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Abstract According to Brazilian National Data Survey diabetes is the fifth cause for hospitalization and is one of the ten major causes of mortality in this country. Aims to stratify the estimated cardiovascular risk (eCVR) in a population of type 2 diabetics (T2DM) according to the Framingham prediction equations as well as to determine the association between eCVR with metabolic and clinical control of the disease. Methods From 2000 to 2001 a cross-sectional multicenter study was conducted in 13 public out-patients diabetes/endocrinology clinics from 8 Brazilian cities. The 10-year risk of developing coronary heart disease (CHD) was estimated by the prediction equations described by Wilson et al (Circulation 1998). LDL equations were preferably used; when patients missed LDL data we used total cholesterol equations instead. Results Data from 1382 patients (59.0% female) were analyzed. Median and inter-quartile range (IQ) of age and duration of diabetes were 57.4 (51-65) and 8.8 (3-13) years, respectively without differences according to the gender. Forty-two percent of these patients were overweight and 35.4% were obese (the prevalence of higher BMI and obesity in this T2DM group was significantly higher in women than in men; p < 0.001). The overall estimated eCVR in T2DM patients was 21.4 (13.5-31.3). The eCVR was high (> 20%) in 738 (53.4%), intermediate in 202 (14.6%) and low in 442 (32%) patients. Men [25.1(15.4-37.3)] showed a higher eCVR than women [18.8 (12.4-27.9) p < 0.001]. The most common risk factor was high LDL-cholesterol (80.8%), most frequently found in women than in men (p = 0.01). The median of risk factors present was three (2-4) without gender differences. Overall we observed that 60 (4.3%) of our patients had none, 154(11.1%) one, 310 (22.4%) two, 385 (27.9%) three, 300 (21.7%) four, 149 (10.5%) five and six, (2%) six risk factors. A higher eCVR was noted in overweight or obese patients (p = 0.01 for both groups). No association was found between eCVR with age or a specific type of diabetes treatment. A correlation was found between eCVR and duration of diabetes (p < 0.001), BMI (p < 0.001), creatinine (p < 0.001) and triglycerides levels (p < 0.001) but it was not found with HbA1c, fasting blood glucose and post-prandial glucose. A higher eCVR was observed in patients with retinopathy (p < 0.001) and a tendency in patients with microalbuminuria (p = 0.06). Conclusion: our study showed that in this group of Brazilian T2DM the eCVR was correlated with the lipid profile and it was higher in patients with microvascular chronic complications. No correlation was found with glycemic control parameters. These data could explain the failure of intensive glycemic control programs aiming to reduce cardiovascular events observed in some studies.

Abstract Background In this study, we sought to evaluate the prevalence of metabolic syndrome (MS) in a cohort of pregnant women with a wide range of glucose tolerance, prepregnancy risk factors for MS during pregnancy, and the effects of MS in the outcomes in the mother and in the newborn. Methods One hundred and thirty six women with positive screening for gestational diabetes mellitus (GDM) were classified by two diagnostic methods: glycemic profile and 100 g OGTT as normoglycemic, mild gestational hyperglycemic, GDM, and overt GDM. Markers of MS were measured between 2428th during the screening. Results The prevalence of MS was: 0%; 20.0%; 23.5% and 36.4% in normoglycemic, mild hyperglycemic, GDM, and overt GDM groups, respectively. Previous history of GDM with or without insulin use, BMI ≥ 25, hypertension, family history of diabetes in first degree relatives, non-Caucasian ethnicity, history of prematurity and polihydramnios were statistically significant prepregnancy predictors for MS in the index pregnancy, that by its turn increased the adverse outcomes in the mother and in the newborn. Conclusion The prevalence of MS increases with the worsening of glucose tolerance; impaired glycemic profile identifies pregnancies with important metabolic abnormalities even in the presence of a normal OGTT, in patients that are not classified as having GDM.

The TyG index was evaluated as a surrogate method for estimation of insulin resistance (IR). TyG index correlated with adiposity, metabolic and atherosclerosis markers related to IR and presented a moderate degree of agreement with hyperglycemic clamp. TyG index represents an accessible tool for assessment of IR in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Graves' disease (GD) is the most common cause of hyperthyroidism and can cause cardiac changes, such as pulmonary hypertension., Methods: This is a prospective study in which we obtained demographic, clinical, laboratory data and characteristics of the GD, in addition to investigating cardiorespiratory function, focusing on the detection of pulmonary hypertension. Patients were separated into two groups: thyrotoxicosis and euthyroidism. Ninety patients with GD of both sexes, over 18 years of age, were included. The cardiorespiratory assessment included an echocardiographic evaluation, a questionnaire of specific symptoms, spirometry and a six-minute walk test., Results: The hyperthyroid group included 42 patients (47.73%) and the euthyroid group 46 patients (52.27%); 78 were women (86.67%). The prevalence of pulmonary hypertension between the hyperthyroidism (48.57%) and the euthyroidism (29.41%) groups was not different. Free thyroxine levels (FT4) (OR 1.266), higher left atrium volume (OR 1.113) and right ventricle diameter were associated with pulmonary hypertension. A direct correlation between FT4 with forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), as also an inverse correlation between initial oxygen saturation (SpO2) with diagnostic time and drop SpO2 with the ratio between the diastolic velocity E of the mitral flow and the diastolic velocity of the mitral ring (E/e') were observed in the euthyroid group. An inverse correlation between FT4 levels with walked distance as % of predicted value, and a direct correlation between E/e' ratio and walked distance as % of predicted value were observed in the hyperthyroid group., Conclusion: We emphasize the importance of a cardiorespiratory reassessment in GD, even after a long-term control of the thyrotoxic state, as we demonstrate that about 30% of these patients remain with PH and are subject to specific treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Araruna, Oliveira, Pereira, Moura Neto, Tambascia and Zantut-Wittmann.)

Aims: The aim of this study is to evaluate the efficacy of a fixed 30 mCi (1110 MBq) 131 I-iodine dose for the treatment of hyperthyroidism due to uninodular or multinodular toxic goiter and identify predictors of success., Materials and Methods: Fifty-nine patients diagnosed with nonautoimmune toxic goiter were treated with a fixed 30 mCi dose of 131 I-iodine and were followed at a tertiary service between 2000 and 2016. The therapy was considered successful if the patient reached euthyroidism or hypothyroidism without needing an extra 131 I-iodine dose or antithyroid drugs for at least 1 year after the radioiodine therapy (RIT)., Results: Patients with a single toxic nodule were younger at diagnosis (52 vs. 63 years; P = 0.007), presented a shorter disease duration until RIT (2 vs. 3.5 years; P = 0.007), smaller total thyroid volume (20 vs. 82 cm 3 ; P = 0.044), and lower pre-RIT thyroid uptake ( P = 0.043) than patients with multinodular goiter. No significant difference was seen with antithyroid drug use, thyroid-stimulating hormone and free thyroxine level, and follow-up after RIT. After RIT, 47 patients (79.66%) met the success criteria, and 12 (20.33%) remained hyperthyroid. Among the success group, 32 (68.08%) reached euthyroidism, while 31.92% developed hypothyroidism after 1 year. Patients with single toxic nodules who achieved success after RIT presented smaller nodules (2.8 vs. 5.75 cm; P = 0.043), while the pre-RIT thyroid uptake was higher among patients with multinodular toxic goiter who achieved success after RIT (5.5% vs. 1.5%; P = 0.007). A higher success rate was observed among patients with a single toxic nodule than those with a toxic multinodular goiter (92.3% vs. 55%; P = 0.001), and a single toxic nodule presentation was found to be an independent predictor of success ( P = 0.009)., Conclusions: The fixed 30 mCi 131 I-iodine dose was particularly effective in the group of patients with single autonomously functioning nodule rather than the group with multiple nodules. A single toxic nodule was an independent predictor of treatment success., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 World Journal of Nuclear Medicine.)

