Serum acylated ghrelin, adiponectin and leptin levels in normal-weight and obese premenopausal women.

Ghrelin, leptin, and adiponectin play an important role in the regulation of energetic homeostasis, but physiological relationships between these hormones have not been elucidated. This study was therefore designed to characterize the association between serum acylated ghrelin, leptin, and adiponectin levels, as well as insulin resistance evaluated by homeostasis model of assessment in 32 normal-weight and 60 age-matched metabolically healthy obese women. In normal-weight, but not in obese women, we found a positive linear correlation between leptin and ghrelin (r=0.375; p=0.034). In the multiply regression analysis we observed the change of direction of leptin influence on acylated ghrelin level from positive in normal-weight (p=0.001) to negative in obese women without insulin-resistance (p=0.033); in obese women with insulin resistance leptin was not significantly associated with ghrelin. In neither group was any linear correlation found between ghrelin and adiponectin. However, by multivariate analysis adiponectin was positively associated with ghrelin, but only in obese women without insulin resistance (p=0.01). In conclusion, in normal-weight women leptin is positively correlated with acylated ghrelin. In obese women without insulin resistance different interactions between both hormones might reflect a physiological mechanism of adaptation to a positive energy balance.

Not insulin but insulin sensitivity, leptin, and cortisol are major factors regulating serum acylated ghrelin level in healthy women.

It has been suggested that insulin and glucose are the most important factors for ghrelin secretion. Most of these studies were performed using total ghrelin assays, detecting two forms of ghrelin (acylated and desacyl), derived from the same peptide precursor but having different biological effects. This study was therefore designed to characterize associations between serum acylated ghrelin levels (Ghr), selected adipocytokines, hormones, and carbohydrate metabolism parameters in healthy women in stable energy metabolism. The study was performed on 32 healthy, normal-weight, non-pregnant women with normal [body mass index (BMI) 18.9-24.2 kg/m2] and stable (the difference between two measurements performed within 1 month being less than 0.5 kg) body weight, aged 22-47 yr. Leptin, Ghr, GH, IGF-I, cortisol, insulin, and glucose were measured in the early follicular phase of the menstruation cycle. Insulin sensitivity was measured using quantitative insulin sensitivity check index (QUICKI). Body composition was assessed by bioimpedance. We found a positive linear correlation between leptin and Ghr (r=0.375; p=0.034) and negative correlation between insulin and Ghr (r=-0.374; p=0.034). GH, IGF-I, adiponectin, and body composition parameters did not correlate with Ghr. In multiple regression analysis only QUICKI, leptin, glucose, and cortisol (positively) and age (negatively) accounted for 50% variation of Ghr. Insulin and BMI did not contribute significantly to the model. Our results suggest that in healthy women basal Ghr level is regulated by multiple factors, mainly by insulin sensitivity, leptin, and adrenal glands activity. However, further studies are needed to elucidate the physiological mechanisms involved in acylated Ghr secretion.

The common C49620T polymorphism in the sulfonylurea receptor gene (ABCC8), pancreatic beta cell function and long-term diabetic complications in obese patients with long-lasting type 2 diabetes mellitus.

HYPOTHESIS: A gene polymorphism associated with accelerated beta-cell failure may lead to a more rapid development of long-term complications of type 2 diabetes (T2DM) due to a worse metabolic control of the disease. AIM OF THE STUDY: Evaluation of an association between the intronic C49620T (exon 16 -3c-->t) polymorphism in the ABCC8 (SUR1) gene and beta-cell function, as well as the prevalence of long-term diabetic complications in obese patients with long-lasting type 2 diabetes. METHODS: Two hundred and fifteen obese patients with at least a 10-year history of T2DM were thoroughly characterized clinically. In all the patients the intravenous glucagon test was performed and the C49620T ABCC8 polymorphism was assessed. Subgroups of patients, classified either according to genotype or to allele carriage, were compared. RESULTS: No difference was found between the groups in variables describing beta-cell function and the prevalence of chronic diabetic complications, with the exception of a significantly lower incidence of brain stroke in CC homozygotes than in patients carrying T allele (CT+TT). Body mass index was higher in patients carrying C allele than in TT homozygotes. HDL-cholesterol was higher in CT heterozygous than in homozygous CC or TT patients. CONCLUSIONS: There is no association between the ABCC8 polymorphism gene and the beta-cell function or the prevalence of chronic diabetic complications in obese patients with long-term T2DM, except for brain stroke. The results might suggest that the homozygous CC subjects are at lower risk of the complication, but additional studies are warranted to test this finding.

