hyperglycaemia in Type 1 diabetes.

Topics: Adult; Atrial Natriuretic Factor; Blood Glucose; Diabetes Mellitus, Type 1; Glucose Clamp Technique; Humans; Hyperglycemia; Infusions, Intravenous; Insulin; Male; Natriuretic Peptide, Brain; Single-Blind Method

Cardiovascular disease (CVD) is a leading cause of death in both men and women. Type 1 and 2 diabetes mellitus (DM1 and DM2) are well-known risk factors for CVD. In addition, gestational diabetes mellitus (GDM) is a female sex-specific risk factor for CVD. Here, we measure circulating concentrations of cardiac troponin T (cTNT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) during pregnancy-a window of time often referred to as a cardiovascular stress test for women.. This study utilized data from 384 pregnant women: 64 with DM1, 16 with DM2, 35 with GDM and 269 euglycemic controls. Blood was predominantly sampled within a week before delivery. Cardiovascular biomarker concentrations were measured in serum using electrochemiluminescence immunoassay.. Circulating cTnT levels were higher in women with DM1, DM2 and GDM as compared to controls, whereas NT-proBNP and GDF-15 levels were only increased in women with DM1. Glucose dysregulation, assessed by third trimester HbA1c levels, positively correlated with all three CVD biomarker levels, whereas pregestational body mass index correlated negatively with GDF-15.. Our results support the presence of myocardial affection in women with diabetic disorders during pregnancy. Although pregestational DM1 in this study was associated with the most adverse CVD biomarker profile, women with GDM displayed an adverse cTnT profile similar to what we found in women with pregestational DM2. This supports that women with GDM should be offered long-term intensified cardiovascular follow-up and lifestyle advice following delivery, similarly to the well-established CV follow-up of women with pregestational DM.

Topics: Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Growth Differentiation Factor 15; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Troponin T

MicroRNA 34a (miR-34a) is elevated in the heart in a setting of cardiac stress or pathology, and we previously reported that inhibition of miR-34a in vivo provided protection in a setting of pressure overload-induced pathological cardiac hypertrophy and dilated cardiomyopathy. Prior work had also shown that circulating or cardiac miR-34a was elevated in a setting of diabetes. However, the therapeutic potential of inhibiting miR-34a in vivo in the diabetic heart had not been assessed. In the current study, type 1 diabetes was induced in adult male mice with 5 daily injections of streptozotocin (STZ). At 8 weeks post-STZ, when mice had established type 1 diabetes and diastolic dysfunction, mice were administered locked nucleic acid (LNA)-antimiR-34a or saline-control with an eight-week follow-up. Cardiac function, cardiac morphology, cardiac fibrosis, capillary density and gene expression were assessed. Diabetic mice presented with high blood glucose, elevated liver and kidney weights, diastolic dysfunction, mild cardiac enlargement, cardiac fibrosis and reduced myocardial capillary density. miR-34a was elevated in the heart of diabetic mice in comparison to non-diabetic mice. Inhibition of miR-34a had no significant effect on diastolic function or atrial enlargement, but had a mild effect on preventing an elevation in cardiac enlargement, fibrosis and ventricular gene expression of B-type natriuretic peptide (BNP) and the anti-angiogenic miRNA (miR-92a). A miR-34a target, vinculin, was inversely correlated with miR-34a expression, but other miR-34a targets were unchanged. In summary, inhibition of miR-34a provided limited protection in a mouse model with established type 1 diabetes-induced cardiomyopathy and failed to improve diastolic function. Given diabetes represents a systemic disorder with numerous miRNAs dysregulated in the diabetic heart, as well as other organs, strategies targeting multiple miRNAs and/or earlier intervention is likely to be required.

Topics: Animals; Blood Glucose; Cardiomegaly; Cardiomyopathy, Dilated; Diabetes Mellitus, Type 1; Disease Models, Animal; Fibrosis; Male; Mice; Mice, Inbred Strains; MicroRNAs; Natriuretic Peptide, Brain; Streptozocin; Vinculin

Poor glycemic control in maternal type 1 diabetes mellitus during pregnancy can affect fetal cardiac and placental function. However, studies concerning fetal central hemodynamics have revealed conflicting results. We hypothesized that in pregnancies complicated by maternal type 1 diabetes, fetal cardiovascular and placental hemodynamics are comparable to the control fetuses at near-term gestation. In addition, we investigated the relation between newborn serum biomarkers of cardiac function and fetal cardiovascular and placental hemodynamics. Furthermore, we studied whether maternal diabetes is associated with placental inflammation.. In this prospective case-control study, fetal central and peripheral hemodynamics were assessed by ultrasonography in 33 women with type 1 diabetes and in 67 controls with singleton pregnancies between 34. Fetal ventricular wall thicknesses were greater and weight-adjusted stroke volumes and cardiac outputs were lower in the type 1 diabetes group than in the control group. Pulsatility in the aortic isthmus and inferior vena cava blood flow velocity waveforms was greater in the type 1 diabetes group fetuses than in the controls. A positive correlation was found between branch pulmonary artery and aortic isthmus pulsatility index values. Umbilical artery pulsatility indices were comparable between the groups. Umbilical cord serum natriuretic peptide and troponin T concentrations were elevated in the type 1 diabetes fetuses. These cardiac biomarkers correlated significantly with cardiovascular hemodynamics. Placental cytokine levels were not different between the groups.. In maternal type 1 diabetes pregnancies, fetal cardiovascular hemodynamics is impaired. Maternal type 1 diabetes does not seem to alter placental vascular impedance or induce placental inflammation.

Topics: Adult; Aorta; Atrial Natriuretic Factor; Biomarkers; Blood Flow Velocity; Cardiac Output; Case-Control Studies; Cytokines; Diabetes Mellitus, Type 1; Female; Fetal Blood; Fetal Heart; Heart Ventricles; Humans; Infant, Newborn; Natriuretic Peptide, Brain; Placenta; Pregnancy; Pregnancy in Diabetics; Pregnancy Trimester, Third; Prospective Studies; Pulmonary Artery; Pulsatile Flow; Stroke Volume; Troponin T; Ultrasonography, Doppler, Color; Ultrasonography, Doppler, Pulsed; Ultrasonography, Prenatal; Vena Cava, Inferior

Few studies have compared midregional proatrial natriuretic peptide (MR-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP). We compared their value as risk markers for all-cause mortality and cardiovascular (CV) and renal complications in individuals with type 1 diabetes.. MR-proANP and NT-proBNP were measured in 664 individuals. Hazard ratios (HRs) were assessed per doubling of NT-proBNP or MR-proANP for risk of a composite of ischemic events, heart failure (HF), a combined renal end point of end-stage kidney disease (ESKD), decline in estimated glomerular filtration rate (eGFR) ≥30%, and all-cause mortality or individual end points. Adjustments included CV risk factors and addition of MR-proANP or NT-proBNP.. Median follow-up was 5.1-6.2 years. MR-proANP was associated with higher risk of all-cause mortality (. Higher NT-proBNP was independently associated with all-cause mortality, CV disease, HF, and the combined renal end point. MR-proANP was associated with all end points but decline in eGFR, although not independent of NT-proBNP. MR-proANP may contribute to the predictive value of NT-proBNP for risk stratification in type 1 diabetes.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments

To report an unusual case of simultaneous presentation of Addison's and Graves' disease in an adolescent female previously diagnosed with type 1 diabetes (T1D) and Hashimoto's.. A 15-year-old female with T1D and hypothyroidism presented to the emergency department with altered mental state, fever, and left arm weakness for one day. Clinical work-up revealed coexistent new-onset adrenal insufficiency and hyperthyroidism. Her clinical course was complicated by severe, life-threating multisystem organ dysfunction including neurologic deficits, acute kidney injury, and fluid overload. Thyroidectomy was ultimately performed in the setting of persistent signs of adrenal crises and resulted in rapid clinical improvement.. Endocrinopathy should be included in the differential diagnosis of altered mental status. This case additionally illustrates the challenges of managing adrenal insufficiency in the setting of hyperthyroidism and supports the use of thyroidectomy in this situation.