Purpose: Graves' ophthalmopathy (GO) is the most common extra-thyroid manifestation of Graves' disease (GD). The Clinical Activity Score (CAS) has been widely used to evaluate GO inflammation severity and response to treatment; however, it is quite subjective. Infrared thermography (IRT) is a portable and low-cost device to evaluate local temperature and assess inflammation. The aim was to evaluate ocular temperature by IRT as an instrument for measuring inflammatory activity in GO and its correlation with CAS., Methods: This is a cross-sectional study involving 136 consecutive GD patients (12 with CAS ≥ 3/7, 62 with CAS < 3 and 62 without apparent GO) with 62 healthy controls. Patients with active ophthalmopathy were prospectively evaluated. Exophthalmometry, CAS, and thermal images from caruncles and upper eyelids were acquired from all subjects., Results: All eye areas of thermal evaluation had higher temperatures in GD patients with active ophthalmopathy (caruncles, p<0.0001 ; upper eyelids, p<0.0001 ), and it was positively correlated with CAS (r=0.60 and p<0.0001 a t caruncles; r=0.58 and p<0.0001 at upper eyelids). No difference in temperature was found between other groups. Patients with active ophthalmopathy were prospectively evaluated after 6 or 12 months of the treatment and a significant difference was found in ophthalmometry ( p=0.0188 ), CAS ( p=0.0205 ), temperature of caruncles ( p=0.0120 ), and upper eyelids ( p=0.0066 )., Conclusions: IRT was an objective and simple tool for evaluation and follow-up of inflammation in GO, allowed evidencing patients with significant inflammatory activity, and had a good correlation with the CAS score.

Purpose: To assess quality of life (QoL) and cognitive function among Graves' disease (GD) patients with different thyroid status, with and without ophthalmopathy., Methods: This is a cross-sectional clinic-based study involving 154 patients with GD (81.27% were female, mean age 45.6 ± SD 11.2 years) and 54 (35.06%) had ophthalmopathy. Data were collected after an informed consent from all patients was obtained. All patients completed the 36-Item Short Form Health Survey and Mini-Mental State Examination. Patients with ophthalmopathy also completed the Graves' Orbitopathy Quality of Life Questionnaire., Results: Patients with hyperthyroidism presented a greater impairment in QoL when compared to euthyroidism group. A lower score in physical role functioning was found in both subgroups with active disease (hyperthyroidism and euthyroidism using thionamides). A lower score was also seen in visual function, only in patients with hyperthyroidism, without difference in appearance. No difference was found in cognition between patients. Younger ages at diagnosis, male sex, euthyroidism and absence of ophthalmopathy were factors associated with better QoL, as well as a shorter disease duration was associated with better recall, attention and calculation., Conclusions: An impairment in QoL among patients with active GD was evidenced, even in those receiving thionamides and in euthyroidism. Ophthalmopathy was a factor associated with a poor QoL and no clear evidence of cognitive impairment was demonstrated.

Several studies have shown the correlation between vitamin D [25(OH)D] deficiency and thyroid autoimmunity and reducing of thyroid autoantibodies in patients with normal levels of vitamin D combining with thyroid hormone replacement. However, other authors not agree with this association. It is still unclear whether the low 25(OH)D levels are the result of HT disease or a part of its cause. We studied 88 patients with HT regarding vitamin D status and thyroid autoimmunity markers as well as the relationship with cytokines produced by Th1, Th2, and Th17 cells compared with a control group of 71 euthyroid healthy subjects. The present study demonstrated that vitamin D concentrations were similar in patients HT and the control group. The reduction of free T4 levels was a predictor of vitamin D insufficiency for Hashimoto's thyroiditis, but not for the control group. Lower concentrations of TNF-α was a predictor of lower levels of vitamin D. Differences in the association between HT and vitamin D insufficiency remain unresolved in the literature. The thyroid hormone status would play a role in the maintenance of vitamin D sufficiency, and its immunomodulatory role would influence the presence of autoimmune thyroid disease. The positive correlation between free T4 and vitamin D concentrations suggests that adequate levothyroxine replacement in HT would be an essential factor in maintaining vitamin D at sufficient levels.

To better understand the genesis of autoimmunity in Graves' disease (GD), it is essential to study the mechanism of apoptosis and cell proliferation in thyroid cells and intrathyroidal lymphocytic infiltrate of GD patients. Methods . A cross sectional, observational study performed by evaluating histopathological samples of thyroidectomy products from GD patients using immunohistochemistry. New histological sections were prepared for immunohistochemical analysis with markers of cell proliferation, antiproliferation, apoptosis, and antiapoptosis. Results . Patients with GD who underwent radioiodine therapy (RIT) had a lower lymphocytic expression level of p27Kip1, and those who took beta-blockers had higher expression levels of BID ( BH3 -interacting domain) and a lower Ki-67 expression level in thyrocytes than those who did not. The association of a shorter diagnostic time with a lower expression level of MCL-1 in thyroid cells suggests that the hyperthyroid state was related to a lower antiapoptotic effect on thyrocytes. In comparison to patients with GD not using antithyroid drugs (ATD), we found a lower expression level of BID in lymphocytes for those who used ATD. Conclusion . In GD, the hyperthyroid state was associated with a lower antiapoptotic effect on thyroid cells. RIT, beta-blockers, and thionamide act by stimulating apoptosis of thyrocytes by intrathyroidal lymphocytes.

Aims: We aimed to explore insulin initiation barriers in the Brazilian Type 2 Diabetes Mellitus (T2DM) elderly population, according to the physician's perspective, and suggest strategies to overcome them., Methods: A 45-questions survey addressing issues as clinical characteristics, barriers to insulinization, and treatment strategies in elderly patients with T2DM, was sent to six endocrinologists from different Brazilian locations. Thereafter, all the respondents participated in a panel discussion to validate their responses and collect additional relevant data., Results: Endocrinologists had at least 15 years of experience, with a mean of 63 elderly patients per month. Nearly 25% of the elderly patients were treated in the Brazilian public healthcare system (SUS, Unified Health System); only a quarter presented proper glycemic control. In contrast, 55% of the patients from private healthcare system presented adequate glycemic control. The main barriers for insulin initiation for patients, according to physicians' perspective, are side effects and negative perception over treatment (100%). For endocrinologists, main barriers were lack of time to guide patients and concern over side effects (83%). Therefore, specialists considered education for both healthcare professionals and patients as one of the most important strategies to circumvent the current scenario related insulin therapy among elderly patients in the country., Conclusion: Insulin therapy remains underused due to several barriers, such as concern over side effects and negative perception. Educational measures for patients and HCPs could improve the current scenario., (Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: Obesity's increasing follows decreased perception of weight status in obese persons, mainly female, undergoing age-related changes., Objective: To study weight perception and psychological alterations associated to MS and T2DM., Methods: 200 patients selected from Metabolic Syndrome Outpatient Clinic of University of Campinas. Instruments: Beck Depression and Beck Anxiety Inventories', Toronto Alexithymia Scale-26s, questionnaire and data from reports. Approved by Unicamp Research Ethic Committee., Results: Patients aged 18-40 years perceived their weight higher than actual (A < D) (p = 0.0272), amongst untreated hypertensive (p = 0.037). ≥41 years old patient's subdivided into A = D and A > D. A = D had 4.3 more chances to be alexithymic than A < D. 35% of A < D accepted their physical appearance, contrarily A = D (66%) and A > D (69%) (p = 0.0018). 50% of A < D felt offended by social aggression due to their weight; A = D (20%) and A > D (34%) (p = 0.007). 3.6 more chances of A > D than A < D using anti-hypertensive drugs (p = 0.021) (≥41 years old) and 3.5 more chances to perceive A = D (41-60 years old) (p = 0.023). A = D presented 3.8 more chances of depression than A < D and 4.3 more chances of alexithymia than A < D (62% of 41-60 year-old patients with higher cholesterol, mainly LDL and hyper-triglycerides). A = D with alexithymia, partially linked with higher cholesterol, suggests neuroinflammation due to hypertriglycerides. Females, who declared had been anteriorly made diet as treatment to lose weight were exactly those who perceived their weight A > D (45%, p = 0.0091)., Conclusions: Age as a period of development, in which cultural influences occurs, was a factor in weight misperception. A < D and A > D were distinct in age, history of obesity and BMI.

