Maternal Moderate Physical Training during Pregnancy Attenuates the Effects of a Low-Protein Diet on the Impaired Secretion of Insulin in Rats: Potential Role for Compensation of Insulin Resistance and Preventing Gestational Diabetes Mellitus

The effects of pregestational and gestational low-to-moderate physical training on insulin secretion in undernourished mothers were evaluated. Virgin female Wistar rats were divided into four groups as follows: control (C, n = 5); trained (T, n = 5); low-protein diet (LP, n = 5); trained with a low-protein diet (T + LP, n = 5). Trained rats ran on a treadmill over a period of 4 weeks before mate (5 days week(-1) and 60 min day(-1), at 65% of VO2max). At pregnancy, the intensity and duration of the exercise were reduced. Low-protein groups were provided with an 8% casein diet, and controls were provided with a 17% casein diet. At third day after delivery, mothers and pups were killed and islets were isolated by collagenase digestion of pancreas and incubated for a further 1 h with medium containing 5.6 or 16.7 mM glucose. T mothers showed increased insulin secretion by isolated islets incubated with 16.7 mM glucose, whereas LP group showed reduced secretion of insulin by isolated islets when compared with both C and LP + T groups. Physical training before and during pregnancy attenuated the effects of a low-protein diet on the secretion of insulin, suggesting a potential role for compensation of insulin resistance and preventing gestational diabetes mellitus.

Identifying common and specific microRNAs expressed in peripheral blood mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients

Abstract Background Regardless the regulatory function of microRNAs (miRNA), their differential expression pattern has been used to define miRNA signatures and to disclose disease biomarkers. To address the question of whether patients presenting the different types of diabetes mellitus could be distinguished on the basis of their miRNA and mRNA expression profiling, we obtained peripheral blood mononuclear cell (PBMC) RNAs from 7 type 1 (T1D), 7 type 2 (T2D), and 6 gestational diabetes (GDM) patients, which were hybridized to Agilent miRNA and mRNA microarrays. Data quantification and quality control were obtained using the Feature Extraction software, and data distribution was normalized using quantile function implemented in the Aroma light package. Differentially expressed miRNAs/mRNAs were identified using Rank products, comparing T1DxGDM, T2DxGDM and T1DxT2D. Hierarchical clustering was performed using the average linkage criterion with Pearson uncentered distance as metrics. Results The use of the same microarrays platform permitted the identification of sets of shared or specific miRNAs/mRNA interaction for each type of diabetes. Nine miRNAs (hsa-miR-126, hsa-miR-1307, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144, hsa-miR-199a-5p, hsa-miR-27a, hsa-miR-29b, and hsa-miR-342-3p) were shared among T1D, T2D and GDM, and additional specific miRNAs were identified for T1D (20 miRNAs), T2D (14) and GDM (19) patients. ROC curves allowed the identification of specific and relevant (greater AUC values) miRNAs for each type of diabetes, including: i) hsa-miR-1274a, hsa-miR-1274b and hsa-let-7f for T1D; ii) hsa-miR-222, hsa-miR-30e and hsa-miR-140-3p for T2D, and iii) hsa-miR-181a and hsa-miR-1268 for GDM. Many of these miRNAs targeted mRNAs associated with diabetes pathogenesis. Conclusions These results indicate that PBMC can be used as reporter cells to characterize the miRNA expression profiling disclosed by the different diabetes mellitus manifestations. Shared miRNAs may characterize diabetes as a metabolic and inflammatory disorder, whereas specific miRNAs may represent biological markers for each type of diabetes, deserving further attention.

