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Introduction Insulin glargine 300 U/mL (Gla-300) is a novel glargine formulation which shows slower and more prolonged absorption following subcutaneous administration in comparison to insulin glargine 100 U/mL. In this prospective, observational, single-arm, multicenter, real-world study conducted in Serbia, we evaluated the effectiveness and safety of Gla-300 in patients with type 2 diabetes mellitus (T2DM) previously inadequately controlled with different basal or premix insulin therapy regimes. Methods A total of 350 patients with T2DM were enrolled by 27 physicians, from date of the first patient in (12 December 2017) to the date of last patient completed/last patient out (30 October 2018), from both medical centers and general hospitals. Patients’ observation and data collection were performed at visit 1 (V1), i.e., the inclusion visit (3–6 months after Gla-300 introduction), including collection of retrospective data from the patients’ medical charts at the time of Gla-300 introduction, and at visit 2 (V2) (3–6 months after V1). The primary objective was to assess the change in glycated hemoglobin (HbA1c) level from day of the Gla-300 initiation to the end of the observational period, while the secondary objectives included other effectiveness, as well as safety and other clinically relevant data. Results The mean age of the 350 patients was 63.4 ± 8.4 years and 56.3% were female. The mean duration of diabetes was 13.4 ± 7.4 years, while the mean duration of insulin therapy prior to Gla-300 initiation was 5.3 ± 3.9 years. There was a significant reduction in HbA1c level at each visit compared to the previous visit (8.63 ± 1.52% at baseline prior to Gla-300 initiation, 7.87 ± 1.13% at V1, 7.45 ± 1.05% at V2; p

The outcome of diabetes treatments can and should be evaluated through the patients' treatment satisfaction. The aim of this study was to examine the patients' satisfaction with the therapy with human insulin analogues compared with previous treatment with human insulin. We evaluated patient satisfaction in patients with T1DM in our institution who were currently on IIT with human insulins. We performed testing with standard World Health Organization Diabetes Treatment Satisfaction Questionnaire (WHO DTSQ) before and after the therapy with insulin analogs. The overall DTSQ score in forty-nine patients after the third month of therapy and after the sixth month of therapy is higher than before the initiation of therapy (p < 0.001). The results of the responses on the perception of hyperglycaemia were lower after three months of therapy (p < 0.05) and after the six months of treatment than before the onset of therapy (p < 0.01). There were no differences in the perception of hypoglycaemia after three months; however, perception of hypoglycaemia after the sixth month of treatment was lower than before the onset of therapy (p < 0.001) and compared to the score after the third month of therapy (p < 0.01). Therapy of T1DM patients with insulin analogue aspart over three months led to an increase in satisfaction with therapy and a reduction of the perception of hyperglycaemia. Therapy of T1DM patients with insulin analogues (aspart and glargine) over three months led to an increase in satisfaction with therapy and a reduction of the perception of both hyperglycaemia and hypoglycamia.

Recent literature evidence indicates the potential use of chokeberry preparations in the prevention and treatment of some chronic noncommunicable diseases. The aim of the present study was to evaluate the effects of the three months oral chokeberry juice supplementation in type 2 diabetic patients, as well as its influence on hematological parameters and certain parameters of the renal dysfunction. The study was designed as an open-label trial, which included 35 patients who have received the herbal supplement, polyphenol-rich chokeberry juice (150 ml/day, three times a day for 50 ml), in addition to their standard therapy. Chokeberry juice as a rich source of polyphenol compounds could be an effective preventive and therapeutic agent in diabetes mellitus type 2. Hematological and biochemical parameters were measured at baseline, after 3 months with the chokeberry juice supplementation and after the next 3 months without the chokeberry juice supplementation (follow-up period). Significant difference was noticed in the levels of LDL-cholesterol, glycated hemoglobin and serum creatinine (p < 0.05), as well as in the levels of some hematological parameters, such as white blood cell and lymphocyte count (p < 0.01), hematocrit, blood hemoglobin, mean corpuscular volume, hemoglobin and hemoglobin concentration and red blood cell count (p < 0.05). The daily consumption of the chokeberry juice could improve the health status in patients with type 2 diabetes mellitus, in combination with their standard therapy.

