Pregravid body mass index as a predictor of gestational diabetes mellitus.

AIMS: It has been well documented that overweight or obesity before pregnancy is a strong predictor of gestational diabetes mellitus (GDM). The aim of this study was to assess the risk of GDM in women who were classified on the basis of pregravid body mass index (BMI) as normal weight and underweight. SUBJECTS AND METHODS: We analysed medical records of 1121 women with GDM who were referred to the Outpatient Clinic for Diabetic Pregnant Women in Szczecin (north-west part of Poland) between January 2001 and December 2005. The control group consisted of 1011 healthy pregnant women. All the women were Caucasian, were aged > or = 18 years and had single pregnancies. RESULTS: The cut point for BMI as a risk indicator for GDM was 22.85 kg/m(2) (odds ratio = 1.91; 95% confidence interval 1.5-2.1; sensitivity 47.8%, specificity 65.9%). In all of the analysed BMI ranges, except for the underweight group, significant relationships between pregravid BMI and GDM were found and BMI was the strongest predictor for GDM treated with insulin. Of all women with GDM, 25.7% were treated with insulin. The percentage of women requiring insulin therapy significantly increased with an increase of BMI across all studied categories. CONCLUSIONS: Not only in overweight but also in normal-weight women, the risk for GDM increases with increases in pregravid BMI and adjustment for confounding variables (age, prior GDM and parity) did not influence this relationship. Pregravid BMI is a strong predictor for GDM requiring insulin treatment.

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.

[Growth hormone, insulin, IGF-1 and estradiol levels during maturation of internal sex organs before and at menarche]. / Zmiany stezen GH, insuliny, IGF 1 i E2 oraz ich wplyw na wzrost wewnetrznych narzadów plciowych u dziewczat przed i w terminie menarche.

INTRODUCTION: The growth hormone (GH) is the main activator of growth, exerting its biological effects through IGF-1 and IGF-2 growth factors. Secretion of GH is partly controlled by steroid sex hormones. MATERIAL AND METHODS: Body mass, height, BMI, and body composition were recorded every three months in 45 healthy girls 8 years of age. Tertiary sex features according to Tanner were determined. Transabdominal ultrasound of the uterus and ovaries was done. GH, insulin, and IGF-1 levels in serum were measured radioimmunologically with commercial test kits. E2 levels were determined with an immunoenzymatic method. RESULTS: GH levels increased until stage M3 of breast maturation and gradually decreased during stage M4 (12 girls with menarche). IGF-1 and insulin levels continued to increase until stage M4. Uterine and ovarian dimensions correlated with levels of hormones studied. CONCLUSION: High levels of GH and IGF-1 during the early and central stages of puberty seem to affect the maturation of internal sex organs.

[The ob gene product (leptin)--a new hormone of adipose tissue]. / Produkt genu ob (leptyna)--nowy hormon tkanki tluszczowej.

Obesity--an important problem in modern societies--is caused by energy balance dysregulation and produces numerous adverse effects on health. Recently a particular attention has been paid to molecular and physiological mechanisms in the development of obesity and to the signalling role of adipose tissue in energy stores maintenance on the hypothalamic level. Leptin, the obese gene product discovered in 1995, may play a key role in the feedback system between adipose tissue and the ventromedial nucleus of the hypothalamus (satiety centre). The level of ob gene expression in adipose tissue and plasma leptin concentrations in humans are highly correlated with BMI. So far no mutations in the ob gene in obese subjects have been reported therefore leptin molecule could be active. Despite markedly increased leptin levels found in obesity its central action decreasing food intake and increasing energy expenditure is hindered. Defective ob protein signalling to the brain may be due to receptor and post-receptor defects. Neuropeptide Y, the hypothalamic neurotransmitter involved in the maintaining of energy homeostasis, is a likely candidate for mediating leptin afferent signals. In adipose tissue, the level of ob mRNA is regulated by insulin and glucocorticoids--hormones responsible for glucose homeostasis as well as for the central regulation of feeding behaviour. Until now the character of interactions between leptin and other hormones that regulate energy balance is not known, neither is the exact nature of leptin hypothalamic receptor defect. Defining of the role of leptin in the regulation of satiety and energy expenditure will undoubtedly contribute to a better understanding of the pathogenesis of obesity and its related metabolic complications and may lead to a new treatment approach to human obesity based on leptin or its analogues. At present research work focuses on leptin receptor studies and on ob gene polymorphism and its expression in feeding disorders including obesity and anorexia nervosa. The ob gene is one of a few genes involved in energy balance, however, very promising one.

