Estimation of diabetes risk in Brazilian population by typing for polymorphisms in HLA-DR-DQ, INS and CTLA-4 genes

The study aimed to further characterise HLA encoded risk factors of type 1 diabetes (T1D) in Brazilian population and test the capability of a low resolution full-house DR-DQ typing method to find subjects at diabetes risk. Insulin and CTLA-4 gene polymorphisms were also analysed. The method is based on an initial DQB1 typing supplemented by DQA1 and DR4 subtyping when informative. Increased frequencies of both (DR3)-DQA1*05-DQB1*02 and DRB1*04-DQA1*03-DQB1*0302 haplotypes were detected among patients. DRB1*0401, *0402, *0404 and *0405 alleles were all common in DQB1*0302 haplotypes and associated with T1D. (DRB1*11/12/1303)-DQA1*05-DQB1*0301, (DRB1*01/10)-DQB1*0501, (DRB1*15)-DQB1*0602 and (DRB1*1301)-*0603 haplotypes were significantly decreased among patients. Genotypes with two risk haplotypes or a combination of a susceptibility associated and a neutral haplotype were found in 78 of 126 (61.9%) T1D patients compared to 8 of 75 (10.7%) control subjects (P < 0.0001). Insulin gene -2221 C/T polymorphism was also associated with diabetes risk: CC genotype was found among 83.1% of patients compared to 69.3% of healthy controls (P = 0.0369, OR 1.98) but CTLA-4 gene +49 A/G polymorphism did not significantly differ between patients and controls. Despite the diversity of the Brazilian population the screening sensitivity and specificity of the used method for T1D risk was similar to that obtained in Europe.Univ Turku, JDRF Ctr Prevent Type 1 Diabet Finland, Turku, FinlandUNIFESP, Escola Paulista Med, Sao Paulo, BrazilFleury Inst, Sao Paulo, BrazilPerkinElmer Life & Analyt Sci, Turku, FinlandUniv Turku, Dept Virol, Turku, FinlandUNIFESP, Escola Paulista Med, Sao Paulo, BrazilWeb of Scienc

Fasting insulin concentration is highly correlated with quantitative insulin sensitivity check index

Given that the gold standard method for evaluating insulin sensitivity in vivo (hyperinsulinemic euglycemic glucose clamp technique) cannot be routinely applied because of technical reasons, simple methods and indexes were developed and are currently available to assess insulin sensitivity in vivo. Quantitative insulin sensitivity check index (QUICKI) has recently been described and is able to accurately estimate insulin sensitivity from a fasting blood sample. We demonstrated that fasting insulin levels strongly inversely correlated with QUICKI in three different groups: 215 healthy nondiabetic nonobese subjects, 62 nondiabetic obese subjects, and 44 patients with glucose intolerance or type 2 diabetes mellitus. Fasting insulin measurement is a simple way of assessing insulin sensitivity in obese and nonobese humans, with or without glucose intolerance or type 2 diabetes mellitus.Fleury Med Diagnost Ctr, Dept Endocrinol, BR-04344090 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Endocrinol, São Paulo, BrazilWeb of Scienc

Vitamin D endocrine system and the genetic susceptibility to diabetes, obesity and vascular disease. A review of evidence

The Vitamin D endocrine system regulates multiple aspects of calcium metabolism and cellular differentiation and replication in the immune system, endocrine pancreas, liver, skeletal muscles and adipocytes. It plays an important role in glucose homeostasis, notably, in the mechanism of insulin release. Actions of vitamin D are mediated by the binding of 1,25-(OH)2D3 to a specific cytosolic/nuclear vitamin D receptor (VDR), a member of the steroid/thyroid hormone receptor superfamily. Several frequent polymorphisms are found in the VDR gene and were reported to be associated with a variety of physiological and pathological phenotypes in many populations. in this paper, we will review the evidences suggesting associations of allelic variations in the VDR gene and phenotypes related to body weight, glucose homeostasis, diabetes and its vascular complications.INSERM, U695, Fac Med Xavier Bichat, F-75018 Paris, FranceFleury Inst, São Paulo, BrazilUniversidade Federal de São Paulo, Lab Mol Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Lab Mol Endocrinol, São Paulo, BrazilWeb of Scienc

Cushing's disease as the first clinical manifestation of multiple endocrine neoplasia type 1 (MEN1) associated with an R460X mutation of the MEN1 gene

Universidade Federal de São Paulo, Dept Med, Div Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Endocrinol, São Paulo, BrazilWeb of Scienc

