Browsing by Author "Fagulha, A"
Now showing 1 - 7 of 7
Results Per Page
Sort Options
- Ataxia de Friedreich e Diabetes Mellitus: estudo de uma famíliaPublication . Melo, M; Fagulha, A; Barros, L; Guimarães, J; Carrilho, F; Carvalheiro, MFriedreich's ataxia (FA) is one of the genetic syndromes sometimes associated with diabetes and the most common hereditary ataxia. It is a autosomal recessive neurodegenerative disease, caused by a mutation in the FRDA gene, which originates decreased expression of frataxin, a mitochondrial protein involved in iron metabolism. The disorder is usually manifest in childhood and is characterised by ataxia, dysarthria, scoliosis and feet deformity. About two thirds of patients have hypertrophic cardiomyopathy, 10% have diabetes and 20% have another glucose homeostasis disorder. Both insulin resistance and beta-cell dysfunction are implicated in this patients' diabetes pathophysiology. The mean half-life is 35 years. Cause of death is usually related to cardiomyopathy or diabetes' complications. We report the case study of two twin sisters with 28 years old, in whom FA was diagnosed in the first decade, both of them with diabetes since their early twenties. A third sister with FA is reported, with no glucose homeostasis disorder. They also have two healthy male brothers. Based in this cases, the FA associated diabetes pathophysiology is discussed, concerning the therapeutic approach to these patients and to their diabetic relatives without neurologic symptoms. The role of molecular genetic testing and genetic counselling are also debated.
- Controlo glicémico e tratamento da diabetes tipo 1 da criança e adolescente em PortugalPublication . Fagulha, A; Santos, I; Grupo de Estudos da Diabetes MellitusOBJECTIVE: The Pediatric Portuguese Society of Endocrinology and Diabetology established in 2001 a Study Group with the aim of investigate glycemic control, prevalence of microvascular complications and modalities of treatments in type1 diabetic patients. PATIENTS AND METHODS: The cases for registration were those who were born between June 1, 1979 and June 1, 2001 (until 22 yr of age). A front sheet was constructed to record, age at diabetes diagnosis, diabetes duration, presence or absence of diabetes microvascular complications, HbA1c, number of capillary glycemic tests per week and type of insulin treatment. RESULTS: Twenty-two Hospitals participated and a total of 1009 patients were registered. The mean age was 13.6 yr+/-4.7, mean age at diabetes diagnosis 8.4 yr+/-4.4, and diabetes duration 5.2 yr+/-3.95. Diagnosis of diabetes was done in 22.8% by the age group 0-4 yr, in 36.4% by the age group 5-9 yr, in 32.4% by the age group 10-14, in 6.7% by the age group 15-19, and in 1.5% by the age group 20-22. Retinopathy was present in 1.4% and nephropathy in 6.4%. Values of HbA1c <7.5% were achieved in 12.5%, > or =7.5 and < 8% in 11.3%, > or =8 and <9.5 in 33.5% and > or =9.5 in 40.9%. Insulin treatment with one daily injection was used in 1.5%, with two daily injections in 35.4%, with three daily injections in 35% and with four or more in 26.4%. CONCLUSIONS: This study showed that this large cohort of type1 diabetic patients had a bad metabolic control and the goal of near normoglycemia was achieved in only a few patients.
- Lack of association of vitamin D receptor gene polymorphisms with susceptibility to type 1 diabetes mellitus in the Portuguese populationPublication . Lemos, MC; Fagulha, A; Coutinho, E; Gomes, L; Bastos, M; Barros, L; Carrilho, F; Geraldes, E; Regateiro, FJ; Carvalheiro, MThe vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. Association studies of VDR polymorphisms and risk of type 1 diabetes often produced conflicting results in different ethnic backgrounds. The aim of this study was to test for association between common VDR polymorphisms and the genetic susceptibility to type 1 diabetes in the Portuguese population. We genotyped 207 patients with type 1 diabetes and 249 controls for the FokI T>C (rs10735810), BsmI A>G (rs1544410), ApaI G>T (rs7975232), and TaqI C>T (rs731236) single nucleotide polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. The distribution of VDR genotype, allele, and haplotype frequencies did not differ significantly between patients and controls. These data suggest that the single nucleotide polymorphisms of the VDR gene are unlikely to contribute significantly to type 1 diabetes susceptibility in the Portuguese population.