Topics: Addison Disease; Adolescent; Adrenal Insufficiency; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Multiple Organ Failure; Natriuretic Peptide, Brain; Peptide Fragments; Thyroidectomy

Cardiovascular disease (CVD) is the major cause of mortality in type 1 diabetes (T1D). Biomarkers, N-terminal pro-brain natriuretic peptide (NT-proBNP) and copeptin have been linked with measures of CVD, but their relationship in adolescents with T1D remains incompletely understood. Accordingly, we examined the associations between NT-proBNP and copeptin and hemodynamic markers of central aortic stiffness in adolescents with T1D.. In this pilot study, forty-nine pubertal adolescents with T1D (mean age 17 ± 2 years, median [Q1-Q3] Tanner Stage 5 [5, 5] and HbA1c 8.5 ± 1.5%), from the EMERALD study, were assessed for copeptin and NT-proBNP, and indices of central aortic stiffness non-invasively assessed by MRI. Pearson correlations and generalized linear regression models, adjusting for confounders, were applied to examine the relationships between biomarkers and vascular measures.. Serum copeptin and NT-proBNP may be associated with central aortic stiffness and elevated WSS in youth with T1D, potentially offering a non-invasive way to identify and monitor the development of early CVD in an at-risk population.

Topics: Adolescent; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Glycopeptides; Hemodynamics; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Vascular Stiffness; Young Adult

Diabetic ketoacidosis (DKA) can cause several complications. Among them, cardiac complications are the most fatal and difficult to detect. Cardiac markers are prognostic factors for morbidity and mortality in adult patients with DKA. But, there have been very few discussed cases in pediatrics. We report a case of severe DKA in child with elevated cardiac enzymes and prolonged QT interval.. A 12-year-old girl admitted by nausea, vomiting, and lethargy for 1 day.. Her blood sugar level was initially undetectable by the capillary blood glucose meter, and blood gas analysis showed severe DKA with elevated cardiac enzymes and prolonged QT interval.. The patient was admitted to hospital and intensive intravenous fluid and regular insulin infusion were administered.. After 5 days of supportive care, the patient was fully recovered, discharged, and followed up in an outpatient clinic.. Since the relationship between DKA and myocardial injury has not been clearly elucidated, pediatricians and emergency physicians should remain careful throughout the recovery time as it can lead to life-threatening conditions in various courses.

Topics: Acid-Base Equilibrium; Administration, Intravenous; Blood Gas Analysis; Blood Glucose; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Echocardiography; Electrocardiography; Female; Fluid Therapy; Heart Diseases; Humans; Hypoglycemic Agents; Insulin; Long QT Syndrome; Natriuretic Peptide, Brain; Treatment Outcome; Troponin I

Patients with type 1 diabetes have a high risk of cardiovascular disease. Yet, the importance of routine assessment of myocardial function in patients with type 1 diabetes is not known. Thus, we examined the prognostic importance of NT-proBNP and E/e', an echocardiographic measure of diastolic function, in type 1 diabetes patients with preserved left ventricular ejection fraction (LVEF) and without known heart disease.. Type 1 diabetes patients without known heart disease and LVEF ≥45% enrolled in the Thousand and 1 study were included and followed through nationwide registries. The risk of major cardiovascular events (MACE) and death associated with levels of NT-proBNP and E/e' was examined. Of 960 patients, median follow-up of 6.3 years (Q1-Q3: 5.7-7.0), 121 (12%) experienced MACE and 51 (5%) died. Increased levels of both NT-proBNP and E/e' were associated with worse outcomes (adjusted hazard ratios for MACE = 1.56 (1.23-1.98) and 4.29 (2.25-8.16) per Loge increase for NT-proBNP and E/e', respectively). NT-proBNP and E/e' combined significantly improved the discrimination power of the Steno T1D risk engine (MACE, C-index: 0.813 (0.779-0.847) vs 0.779 (0.742-0.816); P = 0.0001; All-cause mortality, C-index 0.855 (0.806-0.903) vs 0.828 (0.776-0.880); P = 0.03).. In patients with type 1 diabetes, preserved ejection fraction, and no known heart disease, NT-proBNP and E/e' were associated with increased risk of MACE and all-cause mortality. The risks associated with NT-proBNP and E/e' combined identified patients at remarkably high risk.

Topics: Adult; Aged; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Echocardiography; Female; Humans; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume; Ventricular Function, Left

There is much evidence that diabetes mellitus (DM)-induced hyperglycemia (HG) is responsible for kidney failure or nephropathy leading to cardiovascular complications. Cellular and molecular mechanism(s) whereby DM can damage the kidney is still not fully understood. This study investigated the effect of streptozotocin (STZ)-induced diabetes (T1DM) on the structure and associated molecular alterations of the isolated rat left kidney following 2 and 4 months of the disorder compared to the respective age-matched controls. The results revealed hypertrophy and general disorganized architecture of the kidney characterized by expansion in glomerular borders, tubular atrophy and increased vacuolization of renal tubular epithelial cells in the diabetic groups compared to controls. Electron microscopic analysis revealed ultrastructural alterations in the left kidney highlighted by an increase in glomerular basement membrane width. In addition, increased caspase-3 immunoreactivity was observed in the kidney of T1DM animals compared to age-matched controls. These structural changes were associated with elevated extracellular matrix (ECM) deposition and consequently, altered gene expression profile of ECM key components, together with elevated levels of key mediators (MMP9, integrin 5α, TIMP4, CTGF, vimentin) and reduced expressions of Cx43 and MMP2 of the ECM. Marked hypertrophy of the kidney was highlighted by increased atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression. These changes also correlated with increased TGFβ1 activity, gene expression in the left kidney and elevated active TGFβ1 in the plasma of T1DM rats compared to control. The results clearly demonstrated that TIDM could elicit severe structural changes and alteration in biochemical markers (remodelling) in the kidney leading to diabetic nephropathy (DN).

