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Biomedical subjects

G Jermendy

Publications and source records attributed to G Jermendy.

At least 19 recordsLinked to original sources

Impairment of the NO/cGMP pathway in the fasting and postprandial state in type 1 diabetes mellitus.

The assessment of the postprandial state in diabetes mellitus has gained importance due to postprandial hyperglycemia being considered as an independent risk factor for cardiovascular disease. Hyperglycemia may contribute to vascular dysfunction through the alteration of the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway. The authors assessed the NO/cGMP pathway in the fasting and postprandial state in 20 type 1 diabetic patients (age: 34.1 +/- 2.6 years, body mass index (BMI): 24.1 +/- 1.3 kg/m (2), duration of diabetes: 16 +/- 2.2 years, HbA (1C): 8.3 +/- 0.4 %, [x +/- SEM], 10 without, 10 with late complications) and 20 matched control subjects (age: 39.7 +/- 1.9 years, BMI: 25.3 +/- 1.1 kg/m (2)). In the fasting state NO end product (nitrite/nitrate) levels did not differ between the diabetic and control group, cGMP levels were found to be significantly lower in the diabetic group (2.5 +/- 0.2 vs. 4.6 +/- 0.6 nmol/l, p = 0.01). A higher level of lipid peroxidation end products (TBARS) was found in diabetic subjects (6.7 +/- 0.4 vs. 5.0 +/- 0.3 micro mol/l, p = 0.004). The diabetic subgroup without late complications had significantly higher nitrite/nitrate levels compared to the patients with complications (57.8 +/- 6.6 vs. 30.4 +/- 4.3 micro mol/l, p = 0.006), their TBARS and cGMP levels were similar. The control subjects responded to the test meal with an increase in the cGMP levels (4.6 +/- 0.6 to 5.5 +/- 0.6 nmol/l, p = 0.02), while in the diabetic group no change was detected. Postprandial nitrite/nitrate levels decreased in both groups, they were significantly lower in the diabetic group. There was no difference between postprandial nitrite/nitrate, cGMP, or glucose levels in the diabetic subgroups. Postprandial glucose levels showed a significant negative correlation with cGMP levels in the diabetic group (r = - 0.50, p = 0.02). The results suggest that in subjects with type 1 diabetes mellitus NO might have an impaired ability to induce cGMP production in the fasting state prior to the development of late specific complications or microalbuminuria under hyperglycemic conditions. Postprandial hyperglycemia is suggested to interfere with endothelial NO action, as shown by the decreased nitrite/nitrate and unchanged cGMP plasma levels in the diabetic group. The impairment of the NO/cGMP pathway both in the fasting and postprandial state that was shown in patients without diabetic complications may be an early sign of hyperglycemia induced vascular damage in type 1 diabetes mellitus.

Adult↗

Clinical consequences of cardiovascular autonomic neuropathy in diabetic patients.

A wide range of clinical consequences of cardiovascular autonomic neuropathy (CAN) can be observed in diabetic patients and contributes to the clinical picture of the diabetic heart. Resting heart rate and cardiovascular reflexes as well as circadian heart rate variability may be altered by CAN in diabetes. Moreover, blood pressure is also influenced by sympathovagal imbalance. Postural hypotension is a clinical characteristic in diabetic subjects with CAN. Painless myocardial infarction, ischaemia and left ventricular dysfunction are also observed in some cases. Impairment of cardiac parasympathetic and sympathetic innervation as well as QT-interval prolongation may play a partial role in the pathogenic mechanism of sudden unexpected death in diabetic patients. The risk of surgical intervention and that of anaesthesia are increased due to abnormal cardiovascular reactions. Clinical symptoms and signs of CAN should be assessed as severe diabetic complication and the therapy is difficult in some cases. Taken together, symptoms and signs of CAN carry a poor prognosis in diabetic patients.

Autonomic Nervous System Diseases↗

Effect of indapamide SR on microalbuminuria--the NESTOR study (Natrilix SR versus Enalapril Study in Type 2 diabetic hypertensives with micrOalbuminuRia)--rationale and protocol for the main trial.

