Toe Brachial Pressure Index as Alternative Method to Correlate Arteriosclerotic Disease in Type 2 Diabetes.

AIM: To investigate the association between the ankle brachial pressure index and toe brachial pressure index with the findings of carotid Doppler ultrasonography in patients with diabetes and coronary ischaemic disease. METHODS AND RESULTS: The objective was to evaluate the relationship between insulin resistance and serum homocysteine in subjects with polycystic ovarian syndrome (PCOS). CONCLUSION: We studied 81 type 2 diabetic patients, with established cardiovascular disease, consecutively admitted to our outpatient clinic in the Division of Diabetes of La Paz Hospital. We collected clinic and demographic data, ABI and TBI were measured and at the same time a carotid Doppler ultrasound was performed. Multiple linear regression analysis was used to investigate the association of ABI and TBI with carotid disease. We found a negative correlation between TBI and internal carotid artery peak systolic velocity (ICA PSV) (r = -0,300, p= 0,007), common carotid artery resistance index (CCA RI) (r = -0,232, p= 0,038) and intima-media thickness (IMT) (r -0,236, p=0,035). Toe blood pressure and ICA PSV showed an inverse association (r=- 0,226, p=0,042). Adjusting for clinical and demographic characteristic, only low TBI index is associated with a higher ICA PSV.

Influence of gestational diabetes mellitus on neonatal weight outcome in twin pregnancies.

AIMS: To evaluate the influence of gestational diabetes mellitus on neonatal birthweight, macrosomia and weight discrepancy in twin neonates. METHODS: An observational retrospective study was performed. One hundred and six women with gestational diabetes and twin pregnancy and 166 twin controls who delivered viable fetuses > 24 weeks were included. Impact of maternal pre-pregnancy BMI, smoking habit, method of conception, chorionicity, gestational age at delivery, mode of delivery and hypertensive complications were also analysed. The effect of maternal hyperglycaemia and metabolic control in gestational diabetes pregnancies was assessed. RESULTS: Gestational hypertension and pre-eclampsia were significantly higher in the group with gestational diabetes (21.5% vs. 6.3%, P = 0.007 and 6.2% vs. 0%, P = 0.025). There were no differences in the incidence of macrosomia (5.7% vs. 7.2%, P = 0.803), large for gestational age (10.3% vs. 13.2%, P = 0.570), small for gestational age (10.3% vs. 12.0%, P = 0.701), severely small for gestational age (6.6% vs. 7.8%, P = 0.814) or weight discrepancy (20.6% vs. 15.2%, P = 0.320) in the group with gestational diabetes compared with twin pregnancies without diabetes. There were no differences when comparing insulin-requiring gestational diabetes pregnancies and twins without diabetes for any of the neonatal weight outcomes. There was no relationship between third trimester HbA1c and neonatal birthweight or infant birthweight ratio. CONCLUSION: Gestational diabetes did not increase the risk of macrosomia or weight discrepancy of twin newborns. Furthermore, glycaemic control did not influence the rate of any of the weight outcomes in our study population. In twin pregnancies, gestational diabetes was associated with a higher risk of gestational hypertension and pre-eclampsia.

The usefulness of HbA1c in postpartum reclassification of gestational diabetes.

To investigate the role of HbA1c in postpartum reclassification of gestational diabetes (GDM) we studied 364 women with GDM attending the postpartum reclassification assessment of their glucose tolerance status. A 75-g oral glucose tolerance test (OGTT) was performed and HbA1c was determined. Diabetes was diagnosed in 12 (3.3%), 7 (1.9%) and 2 (0.6%) women according to the fasting plasma glucose (FPG) and/or the 2-hour OGTT, the FPG alone and HbA1c levels, respectively. The sensitivity and specificity for HbA1c to diagnose diabetes was 16.7% and 100%, respectively, for FPG and OGTT criteria. The combination of a cutoff value of 5.5% for HbA1c and FPG allowed us to identify 95.1% of women with any kind of glucose intolerance. We conclude that in the early postpartum period, the cutoff of 6.5% for HbA1c alone has low sensitivity for the diagnosis of diabetes compared with OGTT, but the combination of FPG and HbA1c at a lower cutoff value is very useful to identify women with any kind of glucose intolerance.