Topics: Animals; Atrial Natriuretic Factor; Caspase 3; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Extracellular Matrix; Extracellular Matrix Proteins; Gene Expression Regulation; Glomerular Basement Membrane; Male; Natriuretic Peptide, Brain; Rats; Rats, Wistar; Transforming Growth Factor beta1

Diabetes mellitus (DM) has been demonstrated to have a strong association with heart failure. Conventional echocardiographic analysis cannot sensitively monitor cardiac dysfunction in type I diabetic Akita hearts, but the phenotype of heart failure is observed in molecular levels during the early stages.. Male Akita (Ins2WT/C96Y) mice were monitored with echocardiographic imaging at various ages, and then with conventional echocardiographic analysis and speckle-tracking based strain analyses.. With speckle-tracking based strain analyses, diabetic Akita mice showed changes in average global radial strain at the age of 12 weeks, as well as decreased longitudinal strain. These changes occurred in the early stage and remained throughout the progression of diabetic cardiomyopathy in Akita mice. Speckle-tracking showed that the detailed and precise changes of cardiac deformation in the progression of diabetic cardiomyopathy in the genetic type I diabetic Akita mice were uncoupled.. We monitored early-stage changes in the heart of diabetic Akita mice. We utilize this technique to elucidate the underlying mechanism for heart failure in Akita genetic type I diabetic mice. It will further advance the assessment of cardiac abnormalities, as well as the discovery of new drug treatments using Akita genetic type I diabetic mice.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Diabetic Cardiomyopathies; Disease Models, Animal; Echocardiography; Female; Heart; Heart Rate; Heart Ventricles; Male; Mice; Mice, Inbred C57BL; Myocardium; Natriuretic Peptide, Brain; Severity of Illness Index; Ventricular Dysfunction, Left

High-sensitivity troponin T (hsTnT) is a marker of cardiovascular disease (CVD) and in type 2 diabetes also a marker of renal events, but has not been evaluated in type 1 diabetics. We therefore reviewed a type 1 diabetes cohort of 442 without and 458 with diabetic nephropathy. Baseline samples were analyzed for hsTnT levels. Cox regression analyses assessed predictive value in relation to the development of end-stage renal disease (ESRD) in 99 patients, all-cause mortality in 178, and CVD events in 134 after up to 12 years of follow-up. To assess if hsTnT improved risk prediction beyond traditional clinical risk markers, we calculated c statistics and relative integrated discrimination improvement. HsTnT was significantly higher in patients with diabetic nephropathy compared to normoalbuminuria (median 8.9 vs 3.1 ng/L). For a doubling in hsTnT levels, and after adjustment for well-known risk factors, including NT-proBNP and hsCRP, the hazard ratio for ESRD at 1.26 was not significant in the diabetic nephropathy group, but there was a significant association with GFR decline after adjustment during follow-up (2.9 ml/min/1.73 m

Topics: Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Disease Progression; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Troponin T

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are dominant inherited muscular dystrophies with multiple systemic involvement, often producing cardiac injury. This study sought to determine the clinical significance of elevated high sensitivity cardiac troponin T and I (hs-cTnT and hs-cTnI), and N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in this population.. Sixty DM patients (35 men and 25 women; mean age: 45.1 years, range: 12-73 years) underwent clinical cardiac investigations and measurements of serum hs-cTnT, hs-cTnI, creatine kinase (CK), and NT-proBNP. Left ventricular (LV) ejection fraction (EF) was assessed by echocardiography.. Genetic analysis revealed that 46 of the 60 patients were DM1, and 14 DM2. Blood measurements showed persistent elevation of hs-cTnT and CK in 55/60 DM patients (91.73%). In contrast, hs-cTnI values were persistently normal throughout the study. Only 2 patients showed an EF <50%, being the overall range of this population between 40% and 79%. We found ECG abnormalities in 19 patients. Of these patients, 13 showed first or second-degree atrio ventricular (AV) blocks (PR interval ≥ 200 ms), 4 showed a left bundle branch block (LBBB) prolonged (QRS duration ≥120 ms), and 2 had an incomplete bundle branch block (QRS duration between 110 and 119 ms). After excluding patients with EF <50%, NT-pro-BNP measurement > 125 pg/mL was an independent predictor of ECG abnormalities.. NT-pro-BNP levels may be considered to be used clinically to identify DM patients at increased risk of developing myocardial conduction abnormalities.

Topics: Adolescent; Adult; Aged; Alleles; Biomarkers; Child; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Electrocardiography; Female; Heart Diseases; Humans; Male; Middle Aged; Myotonic Dystrophy; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Prognosis; Protein Domains; Registries; Regression Analysis; Troponin I; Troponin T; Young Adult

To evaluate the relationship between 24-h blood pressure (BP) measurements and diastolic heart function evaluated by Doppler tissue imaging and B-type natriuretic peptide (BNP) levels in children with type 1 diabetes mellitus (DM).. A total of 32 diabetic and 18 healthy children were enrolled. Spectral Doppler analysis and tissue Doppler measurements were performed by conventional echocardiography. The 24-h ambulatory BP and serum BNP levels were measured.. Analysis of ambulatory blood pressure monitoring (ABPM) recordings showed that median daytime diastolic BP load were significantly higher in diabetic patients compared to controls [12.35 (4.23-27.23) vs. 2.5 (0-8.7), p = 0.007]. Patients with elevated daytime systolic and diastolic BP loads had significantly higher BNP values compared to patients with normal BP load (31.4 ± 24.36 vs. 11.84 ± 11.25 pg/mL, p = 0.03 and 23.21 ± 15.12 vs. 12.12 ± 14.65 pg/mL, p = 0.03, respectively). Isovolemic contraction time (47.43 ± 7.84 vs. 42.27 ± 7.47, p = 0.045), isovolemic relaxation time (68.84 ± 10.43 vs. 58.77 ± 10.02, p = 0.02), and myocardial performance index (0.45 ± 0.10 vs. 0.37 ± 0.09, p = 0.02) as determined by tissue Doppler echocardiography were significantly high in diabetic patients compared to that of control cases. Ratio of mitral peak early diastolic flow velocity (E) to peak early diastolic myocardial velocities by tissue Doppler echocardiography (E') was also higher in patients with elevated daytime systolic BP load (E/E', 6.71 ± 1.97 vs. 4.91 ± 1.02, p = 0.04).. Elevated BP loads detected by 24-h ambulatory BP measurements in children with type 1 diabetes are associated with increased BNP levels and abnormal tissue Doppler echocardiography indices, indicating early stage cardiac dysfunction.

Topics: Adolescent; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diastole; Early Diagnosis; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Retrospective Studies; ROC Curve; Ventricular Dysfunction, Left; Ventricular Function, Left

Diabetic cardiomyopathy is a leading cause of morbidity and mortality, and Insulin2 mutant (Ins2+/-) Akita is a genetic mice model of diabetes relevant to humans. Dicer, miRNAs, and inflammatory cytokines are associated with heart failure. However, the differential expression of miRNAs, dicer, and inflammatory molecules are not clear in diabetic cardiomyopathy of Akita. We measured the levels of miRNAs, dicer, pro-inflammatory tumor necrosis factor alpha (TNFα), and anti-inflammatory interleukin 10 (IL-10) in C57BL/6J (WT) and Akita hearts. The results revealed increased heart to body weight ratio and robust expression of brain natriuretic peptide (BNP: a hypertrophy marker) suggesting cardiac hypertrophy in Akita. The multiplex RT-PCR, qPCR, and immunoblotting showed up regulation of dicer, whereas miRNA array elicited spread down regulation of miRNAs in Akita including dramatic down regulation of let-7a, miR-130, miR-142-3p, miR-148, miR-338, miR-345-3p, miR-384-3p, miR-433, miR-450, miR-451, miR-455, miR-494, miR-499, miR-500, miR-542-3p, miR-744, and miR-872. Conversely, miR-295 is induced in Akita. Cardiac TNFα is upregulated at mRNA (RT-PCR and qPCR), protein (immunoblotting), and cellular (immunohistochemistry and confocal microscopy) levels, and is robust in hypertrophic cardiomyocytes suggesting direct association of TNFα with hypertrophy. Contrary to TNFα, cardiac IL-10 is downregulated in Akita. In conclusion, induction of dicer and TNFα, and attenuation of IL-10 and majority of miRNA are associated with cardiomyopathy in Akita and could be used for putative therapeutic target for heart failure in diabetics.

