RESUMO
BACKGROUND: Alström syndrome (AS) is a rare autosomal recessive ciliopathy with a wide spectrum of clinical features, including cone-rod retinal dystrophy, neuronal deafness, severe insulin resistance and major organ failure. The characteristics of renal disease in the syndrome have not been systematically described. The aim of this study is to define the onset and progression of renal disease in AS. METHOD: Prospective observational cohort study. SETTING AND PARTICIPANTS: Thirty-two adult subjects from a national specialist clinic in UK and 86 subjects from an international AS registry were studied. OUTCOMES: First, an international registry cross-sectional study across all age groups to determine change in kidney function was performed. Secondly, a detailed assessment was carried out of adult AS patients with serial follow-up to determine incidence, aetiology and progression of renal disease. ANALYTICAL APPROACH: Generalized estimating equations were used to evaluate the relationship between age and estimated glomerular filtration rate (eGFR). Associations between patient factors and eGFR levels were then assessed in the adult AS cohort. RESULTS: The international registry study of the renal function of 118 subjects with AS (median age 21 years) showed a rapid decline with age, at an average of -16.7 and -10.9 mL/min/1.73 m2 per decade in males and females, respectively. In a UK national cohort of 32 patients with AS (median age 22 years), 20/32 (63%) had chronic kidney disease (CKD) Stage 3 or above based on eGFR <60 mL/min/1.73 m2 or evidence of albuminuria. Hyperuricaemia was noted in 25/32 (79%). Structural abnormalities such as nephrocalcinosis without hypercalcaemia and cysts were observed in 20/32 (63%) subjects. Lower urinary tract symptoms were frequent in 17/19 (70%) of AS patients. Histological evidence showed mixed tubulo-interstitial and glomerular disease. CONCLUSIONS: This is the first study to demonstrate that renal disease is the hallmark of AS, which starts early and progresses with age, leading to a high prevalence of advanced CKD at young age. AS should be considered in the differential diagnosis of rare genetic renal diseases.
Assuntos
Síndrome de Alstrom/complicações , Insuficiência Renal Crônica/patologia , Adulto , Estudos Transversais , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Fenótipo , Estudos Prospectivos , Insuficiência Renal Crônica/etiologia , Adulto JovemRESUMO
Using a randomised cross-over design, free-living lunch intake and subjective appetite were examined in 10 children (9.8 ± 0.6 years) following high-intensity interval training (HIIT) versus a control sedentary (SED) period, within a school setting. The 22-min HIIT took place during a regular PE lesson and consisted of two rounds of 4 × 30 s sprints. Foods were offered at a regular school lunch immediately following HIIT and SED and were matched between conditions. All food was covertly weighed before and after the meal. Hunger, fullness and prospective consumption were reported immediately before and after HIIT/SED, using visual analogue scales. Heart rate was higher during HIIT than SED (159.3 ± 23.1 vs. 76.9 ± 2.2 bpm, P < 0.05). Lunch energy intake was not different (P = 0.52) following HIIT, compared to SED (2.06 ± 0.35 vs. 2.09 ± 0.29 MJ, respectively). There were no significant differences in macronutrient intake or subjective appetite (P > 0.05). Results suggest that HIIT can be implemented in a PE lesson immediately before lunch, without causing a compensatory increase in food consumption.
Assuntos
Apetite/fisiologia , Ingestão de Alimentos/fisiologia , Treinamento Intervalado de Alta Intensidade , Educação Física e Treinamento/métodos , Criança , Estudos Cross-Over , Currículo , Ingestão de Energia , Inglaterra , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Instituições Acadêmicas , Comportamento SedentárioRESUMO
BACKGROUND AND AIMS: Alström syndrome (AS) is a recessive monogenic syndrome characterized by obesity, extreme insulin resistance and multi-organ fibrosis. Despite phenotypically being high risk of non-alcoholic fatty liver disease (NAFLD), there is a lack of data on the extent of fibrosis in the liver and its close links to adipose in patients with AS. Our aim was to characterize the hepatic and adipose phenotype in patients with AS. METHODS: Observational cohort study with comprehensive assessment of metabolic liver phenotype including liver elastography (Fibroscan® ), serum Enhanced Liver Fibrosis (ELF) Panel and liver histology. In addition, abdominal adipose histology and gene expression was assessed. We recruited 30 patients from the UK national AS clinic. A subset of six patients underwent adipose biopsies which was compared with control tissue from nine healthy participants. RESULTS: Patients were overweight/obese (BMI 29.3 (25.95-34.05) kg/m2 ). A total of 80% (24/30) were diabetic; 74% (20/27) had liver ultrasound scanning suggestive of NAFLD. As judged by the ELF panel, 96% (24/25) were categorized as having fibrosis and 10/21 (48%) had liver elastography consistent with advanced liver fibrosis/cirrhosis. In 7/8 selected cases, there was evidence of advanced NAFLD on liver histology. Adipose tissue histology showed marked fibrosis as well as disordered pro-inflammatory and fibrotic gene expression profiles. CONCLUSIONS: NAFLD and adipose dysfunction are common in patients with AS. The severity of liver disease in our cohort supports the need for screening of liver fibrosis in AS.