In type 2 diabetic hypertensive patients, microalbuminuria can be due to hypertension and/or diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors act preferentially on microalbuminuria due to diabetic nephropathy. The objective is to demonstrate the efficacy of a thiazide-like diuretic, indapamide sustained release (SR), at reducing microalbuminuria in hypertensive type 2 diabetic patients in comparison with an ACE inhibitor, enalapril. The study is an international multicentre, 12-month, randomized, double-blind, controlled, two parallel group study of type 2 diabetic patients with hypertension (140 mmHg < or = systolic blood pressure <180 mmHg and diastolic blood pressure <110 mmHg) and microalbuminuria. Intervention is after a 4-week placebo period, patients with microalbuminuria > or = 20 and < or = 200 microg/min are randomized to indapamide SR 1.5 mg or to enalapril 10 mg once a day for a one-year treatment period. An additional label treatment by amlodipine 5-10 mg (1st step) and atenolol 50-100 mg (2nd step) a day is permitted after 6 weeks of treatment based upon blood pressure response. The main outcome measures are microalbuminuria expressed as urinary albumin to creatinine ratio, albumin fractional clearance, and albumin excretion rate evaluated on overnight urine collections. Secondary criteria are supine and standing systolic, diastolic and mean blood pressure; and biological and clinical safety. This study will complete the knowledge of the efficacy of indapamide SR in hypertension and target organ damage and will provide valuable information on the management of type 2 diabetic hypertensives with microalbuminuria.

Adult↗

Intima-media thickness of the carotid arteries in subjects with hyperinsulinaemia (insulin resistance).

The metabolic syndrome is characterised by hyperinsulinaemia (insulin resistance) leading to an increased risk of atherosclerotic cardiovascular diseases. Carotid intima-media thickness (IMT) can be easily measured to detect early atherosclerosis. In order to evaluate the clinical characteristics of the metabolic syndrome a screening procedure was performed and carotid IMT was determined by high-resolution B-mode ultrasonography in a cohort of middle-aged (40-60 years) subjects who proved to be hyperinsulinaemic [fasting plasma insulin >15 microU/ml and/or post-prandial (120 min) insulin > 45 microU/ml; n = 91; men/women: 35/56; homeostasis model assessment (HOMA)-index: 6.42 +/- 3.65; x +/- SD]. Subjects known to have diabetes were not involved. Subjects were divided into subgroups according to the stages of glucose intolerance (normal glucose tolerance, n = 46; impaired glucose tolerance, n = 26; diabetes mellitus, n = 19). As controls, age- and sex-matched non-diabetic and non-hyperinsulinaemic subjects (n = 20; HOMA-index: 2.09 +/- 0.85) were investigated. The values of IMT of the internal carotid arteries were higher in hyperinsulinaemic subjects than in controls (0.93 +/- 0.39 mm vs 0.57 +/- 0.13 mm,p < 0.001), whereas the lumen diameter proved to be smaller than in control subjects (5.04 +/- 0.75 mm vs 5.45 +/- 0.71 mm; p < 0.05). In hyperinsulinaemic subjects only a trend of increasing IMT values and that of decreasing lumen diameter of the internal carotid arteries were observed when subgroups classified according to the stages of glucose intolerance were compared. No significant changes in IMT or lumen diameter of the common carotid arteries were observed. Early and asymptomatic signs of atherosclerosis could be detected in middle-aged subjects who proved to be hyperinsulinaemic in a screening procedure. The prevention of clinically manifest cardiovascular diseases in these subjects could be of great importance.

Adult↗

[Advanced microangiopathic complications at the diagnosis of diabetes mellitus].

A case of a 59-year-old male patient with advanced microangiopathic complications at the diagnosis of diabetes mellitus is reported. The patient was referred to ophthalmological investigation due to progressive loss of visual acuity. Although diabetes mellitus was not known, proliferative diabetic retinopathy with significant visual loss was found at fundus examination. Not only newly diagnosed diabetes mellitus (initial fasting blood glucose 19.0 mmol/, HbA1c: 11.6%) but the presence of advanced sensory, motor and autonomic diabetic neuropathy (nervus peroneus motor conduction velocity: 32.1 m/s, nervus suralis sensory conduction velocity could not be detected, postural decrease in systolic blood pressure: 20 mmHg, beat-to-beat variation 6 beats/min, 30:15 ratio 1.03) as well as signs of advanced diabetic nephropathy (daily urinary protein excretion: 1.2-5.7 g, serum creatinine value: 101 mumol/l, sitting blood pressure: 150/100-180/100 mmHg) could be documented by further investigations at Medical Department. Avoiding short-term strict metabolic control insulin therapy was initiated and adequate long-term diabetic control was achieved later (HbA1c: 6.5-6.2%). In order to classify the diabetes, repeated measurements of serum C-peptide, ICA, GADA and IA2-antibodies were performed and type 2 diabetes was diagnosed. After a transient deterioration the proliferative retinopathy remained unchanged. Although laser photocoagulation was performed, no improvement in the visual acuity could be achieved. Only a minor improvement of neurological alterations was documented by repeated electrophysiological investigation at follow-up. Although the antihypertensive treatment (ACE-inhibitor drug in combination with calcium channel blocker) resulted in a significant decrease of elevated blood pressure, only a transient improvement of proteinuria could be achieved. Despite regular control, the advanced microangiopathic complications of diabetes mellitus carry poor prognosis.