Glycemic control and maternal and fetal outcomes in pregnant women with type 1 diabetes according to the type of basal insulin.

OBJECTIVE: To examine the potential role of the type of basal insulin on glycemic control and maternal and foetal outcomes in pregnant women with type 1 diabetes (T1DM). STUDY DESIGN: Retrospective cohort study of pregnancies attended at 18 Spanish tertiary hospitals. INCLUSION CRITERIA: T1DM, singleton pregnancies, delivery between 2002-2010, and use of the same basal and prandial insulin from before pregnancy until delivery. RESULTS: A total of 1534 pregnancies were included. The basal insulin most commonly used was Neutral Protamine Hagedorn (NPH) (51.7%), followed by glargine (23.2%) and continuous subcutaneous insulin infusion (CSII) (21.1%). CSII users had longer diabetes duration. Multiple logistic regression analysis showed that CSII was independently associated with lower doses of insulin, higher glycated haemoglobin (HbA1c) in all trimesters, and higher rates of miscarriage, preterm birth and neonatal hypoglycemia. Glargine was related to a higher risk of preterm birth and a small-for-gestational age infant (SGA). The odds ratios (OR) of the associations between insulin type and clinical outcomes (from 0.642 to 4.894) have a relevant magnitude. CONCLUSIONS: In this observational study of pregnant women with T1DM, the type of basal insulin was independently associated with metabolic variables and foetal outcomes.

Three-dimensional reconstruction of the connector of bacteriophage phi 29 at 1.8 nm resolution.

The three-dimensional reconstruction of the connector of bacteriophage phi 29 has been obtained from tilt series of negatively stained tetragonal ordered aggregates under low-dose conditions and up to a resolution of (1/1.8) nm-1. These connectors are built up as dodecamers of only one structural polypeptide (p10). Two connectors form the crystal unit cell, each one facing in the opposite direction with respect to the plane of the crystal and partially overlapping. The main features of the two connectors that build the unit cell were essentially the same, although they were negatively stained in slightly different ways, probably due to their situations with respect to the carbon-coated support grid. The main features of the phi 29 connector structure revealed by this three-dimensional reconstruction are: the existence of two clearly defined domains, one with a diameter of around 14 nm and the other narrower (diameter approximately equal to 7.5 nm); an inner hole running all along the structure (around 7 to 8 nm in height) with a cylindrical profile and an average diameter of 4 nm; a general 6-fold symmetry along the whole structure and a 12-fold one in the wider domain; a clockwise twist of the more contrasted regions of both domains from the narrower towards the wider domain (the direction of DNA encapsidation). These features are compatible with an active role for the connector in the process of DNA packaging.

Conformational changes in bacteriophage phi 29 connector prevents DNA-binding activity.

In vitro DNA packaging activity in a defined system derived from bacteriophage phi 29 depends upon the chemical integrity of the connector protein p10. Proteolytic cleavage of p10 rendered the proheads inactive for DNA packaging. A similar treatment on isolated connectors abolished the DNA-binding activity of the native p10, but the general shape and size of the connector was not changed as revealed by electron microscopy. Analytical ultracentrifugation showed that the proteolyzed connectors had a smaller sedimentation coefficient, while amino acid analysis after dialysis of the proteolyzed p10 confirmed the loss of 16 and 19 amino acids from the amino and carboxy termini, respectively. Low angle X-ray scattering revealed that proteolysis was followed by a small decrease in the radius of gyration and a reorganization of the distal domain of the cylindrical inner part of the connector. Characterization of the cleavage sites in the primary sequence allowed us to propose the location of the DNA-binding domain in the connector model.

Bacteriophage T3 connector: three-dimensional structure and comparison with other viral head-tail connecting regions.