- Noninvasive analysis of hepatic glycogen kinetics before and after breakfast with deuterated water and acetaminophenPublication . Jones, JG; Fagulha, A; Barosa, C; Bastos, M; Barros, L; Baptista, C; Caldeira, MM; Carvalheiro, MThe contributions of hepatic glycogenolysis to fasting glucose production and direct pathway to hepatic glycogen synthesis were quantified in eight type 1 diabetic patients and nine healthy control subjects by ingestion of (2)H(2)O and acetaminophen before breakfast followed by analysis of urinary water and acetaminophen glucuronide. After overnight fasting, enrichment of glucuronide position 5 relative to body water (G5/body water) was significantly higher in type 1 diabetic patients compared with control subjects, indicating a reduced contribution of glycogenolysis to glucose production (38 +/- 3 vs. 46 +/- 2%). Following breakfast, G5/body water was significantly higher in type 1 diabetic patients, indicating a smaller direct pathway contribution to glycogen synthesis (47 +/- 2 vs. 59 +/- 2%). Glucuronide hydrogen 2 enrichment (G2) was equivalent to body water during fasting (G2/body water 0.94 +/- 0.03 and 1.02 +/- 0.06 for control and type 1 diabetic subjects, respectively) but was significantly lower after breakfast (G2/body water 0.78 +/- 0.03 and 0.82 +/- 0.05 for control and type 1 diabetic subjects, respectively). The reduced postprandial G2 levels reflect incomplete glucose-6-phosphate-fructose-6-phosphate exchange or glycogen synthesis from dietary galactose. Unlike current measurements of human hepatic glycogen metabolism, the (2)H(2)O/acetaminophen assay does not require specialized on-site clinical equipment or personnel.
- Sources of hepatic glucose production by 2H2O ingestion and Bayesian analysis of 2H glucuronide enrichment.Publication . Delgado, TC; Barosa, C; Castro, MM; Geraldes, CF; Bastos, M; Baptista, C; Fagulha, A; Barros, L; Mota, A; Carvalheiro, M; Jones, JG; Merrit, MThe contribution of gluconeogenesis to hepatic glucose production (GP) was quantified after (2)H(2)O ingestion by Bayesian analysis of the position 2 and 5 (2)H-NMR signals (H2 and H5) of monoacetone glucose (MAG) derived from urinary acetaminophen glucuronide. Six controls and 10 kidney transplant (KTx) patients with cyclosporine A (CsA) immunosuppressant therapy were studied. Seven KTx patients were lean and euglycemic (BMI = 24.3 +/- 1.0 kg/m(2); fasting glucose = 4.7 +/- 0.1 mM) while three were obese and hyperglycemic (BMI = 30.5 +/- 0.7 kg/m(2); fasting glucose = 7.1 +/- 0.5 mM). For the 16 spectra analyzed, the mean coefficient of variation for the gluconeogenesis contribution was 10% +/- 5%. This uncertainty was associated with a mean signal-to-noise ratio (SNR) of 79:1 and 45:1 for the MAG H2 and H5 signals, respectively. For control subjects, gluconeogenesis contributed 54% +/- 7% of GP as determined by the mean and standard deviation (SD) of individual Bayesian analyses. For the lean/normoglycemic KTx subjects, the gluconeogenic contribution to GP was 62% +/- 7% (P = 0.06 vs. controls), while hyperglycemic/obese KTx patients had a gluconeogenic contribution of 68% +/- 3% (P < 0.005 vs. controls). These data suggest that in KTx patients, an increased gluconeogenic contribution to GP is strongly associated with obesity and hyperglycemia
- The CTLA4 +49 A/G polymorphism is not associated with susceptibility to type 1 diabetes mellitus in the Portuguese populationPublication . Lemos, MC; Coutinho, E; Gomes, L; Bastos, M; Fagulha, A; Barros, L; Carrilho, F; Geraldes, E; Regateiro, FJ; Carvalheiro, MCTLA4 genetic polymorphisms have been associated with type 1 diabetes. We genotyped 207 patients and 249 controls for the most frequently investigated polymorphism of the CTLA4 gene (+49A/G (rs231775)). No significant differences were observed, suggesting that this polymorphism is not strongly associated with type 1 diabetes in the Portuguese population.
- Tiroidites agudasPublication . Paiva, S; Bastos, M; Gomes, L; Durão, A; Moreira, A; Barros, L; Rodrigues, D; Ruas, L; Ribeiro, C; Rodrigues, F; Paiva, I; Fagulha, A; Carrilho, F; Geraldes, E; Carvalheiro, M; Ruas, AWe review the pathophysiology, clinical features and therapy of acute thyroiditis. Four cases are reported stressing the role of fine needle aspiration for the diagnosis of this clinical entity.