The MODY Type of Diabetes Mellitus

It is estimated that close to 5% of the individuals classified as having type 2 diabetes mellitus (DM) and about 10% of those considered type 1 DM (previously categorized as juvenile type) are actual carriers of a MODY mutation. In this form of DM, there is evident co-segregation of some mutations and the advent of hyperglycemia, this fact having been reproduced by the study of several families of different populations. Its main characteristic is being one of the few causes of DM in which the transmission of the genetic susceptibility is due to an autossomical dominant inheritance, making part of the group classified as monogenic DM, where the other members are very rare. Mutations occurring in MODY genes, even in the heterozygous form, lead to a profound phenotypic impact (high penetrance), in that 95% of the individual carriers of a MODY mutation will be diabetic or will have altered glicemic metabolism before the age of 55 years. In this paper we approach this form of DM, emphasizing its most relevant clinical and genetic characteristics. The systematic search for MODY mutations is beginning to take place regularly in many countries, and there is a tendency to add this diagnostic tool to the routine exams in the practice of diabetology.Estima-se que perto de 5% dos indivíduos classificados como portadores de diabetes mellitus (DM) tipo 2 e 10% daqueles considerados como tipo 1 (anteriormente classificado como juvenil) sejam, na verdade, portadores de mutações MODY. Nesta forma de DM ocorre uma co-segregação evidente de algumas mutações com a hiperglicemia, fato este reproduzido em inúmeras famílias estudadas em várias populações do mundo. Caracteriza-se por ser uma das poucas causas de DM cujo modo de transmissão da predisposição genética ocorre de uma forma autossômica-dominante, compondo o grupo chamado de DM monogênicos, onde os outros representantes têm uma prevalência bastante rara. As mutações nos genes MODY, mesmo no estado heterozigoto, apresentam um forte impacto no fenótipo (alta penetrância), sendo que 95% dos indivíduos nascidos com alguma mutação MODY serão diabéticos ou apresentarão alterações no âmbito do metabolismo glicídico antes dos 55 anos de idade. Este trabalho objetiva a discussão desta forma de DM, enfatizando suas características clínicas e genéticas mais relevantes. A pesquisa sistemática de mutações MODY começa a ser feita de forma rotineira em vários países, havendo uma tendência de se colocar este recurso diagnóstico como um exame na prática da diabetologia.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Development of a semi-automated method for measuring urinary iodine and its application in epidemiological studies in Brazilian schoolchildren

In this study we developed a semi-automated method for the measurement of urinary iodine using firstly ammonium persulfate for digestion of urine followed by estimation of iodine content in the Sandell-Kolthoff reaction, in which iodine acts as a catalyst for the reduction of cerium. This method was validated in the 3rd Brazilian National Survey of iodine deficiency in 1994. We studied 16,803 casual urine samples from schoolchildren of 401 cities and found 4 moderately-deficient towns (Almas, Arraias, and Parana, in the State of Tocantins, and Cocos, in the State of Bahia), and 116 mildly-deficient. This work suggests that despite the salt iodization program, there was some iodine-deficient areas in Brazil in 1994. Recent surveys, involving less cities, are indicating an excess of iodine ingestion. Therefore, in a country of continental dimensions and very heterogeneous in terms of public health, periodical evaluations are necessary to monitor the real situation of iodine nutrition in Brazil. the method developed in this paper is suitable for these surveys.Univ Estadual Maringa, Dept Med, Ctr Ciencias Saude, Maringa, Parana, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, Disciplina Endocrinol, Dept Med,Escola Paulista Med, BR-04032029 São Paulo, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, Disciplina Endocrinol, Dept Med,Escola Paulista Med, BR-04032029 São Paulo, BrazilWeb of Scienc

HNF1A gene polymorphisms and cardiovascular risk factors in individuals with late-onset autosomal dominant diabetes: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes mellitus (T2DM) is a genetically heterogeneous disease, hepatocyte nuclear factor-1 homeobox A (<it>HNF1A</it>) single-nucleotide polymorphisms (SNPs) playing a minor role in its pathogenesis. <it>HNF1A </it>is a frequent cause of monogenic diabetes, albeit with early-onset. Some uncommon subgroups like late-onset autosomal dominant diabetes mellitus (LOADDM) may present peculiar inheritance patterns with a stronger familial component. This study aims to investigate the relationship of <it>HNF1A </it>SNPs with cardiovascular risk factors in this group, as well as to characterize them in contrast with classical T2DM (CT2DM).</p> <p>Methods</p> <p>eighteen LOADDM (age at onset > 40 y.o.; diabetes in 3 contiguous generations, uniparental lineage) along with 48 CT2DM patients and 42 normoglycemic controls (N group) have been evaluated for cardiovascular risk factors and SNPs of <it>HNF1A</it>.</p> <p>Results</p> <p>LOADDM showed significantly higher frequencies of SNPs A98V (22.2% vs 2.1%, p = 0.02) and S487N (72.2% vs 43.8%, p = 0.049) of <it>HNF1A </it>compared to CT2DM. I27L did not show significant difference (66.7% vs 45.8%), but associated with lower risk of hypertriglyceridemia (OR 0.16, 95% CI 0.04–0.65, p = 0.01). "Protective effect" was independent from other well-known predictive risk factors for hypertriglyceridemia, such as waist circumference (OR 1.09 per 1 cm increase, p = 0.01) and HDL (OR 0.01 per 1 mmol/l, p = 0.005), after logistic regression.</p> <p>Conclusion</p> <p>Late onset autosomal dominant diabetes mellitus is clinically indistinguishable from classical type 2 diabetes individuals. However, LOADDM group is enriched for common <it>HNF1A </it>polymorphisms A98V and S487N. I27L showed "protective effect" upon hypertriglyceridemia in this sample of individuals, suggesting a role for <it>HNF1A </it>on diabetic individuals' lipid profile. These data contribute to the understanding of the complex interactions between genes, hyperglycemia and cardiovascular risk factors development in type 2 diabetes mellitus.</p

