Milica Pesic

Monotherapy with metformin: does it improve hypoxia in type 2 diabetic patients?

Abstract Metformin reduces blood glucose levels predominantly by inhibiting hepatic gluconeogenesis, although it also may enhance insulin receptor number or activity. The full effects of metformin are still poorly understood. In this study the effects of metformin on plasma xanthine oxidase (XO) activity, thiobarbituric acid-reactive substance (TBARS), lactate and fructosamine concentration as well as erythrocyte antioxidant enzyme activities were investigated in 46 patients with type 2 diabetes mellitus. All parameters were measured simultaneously just before metformin therapy (T0), 1 month (T1) and 2 months (T2) later. Results were compared with placebo and control group. We noted significant decrease in XO activity and in TBARS concentration (p<0.001) during monotherapy with metformin vs. placebo and T0 group. A significant correlation was observed between the activity of XO and the concentration of fructosamine (p<0.001). Erythrocyte glutathione peroxidase showed significantly lower activity in T2 group in comparison with T0 group (p<0.01). It is known that diabetic patients produce more TBARS as a result of enhanced free radical generation the source of which may also be the large amounts of XO produced following the conversion of xanthine dehydrogenase in hypoxic diabetic tissues. Thus, our results indirectly suggest that metformin can reduce toxic tissue damage through the inhibition on XO activity.

Susceptibility to oxidative stress, insulin resistance, and insulin secretory response in the development of diabetes from obesity.

BACKGROUND/AIM [corrected] Oxidative stress plays a critical role in the pathogenesis of various diseases. Recent reports indicate that obesity may induce systemic oxidative stress. The aim of the study was to potentiate oxidative stress as a factor which may aggravate peripheral insulin sensitivity and insulinsecretory response in obesity in this way to potentiate development of diabetes. The aim of the study was also to establish whether insulin-secretory response after glucagonstimulated insulin secretion is susceptible to prooxidant/antioxidant homeostasis status, as well as to determine the extent of these changes. METHODS A mathematical model of glucose/insulin interactions and C-peptide was used to indicate the degree of insulin resistance and to assess their possible relationship with altered antioxidant/prooxidant homeostasis. The study included 24 obese healthy and 16 obese newly diagnozed non-insulin dependent diabetic patients (NIDDM) as well as 20 control healthy subjects, matched in age. RESULTS Total plasma antioxidative capacity, erythrocyte and plasma reduced glutathione level were significantly decreased in obese diabetic patients, but also in obese healthy subjects, compared to the values in controls. The plasma lipid peroxidation products and protein carbonyl groups were significantly higher in obese diabetics, more than in obese healthy subjects, compared to the control healthy subjects. The increase of erythrocyte lipid peroxidation at basal state was shown to be more pronounced in obese daibetics, but the apparent difference was obtained in both the obese healthy subjects and obese diabetics, compared to the control values, after exposing of erythrocytes to oxidative stress induced by H2O2. Positive correlation was found between the malondialdehyde (MDA) level and index of insulin sensitivity (FIRI). CONCLUSION Increased oxidative stress together with the decreased antioxidative defence seems to contribute to decreased insulin sensitivity and impaired insulin secretory response in obese diabetics, and may be hypothesized to favour the development of diabetes during obesity.

Hepatitis C virus genotypes and the development of hepatocellular carcinoma.

OBJECTIVE:  The aim of this study was to investigate the prevalence of hepatitis C virus (HCV) infection in patients with hepatocellular carcinoma (HCC) in our geographic area, and to determine if there is a correlation between HCV genotypes and the development of HCC.

