ACTA ENDOCRINOLOGICA (BUC)

Background. Metformin is the first-line oral antidiabetic agent used in the treatment of diabetes mellitus. One of the adverse reactions of the long term use of metformin is cobalamin malabsorption. Clinical and laboratory findings are important in the diagnosis of cobalamin deficiency. Objective. This study aimed to evaluate the risk of cobalamin deficiency symptoms related to long-term use of metformin in type 2 diabetes mellitus patients at Pasar Rebo General Hospital in Jakarta. Setting. This quantitative, observational study with retrospective cohort design was conducted in outpatient department Pasar Rebo General Hospital November 2015 until January 2016. Methods. 200 subjects were recruited and divided into two groups, patients who had been taking metformin for 1-3 years and patients who had been taking metformin for more than 3 years. Each patient was assessed for the presence of cobalamin deficiency symptoms. Main outcome measure. Cobalamin deficiency symptoms evaluated were symptoms of neuropathy (measured by DN4 questionnaire) and hematologic abnormalities associated to cobalamin deficiency, i.e. macrocytic erythrocyte, hypersegmented neutrophils, and giant bands. Results. There are significant differences in the proportions of neuropathy symptoms (RR 2.36, 95%, p=0.000) and hematologic abnormalities (RR 1.5, 95%, p=0.007) between the two groups. Conclusions. Long-term use of metformin (≥3 years) may increase the risk of cobalamin deficiency symptoms in type 2 diabetes mellitus patients.

sitive period in terms of thyroid hypofunction. Iron deficiency has been associated with both thyroid function and thyroid autoimmunity. Objective. We aimed to investigate whether iron deficiency is a risk factor for thyroid autoimmunity in nonpregnant women at childbearing age. Design. This cross- sectional study was conducted in non-pregnant women who presented to the Internal Medicine Policlinic between January 2018 and December 2018 in the University of Health Sciences “Fatih Sultan Mehmet” Training and Research Hospital. Methods. Three hundred fifty-eight non-pregnant women of reproductive ages (203 iron deficient-ID, 155 control) participated in this study. Women with known thyroid disease, currently undergoing treatment for thyroid disease or whose thyroid function tests were outside the reference range were excluded from the study. Blood sample was taken after at least 8-10 hours of fasting for measurement of serum iron (Fe), total iron binding capacity (TIBC), serum ferritin (SF), whole blood count, thyroid function tests (fT4, TSH), anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibody (TgAb). The patients with SF levels ≤ 15 ng/dL were accepted as iron deficiency. Results. The group with ID had higher TSH and lower T4 values that did not reach statistical significance compared to the control group (p=0.101 and p=0.098, respectively). Antibody positivity was more frequent in the ID group than in the control group (35.96% vs. 20.65%, p = 0.002). Conclusions. Iron deficiency is associated with thyroid autoimmunity and it should be considered as a risk factor for screening thyroid antibody, particularly in pregnancy planning women.

Background. Patients with type 2 diabetes mellitus (T2DM) have a higher risk of developing obstructive sleep apnea (OSA) compared to the general population. Our study aims to analyze the usefulness of the STOP-BANG score, tool which was not yet validated in patients with diabetets, as a tool that estimates the severity of OSA, in patients with T2DM. Methods. 120 patients, who answered the STOPBANG questionnaire and underwent polysomnography, were included in the study. The patients were divided into 3 groups, depending on the severity of OSA, defined by the apnea/hypopnea index (AHI). Results. A significant percentage of participants (42.1%) had a severe form of OSA (AHI ≥30) and a high percentage of subjects had a STOP-BANG score ≥5 (58.7%), equivalent to a severe form of the disease. The STOP-BANG score increased proportionally with AHI (p<0.001). The area under the ROC curve for the STOP-Bang score indicated an optimal cut-off value of 4.5, with a sensitivity of 88.2% and a specificity of 62.9% (p <0.001), STOP-BANG score ≥5 being an independent predictor for severe OSA in patients with T2DM. Conclusions. The STOP-BANG score can be used in patients with diabetes to detect severe OSA in order to establish appropriate therapeutic measures.