Female Sexual Function and Gestational Diabetes

Introduction. The number of women with gestational diabetes mellitus (GDM) is growing worldwide in parallel with the obesity epidemic. The diagnosis of GDM leads to substantial modifications in the daily routine of these women, and these adjustments could potentially affect their sexual function. There are no previous studies on the sexual function of patients with GDM. Aim. The aim of this study was to investigate the sexual function of patients with GDM in comparison with healthy pregnant women at the same gestational age. Methods. Brazilian women in the third trimester of pregnancy with and without GDM were invited to participate in this cross-sectional study while waiting for their antenatal care visits at a single public tertiary teaching institution between March and December 2010. The Brazilian version of the Female Sexual Function Index (FSFI) questionnaire was used to assess sexual function. Main Outcome Measures. Desire, arousal, lubrication, orgasm, sexual satisfaction, and pain during and after coitus in the last 4 weeks, measured according to a standardized and validated questionnaire. Results. A total of 87 participants were enrolled (43 healthy women and 44 with GDM). There were no significant differences in the sociodemographic characteristics of both groups. The total FSFI scores of GDM patients was 21.0 +/- 9.59 compared with 22.3 +/- 9.17 for healthy women (P = 0.523). Difficulty in desire was the most common sexual dysfunction symptom in both groups, being reported by 42% and 50% of GDM and healthy women, respectively (P = 0.585). Conclusion. The sexual function of Brazilian patients with GDM does not differ significantly from that of healthy pregnant women at the same gestational age. Ribeiro MC, Nakamura MU, Scanavino Mde T, Torloni MR, and Mattar R. Female sexual function and gestational diabetes. J Sex Med 2012; 9: 786-792.

Effect of Type 2 Diabetes Mellitus on the Pharmacokinetics of Metformin in Obese Pregnant Women

Background and Objective The use of metformin throughout gestation by women with polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) significantly reduces the number of first-trimester spontaneous abortions and the rate of occurrence of gestational diabetes and hypertensive syndromes. Metformin is taken up into renal tubular cells by organic cation transport 2 (OCT2) and eliminated unchanged into the urine. The objective of this study was to analyse the influence of T2DM on the pharmacokinetics of metformin in obese pregnant women and in a control group of non-diabetic obese pregnant women with PCOS. Methods Eight non-diabetic obese pregnant women with PCOS and nine obese pregnant women with T2DM taking oral metformin 850 mg every 12 h were evaluated throughout gestation. Serial blood samples were collected over a 12-h period during the third trimester of pregnancy. Steady-state plasma concentrations of metformin were determined by high-performance liquid chromatography with a UV detector. The pharmacokinetic results of the two groups, reported as median and 25th and 75th percentile, were compared statistically using the Mann Whitney test, with the level of significance set at p < 0.05. Results The pharmacokinetic parameters detected for PCOS versus T2DM patients, reported as median, were, respectively: elimination half-life 3.75 versus 4.00 h; time to maximum concentration 2.00 versus 3.00 h; maximum concentration 1.42 versus 1.21 mu g/mL; mean concentration 0.53 versus 0.56 mu g/mL; area under the plasma concentration time curve from time zero to 12 h 6.42 versus 6.73 mu g.h/mL; apparent total oral clearance 105.39 versus 98.38 L/h; apparent volume of distribution after oral administration 550.51 versus 490.98 L; and fluctuation (maximum minimum concentration variation) of 179.56 versus 181.73%. No significant differences in pharmacokinetic parameters were observed between the groups. Conclusion T2DM in the presence of insulin use does not influence the pharmacokinetics of metformin in pregnant patients, demonstrating the absence of a need to increase the dose, and consequently does not influence the OCT2-mediated transport in pregnant women with PCOS.

Periodontal disease and diabetes mellitus

Periodontal disease (PD) is one of the most commonly known human chronic disorders. The relationship between PD and several systemic diseases such as diabetes mellitus (DM) has been increasingly recognized over the past decades. Objective The purpose of this review is to provide the reader with knowledge concerning the relationship between PD and DM. Many articles have been published in the English and Portuguese literature over the last 50 years examining the relationship between these two chronic diseases. Data interpretation is often confounded by varying definitions of DM, PD and different clinical criteria were applied to determine the prevalence, extent and severity of PD, levels of glycemic control and diabetes-related complications. Methods This paper provides a broad overview of the predominant findings from research conducted using the BBO (Bibliografia Brasileira de Odontologia), MEDLINE, LILACS and PubMed for Controlled Trials databases, in English and Portuguese languages published from 1960 to October 2012. Primary research reports on investigations of relationships between DM/DM control, PD/periodontal treatment and PD/DM/diabetes-related complications identified relevant papers and meta-analyses published in this period. Results 7This paper describes the relationship between PD and DM and answers the following questions: 1- The effect of DM on PD, 2- The effects of glycemic control on PD and 3- The effects of PD on glycemic control and on diabetes-related complications. Conclusions The scientific evidence reviewed supports diabetes having an adverse effect on periodontal health and PD having an adverse effect on glycemic control and on diabetes-related complications. Further research is needed to clarify these relationships and larger, prospective, controlled trials with ethnically diverse populations are warranted to establish that treating PD can positively influence glycemic control and possibly reduce the burden of diabetes-related complications.

