Vitamin D in Hashimoto's thyroiditis and its relationship with thyroid function and inflammatory status.

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.

Neck circumference as a simple tool for identifying the metabolic syndrome and insulin resistance: results from the Brazilian Metabolic Syndrome Study.

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.

The influence of body mass index and low-grade systemic inflammation on thyroid hormone abnormalities in patients with type 2 diabetes.

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.

Metabolic surgery for non-obese type 2 diabetes: incretins, adipocytokines, and insulin secretion/resistance changes in a 1-year interventional clinical controlled study.

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 ß-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 ß-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 ß-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.

Can we prevent beta cell apoptosis in type 2 diabetes?

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.

Interplay Between Thyroid Hormone Status and Pulmonary Hypertension in Graves' Disease: Relevance of the Assessment in Thyrotoxic and Euthyroid Patients.

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.

Fixed 30 mCi (1110 MBq) 131I-iodine therapy in autonomously functioning nodules: Single toxic nodule as a predictive factor of success.

AIMS: The aim of this study is to evaluate the efficacy of a fixed 30 mCi (1110 MBq) 131I-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 131I-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 131I-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 cm3; 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 131I-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.

The relationship between quality of life, cognition, and thyroid status in Graves' disease.

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.

Value of Infrared Thermography Camera Attached to a Smartphone for Evaluation and Follow-up of Patients with Graves' Ophthalmopathy.

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 at 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.

Barriers to insulin initiation in elderly patients with type 2 diabetes mellitus in Brazil.

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.

Value of Apoptotic, Antiapoptotic, and Cell Proliferation Markers in the Treatment of Graves' Disease.

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.

Incretins: clinical physiology and bariatric surgery--correlating the entero-endocrine system and a potentially anti-dysmetabolic procedure.

The digestive tract is well known for its endocrine functions. Recently, many studies have been reinforcing its role as a therapeutic target for both diabetes and obesity. Losing weight is clinically very difficult for most obese patients and the reason for this could be the effect of the physiological adipostatic system that triggers central nervous stimuli to compensate for variations in food intake and in physical activity. Gut hormones seem to have a key role in this complex, regulating body weight and satiety and contributing to glucose homeostasis. The enteroinsular axis appears to be impaired in both obese and diabetic patients. Recent data on bariatric surgery shows its striking effects on glucose control soon after the procedure, before a significant weight loss is achieved. The procedure appears to work beyond anti-obesity having a key metabolic impact possibly sharing a common mechanism with the new class of agents to treat type 2 diabetes mellitus: the incretin mimetics. This symposium discussed new data on the upcoming perspectives on both the pharmacological and the surgical approach to diabetes and obesity.

Depression and alexithymia on weight perception in patients with metabolic syndrome and type 2 diabetes.

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.

[Laboratorial evaluation and diagnosis of insulin resistance]. / Avaliação laboratorial e diagnóstico da resistência insulínica.

Due to the association between insulin resistance (IR) and atherosclerosis, there is an interest in the development of techniques to evaluate insulin sensitivity (IS) in vivo. Fasting blood glucose, easy to use in study populations, has been used to evaluate IS and supplies a good evaluation of hepatic sensitivity, but not muscular sensitivity to insulin. HOMA is a mathematical model that predicts IS simply by measuring insulinemia and fasting blood glucose and shows good correlation with hyperinsulinemic-euglycemic clamp method, considered a gold standard in the measurement of IS. Thus, it has been shown a valuable alternative to the most sophisticated and difficult techniques in the evaluation of IR in humans. In our population, the cut value for the diagnosis of IR is Homa-IR higher than 2,71. QUICKI is another simple method, also based in the measurements of insulinemia and fasting blood glucose, that have good correlations with the metabolic syndrome markers, being able to discriminate satisfactorily different states of IR, in patients with different degrees of obesity and glucose tolerance. Direct methods of IS evaluation include insulin tolerance test (K ITT), insulin suppression test and hyperinsulinemic-euglycemic clamp technique that are described in this article. Hyperinsulinemic-euglycemic clamp technique supplies the best and purest information on the insulin action. Costs involved in its procedure, however, limit its use.

Relation of thyroid hormone abnormalities with subclinical inflammatory activity in patients with type 1 and type 2 diabetes mellitus.

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 HOMA-Adiponectin (HOMA-AD) Closely Mirrors the HOMA-IR Index in the Screening of Insulin Resistance in the Brazilian Metabolic Syndrome Study (BRAMS).

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.

[Chronic renal failure and growth hormone: effects on GH-IGF axis and leptin]. / Insuficiência renal crônica e hormônio de crescimento: efeitos no eixo GH-IGF e na leptina.

AIM: To analyze the changes in IGF-1, IGFBP-3, leptin and insulin after replacement doses of recombinant human growth hormone (rhGH) in short prepubertal children with chronic renal failure (CRF). PATIENTS AND METHODS: Eleven children (3F:8M), with mean age of 9.6 years, were treated with rhGH (0.23 mg/Kg weekly for 12 months). Serum leptin, insulin, glucose, IGF-1 and IGFBP-3 were measured before, 6 and 12 months after beginning rhGH treatment. RESULTS: The serum levels of leptin, insulin and glucose did not vary during the treatment; normal leptin and glucose levels and high insulin were observed. There was a significant increment of IGF-1 and IGFBP-3 during the use of rhGH. CONCLUSIONS: The replacement doses of rhGH during 12 months in a selected group of CRF children determined an increment in IGF-1 and IGFBP-3, associated to normal serum leptin and insulin resistance.

Degludec: the new ultra-long insulin analogue.

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.

Sagittal Abdominal Diameter as a Surrogate Marker of Insulin Resistance in an Admixtured Population--Brazilian Metabolic Syndrome Study (BRAMS).

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.

Thyroid uptake and scintigraphy using 99mTc pertechnetate: standardization in normal individuals.

CONTEXT: Thyroid uptake and scintigraphy using 99mTc-pertechnetate has proven to be more advantageous than with 131I-iodide, since the images have better quality, the procedure is faster and the patient is submitted to a lower radiation dose. OBJECTIVE: The purpose of this study was to standardize a simple and fast methodology for performing thyroid uptake and scintigraphy and to determine the normal values for 99mTc- pertechnetate uptake. TYPE OF STUDY: Prospective, non-randomized. SETTING: Division of Nuclear Medicine, Department of Radiology, School of Medical Sciences, Campinas State University. PARTICIPANTS: The study consisted of 47 normal individuals, 30 women and 17 men, with ages ranging from 19 to 61 years (mean of 33 years). PROCEDURES: The laboratory assessment of thyroid function consisted of serum dosages of ultra-sensitive thyroxin and thyrotrophin. Twenty minutes after an intravenous injection of 10 mCi (370 MBq) of 99mTc-pertechnetate, the images were obtained on a computerized scintillation camera equipped with a low-energy high-resolution parallel hole collimator. RESULTS: All the individuals were euthyroid both on clinical and laboratory evaluation. The baseline thyroid 99mTc-pertechnetate uptake ranged from 0.4 to 1.7%. The uptake values obtained in these normal individuals showed that 95% presented a thyroid uptake that ranged from 0.4 to 1.5% of the injected dose. CONCLUSION: The assessment of thyroid structure and function using 99mTc-pertechnetate is a simple, fast and efficient method, which could easily become a part of the routine studies in nuclear medicine laboratories.