Diabetes Mellitus, Type 2↗

[Thiazolidinediones--a new class of oral antidiabetic drugs].

The discovery of a new class of oral antidiabetic drugs was stimulated by difficulties with the treatment currently available for patients with type 2 diabetes mellitus. Thiazolidinediones can lower blood glucose values due to their special insulin-sensitiser effect. In this way, these drugs seem to be very effective in the treatment of type 2 diabetic patients with characteristics of metabolic syndrome. The intracellular action caused by thiazolidinediones differs markedly from that of other oral antidiabetic drugs available. Apart from antihyperglycaemic effect, thiazolidinediones have further beneficial effects in experimental diabetes which require corroboration by clinical studies. Troglitazone was the first drug which reached the market. Unfortunately, this drug was withdrawn soon due to its hepatotoxicity. Rosiglitazone proved to be much safer in clinical studies. Pioglitazone is being tested nowadays in clinical studies. Thiazolidinediones have been already listed among oral antidiabetic drugs in international therapeutical guidelines. Nevertheless, further clinical studies and experiences are needed to determine the final exact indication of thiazolidinediones for the treatment of type 2 diabetic patients.

Animals↗

[Plasma homocysteine levels in hyperinsulinemic patients].

In order to evaluate the clinical characteristics of metabolic syndrome, a screening procedure was performed and in a cohort of middle-aged (40-60 years) hyperinsulinaemic (fasting plasma insulin > 15 microU/ml) and/or postprandial [120 min after 75 g glucose load] insulin > 45 microU/ml) subjects (n = 91; men/women: 38/53; age mean +/- SD 47.6 +/- 4.3 years; body mass index: 34.6 +/- 4.9 kg/m2; waist-hip ratio: 0.92 +/- 0.07; actual blood pressure 146 +/- 16/87 +/- 9 mmHg; fasting insulin: 24.2 +/- 11.3 microU/ml; postprandial insulin 125.5 +/- 103.8 microU/ml; serum LDL-cholesterol: 3.73 +/- 1.09 mmol/l; HDL-cholesterol: 1.12 +/- 0.30 mmol/l; triglycerides: 2.97 +/- 2.38 mmol/l; uric acid 279 +/- 79 mumol/l) plasma fasting homocysteine, vitamin B12 and folic acid levels were simultaneously determined. The values were separately evaluated according to the stages of glucose tolerance (normal glucose tolerance [n = 47]; impaired glucose tolerance [n = 24] and diabetes mellitus [n = 20]). Laboratory normal values were determined in 47 healthy subjects (control group, age: 45.0 +/- 7.8 years, men/women: 19/28). There was no significant difference between hyperinsulinaemic and control subjects regarding plasma homocysteine (9.28 +/- 3.81 mumol/l vs. 9.63 +/- 2.70 mumol/l), folic acid (8.5 +/- 5.9 ng/ml vs. 7.5 +/- 2.1 ng/ml) and vitamin B12 levels (423 +/- 141 pg/ml vs. 356 +/- 121 pg/ml). Plasma homocysteine levels were significantly (p < 0.001) higher in hyperinsulinaemic men than women (11.34 +/- 4.72 mumol/l [n = 38] vs. 7.86 +/- 2.13 mumol/l [n = 53]). There was no significant difference between subgroups classified according to the stages of glucose tolerance in hyperinsulinaemic groups. Plasma homocysteine values exceeding the upper limit of normal range (> 12.45 mumol/l) were detected at a similar prevalence rate in control (4/47 = 8.5%) and in hyperinsulinaemic subjects (10/91 = 10.9%). A weak but statistically significant correlation was found between plasma homocysteine values and age of subjects (r = 0.222; p < 0.05) whereas a stronger correlation was documented between plasma homocysteine and serum creatinine values (r = 0.658; p < 0.001) in hyperinsulinaemic groups (n = 91). Plasma homocysteine values independently from the stages of glucose tolerance are not elevated in hyperinsulinaemic subjects. Hyperhomocysteinaemia is not a characteristic feature of hyperinsulinism suggesting that plasma homocysteine levels are of no considerable importance in the complex pathomechanism of atherosclerosis at early stages of metabolic syndrome.