Background: The major adverse consequences of obesity are associated with the development of insulin resistance (IR) and adiposopathy. The Homeostasis Model Assessment-Adiponectin (HOMA-AD) was proposed as a modified version of the HOMA1-IR, which incorporates adiponectin in the denominator of the index., Objectives: To evaluate the performance of the HOMA-AD index compared with the HOMA1-IR index as a surrogate marker of IR in women, and to establish the cutoff value of the HOMA-AD., Subjects/methods: The Brazilian Metabolic Syndrome Study (BRAMS) is a cross-sectional multicenter survey. The data from 1,061 subjects met the desired criteria: 18-65 years old, BMI: 18.5-49.9 Kg/m² and without diabetes. The IR was assessed by the indexes HOMA1-IR and HOMA-AD (total sample) and by the hyperglycemic clamp (n = 49). Metabolic syndrome was defined using the IDF criteria., Results: For the IR assessed by the clamp, the HOMA-AD demonstrated a stronger coefficient of correlation (r = -0.64) compared with the HOMA1-IR (r = -0.56); p < 0.0001. In the ROC analysis, compared with the HOMA1-IR, the HOMA-AD showed higher values of the AUC for the identification of IR based on the clamp test (AUC: 0.844 vs. AUC: 0.804) and on the metabolic syndrome (AUC: 0.703 vs. AUC: 0.689), respectively; p < 0.001 for all. However, the pairwise comparison did not show evidence of superiority for the HOMA-AD in comparison with the HOMA1-IR in the diagnosis of IR and metabolic syndrome (p > 0.05). The optimal cutoff identified for the HOMA-AD for the diagnosis of IR was 0.95., Conclusions: The HOMA-AD index was demonstrated to be a useful surrogate marker for detecting IR among adult women and presented a similar performance compared with the HOMA1-IR index. These results may assist physicians and researchers in determining which method to use to evaluate IR in light of the available facilities.

Thyroid hormone (TH) abnormalities are common in patients with diabetes mellitus (DM). These thyroid hormone abnormalities have been associated with inflammatory activity in several conditions but this link remains unclear in DM. We assessed the influence of subclinical inflammation in TH metabolism in euthyroid diabetic patients. Cross-sectional study involving 258 subjects divided in 4 groups: 70 patients with T2DM and 55 patients with T1DM and two control groups of 70 and 63 non-diabetic individuals, respectively. Groups were paired by age, sex, and body mass index (BMI). We evaluated the association between clinical and hormonal variables [thyrotropin, reverse T3 (rT3), total and free thyroxine (T4), and triiodothyronine (T3)] with the inflammation markers C-reactive protein (hs-CRP), serum amyloid A (SAA), and interleukin-6 (IL-6). Serum T3 and free T3 were lower in patients with diabetes (all P < 0.001) compared to the control groups. Interleukin-6 showed positive correlations with rT3 in both groups (P < 0.05). IL-6 was independently associated to FT3/rT3 (B = -0.193; 95% CI -0.31; -0.076; P = 0.002) and FT4/rT3 (B = -0.107; 95% CI -0.207; -0.006; P = 0.039) in the T1DM group. In the T2DM group, SAA (B = 0.18; 95% CI 0.089; 0.271; P < 0.001) and hs-CRP (B = -0.069; 95% CI -0.132; -0.007; P = 0.03) predicted FT3 levels. SAA (B = -0.16; 95% CI -0.26; -0.061; P = 0.002) and IL6 (B = 0.123; 95% CI 0.005; 0.241; P = 0.041) were related to FT4/FT3. In DM, differences in TH levels compared to non-diabetic individuals were related to increased subclinical inflammatory activity and BMI. Altered deiodinase activity was probably involved. These findings were independent of sex, age, BMI, and HbA1c levels.

The development of extended-action insulin analogues was motivated by the unfavorable pharmacokinetic (PK) profile of the conventional long-acting insulin formulations, generally associated with marked inter and intra patient variability and site- and dose-dependent effect variation. The new ultra-long insulin analogue degludec (IDeg) has the same amino acid sequence as human insulin except for the removal of threonine in the position 30 of the B chain (Des-B30, "De") and the attachment, via a glutamic acid linker ("glu"), of a 16-carbon fatty diacid (hexadecanoic diacid, "dec") to lysine in the position 29 of the B chain. These modifications allow that, after changing from the pharmaceutical formulation to the subcutaneous environment, IDeg precipitates in the subcutaneous tissue, forming a depot that undergoes a highly predictable gradual dissociation. Thus, once-daily dosing of IDeg results in a low peak: trough ratio, with consequent low intra-individual variability and plasmatic concentrations less critically dependent upon the time of injections. The clinical development program of IDeg (BEGIN) was comprised of 9 therapeutic confirmatory trials of longer duration (26-52 weeks) and showed that the efficacy of IDeg is comparable to insulin glargine in type 1 (T1D) and type 2 (T2D) diabetes patients across different age, body mass index and ethnic groups. This new ultra-long insulin analogue presents as advantages flexibility in dose timing and lower risk of hypoglycemia.

Background: Sagittal abdominal diameter (SAD) has been proposed as a surrogate marker of insulin resistance (IR). However, the utilization of SAD requires specific validation for each ethnicity. We aimed to investigate the potential use of SAD, compared with classical anthropometrical parameters, as a surrogate marker of IR and to establish the cutoff values of SAD for screening for IR., Methods: A multicenter population survey on metabolic disorders was conducted. A race-admixtured sample of 824 adult women was assessed. The anthropometric parameters included: BMI, waist circumference (WC), waist-to-hip ratio and SAD. IR was determined by a hyperglycemic clamp and the HOMA-IR index., Results: After adjustments for age and total body fat mass, SAD (r = 0.23 and r = -0.70) and BMI (r = 0.20 and r = -0.71) were strongly correlated with the IR measured by the HOMA-IR index and the clamp, respectively (p < 0.001). In the ROC analysis, the optimal cutoff for SAD in women was 21.0 cm. The women with an increased SAD presented 3.2 (CI 95%: 2.1-5.0) more likelihood of having IR, assessed by the HOMA-IR index compared with those with normal SAD (p < 0.001); whereas women with elevated BMI and WC were 2.1 (95% CI: 1.4-3.3) and 2.8 (95% CI: 1.7-4.5) more likely to have IR (p < 0.001), respectively. No statistically significant results were found for waist-to-hip ratio., Conclusions: SAD can be a suitable surrogate marker of IR. Understanding and applying routine and simplified methods is essential because IR is associated with an increased risk of obesity-related diseases even in the presence of normal weight, slight overweight, as well as in obesity. Further prospective analysis will need to verify SAD as a determinant of clinical outcomes, such as type 2 diabetes and cardiovascular events, in the Brazilian population.

Objective: Retinol-binding protein 4 (RBP4) is an adipokine responsible for vitamin A (retinol) transportation. Studies associated RBP4 increased levels with severity of type 2 diabetes mellitus (T2DM) and insulin resistance (IR). The study aimed to quantify RBP4 serum standards in women with a wide range of body mass index (BMI) and glucose tolerance level., Subjects and Methods: Cross-sectional study was performed with 139 women divided into three groups: Group 1 (lean-control, n = 45) and Group 2 (obese, n = 53) with normal glucose tolerance and group 3 (obese with T2DM, n = 41), called G1, G2 and G3. Were assessed clinical, biochemical, anthropometric and body composition parameters., Results: According to data analysis, we obtained in G1 higher RBP4 levels (104.8 ± 76.8 ng/mL) when compared to G2 (87.9 ± 38 ng/mL) and G3 (72.2 ± 15.6 ng/mL) levels. Also, were found: in G1 positive correlations of RBP4 with BMI (r = 0.253), glycated hemoglobin (r = 0.378) and fasting insulin (r = 0.336); in G2 with glycated hemoglobin (r = 0.489); in G3 with glycated hemoglobin (r = 0.330), fasting glucose (r = 0.463), HOMA-IR (r = 0.481)., Conclusions: Although RBP4 have shown lower levels in diabetic and obese, a strong correlation with HOMA-IR index highlights that, in our study, there is growing IR when there is an increasing in RBP4 levels.