Topics: Animals; Cardiomegaly; DEAD-box RNA Helicases; Diabetes Mellitus, Type 1; Gene Expression Regulation; Insulin; Interleukin-10; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; MicroRNAs; Natriuretic Peptide, Brain; Ribonuclease III; Tumor Necrosis Factor-alpha

Although low dietary salt intake has beneficial effects on BP (blood pressure), low 24hUNa (24 h urinary sodium excretion), the most accurate estimate of dietary salt intake, is associated with increased mortality in people with diabetes. In the non-diabetic population, low salt intake is associated with increased RAAS (renin-angiotensin-aldosterone system) activity. In this cross-sectional study, we examined the relationship between 24hUNa, PRA (plasma renin activity), serum aldosterone and BNP (brain natriuretic peptide) in patients with diabetes. Clinical characteristics, 24hUNa, PRA, serum aldosterone and BNP were recorded in 222 consecutive patients (77% with Type 2 diabetes) attending a diabetes clinic at a tertiary hospital. The relationship between 24hUNa, serum aldosterone, PRA, BNP, urinary potassium excretion, serum potassium, serum sodium, eGFR (estimated glomerular filtration rate), urinary albumin excretion and HbA1c (glycated haemoglobin) was examined by a multivariable regression model. Levels of 24hUNa significantly predicted serum aldosterone in a linear fashion (R²=0.20, P=0.002). In the subgroup of patients (n=46) not taking RAAS-modifying agents, this relationship was also observed (R²=0.10, P=0.03), and the effect of 24hUNa on serum aldosterone was found to be more pronounced than in the whole cohort (coefficient=-0.0014, compared with -0.0008). There was no demonstrable relationship between 24hUNa and PRA or BNP. Low 24hUNa is associated with increased serum aldosterone in people with diabetes, in the presence and absence of RAAS-modifying agents. This raises the possibility that stimulation of the RAAS may be a mechanism that contributes to adverse outcomes observed in patients with low 24hUNa.

Topics: Aged; Aldosterone; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diuretics; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Renin; Renin-Angiotensin System; Sodium

Diabetic cardiomyopathy is an important complication of type 1 diabetes mellitus. Diastolic heart failure is an early manifestation of diabetic cardiac disease. Nt-proBNP is a valuable marker of ventricular dysfunction. The aim of this study was to determine Nt-proBNP concentrations in type 1 diabetic patients and determine their relationship with ventricular diastolic dysfunction (DD) and carotid artery intima media thickness (CIMT) measurements. Sixty-seven type 1 diabetic patients (30.2 ± 8.0 years; W/M: 24/43) without known cardiovascular disease and 48 healthy controls (30.5 ± 6.4 years; W/M: 19/29) were recruited. Nt-proBNP levels were measured. Conventional and tissue Doppler echocardiography were used to evaluate left ventricular diastolic function and CIMT. Nt-proBNP in diabetic patients was significantly higher than in controls (38 ± 34.8 vs. 15.1 ± 12.7 pg/ml) (P = 0.004). Ea level was higher (12.3 ± 3 vs. 10.3 ± 4 cm/s, P = 0.003) and E/Ea ratio was lower in patients (6.6 ± 2.5 vs. 9.7 ± 5.9, P = 0.001) compared with controls. Ratio of DD was higher in patients than controls (11.1 vs. 2.1%, P = 0.01). CIMT measurements in diabetic patients were higher than controls (0.54 ± 0.11 vs. 0.48 ± 0.05 mm, P = 0.02). Logistic regression revealed age and HbA1c to be independently associated with the presence of DD. Nt-proBNP levels are elevated in type 1 diabetic patients without overt cardiovascular disease and the presence of DD is increased in diabetic patients in comparison with controls. Nt-proBNP levels do not seem to be related to the presence of DD and subclinical atherosclerosis in this group of patients.

Topics: Adult; Cardiovascular Diseases; Carotid Arteries; Carotid Intima-Media Thickness; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diastole; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left

N-terminal-pro-brain natriuretic peptide (NT-proBNP) is elevated in gestational hypertension and preeclampsia. This trial aimed to generate data for gestational diabetes mellitus patients, who are at risk to develop these complications.. We have measured NT-proBNP in 223 otherwise healthy women between gestational week 24 and 32 referred to the outpatient diabetes unit in a cross-sectional study.. 88 control subjects, 45 patients with indication for medical nutrition therapy (MNT) alone and 90 patients who required insulin therapy were included. Groups of women were comparable regarding gestational week. Body mass index before pregnancy and at blood draw was significantly higher in subjects with insulin dependent gestational diabetes mellitus compared to MNT controlled gestational diabetes mellitus. NT-proBNP was significantly lower in patients with insulin dependent gestational diabetes mellitus (35 ± 25 pg/ml) compared to controls (53 ± 43 pg/ml, p = 0.012).. NT-proBNP is within the reference range of normal subjects in women with gestational diabetes mellitus. Differences in body mass index, changes in glomerular filtration rate and haemodynamics may explain lower NT-proBNP concentrations in insulin dependent gestational diabetes mellitus. A false negative interpretation needs to be considered in these women.

Topics: Biomarkers; Body Mass Index; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Pregnancy Complications, Cardiovascular; Prospective Studies; Protein Precursors; Reference Values

Patients with diabetes mellitus have a substantially increased risk of developing cardiovascular disease. However, the absolute risk greatly varies not only among patients, but the risk profile for an individual patient may also change over time. We investigated the prognostic role of repetitive measurements of Glycated haemoglobin A(1c) (HbA(1c) ) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with longstanding diabetes.. For this prospective, observational study data from 544 consecutive patients were collected between 2005 and 2008. HbA(1c) and NT-proBNP were measured at baseline and after 1 year. The median observation period was 40 months. Endpoints were all-cause mortality, cardiac, cardiovascular and all-cause hospitalizations.. N-terminal pro-B-type natriuretic peptide concentrations significantly increased from 230 ± 385 to 280 ± 449 pg mL(-1) (P < 0·001); during the same time, HbA(1c) significantly decreased from 7·6 ± 1·5 to 7·3 ± 1·2 (P < 0·001). NT-proBNP was the best baseline predictor in a Cox regression model consisting of NT-proBNP, HbA(1c) , age, gender and duration of diabetes for all endpoints (P < 0·001). NT-proBNP at follow-up was the best predictor for the remaining period (P < 0·001, all endpoints). HbA(1c) at baseline and follow-up was predictive for all-cause hospitalizations (P = 0·005 both). In a third model that investigated the plasticity of both markers, changes in HbA(1c) concentration had no predictive value, but a change of NT-proBNP concentration was highly predictive (P = 0·025 all-cause mortality, P < 0·001 all other endpoints).. N-terminal pro-B-type natriuretic peptide and HbA(1c) concentrations significantly diverged over a 1-year period. NT-proBNP was the most potent predictor of outcome at baseline and follow-up, and changes in NT-proBNP concentrations were linked to an altered risk profile, unlike changes in HbA(1c) levels.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Regression Analysis; Risk Factors

The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting that preeclampsia is associated with cardiovascular changes in early pregnancy.