Background. We know that mortality had increased in diabetic patients with COVID-19 pneumonia. The aim of this study was to compare the mortality and inflammation parameters difference in critically ill COVID-19 patients according to their admission HbA1c levels and diabetes mellitus status. Secondary aim was to evaluate the effect of the first week hyperglycemic episode frequency on mortality. Methods. Critically ill COVID-19 patients who were tested for HbA1c levels on ICU admission were analyzed retrospectively. Results. Of 218 COVID PCR(+) patients, 139 met the inclusion criteria in study period. The median age was 67[57-76] years and 55(40%) of them were female. Seventy-six (55%) of the patients required invasive mechanical ventilation (IMV). The IMV requirement was higher in diabetic patients (p=0.01). When the groups were compared in terms of inflammatory parameters no significant difference was found except for admission and first week’s highest fibrinogen levels (p=0.02 and p=0.03, respectively). In multivariate analysis, fibrinogen levels were not determined as a risk factor for mortality. Overall ICU mortality was 43% (60/139). In group-1 23(37%), in group-2 27(57%), and in group-3 10(34%) patients had died. There was no statistically significant difference between groups in terms of mortality (p=0.05). Records of 96(69%) patients revealed there were more than five glucose readings over 180mg/dL during the first week. Mortality was higher in patients with more frequently hyperglycemic recordings (p=0.03). Conclusions. There was no significant mortality and inflammatory parameters difference in patients with and without diabetes. However, more than five glucose readings over 180mg/dL during the first week were found with increased mortality.

Context. Type 2 diabetes is a chronic metabolic disease which affects bone. There is evidence in the literature about some serum markers that reflect the bone turnover metabolism, such as RANKL (Receptor Activator of Nuclear factor Kappa-b Ligand) and Fibroblast Growth Factor (FGF) 23. Objective. We aimed to investigate the correlations between RANKL and FGF23 and other diabetes-related factors possibly influencing early bone turnover changes. Subjects and Method. We conducted a crosssectional analytical study on a group of 171 patients with type 2 diabetes, without Charcot’s arthropathy or a history of amputations, in which a complete history and anthropometric, clinical, biochemical and dietary evaluation were performed. We evaluated the serum level of RANKL and FGF 23. Results. RANKL was significantly lower in patients with macroangiopathy (0.42±0.15 pmol/L vs. 0.47±0.2 pmol/L, p=0.001). The level of FGF23 was lower in patients with neuropathy (0.37±0.36 pmol/L vs. 0.41±0.17 pmol/L, p=0.001). We found that FGF23 increased with age, but decreased with the duration of diabetes. We also found an inverse relationship between FGF23 levels and HbA1c, triglycerides, diastolic blood pressure, total proteins, albuminemia. Conclusions. RANKL was significantly lower in patients with macroangiopathy, and FGF 23 in patients with neuropathy. Therefore, more studies are needed to elucidate their role in early bone turnover changes.

Objectives. It was aimed to evaluate the relationship of Dehydroepiandrosterone-sulphate(DHEAS) level with pregnancy, fertility, abortion, ovarian reserve and endothelial functions. Patients and Method. Ninety-six fertile women aged 20-35 years whose DHEAS levels were measured and 28 women aged 40-55 years with oligomenorrheaamenorrhea were included in the study.The DHEAS values of the patients,which were measured at least 12 months apart,were recorded. Results. The first measured mean DHEAS level was 208.34±119.7ug/dL and the last measured mean DHEAS level was 187.5±101.7ug/dL. Among 28 patients with oligomenorrhea-amenorrhea, the levels of DHEAS increased in 10 patients and decreased in 18 patients. Although the annual decrease in DHEAS levels was greater in those who had pregnancy than in those who had not given birth, the difference was not statistically significant (p=0.085). Although the initial DHEAS level in 5 patients who had an abortion was higher than in those who did not have an abortion, the difference was not statistically significant (p=0.427). The increase in systolic blood pressure was statistically significant in patients with decreased DHEAS levels (p=0.03). While the mean DHEAS level was 85.3±47.3ug/dL in menopausal patients, the DHEAS level was 82.1±49.2ug/dL in non-menopausal patients (p=0.435). Conclusion. The age at which the DHEAS level reaches its peak level shows individual differences. While pregnancy slows down the decrease in DHEAS levels,abortion accelerates the decrease in DHEAS levels. A decrease in serum DHEAS levels can increase systolic blood pressure.

Context. Cardiomyopathy is the most frequent cardiovascular complication in acromegaly. Objective. We aimed to compare some echocardiographic markers in acromegaly patients with controls and find a correlation with disease duration, disease activity, levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Design. We conducted a cross-sectional casecontrol study for the period of 2008-2012. Subjects and methods. Acromegaly patients altogether 146 (56 men and 90 women), were divided into four groups according to disease activity and the presence of arterial hypertension (AH). The control group included 83 subjects, matching the patient groups by age, gender and presence of AH. GH was measured by an immunofluorometric method, while IGF-1 by IRMA method. All patients and controls were subjected to one- and two-dimensional transthoracic echocardiography, color and pulse Doppler. Results. We found a thickening of the left ventricular walls and an increase in the left ventricular mass. However, these changes were not statistically significant in all groups and no correlation with disease duration could be demonstrated. As markers of diastolic dysfunction, increased deceleration time and isovolumetric relaxation were registered, which were dependent mainly on age in a binary logistic regression analysis, but not GH or IGF-1. Using absolute values, ejection and shortening fractions were increased in some groups. Using cut-off values, a higher percentage of systolic dysfunction was demonstrated in patients compared to their corresponding controls. Engagement of the right heart ventricle was also found – increased deceleration time and decreased e/a tric ratio. Conclusions. In conclusion, functional impairments of both ventricles were present, with a predominance of left ventricular diastolic dysfunction.

