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1.
Diabetes Obes Metab ; 22(6): 978-987, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32048396

RESUMO

AIM: To evaluate the effect of adding the dipeptidyl-peptidase-4 inhibitor vildagliptin to insulin on the glycaemic control of patients with type 2 diabetes undergoing haemodialysis. METHODS: Overall, 65 insulin-treated patients with type 2 diabetes undergoing haemodialysis (HbA1c: 7.3% ± 1.1%; age: 70.5 ± 8.5 years) were randomized (1:1) either to receive vildagliptin 50 mg/day in addition to insulin (vildagliptin-insulin group) or to pursue their usual insulin regimen (insulin-only group). Continuous glucose monitoring (CGM) was performed for 48 ± 6 hours at baseline and at week 12. The primary study endpoint was change from baseline in mean interstitial glucose using CGM. The secondary endpoints included other CGM variables and glucose control markers. RESULTS: After 12 weeks, a greater reduction in mean CGM glucose from baseline was observed in the vildagliptin-insulin group compared with the insulin-only group, although the between-treatment difference was not statistically significant (mean difference [CI 95%]: -0.96 mmol/L [-2.09; 0.18] vs. -0.29 mmol/L [-1.29; 0.76], P = 0.32). However, a significant decrease from baseline in HbA1c, glycated albumin and insulin daily doses was observed in the vildagliptin-insulin group versus the insulin-only group (-0.6% [-1.19; -0.1], P < 0.01), in the vildagliptin-insulin group versus no change in the insulin-only group (-130.6 µmol/L [-271; 10.7] vs. +36.2 µmol/L [-164.4; 236.9], P = 0.04 and - 5.9 IU/day [-1.8; 7.1] vs. +1.1 IU/day [-14.5; 16.6], P = 0.01, respectively). There was no significant difference in the percentage of time spent in hypoglycaemia using CGM, occurrence of severe hypoglycaemia or number of adverse events. CONCLUSION: In this study, vildagliptin added to insulin improved glycaemic control with an associated insulin-sparing effect in patients with type 2 diabetes undergoing haemodialysis and was well tolerated.


Assuntos
Adamantano , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Insulina , Diálise Renal , Vildagliptina , Adamantano/efeitos adversos , Idoso , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Estudos Prospectivos , Pirrolidinas , Vildagliptina/uso terapêutico
2.
Am J Hum Genet ; 92(5): 707-24, 2013 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-23643381

RESUMO

Transcription factor SOX10 plays a role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation and is a major actor in the development of the neural crest. It has been implicated in Waardenburg syndrome (WS), a rare disorder characterized by the association between pigmentation abnormalities and deafness, but SOX10 mutations cause a variable phenotype that spreads over the initial limits of the syndrome definition. On the basis of recent findings of olfactory-bulb agenesis in WS individuals, we suspected SOX10 was also involved in Kallmann syndrome (KS). KS is defined by the association between anosmia and hypogonadotropic hypogonadism due to incomplete migration of neuroendocrine gonadotropin-releasing hormone (GnRH) cells along the olfactory, vomeronasal, and terminal nerves. Mutations in any of the nine genes identified to date account for only 30% of the KS cases. KS can be either isolated or associated with a variety of other symptoms, including deafness. This study reports SOX10 loss-of-function mutations in approximately one-third of KS individuals with deafness, indicating a substantial involvement in this clinical condition. Study of SOX10-null mutant mice revealed a developmental role of SOX10 in a subpopulation of glial cells called olfactory ensheathing cells. These mice indeed showed an almost complete absence of these cells along the olfactory nerve pathway, as well as defasciculation and misrouting of the nerve fibers, impaired migration of GnRH cells, and disorganization of the olfactory nerve layer of the olfactory bulbs.


