A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.

OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.

Antibiotic prophylaxis for clean neck surgery.

The frequency of surgical site infections (SSIs) after clean neck surgery is low and antibiotic prophylaxis is not recommended. This retrospective study investigated the effect of perioperative prophylactic antimicrobial therapy on the development of infections. A total of 807 consecutive patients undergoing clean neck surgery were included in the study. Antimicrobial prophylaxis with intravenous cefuroxime was administered in 518 cases. Although patients who received prophylaxis had a lower rate of SSIs than those who did not receive antibiotics, this was not statistically significant (0.4% vs 1.4% respectively, p=0.19). Older age was the only variable associated with the development of SSIs (p=0.014).

Effect of Advanced Glycation End Products on Human Thyroglobulin's Antigenicity as Identified by the Use of Sera from Patients with Hashimoto's Thyroiditis and Gestational Diabetes Mellitus.

Advanced glycation end products (AGEs) are formed on proteins after exposure to high concentrations of glucose and modify protein's immunogenicity. Herein, we investigated whether the modification of thyroglobulin (Tg) by AGEs influences its antigenicity and immunogenicity. Human Tg was incubated in vitro with increasing concentrations of D-glucose-6-phosphate in order to produce Tgs with different AGE content (AGE-Tg). Native Tg and AGE-Tgs were used in ELISA to assess the serum antibody reactivity of two patient groups, pregnant women with gestational diabetes (GDM), and patients with Hashimoto's thyroiditis (HT). We produced in vitro AGE-Tg with low and high AGE content, 13 and 49 AGE units/mg Tg, respectively. All HT patients' sera presented the same antibody reactivity profile against native Tg and AGE-Tgs, indicating that the modification of Tg by AGEs did not alter its antigenicity. Similarly, the GDM patients' sera did not discriminate among the two forms of Tg, native or artificially glycated, suggesting that the modification of Tg by AGEs might not alter its immunogenicity. The modification of Tg by AGEs has no obvious effect on neither its antigenicity nor, most likely, its immunogenicity. It seems that other Tg modifications might account for the production of aTgAbs in patients with GDM.

Genetic screening of patients with medullary thyroid cancer in a referral center in Greece during the past two decades.

OBJECTIVE: Mutations in the RET gene are responsible for hereditary medullary thyroid cancer (MTC) and may vary between ethnic groups. We report the spectrum of mutations detected in patients with MTC in a referral center in Greece. PATIENTS AND METHODS: Screening for RET mutations was performed in 313 subjects from 188 unrelated families: 51 patients had clinical suspicion for familial disease, 133 were apparently sporadic, four patients had only C cell hyperplasia, and 125 were family members. Exons 8, 10, 11, and 13-16 were screened. RESULTS: A total of 58 individuals (30.85%) were RET mutations carriers, 120 (63.8%) were finally classified as sporadic, 13 apparently sporadic cases (9.8%) were identified with RET mutation: ten carried the exon 8 at codon 533 mutation (previously reported), two the exon 14 at codon 804 mutation, and one the exon 13 at codon 768 mutation. Six patients (3.19%) with clinical features of multiple endocrine neoplasia type 2A and negative for RET mutations were classified as 'unknown cause'. The mutations of hereditary cases were as follows: 21 cases (36.2%) in exon 8 codon 533, 19 (32.8%) in exon 11 codon 634, nine (15.5%) in exon 10, five (8.6%) in exon 16, three (5.2%) in exon 14 codon 804, and one in exon 13 codon 768 (1.7%). CONCLUSION: The spectrum of RET mutations in Greece differs from that in other populations and the prevalence of familial cases is higher. The exon 8 (Gly533Cys) mutation was the most prevalent in familial cases unlike other series, followed by exon 11 (codon 634) mutations which are the most frequent elsewhere. The wide application of genetic screening in MTC reveals new molecular defects and helps to characterize the spectrum of mutations in each ethnic group.

Recycled sand in lime-based mortars.

