Comparison of Diet, Metformin and Insulin in the Treatment of Gestational Diabetes Mellitus

Objective: The aim of the study was to compare maternal and neonatal outcomes in patients with gestational diabetes mellitus (GDM) treated with metformin versus those with insulin, or diet alone. Material and methods: The study included 24 GDM women treated with metformin, 21 treated with insulin, and 17 women only on diet. All patients were from Outpatient Department of Endocrinology in the period from May, 2008 to October, 2010. Results: The three groups were comparable with respect to age, pre-pregnancy body mass index (BMI), weight gain during pregnancy, gestational week at enrolment, smoking cigarettes and positive family history for diabetes. Mean glycosylated haemoglobin (HbA1c) at 37 gestation week was lower in diet and metformin groups than insulin group (4,5±0,9, 5,3±0,7, and 6,1± 1,3 %, respectively, p< 0,01). Postprandial glycaemia (PPG) statistically significant differed in diet from metformin group (6,2±2,1 v.s. 7,5±1,1 mmol/L, p< 0,05) and in diet as to insulin group (6,2±2,1 v.s. 8,3±2,3 mmol/L, p< 0,01). There were statistically significant difference in mean gestational age at delivery, between the three (diet, metformin and insulin) groups (39,1±2,2; 38,7±1,6 and 37,3±2,4 gestation week, respectively, p< 0,05). The incidence of neonatal hypoglycemia was higher in the insulin group (52,4%) than in the metformin (33,3%) and diet group (17,6%), but there was statistically difference between insulin and diet group (p=0,04). No differences between the groups were observed in mode of delivery, birth weight, and incidence for large or small for gestational age. Conclusion: Metformin is effective, easy and safe in controlling GDM. Author Keywords: Gestational diabetes mellitus, metformin, insulin, glycaemia

A classification of the torsion tensors on almost contact manifolds with B-metric

The space of the torsion (0,3)-tensors of the linear connections on almost contact manifolds with B-metric is decomposed in 15 orthogonal and invariant subspaces with respect to the action of the structure group. Three known connections, preserving the structure, are characterized regarding this classification.Comment: 17 pages, exposition clarified, references adde

Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder mainly affecting females and is associated with mutations in MECP2, the gene encoding methyl CpG-binding protein 2. Mouse models suggest that recombinant human insulin-like growth factor 1 (IGF-1) (rhIGF1) (mecasermin) may improve many clinical features. We evaluated the safety, tolerability, and pharmacokinetic profiles of IGF-1 in 12 girls with MECP2 mutations (9 with RTT). In addition, we performed a preliminary assessment of efficacy using automated cardiorespiratory measures, EEG, a set of RTT-oriented clinical assessments, and two standardized behavioral questionnaires. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40–120 μg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities

Association of Subclinical hypothyroidism with clinical symptomatology

Introduction: Subclinical hypothyroidism (SCH) often remains undetected because of the absence of clinical symptoms or unspecific symptomatology. The aim of the study was to discover whether SCH is associated with relevant clinical symptomatology. Material and methods: The study included 69 consecutive patients, in whom SCH was detected for the first time (level of serum thyrotropin (TSH) between 4.2-20 mU/l with the reference values of free thyroxine (fT4) 10.3-24.45 pmol/l) and a control group of 30 healthy subjects without goiter and with reference values of fT4 and TSH (0.2-4.2 U/l). All participants completed a previously prepared anamnestic questionnaire and blood was taken for evaluation of TSH and fT4. Results: Patients with SCH unlike the control group presented significantly more often with: fatigue, dry skin, insomnia and menorrhagia (in all cases p<0.05). There was a positive correlation between serum concentrations of TSH and percentage of symptoms of hypothyroidism (r= 0.25, p=0.04). Value of TSH over 7.1mU/l was associated with a significantly larger number of symptoms. Conclusion: SCH is associated with fatigue, dry skin, insomnia and menorrhagia, that justifies initiating thyroid replacement therapy at low values of TSH. Instead of the current recommendations for beginning thyroid replacement therapy when TSH >10mU/l, the cut-off value should be moved to TSH >7,1mU/l

Ehogenicity of thyroid gland on ultrasonography in primary hypothyroidism

Background. The aim of this study was to investigate the association between echogenicity of thyroid gland and low thyroid function. Methods. The study group included 60 patients, with normal and low thyroid function, who visited the Outpatient Department of the Clinic of Endocrinology, Diabetes and Metabolic Disorders in the period from April 2008 to October 2009. Echogenicity of the thyroid gland in all patients was evaluated by ultrasonography as well as serum concentrations of TSH, fT4 and thyroid autoantibody (anti-TPO). To find out the association between thyroid ehogenicity with mean TSH and anti-TPO in different ages, we divided the patients into five subgroups according to age. Results. Patients with decreased echogenicity had a higher mean TSH compared with patients with normal echogenicity (2.77 mIU/l vs. 1.75 mIU/l) (p=0.04). Differences were more significant in patients with markedly decreased echogenicity (6.34 mIU/l vs. 1.75 mIU/l) (p< 0.0001). Patients with reduced echogenicity had a higher risk of having anti-TPO than patients without normal echogenicity (p<0.001). This association was stronger when echogenicity was markedly decreased. According to age, only younger population (19-29 years) with decreeased and markedly decreased echogenicity had significantly higher mean TSH and anti-TPO values. Conclusions. Thyroid ultrasonography changes can be used as an early sign of low thyroid function, especially in younger population