Hyperprolactinaemia in pregnancy leads to mild and reversible changes in the maternal skeletal system, and medicamentous hyperprolactinemia causes more detrimental effects. We conducted an experimental study to evaluate differences between Prlr gene expression in the duodenum, vertebrae and kidneys during physiological and medicamentous hyperprolactinaemia, which could influence calcium homeostasis. Experimental animals (18 weeks old, Wistar female rats) were divided as follows: group P (nine rats that were 3 weeks pregnant), group M (ten rats that were intramuscularly administrated sulpiride (10 mg/kg) twice daily for 3 weeks), and the control group (C, ten age-matched nulliparous rats, 18-week-old). Laboratory investigations included measurements of serum ionized calcium, phosphorus, urinary calcium and phosphorus excretion, osteocalcin (OC), serum procollagen type 1 N-terminal propeptide (P1NP), vitamin D, parathyroid hormone (PTH) and prolactin (PRL). Relative quantification of gene expression for prolactin receptors in the duodenum, vertebrae and kidneys was determined using real-time PCR. Expression of the Prlr gene was significantly higher in the duodenum (p

The aim of the study was to determine the correlation between body mass index (BMI), thyroid stimulating hormone (TSH), and thyroid hormones in euthyroid persons. The study included 396 euthyroid participants. The subjects with already established disease of the thyroid function were excluded. In all subjects we measured weight, height and determined BMI. According to BMI values, the subjects were divided into three groups: group A - BMI up to 24.9 (normal weight); group B - BMI from 25 to 29.9 (overweight); group C - BMI over 30 (obesity). In all subjects we determined serum TSH and free thyroxine (FT4) levels and antibodies to thyroid peroxidase (TPOAb). According to TSH levels, the subjects were divided into two groups: TSH up to 2.5, and TSH higher than 2.5. There is an increase in TSH levels with increasing of BMI. In group C, TSH values were significantly higher than in the groups A and B, and were also higher than the mean values of TSH in all subjects. TSH level in group B were slightly higher compared to the group A but there is no statistically significant difference. TPOAb values increase with increasing of BMI. The mean value of BMI was significantly lower in the group of patients with TSH values lower than 2.5, compared to the mean value of BMI in the group of patients with TSH values higher than 2.5. The relationship of BMI and TSH points to significant positive correlations of two parameters, except in group A. We found a significant degree of positive correlation between BMI and TSH, which remains within the normal range. There are also significant changes in the of TPOAb values. There is no significant changes in the FT4 levels.

Background/Aim. The value of ultrasound in functional disorders can be significant. That is why the question arises on the use of ultrasound examination of thyroid gland and its echogenicity as a screening method in early detection of disfunctions, of the gland primarily subclinical and clinical forms of hypothyreoidism. The objective of this paper was to determine antibodies of thyroid peroxidase (anti-TPO) and thyroglobuline antibodies (anti-TG) increase frequency in relation to the character of ultrasound echogenicity as well as to estimate the frequency of subclinically and clinically obvious hypothyreoidism in relation to the changed echogenicity. Methods. Study included 656 patients in outpatient clinic during 2014. All examinees underwent ultrasound examination of thyroid gland, the blood was taken for determination of free thyroxine (FT4), thyroidstimulating hormone (TSH), anti-TPO and anti-TG. The patients were divided into two groups; the group A with normal echogenicity of thyroid gland tissue, and the group B with decreased echogenicity. The group B was divided into two subgroups, B1 with a mildly decreased and B2 with significantly decreased echogenicity. Results. TPO antibody, TSH and TG antibody positivity and their mean values in the group B were significantly higher, as well as in subgroups B1 and B2, in relation to the group A (p < 0.001). In the group A, only 4 (1%) examinees were indicated with subclinical hypothyreoidism. In the group B, the sublinical hypothyreoidism was indicated in 42, while the clinical hypothyreoidism was indicated in 16 examinees. Fifty-eight (25%) examinees suffered from thyroid gland altered function. In the subgroup B1, 16 examinees were indicated with subclinical and 4 with clinical hypothyreoidism. Twenty (11%) examinees suffered from altered thyroid function. In the group B2, the subclinical hypothyreoidism was found in 26 examinees, while the clinical hypothyreoidism was found in 12. Thirty-eight (76%) examinees suffered from altered thyroid function. Conclusion. The ultrasound screening of thyroid gland plays an important role in early detection of thyroid disfunction, i.e., sublinical and clinical hypothyreoidism. Decreased ultrasound echogenicity represents the significant marker of altered thyroid gland function. In these persons we have determined the high percentage of subclinical and clinical hypothyreoidism frequency.

