Search PubMed⌕ Search

Biomedical subjects

Michaela Diamant

Publications and source records attributed to Michaela Diamant.

16 recordsLinked to original sources
PubMed2006

Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study.

Alanine aminotransferase (ALT) is a marker of non-alcoholic fatty liver disease (NAFLD) and predicts incident type 2 diabetes mellitus (DM2). Recently, ALT was shown to be also associated with endothelial dysfunction and carotid atherosclerosis. We studied the predictive value of ALT for all-cause mortality, incident cardiovascular disease (CVD) and coronary heart disease (CHD) events in a population-based cohort of Caucasian men and women aged 50-75 years, at baseline. The 10-year risk of all-cause mortality, fatal and non-fatal CVD and CHD events in relation to ALT was assessed in 1439 subjects participating in the Hoorn Study, using Cox survival analysis. Subjects with prevalent CVD/CHD and missing data were excluded. As compared with the first tertile, the age- and sex-adjusted hazard ratios (95% confidence intervals) for all-cause mortality, CVD events and CHD events were 1.30 (0.92-1.83), 1.40 (1.09-1.81) and 2.04 (1.35-3.10), respectively, for subjects in the upper tertile of ALT. After adjustment for components of the metabolic syndrome and traditional risk factors, the association of ALT and CHD events remained significant for subjects in the third relative to those in the first tertile, with a hazard ratio of 1.88 (1.21-2.92) and 1.75 (1.12-2.73), respectively. In conclusion, the predictive value of ALT for coronary events, seems independent of traditional risk factors and the features of the metabolic syndrome in a population-based cohort. Further studies should confirm these findings and elucidate the pathophysiological mechanisms.

Aged↗
PubMed2006

Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes.

Chronic hyperglycemia underlies microvascular complications in patients with type 1 diabetes. The mechanisms leading to these vascular complications are not fully understood. Recently, we observed that acute hyperglycemia results in endothelial glycocalyx damage. To establish whether glycocalyx is associated with microvascular damage, we performed glycocalyx perturbation volume measurements in type 1 diabetic patients with microalbuminuria (DM1-MA group; n = 7), without microalbuminuria (DM1-NA group; n = 7), and in age-matched control subjects (CON; n = 7). Systemic glycocalyx volume was determined comparing intravascular distribution volume of a glycocalyx-permeable tracer (dextran 40) to that of a glycocalyx-impermeable tracer (labeled erythrocytes). Sublingual capillaries were visualized using orthogonal polarization spectral microscopy to estimate microvascular glycocalyx. Patients and control subjects were matched according to age and BMI. Glycocalyx volume decreased in a stepwise fashion from CON, DM1-NA, and finally DM1-MA subjects (1.5 +/- 0.1, 0.8 +/- 0.4, and 0.2 +/- 0.1 l, respectively, P < 0.05). Microvascular glycocalyx in sublingual capillaries was also decreased in type 1 diabetes versus the control group (0.5 +/- 0.1 vs. 0.9 +/- 0.1 microm, P < 0.05). Plasma hyaluronan, a principal glycocalyx constituent, and hyaluronidase were increased in type 1 diabetes. In conclusion, type 1 diabetic patients are characterized by endothelial glycocalyx damage, the severity of which is increased in presence of microalbuminuria.

Adult↗
PubMed2005

Dynamic cerebral autoregulation in acute lacunar and middle cerebral artery territory ischemic stroke.

BACKGROUND AND PURPOSE: We addressed whether dynamic cerebral autoregulation (dCA) is affected in middle cerebral artery (MCA) territory (MCAS) and lacunar ischemic stroke (LS). METHODS: Blood pressure (MAP) and MCA velocity (V) were measured in 10 patients with large MCAS (National Institutes of Health Stroke score, 17+/-2; mean+/-SEM), in 10 with LS (score, 9+/-1), and in 10 reference subjects. dCA was evaluated in time (delay of the MCA Vmean counter-regulation during changes in MAP) and frequency domains (cross-spectral MCA Vmean-to-MAP phase lead). RESULTS: In reference subjects, latencies for MAP increments (5.3+/-0.5 seconds) and decrements (5.6+/-0.5 seconds) were comparable, and low frequency MCA Vmean-to-MAP phase lead was 56+/-5 and 59+/-5 degrees (left and right hemisphere). In MCAS, these latencies were 4.6+/-0.7 and 5.6+/-0.5 seconds in the nonischemic hemisphere and not detectable in the ischemic hemisphere. In the unaffected hemisphere, phase lead was 61+/-6 degrees versus 26+/-6 degrees on the ischemic side (P<0.05). In LS, no latency and smaller phase lead bilaterally (32+/-6 and 33+/-5 degrees) conformed to globally impaired dCA. CONCLUSIONS: In large MCAS infarcts, dynamic cerebral autoregulation was impaired in the affected hemisphere. In LS, dynamic cerebral autoregulation was impaired bilaterally, a finding consistent with the hypothesis of bilateral small vessel disease in patients with lacunar infarcts.