Objective: To estimate the impact of aging and diabetes on insulin sensitivity, beta-cell function, adipocytokines, and incretin production., Methods: Hyperglycemic clamps, arginine tests and meal tolerance tests were performed in 50 non-obese subjects to measure insulin sensitivity (IS) and insulin secretion as well as plasma levels of glucagon, GLP-1 and GIP. Patients with diabetes and healthy control subjects were divided into the following groups: middle-aged type 2 diabetes (MA-DM), aged Type 2 diabetes (A-DM) and middle-aged or aged subjects with normal glucose tolerance (MA-NGT or A-NGT)., Results: IS, as determined by the homeostasis model assessment, glucose infusion rate, and oral glucose insulin sensitivity, was reduced in the aged and DM groups compared with MA-NGT, but it was similar in the MA-DM and A-DM groups. Insulinogenic index, first and second phase insulin secretion and the disposition indices, but not insulin response to arginine, were reduced in the aged and DM groups. Postprandial glucagon production was higher in MA-DM compared to MA-NGT. Whereas the GLP-1 production was reduced in A-DM, no differences between groups were observed in GIP production., Conclusions: In non-obese subjects, diabetes and aging impair insulin sensitivity. Insulin production is reduced by aging, and diabetes exacerbates this condition. Aging associated defects superimposed diabetic physiopathology, particularly regarding GLP-1 production. On the other hand, the glucose-independent secretion of insulin was preserved. Knowledge of the complex relationship between aging and diabetes could support the development of physiopathological and pharmacological based therapies., (Copyright © 2014. Published by Elsevier Inc.)

The maintenance of glucose homeostasis is complex and involves, besides the secretion and action of insulin and glucagon, a hormonal and neural mechanism, regulating the rate of gastric emptying. This mechanism depends on extrinsic and intrinsic factors. Glucagon-like peptide-1 secretion regulates the speed of gastric emptying, contributing to the control of postprandial glycemia. The pharmacodynamic characteristics of various agents of this class can explain the effects more relevant in fasting or postprandial glucose, and can thus guide the individualized treatment, according to the clinical and pathophysiological features of each patient.

Alterations in thyroid hormone levels are found associated with inflammation in patients with non-thyroidal illness (NTIS) and are common in patients with type 2 diabetes mellitus (T2DM). Inflammation has also been linked with development of cardiovascular events (CVE) in T2DM. Our objective was to assess whether thyroid hormone abnormalities typical of NTIS in patients with T2DM are related to inflammation and CVE. This was a cross-sectional study of 140 subjects; 70 with T2DM and 70 as a control group paired by age, sex and body mass index (BMI). We recorded age, sex, BMI, waist/hip ratio, diabetes duration, HbA1c, CVE history, serum amyloid A (SAA), TSH, total (T) and free (F) T4 and T3, reverse T3 (rT3) and TT3/rT3 ratio. Patients with T2DM had lower levels of TT4 (p = 0.012), TT3 (p < 0.001), FT3 (p < 0.001) and TT3/rT3 (p = 0.002). They also showed higher FT4 (p < 0.001) and similar TSH levels (p = 0.627) compared to the control group. SAA levels correlated positively with rT3 (r = 0.45; p < 0.001) and inversely with TT3/rT3 (r = -0.38; p = 0.001). Patients with T2DM and history of CVE had higher rT3 (p = 0.006) and lower TT3/rT3 (p = 0.002), along with higher SAA levels (p = 0.002) than patients without this characteristic. Multiple logistic regression showed that factors independently associated with CVE were older age (OR = 1.159, 95 % CI 1.011-1.329), male sex (OR = 4.391, 95 % CI 1.081-17.829) and higher TT3/rT3 (OR = 0.993, 95 % CI 0.987-0.999). We have confirmed the presence of NTIS in T2DM. We also showed that thyroid hormone abnormalities are associated to inflammatory activity and to CVE in these patients.

Brazil is expected to have 19.6 million patients with diabetes by the year 2030. A key concept in the treatment of type 2 diabetes mellitus (T2DM) is establishing individualized glycemic goals based on each patient's clinical characteristics, which impact the choice of antihyperglycemic therapy. Targets for glycemic control, including fasting blood glucose, postprandial blood glucose, and glycated hemoglobin (A1C), are often not reached solely with antihyperglycemic therapy, and insulin therapy is often required. Basal insulin is considered an initial strategy; however, premixed insulins are convenient and are equally or more effective, especially for patients who require both basal and prandial control but desire a more simplified strategy involving fewer daily injections than a basal-bolus regimen. Most physicians are reluctant to transition patients to insulin treatment due to inappropriate assumptions and insufficient information. We conducted a nonsystematic review in PubMed and identified the most relevant and recently published articles that compared the use of premixed insulin versus basal insulin analogues used alone or in combination with rapid-acting insulin analogues before meals in patients with T2DM. These studies suggest that premixed insulin analogues are equally or more effective in reducing A1C compared to basal insulin analogues alone in spite of the small increase in the risk of nonsevere hypoglycemic events and nonclinically significant weight gain. Premixed insulin analogues can be used in insulin-naïve patients, in patients already on basal insulin therapy, and those using basal-bolus therapy who are noncompliant with blood glucose self-monitoring and titration of multiple insulin doses. We additionally provide practical aspects related to titration for the specific premixed insulin analogue formulations commercially available in Brazil.

Objective: To investigate the relationship of the neck circumference (NC) with the metabolic syndrome (MetS) and insulin resistance (IR) in a large Brazilian population-based sample, within a wide range of adiposity and glucose tolerance, and to establish cut-off values of the NC for MetS and IR., Context: The NC correlates with cardiovascular risk factors, IR and components of MetS. Upper-body subcutaneous (sc) fat, as estimated by the NC, is associated with cardiovascular risk factors as much as abdominal fat, which is usually estimated by the waist circumference (WC). There are few epidemiological population-based studies on the clinical significance of the NC to MetS and IR., Design: This is a cross-sectional study., Patients: About 1053 Brazilian adults (18-60 years)., Measurements: Patients with BMI 18.5-40.0 kg/m(2), with normal glucose tolerance or type 2 diabetes (T2DM), were submitted to anthropometric measurements including waist circumference (WC), NC and BMI. Abdominal visceral fat (VF) was assessed by ultrasound. Insulin sensitivity (IS) was assessed by euglycaemic-hyperinsulinaemic clamp (10% of total sample) and HOMA-IR. Spearman correlations were used to evaluate the association between NC and IR and MetS risk factors. Receiver operating characteristic (ROC) curves were used for gender-specific cut-off values for the prediction of IR and MetS. Binary logistic regression analysis was used to assess the chance of developing IR or MetS according to the enlargement of NC and WC., Results: The sample consisted of 28.6% men, with a mean age of 39.4 (12 years). T2DM diagnosis was present in 306 individuals, of whom 34% were men. NC correlated with WC and BMI in both men and women (P < 0.001). In both genders, NC showed a positive correlation with triglycerides, fasting glucose, fasting insulin and HOMA-IR, and NC had a negative association with high-density lipoprotein (HDL). NC and IS showed a moderate negative correlation. A significant correlation was demonstrated between VF and NC. In the ROC curves, NC presented the largest AUC for IR in women (P < 0.001), while NC presented a large AUC for MetS in both genders., Conclusions: Neck circumference measurements are an alternative and innovative approach for determining body fat distribution. The NC is positively associated with MetS risk factors, IR and VF, with established cut-off values for the prediction of MetS and IR., (© 2012 John Wiley & Sons Ltd.)

