Is there a connection between postprandial hyperglycemia and IGT related sensory nerve dysfunction?

BACKGROUND AND AIMS: To assess the risk factors for sensory nerve dysfunction in subjects with isolated impaired glucose tolerance (IGT). METHODS AND RESULTS: Seventy-two people with isolated IGT (WHO 1999 criteria) and 39 gender and age-matched healthy volunteers underwent detailed clinical and neurological assessment including quantitative sensory testing using the Neurometer device (current perception threshold measurement on four limbs at three different frequencies). Sensory nerve dysfunction was defined as at least two abnormalities on any frequencies on the upper or lower limbs. Sensory nerve dysfunction was more prevalent among subjects with IGT compared to controls (58.3 vs. 10.3%, OR: 11.23, 95%CI: 3.57-35.35). This association was not influenced by BMI, systolic and diastolic blood pressure, heart rate and autonomic neuropathy (multiple adjusted OR: 13.87, 95%CI: 3.18-60.58), but further adjustment for glycaemic measures abolished the association (OR: 1.58, 95%CI: 0.07-35.68). Assessing the components of glycaemic measures separately, the association between sensory nerve dysfunction and IGT was not affected by HbA1c (OR: 13.94, 95%CI: 1.84-105.5). It was, however, substantially attenuated by fasting plasma glucose (OR: 6.75, 95%CI: 1.33-34.27) while the significance was lost after adjustment for 120 min postload glucose level (OR: 3.76, 95%CI: 0.26-54.10). In the pooled population assessed, independent determinants of sensory nerve dysfunction were older age, 120 min glucose, higher height and cardiovascular autonomic neuropathy at near significance. CONCLUSIONS: Sensory nerve dysfunction amongst subjects with IGT was not explained by cardiovascular covariates, only by glycaemic measures. In addition to 120 min glucose, cardiovascular autonomic neuropathy at borderline significance, age, and height were the independent determinants of sensory nerve dysfunction.

Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer.

OBJECTIVE: The aims of the present study were to examine gene and protein expression of the vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzyme in human papillary thyroid cancer (PTC), furthermore, to investigate the association between CYP24A1 expression and numerous clinical, histological parameters and somatic oncogene mutation status of thyroid tumor tissues. MATERIALS AND METHODS: Gene expression analysis was carried out in 100 Hungarian thyroid samples, both normal and papillary tumor tissue sections of the same patient. The specific mRNA to the selected genes was analyzed by TaqMan probe-based quantitative real-time RT-PCR. The somatic oncogene mutation states of BRAF, NRAS, HRAS and KRAS were also tested. RESULTS: CYP24A1 mRNA expression was markedly increased in 52 cases (52%) of the examined papillary cancers compared with that of normal thyroid tissue. There was a tendency toward difference in the distribution of high-level CYP24A1 in the PTC accompanied with somatic oncogene mutation. Positive correlation was seen between increased CYP24A1 expression rate and a group of variables reflecting tumor malignity (mainly vascular invasion, lymph node metastasis, tumor size, hypothyreosis) by principal components analysis. No significant alteration was seen in CYP27B1 gene expression between neoplastic and normal tissues. CONCLUSIONS: A definite alteration was seen in vitamin D3-inactivating CYP24A1 gene activity in PTC compared to their normal tissues on a relatively large patient population. Our findings raise the possibility that CYP24A1 may also directly be involved in thyroid carcinogenesis.

Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance.

AIMS: To assess circadian blood pressure variability in people with impaired glucose tolerance and a healthy control population. METHODS: Seventy-five people with impaired glucose tolerance and 40 healthy volunteers (frequency matched on 10-year age bands and sex) underwent a detailed neurological assessment. Autonomic neuropathy was detected by the five standard cardiovascular autonomic tests and heart rate variability was characterized by the triangle index. Diurnal indices were assessed by 24-h ambulatory blood pressure monitoring. Systolic and diastolic diurnal indices were defined as: (mean daytime blood pressure - mean night-time blood pressure) × 100/mean daytime blood pressure. RESULTS: Mean 24-h systolic and diastolic blood pressure was significantly higher in the group with impaired glucose tolerance compared with the control group [126 ± 12 (mean ± SD) vs. 117 ± 10, 75 ± 7 vs. 71 ± 6 mmHg, both P < 0.05). Systolic and diastolic diurnal indices and heart rate variability triangular index were significantly lower in people with impaired glucose tolerance compared with control subjects (9.1 ± 7.8 vs. 13.2 ± 5.4, 14.5 ± 9.7 vs. 18.4 ± 7.1 mmHg, 28.0 ± 8.4 vs. 39.5 ± 9.3, all P < 0.05). Differences in mean diastolic blood pressure, heart rate variability triangular index and the frequency of non-dippers between those with impaired glucose tolerance and control subjects seemed to be independent of BMI and the presence of cardiovascular autonomic neuropathy, as simultaneous adjustment for BMI and cardiovascular autonomic neuropathy had no major effect on the results. CONCLUSION: Our data suggest that people with impaired glucose tolerance have increased diastolic blood pressure and abnormal circadian blood pressure regulation, independent of obesity and the presence of cardiovascular autonomic neuropathy.