Screening for macroprolactinaemia and pituitary imaging studies

OBJECTIVE Hyperprolactinaemia is caused by high levels of monomeric, dimeric or macro forms of prolactin in circulation, the monomeric form being predominant in patients with prolactinomas. Macroprolactinaemia, however, is common and is associated with asymptomatic cases. in this study, we reviewed our records regarding clinical and imaging investigations in patients who were found to have hyperprolactinaemia predominantly due to the presence of macroprolactin and compared them with the findings observed in patients whose prolactin molecular size consisted predominantly of the monomeric form.PATIENTS and METHODS We conducted a retrospective study of 113 consecutive patients (nine men and 104 women, aged 19-67 years, median age 39 years) with hyperprolactinaemia who were screened for the presence of macroprolactin by polyethylene glycol precipitation and/or chromatography and submitted to pituitary magnetic resonance imaging (MRI) and/or computerized tomography (CT).RESULTS Fifty-two of 113 patients (46%) had hyperprolactinaemia due to macroprolactin, whereas the remaining 61 patients (54%) had their hyperprolactinaemia confirmed by the predominance of the monomeric form. Both groups shared similar mean prolactin levels (79.9 +/- 63.6 mug/l, median of 62.0 mug/l, and 97.9 +/- 155.4 mug/l, median of 61.0 mug/l, respectively). of the patients with macroprolactinaemia, 46% had no symptoms of hyperprolactinaemia, whereas only 10% of the patients who screened negative for macroprolactin were asymptomatic. There was an association between macroprolactinaemia and negative pituitary imaging findings: normal pituitary images were found in 78.9% of patients who had macroprolactinaemia and in 25% of patients with monomeric hyperprolactinaemia. in addition, none of the patients with macroprolactinoma (seven cases) had macroprolactinaemia.CONCLUSIONS the presence of macroprolactinaemia does not exclude the possibility of a pituitary adenoma and consequently may not prevent pituitary imaging studies. However, our data demonstrate that all asymptomatic patients who screened positive for macroprolactin had normal pituitary imaging studies. Patient samples showing hyperprolactinaemia should be first tested for macroprolactin, before the patient is submitted to imaging studies. We suggest that imaging studies should be ordered in patients with macroprolactinaemia when indicated by clinically relevant features. As a result, unnecessary anxiety and costly medical procedures may be prevented.Universidade Federal de São Paulo, Fleury Diagnost Ctr, Dept Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Fleury Diagnost Ctr, Dept Radiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Fleury Diagnost Ctr, Dept Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Fleury Diagnost Ctr, Dept Radiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Endocrinol, São Paulo, BrazilWeb of Scienc

Analysis of the diagnostic presentation profile, parathyroidectomy indication and bone mineral density follow-up of Brazilian patients with primary hyperparathyroidism

Primary hyperparathyroidism is an endocrine disorder with variable clinical expression, frequently presenting as asymptomatic hypercalcemia in Western countries but still predominantly as a symptomatic disease in developing countries. The objective of this retrospective study was to describe the diagnostic presentation profile, parathyroidectomy indication and post-surgical bone mineral density follow-up of patients with primary hyperparathyroidism seen at a university hospital. We found 115 patients (92 women, median age 56 years) with primary hyperparathyroidism diagnosed during the last 20 years. We defined symptomatic patients based on the presence of any classical symptom affecting bone, kidney or the neuromuscular system. Surgical criteria followed the guidelines of the National Institutes of Health regarding asymptomatic primary hyperparathyroidism. Symptomatic patients and patients meeting surgical criteria for parathyroidectomy were 66 and 93% of the sample, respectively. Median calcium and parathyroid hormone values were 11.9 mg/dL and 189 pg/mL, respectively. After surgical treatment, 97% of patients were cured, with increases in bone mineral density of 19.4% in the lumbar spine and 15.7% in the femoral neck 3 years after surgery. Greater bone mass increases were detected in pre-menopausal women, men, and in symptomatic and younger patients, both in the lumbar spine and femoral neck. Our results support the previous findings of a predominantly symptomatic disease with a presentation profile that could be mainly related to a delayed diagnosis. Nevertheless, genetic and racial backgrounds, and nutritional factors such as calcium and vitamin D deficiency may play a role in the clinical presentation of primary hyperparathyroidism of Brazilian patients

Identification and functional analysis of a novel inactivating mutation (A804D) of the calcium-sensing receptor gene

Universidade Federal de São Paulo, Mol Endocrinol Lab, Disciplina Endocrinol, Escola Paulista Med, BR-04023062 São Paulo, BrazilInst Crianca, Fac Med, Unidade Endocrinol Pediat, São Paulo, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, Disciplina Endocrinol, Escola Paulista Med, BR-04023062 São Paulo, BrazilWeb of Scienc