The increasing awareness of the society about safe guarding heritage buildings and at the same time protecting the environment promotes strategies of combining principles of restoration with environmentally friendly materials and techniques. Along these lines, an experimental program was carried out in order to investigate the possibility of producing repair, lime-based mortars used in historic buildings incorporating secondary materials. The alternative material tested was recycled fine aggregates originating from mixed construction and demolition waste. Extensive tests on the raw materials have been performed and mortar mixtures were produced using different binding systems with natural, standard and recycled sand in order to compare their mechanical, physical and microstructure properties. The study reveals the improved behavior of lime mortars, even at early ages, due to the reaction of lime with the Al and Si constituents of the fine recycled sand. The role of the recycled sand was more beneficial in lime mortars rather than the lime-pozzolan or lime-pozzolan-cement mortars as a decrease in their performance was recorded in the latter cases due to the mortars' structure.

Relation of the Mediterranean diet with the incidence of gestational diabetes.

BACKGROUND/OBJECTIVES: Some studies document relationships of the incidence of gestational diabetes mellitus (GDM) with individual components of the diet, but studies exploring relationships with patterns of eating are lacking. This observational study aimed to explore a possible relationship between the incidence of GDM and the Mediterranean diet (MedDiet) pattern of eating. SUBJECTS/METHODS: In 10 Mediterranean countries, 1076 consecutive pregnant women underwent a 75-g OGTT at the 24th-32nd week of gestation, interpreted both by the ADA_2010 and the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)_2012 criteria. The dietary habits were assessed by a previously validated questionnaire and a Mediterranean Diet Index (MDI) was computed, reflecting the degree of adherence to the MedDiet pattern of eating: a higher MDI denoting better adherence. RESULTS: After adjustment for age, BMI, diabetes in the family, weight gain and energy intake, subjects with GDM, by either criterion, had lower MDI (ADA_2010, 5.8 vs 6.3, P=0.028; IADPSG_2012, 5.9 vs 6.4, P<0.001). Moreover, the incidence of GDM was lower in subjects with better adherence to the MedDiet (higher tertile of MDI distribution), 8.0% vs 12.3%, OR=0.618, P=0.030 by ADA_2010 and 24.3% vs 32.8%, OR=0.655, P=0.004 by IADPSG_2012 criteria. In subjects without GDM, MDI was negatively correlated with both fasting plasma glucose and AUC glucose, P<0.001 for both. CONCLUSIONS: Adherence to a MedDiet pattern of eating is associated with lower incidence of GDM and better degree of glucose tolerance, even in women without GDM. The possibility to use MedDiet for the prevention of GDM deserves further testing with intervention studies.

High prevalence of exon 8 G533C mutation in apparently sporadic medullary thyroid carcinoma in Greece.

OBJECTIVE: Genetic screening for ret mutation has become routine practice in the evaluation of medullary thyroid carcinoma (MTC). Approximately 25% of these tumours are familial, and they occur as components of the multiple endocrine neoplasia type 2 syndromes (MEN 2A and 2B) or familial MTC. In familial cases, the majority of mutations are found in exons 10, 11, 13, 14 or 15 of the ret gene. A rare mutation involving exon 8 (G533C) has recently been reported in familial cases of MTC in Brazil and Greece; some of these cases were originally thought to be sporadic. The aim of this study was to re-evaluate a series of sporadic cases of MTC, with negative family history, and screen them for germline mutations in exon 8. DESIGN AND PATIENTS: Genomic DNA was extracted from peripheral lymphocytes in 129 unrelated individuals who had previously been characterized as 'sporadic' based on the negative family history and negative screening for ret gene mutations. Samples were analysed in Applied Biosystems 7500 real-time PCR and confirmed by sequencing. MEASUREMENTS AND RESULTS: The G533C exon 8 mutation was identified in 10 of 129 patients with sporadic MTC. Asymptomatic gene carriers were subsequently identified in other family members. CONCLUSION: In our study, we found that 7·75% patients with apparently sporadic MTC do carry G533C mutation involving exon 8 of ret. We feel that there is now a need to include exon 8 mutation screening in all patients diagnosed as sporadic MTC, in Greece.