Relationship between autonomic neuropathy and hypertension--are we underestimating the problem?

BACKGROUND: Cardiac autonomic neuropathy (CAN) is associated with significant morbidity and mortality in diabetes and the risk is even greater in those with hypertension. AIMS: The aim of our study was to investigate the relationship between CAN and 24-h blood pressure profile in normoalbuminuric patients with Type 2 diabetes mellitus. METHODS: Seventy patients with Type 2 diabetes (31 without CAN, 39 with CAN), who had no history of hypertension, and 29 healthy volunteers underwent five standard cardiovascular reflex tests to assess autonomic function and 24-h ambulatory blood pressure monitoring. RESULTS: Twenty-four-hour mean systolic blood pressure, blood pressure load and hyperbaric impact values were significantly higher in diabetic patients with CAN compared with control subjects and diabetic patients without CAN (P < 0.05). In spite of normal clinic blood pressures, 54% of diabetic subjects with CAN and 29% without CAN were hypertensive (systolic blood pressure load > 20%, P < 0.05). In the diabetes group as a whole, Valsalva ratio, postural systolic blood pressure changes and diastolic blood pressure responses during sustained handgrip correlated significantly and negatively with 24-h mean systolic blood pressure (P < 0.01, P < 0.001, P < 0.05) and blood pressure load (P < 0.05, P < 0.001, P < 0.05). CONCLUSIONS: Cardiovascular autonomic neuropathy is independently associated with hypertension in normoalbuminuric Type 2 diabetic patients with no history of hypertension. Relying on clinic blood pressures in subjects with CAN could lead to a failure to diagnose hypertension in over half of cases. All normotensive patients with CAN should be screened for hypertension using ambulatory blood pressure monitoring in order to institute early aggressive interventions to improve their long-term outlook.

Radioimmunoassay of three deoxycorticoids in human plasma following HPLC separation.

A radioimmunoassay of three deoxycorticoids, namely 11 beta,17 alpha-dihydroxy-4-pregnene-3,20-dione (21-deoxycortisol), 17 alpha,21-dihydroxy-4-pregnene-3,20-dione (11-deoxycortisol), and 21-hydroxy-4-pregnene-3,20-dione (11-deoxycorticosterone) which are important for differential diagnosis of congenital adrenal disorders, is described and evaluated. Antisera against 3-(O-carboxymethyl)oximes conjugated to bovine serum albumin were raised in rabbits. The radioligands were prepared by radioiodination of previously synthesized homologous tyrosine methyl ester derivatives. Following diethyl ether extraction, the steroids were separated from each other and from cross-reactants by HPLC using a Nucleosil C8 reverse-phase column and a methanol-water mixture (7:5, v/v) as an eluent. Normal levels of analyzed steroids ranged from 0.02 to 0.348, 0.185 to 3.80, and 0.013 to 0.299 nmol/l, for 21-deoxycortisol, 11-deoxycortisol and 11-deoxycorticosterone, respectively. The levels of both deoxycortisols rose significantly after ACTH treatment. Data are given with respect to the concentrations of these steroids in some pathological situations such as 21-hydroxylase and 11 beta-hydroxylase block, hyperaldosteronism, and polycystic ovary syndrome.

Daily variation of serum cortisol, 17-hydroxyprogesterone and five androgens in healthy women.

Serum cortisol, 17-hydroxyprogesterone and five androgens (androstenedione, 11-hydroxyandrostenedione, dehydroepiandrosterone and its sulphate, and testosterone) were measured by radioimmunoassay at 8:00, 16:00, 20:00 and 24:00 h and again at 8:00 h on the next day in eight healthy female subjects aged 16-40 years in the midfollicular phase of the menstrual cycle. Regression analysis revealed a significant (alpha = 0.05) circadian periodicity, with estimated peaks between 8:00 a.m. (testosterone) and 2:00 p.m. (dehydroepiandrosterone sulphate), and with estimated amplitudes between 76% (11-hydroxyandrostenedione) and 33% (17-hydroxyprogesterone, testosterone and dehydroepiandrosterone sulphate) of the rhythm adjusted mean. The inferential statistical approach illustrated here should contribute significantly to the diagnostic elucidation of adrenocortical disorders.