Subclinical hypothyroidism: association with cardiovascular risk factors and components of metabolic syndrome

The aim of this cross-sectional study was to evaluate the cardiovascular risk in patients with subclinical hypothyroidism (SH) and metabolic syndrome (MetS) components. The study included 60 patients with SH and a control group of 60 healthy volunteers, gender and age matched, with normal thyroid-stimulating hormone (TSH) and free thyroxin (FT4) concentration. The following measurements were made in all participants: TSH, FT4, thyroid peroxidase antibodies, anti-thyroglobulin antibodies, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose, total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), TC/HDL cholesterol and LDL/HDL cholesterol ratio, basal insulin level and homeostatic model assessment insulin resistance (HOMA-IR) index. MetS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The results showed that the following indices were statistically significantly higher in the SH group: BMI (p < 0.05), diastolic blood pressure (p < 0.001), TC (p < 0.05), TG (p < 0.05) and basal insulin level (p < 0.05). Although MetS parameters were present in a higher per cent in the SH group, there was a significantly higher number of patients with hypertension and decreased HDL cholesterol (p < 0.05). More frequently, MetS was diagnosed in SH patients (46.67%) than in the control group (33.33%), although the difference was not statistically significant. These results indicated that the traditional cardiovascular risk factors were more frequently present in SH patients as compared to euthyroid participants. Our results did not confirm significantly higher presence of MetS in SH patients in comparison with euthyroid respondents.

C-reactive protein and chitinase 3-like protein 1 as biomarkers of spatial redistribution of retinal blood vessels on digital retinal photography in patients with diabetic retinopathy

The aim of the study was to investigate the correlation between the levels of C-reactive protein (CRP) and chitinase 3-like protein 1 (YKL-40) in blood samples with morpohometric parameters of retinal blood vessels in patients with diabetic retinopathy. Blood laboratory examination of 90 patients included the measurement of glycemia, HbA1C, total cholesterol, LDL-C, HDL-C, triglycerides and CRP. Levels of YKL-40 were detected and measured in serum by ELISA (Micro VueYKL-40 EIA Kit, Quidel Corporation, San Diego, USA). YKL-40 correlated positively with diameter and negatively with number of retinal blood vessels. The average number of the blood vessels per retinal zone was significantly higher in the group of patients with mild non-proliferative diabetic retinopathy than in the group with severe form in the optic disc and all five retinal zones. The average outer diameter of the evaluated retinal zones and optic disc vessels was significantly higher in the group with severe compared to the group with mild diabetic retinopathy. Morphological analysis of the retinal vessels on digital fundus photography and correlation with YKL-40 may be valuable for the follow-up of diabetic retinopathy.

Optimal surgical treatment for bilateral multinodular goitre

Objective:  In the present study, we compared subtotal thyroidectomy (STT) with total thyroidectomy (TT) in the management of bilateral multinodular goitre.

Localised Langerhans cell histiocytosis of the hypothalamic-pituitary region: case report and literature review

IntroductionLangerhans 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.Case descriptionWe 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.ConclusionsAnterior 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.

Expression of prolactin receptors in the duodenum, kidneys and skeletal system during physiological and sulpiride-induced hyperprolactinaemia

Introduction and aimHyperprolactinaemia 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.MethodsExperimental 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.ResultsExpression of the Prlr gene was significantly higher in the duodenum (p < 0.001) and lower in vertebrae (p < 0.001) and kidneys (p < 0.01) in rats with physiological hyperprolactinaemia (PHP) than in the control group. Significantly lower Prlr expression in the duodenum was verified (p < 0.001), along with increased Prlr gene expression in vertebrae (p < 0.001) and kidneys (p < 0.01), in rats with medicamentous hyperprolactinaemia (MHP) than in the C group.ConclusionsDownregulation of Prlr gene expression in the duodenum may explain the diminished intestinal calcium absorption in medicamentous hyperprolactinaemia. Prolactin takes calcium from the skeletal system following increased Prlr gene expression in the vertebrae to maintain calcium homeostasis, which increases the harmful effect on bone metabolism compared to that of physiological hyperprolactinaemia.

Decreased ultrasound echogenicity as a thyroid hypofunction marker and correlation with autoantibody 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.

Epileptic seizure as the first sign of hypoparathyroidism

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.