Prescription patterns for diabetes mellitus and therapeutic implications: a population-based analysis

Objective: To analyze drug prescriptions for insulin and oral antidiabetic drugs in type 1 and type 2 diabetes mellitus patients seen in the Brazilian Public Healthcare System (Unified Health System - SUS) in Ribeirao Preto, SP, Brazil. Subjects and methods: All the patients with diabetes seen in the SUS in the western district of Ribeirao Preto, SP, Brazil between March/2006 and February/2007 were included in the study. Results: A total of 3,982 patients were identified. Mean age of the patients was 60.6 years, and 61.0% were females. Sixty percent of the patients were treated with monotherapy. Doses of oral antidiabetic drugs were lower in monotherapy than in polytherapy. Ten patients received doses of glibenclamide or metformin above the recommended maximum doses, and in elderly patients there was no reduction in drug doses. Conclusion: Monotherapy with oral antidiabetic drugs was the predominant procedure, and the doses were not individualized according to age. Arq Bras Endocrinol Metab. 2012;56(2):120-7

Gene expression profiles displayed by peripheral blood mononuclear cells from patients with type 2 diabetes mellitus focusing on biological processes implicated on the pathogenesis of the disease

Patients with type 2 diabetes mellitus (T2DM) exhibit insulin resistance associated with obesity and inflammatory response, besides an increased level of oxidative DNA damage as a consequence of the hyperglycemic condition and the generation of reactive oxygen species (ROS). In order to provide information on the mechanisms involved in the pathophysiology of T2DM, we analyzed the transcriptional expression patterns exhibited by peripheral blood mononuclear cells (PBMCs) from patients with T2DM compared to non-diabetic subjects, by investigating several biological processes: inflammatory and immune responses, responses to oxidative stress and hypoxia, fatty acid processing, and DNA repair. PBMCs were obtained from 20 T2DM patients and eight non-diabetic subjects. Total RNA was hybridized to Agilent whole human genome 4x44K one-color oligo-microarray. Microarray data were analyzed using the GeneSpring GX 11.0 software (Agilent). We used BRB-ArrayTools software (gene set analysis - GSA) to investigate significant gene sets and the Genomica tool to study a possible influence of clinical features on gene expression profiles. We showed that PBMCs from T2DM patients presented significant changes in gene expression, exhibiting 1320 differentially expressed genes compared to the control group. A great number of genes were involved in biological processes implicated in the pathogenesis of T2DM. Among the genes with high fold-change values, the up-regulated ones were associated with fatty acid metabolism and protection against lipid-induced oxidative stress, while the down-regulated ones were implicated in the suppression of pro-inflammatory cytokines production and DNA repair. Moreover, we identified two significant signaling pathways: adipocytokine, related to insulin resistance; and ceramide, related to oxidative stress and induction of apoptosis. In addition, expression profiles were not influenced by patient features, such as age, gender, obesity, pre/post-menopause age, neuropathy, glycemia, and HbA(1c) percentage. Hence, by studying expression profiles of PBMCs, we provided quantitative and qualitative differences and similarities between T2DM patients and non-diabetic individuals, contributing with new perspectives for a better understanding of the disease. (C) 2012 Elsevier B.V. All rights reserved.