Topics: Adult; Atrial Natriuretic Factor; Diabetes Mellitus, Type 1; Female; Gestational Age; Humans; Natriuretic Peptide, Brain; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Young Adult

Topics: Diabetes Mellitus, Type 1; Female; Fetal Macrosomia; Humans; Infant, Newborn; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Pregnancy in Diabetics; Troponin T

To evaluate N-terminal pro brain natriuretic peptide (NT-proBNP) as a marker of long-term micro- and macrovascular complications in type 1 diabetes.. This was a cross-sectional study of 208 long-term surviving type 1 diabetic patients from a population-based cohort from Fyn County, Denmark. In a clinical examination in 2007-2008, NT-proBNP was measured and related to proliferative diabetic retinopathy (PDR), nephropathy, neuropathy and macrovascular disease.. Median age and duration of diabetes was 58.7 and 43 years, respectively. Median NT-proBNP concentration was 78 pg/ml (10th-90th percentile 25-653 pg/ml). The NT-proBNP level (89 vs. 71 pg/ml, p = 0.02) was higher in women. In univariate analyses, NT-proBNP was associated with age, duration of diabetes, diastolic blood pressure (inversely), nephropathy, neuropathy and macrovascular disease. For instance, median NT-proBNP concentrations were 70, 91 and 486 pg/ml for patients with normo-, micro- and macroalbuminuria, respectively (p < 0.01). When adjusted for age, sex, duration of diabetes, high sensitivity CRP, HbA(1c), diastolic blood pressure and smoking, higher NT-proBNP concentrations (4th vs. 1st quartile) were related to nephropathy (odds ratio [OR] 5.03; 95% confidence interval [CI] 1.77-14.25), neuropathy (OR 4.08; 95% CI 1.52-10.97) and macrovascular disease (OR 5.84; 95% CI 1.65-20.74). There was no association with PDR.. NT-proBNP has traditionally been described as a marker of heart failure and left ventricular dysfunction. In this study of long-term surviving type 1 diabetic patients, we found NT-proBNP associated with nephropathy, neuropathy and macrovascular disease. If confirmed by prospective studies, NT-proBNP might be a useful prognostic marker of diabetes-related complications.

Topics: Adult; Aged; Albuminuria; Blood Pressure; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments

Cardiomyopathy is noted in up to 40% of infants of diabetic mothers, and the exact mechanisms are unknown. The aim of this study was to determine whether fetal serum markers of cardiac function differ between normal and type 1 diabetic pregnancies and to examine the relationship between these markers and fetal cardiac structure and function.. This was a prospective observational study of 45 type 1 diabetic pregnancies and 39 normal pregnancies. All participants had concentrations of fetal pro-B-type natriuretic peptide (proBNP) and troponin-T (TnT) measured at the time of delivery. All patients with type 1 diabetes had Doppler evaluation of the umbilical artery, middle cerebral artery, and ductus venosus in the third trimester, and a subset (n = 21) had detailed fetal echocardiograms performed in each trimester.. Fetal proBNP and TnT concentrations were higher in the diabetic cohort than in the normal cohort (P < 0.05). ProBNP correlated positively with interventricular septum thickness (P < 0.05) but not with cardiac function indexes in the third trimester. In patients with poor glycemic control, there was a significant positive correlation (P < 0.05) between fetal TnT and the third trimester umbilical artery pulsatility index. There were also increased levels of fetal TnT in infants with poor perinatal outcome (P < 0.05).. Biochemical markers of cardiac dysfunction are elevated in infants of diabetic mothers, especially those with cardiomyopathy or poor perinatal outcome. Hyperglycemia in early pregnancy may affect myocardial and placental development, thus contributing to the susceptibility to hypoxia seen in these infants.

Topics: Adult; Age of Onset; Apgar Score; Birth Weight; Body Mass Index; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Female; Fetal Blood; Fetal Macrosomia; Glycated Hemoglobin; Humans; Infant, Newborn; Natriuretic Peptide, Brain; Parity; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Prospective Studies; Reference Values; Troponin T

The spectrum of diabetic heart disease involves a progression from normal heart to preclinical left ventricular diastolic and systolic dysfunction followed by overt echocardiographic evidence of left ventricular (LV) dysfunction and finally symptomatic heart failure.. To compare the value of tissue Doppler imaging (TDI) over the conventional echocardiography in the assessment of early myocardial dysfunction in type 1 diabetics in correlation with serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP), state of metabolic control, and diabetes duration.. Sixty subjects were included; 40 type 1 diabetics (aged 12-18 years). Twenty matched subjects served as controls. They were subjected to clinical examination with assessment of cardiovascular reflexes for autonomic neuropathy. Laboratory investigations included mean random blood sugar (MRBS), hemoglobin A1c (HbA1c), urinary microalbumin, and serum determination of NT-pro-BNP. Echocardiography for chamber dimensions, systolic and diastolic function, Tie index, and longitudinal myocardial global biventricular function by pulsed TDI of 6 LV walls and right ventricle (RV) free wall.. All diabetics and controls had normal LV dimensions, LV mass index and systolic functions except for higher left ventricular posterior wall (LVPW) in diabetics (P < 0.05). LV and RV diastolic dysfunction diagnosed in 25% of diabetics by conventional Doppler with higher peak A (P < 0.05, P < 0.05) and lower E/A (P < 0.05, P < 0.05) compared to controls. Diabetics had larger Tie index (P < 0.05). TDI showed delayed myocardial relaxation in 52.5% of diabetics with lower LV and RV peak Em (P < 0.05, P < 0.01) and Em/Am (P < 0.01, P < 0.001) compared to controls. NT-pro-BNP was elevated in diabetics (P < 0.01) with best cut-off value = 62.5 Fmol/mL, sensitivity (82%), and specificity (95%) for detection of isolated diastolic dysfunction in diabetics. It was correlated negatively with LV Em (P < 0.05), Em/Am (P < 0.01) and positively with Am (P < 0.01), impaired diastolic velocities were associated with higher HbA1c.. Asymptomatic diabetics had evidence of subtle right and LV dysfunction with delayed myocardial relaxation which was related to metabolic control. Tissue Doppler (TD) has an additional value in evaluating ventricular filling. NT-pro-BNP is considered a sensitive, specific, and predictive marker for diastolic dysfunction.

Topics: Adolescent; Child; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diastole; Early Diagnosis; Echocardiography; Female; Heart Failure; Heart Function Tests; Humans; Hyperglycemia; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Risk Factors; ROC Curve; Sensitivity and Specificity; Systole; Ventricular Dysfunction, Left

To determine whether plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, a marker for cardiac failure and potentially for the severity of coronary artery disease (CAD), predicts silent myocardial ischaemia (SMI) and silent CAD in asymptomatic high-risk diabetic patients.. Five hundred and seventeen asymptomatic diabetic patients with > or = 1 additional cardiovascular risk factor but without heart failure were prospectively screened between 1998 and 2008 for SMI, defined as an abnormal stress myocardial scintigraphy, and subsequently for significant (> 70%) angiographic CAD. The 323 patients with interpretable echocardiography and for whom NT-proBNP was measured were included in this analysis.. SMI was found in 108 (33.4%) patients, 39 of whom had CAD. NT-proBNP was higher in the patients with CAD than in the patients without CAD [45.0 (1-3199) vs. 20.0 (1-1640) pg/ml; P < 0.0001 median (range)], even after adjustment for confounding factors: age, gender, body mass index, glycated haemoglobin (HbA(1c)), retinopathy, nephropathy, hypertension, echocardiographic parameters (P < 0.05). NT-proBNP in the third tertile (> or = 38 pg/ml) predicted CAD with a sensitivity of 59% and a specificity of 67%. In a multiple logistic regression analysis including NT-proBNP > or = 38 pg/ml, age, body mass index, gender, HbA(1c), hypertension, retinopathy, nephropathy, peripheral occlusive arterial disease, left ventricular systolic dysfunction, dilatation and hypertrophy and Type 1 transmitral flow, NT-proBNP > or = 38 pg/ml was the only significant independent predictor of silent CAD [odds ratio (OR) 3.1 (95% confidence interval 1.3-7.6), P = 0.015].. NT-proBNP measurement helps to better define asymptomatic diabetic patients with an increased likelihood for CAD, independently of cardiac function and structure.