The bacteriophage T3 connector, which consists of 12 copies of protein gp8, has been studied by image processing of electron micrographs from negatively stained ordered aggregates. A three-dimensional reconstruction of T3 connectors was obtained by collection of tilted views and using the direct Fourier method, up to 2.3 nm resolution. The reconstructed unit cell contains two connectors whose main structural features are essentially identical, but facing in opposite directions. The T3 connector has a height of about 10.9 nm, with two clearly defined domains: a wider one 14.4 nm in diameter, with 12 morphological units in the periphery, and a narrower one, 9.7 nm in diameter. There is a channel clearly defined in the narrower domain that almost closes along the wider domain. Comparison of the three-dimensional structure obtained for the connector of phages T3 and phi 29, and that of the neck extracted from phage phi 29 particles, reveals striking similarities and significant differences. A model for a general connector to account for the common functions carried out by these viral assemblies is discussed together with the possible role of the channel for DNA translocation.

Early postpartum metabolic assessment in women with prior gestational diabetes.

OBJECTIVE: To present the results of early postpartum metabolic assessment in women with gestational diabetes mellitus (GDM), to determine predictive factors for subsequent diabetes, and to investigate the association of postpartum glucose tolerance with other components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A total of 788 women were evaluated 3-6 months after a GDM pregnancy. A 75-g oral glucose tolerance test (OGTT) was performed. Cholesterol, HDL cholesterol, triglycerides, blood pressure, BMI, and body fat distribution were assessed. Clinical and obstetric history, baseline variables at the diagnosis of GDM, metabolic control during pregnancy, and index pregnancy outcome were compared in women with diabetes and women without diabetes (American Diabetes Association [ADA] criteria) after pregnancy. Multivariate logistic regression analysis was used to ascertain independent predictors of subsequent diabetes. Correlation coefficients were assessed between postpartum glucose tolerance and lipid levels, blood pressure, BMI, and body fat distribution. RESULTS: According to ADA criteria, 588 (74.6%) women were normal, 46 (5.8%) had impaired fasting glucose, 82 (10.4%) had impaired glucose tolerance, 29 (3.7%) had both impaired fasting glucose and impaired glucose tolerance, and 43 (5.4%) had diabetes. Prepregnancy obesity, recurrence of GDM, gestational age at diagnosis of GDM, glucose values in the 100-g OGTT, number of abnormal values in the 100-g OGTT, fasting C-peptide levels in pregnancy, C-peptide/glucose score in pregnancy, insulin requirement in pregnancy, 3rd trimester HbA1c levels, and macrosomia differed significantly in women with subsequent diabetes. Independent predictors of postpartum diabetes were prepregnancy obesity, C-peptide/glucose score during pregnancy, and the number of abnormal values in the 100-g diagnostic OGTT. The area under the postpartum glucose curve was positively associated with BMI, waist circumference, waist-to-hip ratio, triglycerides, and systolic and diastolic blood pressures. CONCLUSIONS: Low C-peptide/glucose score during pregnancy together with prepregnancy obesity and severity of GDM (number of abnormal values in the 100-g diagnostic OGTT) are independent predictors of subsequent diabetes. Our data suggest that regardless of obesity and severity of GDM, a beta-cell defect increases the risk of postpartum diabetes. The association of postpartum glucose tolerance with triglyceride levels, blood pressure, obesity, and regional distribution of body fat suggests that postpartum glucose intolerance anticipates a high-risk cardiovascular profile that comprises other risk factors besides diabetes.

Efficacy of octreotide in the regression of a metastatic carcinoid tumour despite negative imaging with In-111-pentetreotide (Octreoscan).

We present the case of a 52-year old patient diagnosed with carcinoid tumour of the rectum with liver metastases in which treatment with somatostatin analogues (octreotide) proved very effective in the disappearance of the symptomatology and dramatic efficacy in the regression of the tumour. Imaging by octreoscan was always negative. The role of octreotide in the treatment of carcinoid tumour and the usefulness of In-111-pentetreotide (octreoscan) in the localization and prediction of the response to treatment with octreotide is discussed. We conclude that the negative result of the scintigraphic image with octreoscan does not necessarily suppose the inefficacy of octreotide treatment. We believe that this may constitute an important issue since some patients may be denied octreotide treatment in the absence of a positive octreoscan result.

[Effect of preconceptional metabolic control in the course of pregnancy in diabetic patients]. / Influencia del control metabólico preconcepcional en la evolución de la gestación de la paciente diabética.