Blood Flow Velocity↗
PubMed2005

Modular kinetic analysis of the adenine nucleotide translocator-mediated effects of palmitoyl-CoA on the oxidative phosphorylation in isolated rat liver mitochondria.

To test whether long-chain fatty acyl-CoA esters link obesity with type 2 diabetes through inhibition of the mitochondrial adenine nucleotide translocator, we applied a system-biology approach, dual modular kinetic analysis, with mitochondrial membrane potential (Deltapsi) and the fraction of matrix ATP as intermediates. We found that 5 mumol/l palmitoyl-CoA inhibited adenine nucleotide translocator, without direct effect on other components of oxidative phosphorylation. Indirect effects depended on how oxidative phosphorylation was regulated. When the electron donor and phosphate acceptor were in excess, and the mitochondrial "work" flux was allowed to vary, palmitoyl-CoA decreased phosphorylation flux by 38% and the fraction of ATP in the medium by 39%. Deltapsi increased by 15 mV, and the fraction of matrix ATP increased by 46%. Palmitoyl-CoA had a stronger effect when the flux through the mitochondrial electron transfer chain was maintained constant: Deltapsi increased by 27 mV, and the fraction of matrix ATP increased 2.6 times. When oxidative phosphorylation flux was kept constant by adjusting the rate using hexokinase, Deltapsi and the fraction of ATP were not affected. Palmitoyl-CoA increased the extramitochondrial AMP concentration significantly. The effects of palmitoyl-CoA in our model system support the proposed mechanism linking obesity and type 2 diabetes through an effect on adenine nucleotide translocator.

Animals↗
PubMed2004

The association between abdominal visceral fat and carotid stiffness is mediated by circulating inflammatory markers in uncomplicated type 2 diabetes.

Central obesity, insulin resistance, inflammation, as well as vascular changes are common in patients with type 2 diabetes. In this study we assessed the relationship among stiffness of the carotid artery, visceral fat, and circulating inflammatory markers in type 2 diabetic subjects. Carotid stiffness, quantified as the distensibility coefficient (DC), was measured by ultrasound in asymptomatic, normotensive patients with uncomplicated, well-controlled type 2 diabetes and in controls. Body fat distribution was quantified by magnetic resonance imaging. In patients, the carotid DC was inversely associated with visceral fat area (r = -0.660; P = 0.005) and plasma levels of C-reactive protein (CRP; r = -0.687; P = 0.002), but most strongly with plasma IL-6 (r = -0.766; P < 0.001). In multivariate analysis, the association between DC and visceral fat disappeared after adjustment for CRP and IL-6. Correction for age, body mass index, blood pressure, glycosylated hemoglobin, or fasting plasma glucose did not affect the association between carotid DC and inflammatory markers. Thus, carotid stiffness is associated with visceral obesity in patients with uncomplicated type 2 diabetes, but this association seems to be mediated by circulating IL-6 and CRP, of which IL-6, at least in part, originates from adipose tissue and stimulates hepatic CRP production.

Abdomen↗
PubMed2004

Admission blood glucose level as risk indicator of death after myocardial infarction in patients with and without diabetes mellitus.