Assuntos
Tecido Adiposo/patologia , Síndrome de Alstrom/complicações , Cirrose Hepática/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Estudos de Coortes , Feminino , Fibrose , Expressão Gênica , Humanos , Resistência à Insulina , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/complicações , Reino Unido , Adulto JovemRESUMO
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a common cause of abnormal LFTs in primary care, but there are no data defining its contribution nor reporting the range of NAFLD severity in this setting. This study seeks to calculate the range of disease severity of NAFLD in a primary care setting. METHODS: Adult patients with incidental abnormal LFTs, in the absence of a previous history, or current symptoms/signs of liver disease were prospectively recruited from eight primary care practices in Birmingham. NAFLD was diagnosed as fatty liver on ultrasound, negative serological liver aetiology screen, and alcohol consumption ≤30 and ≤20 g/day in males and females, respectively. The NAFLD Fibrosis Score (NFS) was calculated to determine the presence or absence of advanced liver fibrosis in subjects identified with NAFLD. RESULTS: Data from 1118 adult patients were analysed. The cause of abnormal LFTs was identified in 55% (614/1118) of subjects, with NAFLD (26.4%; 295/1118) and alcohol excess (25.3%; 282/1118) accounting for the majority. A high NFS (>0.676) suggesting the presence of advanced liver fibrosis was found in 7.6% of NAFLD subjects, whereas 57.2% of NAFLD patients had a low NFS (<-1.455) allowing advanced fibrosis to be confidently excluded. CONCLUSIONS: NAFLD is the commonest cause of incidental LFT abnormalities in primary care (26.4%), of whom 7.6% have advanced fibrosis as calculated by the NFS. This study is the first of its kind to highlight the burden of NAFLD in primary care and provide data on disease severity in this setting.
Assuntos
Fígado Gorduroso/epidemiologia , Idoso , Estudos de Coortes , Inglaterra/epidemiologia , Fígado Gorduroso/patologia , Fígado Gorduroso/fisiopatologia , Feminino , Humanos , Cirrose Hepática/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Atenção Primária à Saúde , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
Lipoprotein(a), Lp(a), is a modified atherogenic low-density lipoprotein particle that contains apolipoprotein(a). Its levels are highly heritable and variable in the population. This consensus statement by HEART UK is based on the evidence that Lp(a) is an independent cardiovascular disease (CVD) risk factor, provides recommendations for its measurement in clinical practice and reviews current and emerging therapeutic strategies to reduce CVD risk. Ten statements summarise the most salient points for practitioners and patients with high Lp(a). HEART UK recommends that Lp(a) is measured in adults as follows: 1) those with a personal or family history of premature atherosclerotic CVD; 2) those with first-degree relatives who have Lp(a) levels >200â¯nmol/l; 3) patients with familial hypercholesterolemia; 4) patients with calcific aortic valve stenosis and 5) those with borderline (but <15%) 10-year risk of a cardiovascular event. The management of patients with raised Lp(a) levels should include: 1) reducing overall atherosclerotic risk; 2) controlling dyslipidemia with a desirable non-HDL-cholesterol level of <100â¯mg/dl (2.5â¯mmol/l) and 3) consideration of lipoprotein apheresis.
Assuntos
Dislipidemias/sangue , Lipoproteína(a)/sangue , Biomarcadores/sangue , Remoção de Componentes Sanguíneos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Tomada de Decisão Clínica , Consenso , Regulação para Baixo , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Dislipidemias/terapia , Humanos , Hipolipemiantes/uso terapêutico , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND AND AIMS: In 2008, the National Institute of Health and Care Excellence in the UK recommended that patients undergoing lipoprotein apheresis (LA) should be included in an anonymised registry. The UK Lipoprotein Apheresis Registry was subsequently established in 2011. METHODS: Between 2011 and 2017, data was entered retrospectively and prospectively by seven LA centres in the UK for 151 patients. Twenty-two patients were involved in a research study and were therefore excluded from the analysis. Observational data was analysed for the remaining 129 patients. RESULTS: Most patients had heterozygous familial hypercholesterolaemia (HeFH) (45.0%); 23.3% had homozygous FH (HoFH); 7.8% had hyper-lipoproteinaemia (a) (Lp(a)) and 24.0% had other forms of dyslipidaemia. Detailed treatment data is available for 63 patients relating to 348 years of LA treatment. The number of years of treatment per patient ranged from 1 to 15. The mean reduction in interval mean LDL-C from the pre-procedure baseline was 43.14%. The mean reduction in interval mean Lp(a) from baseline was 37.95%. The registry data also shows a 62.5% reduction in major adverse cardiovascular events (MACE) between the 2 years prior to, and the first 2 years following introduction of LA. CONCLUSIONS: The data generated by the UK Lipoprotein Apheresis Registry demonstrates that LA is a very efficient method of reducing LDL-C and Lp(a) and lowers the incidence rate of MACE. LA is an important tool in the management of selected patients with HoFH and drug-resistant dyslipidaemias.
