Clinical endocrinology
This program is designed to identify patients in whom diabetes mellitus resists therapy with oral hypoglycemic agents (OHA) and basal insulin administration is needed to maintain the HbA1c at the desired level below 7. Data from 2895 patients (2034 women and 851 men) were available for analysis. Only 2.6% of the patients had the glycated hemoglobin (HbA1c) level within the normal values prior to the onset of therapy. The remaining ones had decompensated diabetes mellitus that required supplementation of regular OHA therapy with Lantus insulin. Characteristics of carbohydrate metabolism significantly improved and decreased to the desired values within 12 weeks after the initiation of the combined treatment without enhancement of the risk of hypoglycemia. Results of the study demonstrate beneficial effect of the early prescription of basal insulin. Administration of glargine insulin permits to rapidly and safely reach optimal parameters of carbohydrate metabolism in the majority of the patients.
ADVANCE is a multicentre placebo-controlled randomized trial undertaken to investigate effects of intensive decrease of blood pressure and blood glucose level on the development of major micro- and macrovascular complications in patients with type 2 diabetes mellitus. Patients included in the study designed to evaluate results of intense glycemic control were given glyclazide modified release (diabeton MR) as the basic treatment. The main results of ADVANCE indicate that intense hypoglycemic therapy with the use of diabeton MR allows for efficient and safe control of blood glucose level with the reduction of the mean HbA1c level to 6.5% or less. Also, this treatment significantly decreases the risk of severe diabetic complications by 10% including nephropathy and proteinuria (by 21% and 30% respectively).
According to official statistics, malignant insulinomas account for a small fraction of gastroenteropathic endocrine neoplasms, the majority of insulinomas being essentially benign tumours. This paper reports a clinical case of malignant insulin-producing neuroendocrine tumour of the pancreas tail in a 28 year-old woman. She had multiple liver metastases and organic hyperinsulinism. Results of comprehensive examination of the patient at the Endocrinological Research Centre including laboratory diagnostic data and their evaluation are presented. Her surgical treatment was accomplished in N.N. Burdenko Facultative Surgery Clinic, I.M. Sechenov Moscow Medical Academy. Treatment strategy in the post-operative period and follow-up observations are described.
The objective of this study was to study dynamics of prevalence of functional thyroid dysfunctions among pregnant women. The levels of TSH, free T4, and antithyroid peroxidase antibodies (ATP-AB) were measured in randomly selected women of different gestational age who applied to be registered in a maternity welfare centre in 1999-2003 (n = 215) and 2006-2008 (n = 325). The available data indicate that iodine consumption by the study populations increased during the above periods even if still remains subnormal. No statistically significant decrease in the occurrence of ATP-AB and hypothyroidism was recorded. Women carrying ATP-AB in the first and seconds trimesters of pregnancy had significantly higher TSH levels compared to those without ATP-AB. A change of diagnostic criteria for hypothyroidism (lowering the reference TSH threshold from 4.0 to 2.5 mU/l accounts for a several-fold rise (by a factor of 2-7) in the prevalence of hypothyroidism among pregnant women.
This paper presents results of examination of 59 boys aged from 14 to 16 years with delayed sexual development (DSP). All children were allocated to 3 groups depending on specific clinical features of the disorder. Group 1 comprised boys (n = 20) with retardation of growth and sexual development, group 2 (n = 14) boys with DSP and cryptorchidism, group 3 (n = 25) boys with DSP and obesity. The examination included evaluation of the patients' physical and pubertal development, measurement of serum sex hormones, and difereline stimulation test. Constitutional form of DSP was diagnosed in 90% of the boys in group 1. Hypogonadotropic hypogonadism occurred in 42.8% of the patients in group 2, and boys of group 3 suffered DSP etiologically associated with excessive body weight. It is concluded that correlation between clinical and hormonal characteristics of the examined boys reflects the cause behind DSP.