BACKGROUND: High admission blood glucose levels after acute myocardial infarction (AMI) are common and associated with an increased risk of death in subjects with and without known diabetes. Recent data indicate a high prevalence of abnormal glucose metabolism in patients with unknown diabetes at the time of AMI. We investigated the predictive value of admission blood glucose levels after AMI for long-term prognosis in patients with and without previously diagnosed diabetes mellitus, particularly in those with unknown diabetes but with blood glucose levels in the diabetic range. METHODS: In a retrospective study with prospective follow-up, 846 patients (737 without and 109 with known diabetes) were eligible for follow-up during a median of 50 months (range, 0-93 months). RESULTS: During follow-up, 208 nondiabetic patients (28.2%) and 47 diabetic patients (43.1%) died (P =.002). An increase of 18 mg/dL (1 mmol/L) in glucose level was associated with a 4% increase of mortality risk in nondiabetic patients and 5% in diabetic patients (both P<.05). Of the 737 previously nondiabetic subjects, 101 had admission blood glucose levels of 200 mg/dL (11.1 mmol/L) or more, and mortality in these patients was comparable to that in patients who had established diabetes (42.6% vs 43.1%). CONCLUSIONS: Admission blood glucose level after AMI is an independent predictor of long-term mortality in patients with and without known diabetes. Subjects with unknown diabetes and admission glucose levels of 200 mg/dL (11.1 mmol/L) or more after AMI have mortality rates comparable to those of subjects with established diabetes. Admission blood glucose level may serve to identify subjects at high long-term mortality risk, in particular among those with unknown diabetes.

Aged↗
PubMed2004

Genetically defined hyperlipidemia.

The unraveling of genetic defects associated with disorders in lipid metabolism has contributed to the understanding of lipoprotein metabolism and the pathophysiological consequences of a particular mutation. The translation, however, of a single genetic defect into the individual's risk of cardiovascular disease and subsequent treatment strategies is an extremely complex issue that involves the identification of multiple additional determinants, including genetic, metabolic and environmental factors. The discovery of these factors, including genetic determinants of drug efficacy, provides insight into the interaction between regulatory systems traditionally thought to be unrelated and may, in the future, lead to a more complete diagnostic and therapeutic appreciation of the individual patient.

Animals↗
PubMed2003

Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus.

OBJECTIVES: This study evaluated myocardial function in relation to high-energy phosphate (HEP) metabolism in asymptomatic patients with uncomplicated type 2 diabetes mellitus using magnetic resonance (MR) techniques. BACKGROUND: Myocardial dysfunction may occur in patients with type 2 diabetes mellitus in the absence of coronary artery disease or left ventricular (LV) hypertrophy. The mechanisms underlying this diabetic cardiomyopathy are largely unknown, but may involve altered myocardial energy metabolism. METHODS: We assessed myocardial systolic and diastolic function and HEP metabolism in 12 asymptomatic normotensive male patients with recently diagnosed, well-controlled type 2 diabetes and 12 controls, using MR imaging and phosphorus-31-nuclear MR spectroscopy (31P-MRS) on a 1.5 T clinical scanner; 31P-MR spectra were quantified, and myocardial HEP metabolism was expressed as phosphocreatine to adenosine-triphosphate (PCr/ATP) ratio. RESULTS: No differences were found in LV mass and systolic function between patients and controls. However, early (E) acceleration peak, deceleration peak, peak filling rate, and transmitral early-to-late diastolic peak flow (E/A) ratio, all indexes of diastolic function, were significantly decreased in patients compared with controls (p < 0.02). In addition, myocardial PCr/ATP in patients was significantly lower than in controls (1.47 vs. 1.88, p < 0.01). Inverse associations were found between myocardial PCr/ATP and E acceleration peak, E deceleration peak, and E peak filling rate (all, p < 0.05). CONCLUSIONS: These results indicate that altered myocardial energy metabolism may contribute to LV diastolic functional changes in patients with recently diagnosed, well-controlled and uncomplicated type 2 diabetes.

Adenosine Triphosphate↗
PubMed2003

Effects of low-iodide diet on postsurgical radioiodide ablation therapy in patients with differentiated thyroid carcinoma.