The circalunar cycle of salivary testosterone and the visual-spatial performance.

BACKGROUND: A circalunar cycle is thought to be female sex specific. Results of studies observing the relationship of testosterone and spatial abilities are controversial. OBJECTIVE: To describe the infradian variations of testosterone and the correlations between salivary testosterone levels and spatial abilities in young healthy volunteers of both sexes. SUBJECTS AND METHODS: Testosterone levels in saliva were determined in 53 young adult male and female subjects (mean age--20.89 +/- 0.91 years). The samples of saliva were collected either once (22 subjects) or daily during a period of 30 days (31 subjects). Salivary testosterone was analyzed by RIA. Both groups of subjects were tested on their visual-spatial performance (mental rotation and spatial visualization). All important data about the menstrual cycle of female subjects were also collected. This data and the results of the visual-spatial tests as well as the circalunar cycle in their relationship to the testosterone levels were analyzed. RESULTS: In this study a circalunar rhythm of testosterone related to the menstrual cycle with a maximum peak in the periovulatory phase was confirmed in women and an analogical circalunar cycle in men was described. A positive correlation of the salivary testosterone levels and the performance in visual-spatial tests in women and a negative dependence in men was found. The outcomes showed a significant statistical difference between the results of the test during the high-testosterone and the low-testosterone phase in both sexes. CONCLUSIONS: The levels of testosterone between the high female and low male range seem to be associated with the best spatial ability performance in adults. A male circalunar rhythm similar to the female one is very likely. Recognizing of the infradian fluctuations in women as in men should have many various clinical implications. (Tab. 2, Fig. 7, Ref. 143.)

[Salivary testosterone and cognitive ability in children]. / Slinný testosterón a kognitívne schopnosti u detí.

There are suggestive data with indicate the link of testosterone levels with specific cognitive abilities in humans. As soon as during intrauterine development, testosterone is supposed to influence to organization of fetal specific brain structures. This influence is permanent and it is reflected in cognitive abilities during prepubetal period. In puberty, the testosterone level rapidly increases mainly in boys and it appears to influence the definitive development of cognitive functions. In this paper, results of the first four years of our logitudinal study are presented. Salivary testosterone levels in children were determined, and their effect on spatial ability was studied. Radioimmunoanalytical method of testosterone determination in saliva was developed, since saliva reflects free fraction of testosterone directly available for uptake by receptors in the central nervous system. The sampling of saliva is non-invasive and unstressful, which is important for relevant evaluation of cognitive performance. One hundred and forty-seven children (78 boys and 69 girls) at the ae of 8 to 12 were examined. The data received from intellectually gifted children attending the School for gifted children in Bratislava (100 measurements) were compared with the data received from age-matched children attending randomly chosen elementary schools (151 measurements). Lower salivary testosterone levels were found in intellectually gifted children of both sexes, and negative relationship between testosterone levels and cognitive abilities in preadolescent children was observed.

[Parenteral, depot and repeatable forms of Parlodel LAR bromocriptine in the treatment of hyperprolactinemia syndrome. Comparison with oral Parlodel]. / Parenterální, depotní, opakovatelný bromokriptin Parlodel LAR v lécbe hyperprolaktinemického syndromu. Porovnání s perorálním Parlodelem.

Parenteral, depot, repeatable bromocriptine Parlodel LARR (PLO LAR) was used in the treatment of 10 women with hyperprolactinaemia. Two of them had previously an operation of a prolactinoma, eight did not have adenomas. Twenty eight days following administration of 50 mg PLO LAR, the PRL levels ere significantly lower than before treatment; in patients without adenomas they were quite normal. The action of the mentioned 50 mg PLO LAR corresponded roughly to a daily dose of 7.5 mg ParlodelR (PLO) by the oral route, i.e. in 28 days a total of 185 mg bromocriptine. After administration of five PLO LAR injections (50 and later 100 mg), the mean PRL levels in patients without adenomas were normal after 6 months. There were no significant nor pathological changes 28 days following i.m. PLO LAR 50 mg as regards T3, T4 levels, the blood sugar, cholesterol, FSH, LH, STH, TSH, testosterone cortisol, progesterone, 17 beta-estradiol, androstendione, 11 beta-OH androstendione, DHEA-S, 17 alpha-OH progesterone, aldosterone, 17-ketosteroids and 17-ketogenic steroids (in urine). LHRH + TRH + insulin tolerance tests were made repeatedly. Significant changes were found only in PRL levels (decline). In three amenorrhoic patients the originally low progesterone level rose significantly to levels of postovulation progesterone. One of these three women became pregnant after 18 years of unsuccessful treatment of sterility, incl. various oral dopaminergic preparations. The patients tolerated the preparation well and various biochemical and haematological tests were normal. The effect on galactorrhoea was favourable, seven amenorrhoic women had normal menstruation.