Visfatin, TNF-alpha and IL-6 mRNA expression is increased in mononuclear cells from type 2 diabetic women.

Visfatin, is a new adipokine, highly expressed in the visceral fat of both mice and humans. To examine whether visfatin is expressed in human peripheral monocyte-enriched mononuclear cells and whether its expression is altered in type 2 diabetes (DM2), we compared 24 DM2 women [17 overweight (BMI >25) and 7 lean (BMI<25)] to 26 healthy women (14 overweight and 12 lean), all premenopausal. Relative visfatin mRNA levels were significantly higher (approximately 3-fold) in DM2 compared to healthy control women (p<0.02), independently of the presence of overweight/obesity. Mononuclear TNF-alpha and IL-6 mRNA expression was also elevated in DM2 compared to control women (p=0.001 and p=0.004, respectively), an increase observed in both lean and overweight DM2 women. By contrast, circulating visfatin, TNF-alpha, and IL-6 levels showed no difference between DM2 and control women, while adiponectin plasma levels were significantly decreased in the DM2 women (p<0.001). Circulating visfatin and TNF-alpha levels did not differ either between the lean and the overweight subgroups of DM2 and control women, while IL-6 plasma levels were significantly higher in both overweight subgroups compared to their lean counterparts. In conclusion, visfatin, TNF-alpha, and IL-6 mRNA expressions are increased in peripheral mononuclear-monocytic cells from women with type 2 diabetes, independent of their BMI, which may enhance the effects of their adipose-derived levels and may contribute to the increased insulin resistance and atherogenic risk of these patients.

Arterial stiffness in type 1 diabetes mellitus is aggravated by autoimmune thyroid disease.

OBJECTIVE: The aim of our study was to measure arterial stiffness in patients with Type 1 diabetes mellitus, its contributing factors and its relation to macrovascular arterial changes. MATERIALS AND METHODS: Thirty-one female Type 1 diabetic patients were studied; 11 had concomitant autoimmune thyroid disease although euthyroid during the study period. Stiffness was studied using applanation tonometry and pulse wave analysis for evaluation of systolic arterial pressure augmentation secondary to arterial stiffening and early wave reflection. Results were compared to 24 healthy individuals. In all patients, endothelium-related flow-mediated dilation (FMD) of the brachial artery and intima-media thickness (IMT) of the carotid artery were measured. RESULTS: Augmentation pressure (AP) and augmentation index (AI) were higher in Type 1 diabetic patients suggesting stiffer arteries compared to controls (AP: 5.8 +/- 3.6 vs 2.8 +/- 2.2 mmHg, p < 0.001; and AI:18.3 +/- 9 vs 11.1 +/- 8.8%, p = 0.004). The subgroup of diabetic patients with autoimmune thyroid disease presented stiffer arteries than those without (AP: 6.5 +/- 2.9 vs 5.5 +/- 3.9 mmHg, p < 0.05; and AI: 21.3 +/- 5.4 vs 16.7 +/- 10.3%, p < 0.05), though the two groups did not differ statistically by means of age, disease duration, hemoglobin A1c (HbA1c), lipid levels, FMD and IMT. In multiple regression analysis, variables independently associated to AI in the diabetes group were: age (p = 0.028), IMT of the carotid artery bifurcation (p = 0.045), disease duration (p = 0.031) and autoimmune thyroid disease (p = 0.015). No correlation was observed between AI and metabolic control, blood pressure, microalbuminuria, presence of retinopathy and endothelial function (FMD). CONCLUSIONS: Women with Type 1 diabetes have increased arterial stiffness, which indicates macroangiopathy. An independent correlation between these indices and carotid IMT was observed. Concomitant autoimmune thyroid disease seems to aggravate arterial compliance in these patients, a finding that merits further investigation.