OBJECTIVE: Most patients with differentiated thyroid carcinoma (DTC) undergo total thyroidectomy followed by routine radioiodide thyroid remnant ablation. Most centres that routinely perform radioiodide ablation prescribe a low-iodide diet (LID) to increase the radioiodide accumulation in thyroid remnants. The efficacy of an LID on thyroid remnant ablation, however, has never been demonstrated convincingly. DESIGN AND METHODS: In a retrospective study, we studied two groups of DTC patients without distant metastases, who had received either a standard diet or an LID during ablation (LID group, n = 59, and control group, n = 61). Both groups were compared for radioiodide uptake in thyroid remnants during ablation and efficacy parameters of remnant ablation, 6 months after ablation. A subgroup without extrathyroidal tumour growth was analysed separately (stages T1-3, N0). RESULTS: In the total group, the LID during ablation decreased the 24-h urinary iodide excretion to 26.6 micro g compared with 158.8 micro g in controls whereas radioiodide uptake in thyroid remnants was increased by 65% (P < 0.001). Six months after ablation, patients were investigated after thyroid hormone withdrawal. In the total group, no significant effects of the LID during ablation were observed on thyroglobulin (Tg) or the percentage of patients with persistent neck activity after 185 MBq 131I. However, in the LID group, 65% of patients without Tg antibodies had undergone successful ablation (defined by absent neck activity and Tg < 2 micro g/l) compared with 48% in the control group (P < 0.001). In the subgroup (T1-3, N0), 8% of the patients who had undergone the LID had Tg >/= 2 micro g/l vs. 32% in the control group (P = 0.012), whereas successful ablation was achieved in 71% of patients without Tg antibodies in the LID vs. 45% in the control group (P < 0.001). CONCLUSION: We conclude from this study that a low-iodide diet during thyroid remnant ablation improves the efficacy of this treatment.

Adult↗
PubMed2003

Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence.

Type 2 diabetes mellitus is characterised by insulin resistance as well as progressive pancreatic beta cell dysfunction. The cornerstone of current oral blood-glucose lowering therapy consists of metformin, which primarily lowers hepatic glucose production, and the sulphonylureas that act by stimulating pancreatic beta-cells to secrete insulin. Recently, a novel class of agents, the thiazolidinediones, has been introduced that favourably influence insulin sensitivity and possibly also pancreatic beta-cell function. The thiazolidinediones are synthetic ligands that bind to the nuclear peroxisome proliferator-activated receptor-gamma and exert their action by activating transcription of genes that, among others, regulate adipocyte differentiation and adipogenesis as well as glucose and lipid metabolism. To date, the precise mechanisms underlying the actions of thiazolidinediones are largely unknown. When given as monotherapy or in combination with sulphonylureas, metformin or insulin in patients with type 2 diabetes, the currently available thiazolidinediones (rosiglitazone and pioglitazone) ameliorate glycaemic control, by lowering fasting and postprandial blood glucose levels, and improve insulin sensitivity in placebo-controlled trials. They seem to have differential effects on dyslipidaemia in patients with type 2 diabetes; rosiglitazone increases total cholesterol as well as high-density lipoprotein (HDL) and low-density lipoprotein cholesterol levels and affects plasma triglyceride levels depending on the baseline values, whereas pioglitazone lowers triglycerides and increases HDL cholesterol levels. The adverse events of both agents that occur with greater frequency than in patients treated with placebo are fluid retention and oedema. As demonstrated, mainly in preclinical studies to date, rosiglitazone and pioglitazone possess beneficial effects on other cardiovascular risk factors associated with the insulin resistance syndrome. Thus, these agents were shown to decrease blood pressure, enhance myocardial function and fibrinolysis, as well as possess anti-inflammatory and other beneficial vascular effects. Long-term efficacy and surveillance of this promising class of drugs in patients, however, still need to be demonstrated in outcome trials.

Cardiovascular Diseases↗
PubMed2002

Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes is associated with accelerated atherosclerosis. Because cell-derived microparticles support coagulation and inflammation, they may be involved in atherogenesis. We characterized circulating microparticles both in patients with uncomplicated, well-regulated type 2 diabetes and in healthy subjects, as well as their relationship with coagulation and metabolic control. METHODS AND RESULTS: Microparticles were isolated from plasma, stained with annexin V, cell-specific monoclonal antibodies (MoAbs) and a MoAb directed against tissue factor (TF), and analyzed by flow cytometry. Microparticle numbers and origin were comparable in the two groups, but the median number of TF-positive microparticles was twice as high in patients than in controls (P=0.018). Patients had higher percentages of TF-positive microparticles from T-helper cells (P=0.045), granulocytes (P=0.004), and platelets (P=0.002). Subpopulations of TF-positive microparticles from platelets and T-helper cells exposed granulocytic markers. Correlations were found between the numbers of various TF-positive microparticle subpopulations and body mass index, fasting plasma glucose and insulin, or tumor necrosis factor-alpha and serum HDL cholesterol. Microparticles from patients generated less thrombin in vitro (P=0.007). Microparticle numbers did not correlate with in vivo coagulation markers prothrombin fragment F(1+2) and thrombin-antithrombin complexes. CONCLUSIONS: TF, possibly of granulocytic origin, is exposed on microparticle subpopulations in asymptomatic patients with well-regulated type 2 diabetes. TF-positive microparticles are associated with components of the metabolic syndrome but not with coagulation. Thus, TF on microparticles may be involved in processes other than coagulation, including transcellular signaling or angiogenesis.