Topics: Biomarkers; Coronary Artery Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ultrasonography; Ventricular Dysfunction, Left

Diabetic cardiomyopathy is an important contributor to diastolic and systolic heart failure. We examined the nature and mechanism of the cardiomyopathy in Akita (Ins2(WT/C96Y)) mice, a model of genetic nonobese type 1 diabetes that recapitulates human type 1 diabetes. Cardiac function was evaluated in male Ins2WT/C96Y and their littermate control (Ins2WT/WT) mice using echocardiography and tissue Doppler imaging, in vivo hemodynamic measurements, as well as ex vivo working heart preparation. At 3 and 6 mo of age, Ins2WT/C96Y mice exhibited preserved cardiac systolic function compared with Ins2WT/WT mice, as evaluated by ejection fraction, fractional shortening, left ventricular (LV) end-systolic pressure and maximum rate of increase in LV pressure in vivo, cardiac work, cardiac power, and rate-pressure product ex vivo. Despite the unaltered systolic function, Ins2WT/C96Y mice exhibited significant and progressive diastolic dysfunction at 3 and 6 mo of age compared with Ins2WT/WT mice as assessed by tissue and pulse Doppler imaging (E-wave velocity, isovolumetric relaxation time) and by in vivo hemodynamic measurements (LV end-diastolic pressure, time constant of LV relaxation, and maximum rate of decrease in LV pressure). We found no evidence of myocardial hypertrophy or fibrosis in the Ins2WT/C96Y myocardium. Consistent with the lack of fibrosis, expression of procollagen-alpha type I, procollagen-alpha type III, and fibronectin were not increased in these hearts. Ins2WT/C96Y hearts showed significantly reduced sarcoplasmic reticulum Ca2+-ATPase 2a (cardiac sarcoplasmic reticulum Ca2+ pump) levels, elevated beta-myosin heavy chain isoform, increased long-chain fatty acids, and triacylglycerol with evidence of lipotoxicity, as indicated by a significant rise in ceramide, diacylglycerol, and lipid deposits in the myocardium. Consistent with metabolic perturbation, and a switch to fatty acid oxidation from glucose oxidation in Ins2WT/C96Y hearts, expression of mitochondrial long-chain acyl-CoA dehydrogenase and pyruvate dehydrogenase kinase isoform 4 were increased. Insulin treatment reversed the diastolic dysfunction, the elevated B-type natriuretic peptide and beta-myosin heavy chain, and the reduced sarcoplasmic reticulum Ca2+-ATPase 2a levels with abolition of cardiac lipotoxicity. We conclude that early type 1 diabetic cardiomyopathy is characterized by diastolic dysfunction associated with lipotoxic cardiomyopathy with preserved systolic function in t

Topics: Acyl-CoA Dehydrogenase, Long-Chain; Age Factors; Animals; Blood Glucose; Cardiomyopathies; Ceramides; Diabetes Mellitus, Type 1; Diastole; Diglycerides; Disease Models, Animal; Disease Progression; Echocardiography, Doppler, Pulsed; Fatty Acids; Hypoglycemic Agents; Insulin; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mitochondria, Heart; Myocardial Contraction; Myocardium; Myosin Heavy Chains; Natriuretic Peptide, Brain; Protein Serine-Threonine Kinases; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Stroke Volume; Systole; Triglycerides; Ventricular Dysfunction, Left; Ventricular Pressure

To measure left ventricular mass (LVM), left ventricular volumes, and left ventricular function (LVF) in a cohort of type 1 diabetic patients and to correlate measures of imaging to NH(2)-terminal pro-brain natriuretic peptide (NT-proBNP).. In a cross-sectional study, all patients with type 1 diabetes underwent cardiovascular magnetic resonance imaging. We included 63 patients with diabetic nephropathy and 73 patients with normoalbuminuria.. All patients had normal global LVF. LVM was increased in patients with diabetic nephropathy compared with patients with persistent normoalbuminuria. Patients with nephropathy had smaller left ventricular volumes and increased levels of NT-proBNP. Linear regression analysis in patients with diabetic nephropathy showed that NT-proBNP and creatinine were associated with LVM.. Increased LVM is identified in asymptomatic type 1 diabetic patients with nephropathy compared with normoalbuminuric patients. Elevated levels of NT-proBNP were associated with increased LVM, which are both markers of increased cardiovascular risk.

Topics: Adult; Age of Onset; Albuminuria; Body Mass Index; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Function, Left

We hypothesised that human fetal cardiac natriuretic peptide secretion is increased in type-1 diabetic pregnancies with normal placental hemodynamics, and this increase is related to the first trimester maternal glycemic control.. Thirty-two neonates of type-1 diabetic mothers and 60 neonates born after uncomplicated pregnancy and labour (control group) were included in this study. Diabetic pregnancies were divided into two subgroups based on the first trimester HbA1c value. Group 1 pregnancies (n =22) had a good glycemic control (HbA1c <7.5%) and Group 2 pregnancies (n =10) had a poor glycemic control (HbA1c > or =7.5%). At delivery, an umbilical artery (UA) blood sample was obtained for assessment of N-terminal peptide of proatrial (NT-proANP) and proB-type (NT-proBNP) natriuretic peptide levels. In diabetic pregnancies, each fetus had normal UA Doppler velocimetry for gestational age.. The newborn UA NT-proANP and NT-proBNP concentrations were significantly higher in type-1 diabetic pregnancies than in the control group. Group 2 fetuses with poor glycemic control showed significantly higher UA NT-proANP levels than Group 1 fetuses. UA NT-proANP levels correlated significantly with maternal HbA1c values in the first, second and third trimesters, while UA NT-proBNP levels did not correlate with maternal HbA1c values.. In type-1 diabetic pregnancies, fetal cardiac natriuretic peptide secretion is increased, even in the presence of good glycemic control and normal placental hemodynamics. In addition, fetal NT-proANP levels are already related to maternal glycemic control in the first trimester of pregnancy.

Topics: Atrial Natriuretic Factor; Blood Flow Velocity; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Female; Humans; Infant, Newborn; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Pregnancy in Diabetics; Protein Precursors; Ultrasonography; Umbilical Arteries

Maternal diabetes increases the risk of hypertrophic cardiomyopathy in the fetus. As signaling via the C-type natriuretic peptide (CNP) specific receptor protects against cardiac hypertrophy, we examined whether maternal type 1 diabetes affects the plasma concentrations of proCNP-derived peptides in newborn infants.. Plasma concentrations of proCNP-derived peptides were measured in umbilical cord plasma and human placental tissue extracts using sequence-specific radioimmunoassays raised against N-terminal and C-terminal proCNP regions, respectively.. The median proCNP concentrations were similar in umbilical cord plasma from pregnant women with and without type 1 diabetes (17 pmol/L vs. 19 pmol/L, P not significant) and did not correlate with the proBNP concentrations in the same samples. However, the molar ratio between the proCNP and the CNP peptide was increased in umbilical cord plasma compared to adult plasma (4.6 vs. 1.1), which parallels our earlier findings for proBNP and BNP peptides.. There is a discordant expression of CNP and BNP peptides in newborn infants of mothers with diabetes. Moreover, fetal metabolism of proCNP and CNP appears to differ from healthy adults. The precise mechanism underlying these differences warrants further investigation.