BACKGROUND: We analysed the relationship between metabolic control parameters during the preconception stage and pregnancy outcome in diabetic patients. PATIENTS AND METHOD: We examined 69 diabetic patients who underwent a preconception control at the Diabetes and Pregnancy Unit between 1992-1998. At the end of the preconception care period, 50 women (72.6%) became pregnant. Eight out of them (16%) had an abortion. RESULTS: Women who had an abortion did not differ from those who had not an abortion with regard to HbA1c levels at the end of the preconception period, age, duration of diabetes, age at diagnosis,anti-thyroid antibodies or microvascular disease. Among 41 single age stations, fetal macrosomia was observed in 36.6% cases, neonatal hypoglycemia in 19.5% and major congenital malformations in one case. Average level of HbA1c was 7.6 +/- 1.3%and 6.5 +/- 0.7 at the beginning and at the end of the preconception period, respectively (p < 0.001). In the group with macrosomia,average HbA1c at the end of the preconception period was 6.8 +/- 0.66% as opposed to 6.3 +/- 0.7% for the non-macrosomic group (p < 0.05). A linear correlation was seen between HbA1c levels at the end of the preconception period and infant weight (r = 0,432; p = 0,014), birth weight ratio (r = 0,450; p = 0,009), and a morbidity score (r = 0,458;p = 0,007). CONCLUSIONS: A better metabolic control during the preconception period may contribute to lessen the risk of fetal macrosomia and neonatal morbidity.

[Our experience in the nutritional treatment of anorexia nervosa (1989-1991)]. / Nuestra experiencia en el tratamiento nutricional de la anorexia nerviosa (1989-1991).

The purpose of this study was to assess the evolution in the nutritional situation of patients diagnosed with anorexia nervosa in the Clinical Nutrition Service between January 1 1989 and December 31 1991. Twenty-eight admitted patients (4 men and 24 women) and 38 outpatients (3 men and 35 women) were monitored, with an age of 22.4 +/- 6.4 years and average evolution time of the illness of 3.8 +/- 5 years. Nutritional state was evaluated with anthropometric, biochemical and immunological parameters. Following nutritional therapy, malnutrition and BMI (Body Mass Index) improved significantly over the initial evaluation in all patients, whether admitted or outpatients. All anthropometric parameters improved significantly during the period of treatment of admitted patients, but AMC (arm muscle circumference) rose only in outpatients. An unrestricted diet plus nutritional counselling was the most-used therapeutic procedure in outpatients while most of the admitted patients required dietary supplements. Calorie malnutrition is very common in patients diagnosed with anorexia nervosa: vitamin or trace element deficiencies are very infrequent. Nutritional therapy, suitably coordinated with psychotherapeutic treatment, is effective, enhancing both the nutritional state and anomalous dietary habits.

Body weight, weight gain and hyperglycaemia are associated with hypertensive disorders of pregnancy in women with gestational diabetes.

AIM: The aim of this study was to measure the capacity of glucose- and weight-related parameters to predict pregnancy-induced hypertensive disorders in women with gestational diabetes. METHODS: An observational study was conducted involving 2037 women with gestational diabetes. The associations of glycaemic and weight-related parameters with pregnancy-induced hypertensive disorders were obtained by univariate and adjusted multivariate analyses. Also, model predictability and attributable predictor risk percentages were calculated, and collinearity and factor interactions examined. RESULTS: Multivariate analyses revealed that hypertensive disorders were mainly predicted by average third-trimester glycated haemoglobin (HbA(1c)) levels ≥ 5.9%, by being overweight or obese before pregnancy and by excess gestational weight gain after adjusting for age, tobacco use, chronic hypertension, parity, urinary tract infections and gestational age at delivery. Prepregnancy body weight (overweight and obesity) had the strongest impact on pregnancy-related hypertensive disorders (attributable risk percentages were 51.5% and 88.8%, respectively). The effect of being overweight or obese on hypertensive disorders was enhanced by HbA(1c) levels and gestational weight gain, with elevated HbA(1c) levels multiplying the effect of being overweight before pregnancy. CONCLUSION: The average third-trimester HbA1c level is a novel risk factor for pregnancy-induced hypertensive disorders in women with gestational diabetes. HbA(1c) levels ≥ 5.9%, prepregnancy overweight or obesity and excess gestational weight gain are all independent risk factors of pregnancy-related hypertensive disorders in such women. In treated gestational diabetes patients, the strongest influence on hypertensive disorders is prepregnancy obesity.