Adult↗
PubMed2002

Does radioiodine therapy have disadvantageous effects in non-iodine accumulating differentiated thyroid carcinoma?

BACKGROUND: Although radioiodine therapy in differentiated thyroid carcinoma without radioiodine accumulation has not been considered harmful, increased thyrotrophin levels during thyroxine withdrawal without the benefit of radiotoxicity as well as the selection of de-differentiated cells may have disadvantageous effects on tumour course. OBJECTIVE: We therefore analysed retrospectively the effects of radioiodine therapy on the course of serum thyroglobulin levels as a tumour marker in patients with progressive residual or metastatic differentiated thyroid carcinoma, with or without radioiodine accumulation on post-therapeutic whole body scintigraphy. PATIENTS AND METHODS: Patients who had undergone radioiodine therapies with sufficient pre- and post-therapy thyroglobulin measurements to allow for regression analysis and not preceded or followed by other treatment modalities within a 1-year interval were selected. All patients had undergone total thyroidectomy and ablative therapy. Thirty-nine patients and radioiodine therapies were included (10 males, 29 females, mean age 57 years), and divided into a negative- (n = 17) and a positive post-therapeutic whole body scintigraphy group (n = 22). Pre- and post-therapeutic thyroglobulin course were analysed using non-linear regression, comparing the difference in the thyroglobulin growth coefficient b1 post- and pre-therapy (delta b1: b1(post-therapy)-b1(pre-therapy)). In addition, absolute post- and pre-therapeutic thyroglobulin levels, radiological follow-up and clinical outcome were also analysed. RESULTS: The two groups were comparable with respect to age, sex, tumour stage, histology and prior therapies. Differences between post- and pre-therapeutic b1 values differed significantly in the positive post-therapeutic whole body scintigraphy group (delta b1: -0.65 microg/l-1 years-1, P < 0.001) but not in the negative post-therapeutic whole body scintigraphy group (delta b1: -0.14). Absolute serum thyroglobulin levels and radiological follow-up revealed a favourable response of radioiodine therapy in the positive whole body scintigraphy group but not in the negative group. Delta b1 was related significantly with clinical outcome as revealed by receiver operator curves (ROC): all patients with a positive delta b1 (n = 8) had an unfavourable outcome (progression or death), whereas from the 31 patients with negative delta b1, 61% had an unfavourable outcome. CONCLUSION: We did not find disadvantageous effects of a single radioiodine therapy on serum thyroglobulin increments in patients with negative post-therapeutic whole body scintigraphy. However, as we did not observe a beneficial effect either, we would not advise the continuation of radioiodine therapy in patients with negative post-therapeutic whole-body scintigraphy, unless a positive response is observed in individual cases.

Biomarkers↗
PubMed2002

Genetically defined pancreatic beta cell failure.

The major subtypes of diabetes mellitus (DM) are complex diseases in which the interactions between genetic susceptibility and metabolic, immunologic and environmental factors ultimately lead to the clinical phenotype. The unraveling of these factors and the study of their contribution to the pathogenesis of DM is a process of unimaginable complexity. As a result, despite the individual differences in DM phenotype, most patients with DM receive treatment according to generalized treatment protocols, only discriminating between Type 1 and Type 2 DM and not related to the individual genetic background of the patients. Nevertheless, in recent years, much progress has been made in the search for genetic factors in DM. As an example, the recognition of monogenetic defects in beta cell function has lead to the definition of novel DM subtypes, which have important implications for the individual therapeutic approach for these patients and the understanding of the etiology of DM.

Animals↗