Glycosylated Haemoglobin and Adverse Pregnancy Outcomes in Women with Diabetes Mellitus Type 1 Compared to Pregnancies in the General Population

Aim: to compare pregnancy outcomes in type 1 diabetic pregnancies with the general population and the impact of glycemic control (HbA1c) on pregnancy outcomes. Material and methods: The study group included 55 consecutive pregnant women with type 1 diabetes who attended the Outpatient department of Endocrinology, Diabetes and Metabolic disorders in their first trimester of pregnancy. For comparison, data of 22767 deliveries in 2004 year were used, published in “Perinatal outcomes in Republic of Macedonia for year 2004”. The following parameters were studied: age, maternal body mass index, diabetes duration, planning of pregnancy, HbA1c values in first, second and third trimester, pre-eclampsia, birth weight, gestational age at delivery, mode of delivery, and pregnancy outcomes (spontaneous abortions, perinatal mortality, and major congenital malformations). Results: The perinatal mortality rate was 10,9% and congenital malformation rate was 7,3%, in type 1 diabetic pregnancies compared with 1,1% and 1,9%, respectively in the general population. Macrocosmic babies were born in 9,1% of type 1 diabetic pregnancies compared with 1,01% in the general population. The caesarean section rate was 61,8% and 16,1%, respectively, and the preterm delivery rate was 25,5% and 6,1%, respectively. Pregnancies with serious adverse outcomes (spontaneous abortion, perinatal mortality and congenital malformations) were characterized by higher Values of HbA1c in the first trimester of diabetes type 1 pregnancies Conclusion: Type 1 diabetic pregnancies have worse outcomes then general population. Planning of pregnancy and rigorous glycaemic control using glucose monitoring before and during early pregnancy are crucial for better pregnancy outcomes. Key words: pregnancy outcomes, diabetes mellitus type 1, glycated haemoglobin, congenital malformations

Gestational Diabetes Mellitus – The Impact оf Maternal Body Mass Index аnd Glycaemic Control оn Baby’s Birth Weight

Abstract: Objectives. To asses the influence of the maternal BMI and glycaemic control in women with GDM on the baby's birth weight (BW). Material and methods: We analysed 180 women with GDM. Macrosomia has been defined as BW > 4000 gm, small for gestational age < 2700 gm and appropriate for gestational age between both. According to the baby´s BW the pregnant women were divided into three groups: group 1 (G1) with BW < 2700 gm (n = 26); group 2 (G2) with BW between 2700 to 4000 gm (n = 117), and group 3 (G3) with BW > 4000 gm (n = 37). We also analysed BMI (kg/m²), HbA1c (%), PPG (mmol/L) and time of delivery (WG). Results: Comparisons between G1 and G2 showed: BMI (30.7 ± 5 & 31 ± 5.2; p < 0.7), HbA1c (6.4 ± 0.8 & 5.1 ± 0.8, p < 0.002), PPG (8.2 ± 1.7 & 6.9 ± 1.5, p < 0.02), time of delivery (35.2 ± 3.8 & 38.6 ± 1.5, p < 0.0001) and BW (2289 ± 504 & 3474 ± 334, p < 0.0001). Comparisons between G2 and G3 showed: BMI (31 ± 5. 2 & 33.4 ± 6.1; p < 0.02), HbA1c (5.2 ± 1.1 & 6.4 ± 2.3, p < 0.02), PPG (6.9 ± 1.5 & 8.2 ± 1.9, p < 0.02), time of delivery (38.6 ± 1.5 & 39.3 ± 1.4, p < 0.01) and BW (3474 ± 334 & 4431 ± 302, p < 0.0001). Comparisons between G1 and G3 showed the difference at delivery time and the baby's BW (p < 0.0001). Conclusions: Maternal obesity and PPG contribute to macrosomia and also PPG to SGE. Key words: gestational diabetes, large for gestational age, small for gestational age, birth weight, postprandial glycaemia

Maternal 75 g OGTT glucose levels as predictive factors for large-for-gestational age newborns in women with gestational diabetes mellitus

Objective: Our goal was to investigate the effects of glucose levels from 75-g oral glucose tolerance test (OGTT) on large for gestational age (LGA) newborns in women with gestational diabetes mellitus (GDM). Material and methods: A prospective study was undertaken in Outpatient Department of Clinics for Endocrinology, Diabetes and Metabolic Disorders. One hundred and eighteen pregnant women were prospectively screened for GDM between 24 and 28 weeks of pregnancy. Results: From 118 pregnancies, 78 (66.1%) women were with GDM, and 40 (33.9%) without GDM. Twenty-one (30.4%) of the neonates in the GDM group were LGA (adjusted weight at or above the 90th percentile). This proportion significantly differ from the proportion (5.5%) for the control group (P<0.01). There were significant correlations between LGA from GDM pregnancies with fasting, and 1-h OGTT plasma glucose levels (r=0.46 and 0.23 respectively, P<0.05). Gestation week of delivery and fasting glucose levels were independent predictors for LGA (β=0.58 and β=0.37 respectively, P<0.001). Areas under the receiver operator characteristic curve (AUC) were compared for the prediction of LGA. The AUC were: 0.782 (0.685–0.861) for fasting, 0.719 (0.607–0.815) for 1-h, and 0.51 (0.392–0.626) for 2-h OGTT plasma glucose levels. Conclusion: Fasting and 1-h plasma glucose levels from OGTT may predict LGA babies in GDM pregnancies. Key Words: gestational diabetes, oral glucose tolerance test (OGTT), large for gestational age