CYBA C242T polymorphism is associated with obesity and diabetes mellitus in Brazilian hypertensive patients

Diabet. Med. 29, e55e61 (2012) Abstract Aims The CYBA C242T polymorphism has been associated with cardiovascular phenotypes such as hypertension and atherosclerosis, but available data are conflicting. This report investigated the impact of this variant on hypertension and metabolic determinants of cardiovascular risk in a large Brazilian sample. Methods We cross-sectionally evaluated 1856 subjects (826 normotensive subjects and 1030 hypertensive patients) by clinical history, anthropometry, laboratory analysis and genotyping of the CYBA C242T polymorphism. Results Genotype frequencies in the whole population were consistent with the HardyWeinberg equilibrium and genotype distributions were not different between hypertensive and normotensive subjects. Hypertensive patients with the CC genotype presented lower fasting plasma glucose levels (5.9 +/- 0.1 vs. 6.2 +/- 0.1 mmol/l, P = 0.020) and waist circumference (94.5 +/- 0.6 vs. 96.3 +/- 0.6 cm, P = 0.028) than CT + TT ones. Similarly, the prevalence of diabetes mellitus and obesity was also lower in hypertensive patients carrying the CC genotype (16% vs. 21%, P = 0.041; 36% vs. 43%, P = 0.029, respectively). In addition, multiple and logistic regression analysis demonstrated that the CYBA C242T polymorphism was associated with glucose levels, waist circumference, obesity and diabetes mellitus in hypertensive patients independently of potential confounders. Conversely, in normotensive subjects, no significant difference in studied variables was detected between the genotype groups. Conclusions These data suggest that the T allele of the CYBA C242T polymorphism may be used as a marker for adverse metabolic features in Brazilian subjects with systemic hypertension.

LIRAGLUTIDE: NEW RESULTS IN THE TREATMENT OF TYPE 2 DIABETES MELLITUS

New drugs for type 2 diabetes that act on incretin metabolism have been shown to improve glycemic control, reduce body weight and have a low risk for hypoglycemia. Among these, liraglutide is the first glucagon-like peptide 1 (GLP-1) analogue approved for subcutaneous, once-daily administration. According to results from clinical trials, liraglutide is on attractive alternative for the early treatment of type 2 diabetes. The results of the LEAD (Liraglutide Effect and Action in Diabetes) study program demonstrated the efficacy and safety of liraglutide in terms of reduction of glycated hemoglobin (HbA(tc)) levels, significant loss of body weight that was maintained over the long term, better control of the lipid profile and systolic arterial pressure, reduction of the risk for hypoglycemia and reduction of cardiovascular risk. Moreover, the drug was demonstrated to be safe and can be co-administered with oral antidiabetic agents. The product's tolerability has been demonstrated, with nausea as the most common adverse event, which waned from the fourth week of treatment.

BDKRB2+9/-9 Polymorphism Is Associated with Higher Risk for Diabetes Mellitus in the Brazilian General Population

Some mechanisms have been proposed to explain the role of bradykinin on glucose homeostasis and some studies reported that the BDKRB2 +9/-9 polymorphism was associated to the transcriptional activity of the receptor. In this scenario, the main aim of this study was to evaluate the association of the BDKRB2 +9/-9 polymorphism with diabetes mellitus risk in the Brazilian general population. This study included 1,032 subjects of the general urban population. Anthropometrical, blood pressure, biochemical, and genotype analyses for the BDKRB2 +9/-9 bp insertion/deletion polymorphism were performed. Individuals carrying +9/+9 or +9/-9 genotypes had higher glucose values (84.5 mg/dL versus 80.6 mg/dL, resp.) and higher frequency of diabetes mellitus (7.6% versus 3.6%, resp.) compared to individuals carrying -9/-9, adjusting for age and gender. In addition, higher diabetes mellitus risk was associated to presence of the +9/+9 or +9/-9 genotypes (OR = 1.91; 95% CI = 1.09-4.19; P = 0.03). Our data suggest that the BDKRB2 +9/-9 polymorphism may act as a genetic modulator of glucose homeostasis. It was previously associated to insulin sensitivity, glucose uptake, and insulin secretion, and, in this study, data suggest that the polymorphism may increase susceptibility to chronic metabolic conditions such as diabetes in the Brazilian population.