[An intracranial tumor in an unusual location associated with Cushing's syndrome]. / Intrakraniálni nádor neobvyklé lokalizace s Cushinogvým syndromem.

In a 58 year-old woman with peracute Cushing's syndrome high levels of ACTH were proved by RIA method. Autopsy showed normal pituitary gland in addition to a voluminous tumour situated in planum sphenoidale and lamina cribrosa ossis ethmoidalis. Tumour cells with epithelial features produced ACTH which was found by an indirect immunoperoxidase technique. Tumour was classified as ectopic corticotropic pituitary adenoma.

[Laboratory monitoring of therapy in Addison's disease]. / Laboratórny monitoring terapie morbus Addisoni.

UNLABELLED: Views on the usefulness of monitoring of substitution therapy in Addison's disease by hormonal laboratory indicators are controversial. The authors analysed the problem therefore in a group of 20 of their own patients. It was revealed that the adequacy of substitution of the cortisol deficiency can be very readily evaluated by diurnal profiles of cortisolaemia. The values of plasma ACTH provided less information, but were not unreliable. Assessment of free urinary cortisol did not prove useful. The adequacy of substitution of aldosterone deficiency reflected sensitively the plasma renin activity. CONCLUSIONS: monitoring by hormonal indicators is useful, basic means are the diurnal profile of cortisolaemia and the plasma renin activity.

[Dehydrdoepiandrosterone, dehydroepiandrosteron-sulfate and insulin in acute myocardial infarct]. / Dehydroepiandrosterón, dehydroepiandrosterón-sulfát a inzulín u akútneho infarktu myokardu.

The authors discuss the relationship between dehydroepiandsoterone, its sulphate conjugate and insulin and ischaemic heart disease in patients with acute myocardial infarction. In the examined group of patients they found lower values of dehydroepiandosterone and its sulphate in men, lower values of dehydroepiandosterone in women as compared with mean values with regard to age and a close inverse correlation of insulin and dehydroepiandrosterone and insulin and dehydroepiandrosterone sulphate. Whether dehydroepiandosterone is the "missing link" of hyperinsulinaemia and arterosclerosis is so far only a theoretical issue.

[Cushing's syndrome in pregnancy]. / Cushingov syndróm v gravidite.

Active Cushing's syndrome during pregnancy is a rare phenomenon which was so far described in the literature only in 85 women. The authors give an account of a patient who developed Cushing's syndrome during pregnancy and who was delivered during the eighth month of a healthy foetus by caesarean section, afterwards the hypercortisolism associated with hyperaldosteronism was treated by dextrolateral adrenalectomy. In the removed adrenal gland was a cortical adenoma made up of clear cells and cells reminding of the zona glomerulosa. Subsequently the authors summarize data from the literature on the prevalence of different pathogenetic forms of Cushing's syndrome in pregnant women, on the influence of hypercortisolism on mother and foetus, on the optimal diagnosis and therapy of this syndrome during pregnancy.

[Multicenter study with gliquidone in type 2 diabetes mellitus]. / Multicentrová stúdia s gliquidonom pri diabetes mellitus 2. typu.

The effectiveness and tolerance of the new sulphonyl urea antidiabetic gliquidone (commercial name Glurenorm) was tested by three-month administration of this preparation in a group of 39 type 2 diabetics. Gliquidone proved a medium-strength beta-cytotropic antidiabetic preparation. As to side-effects, the authors noted only dyspepsia in one patient (2.5%). Symptomatic hypoglycaemia did not develop in any of the patients. In the subgroup of six patients with diabetic nephropathy the indicators of renal functions did not deteriorate. In a sub-group of 6 patients with concurrent hepatopathy the originally elevated gamma-glutamyl transpeptidase activity receded. The authors confirmed thus the good tolerance of gliquidone in diabetes associated with nephropathy and diabetes with hepatopathy.

