RESUMEN
AIMS/HYPOTHESIS: Adults with type 2 diabetes mellitus have impaired microvascular function. It has been hypothesised that microvascular function may be restored through regular exercise. The aim of this study was to investigate whether 6 months of regular aerobic exercise would improve microvascular function in adults with type 2 diabetes. MATERIALS AND METHODS: Fifty-nine patients with type 2 diabetes (32 males, age 62.9+/-7.6 years, HbA(1c) 6.8+/-0.9%) were randomised to either a 6-month aerobic exercise programme (30 min, three times a week, 70-80% of maximal heart rate) or a 'standard care' control group. Before and after the intervention period, microvascular function was assessed as the maximum skin hyperaemia to local heating and endothelial and non-endothelial responsiveness following the iontophoretic application of acetylcholine and sodium nitroprusside. Maximal oxygen uptake, as an index of aerobic fitness, was assessed using a maximal exercise test. RESULTS: No significant improvement was seen in the exercise group compared with the control group for any of the variables measured: maximal oxygen uptake (control pre: 1.73+/-0.53 [means+/-SD] vs post: 1.67+/-0.40; exercise pre: 1.75+/-0.56 vs post: 1.87+/-0.62 l/min, p=0.10); insulin sensitivity (insulin tolerance test) (control pre: -0.17+/-0.06 vs post: -0.17+/-0.06; exercise pre: -0.16+/-0.1 vs post: -0.17+/-0.07 mmol l(-1) min(-1), p=0.97); maximal hyperaemia (control pre: 1.49+/-0.43 vs post: 1.52+/-0.57; exercise pre: 1.42+/-0.36 vs post: 1.47+/-0.33 V, p=0.85); peak response to acetylcholine (control pre: 1.37+/-0.47 vs post: 1.28+/-0.37; exercise pre: 1.27+/-0.44 vs post: 1.44+/-0.23 V, p=0.19) or to sodium nitroprusside (control pre: 1.09+/-0.50 vs post: 1.10+/-0.39; exercise pre: 1.12+/-0.28 vs post: 1.13+/-0.40 V, p=0.98). CONCLUSIONS/INTERPRETATION: In this group of type 2 diabetic patients with good glycaemic control a 6-month aerobic exercise programme did not improve microvascular function or aerobic fitness.
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Ejercicio Físico/fisiología , Microcirculación/fisiología , Adulto , Edad de Inicio , Anciano , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/prevención & control , Hemoglobina Glucada/análisis , Humanos , Persona de Mediana Edad , Consumo de Oxígeno , Cooperación del Paciente , Grosor de los Pliegues Cutáneos , FumarRESUMEN
AIMS/HYPOTHESIS: Insulin resistance is associated with abnormal microvascular function. Treatment with insulin sensitisers may provoke oedema, suggesting microvascular effects. The mechanisms underlying the peripheral oedema observed during glucose-lowering treatment with thiazolidinediones are unclear. Therefore we examined the effect of pioglitazone on microvascular variables involved in oedema formation. METHODS: Subjects (40-80 years) with type 2 diabetes and on insulin were randomised to 9 weeks of pioglitazone therapy (30 mg/day; n=14) or placebo (n=15). The following assessments were performed at baseline and 9 weeks: microvascular filtration capacity; isovolumetric venous pressure; capillary pressure; capillary recruitment following venous or arterial occlusion; postural vasoconstriction; and maximum blood flow. A number of haematological variables were also measured including vascular endothelium growth factor (VEGF), IL-6 and C-reactive protein (CRP). RESULTS: Pioglitazone did not significantly influence any microcirculatory variable as compared with placebo (analysis of covariance [ANCOVA] for microvascular filtration capacity for the two groups, p=0.26). Mean VEGF increased with pioglitazone (61.1 pg/ml), but not significantly more than placebo (9.76 pg/ml, p=0.94). HbA(1c) levels and the inflammatory markers IL-6 and CRP decreased with pioglitazone compared with placebo (ANCOVA: p=0.009, p=0.001 and p=0.004, respectively). CONCLUSIONS/INTERPRETATION: Pioglitazone improved glycaemic control and inflammatory markers over 9 weeks but had no effect on microcirculatory variables associated with oedema or insulin resistance in type 2 diabetic patients treated with insulin.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina/uso terapéutico , Microcirculación/fisiología , Tiazolidinedionas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Presión Sanguínea , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/fisiopatología , Método Doble Ciego , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Microcirculación/efectos de los fármacos , Persona de Mediana Edad , Pioglitazona , PlacebosRESUMEN
Autistic disorder (AutD) is a complex genetic disease. Available evidence suggests that several genes contribute to the underlying genetic risk for the development of AutD. However, both etiologic heterogeneity and genetic heterogeneity confound the discovery of AutD-susceptibility genes. Chromosome 15q11-q13 has been identified as a strong candidate region on the basis of both the frequent occurrence of chromosomal abnormalities in that region and numerous suggestive linkage and association findings. Ordered-subset analysis (OSA) is a novel statistical method to identify a homogeneous subset of families that contribute to overall linkage at a given chromosomal location and thus to potentially help in the fine mapping and localization of the susceptibility gene within a chromosomal area. For the present analysis, a factor that represents insistence on sameness (IS)--derived from a principal-component factor analysis using data on 221 patients with AutD from the repetitive behaviors/stereotyped patterns domain in the Autism Diagnostic Interview-Revised--was used as a covariate in OSA. Analysis of families sharing high scores on the IS factor increased linkage evidence for the 15q11-q13 region, at the GABRB3 locus, from a LOD score of 1.45 to a LOD score of 4.71. These results narrow our region of interest on chromosome 15 to an area surrounding the gamma-aminobutyric acid-receptor subunit genes, in AutD, and support the hypothesis that the analysis of phenotypic homogeneous subtypes may be a powerful tool for the mapping of disease-susceptibility genes in complex traits.
Asunto(s)
Trastorno Autístico/genética , Cromosomas Humanos Par 15 , Trastorno Autístico/clasificación , Biometría , Aberraciones Cromosómicas , Mapeo Cromosómico , ADN/sangre , ADN/genética , Familia , Genes Dominantes , Genes Recesivos , Ligamiento Genético , Marcadores Genéticos , Humanos , Escala de Lod , Análisis Multivariante , FenotipoRESUMEN
We describe a patient with cutaneous Crohn's disease with extensive cutaneous ulcerations preceding the diagnosis of gastrointestinal Crohn's. The cutaneous lesions responded to mesalamine and prednisone. The patient has been maintained on a regimen of mesalamine alone without recurrence. We discuss available forms of mesalamine and their function in cutaneous disease.