Low iodine diet does not improve the efficacy of radioiodine for the treatment of Graves&apos; disease

ABSTRACT Objective: Consuming a low-iodine diet (LID) is a widely accepted practice before administering radioiodine ( 131 I) to evaluate and to treat thyroid disease. Although this procedure is well established for the management of patients with differentiated thyroid cancer, its use in patients with benign disease is unclear. So, we aimed to evaluate the influence of a LID on the outcome in patients with Graves&apos; disease (GD) treated with 131 I. Subjects and methods: We evaluated 67 patients with GD who were divided into 2 groups: one group (n = 31) consumed a LID for 1-2 weeks, and the second group (n = 36) was instructed to maintain a regular diet (RD). Results: The LID group experienced a 23% decrease in urinary iodine after 1 week on the diet and a significant 42% decrease after 2 weeks on the diet. The majority (53%) of the patients in the LID group had urinary iodine levels that were consistent with deficient iodine intake. However, there was no difference in the rate of hyperthyroidism&apos;s cure between the LID and the RD groups 6 months after 131 I therapy. Furthermore, the therapeutic efficacy did not differ in patients with varying degrees of sufficient iodine intake (corresponding urinary iodine levels: &lt; 10 μg/dL is deficient; 10-29.9 μg/dL is sufficient; and &gt; 30 μg/dL is excessive). Conclusion: In the present study, we demonstrated that although a LID decreased urinary iodine levels, those levels corresponding with sufficient or a mild excess in iodine intake did not compromise the therapeutic efficacy of 131 I for the treatment of GD. Arch Endocrinol Metab. 2015;59(6):501-

The MODY Type of Diabetes Mellitus

It is estimated that close to 5% of the individuals classified as having type 2 diabetes mellitus (DM) and about 10% of those considered type 1 DM (previously categorized as juvenile type) are actual carriers of a MODY mutation. In this form of DM, there is evident co-segregation of some mutations and the advent of hyperglycemia, this fact having been reproduced by the study of several families of different populations. Its main characteristic is being one of the few causes of DM in which the transmission of the genetic susceptibility is due to an autossomical dominant inheritance, making part of the group classified as monogenic DM, where the other members are very rare. Mutations occurring in MODY genes, even in the heterozygous form, lead to a profound phenotypic impact (high penetrance), in that 95% of the individual carriers of a MODY mutation will be diabetic or will have altered glicemic metabolism before the age of 55 years. In this paper we approach this form of DM, emphasizing its most relevant clinical and genetic characteristics. The systematic search for MODY mutations is beginning to take place regularly in many countries, and there is a tendency to add this diagnostic tool to the routine exams in the practice of diabetology.Estima-se que perto de 5% dos indivíduos classificados como portadores de diabetes mellitus (DM) tipo 2 e 10% daqueles considerados como tipo 1 (anteriormente classificado como juvenil) sejam, na verdade, portadores de mutações MODY. Nesta forma de DM ocorre uma co-segregação evidente de algumas mutações com a hiperglicemia, fato este reproduzido em inúmeras famílias estudadas em várias populações do mundo. Caracteriza-se por ser uma das poucas causas de DM cujo modo de transmissão da predisposição genética ocorre de uma forma autossômica-dominante, compondo o grupo chamado de DM monogênicos, onde os outros representantes têm uma prevalência bastante rara. As mutações nos genes MODY, mesmo no estado heterozigoto, apresentam um forte impacto no fenótipo (alta penetrância), sendo que 95% dos indivíduos nascidos com alguma mutação MODY serão diabéticos ou apresentarão alterações no âmbito do metabolismo glicídico antes dos 55 anos de idade. Este trabalho objetiva a discussão desta forma de DM, enfatizando suas características clínicas e genéticas mais relevantes. A pesquisa sistemática de mutações MODY começa a ser feita de forma rotineira em vários países, havendo uma tendência de se colocar este recurso diagnóstico como um exame na prática da diabetologia

Low iodine diet does not improve the efficacy of radioiodine for the treatment of Graves’ disease

Objective Consuming a low-iodine diet (LID) is a widely accepted practice before administering radioiodine (131I) to evaluate and to treat thyroid disease. Although this procedure is well established for the management of patients with differentiated thyroid cancer, its use in patients with benign disease is unclear. So, we aimed to evaluate the influence of a LID on the outcome in patients with Graves’ disease (GD) treated with131I. Subjects and methods We evaluated 67 patients with GD who were divided into 2 groups: one group (n = 31) consumed a LID for 1-2 weeks, and the second group (n = 36) was instructed to maintain a regular diet (RD). Results The LID group experienced a 23% decrease in urinary iodine after 1 week on the diet and a significant 42% decrease after 2 weeks on the diet. The majority (53%) of the patients in the LID group had urinary iodine levels that were consistent with deficient iodine intake. However, there was no difference in the rate of hyperthyroidism’s cure between the LID and the RD groups 6 months after 131I therapy. Furthermore, the therapeutic efficacy did not differ in patients with varying degrees of sufficient iodine intake (corresponding urinary iodine levels: 30 μg/dL is excessive). Conclusion In the present study, we demonstrated that although a LID decreased urinary iodine levels, those levels corresponding with sufficient or a mild excess in iodine intake did not compromise the therapeutic efficacy of131I for the treatment of GD