The authors discuss results of investigations into the structure and functional status of erythrocyte membranes in patients with metabolic syndrome. It is shown that the pathological process involves not only well known changes in serum lipid metabolism but also highly specialized cells, such as erythrocytes. Specifically, erythrocytes undergo marked disorganization of membranous lipid phase in conjunction with a relative increase of cholesterol fraction and a decrease in phospholipids levels. Analysis of fractional lipid composition in erythrocyte membranes reveals reduced content of phospholipids, sphingomyelin, and phosphatidylcholine coupled to increased content of cholesterol, lysophosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine. It is concluded that disturbances of carbohydrate metabolism in patients with metabolic syndrome aggravate manifestations of the underlying disease.
Experimental endocrinology
The objective of this study was to evaluate the influence of glycorazmulin on carbohydrate and lipid metabolism and on the function of liver in animals with alloxan-induced diabetes. It was shown that glycorazmulin produces a well-apparent decrease in blood glucose level and has beneficial effect on lipid metabolism. In addition, the preparation contributes to the normalization of liver function.
This experimental study was designed to evaluate effects of hypo- and hyperthyroidism on the density of 3H-muscimol and 3H-diazepam-binding sites in synaptic membranes of the rat brain. It was shown that density of both 3H-muscimol and 3H-diazepam-binding sites increases in animals with hypothyroidism and decreases in hyperthyroidism. This difference may account for the predominance of general inhibitory reaction in animals with hypothyroidism and general excitation in hyperthyroid rats.
Reviews
This review summarizes experimental findings obtained in immunological studies of diabetes mellitus. Principal immunotherapeutic approaches to the treatment of diabetes are described. Putative mechanisms behind the development of immunotolerance are considered. A brief summary of previously reported and on-going clinical studies is presented.
Type 1 diabetes mellitus (DM) has negative effect on the development and functioning of the reproductive system in young girls. The time of onset of type 1 DM (especially in the puberty period), duration of the disease, and poor compensation of disturbed carbohydrate metabolism are supposed to be the most probable causes of delayed pubertal development exerting negative effect on the age of menarche and increasing the frequency of menstrual problems (largely oligo- and amenorrhea). Despite a wealth of relevant investigations, the cause of reproductive dysfunction remains unknown even though negative effect of type 1 DM on different components of the hypothalamo-pituitary-ovarian axis has been fairly well documented. The pathogenetic mechanisms of reproductive disorders may consist of suppression of pulsed production of gonadotropin releasing hormone (GnRH) due to enhanced central dopaminergic and opiate activities, decreased concentration of insulin receptors on GnRH-synthesizing neurones, and changes of serum leptin level in the affected girls. In patients with type 1 DM, hypothalamic effects on the pituitary may be supplemented by the direct action of products of free radical oxidative activity leading to a decrease in the production of trophic hormones. Also considered, is primary ovarian origin of menstrual disturbances in girls with type 1 DM. Of great importance are studies concerning autoantibodies against different ovarian structures, variations in concentrations of insulin-like growth factor-1 (IGF-1) and hormone ghrelin.
This review deals with the role of adipose tissue inflammation (ATI) in the development of type 2 diabetes mellitus (DM2). ATI is regarded as a link between obesity and DM2. The review illustrates the involvement of main adipokines in pathogenesis of DM2 and provides a detailed description of such factors as impaired adiponectin and stimulation of cytokine production responsible for metabolic disorders, activation of lipolysis, in adipocytes, increased fatty acid and triglyceride levels, suppression of insulin activity at the receptor and intracellular levels. Adipokines, in the first place cytokines, act on the insulin signal pathway and affect the intracellular inflammatory kinase cascade. At the intercellular level, ATI stimulates JNK and IKK-beta/kB responsible for the development of insulin resistance via such mechanisms as activation of cytokine secretion in the adipose tissue, oxidative stress, and induction of endoplasmic reticulum enzymes. The key role of JNK and IKK-beta/kB in the inhibition of the insulin signal pathway is mediated through inactivation of insulin receptor substrate 1. Also, it is shown that ATI modulates B-cell function and promotes progressive reduction of insulin secretion.
Statistical analysis is an integral component of any clinical study. The objective of the present work was to assist clinicians in understanding various methods of statistical treatment of medical findings without going into details of mathematical computation. The most strongly sought for and popular analytical procedures are considered in application to clinical and experimental medical research. Part 1 of this communication is focused on descriptive statistics and methods of univariate statistical analysis. Part II will be concerned with the analysis of survivorship and multivariate statistics.

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