Plasma concentrations of atrial natriuretic peptide and cyclic guanosine monophosphate in patients with hyperthyroidism before and after short-term treatment with methimazole.

The aim of the study was to answer the question whether a rapid decrease in serum triiodothyronine (T3) and thyroxine (T4) levels resulting from the treatment with a full dose (3 x 20 mg daily) of methimazole applied in patients with thyrotoxicosis is associated with the parallel diminution of plasma atrial natriuretic peptide (ANP) and its second messenger-cyclic guanosine monophosphate (cGMP) concentrations. Sixteen patients with thyrotoxicosis of mean age 41.5 +/- 10.5 years participated in the study. Short-term (10 days) methimazole treatment resulted in a significant decrease in serum T3 and T4 concentrations to the values found in 14 healthy subjects serving as control group. Plasma ANP and cGMP levels also decreased significantly during the treatment attaining the normal range. A significant correlation was found between the decrease in serum T3 and T4 concentrations during the treatment and the decrease in plasma ANP level. The decrease in plasma ANP was not closely correlated with the reduction of cGMP levels. These results indicate that: 1) a steep decrease in serum thyroid hormone concentrations induced by a full methimazole treatment during ten days in patients with thyrotoxicosis due to Graves' disease was accompanied by the return of elevated plasma ANP levels to normal range; 2. diminution of serum concentrations of both T3 and T4 during the treatment was correlated with the decrease in plasma ANP; 3) reduction in plasma cGMP concentration associated with short-term methimazole treatment in thyrotoxicosis seems to depend not only on the diminution of plasma ANP level.

[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.

[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.

The association between past Chlamydia pneumoniae infection and markers of chronic inflammation in obese women.

It has been widely accepted that obesity is associated with chronic, low-grade inflammation that affects the adipose tissue as well as the entire system. The aim of this study was to assess whether past Chlamydia pneumoniae infection influences obesity phenotypes and serum levels of low-grade inflammation markers in obese, healthy premenopausal women. The study was performed on 48 obese and 42 normal-weight women, aged 31.2 +/- 7.2 years. Serum levels of C-reactive protein (CRP), tumor necrosis factor alpha (TNFalpha) and its soluble receptor R2 (sTNF-R2), and interleukin 6 (IL-6) were measured. Body composition was assessed by bioimpendance. Insulin sensitivity was assessed by quantitative insulin sensitivity check index (QUICKI). The seroprevalence of C. pneumoniae infection was 69.1% and was similar in obese and normal-weight women (75.2% and 61.9%, respectively; P = 0.18). Obese women had higher CRP than healthy controls (P < 0.05). IL-6, TNFalpha, and sTNF-R2 showed no significant differences when comparing obese and normal-weight or C. pneumoniae infected and uninfected women. In multivariate regression analysis, fat mass (P < 0.001) and QUICKI (P < 0.01), accounting for 35% of the variance of CRP and C. pneumoniae infection, did not significantly contribute to this model (P = 0.51). In conclusion, past C. pneumoniae infection was not associated with changes in chronic inflammation markers in premenopausal obese women.

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.

Is neuropeptide Y responsible for constitutional delay of puberty in girls? A preliminary report.