Lack of suppression of plasma glucagon levels in late pregnancy persists postpartum only in women with previous gestational diabetes mellitus.

The aim of the present study was to examine fasting (0') and postglucose glucagon levels in normal and gestational diabetes mellitus (GDM) pregnancy, as available data are somewhat conflicting. To this end we studied 18 women with GDM at 26-32 weeks of pregnancy and compared these with 26 normal pregnant women matched for age and BMI. We also examined glucagon suppressibility postpartum (2-4 months) in the same ex-GDM women, in whom normal glucose tolerance was confirmed (WHO criteria) and compared these with 17 controls matched for age and BMI. Glucose, insulin and glucagon levels were measured during a 100 or 75 g oral glucose tolerance test (OGTT) respectively. In pregnant women, baseline and 3 h after glucose ingestion, plasma glucagon levels were significantly higher (p < 0.05) in women with GDM compared to normal women. Interestingly, in normal pregnancy a significant increase (p < 0.01) of postglucose plasma glucagon levels at 1 and 2 h compared to baseline levels was observed, while there was no change in GDM pregnancy. In postpartum euglycaemic women, there was no difference in basal glucagon levels between the two groups. A differential glucagon response during OGTT was observed: in control women there was a significant glucagon suppression (p < 0.01) at 2 h, while there was a significant glucagon increase (p < 0.01) 1 h after glucose ingestion, in ex-GDM women. We conclude that (a) absence of the suppressibility of glucagon in ex-GDM women with normal OGTT may indicate insulin resistance and might be involved in the natural history towards glucose intolerance; and (b) nonsuppression of glucagon in normal late pregnancy as well as in pregnancy complicated by GDM may be due to "physiological" insulin resistance of the alpha cells during this period.

Improvement of iodine deficiency after iodine supplementation in schoolchildren of Azerbaijan was accompanied by hypo and hyperthyrotropinemia and increased title of thyroid autoantibodies.

OBJECTIVE: In the mountainous areas of Azerbaijan the schoolchildren suffer from severe Iodine Deficiency (ID) with median Urinary iodine excretion (UIE) 36 mcg/l and prevalence of goiter 99% (estimated by US). In a population of 293,000 schoolchildren aged 8-14 y.o. we administered capsules containing 190 mg of iodized oil (Lipiodol-Guerbet, Cedex, France) twice yearly in 6 months apart (total 380 mg). The aim of the present study was to evaluate the efficacy, the benefits, as well as the possible side-effects in a follow-up period of 6 and 12 months after the initial administration of iodized oil. METHODS: Six and 12 months after the initial administration of iodide, two representative samples of 391 and 326 children respectively were examined. The evaluation included: estimation of goiter by US, determination of UIE and serum measurements of T3, T4, TSH, Tg, autoantibodies against thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg). RESULTS: There was an improvement in median UIE which increased from 36 mcg/l to 68 and 81 mcg/l after 6 and 12 months of treatment respectively. The prevalence of goiter decreased from 99% to 54% and 26% respectively. Tg was decreased at 6 and 12 months from the first administration, whereas TSH remained unchanged at 6 months and decreased at 12 months when compared to the latter value. Hypothyroidism was detected in 7% of children after iodide administration both at 6 and 12 months, but overt hypothyroidism was observed only in 0.5% at 12 months. Subclinical hyperthyroidism was detected in 2% and 6% after iodide administration both at 6 and 12 months. There was a significant increase in the title of thyroid auto antibodies in 6 months which was retained and increased in 12 months. There was no relation between the appearance of thyroid dysfunction and the positive thyroid auto antibodies. CONCLUSION: The dose of 190 mg iodide administered twice yearly, improved iodine deficiency and endemic goiter in schoolchildren. The increase of UIE resulted from iodide administration, was accompanied by an increased title of thyroid auto-antibodies and an increased prevalence of hyper- and hypothyrotropinemia apparently of no autoimmune etiology.

