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.

Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations.

OBJECTIVE: Mutations in LMNA have been linked to diverse disorders called laminopathies, which display heterogeneous phenotypes and include diseases affecting muscles, axonal neurons, progeroid syndromes, and lipodystrophies. Among the lipodystrophies, LMNA mutations have been reported most frequently in patients with familial partial lipodystrophy (FPLD) of the Dunnigan variety; however, phenotypic heterogeneity in the pattern of body fat loss has been observed. In this study, we searched for LMNA mutations in patients with various forms of lipodystrophy. DESIGN AND METHODS: We studied 21 unrelated individuals with lipodystrophy. Subjects underwent a complete clinical evaluation and were classified as typical FPLD (n=12), atypical partial lipodystrophy (n=7), or generalized lipodystrophy (n=2). Molecular analysis of LMNA gene, analysis of body fat by dual-energy X-ray absorptiometry, and biochemical measurements were performed. RESULTS: ALL PATIENTS WITH TYPICAL FPLD WERE FOUND TO CARRY LMNA MUTATIONS: seven patients harbored the heterozygous p.R482W (c.1444C>T), two patients harbored the p.R482Q (c.1445G>A), and two individuals harbored the novel heterozygous variant p.N466D (c.1396A>G), all in exon 8. Also, a homozygous p.R584H (c.1751 G>A) mutation in exon 11 was found. Among patients with atypical partial lipodystrophy, two of them were found to have LMNA mutations: a novel heterozygous p.R582C variation (c.1744 C>T) in exon 11 and a heterozygous substitution p.R349W (c.1045C>T) in exon 6. Among patients with generalized lipodystrophy, only one harbored LMNA mutation, a heterozygous p.T10I (c.29C>T) in exon 1. CONCLUSIONS: We have identified LMNA mutations in phenotypically diverse lipodystrophies. Also, our study broadens the spectrum of LMNA mutations in lipodystrophy.

Identification of novel mutations of the WFS1 gene in Brazilian patients with Wolfram syndrome.

OBJECTIVE: Wolfram syndrome (WS) is a rare, progressive, neurodegenerative disorder with an autosomal recessive pattern of inheritance. The gene for WS, WFS1, was identified on chromosome 4p16 and most WS patients carry mutations in this gene. However, some studies have provided evidence for genetic heterogeneity and the genotype-phenotype relationships are not clear. Our aim was to ascertain the spectrum of WFS1 mutations in Brazilian patients with WS and to examine the phenotype-genotype relationships in these patients. DESIGN AND METHODS: Clinical characterization and analyses of the WFS1 gene were performed in 27 Brazilian patients with WS from 19 families. RESULTS: We identified 15 different mutations in the WFS1 gene in 26 patients, among which nine are novel. All mutations occurred in exon 8, except for one missense mutation which was located in exon 5. Although we did not find any clear phenotype-genotype relationship in patients with mutations in exon 8, the homozygous missense mutation in exon 5 was associated with a mild phenotype: onset of diabetes mellitus and optic atrophy during adulthood with good metabolic control being achieved with low doses of sulfonylurea. CONCLUSIONS: Our data show that WFS1 is the major gene involved in WS in Brazilian patients and most mutations are concentrated in exon 8. Also, our study increases the spectrum of WFS1 mutations. Although no clear phenotype-genotype relationship was found for mutations in exon 8, a mild phenotype was associated with a homozygous missense mutation in exon 5.

[Diabetes mellitus associated with the mitochondrial mutation A3243G: frequency and clinical presentation]. / Diabetes mellitus associado à mutação mitocondrial A3243G: freqüência e caracterização clínica.

UNLABELLED: Maternal inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial RNA Leu (UUR) at base pair 3243. The prevalence of MIDD in the diabetes population ranges between 0.5-3.0% depending on the ethnic background. AIM: To examine the frequency and clinical features of diabetes associated with this mutation in Brazilian patients with glucose intolerance. METHODS: The study population comprised: 78 type 1 diabetic subjects (group I), 148 patients with type 2 diabetes (group II), 15 patients with either type 1 or type 2 diabetes and hearing loss (group III) and 492 Japanese Brazilians with varying degrees of glucose intolerance. DNA was extracted from peripheral blood leucocytes and the A3243G mutation was determined by PCR amplification and Apa 1 digestion. In some individuals DNA was also extracted from buccal mucosa and hair follicles. The 3243 bp mutation was found in three individuals, all from group III, resulting in a prevalence of 0.4%. These subjects had an early age of diagnosis of diabetes, low or normal body mass index and requirement of insulin therapy. In conclusion MIDD is rare in our population and should be investigate in patients with diabetes and deafness.

Diabetes mellitus associado à mutação mitocondrial A3243G: freqüência e caracterização clínica / Diabetes mellitus associated with the mitochondrial mutation A3243G: frequency and clinical presentation

Diabetes mitocondrial é freqüentemente associado à mutação mitocondrial A3243G. A prevalência desse subtipo de diabetes na população diabética varia de 0,5 a 3 por cento, dependendo do grupo populacional estudado. OBJETIVO: Examinar a freqüência e o quadro clínico do diabetes associado com a mutação mitocondrial A3243G em pacientes brasileiros com tolerância a glicose alterada. MÉTODOS: A população estudada foi composta por 78 indivíduos portadores de diabetes mellitus tipo 1 (grupo I), 148 diabéticos tipo 2 (grupo II), 15 diabéticos tipo 1 ou tipo 2 portadores de disacusia (grupo III) e 492 indivíduos da comunidade nipo-brasileira com vários graus de intolerância a glicose. O DNA foi extraído de leucócitos do sangue periférico e a mutação A3243G foi determinada através da amplificação por PCR e digestão por Apa 1. Em alguns pacientes, o DNA também foi extraído da mucosa oral e folículo capilar. A mutação A3243G foi identificada em três indivíduos, todos do grupo III, resultando em uma prevalência de 0,4 por cento. Os carreadores da mutação apresentavam diagnóstico do diabetes em idade jovem, índice de massa corpórea normal ou baixo e requerimento de insulina. CONCLUSÃO: Diabetes mitocondrial é um subtipo raro de diabetes em nossa população e deve ser investigado naqueles indivíduos portadores de diabetes e surdez.

Maternal inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial RNA Leu (UUR) at base pair 3243. The prevalence of MIDD in the diabetes population ranges between 0.5-3.0 percent depending on the ethnic background. AIM: To examine the frequency and clinical features of diabetes associated with this mutation in Brazilian patients with glucose intolerance. METHODS: The study population comprised: 78 type 1 diabetic subjects (group I), 148 patients with type 2 diabetes (group II), 15 patients with either type 1 or type 2 diabetes and hearing loss (group III) and 492 Japanese Brazilians with varying degrees of glucose intolerance. DNA was extracted from peripheral blood leucocytes and the A3243G mutation was determined by PCR amplification and Apa 1 digestion. In some individuals DNA was also extracted from buccal mucosa and hair follicles. The 3243 bp mutation was found in three individuals, all from group III, resulting in a prevalence of 0.4 percent. These subjects had an early age of diagnosis of diabetes, low or normal body mass index and requirement of insulin therapy. In conclusion MIDD is rare in our population and should be investigate in patients with diabetes and deafness.