Association between the Pro12Ala variant of the peroxisome proliferator-activated receptor-gamma2 gene and increased 24-h diastolic blood pressure in obese patients with type II diabetes.

The aim of the study was to examine an association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR)-gamma2 gene and blood pressure values assessed by 24-h ambulatory blood pressure monitoring (ABPM) in obese patients with long-lasting type II diabetes. Two hundred and fourteen obese patients (95 men and 119 women) with above 10-year history of type II diabetes were recruited for the study. In all the patients, ABPM was performed and other parameters, including age, body mass index (BMI), waist/hip ratio (WHR), haemoglobin A1c (HbA(1c)), serum lipids and creatinine were also evaluated. The Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism. Two subgroups of patients were compared: (a) Pro/Pro: homozygotic Pro/Pro (n=154) and (b) Ala: Ala allele carriers (Ala/Ala+Ala/Pro) (n=60). The studied groups were not different when age, BMI, WHR, HbA(1c), lipids, creatinine and frequency of hypertension were compared. A similar ratio of patients from both groups were treated with angiotensin-converting enzyme inhibitors, calcium channel blockers, diuretics, beta-blockers and alpha-blockers. A difference was observed in a mean 24-h (Ala: 71.9+/-8.1 vs Pro/Pro: 69.4+/-7.8 mm Hg, P=0.034) and a mean night time (Ala: 67.1+/-7.8 vs Pro/Pro: 64.5+/-8.4 mm Hg, P=0.025) diastolic blood pressure, which was significantly higher in patients with Ala variant. There was also a trend towards a higher mean daytime diastolic blood pressure in this group. It seems that the Pro12Ala variant is associated with an increased mean 24-h diastolic blood pressure in obese diabetic patients. Different reaction for antihypertensive medication depending on a variant of the PPAR-gamma2 gene should also be considered as a possible cause of the presented results.

[The assessment of urinary glycosaminoglycans (GAG) excretion during therapy of patients with progressive Graves' ophthalmopathy]. / Ocena wydalania z moczem glikozaminoglikanów (GAG) w trakcie leczenia postepujacej oftalmopatii obrzekowo-naciekowej w przebiegu choroby Gravesa i Basedowa.

Excessive accumulation of hydrophilic glycosaminoglycans (GAG) in the retrobulbar tissue leads to many of the clinical manifestations of Graves' ophthalmopathy (GO). We examined the quantitative urinary GAG excretion in 35 patients with GO. GAG were isolated from 24-h urine collections by precipitation with cetylpyridinum chloride and ethanol according to Bitter. Patients with progressive ophthalmopathy showed on the average a twofold increase in urinary GAG excretion in comparison to patients with stable ophthalmopathy. The elevated values of GAG decreased significantly under treatment and correlated with the clinical picture of GO, however no correlation was found between the urinary GAG values and actual severity of ophthalmopathy classified according to Werner and Donaldson. There was no significant difference in GAG excretion between group 1, treated with methylprednisolon and irradiation of retrobulbar tissue and group 2, under therapy with methylprednisolon. In conclusion, elevated urinary GAG excretion is characteristic for the clinical picture of the progressive GO. The remarkable decrease in GAG values during treatment correlated to the positive response to immunosuppressive therapy.

[The role od adhesion molecules in the pathogenesis of Graves ophthalmopathy]. / Znaczenie czastek adhezyjnych w patogenezie oftalmopatii obrzekowo-naciekowej w przebiegu choroby Gravesa-Basedowa.

Graves' ophthalmopathy (GO) is an autoimmune condition characterized by mononuclear cell infiltration of the extraocular muscles and/or orbital connective tissue. Adhesion molecules play an important role in the initiation and maintenance of the inflammatory immune process. Cellular activation and local expression of adhesion molecules lead to leucocyte recruitment, migration to inflammatory sites and targeting in the extravascular space. Vascular endothelium in retroocular connective tissues of patients with GO is strongly positive for EMAL-1 and VCAM-1, whereas VCAM-1 immunoreactivity is minimal and ELAM-1 immunoreactivity is generally absent in normal retroocular tissue. Interactions between matched activated T lymphocytes and orbital endothelial cells are mediated by integrin dependent ICAM-1/LFA-1 and VCAM-1/VLA-4 pathways and reveal marked differences when comparing GO orbital endothelial cells to normal ones. Higher soluble ICAM-1 volumes in patients with Graves' disease with GO than those in patients with Graves' disease without ophthalmopathy can reflect the degree of inflammatory activity. Increased soluble ELAM-1 concentration only in patients with GO suggests that soluble ELAM-1 could be a specific marker of endothelium activation in GO.