The androgen receptor gene CAG polymorphism is associated with the severity of coronary artery disease in men.

OBJECTIVE: The role of androgens in the pathogenesis of coronary artery disease (CAD) remains controversial. The length of the polyglutamine stretch of the transactivation domain (CAG repeat) of the androgen receptor (AR) inversely affects androgen activity. The aim of this study was to investigate the effect of this polymorphism of the AR gene in the extent of CAD in male patients. DESIGN AND PATIENTS: The relationship of the length of the AR gene CAG repeat on the severity of CAD was examined in 131 men (36-86 years old) undergoing coronary angiography. MEASUREMENTS: The severity of CAD was assessed by the number (0-3) of coronary vessels with > 50% reduction in the luminal diameter. The interaction of the AR gene polymorphism with the intima media thickness (IMT) of peripheral arteries and serum levels of sex steroids, insulin and biochemical parameters were also studied. RESULTS: The upper quartile of CAG length (range 9-30) was > or = 23 repeats (longAR). The mean body mass index (BMI) of patients with shorter repeats (< 23; shortAR) was significantly lower than in men with longAR (26.1 vs. 27.6, respectively; P = 0.043 M-W Rank test). There was no correlation between the AR gene repeat length and serum testosterone. Oestradiol levels were significantly higher in longAR (0.19 +/- 0.08 nmol/l vs. 0.14 +/- 0.07 in shortAR, P = 0.031). This difference was independent of BMI. Men with shortAR had significant CAD (i.e. one to three arteries with stenosis) more frequently (79.5%) than men with longAR (20.5%); of the subjects with stenosis in no arteries, 56.5% had shortAR and 43.5% longAR (chi2 = 4.3, P = 0.038). This association was independent of age and BMI. The IMT of peripheral arteries, lipid parameters, basal insulin resistance, blood pressure and family history for early CAD, did not differ according to AR length. CONCLUSIONS: The shorter CAG repeat of the AR gene is associated with more severe CAD, which suggests a role for the sensitivity to androgens in the increased frequency of CAD in males. In addition, a protective role of endogenous oestrogen, which is higher in the longAR subgroup, can contribute to the observed difference.

High plasma amylin/islet amyloid polypeptide levels in patients with residual medullary thyroid carcinoma after total thyroidectomy.

OBJECTIVE: We have previously reported that amylin/islet amyloid polypeptide (IAPP) mRNA is detected in a substantial subset of medullary carcinomas of the thyroid (MTCs). The aim of this study was to determine if the amylin/IAPP gene is expressed as the IAPP peptide in MTC tissues. DESIGN AND METHODS: In 10 patients with a histological diagnosis of MTC and with persisting or recurrent disease (basal calcitonin levels >250 pg/ml), the fasting serum insulin and plasma glucose, IAPP and calcitonin levels were measured and compared with those of 18 normal control subjects matched for age and body mass index. IAPP expression was studied by immunohistochemistry in MTCs and lymph-node metastasis tissues. RESULTS: Seven of ten MTC patients had abnormally elevated IAPP levels. Plasma IAPP and serum insulin levels were correlated in both patients and controls, but the slope of the regression line was significantly higher for MTC patients. IAPP staining was detected in four out of 12 random MTC samples and in two out of five lymph-node metastases, using immunohistochemistry. CONCLUSIONS: These results indicate that MTC cells express IAPP at the peptide level and that this raises the peripheral plasma levels. Further studies may reveal whether this is a feature of malignant disease.

Sustained remission of metastatic adrenal carcinoma during long-term administration of low-dose mitotane.