Constitutional delay of puberty (CDP). in otherwise healthy girls is defined as failure to develop secondary sexual features past the age of 13 years (two standard deviations above the mean age at which secondary sexual features appear in the population of girls). The inhibitory action of neuropeptide Y (NPY) on the gonadotropic and somatotropic systems in experimental animals and stimulation by NPY of the hypothalamic-pituitary-adrenal axis have been reported, prompting us to study the levels of NPY, insulin-like growth factor-I (IGF-I) and cortisol in eight girls with CDP and normal weight (body mass index (BMI) 21.7+/-4.5 kg/mn2). The results were compared with those from a group of 40 girls (BMI = 20.0+/-3.1 kg/m2) who demonstrated a normal course of puberty (NP). All girls were studied at menarche (mean age at menarche, study vs. control: 16.4+/-0. 7 vs. 12.6+/-0.9 years). To measure NPY and IGF-1 we used a radioimmunoassay method, whereas cortisol was measured with an enzyme immunoassay. Blood was collected between 08.00 and 09.00 following an overnight fast. NPY was higher in girls with CDP (181.6+/-106.4 pg/ml) than in girls with NP (55.5+/-26.3 pg/ ml; p < 0.001). In the former group, cortisol was higher (397.3+/-241.6 nmol/l) than in NP girls (142.7+/-98.0 nmol/l; p < 0.01). Levels of IGF-I in CDP girls were lower than in NP girls (558.0+/-122.6 vs. 756.5+/- 226.8 ng/ml; p < 0.01). The results corroborate the involvement of NPY in sexual maturation and its role in delayed puberty.

[Effect of treatment of arterial hypertension on renal function in patients with imminent and overt diabetic nephropathy]. / Wplyw efektywnego leczenia nadcisnienia tetniczego na czynnosc nerek u chorych z zagrazajaca i jawna nefropatia cukrzycowa.

The effect was studied of blood pressure lowering treatment on renal failure and albuminuria (UAE) in patients with type I diabetes (IDDM) and imminent nephropathy as well as in patients with over diabetic nephropathy. The group of 24 patients with imminent nephropathy was subdivided: 1. twelve patients with borderline or overt hypertension with mean BP lowered not below 100 mmHg, and 2. twelve patients with BP within the normal limits, taking no hypotensive agents. In the other group of 12 patients with overt diabetic nephropathy hypertension was lowered below 105 mmHg and kept so for at least two years. All patients estimated their glycemia and glycosuria by themselves, ate 0.8 g protein/kg/24 h and about 100 mmol Na/24h. Under hospital conditions the following were estimated: albuminuria, glomerular filtration rate (51Cr EDTA) and effective renal blood flow (131I hippurate). The same examinations were repeated 1 year and 2 years later. The lowering of BP below 100 mmHg in patients with imminent diabetic nephropathy significantly lowered microalbuminuria without changing GFR, ERPF despite good or satisfactory compensation of diabetes. Maintaining BP below 105 mmHg for 2 years did not prevent the patients with overt nephropathy to develop progressive renal failure despite the rate of GFR deterioration and of the increase of albuminuria slowed down.

Leptin, neuropeptide Y, beta-endorphin, gonadotropin, and estradiol levels in girls before menarche.

More than two decades of clinical studies have provided us with the opportunity to develop and implement criteria that distinguish three phases during pre-menarche, paralleling rising levels of estrogens, namely 'pre-estrogenization', 'onset of estrogenization' and 'full estrogenization'. The aim of this study was to examine the relationships between somatic features and levels of leptin, neuropeptide Y (NPY), beta-endorphin, gonadotropin and estradiol in pubertal girls before menarche. Weight, height, body mass index (BMI), tertiary sex features, estrogen-related changes in hymen, fat and lean body mass were studied on a quarterly basis in 45 girls. At the same time, ovarian and uterine dimensions were established sonographically and serum was obtained for the determination of leptin, NPY, beta-endorphin, gonadotropin, and estradiol levels. Onset of estrogenization in girls was marked by weight loss, followed by an increase in total, fat and lean body mass, and pubertal acceleration of growth. At the time of full estrogenization, lower NPY and beta-endorphin levels were observed, accompanied by an increase in gonadotropin secretion. Changes in leptin levels are consistent with a role of this hormone in metabolic signaling.