[The influence of treatment of progressive edematous infiltrative ophthalmopathy on intraocular pressure]. / Wplyw leczenia postepujacej oftalmopatii obrzekowo-naciekowej na wartosc cisnienia wewnatrzgalkowego.

PURPOSE: To evaluate the influence of systemic steroid therapy and retrobulbar irradiation on intraocular pressure (IOP) in patients with infiltrative--oedematous Graves' ophthalmopathy. MATERIAL AND METHODS: We examined 76 patients divided into 3 groups: I--treated by irradiation only (15 patients), II--treated by irradiation and oral prednisone therapy (26 patients), III--treated by irradiation and intravenous methylprednisolone pulse therapy (35 cases). All patients underwent full ophthalmological examination (including IOP measurement, perimetry and gonioscopy) before, during, immediately after and 2-20 months after treatment. RESULTS: Increased IOP (21-31 mm Hg) was observed in 54 patients (71%) before treatment. The iridocorneal angle was open in all eyes. Changes in perimetry were not characteristic for glaucoma. IOP was higher in patients with more severe ophthalmopathy. We recorded transient increase of IOP during treatment in only 3 patients. Increased IOP immediately after therapy was observed in 16 patients with severe symptoms and signs of ophthalmopathy: in group I--4/15 (27%), in group II--4/26 (15%), in group III--8/35 (23%). Higher IOP was recorded in 10 patients two to twenty months after completion of treatment: from group I--4/15 (27%), from group II--1/26 (4%) and from group III--5/35 (14%). In 6 of these 10 persons we observed recurrence of ophthalmopathy, in 4 patients higher IOP was the only deviation, they needed local therapy. The mean values of IOP were lower in patients treated by steroid therapy in comparison to patients treated by irradiation only. The most rapid improvement of clinical status was observed in patients treated by methylprednisolone pulse therapy. CONCLUSIONS: The increase of IOP in patients with Graves' ophthalmopathy correlates with severity and duration of eye disease. Systemic steroid therapy is more efficient in reduction of IOP than irradiation of the retrobulbar tissue. Our results suggest that combined therapy is a preferable method of treatment of progressive ophthalmopathy, including cases with increased intraocular pressure.

[Individual choice of treatment in patients with progressive infiltrative ophthalmopathy in Graves-Basedow disease]. / Indywidualny wybór metody leczenia postepujacej oftalmopatii obrzekowo-naciekowej w chorobie Gravesa-Basedowa.

The results of different methods of treatment of infiltrative endocrine ophthalmopathy in 68 patients (52 women and 16 men) aged 28-63 years were evaluated. The analysis of the results indicates that combined treatment with glucocorticoids and tele-cobalt therapy may be considered as the method of choice. In patients with rapidly progressive ophthalmopathy and in patients with inactive peptic ulcer intravenous pulsed glucocorticoid administration may be used instead of oral treatment. When contraindications to corticotherapy exist, good results of treatment may be achieved with tele-cobalt therapy alone. Plasmapheresis seems less effective but may be used in rapidly progressive, short term lasting ophthalmopathy in patients refusing tele-cobalt therapy, in connection with glucocorticoids or after unsuccessful glucocorticoid therapy alone. The consecutive treatment with glucocorticoids and tele-cobalt therapy is effective but requires much more time.

[Effect of naloxone on beta-endorphin and insulin concentrations during glucose tolerance testing in patients with simple obesity]. / Wplyw naloksonu na stezenia beta-endorfiny i insuliny w czasie testu doustnej tolerancji glukozy w otylosci prostej.