We present our experience with two female patients suffering from metastatic, recurrent adrenocortical carcinomas, to whom o,p'-DDD (mitotane) was administered for unusually long duration. The first patient received mitotane as monotherapy after relapse (in doses ranging from 3 to 6 g/day initially and 1 g/day thereafter, for 13 yr). The second patient presented with metastatic disease and underwent radical surgical excision of the adrenal. Mitotane was administered initially at 2.5 g/day, and the dose was gradually lowered over 8 yr to 1 g/day, without interruption. Both patients tolerated the medication well, regardless of the daily dosage, with complaints limited to epigastric pain and nausea, while their disease has been kept under control for 14 and 16 yr, respectively. The blockade of steroid synthesis with mitotane resulted in hypercholesterolemia in both patients and in premature menopause in the second patient; however, these abnormalities were taken care of with the appropriate therapy. The excellent follow-up of these patients suggests that even in hopeless cases with metastatic adrenocortical carcinoma, mitotane should be administered for very long periods of time as it can be well-tolerated and may be beneficial in the long run.

HLA DQA1*0501 and DRB1*0301 antigens do not independently convey susceptibility to Graves' disease.

Genes of, or closely associated to, the HLA complex are assumed to contribute to the genetic predisposition of Graves' disease. The aim of this study was to investigate the presence of the HLA DQA1*0501 and DRB1*0301 antigens in Greek patients with Graves' disease. In addition, we tried to establish if there is any association between these antigens and any of the clinical manifestations of the disease. We examined 117 patients with Graves' disease and 104 healthy controls. DNA was extracted from peripheral lymphocytes and the HLA DQA1*0501 and DRB1*0301 genomic regions were amplified by PCR and characterized by hybridization with sequence specific oligonucleotides (SSO). Two of the patients had a positive family history for Graves' disease and 46 had clinical thyroid eye disease (TED). The frequencies of both DQA1*0501 and DRB1*0301 antigens were significantly increased in patients compared to controls (relative risk [RR] 4.2 and 4.5 for each antigen respectively). Neither of these two antigens was an independent risk factor for Graves' disease. However, the combination of both these HLA antigens resulted in a striking increase in the RR for development of Graves' disease especially in females (RR/F=27, RR/M=8.4). No association was found between these antigens and positive family history or the presence of TED. These data suggest that HLA DQA1*0501 and DRB1*0301 antigens are not independent risk factors for the development of Graves' disease. On the contrary, the presence of both these alleles results in a significant increase in the RR for the development of Graves' disease in the Greek population, particularly in females.

Iodine deficiency in Azerbaijan after the discontinuation of an iodine prophylaxis program: reassessment of iodine intake and goiter prevalence in schoolchildren.

The goal of this study was to assess the prevalence of iodine deficiency (ID) in Azerbaijan after the discontinuation of an iodine prophylaxis program by assessing the prevalence of goiter, iodine intake, and thyroid function. The study included 942 schoolchildren (475 boys and 467 girls) ages 8-14 years, from 13 distinct regions. The survey included the following: (1) clinical evaluation; (2) assessment of thyroid volume both by ultrasound and by palpation; (3) determination of iodide in a morning urine specimen using the classic Sandel-Kolthoff reaction in 347 schoolchildren; (4) determinations of thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), thyroglobulin (Tg), and anti-thyroid peroxidase (TPO) in serum (n = 165) and TSH in whole blood spotted on filter paper (n = 942). The prevalence of goiter for the whole country was determined by ultrasound (US) to be 86% and by palpation 66%, reaching 100% in the mountainous regions of Caucasus. The median urinary iodine excretion (UIE) was 54 microg/L, reaching level of 26 and 39 microg/L in the Caucasus region. In conclusion, according to the World Health Organization (WHO) classification, Azerbaijan now has mild to moderate ID (median UIE, 54 microg/L) and in the mountainous regions with severe ID. The high prevalence of goiter and the low UIE emphasizes the need for urgent medical reintervention. An iodination program is now implemented by our team in the mountainous regions under the auspice of the government of Azerbaijan.

Study of the Trp64Arg polymorphism of the beta3-adrenergic receptor in Greek women with gestational diabetes.