Assuntos
Surdez/genética , Predisposição Genética para Doença/genética , Síndrome de Kallmann/genética , Neuroglia/patologia , Condutos Olfatórios/patologia , Fatores de Transcrição SOXE/genética , Animais , Análise Mutacional de DNA , Surdez/patologia , Feminino , França , Galactosídeos , Células HeLa , Humanos , Indóis , Síndrome de Kallmann/patologia , Masculino , Camundongos , Mutação/genética , Plasmídeos/genética
3.
Diabetes Care ; 26(11): 2990-3, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14578228

RESUMO

OBJECTIVE: To evaluate perinatal outcome in pregnancies in women with type 1 and type 2 diabetes and the influence of preconception care 10 years after the St. Vincent's declaration. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted in 12 perinatal centers in France in 2000-2001. The main investigated outcomes were perinatal mortality, major congenital malformations, and preterm delivery. RESULTS: Among 435 single pregnancies, 289 (66.4%) were from women with type 1 and 146 (33.6%) from women with type 2 diabetes. Perinatal mortality rate was 4.4% (0.7% national rate), severe congenital malformations rate was 4.1% (2.2% national rate), and preterm delivery rate was 38.2% (4.7% national rate). Preconception care was provided in 48.5% women with type 1 diabetes and in 24.0% women with type 2 diabetes. Women whose first trimester HbA(1c) was >8% had higher rates of perinatal mortality (9.2 vs. 2.5%; odds ratio 3.9; 95% CI 1.5-9.7; P < 0.005), major congenital malformations (8.3 vs. 2.5%; 3.5; 1.3-8.9; P < 0.01), and preterm delivery (57.6 vs. 24.8%; 1.4; 1.1-1.7; P < 0.005) than those with first trimester HbA(1c) <8%. These results are similar to those reported in France in 1986-1988. CONCLUSIONS: Pregnancies in women with diabetes are still poorly planned and complicated by higher rates of perinatal mortality and major congenital malformations. Despite knowledge of the importance of intensified glycemic control before pregnancy, reaching the St. Vincent's target needs further implementation in France.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Resultado da Gravidez/epidemiologia , Gravidez em Diabéticas/epidemiologia , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Modelos Logísticos , Gravidez , Prevalência
4.
J Clin Endocrinol Metab ; 99(10): E2138-43, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25077900

RESUMO

CONTEXT: Mutations in CHD7, a gene previously implicated in CHARGE (coloboma, heart defect, choanal atresia, retardation of growth and/or development, genital hypoplasia, ear anomalies) syndrome, have been reported in patients presenting with Kallmann syndrome (KS) or congenital hypogonadotropic hypogonadism (CHH). Most mutations causing CHARGE syndrome result in premature stop codons and occur de novo, but the proportion of truncating vs nontruncating mutations in KS and CHH patients is still unknown. OBJECTIVE: The objective of the study was to determine the nature, prevalence, mode of transmission, and clinical spectrum of CHD7 mutations in a large series of patients. DESIGN: We studied 209 KS and 94 CHH patients. These patients had not been diagnosed with CHARGE syndrome according to the current criteria. We searched for mutations in 16 KS and CHH genes including CHD7. RESULTS: We found presumably pathogenic mutations in CHD7 in 24 KS patients but not in CHH patients. Nontruncating mutations (16 missense and a two-codon duplication) were more prevalent than truncating mutations (three nonsense, three frame shift, and a splice site), which contrasts with patients presenting with typical CHARGE syndrome. Thus, the clinical spectrum associated with CHD7 mutations may be partly explained by genotype/phenotype correlations. Eight patients also had congenital deafness and one had a cleft lip/palate, whereas six had both. For 10 patients, the presence of diverse features of the CHARGE spectrum in at least one relative argues against a de novo appearance of the missense mutation, and this was confirmed by genetic analysis in five families. CONCLUSION: Considering the large prevalence and clinical spectrum of CHD7 mutations, it will be particularly relevant to genetic counseling to search for mutations in this gene in KS patients seeking fertility treatment, especially if KS is associated with deafness and cleft lip/palate.


Assuntos
Síndrome CHARGE/epidemiologia , Síndrome CHARGE/genética , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Síndrome de Kallmann/epidemiologia , Síndrome de Kallmann/genética , Adolescente , Adulto , Criança , Pré-Escolar , Saúde da Família , Feminino , Mutação da Fase de Leitura , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Prevalência , Adulto Jovem
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