Objectives. Assess the prevalence of thyroid nodules and predictors of malignant origin in patients with autoimmune thyroid diseases. Patients and Methods. Retrospective study including 275 patients, 198 with Graves' disease and 77 with Hashimoto's thyroiditis. Clinical and demographical data, ultrasonographical nodule characteristics, total thyroid volume and histological characteristics were recorded. Results. Graves' disease: the prevalence of thyroid nodules and thyroid carcinoma were 27.78% and 5.05%, respectively. Older age (OR = 1.054; 95% CI = 1.029-1.080) and larger thyroid volumes (OR = 1.013; 95% CI = 1.003-1.022) increased the chance of nodules. Younger age (OR = 1.073; 95% CI = 1.020-1.128) and larger thyroid volume (OR = 1.018; 95% CI = 1.005-1.030) predicted thyroid carcinoma. Hashimoto's thyroiditis: the prevalence of thyroid nodules and carcinomas were 50.7% and 7.8%, respectively. Nodules were predicted by thyroid volume (OR = 1.030; 95% CI = 1.001-1.062). We found higher number of nodules in patients with thyroid carcinoma than in those with benign nodules (3 versus 2; P = 0.03). Patients with Hashimoto's thyroiditis presented nodules more frequently than patients with Graves' disease (50.65% versus 27.28%; P < 0.001), while the prevalence of carcinoma was similar (P = 0.751). Conclusions. Larger goiter was associated with carcinoma in Graves' disease and Hashimoto's thyroiditis. Younger patients presented higher risk of papillary thyroid carcinoma in Graves' disease. The prevalence of carcinoma was similar in both conditions.

Previous reports highlight the role of systemic inflammation in the genesis of non-thyroidal illness syndrome and type 2 diabetes mellitus (T2DM). Our objective was to assess whether body mass index and the low-grade systemic inflammation would be associated with changes in thyroid hormone metabolism in patients with type 2 diabetes. This was a cross-sectional study of 104 subjects; 52 patients with type 2 diabetes and 52 in a control group, paired by age, gender and body mass index. We measured total (T) and free (F) thyroxine (T4) and triiodothyronine (T3), reverse T3 (rT3), the ratios FT3/rT3, FT3/FT4 and FT4/rT3, clinical parameters (age, gender, diabetes duration and complications, body mass index, waist circumference, hypertension, HbA1c), and high sensitivity C-reactive protein. Patients with DM presented lower levels of TT4 (p=0.006), TT3 (p<0.001) and FT3 (p<0.001) and higher of FT4 (p<0.001), waist circumference (p=0.047) and C-reactive protein (p<0.001). Body mass index was inversely correlated with FT4 (p=0.036) and TT3 (p=0.008). C-reactive protein was positively correlated with rT3 (p=0.001) and inversely with FT4/rT3 (p<0.001) and FT3/rT3 (p=0.014). Body mass index was an independent predictor for FT4 (B=-0.011, p=0.029) and TT3 levels (B=-1.118, p=0.003). Inflammation predicted the FT4/rT3 ratio (B=-0.190, p<0.001). C-reactive protein (B=0.235, p<0.001) and body mass index (B=-0.008, p=0.047) were independent predictors for rT3. In conclusion, type 2 diabetes was associated with a low T3 state. Body mass index and the low-grade systemic inflammation are related to the non-thyroidal illness syndrome in these patients, possibly by altering the activity of peripheral deiodinases.

Since the publication of the United Kingdom Prospective Diabetes Study (UKPDS), the progressive nature of type 2 (DM2) diabetes has been identified as the main cause of failure to maintain a long term glycemic control.[1] The need to adjust treatment as the disease progressed was recognized and algorithms for treatments in line with this concept were developed.[2] The UKPDS showed that the progressive character of the disease results from a steady reduction, of approximately 5% per year, in the ability of beta cells to secrete insulin, a process estimated to begin 10 to 12 years before diagnosis, which triggers the onset of diabetes when approximately 50% of beta cell function has been lost. [1] Copyright © 2012 John Wiley & Sons, Ltd., (Copyright © 2012 John Wiley & Sons, Ltd.)

The objective of this case report is to present a rare association of a mucosa-associated lymphoid tissue lymphoma masquerading as Graves' orbitopathy in a patient with autoimmune hyperthyroidism, without evidence of Graves' ophthalmopathy. A 66-year-old male patient had pain and swelling of the right eye. Evaluation of serum thyroid hormone revealed low thyrotropin, elevated free thyroxin and antithyroperoxidase antibody levels, confirming the diagnosis of Graves' disease. Computed tomographic scan showed intraorbital muscle asymmetry. Biopsy demonstrated a low-grade, B-cell type non-Hodgkin's lymphoma of the mucosa-associated lymphoid tissue. Treatment included radiotherapy and chemotherapy, with regression of the orbital lesion and medical treatment with methimazole and (131)I. Detailed orbital evaluation should be considered in all patients who present any atypical signs and symptoms of the eyes, to prevent missing important and progressive diagnoses.

Objective: To compare duodenal-jejunal bypass (DJB) with standard medical care in nonobese patients with type 2 diabetes and evaluate surgically induced endocrine and metabolic changes., Methods: Eighteen patients submitted to a DJB procedure met the following criteria: overweight, diabetes diagnosis less than 15 years, current insulin treatment, residual β-cell function, and absence of autoimmunity. Patients who refused surgical treatment received standard medical care (control group). At baseline, 3, 6, and 12 months after surgery, insulin sensitivity and production of glucagon-like peptide-1 and glucose-insulinotropic polypeptide were assessed during a meal tolerance test. Fasting adipocytokines and dipeptidyl-peptidase-4 concentrations were measured., Results: The mean age of the patients was 50 (5) years, time of diagnosis: 9 (2) years, time of insulin usage: 6 (5) months, fasting glucose: 9.9 (2.5) mmol/dL, and HbA1c (glycosylated hemoglobin) level: 8.9% (1.2%). Duodenal-jejunal bypass group showed greater reductions in fasting glucose (22% vs 6% in control group, P < 0.05) and daily insulin requirement (93% vs 15%, P < 0.01). Twelve patients from DJB group stopped using insulin and showed improvements in insulin sensitivity and β-cell function (P < 0.01), and reductions in glucose-insulinotropic polypeptide levels (P < 0.001), glucagon during the first 30 minutes after meal (P < 0.05), and leptin levels (P < 0.05). Dipeptidyl-peptidase-4 levels increased after surgery (P < 0.01), but glucagon-like peptide-1 levels did not change., Conclusions: Duodenal-jejunal bypass improved insulin sensitivity and β-cell function and reduced glucose-insulinotropic polypeptide, leptin, and glucagon production. Hence, DJB resulted in better glycemic control and reduction in insulin requirement but DJB did not result in remission of diabetes.

Purpose: To investigate the factors influencing the success rate in a fixed, 15 mCi approach for treatment of Graves' hyperthyroidism., Material and Methods: The thyroid function outcome (hyperthyroidism or euthyroidism/hypothyroidism) was verified at least 1 year after radioiodine therapy (RIT) retrospectively and compared with presenting clinical characteristics and pre-RIT parameters in 87 patients treated with I-iodide for Graves' disease in a tertiary care center., Results: After RIT, 16 patients (18.4%) became euthyroid, 54 patients (62.1%) became hypothyroid, and 17 (19.5%) remained hyperthyroid. We found no statistically significant association between thyroid function outcome and gender (P = 0.50), ophthalmopathy (P = 0.69), drug used (methimazole or propylthiouracil; P = 1.00), maintenance or withdrawal of thionamides pre-RIT (P = 0.98), or 99mTc sodium pertechnetate thyroid uptake prior to RIT (P = 0.75). The only variable associated with the success rate was thyroid mass <62 g (P < 0.001)., Conclusions: Our study has shown that a fixed 15 mCi approach for treatment of Graves' disease was effective, but high failure rates were observed in patients presenting larger goiters, particularly those with estimated thyroid mass >62 g.