Interaction of the bacteriophage phi 29 connector protein with the viral DNA.

The protein that forms the connector of phage phi 29, p10, binds to DNA. Apparently, p10 binding is not sequence specific. Nevertheless, the presence of the terminal protein (p3) covalently attached to the ends of phi 29 DNA produces a significant increase of p10 molecules bound to the DNA ends, thus suggesting a terminal protein-mediated recognition of DNA ends by the phage connector. As the p3-DNA complex is the substrate for phage phi 29 DNA packaging, these results may reflect a direct implication of the phage connector in the packaging process.

DNA conformational change induced by the bacteriophage phi 29 connector.

Translocation of viral DNA inwards and outwards of the capsid of double-stranded DNA bacteriophages occurs through the connector, a key viral structure that is known to interact with DNA. It is shown here that phage phi 29 connector binds both linear and circular double-stranded DNA. However, DNA-mediated protection of phi 29 connectors against Staphylococcus aureus endoprotease V8 digestion suggests that binding to linear DNA is more stable than to circular DNA. Endoprotease V8-protection assays also suggest that the length of the linear DNA required to produce a stable phi 29 connector-DNA interaction is, at least, twice longer than the phi 29 connector channel. This result is confirmed by experiments of phi 29 connector-protection of DNA against DNase I digestion. Furthermore, DNA circularization assays indicate that phi 29 connectors restrain negative supercoiling when bound to linear DNA. This DNA conformational change is not observed upon binding to circular DNA and it could reflect the existence of some left-handed DNA coiling or DNA untwisting inside of the phi 29 connector channel.

Protein intake during aggressive calorie restriction in obesity determines growth hormone response to growth hormone-releasing hormone after weight loss.

OBJECTIVE: We evaluated the influence of two types of calorie restriction, total fast or very low calorie diet, on GH responsiveness to GHRH in severely obese patients. DESIGN: Twenty patients with massive obesity underwent one of two types of calorie restriction, total fast (10 patients) or very low calorie diet (10 patients). MEASUREMENTS: Fasting GH, IGF-I, glucose, insulin and GH secretion after GHRH (100 ug i.v.) were assessed in all patients before and after diet therapy. RESULTS: Both types of diet produced similar weight reduction (total fast, 5.6 +/- 1.6 kg/m2 vs very low calorie diet, 5.6 +/- 1.5 kg/m2 mean +/- SD). A significant increase in the integrated GH secretion was observed after weight loss with very low calorie diet (17 +/- 9 vs 27 +/- 12 mU/l min; P < 0.05). However, no change was found in GH response after weight loss with total fast (13 +/- 5 vs 15 +/- 7 mU/l min). Glucose, insulin and IGF-I levels showed a significant decrease with weight reduction which was similar for both groups. CONCLUSION: These findings suggest that the type of dietary manipulation during calorie restriction in obese patients may influence the changes in GH response to GHRH after weight loss.

Dehydroepiandrosterone sulphate, body fat distribution and insulin in obese men.

Sex steroid hormones may be involved in determining body fat distribution in men. Recent evidence suggests that insulin may be an important regulator of sex hormones metabolism in men. Few data, however, are available on the relationship of dehydroepiandrosterone sulphate (DHEA-SO4), a major secretory product of the adrenal gland, to regional distribution of body fat or to insulin levels in men. We therefore examined the association of DHEA-SO4, total testosterone and free testosterone to waist-to-hip ratio (WHR) and to subscapular-to-triceps ratio (STR) in 34 obese, otherwise healthy men. In addition, we examined the relation between these sex steroid hormones and insulin response to an oral glucose tolerance test. DHEA-SO4 was significantly positively related to STR and significantly negatively related to insulin area. These associations remained significant after adjustment for age and obesity. Using multiple linear regression, DHEA-SO4 was independently related to both STR and insulin area. Without claiming any causality in the observed associations, we conclude that, in obese men, high DHEA-SO4 levels are related to centralized adiposity, while low DHEA-SO4 levels are related to hyperinsulinemia.