[Effect of intravenous sodium chloride load on levels of atrial natriuretic peptide (ANP) and 3'5' guanosine monophosphate (cGMP) in plasma of patients with uncomplicated sodium-sensitive arterial hypertension maintained on different dietary sodium intake]. / Wplyw dozylnego obciazenia ladunkiem sodu na stezenie przedsionkowego peptydu natriuretycznego (ANP) i 3'5' guanozynomonofosforanu (cGMP) w osoczu chorych z niepowiklanym samoistnym nadcisnieniem tetniczym sodowrazliwym zywionych dieta o róznej zawartosci sodu.

The aim of this work was an evaluation of the effect of the acute hypervolemia induced by 90 min intravenous infusion of 1500 ml 0.9% NaCl (16.7 ml/min) on blood pressure, plasma concentration of the atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), aldosterone (ALDO), plasma renin activity (PRA) in patients with essential hypertension on the normal, low and high sodium intake. Twelve patients with noncomplicated essential sodium-sensitive arterial hypertension participated in the study. Sodium chloride infusions were performed three times: first--on the fifth day of normal daily sodium u intake (110-120 mmol/day), second--on the fifth day of low sodium intake (10-20 mmol/day), third--on the fifth day of high sodium intake (200-220 mmol/day). Acute intravenous sodium chloride load induced a significant increase of the mean arterial pressure (MBP) only when the patients were on the high sodium diet. This increase of the MBP was associated with a significantly lower increment of plasma ANP, cGMP, lower decrement of ALDO and PRA when compared to normal- or low- sodium intake. The results suggest an impairment of the adaptive homeostatic mechanisms induced by an acute intravenous sodium load in patients with noncomplicated salt-sensitive essential hypertension ingesting high-sodium diet.

Atrial natriuretic peptide and cyclic guanosine monophosphate plasma concentrations in patients with thyrotoxicosis and atrial fibrillation. Effect of short-term methimazole therapy.

Plasma immunoreactive atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP), serum thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) concentrations were measured in 11 patients with thyrotoxicosis and atrial fibrillation (group 1), in 5 patients with thyrotoxicosis and sinus cardiac rhythm (group 2) and in 8 healthy subjects in comparable age. Patients with thyrotoxicosis were studied before and after treatment with methimazole (3 x 20 mg daily) during 10 days. During treatment sinus cardiac rhythm returned in 6 patients with initial fibrillation (group 1a) while 5 patients still presented atrial fibrillation at the end of the study (group 1b). All patients from group 2 maintained a sinus cardiac rhythm throughout the study. Median plasma concentrations of ANP and cGMP before treatment in patients from group 1 were higher: 43.8 pmol/l and 11.0 nmol/l, respectively than in patients from group 2: 20.0 pmol/l (p < 0.005) and 6.5 nmol/l (p < 0.01), respectively. In all groups of patients methimazole treatment resulted in a significant decrease of plasma ANP and cGMP concentrations in parallel to a reduction of serum T3 and T4 levels. After therapy, plasma ANP and cGMP levels in patients from group 1a were not significantly different from those in patients from group 2, while in patients from group 1b remained slightly elevated. Presented results suggest that atrial fibrillation in patients with thyrotoxicosis represents an important factor augmenting plasma ANP and cGMP levels, in addition to the stimulatory effect exerted by thyroid hormones. However, the marked reduction of serum thyroid hormones produced by short-term methimazole treatment in patients with thyrotoxicosis was associated with parallel decrease of plasma ANP and cGMP levels toward normal values. Therefore, the influence of thyroid hormones on plasma ANP and cGMP concentrations seems relatively more important than the effect of atrial fibrillation.