Purpose of the Report: To compare thyroid imaging using Tc-99m sestamibi with the standard Tc-99m pertechnetate scintigraphy in patients on chronic use of amiodarone., Materials and Methods: A total of 23 patients on oral amiodarone for at least 4 months had thyroid scintigraphy and uptake measurement using Tc-99m pertechnetate and Tc-99m sestamibi. Thyroid function was evaluated by measuring serum concentrations of thyrotropin, free thyroxine, and free triiodothyronine, and antithyroglobulin and antithyroperoxidase antibodies., Results: Ten of the 23 patients were euthyroid, 9 hypothyroid, and 4 hyperthyroid, with normal, increased, and decreased serum thyrotropin, respectively. All euthyroid patients had markedly decreased thyroid Tc-99m pertechnetate uptake and normal or slightly increased Tc-99m sestamibi uptake, except for one patient who had increased uptake of both radiotracers. One of the 4 hyperthyroid patients had Graves' disease and markedly increased thyroid uptake of both tracers. The other 3 hyperthyroid patients had normal or decreased Tc-99m pertechnetate uptake and increased Tc-99m sestamibi uptake. Differently than expected, all 9 hypothyroid patients had normal or increased uptake of both radiopharmaceuticals., Conclusions: This study suggests that Tc-99m sestamibi may be an alternative tracer for thyroid scintigraphy and uptake measurement of patients on chronic use of amiodarone. Tc-99m sestamibi seems to be better than Tc-99m pertechnetate for the scintigraphic evaluation of the thyroid of euthyroid and hyperthyroid patients.

Background: A 24-week interventional prospective trial was performed to compare the benefits of open duodenal-jejunal exclusion surgery (GJB) with a matched control group on standard medical care., Methods: One-hundred eighty patients were screened for the surgical approach. Twelve patients accepted to be operated and presented the full eligibility criteria for surgery that includes overweight BMI (25-29.9 kg/m2), T2DM diagnosis for less than 15 years, insulin-treated patients, no history of major complications, preserved beta-cell function, and absence of autoimmunity. A matched control group (CG) of patients whom refused surgical treatment was placed to receive standard care. Patients had age of 50 (5) years, time of diagnosis 9 years (range, 3 to 15 years), time of insulin usage 6 months (range, 3 to 48 months), fasting glucose (FG), 9.8 (2.5) mg/dL, and glycated hemoglobin (A1C) 8.90 (2.12)%., Results: At 24 weeks after surgery, patients experienced greater reductions on FG (14% vs. 7% on CG), A1C (from 8.78 to 7.84 in GJB-p<0.01 and 8.93 to 8.71 in CG; p<0.05 between groups) and reductions on average daily insulin requirement (93% vs. 29%, p<0.01). Ten patients stopped insulin usage in GJB but they remain taking oral medications. No differences were observed in both groups regarding BMI, body distribution and composition, blood pressure, and lipids., Conclusions: In conclusion, duodenal-jejunal exclusion was an effective treatment for nonobese T2DM subjects. GJB was superior to standard care in achieving better glycemic control along with reduction in insulin requirements.

Objective: To investigate cut-off values for HOMA1-IR and HOMA2-IR to identify insulin resistance (IR) and metabolic syndrome (MS), and to assess the association of the indexes with components of the MS., Methods: Nondiabetic subjects from the Brazilian Metabolic Syndrome Study were studied (n = 1,203, 18 to 78 years). The cut-off values for IR were determined from the 90th percentile in the healthy group (n = 297) and, for MS, a ROC curve was generated for the total sample., Results: In the healthy group, HOMA-IR indexes were associated with central obesity, triglycerides and total cholesterol (p < 0.001). The cut-off values for IR were: HOMA1-IR > 2.7 and HOMA2-IR > 1.8; and, for MS were: HOMA1-IR > 2.3 (sensitivity: 76.8%; specificity: 66.7%) and HOMA2-IR > 1.4 (sensitivity: 79.2%; specificity: 61.2%)., Conclusion: The cut-off values identified for HOMA1-IR and HOMA2-IR indexes have a clinical and epidemiological application for identifying IR and MS in Westernized admixtured multi-ethnic populations.

Objective: To assess the relationship between adiponectin and metabolic parameters in severely obese women during surgical-induced weight loss., Methods: Nineteen lean (CT - BMI:21.2 +/- 0.3 kg.m(2)), 14 overweight/class II obese (OB/OW - BMI: 29.7 +/- 0.7 kg/m(2)) and 8 morbidly obese (OBIII - BMI: 56.4 +/- 3.6 kg/m(2)) were evaluated by hyperinsulinemic-euglycemic clamp, adiponectin, and lipids. OBIII were evaluated at 5th and 16th month post-operatively., Results: Compared to lean, obese groups had lower adiponectin (OB/OW: 9.4 +/- 0.9, OBIII: 7.1 +/- 1.3 versus 12.2 +/- 0.9 ng/dL; p < 0.01), lower HDL-cholesterol (OB/OW:1.05 +/- 0.05, OBIII: 0.88 +/- 0.04 versus 1.22 +/- 0.07 mmol/L; p < 0.01) and insulin resistance-IR (glucose uptake, M-value - OB/OW: 43.6 +/- 2.7, OBIII: 32.4 +/- 3.2 versus 20.0 +/- 1.8 umol/kgFFM.min; p < 0.001). Considering all subjects, adiponectin levels were inversely correlated to BMI and waist circumference, and directly to M-value and HDL-cholesterol (p < 0.01). During weight loss, improvements in IR (Study III: 36.1 +/- 3.9 umol/kg/FFM.min, p < 0.0001), adiponectin (11.8 +/- 1.4 ng/dL, p = 0.006) and HDL-cholesterol were observed (1.10 +/- 0.04 mmol/L, p = 0.007). Moreover, HDL-cholesterol improvement was significantly and independently related to variations of adiponectin and BMI (r(2) = 0.86; p < 0.0002)., Conclusions: The improvements of IR and adiponectin were related to surgical-induced weight loss, suggesting an important role of adiponectin in HDL-cholesterol regulation.

There is an association between insulin resistance, glucose intolerance, and essential hypertension, but the relation between insulin resistance, glucose intolerance, and hypertension diagnosed during pregnancy is not well understood. Transient hypertension of pregnancy, the new-onset nonproteinuric hypertension of late pregnancy, is associated with a high risk of later essential hypertension and glucose intolerance; thus, these conditions may have a similar pathophysiology. To assess the association between insulin resistance, glucose intolerance, essential hypertension, and subsequent development of proteinuric and nonproteinuric hypertension in pregnancy in women without underlying essential hypertension, we performed a prospective study comparing glucose (fasting, 1 and 2 hours postglucose load), insulin, glycosylated hemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-C), and triglycerides levels on routine screening for gestational diabetes mellitus. Women who developed hypertension in pregnancy (n = 37) had higher glycemic levels (fasting, 1 and 2 hours postglucose load) on a 100-gram oral glucose loading test, although only the fasting values showed a statistical significance (p < 0.05), and a significantly higher frequency of abnormal glucose loading tests, two hours after glucose load (>or=140 mg/dL) (p < 0.05) than women who remained normotensive (n = 180). Glucose intolerance was common in women who developed both subtypes of hypertension, particularly preeclampsia. Women who developed hypertension had greater prepregnancy body mass index (p < 0.0001), higher frequency and intensity of acanthosis nigricans (p < 0.0001), and higher baseline systolic and diastolic blood pressures (p