Primary hypothyroidism can affect lipid metabolism, cardiovascular (CV) function, and overall patients’ quality of life (QoL). Decrease in serum nitric oxide (NO) levels could promote the atherosclerosis acceleration in hypothyroid patients. Our hypothesis is that serum NO level is altered in hypothyroidism; more specifically, we hypothesize that the early vascular changes that can be observed in hypothyroidism could be due to these alterations and that serum NO levels are associated with lipid levels in female patients diagnosed with subclinical hypothyroidism (SCH) or clinical hypothyroidism (CH). Furthermore, since serum NO level is an early marker of atherosclerosis and related CV disorders, which are commonly present and follow hypothyreosis and greatly contribute to overall QoL, we further hypothesized that NO level would correlate with Thyroid Symptom Questionnaire (TSQ) and General Health Questionnaire 12 (GHQ12) scores in hypothyroid patients. A collaterally of our hypothesis was that levothyroxine (LT4) treatment would affect serum NO levels as well as TSQ and GHQ12 scores. Therefore, we have analyzed lipid profile, the level of NO and QoL scores in female patients diagnosed with SCH and CH in order to determine the correlation between NO and generic and thyroid disease symptoms in treatment naïve SCH and CH patients and after LT4 treatment and laboratory euthyroidism achievement. As a consequence of our hypothesis is that measurement of serum NO level in SCH and CH patients may be an innovative way to improve LT4 treatment efficacy. This assumption could have a practical significance for future investigations regarding the management of hypothyroidism treatment protocols in current guidelines. © 2019 Elsevier Ltd

Langerhans cell histiocytosis (LCH) localised in the hypothalamic-pituitary region (HPR) is very rare, especially in adults. Diabetes insipidus (DI) is considered to be a hallmark of HPR LCH, while anterior pituitary abnormalities are usually seen as consequences of surgery, radiotherapy or chemotherapy. We present a patient with localised HPR LCH with dominant anterior pituitary dysfunction and tumour mass effects but without DI. Seven years after surgery and local radiotherapy, she is stable. Control MRI shows no residual tumour growth and thorough physical examination is still without any signs of disease spread. Anterior pituitary deficiency can appear without DI and not only as a consequence of LCH treatment. All patients with LCH should be screened for this endocrine abnormality so that appropriate substitution therapy may be provided.

Background Intensive insulin therapy should be proposed for most type 1 diabetic patients. It can be achieved by a continuous subcutaneous insulin infusion (CSII) or by multiple daily injections (MDI). Debate remains regarding the optimal delivery of such therapy.