Role of glycated hemoglobin in the care of diabetes mellitus

Introduction: Persistently high glycemic levels are extremely harmful to the organism and can lead patients to several complications of diabetes mellitus. Glycated hemoglobin represents the glycemic levels for what patient is chronically exposed. Methods: Two virtual databases were surveyed in two languages: Portuguese and English. 12 articles were selected and reviewed. Results and discussion: The HbA1c is used since 1958 in the assessment of glycemic control in diabetic patients. It is formed by a chemical reaction between hemoglobin A and acarbohydrate. Each percentage point of glycated hemoglobin represents approximately 35mg/dL in patient's averageglycemia. Conclusion: The glycated hemoglobin should be measured at least twice per year in patients with diabetes in general. In case of change of hypoglycemic therapy, this frequency should be doubled.

Correlates of the incidence of disability and mortality among older adult Brazilians with and without diabetes mellitus and stroke

Background: The combined effect of diabetes and stroke on disability and mortality remains largely unexplored in Brazil and Latin America. Previous studies have been based primarily on data from developed countries. This study addresses the empirical gap by evaluating the combined impact of diabetes and stroke on disability and mortality in Brazil. Methods: The sample was drawn from two waves of the Survey on Health and Well-being of the Elderly, which followed 2,143 older adults in Sao Paulo, Brazil, from 2000 to 2006. Disability was assessed via measures of activities of daily living (ADL) limitations, severe ADL limitations, and receiving assistance to perform these activities. Logistic and multinomial regression models controlling for sociodemographic and health conditions were used to address the influence of diabetes and stroke on disability and mortality. Results: By itself, the presence of diabetes did not increase the risk of disability or the need for assistance; however, diabetes was related to increased risks when assessed in combination with stroke. After controlling for demographic, social and health conditions, individuals who had experienced stroke but not diabetes were 3.4 times more likely to have ADL limitations than those with neither condition (95% CI 2.26-5.04). This elevated risk more than doubled for those suffering from a combination of diabetes and stroke (OR 7.34, 95% CI 3.73-14.46). Similar effects from the combination of diabetes and stroke were observed for severe ADL limitations (OR 19.75, 95% CI 9.81-39.76) and receiving ADL assistance (OR 16.57, 95% CI 8.39-32.73). Over time, older adults who had experienced a stroke were at higher risk of remaining disabled (RRR 4.28, 95% CI 1.53, 11.95) and of mortality (RRR 3.42, 95% CI 1.65, 7.09). However, risks were even higher for those who had experienced both diabetes and stroke. Diabetes was associated with higher mortality. Conclusions: Findings indicate that a combined history of stroke and diabetes has a great impact on disability prevalence and mortality among older adults in Sao Paulo, Brazil.

Therapeutic communication between health workers and patients concerning diabetes mellitus care

The objective of this cross-sectional study was to analyze therapeutic communication techniques used by health workers with patients under care for diabetes mellitus. Data were collected in 2010 in a public facility in the interior of Ceara, Brazil using video camera equipment and direct observation. Results showed that the most frequently used techniques within the "expression" group were: asking questions, voicing interest, and using descriptive phrases. The most frequently used technique within the "clarification" group was: asking the patient to specify the agent of action. Finally, in regard to the "validation" group, only the technique "summarizing content of the interaction" was employed. The conclusion is that despite the use of communication techniques on the part of professionals, there is still an alarming gap concerning communication skills. Such skills should be allied with technical expertise to enable the delivery of qualified care to individuals with diabetes mellitus.

Minimal change disease associated with type 1 and type 2 diabetes mellitus

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents. Arq Bras Endocrinol Metab. 2012;56(5):331-5

Relationship among social support, treatment adherence and metabolic control of diabetes mellitus patients

This cross-sectional and quantitative study aimed to analyze the relationship among social support, adherence to non-pharmacological (diet and physical exercise) and pharmacological treatments (insulin and/or oral anti-diabetic medication) and clinical and metabolic control of 162 type 2 diabetes mellitus patients. Data were collected through instruments validated for Brazil. Social support was directly correlated with treatment adherence. Adherence to non-pharmacological treatment was inversely correlated with body mass index, and medication adherence was inversely correlated with diastolic blood pressure. There were no associations between social support and clinical and metabolic control variables. Findings indicate that social support can be useful to achieve treatment adherence. Studies with other designs should be developed to broaden the analysis of relations between social support and other variables.