The concentrations of beta-endorphin, ACTH, insulin (IRI), glucagon (IRG), cortisol and growth hormone were determined by radioimmunoassay during oral glucose tolerance test (OGTT) performed in 13 obese patients with normal glucose tolerance and without arterial hypertension. The test was performed in random, before and after intravenous administration of 0.8 mg of naloxone. Six persons with normal body weight served as controls. Higher basal concentrations of beta-endorphin and significant increase in beta-endorphin levels during OGTT, without concomitant increase in ACTH concentrations, have been found in obese patients. No effect of naloxone on beta-endorphin liberation during OGTT was observed, though the drug caused lowering in maximal increment of beta-endorphin and paradoxically lowered the concentrations of ACTH and cortisol. The basal concentrations of beta-endorphin did not correlate with the concentrations of insulin, ACTH, cortisol and growth hormone. Elevated concentrations of insulin, lowered concentration of growth hormone and normal levels of glucose and glucagon were observed in basal conditions, and excessive responses of insulin, glucose and glucagon were observed in obese patients during OGTT. Naloxone lowered insulin response and inhibited the fall of growth hormone during OGTT but did not influence the concentrations of glucose and glucagon. No correlation was found during OGTT after naloxone between insulin and beta-endorphin, ACTH or cortisol, whereas negative correlation was observed between insulin and growth hormone. The obtained results suggest that the elevated concentrations of beta-endorphin in simple obesity may be of both hypophyseal and peripheral origin. Hyper-beta-endorphinemia observed in obesity is probably not directly responsible for hyperinsulinemia, it may, however, be responsible for lower sensitivity of tissues to the action of insulin.

[Analysis of early and late results of progressive Graves-Basedow ophthalmopathy treatment with different methods]. / Analiza wstepnych i odleglych wyników leczenia oftalmopatii obrzekowo-naciekowej w chorobie Gravesa-Basedowa róznymi metodami.

The early (immediately after the end of treatment) and late (from 12 to 91, mean 46.3 months after the end of treatment) results of progressive Graves-Basedow ophthalmopathy treatment were evaluated in 71 patients (57 women and 14 men, aged 25-66, mean 47.3 years). In all patients the thorough ophthalmological evaluation was performed early and late after treatment and the abnormalities found were classified according to Werner's method and Donaldson's ophthalmopathy index. The patients were divided into 7 groups according to different methods of treatment. Groups I-V consisted of 31 patients treated with glucocorticoids or glucocorticoids with azathioprine (Imuran) in the first stage of medication (30 patients). Plasmapheresis (7 patients) or tele-cobalt irradiation (3 patients) was applied as the second stage of treatment when the first stage was ineffective. In one person plasmapheresis and tele-cobalt irradiation was applied without previous glucocorticoid therapy. Two patients were treated successively by glucocorticoids, plasmapheresis and tele-cobalt irradiation. Very good and good late results of treatment were found in 95% of patients out of 22 reexamined persons of groups 1-5. Group 6 consisted of 7 patients treated with cobalt irradiation alone, in all 6 patients evaluated late results were good or very good. Out of 33 patients of group 7 treated by combination of glucocorticoids and telecobalt irradiation 23 were evaluated late and the results were found good or very good in 96%. The results suggest that combined treatment of progressive endocrine ophthalmopathy with glucocorticoids and cobalt irradiation is the most effective method of treatment at present. The affectivity of stage treatment is comparable with combined treatment but lasts longer and usually is more expansive.(ABSTRACT TRUNCATED AT 250 WORDS)

[Titers of antibodies against thyroid membrane antigens in patients with Graves-Basedow disease and progressive infiltrative ophthalmopathy during treatment with glucocorticoids and retro-orbital tissue irradiation]. / Miano przeciwcial przeciw antygenom blon komórek tarczycy u chorych na chorobe Gravesa-Basedowa i postepujaca oftalmopatie obrzekowo-naciekowa w przebiegu leczenia glikokortykoidami i napromienianiem tkanki pozagalkowej.