Background/Aim. Nipple discharge syndrome is a clinical entity capable of presenting various disorders such is mammary infection (nonpuerperal and puerperal mastitis), intraductal papillomas, fibrodenoma, breast cancer and hyperprolactinemia syndrome. The aim of the study was to determine differencies in cytological features of mammary secretion in patients with hyperprolactinemia and those with normal serum prolactin levels and to define the role of growth hormone, follicle-stimulating hormone, luteinizing hormone and thyroid-stimulating hormone in creating cellular profile of breast secretion. Methods. The study included 50 patients with nipple discharge syndrome. The patients were devided into the clinical group (27 patients with hyperprolactinemia and nipple discharge) and the control group I (23 patients with normal serum prolactin and nipple discharge). The control group II included the patients of the clinical group achiving normalised serum prolactin levels after the treatment of hyperprolactinemia. Serum prolactin, follicle-stimulating hormone and luteinizing hormone levels were assessed by RIA using commercial kits IRMA hPRL, hLH and hFSH, (INEP, Zemun, Serbia) while serum growth hormone and thyroid-stimulating hormone levels were assessed by RIA using commercial kits LKB-wallac. Cytologic evaluation of samples, taken from all the patients with mammary secretion, was done using standard techniques of staining Haemathoxilin-eozine and May- Gr?nwald/Giemsa. Results. Our results showed a significantly higher presence of lipid and protein material in clinical group, in comparison with the control group I (p < 0.01). Also, our data demonstrated significantly higher number of ductal epithelial cells (p < 0.05) and ductal histiocities (p < 0.001) in the clinical group, compared with the control group I. Macrophagies frequency was proportionally higher in clinical group (44.44%) compared the control group I (17.39%). Erythrocites were significantly lower in the clinical group (p < 0.001) than in the control group I. Significantly decreased mammary secretion (p < 0.01), lower lipid (p < 0.01) and protein synthesis (p < 0.01), and less presence of all cellular categories (p < 0.01) were obtained after normalization of serum prolactin levels. Conclusion. Growth hormone, follicle-stimulating hormone, luteinizing hormone and thyroid-stimulating hormone did not show significant influence on creating cytological features of mammary secretion. The most expressive role, hyperprolactinemia demonstrated in the domain of mammary ductal secretory activity, making mammary secretion reach in lipid and protein material and simultaneously increasing number of ductal epithelial cells, ductal histiocytes and 'foam cells'- macrophages. These cytological findings indicate that hyperprolactinemia promote periductal and intraductal steril inflammation which withdraws after serum prolactin normalization.

Objective: In the present study, we compared subtotal thyroidectomy (STT) with total thyroidectomy (TT) in the management of bilateral multinodular goitre. Methods: A total of 204 consecutive patients with bilateral multinodular goitre were assigned to have either TT (n = 73) or STT (n = 131). Demographic details, hospital stay, biochemical findings, indications for operation and complications were noted. Results: There was no significant difference in the age and sex ratio between the two groups (P = 0.695 and P = 0.733). According to thyroid functional status, the majority of patients were euthyroid in both groups (73.28%vs 84.90%). Goitre grades II and III presented the most common indication for STT and TT. Hospital stay for patients who underwent TT was significantly longer compared to STT (P

Background/Aims. Overt hypothyroidism is disease associated with accelerated arteriosclerosis and coronary heart disease. Whether subclinical hypothyroidism (SH) is associated with increased cardiovascular risk is contraversial. As SH is a high prevalence thyroid dysfunction, specially in older women, it is important to evaluate cardiovascular risk factors in these patients and that was the aim of this study. Methods. We examined 30 patients with SH and 20 healthy controls. Subclinical hypothireoidism was defined as an elevated thyrotropin (TSH) (> 4.5 mU/L) and normal free thyroxine (FT4) level. In all the participants we determined body mass index (BMI), blood pressure, TSH, FT4, antibodies to thyroid peroxidase, antibodies to thyroglobulin, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglicerides, total cholesterol/HDL cholesterol ratio and LDL/HDL cholesterol ratio. Results. Mean BMI in patients with SH was significantly higher (p < 0.05), as well as diastolic blood pressure (p < 0.01) compared with the controls. Average levels of total cholesterol (5.40?0.62 vs 5.06?0.19 mmol/l, p < 0.01) and triglycerides (2.16?0.56 vs 1.89?0.24 mmol/l, p < 0.05) were also significantly higher in the group with SH. Individual analysis revealed that the percentage of patients with SH having borderline elevated total cholesterol (63.33%), hypertrigliceridemia (43.33%) and elevated total cholesterol/HDL cholesterol ratio (26.67%) were significantly higher than the percentage in the controls. No significant correlation between TSH and lipid parameters was detected. Conclusion. Subclinical hypothyroidism was associated with higher BMI, diastolic hypertension, higher total cholesterol and triglicerides levels and higher total cholesterol/HDL cholesterols ratio. This might increase the risk of accelerated arteriosclerosis in patients with SH.