Introduction. Salusins are multifunctional endogenous peptides shown in human and rat tissues. Serum salusin α level is decreased in coronary artery disease and lack of salusin α enhances coronary atherosclerosis. Hypothyroidism is a chronic inflammatory disease that has a high risk of developing cardiovascular disease. Here we aimed to search the relationship of overt hypothyroidism and subclinical hypothyroidism with salusin α and other inflammatory markers, also the effect of L-thyroxine treatment on these findings. Material and Methods. 32 patients with overt hypothyroidism taking L-thyroxine treatment, 18 patients with subclinical hypothyroidism without treatment and 25 healthy patients as control group were included in the study. Serum salusin α, TNF α, sCRP, glucose, insulin and lipid levels were tested for all groups and results were evaluated with SPSS statistical analysis method. Results. HDL, sCRP, salusin mean values were statistically significantly different in all 3 groups. HDL level was statistically significantly higher in control group compared to treatment group. sCRP level was higher and salusin level was lower in both treatment and non-treatment hypothyroidism groups compared to control group. When treatment and non-treatment hypothyroidism groups were compared, there was no statistically significant difference for salusin α, but HDL level was high and insulin level was low statistically significant in treatment group. Conclusions. Salusin α that is shown to be protective for coronary artery disease and hypertension, is found to be significantly low in hypothyroidism, thus it is a marker that increases the cardiovascular disease risk in this specific patient group.

Context: Vitamin D deficiency is extremely prevalent in nursing home residents and could be a risk factor for metabolic syndrome. Objective: To examine the association of serum vitamin D level with metabolic syndrome (MetS) in nursing home residents. Design: This was a case-control study. Subjects and Methods: We have investigated the status of vitamin D by measuring serum 25-hydroxyvitamin D (25OHD) concentrations in 45 older adults (28 women and 17 men, aged 58-89 years) living in a nursing-home in Iasi, Romania. Their vitamins D status (25-hydroxyvitamin D), C-reactive protein, fasting blood glucose, insulin, triglicerides, total and HDL cholesterol were assessed using venous blood. Systolic and diastolic blood pressure, weight, height and waist circumference were measured following standard protocols. Data was analysed using t-test, chi-square test, General Linear Model and multiple logistic regression. Results: In our study 56% of nursing home residents have serum 25(OH)D less than 30 nmol/l (vitamin D deficiency). Considering NCEP-ATP III criteria, the overall prevalence of the MetS in participants of this study was 35.5%. In the multivariate model (adjusted for sex, fasting serum glycemia, and triglycerides), vitamin D deficiency was significantly associated with being female (OR: 1.49; 95% CI: 0.38-5.73), abdominal obesity (OR: 1.34; 95% CI: 0.39-4.7), high systolic blood pressure (OR: 6.83; 95% CI: 1.09-42.9), low HDL-cholesterol (OR: 3.82; 95% CI: 0.55-26.6), and MetS (OR: 1.73; 95% CI: 0.27-10.8). Conclusions. This study highlights the high prevalence of vitamin D deficiency among nursing home residents and its association with multiple risk factors for metabolic syndrome.

Objective. To evaluate obstetric and neonatal outcomes of patients with type 1 diabetes mellitus (T1DM) and compare multidose injection (MDI) and continuous subcutaneous insulin infusion (CSII). Study Design. Retrospective study of 53 pregnant patients with T1DM reaching at least 24th gestational week. Results. Fourteen patients (26.4%) hospitalized for insulin dose regulation. Ten patients had hypertensive diseases. Perinatal mortality occurred in 2 neonates owing to cardiac malformations. Neonatal hypoglycemia, small for gestational age, large for gestational age, and neonatal jaundice were demonstrated in 8, 4, 12 and 19 newborns, respectively. Sixteen newborns were admitted to the NICU for various reasons. Congenital malformations were detected in 7 newborns (6 cardiovascular and 1 central nervous system anomaly). Despite lack of statistical significance, total daily insulin doses were higher in the MDI group than in the CSII group with doses of 62 IU (18–166) and 51 IU (20–114), respectively (p=0.119). Gestational and perinatal outcomes also showed no statistical significance. However, all congenital abnormalities and perinatal deaths occurred in the MDI group. Conclusion. T1DM in pregnancy is a challenging problem in terms of having better obstetric and perinatal results. CSII may be used safely instead of MDI in appropriate patients.