Objective: The aims of this study were to evaluate the prevalence of metabolic syndrome (MS) in a cohort of pregnant women with a wide range of glucose tolerance, pre-pregnancy risk factors for MS during pregnancy and the effects of MS in the occurrence of adverse perinatal outcomes., Research Design and Methods: One hundred and thirty six women with positive screening for gestational diabetes (GDM) were classified by two diagnostic methods: glycaemic profile and 100 g oral glucose tolerance test (OGTT) as normoglycaemic, mild gestational hyperglycaemic, GDM, and overt GDM. Markers of insulin resistance were measured between 24-28 and 36th week of gestation, and 6 weeks after delivery., Results: The prevalence of MS was 0; 20.0; 23.5 and 36.4% in normoglycaemic, mild hyperglycaemic, GDM and overt GDM groups, respectively. Previous history of GDM with or without insulin use, body mass index (BMI) > or = 25, hypertension, family history of diabetes in first-degree relatives, non-Caucasian ethnicity, history of prematurity and polyhydramnios were statistically significant pre-pregnancy predictors for MS in the index pregnancy, that by its turn increased the occurrence of adverse perinatal outcomes (p = 0.01)., Conclusions: The prevalence of MS increases with the worsening of glucose tolerance and is an independent predictor of adverse perinatal outcomes; impaired glycaemic profile identifies pregnancies with important metabolic abnormalities that are linked to the occurrence of adverse perinatal outcomes even in the presence of a normal OGTT, in patients that are not currently classified as having GDM., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

Background: Researchers have found that zinc nutritional status in obese and diabetic subjects is altered: low zinc concentrations in plasma and erythrocytes, with high urinary zinc excretion, were observed. This study evaluated the effect of Roux-en-Y gastric bypass (RYGBP) on plasma, erythrocyte and urinary zinc concentration., Methods: 22 morbidly obese patients were studied before and 6 months after RYGBP. Fasting blood sample and 24-hour urine were collected in the pre- and postoperative phases. A software analyzed the diet information from 3-day food records after RYGBP. Zinc nutritional status was evaluated by determination of the concentration of this mineral in plasma and erythrocytes, and the urinary excretion of zinc / 24 hours by atomic absorption spectrophotometry., Results: The diets consumed by the patients had adequate average concentrations of zinc. Zinc concentration in plasma, erythrocytes and urine were within the values of normality before RYGBP, with mean values of 93.25 +/- 19.34 microg/dL, 43.85 +/- 7.76 microg Zn/gHb and 583.05 +/- 359.30 microg Zn/24 hours, respectively. At 6 months after RYGBP, there was a change in these parameters to 69.82 +/- 10.95 microg/dL, 51.80 +/- 6.92 microg Zn/gHb, 535.29 +/- 216.40 microg Zn/24 hours in the concentration of plasma, erythrocyte and urinary zinc., Conclusion: These results suggest that RYGBP promoted, besides change in body composition, an alteration in the zinc plasma and erythrocytes concentrations which in the medium and long term, could cause problems for these patients.

Leptin is thought to be a lipostatic signal that contributes to body weight regulation. Zinc might play an important role in appetite regulation and its administration stimulates leptin production. However, there are few reports in the literature on its role on leptin levels in the obese population. The present work assesses the effect of zinc supplementation on serum leptin levels in insulin resistance (IR). A prospective double-blind, randomized, clinical, placebo-controlled study was conducted. Fifty-six normal glucose-tolerant obese women (age: 25-45 yr, body mass index [BMI] = 36.2 +/- 2.3 kg/m2) were randomized for treatment with 30 mg zinc daily for 4 wk. Baseline values of both groups were similar for age, BMI, caloric intake, insulin concentration, insulin resistance, and zinc concentration in diet, plasma, urine, and erythrocytes. Insulin and leptin were measured by radioimmunoassay and IR was estimated by the homeostasis model assessment (HOMA). The determinations of zinc in plasma, erythrocytes, and 24- h urine were performed by using atomic absorption spectrophotometry. After 4 wk, BMI, fasting glucose, and zinc concentration in plasma and erythrocyte did not change in either group, although zinc concentration in the urine increased from 385.9 +/- 259.3 to 470.2 +/- 241.2 +/- microg/24 h in the group with zinc supplementation (p < 0.05). Insulin did not change in the placebo group, whereas there was a significant decrease of this hormone in the supplemented group. HOMA also decreased from 5.8 +/- 2.6 to 4.3 +/- 1.7 (p < 0.05) in the zinc-supplemented group but did not change in the placebo group. Leptin did not change in the placebo group. In the zinc group, leptin was 23.6 +/- 12.3 microg/L and did not change. More human data from a unique population of obese individuals with documented insulin resistance would be useful in guiding future studies on zinc supplementation (with higher doses or longer intervals) or different measures.

Severe pancytopenia is a rare but severe complication of thyrotoxicosis. In this report, we describe four patients with Graves' disease who presented with pancytopenia at diagnosis. Methimazole (30-40 mg/d) or propylthiouracil (400 mg/d) restored normal hematopoiesis in three of the patients. The remaining patient evolved to aplastic anemia under therapy with methimazole (60 mg/d), but had an increased peripheral blood count that almost reached normal values after radioiodinetherapy and standard immunosuppressive treatment with antithymocyte globulin (700 mg/d, intravenous infusion for 5 days), oral cyclosporin (400 mg/d), prednisone (30-60 mg/d), and granulocyte colony-stimulating factor (150 microg subcutaneous injection, 3 times per week). We conclude that: (1) a hematologic evaluation of all patients with Graves' disease should be performed before administering antithyroid drugs, (2) antithyroid drugs may be administered to patients with pancytopenia and bone marrow hypercellularity but a reevaluation of the bone marrow must be done if there is no recovery of the peripheral blood cell count when euthyroidism state is achieved, (3) standard immunosuppressive treatment of aplastic anemia caused by antithyroid drugs restores normal hematopoiesis, and (4) a thyroid evaluation of patients with pancytopenia should be done, even though no related symptoms are found.

The hyperandrogenism found in polycystic ovary syndrome (PCOS) can be a consequence of hyperinsulinemia as a result of peripheral insulin resistance. Metformin and insulin sensitizers have become a potential therapeutic tool for treating these patients; however, there are few studies with pioglitazone in PCOS. Elevated luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratios and LH hyper-responsivity to stimulation with gonadotropin-releasing hormone (GnRH) are common findings in PCOS. The reason why hyperinsulinemia produces hyperandrogenism and whether insulin action on the pituitary alters gonadotropin liberation remain unknown. In the present study, we evaluated the effect of pioglitazone (30 mg/day for 2 months) on insulin response to an oral glucose tolerance test (OGTT), serum levels of androgens and sex hormone-binding globulin (SHBG), and pituitary gonadotropin response to GnRH stimulation in 15 obese PCOS women. We found a significant decrease in insulin response to the OGTT and also in total and free testosterone levels, an increase in SHBG and a reduction in the LH response to GnRH stimulation after pioglitazone treatment. In conclusion, this short-term treatment with pioglitazone decreased hyperinsulinemia and hyperandrogenemia in obese PCOS patients, and there was a significant reduction in LH response to GnRH stimulation. Further research should be carried out to establish the risks and benefits of pioglitazone, which would assist in the physiopathologic comprehension of PCOS.

Background and Objective: Several factors may interfere with the success rate of radioiodine therapy (RIT) in Graves' disease. Our aim was to evaluate, retrospectively, some of these factors in the outcome of RIT., Methods: Patient gender, age at diagnosis, ophthalmopathy, disease duration, thyroid size, drug used as clinical treatment, thionamide withdrawal period during RIT preparation, FT4, TSH and [99mTc]pertechnetate thyroid uptake prior to RIT were studied as potential interference factors for RIT success. Eighty-two Graves' disease patients were submitted to RIT after thionamide treatment failure. Prior to RIT, 67 patients were receiving methimazole and 15 propylthiouracil. Thirty-three patients received thionamides during RIT; in 49 patients the medication was withdrawn for 2-30 days. [99mTc]pertechnetate thyroid uptake was determined before RIT. Fixed doses of 370 MBq of [131I]iodide were administered to all patients., Results: Eleven patients became euthyroid; 40 became hypothyroid and 31 remained hyperthyroid. There was no association between outcome and age at diagnosis, gender, ophthalmopathy, pre-RIT FT4, TSH, antithyroid antibodies or thyrostatic drug. Multiple logistic regression showed higher probability of treatment success in patients with thyroid mass <53 g (odds ratio (OR)=8.9), with pre-RIT thyroid uptake <12.5% (OR=4.1) and in patients who withdrew thionamide before RIT (OR=4.9)., Conclusions: Fixed doses of 370 MBq of radioiodine seem to be practical and effective for treating Graves' disease patients with [99mTc]pertechnetate uptake <12.5% and thyroid mass <53 g. This treatment is clearly not recommended for patients with large goitre. In contrast to what could be expected, patients with a high pre-RIT thyroid uptake presented a higher rate of RIT failure.