Bacground/Aim. Visceral fat is highly active metabolic and endocrine tissue which secretes many adipokines that act both on local and systemic level. It is believed that adipokines and "low-grade inflammatory state" represent a potential link between obesity, metabolic syndrome, insulin resistance and cardiovascular disease. Leptin and adiponectin are considered to be the most important adipokines with the potential metabolic and cardiovascular effects. Body weight loss improves insulin sensitivity and decreases risk for most complications associated with obesity. The aim of this study was to determine the effects of moderate loss of body weight on the level of leptin and adiponectin, insulin sensitivity and abnormalities of glycoregulation in obese women, to determine whether and to what extent the secretory products of adipose tissue, leptin and adiponectin contribute to insulin sensitivity, as well as to assess their relationship and influence on glycemia and insulinemia during the period of losing body weight using a calorie restricted diet. Methods. The study involved 90 obese female subjects (BMI 􀂕 30 kg/m2) of different age with weight loss no less than 5% during a six-month period by application of restricted dietary regime. The calorie range was between 1,100-1,350 kcal. Serum levels of leptin and adiponectin, fasting glucose, fasting insulinemia, and Homeostasis Model Assessment of Insulin Resistance (HOMA-R) index were determined in all the subjects initially and after weight reduction. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test - OGTT. Results. Applying a 6-month restrictive dietary regime the subjects achieved an average weight loss of 8.73 ± 1.98 kg and 8.64 ± 1.96%, which led to the reduction of fasting glycemia, fasting insulinemia and HOMA-R index at the maximum level of statistical significance (p < 0.001). The achieved reduction led to a statistically significant decrease of leptin level and increase of adiponectin level (p < 0.001). The correction of the established pre-diabetic disorders of glycoregulation was not statistically significant. There was a statistically significant correlation between the anthropometric parameters, leptin, adiponectin, fasting glycemia, fasting insulinemia and HOMA-R index. There was a positive correlation between leptin, fasting insulinemia and HOMA-R, as well as a statistically significant negative correlation between adiponectin, fasting insulinemia and HOMA-R index (p < 0.01). Conclusion. Body weight increase and central fat accumulation lead to changes in serum levels of leptin and adiponectin, reduction of insulin sensitivity and development of glycemic dysregulation. Secretory products of adipose tissue, leptin and adiponectin contribute to the genesis of these disorders. The obtained results show that the effect of adiponectin on insulin sensitivity is more significant. The analysis of the effects of weight loss on the investigated parameters shows that moderate weight reduction by restrictive dietary regime lead to changes of investigated parameters at the maximum level of statistical significance. Such results emphasize the importance of weight reduction in obese persons, as well as the need for consistent implementation of restricted dietary regime in the process of treatment of obesity.

Background. Hypoparathyroidism refers to a group of disorders in which extracellular calcium levels cannot be maintained within the normal range due to relative or absolute deficiency of parathyroid hormone (PTH). The clinical features of hypoparathyroidism are consistent with hypocalcaemia and, predominantly, neuromuscular dysfunction. Although hypocalcaemia-induced seizures are well documented hypoparathyroidism-induced epilepsy is often misdiagnosed as idiopathic epilepsy. Case report. We reported a 57-year-old woman with new-onset seizure due to hypoparathyroidism. At first, diagnosis of epilepsy was established and the antiepileptic therapy was initiated with gradual increase of the dose. Computerized tomography scan of the head revealed bilateral basal ganglia and cerebellar calcification and many punctiform calcifications between cortical and subcortical parts. During hospitalization, laboratory tests showed hypocalcemia, hyperphosphatemia and low PTH level. Once the diagnosis of hypoparathyroidism was established, a proper treatment with calcium and vitamin D was started, and the patient was discharged from hospital with full seizure control. Conclusion. Standard evaluation of serum calcium levels in patients with new-onset epileptic seizures should be obligatory part of a diagnostic algoritam to avoid misdiagnosis of idiopathic epilepsy.

Background/Aim. Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. Methods. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IIT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. Results. Fasting blood glucose (FBG) was lower in the glargine group (7.30?0.98 mmol/l) than in the twice daily NPH group (7.47?1.06 mmol/l), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44?0.85 mmol/l; p < 0.05). HbA1c after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72?0.86% to 6.87?0.50%), as well as in the twice daily NPH group (from 7.80?0.83% to 7.01?0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56?2.09) than in both NPH groups (9.0?1.65 in twice daily NPH group and 8.13?1.30 in other NPH group) (episodes/patients-month, p < 0.05). Conclusion. Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbA1c and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.