In 22 patients with progressive endocrine ophthalmopathy (classes 4-6 according to Werner's scale and ophthalmopathy index at least 4 and evidences of infiltrative changes in retro-ocular tissues in computerised tomography, after achievement of euthyroid state) the titers of antibodies against thyroid membrane antigens (ATMA) were determined by Gardas and all. method. Control group consisted of 26 patients with Graves-Basedow disease without clinical signs of ophthalmopathy who were investigated for ATMA before and after conventional methimazole treatment. The determinations of ATMA were performed before treatment, after 3-4 weeks and subsequently once a month. ATMA's titers exceeding 1:1000 were found in 68% of patients with progressive infiltrative ophthalmopathy and in 77% of patients with Graves-Basedow disease without ophthalmopathy. The incidence of elevated ATMA titers during treatment of ophthalmopathy with supervoltage retro-orbital tissues irradiation with high dose of prednisone, decreased markedly in 6th month of treatment with subsequent increase to average 55% at the end of treatment what suggests the influence of therapy on antibodies production. The changes in the incidence of elevated ATMA titers during conventional Graves-Basedow disease treatment were different. No relations between increased ATMA titers and intensity of infiltrative ophthalmopathy and the course of treatment in the patients with ophthalmopathy were found.

[Effectiveness of iodine prophylaxis and frequency of thyroid enlargement (thyroid goiter) and clinical diagnosis of thyroid diseases in inhabitants of the Szczecin region after the Czernobyl accident]. / Efektywnosc profilaktyki jodowej oraz czestosc wystepowania powiekszenia tarczycy (wola) i klinicznego rozpoznania chorób tarczycy u mieszkanców regionu szczecinskiego po awarii elektrowni atomowej w Czarnobylu.

The study, supported by program MZ-XVII, was carried on 4567 inhabitants of the area of Szczecin (2350 females and 2217 males). The population was chosen randomly, according to a simple drawing scheme. All subjects were clinically examined using standardised questionnaires. In 3468 persons (including 1807 girls and women, 1661 boys and men) apart form clinical examination, the assessment of thyrotropin, thyroxine and triiodothyronine in serum and frequency of antithyroglobulin antibodies and antithyroid membrane antibodies were evaluated. The data indicate that 94% of children in Szczecin's region received the prophylactic dose of iodine, mostly between the 1st and the 5th of May 1986. Only 17% of the adults received iodine. The most common preparation was Lugol solution given in a single dose. Among all persons who received iodine, only in 5% of subjects the side effects were noted (mostly in children), including symptoms of gastrointestinal tract (vomiting, abdomen pain) and occasionally intrathyroid side effects (thyroid pains). In examined population the high frequency of thyroid enlargement, mainly in women (up to 43-44% at the age group 30-50 years) was found. The frequency of clinical diagnosis of thyroid disease was higher in women than in man (most often the diffuse goiter, rarely the nodular goiter). The frequency of thyroid enlargement and clinical diagnosis of thyroid disease was not dependent on prophylactic iodine intake. The iodine prophylaxis did not influence on thyroid hormones and TSH serum levels and on frequency of antithyroid antibodies.

[Analysis of early results of combined treatment with glucocorticoids and telecobalt therapy for Graves' disease ophthalmopathy]. / Ocena wczesnych wyników skojarzonego leczenia glukokortykoidami i telekobaltoterapia postepujacej oftalmopatii obrzekowo-naciekowej w chorobie Graves-Basedowa.

Early results of combined use of glucocorticoid administration and irradiation with radioactive cobalt for treatment of oedematous-infiltrative ophthalmopathy associated with Graves' disease have been analyzed in a group of 33 patients including 28 women and 5 men of age between 25 and 66 years (mean age 47.3 years). The combined therapy was a modification of the original method of Bartalena et al. which consisted in the gradual increase of the initial dose of glucocorticoids and prolongation of the period of administration of the drug. The ophthalmic lesions were assessed by thorough ophthalmologic examination and classified according to Werner. The ophthalmopathy index was calculated according to Donaldson. Satisfactory results of treatment have been obtained in 32 patients, with 9 patients being completely relieved from any objective or subjective ophthalmic symptoms (very good results), and 23 patients having still small afflictions originating from the soft tissues of the eye socket, exophthalmos, diplopia during marginal vision and a decreased visual acuity (good results). The clinical recovery was mostly connected with the improvement in the condition of soft tissues of the eye socket, cornea and external ocular muscles and, to a smaller extent, exophthalmos which persisted to some degree and acuity of vision not always attaining normal values. In one person the results of treatment were unsatisfactory despite some improvement. Very good and good results obtained in 97% of patients indicate that the administration of glucocorticoids combined with the irradiation of retrobulbar tissues with radioactive cobalt can now be regarded as the most effective method of treatment of the progressive oedematous-infiltrative ophthalmopathy.