Topics: Adult; Diabetes Mellitus, Type 1; Female; Fetal Blood; Gene Expression; Glycated Hemoglobin; Humans; Infant, Newborn; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Placenta; Pregnancy; Protein Precursors; Radioimmunoassay; White People

Circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are elevated in patients with diabetic nephropathy and independently predict excess cardiovascular morbidity and mortality. Therefore, we investigated the association between two polymorphisms -381T/C and 1551G/A of the BNP gene, plasma NT-proBNP levels and mortality prognosis in 380 type 1 diabetic patients with and without diabetic nephropathy.. In a prospective observational follow-up study, 197 type 1 diabetic patients with diabetic nephropathy {121 men, age [mean (SD)] 41 +/- 9.5 years, duration of diabetes 28 +/- 8.0 years, glomerular filtration rate 67 +/- 28 ml/min/1.73 m2}, and a matched control group of 183 patients with longstanding type 1 diabetes and persistent normoalbuminuria (111 men, age 43 +/- 10.0 years, duration of diabetes 27 +/- 8.3 years) were followed for 12.6 (0.0-12.9) years. Plasma NT-proBNP concentration was determined by immunoassay at baseline. The BNP genotypes were determined by TaqMan chemistry based assays.. The two polymorphisms were in almost complete linkage disequilibrium (r2 = 0.883) and thus only the results of the -381T/C promoter polymorphism are shown. There was no significant difference between cases and controls in either genotype distributions (cases TT 32%, TC 53%, CC 15%; controls TT 28%, TC 52%, CC 20%) or allele frequencies (cases T/C 0.58/0.42; controls T/C 0.54/0.46) for the -381T/C polymorphism. Among the 164 normoalbuminuric patients without antihypertensive treatment and previous major cardiovascular disease (CVD), the -381T/C polymorphism was associated with circulating levels of NT-proBNP [median (interquartile range) 21 (5-32), 34 (12-67) and 32 (12-58) ng/l for TT, TC and CC, respectively (P = 0.041)] persisting after adjustment for covariates (P = 0.018). During follow-up, the -381T/C polymorphism did not predict all-cause or cardiovascular mortality among type 1 diabetic patients with or without diabetic nephropathy.. The BNP -381T/C and 1551G/A polymorphisms are associated with circulating levels of NT-proBNP but not with prevalent overt diabetic nephropathy. These polymorphisms do not predict all-cause or cardiovascular mortality in Caucasian type 1 diabetic patients with or without diabetic nephropathy.

Topics: Adult; Body Mass Index; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Polymorphism, Genetic

Aims The incidence of diabetic cardiomyopathy, independent of arterial hypertension (AH) and coronary heart disease (CHD), remains controversial. The present study aimed to determine the influence of type 1 diabetes mellitus (T1DM) of long duration (>10 years) on myocardial function estimated by echocardiography (ECHO) and serum level of N-terminal pro-B type natriuretic peptide (NT-proBNP) in patients without CHD and AH. We also retrospectively investigated the relationship between the structural changes in the hearts of other deceased T1DM patients, and had their myocardial function echocardiographically assessed before death. Methods and results In 185 patients (96 males) with T1DM (mean duration 22.8 years) and 105 non-diabetic control subjects (57 males), detailed ECHO parameters and NT-proBNP were assessed. No significant differences were found between the respective groups. Histological studies of 17 hearts of deceased T1DM patients were carried out and retrospectively compared with their ECHO performed before death. Histological changes were identified, although without the signs of myocardial dysfunction on ECHO prior to death. Conclusion Even the application of echocardiographic, biochemical and morphologic techniques hardly gives sufficient grounds to believe that type 1 diabetes alone may actually precipitate myocardial dysfunction, despite long-term course of the disease and typical histological changes in the myocardium.

Topics: Adult; Age Factors; Biomarkers; Cardiomyopathies; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Echocardiography; Female; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Sex Factors; Statistics as Topic; Time Factors

Topics: Age Factors; Animals; Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Heart Failure; Humans; Male; Mice; Natriuretic Peptide, Brain; Rats; Sex Factors

Diabetes may cause cardiomyopathy characterized by cardiac fibrosis. Recent studies of genetically modified mice have elucidated a role of the natriuretic peptides (NP), type-A and type-B (ANP and BNP), and their common receptor [natriuretic peptide receptor (NPR), type-A] in development of cardiac fibrosis. The role of NP type-C (CNP) and NPR type-B (NPR-B) in the heart is less well established. In this study we examined if diabetes alters heart expression of the genes encoding the NP and its receptors.. Cardiac mRNA was quantified by real-time PCR in diabetic streptozotocin (STZ)-treated and ob/ob-mice and nondiabetic control mice.. The ob/ob-mice with type-II diabetes displayed highly significant increases of the cardiac mRNA expression of NPR-B and NPR-C while the expression levels of NPR-A, ANP, BNP, and CNP mRNA were similar in ob/ob-mice and controls. Mice with STZ-induced type-I diabetes also showed an increase of heart NPR-B mRNA expression at 12 weeks, but not at 3, 6 or 9 weeks after STZ-treatment. The ANP and NPR-C mRNA expressions were only altered after 3 weeks, whereas BNP, CNP and NPR-A mRNA expressions were not altered in STZ-treated-mouse hearts at any of the time points.. The results show that diabetes in mice confers increased NPR-B gene expression in the heart, suggesting that increased NPR-B signalling may affect development of diabetic cardiomyopathy.

Topics: Animals; Atrial Natriuretic Factor; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Guanylate Cyclase; Heart; Male; Mice; Mice, Inbred C57BL; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Receptors, Atrial Natriuretic Factor; RNA, Messenger; Up-Regulation

Raised N-terminal pro-brain natriuretic peptide (NT-proBNP) is independently associated with an increased risk of death in chronic heart failure and acute coronary syndromes in nondiabetic populations. Diabetic nephropathy is characterised by an increased risk of cardiovascular morbidity and mortality. This study investigated the prognostic value of NT-proBNP in a large cohort of type 1 diabetic patients with and without diabetic nephropathy.. In a prospective observational follow-up study, 198 type 1 diabetic patients with overt diabetic nephropathy (122 men, age [mean+/-SD] 41+/-10 years, duration of diabetes 28+/-8 years, GFR 74+/-33 ml min(-1)) and a matched control group of 188 patients with longstanding type 1 diabetes and persistent normoalbuminuria (114 men, age 43+/-10 years, duration of diabetes 27+/-9 years) were followed for 9.3 (0.0-9.5) years. Plasma NT-proBNP concentration was determined by immunoassay at baseline.. In patients with diabetic nephropathy, plasma NT-proBNP concentration was elevated to (median [range]) 110 (5-79640) ng l(-1) vs. 27 (5-455) ng l(-1) in normoalbuminuric patients (p<0.0001). Among patients with nephropathy, 39 (39%) patients with plasma NT-proBNP concentrations above the median and 12 (12%) with values below the median died from any cause (unadjusted hazard ratio 3.86 [95% CI 2.02-7.37], p<0.0001; covariate-adjusted hazard ratio 2.28 [1.04-4.99], p=0.04). This lower mortality rate was attributable to fewer cardiovascular deaths: 31 (31%) and 7 (7%) above and below the median NT-proBNP level respectively (unadjusted hazard ratio 5.25 [2.31-11.92], p<0.0001; covariate-adjusted hazard ratio 3.81 [1.46-9.94], p=0.006).. Elevated circulating NT-proBNP is a new independent predictor of the excess overall and cardiovascular mortality in diabetic nephropathy patients without symptoms of heart failure.