[Occurrence of primary aldosteronism in a group of ambulatory hypertensive patients]. / Výskyt primárneho aldosteronizmu v súbore ambulantných hypertonikov.

Findings pertaining to the diagnosis and treatment of primary aldosteronism are rapidly expanding. In the present work the authors focused attention on the clinical application of some progressive methods. They examined a group of 115 ambulatory patients with arterial hypertension, not suspected of secondary arterial hypertension, in the course of one year. As a screening method of primary aldosteronism they selected the aldosterone renin ratio (ARR). Using this method the authors diagnosed 125 cases of primary aldosteronism, i.e. a 13% prevalence in the examined group. Only in one instance they detected an adenoma by computed tomography (CT), in the remaining patients, i.e. four times, the adenoma was verified by selective catheterization of adrenal veins and assessment of aldosterone and cortisol. The authors did not confirm a more accurate localization of the adenoma by the aldosterone/cortisol ration than when assessing aldosterone only. In two patients adrenalectomy was performed by laparoscopy and this surgical technique, as regards adrenal glands, was implemented for the first time in Slovakia in our department. It has certain advantages over classical adrenalectomy.

[Microcirculation in the subcutaneous layer and in muscles in diabetes mellitus]. / Mikrocirkulácia v podkozí a vo svale pri diabetes mellitus.

The work is focused on the possibility of early diagnosis of diabetic microangiopathy. The authors used examination of microcirculation by the method of tissue clearance of Na 131I. In a group of 106 patients with diabetes thus the microcirculation of the lower extremities in the subcutaneous layer and the calf muscle was examined. A group of 36 healthy subjects served as control. An altered microcirculation was found in 75% type 1 diabetics and in all type 2 diabetics. In those with an altered microcirculation only in 23% type 1 diabetics and in 17% type 2 diabetics organ manifestations of diabetic microangiopathy (i.e. retinopathy and nephropathy) were lacking. It seems thus that altered Na 131I absorption in the lower extremities is an earlier sign of microangiopathic affection than identifiable organ changes. Examination of tissue clearance of Na 131I thus could reveal in time individuals threatened by this complication of diabetes.

[Epidemiological profile of thyroid volume and disorders in Slovakia]. / Epidemiologický profil objemu stítnej zl'azy a tyreopatií na Slovensku.

UNLABELLED: After 45 years of successful iodine prophylaxis a total of 6324 subject aged 7 to 70 years from East (72.0%), Central (16.2%) and West Slovakia (11.8%) were examined. The thyroid volume (ThV) by ultrasound was examined in a total of 6045 subjects. Serum level of thyrotropin (TSH) was estimated in 1919 (30.3%) and anti-thyroperoxidase antibodies (anti-TPO) in 2589 (40.9%) subjects. Iodine was estimated in 1983 (31.3%) spot urine samples. The median and 75th percentile of ThV were increasing (respectively) from 3.9 and 5.2 ml (10 yr), 8.2 and 10.2 ml (17 yr), 12.4 and 16.3 ml (31-40 yr) up to 14.1 and 19.9 ml (61-70 yr). The frequency of ultrasound hypoechogenicity as an early sign of autoimmune thyroiditis increased from 3.9% (28/709; 10 yr), 16.3% (66/403; 21-40 yr) and 30.3% (205/665; 41-60 yr) up to 51.0% (48/94; 61-70 yr). Positive anti-TPO level as an other sign of autoimmune thyroiditis was found in 1.6% (11/683; 7-13 yr), 7.3% (47/644; 17-30 yr) and 20.4% (257/1262; 31-70 yr). In the adults 19.0% (268/1409) positive anti-TPO were found. Among 1367 adults 6.2% (N = 85) of TSH levels were higher than 4.0 mU/l and 7.5% (N = 103) were lower than 0.2 mU/l. Among 1504 adults a total of 93 (6.1%) of nodules larger than 10 mm in diameter was found (14 in males and 75 in females). In this study the nature of nodules remained unidentified, since all subjects were referred to additional examinations. Malignant nodules were suspected in 3 females with high serum thyroglobulin level and in one additional female with occasionally found very large nodule. The estimation of urinary iodine showed a majority of values in optimal range (> 100-200 microg/l). CONCLUSIONS: Thyroid volume in about 75% examined subjects of all age groups may be considered as relatively small which is apparently due to 45 years of effective iodine prophylaxis. In spite of that the volume of remaining about 25% thyroids were apparently increased which may be presubambly explained by the effect of mainly genetic, but also environmental factors.