Adult↗

Practical aspects of measuring microalbuminuria in diabetic patients.

The importance of measuring microalbuminuria is well established; however, controversy still exists regarding the type of urine specimen to be used for detecting early renal impairment of diabetic patients. To evaluate practical aspects, albumin concentration and albumin/creatinine ratio of first void urine samples as well as urinary albumin excretion in timed specimens were determined by immunoturbidimetric method 3 times within 3 weeks in 192 adult diabetic patients (136 men, 56 women; Type 1/Type 2 diabetes: 90/102; age: 51.4+/-10.8 yr; duration of diabetes: 15.3+/-9.1 yr; body mass index: 27.9+/-4.6 kg/m2; HbA1c: 8.54+/-1.46%; actual blood pressure: 138+/-14/82+/-8 mmHg; serum creatinine: 94+/-20 pmol/l; x+/-SD). According to the urinary albumin excretion values one-third of patients (31.2%-30.7%-34.4%) were normoalbuminuric (<30 mg/24 hr), more than half of the patients (55.8%-57.3%-53.6%) proved to be microalbuminuric (30-300 mg/24 hr), while the remaining group of patients (13.0%-12.0%-12.0%) was macroalbuminuric (>300 mg/24 hr). Comparing the results of successive measurements, good correlation was found between the same laboratory values (urinary albumin excretion: kappa=0.64, kappa=0.67; urinary albumin concentration: kappa=0.60, kappa=0.62; albumin/creatinine ratio: kappa=0.54, kappa=0.61; first vs second and second vs third measurements, respectively). The percentage of patients being in the same range of albuminuria (ie normo-, micro- or macroalbuminuria) at successive measurements was 79.7-81.2% with urinary albumin excretion values, 77.1-77.6% with urinary albumin concentration and 74.5-78.6% with albumin/creatinine ratio. Good correlation was found between urinary albumin excretion and urinary albumin concentration (kappa=0.54; 0.54; 0.57) and nearly the same correlation was observed between urinary albumin excretion and albumin/creatinine ratio (kappa=0.49; 0.47; 0.54) at the three consecutive measurements (n=192). Using values of urinary albumin excretion for comparison at all measurements, 79.3% sensitivity and 69.5% specificity were found for urinary albumin concentration, whereas 74.6% sensitivity and 68.8% specificity were documented for albumin/creatinine ratio. Beside the standard measurement of urinary albumin excretion in timed urine samples, the use of the more convenient morning urinary spot collection could also provide useful results (urinary albumin concentration or albumin/creatinine ratio) for detecting early renal involvement in diabetic patients.

Adult↗

[Metabolic syndrome-x at the turn of the millennium (Theoretical aspects with practical consequences)].

The authors give an overview on the hypothesis of the metabolic syndrome-x in accordance with insulin resistance and hyperinsulinism in triggering the development of type 2 diabetes mellitus with its clinical complexity. Dealing with the criticism of the original hypothesis, they touch the problem of protein-insufficient feeding in utero and consequences later in life. They discuss the recently emerging importance of postprandial hyperglycaemic condition, which might be even more responsible in leading to atherosclerotic lesions than the hyperinsulinism itself. Finally, they deal with the non-pharmacological intervention and drug therapy as well. A short overview of the results of the UKPDS (United Kingdom Prospective Diabetes Study) are also given, pointing out the clinical importance of correct antihyperglycaemic and antihypertensive treatment. The authors emphasise the utmost importance of early prevention in behalf of avoiding type 2 diabetes and cardiovascular complications as well.

Combined Modality Therapy↗

[Human insulin-induced lipoatrophy].

The medical history of a 14-year-old diabetic adolescent female patient is presented. The patient has been exclusively treated by human insulin since the manifestation of diabetes at age of 11. As a clinical curiosity lipoatrophy developed at different sites of insulin injections (upper arm, thigh, abdominal wall, buttock). The insulin administration technique by pen-devices was correct. The patient proved to be non-atopic without signs of insulin allergy on intracutan tests. On histological examination, "lipoblastoma-like" alterations without signs of local immune mechanisms and no inflammatory cell infiltrates were found at the site of lipoatrophy. The histological findings suggested dedifferentiation of adipose tissue mediated probably by elevated local tumor necrosis factor-alpha. Immunological consequences of previous human insulin treatment were documented by high insulin-specific IgG and IgE antibody titer, however, no clinical signs of immunogenic insulin resistance were found. Switching to insulin analogue (insulin lispro) before main meals no further lipoatrophic areas were observed despite of using human NPH-insulin for basal insulin supplementation. Insulin analogue (insulin lispro) may be useful for treating diabetic patients with lipoatrophy secondary to previous human insulin treatment.