OBJECTIVE: This study assessed whether the Trp(64)Arg polymorphism of the beta3-adrenergic receptor (beta3-AR), which has been associated with obesity, insulin resistance, weight gain, and earlier onset of type 2 diabetes, is more frequent in women who develop gestational diabetes mellitus (GDM) or whether it is associated with weight gain during pregnancy RESEARCH DESIGN AND METHODS: A total of 311 Greek pregnant women (180 with GDM and 131 without GDM [control]) who underwent a 100-g oral glucose tolerance test (OGTT) in the third trimester of pregnancy were genotyped for the beta3-AR Arg(64) polymorphism. Insulin levels were also determined during the OGTT. RESULTS: The frequency of Trp(64)Arg heterozygotes in this population was approximately 7% and was similar in the GDM and control groups (6.7 vs. 6.9%) as well as in the obese (BMI > or =27 kg/m2) and the nonobese (6.3 vs. 6.8%) subgroups. In the GDM group, BMI, fasting insulin resistance index, and diastolic blood pressure were significantly higher in Trp(64)Arg carriers; these differences were no longer observed when obesity was considered. In the 4 subgroups (control Trp(64)Trp and Trp(64)Arg and GDM Trp(64)Trp and Trp(64)Arg), a highly significant trend was evident of an increase in the percentage of subjects with shorter height. CONCLUSIONS: The frequency of the Arg(64) allele in Greek pregnant women is relatively rare compared with other ethnic groups and is probably not related to the development of GDM or obesity The observed tendency for shorter body height in Arg(64) carriers merits further evaluation in larger population samples.

Three mRNA transcripts of the proopiomelanocortin gene in human placenta at term.

The proopiomelanocortin (POMC) gene whose normal pituitary specific mRNA product is 1200 bases (b) is also expressed in placenta and its peptide derivatives such as ACTH and beta-endorphin may play an important role in the initiation of labor. So far, two mRNA transcripts, one small (800b) and one large (1380b) have been reported in placenta by Northern blot analysis, similar to other endocrine tissues and various extrapituitary tumors; however, it is questionable whether both of these transcripts are effectively translated to a functional protein. We examined by Northern blot analysis the size and the differential expression of placental POMC gene transcripts in pregnant women with different modes of delivery. Placental tissues were collected from two groups of pregnant women, six with vaginal delivery (VD) and five with cesarean section (CS). In both groups of placentae three POMC gene transcripts were detected of 800, 1200 and 1380 bases; the 1200b pituitary specific species often predominated and was always present. The 800b transcript was also always present, while the large transcript (1380b) was expressed in 3/6 VD and 2/5 CS placental tissues. No differences in the relative levels of any of these mRNA species showing effect of the mode of delivery were observed. We conclude that POMC gene transcription in placental tissue at term gives rise to three mRNA transcripts, thus resembling extrapituitary tumors. The reported changes in the levels of the derivative peptides according to the mode of delivery do not reflect changes in POMC mRNA levels and could be attributed to a post-translational effect.

Hormonal parameters in gestational diabetes mellitus during the third trimester: high glucagon levels.

Hormonal parameters during the last trimester of pregnancy contribute to a natural increase of insulin resistance. It is not known whether any of these are further involved in the manifestation of gestational diabetes mellitus (GDM) in affected individuals. Basal levels of adrenocorticotropic hormone, cortisol, growth hormone, insulin-like growth factor-I, prolactin, glucagon, estradiol, progesterone, human placental lactogen and human chorionic gonadotropin were investigated in 15 nonobese women with GDM and 26 matched normal pregnant women (N). A linear discriminant analysis was performed to further compare the predictive value of the basal hormone levels. Plasma glucagon levels were significantly higher in the GDM group (p = 0.014); this difference was even higher (p = 0.007) when the number of women was increased (GDM = 33, N = 62). No significant differences were found in the levels of any of the other hormones. It is not clear whether elevated glucagon levels have any involvement in the pathogenesis of GDM or simply reflect the relative insulin deficiency of these women.