Topics: Adult; Biomarkers; Blood Pressure; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Reproducibility of Results; Risk Factors; Smoking; Time Factors

Up to 40% of newborn infants of women with type 1 diabetes have echocardiographic signs of cardiomyopathy. Increased plasma concentrations of B-type natriuretic peptide (BNP) and its precursor (proBNP) are markers of cardiac failure and hypoxia in adults. In this study, we investigated whether plasma concentrations of proBNP and/or BNP are increased in infants of women with type 1 diabetes.. Plasma BNP and proBNP were measured with RIAs. The proBNP assay measures both intact proBNP and NH(2)-terminal fragments derived from this precursor, whereas the BNP assay measures only BNP-32 and not proBNP.. Infants of women with diabetes and hemoglobin A(1c) (Hb A(1c)) > or =6.2% before delivery had a higher median plasma proBNP concentration (31 pmol/L; interquartile range, 21-47 pmol/L; n = 16) than infants of healthy women [16 (9-32) pmol/L; n = 21; P = 0.01]. Infants of women with diabetes and Hb A(1c) <6.2% (n = 15) had intermediate values. The plasma BNP and proBNP concentrations were closely associated (r(2) = 0.80; P < 0.0001); within the group of infants of women with diabetes and Hb A(1c) > or =6.2%, both correlated with the degree of fetal stress during labor.. Maternal diabetes and suboptimal metabolic control may affect the fetal heart and predominantly stimulate proBNP secretion in conjunction with perinatal stress.

Topics: Case-Control Studies; Diabetes Mellitus, Type 1; Female; Fetal Blood; Humans; Infant, Newborn; Natriuretic Peptide, Brain; Pregnancy; Pregnancy in Diabetics; Protein Precursors

Plasma N-terminal pro-brain natriuretic peptide (NT proBNP) is produced and released from cardiac ventricles; it is elevated in patients with heart failure, hypertension and chronic renal failure. This study aimed to examine the plasma levels of NT proBNP and their relationship in Type 1 diabetic patients with and without diabetic nephropathy.. We developed a non-competitive immunoluminometric assay with in-house antibodies to the N- and C-terminal domains of NT proBNP. We compared NT proBNP levels between 47 normoalbuminuric patients (group 1), 12 microalbuminuric patients (group 2) and 12 patients with macroalbuminuria (group 3).. There were significant differences in 24-h systolic and diastolic blood pressure, diabetes duration, serum creatinine, LDL-cholesterol and HbA1c between the three groups; other parameters did not differ significantly. NT proBNP (median and range) levels were 5 (0.75-68), 22 (0.75-82) and 23 (0.75-374) fmol/ml for groups 1-3, respectively. Log-transformed data of NT proBNP were used to compare all three groups (P=0.016). The Pearson correlation between NT proBNP and albuminuria (R=0.27; P=0.02) was positive; HbA1c (R=0.25; P=0.03) and age (R=0.33; P=0.005) correlated significantly as well. On the basis of multiple regression analysis, the adjusted difference remained significant between the three groups.. This is the first demonstration that NT proBNP levels are significantly higher in Type 1 diabetic patients with albuminuria. This may be caused by a down-regulation of A-type guanylate cyclase-coupled natriuretic peptide receptors in renal tubules or by elevated NT proBNP levels leading to higher glomerular hydraulic pressure or higher capillary permeability and possibly increased albumin excretion. Further studies are required to investigate the potential role of NT proBNP in patients with diabetic nephropathy and such other co-morbidities as cardiovascular disease.

Topics: Adult; Albuminuria; Blood Pressure; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Down-Regulation; Female; Humans; Immunoassay; Male; Natriuretic Peptide, Brain; Regression Analysis

Routine screening of diabetic patients with echocardiography is not feasible due to its limited availability and high cost. B-type natriuretic peptide (BNP) is secreted from the left ventricle in response to pressure overload and is elevated in both systolic and diastolic dysfunction.. BNP levels were compared to echocardiographic findings in 263 patients. Patients were divided into two groups: clinical indication for echocardiography (CIE) (n = 172) and those without clinical indication for echocardiography (no-CIE) (n = 91). Cardiologists making the assessment of left ventricular function were blinded when measuring plasma levels of BNP.. The 91 patients with no-CIE with echoes had similar BNP levels (83 +/- 16 pg/ml) to the 215 patients with no-CIE without echoes (63 +/- 10, P = 0.10). Patients with CIE and subsequent abnormal left ventricular function (n = 112) had a mean BNP concentration of 435 +/- 41 pg/ml, compared with those with no-CIE, but had abnormal left ventricular function on echo (n = 32) (161 +/- 40 pg/ml). Twenty-one of 32 patients with no-CIE but with abnormal left ventricular function had diastolic dysfunction (BNP 190 +/- 60 pg/ml). A receiver-operating characteristic (ROC) curve revealed that the area under the curve was 0.91 for CIE patients and 0.81 for no-CIE patients (P < 0.001). For those with no congestive heart failure (CHF) symptoms, BNP levels showed a high negative predictive value (91% for BNP values <39 pg/ml), while in those patients who had a CIE, BNP levels showed a high positive predictive value for the detection of left ventricular dysfunction (96% with BNP levels >90 pg/ml).. BNP can reliably screen diabetic patients for the presence or absence of left ventricular dysfunction.

Topics: Atrial Fibrillation; Biomarkers; Coronary Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Echocardiography; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left; Ventricular Function, Left

We investigated whether plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) reflect impaired diastolic relaxation or its improvement after ACE inhibition.. 7 long-term Type 1 diabetic patients with normal systolic but impaired diastolic function and with sympathetic myocardial dysinnervation and 10 controls were included. Exercise tolerance and maximal O 2 uptake were evaluated by bicycle exercise prior to the study. ANP, BNP and norepinephrine/epinephrine (NE/E) were determined at baseline and at 80 % .VO2 max workload and after recovery, before and following 12 weeks of treatment with fosinopril (10 mg/d).. Isovolumetric relaxation time (IVRT) and A/E wave ratio were increased by 26.7 +/- 11.5 % and 54.4 +/- 26.1 % in diabetic patients as compared to controls, respectively (p < 0.02). After 12 weeks of fosinopril treatment, no differences in IVRT or A/E wave ratio were detectable between groups. ANP was enhanced in Type 1 diabetes as compared to controls (baseline: 9.2 +/- 3.0 vs. 4.5 +/- 1.1; exercise: 22.4 +/- 7.7 vs. 7.9 +/- 1.2; recovery: 20.3. +/- 4.6 vs. 9.5 +/- 2.0 fmol/ml, p < 0.02). Fosinopril treatment abolished any differences between groups. BNP plasma levels did not differ between groups and no exercise dependent changes were observed. NE- and E-increase was greater at 80 % .VO2 max work load in Type 1 diabetes than in controls (p < 0.05). Again, fosinopril abolished differences between groups.. In Type 1 diabetes, impaired diastolic function is associated with elevated ANP and catecholamine plasma levels that are normalized after ACE inhibition. Thus, ANP but not BNP appears to be a sensitive biochemical marker for early diastolic dysfunction in Type 1 diabetes.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Cardiomyopathies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diastole; Female; Fosinopril; Glycated Hemoglobin; Heart; Hemodynamics; Humans; Male; Natriuretic Peptide, Brain