Adipose Tissue↗

Endothelial nitric oxide in diabetes mellitus: too much or not enough?

Vascular complications are the leading cause of increased mortality in patients with diabetes mellitus. Endothelial dysfunction, characterised by impaired endothelium-dependent vasoreactivity, is the first sign of blood vessel damage that precedes morphological changes of the vessel wall. With other factors altered bioavailability of nitric oxide, the most potent endothelium-derived vasodilator, contributes to the changes in vascular tone and integrity. In addition to the impairment of vascular reactivity and permeability, other anti-atherosclerotic functions of nitric oxide are also diminished, which may result in activated monocyte, leukocyte and platelet adhesion to the endothelium, increased platelet aggregation, lipoprotein influx to the subendothelial space and smooth muscle proliferation. Hyperglycaemia-induced increased oxidative stress and impairment of antioxidant defence are suggested to play a role in the pathomechanism of vascular damage, partly by influencing nitric oxide. Both in experimental and clinical Type 1 and Type 2 diabetes mellitus the apparently conflicting data of increased, unaltered or diminished nitric oxide action suggests a complex, time and localisation-dependent alteration of vascular function. The understanding of the mechanisms that lead to diabetic endothelial dysfunction and its early detection are necessary to establish appropriate intervention to prevent irreversible atherosclerotic vessel damage in patients with diabetes mellitus.

Animals↗

[A new method of molecular testing in the differential diagnosis of hereditary hemochromatosis].

Hereditary hemochromatosis is an autosomal, recessive disorder of the iron metabolism. The hemochromatosis gene (HFE) was previously located on chromosome 6 and recently identified by positional cloning. A point mutation, C282Y, was found to be present in the HFE gene in homozygous form in 64 to 100% of patients with established hemochromatosis. The relationship of a second polymorphic variant of the HFE gene, H63D to the formation of iron overload is debated. Although hemochromatosis is one of the most common inherited disorders among Caucasians, in the absence of specific signs it is rarely diagnosed. In order to obtain comparable epidemiological data for Hungary, we tested 1271 and 277 randomly selected, unrelated, healthy subjects for C282Y and H63D respectively. In addition C282Y testing was carried out in 58 patients suffering from liver cirrhosis, and in 191 individuals with suspected hemochromatosis. For C282Y and H63D mutation analyses polymerase chain reaction technique followed by Rsa I and Bcl I restriction enzyme digestion was used. We developed an alternative method for the detection of C282Y based on an amplification-generated Kpn I restriction site. The allele frequencies were 3.8% and 12.3% for C282Y and H63D respectively in the normal Hungarian population. There was no significant difference in C282Y allele frequencies between liver disease patients (1.7%) and the normal population. We identified 15 homozygous and 25 heterozygous individuals among 191 individuals with suspected hemochromatosis. The C282Y and the H63D allele frequencies in the normal Hungarian population were found to be similar to the allele frequencies observed in other European populations, indicating that there is a large number of individuals susceptible for iron overload in Hungary (1:700). Mutation analysis is a novel, non-invasive method in the diagnostics of hereditary hemochromatosis, which increasingly becomes part of the routine clinical work.

Alleles↗

[Rapid hemoglobin A1c determination (a new possibility in diabetes care)].

To assess the long-term metabolic control, immunochemical method was used for hemoglobin A1c (HbA1c) determinations in diabetic patients. The use of DCA 2000 device (Bayer) resulted in immediate (< 6 min) HbA1c values. The reproducibility of this method was acceptable (within-run coefficients of variations were 3.48% and 4.80%). A close, linear correlation (r = 0.974; p < 0.001; n = 106) between HbA1c-values measured simultaneously by DCA 2000 and DIAMAT (Bio-Rad, method: high pressure liquid chromatography) was observed in diabetic patients. The new immunochemical method proved to be simple and reliable. The immediate (within 6 min) result makes the therapeutic decision easier during the care of diabetic patients.

Adolescent↗