Purpose: We investigated the biokinetics of (99m)Tc-sestamibi in the thyroid of euthyroid volunteers (EVs) and in patients with autoimmune thyroid diseases and determined the best time interval between (99m)Tc-sestamibi injection and calculation of uptake., Methods: Forty EVs, 30 patients with Graves' disease (GD), 15 patients with atrophic Hashimoto's thyroiditis (AHT) and 15 patients with hypertrophic Hashimoto's thyroiditis (HHT) underwent (99m)Tc-sestamibi thyroid scintigraphy. Dynamic images were acquired for 20 min, and static images were obtained 20 min, 60 min and 120 min post injection. Five-, 20-, 60- and 120-min uptake, time to maximal uptake (T(max)) and T(1/2) of tracer clearance were calculated. Thyroid hormones and antibodies were measured. (99m)Tc-pertechnetate uptake was investigated in GD patients., Results: T(max) was approximately 5 min in all four groups. The mean T(1/2) value for EVs was similar to the GD value and lower than the HHT and AHT values. The mean (+/-SD) 5-min uptake was 0.13% (+/-0.05%) for EVs. The 5-min uptake in GD was higher than that in EVs(P<0.001) and correlated with free thyroxine (r=0.54) and with (99m)Tc-pertechnetate uptake (r=0.68). Uptake in HHT was higher than that in AHT (P=0.0003) and EVs (P=0.002). Uptake in AHT was lower than uptake in EVs (P=0.0001)., Conclusion: Five minutes is the optimal time interval between (99m)Tc-sestamibi injection and calculation of thyroid uptake. Five-minute uptake differentiates euthyroid individuals from GD patients. There is a high correlation between (99m)Tc-sestamibi and (99m)Tc-pertechnetate uptake in GD. The reduced (99m)Tc-sestamibi uptake in AHT patients is probably due to glandular destruction and fibrosis. Inflammatory infiltrate and high mitochondrial density in thyrocytes possibly explain the increased uptake in GD and HHT.

Cardiovascular disease is the primary cause of death in Brazil. Recent studies have shown that low birth weight and preterm birth are linked to a higher prevalence of cardiovascular disease. The aim of the present study was to compare the levels of lipids and apolipoproteins and atherogenic indexes between term and near-term newborn infants. A sample of umbilical cord blood was obtained from 135 newborns (66 males) divided into two groups: 25 near-term neonates (35-36.6 weeks of gestational age) and 110 term neonates (37-42 weeks of gestational age). The total cholesterol concentrations were higher in the near-term neonates than in the term group (94.04 +/- 8.02 vs 70.42 +/- 1.63 mg/dl, P < 0.01), due to an increase in the LDL-cholesterol fraction in the near-term group (57.76 +/- 6.39 vs 34.38 +/- 1.29 mg/dl, P < 0.001). The atherogenic indexes (total cholesterol/HDL-cholesterol, LDL-cholesterol/HDL-cholesterol and apolipoprotein B/apolipoprotein A-I) were higher in the near-term group (P < 0.001, P < 0.001, and P < 0.05, respectively). The gestational age of the newborns was inversely correlated with total cholesterol and LDL-cholesterol, and also with the total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol indexes. These findings demonstrate that the lipid profile is worse in the group of near-term neonates compared with the term group. Future studies are needed to determine if this atherogenic profile in near-term neonates can affect body metabolism, increasing the risk for cardiovascular diseases in adult life.

Background: Maternal smoking is linked with several neonatal metabolic disorders. Adiponectin is an adipose-specific hormone with anti-inflammatory and antiatherogenic properties., Aim: The aim of this study was to evaluate the effect of maternal smoking on cord blood adiponectin concentrations., Methods: We evaluate the effect of maternal smoking on cord blood adiponectin concentrations comparing 14 full-term and seven preterm newborns born to mothers who smoked during pregnancy with 77 full-term and 10 preterm neonates born to non-smokers mothers., Results: Maternal smoking during pregnancy was significantly associated with decreased adiponectin levels of preterm newborns (p < 0.05)., Conclusions: Our findings also reveal a significant relationship between the reported number of cigarettes smoked during pregnancy and cord blood adiponectin concentrations (p = 0.01), suggesting that this association could have a causal relationship.

Autoimmune chronic lymphocytic thyroiditis appears in two forms, goitrous and atrophic. The evidence available is not enough to prove that the goitrous precedes the atrophic form, but immunogenetic analysis suggests that they may be distinct entities. The distribution of HLA class II alleles DRB1* and DQB1* was verified in patients from the region of Campinas, São Paulo, Brazil with both forms of thyroiditis. Ninety-one patients with primary hypothyroidism through autoimmune thyroiditis were classified as goitrous - 54 patients, 42.27 +/- 11.72 years old, having had hypothyroidism for 8.57 +/- 6.63 years - or atrophic - 37 patients, 42.72 +/- 12.01 years old, hypothyroidism for 6.73 +/- 4.07 years. The distribution of class II alleles was determined, DRB1* and DQB1* were genotyped after purifying DNA blood samples using the DNAzol technique, and the low-resolution PCR-SSP system was utilized for determination of generic alleles. Chi-square and Fisher's exact test were utilized to compare the distribution frequency of HLA alleles and the significant p-values were subjected to Bonferroni correction. We have demonstrated that the DRB1*04 allele is associated with autoimmune thyroiditis, and that there are genotypic differences regarding the presentation forms with a strong association between DRB1*04 and DQB1*03 and the atrophic form only.

Objectives: Leptin, a hormone produced in adipose tissue and the placenta, is correlated with neonatal growth. The aim of this study was to investigate the effect of maternal smoking during pregnancy on cord blood leptin concentrations in term, appropriate-for-gestational-age infants., Methods: Two groups of term, appropriate-for-gestational-age newborns were selected: 19 infants of smoking mothers and 91 infants of non-smoking mothers. Neonatal anthropometric measurements were taken and leptin levels were measured by radioimmunoassay., Results: Leptin concentrations were similar (p=0.915) between the groups. Leptin levels correlated only with ponderal index (p < 0.01) and gestational age of the newborns (p < 0.05)., Conclusions: This study indicates that maternal smoking during pregnancy does not affect cord blood leptin levels in term, appropriate-for-gestational-age infants.

Objective: Adiponectin is the only adipose-specific hormone that, despite its exclusive production by adipose tissue, is reduced in obesity and is inversely correlated with leptin levels in adults. The aim of this study was to evaluate the adiponectin concentration in umbilical cord blood at different gestational ages and to investigate its possible associations with leptin levels and birth weight., Research Methods and Procedures: Umbilical cord blood was obtained from 132 newborns (male = 65, female = 67, gestational age: 35 to 42 weeks). The anthropometric variables of the newborns studied were birth weight, birth length, body weight/body length, and ponderal index. Adiponectin, insulin, and leptin levels were measured by radioimmunoassay methods., Results: Adiponectin levels in males were not different from those in females (24.10 +/- 0.81 vs. 25.62 +/- 0.84 micro g/mL, p = 0.280). Adiponectin concentrations were positively correlated with birth weight (p < 0.05), birth length (p < 0.05), body weight/body length (p < 0.05), gestational age (p < 0.01), and leptin levels (p < 0.01)., Discussion: These findings indicate that adiponectin is present in umbilical cord blood after 35 to 42 weeks of gestation, with higher levels than those usually found in adults, no gender differences, and a positive correlation with birth weight and leptin. These results suggest that not only could neonatal hyperadiponectinemia be associated with the increase of adiponectin production by fetal adipose tissue but also with a possible reduction in an unknown mechanism related to the suppression of adiponectin observed in adults.