Assuntos
Remoção de Componentes Sanguíneos , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/terapia , Lipoproteína(a)/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Remoção de Componentes Sanguíneos/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Reino Unido/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Targets for cholesterol reduction are part of the Quality Outcomes Framework and general practitioners have to meet these targets to fulfil their remuneration package. By contrast, there are no targets for the accuracy of cholesterol or other lipid measurements and no recent surveys on performance of these assays. We have assessed the performance of lipid measurement of the available methods in the UK. METHODS: Serum samples collected from individual donors attending the national blood service were distributed after values were obtained from a secondary reference laboratory. Samples were sent to participant laboratories to assess different methods' analytical performance on single donation specimens, on routine external quality assessment pooled specimens, on specimens subjected to a range of freeze-thaw cycles and on frozen-stored specimens. RESULTS: Differences in measured cholesterol were found that were method-dependent and related to triglyceride content. HDL-cholesterol (HDL-C) showed significant positive bias in all assays. Individual donor specimens showed no significant changes with differing numbers of freeze-thaw cycles. Pooled serum was stable for up to six months. CONCLUSIONS: Most cholesterol measurements are accurate but some methods are affected by triglyceride interference. HDL-C methods show significant positive bias. Although there are potential matrix effects introduced as a result of specimen preparation, additional work is needed to show if these effects are present in fresh patient samples.
Assuntos
Lipídeos/sangue , Calibragem , Colesterol/análise , Colesterol/normas , HDL-Colesterol/análise , HDL-Colesterol/normas , Humanos , Lipídeos/normas , Garantia da Qualidade dos Cuidados de Saúde , Controle de Qualidade , Padrões de Referência , Valores de Referência , Reprodutibilidade dos Testes , Triglicerídeos/análise , Triglicerídeos/normasRESUMO
BACKGROUND: Persistent hepatitis E virus genotype 3 (HEV G3) infections affect solid organ transplant (SOT) recipients and hematopoietic stem cell transplant (HSCT) recipients, but the burden in these cohorts in the United Kingdom is unknown. We established an audit to determine the point prevalence of HEV viremia in SOT and HSCT patients in the United Kingdom and compare different testing approaches to inform screening strategies. METHODS: Between January 5, 2016, and September 21, 2016, 3044 patients undergoing therapeutic drug monitoring at a single transplant center were screened for HEV ribonucleic acid (RNA) in minipools. A total of 2822 patients who could be characterized included 2419 SOT patients, 144 HSCT patients and 259 patients with no available transplant history. HEV RNA-positive samples were characterized by serology and genomic phylogeny. HEV antigen (HEV-Ag) testing was performed on RNA-positive samples, 420 RNA-negative samples and 176 RNA-negative blood donor samples. RESULTS: Nineteen of 2822 patients were viremic with G3 HEV giving a prevalence of 0.67%. The median alanine aminotransferase was significantly higher in the HEV viremic patients (P < 0.0001); however, 2 viremic patients had an alanine aminotransferase value within the normal range at the time of screening. The HEV-Ag assay identified 18/19 viremic patients and all those patients with proven viremia longer than 4 weeks. CONCLUSIONS: Transplant recipients in the United Kingdom are at a low but significant risk of HEV infection. HEV-Ag detection could be an alternative to RNA detection where the goal is to identify established persistent HEV infection, particularly where expertise, facilities, or cost prohibit RNA testing.
Assuntos
Vírus da Hepatite E/isolamento & purificação , Hepatite E/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Viremia/epidemiologia , Adulto , Idoso , Efeitos Psicossociais da Doença , Feminino , Antígenos de Hepatite/isolamento & purificação , Hepatite E/epidemiologia , Hepatite E/virologia , Vírus da Hepatite E/genética , Vírus da Hepatite E/imunologia , Humanos , Masculino , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/virologia , Prevalência , Estudos Prospectivos , RNA Viral/isolamento & purificação , Transplantados/estatística & dados numéricos , Reino Unido/epidemiologia , Viremia/virologia , Adulto JovemRESUMO
Data presented in this article are supplementary material to our article entitled "Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recommendations and proposal of an "FCS Score" (Moulin et al., 2018, in press). The data describe the genotypes of patients with familial chylomicronaemia syndrome (FCS) and multifactorial chylomicronaemia syndrome (MCS), from the validation and replication cohorts.
RESUMO
Familial chylomicronaemia syndrome (FCS) is a rare, inherited disorder characterised by impaired clearance of triglyceride (TG)-rich lipoproteins from plasma, leading to severe hypertriglyceridaemia (HTG) and a markedly increased risk of acute pancreatitis. It is due to the lack of lipoprotein lipase (LPL) function, resulting from recessive loss of function mutations in the genes coding LPL or its modulators. A large overlap in the phenotype between FCS and multifactorial chylomicronaemia syndrome (MCS) contributes to the inconsistency in how patients are diagnosed and managed worldwide, whereas the incidence of acute hypertriglyceridaemic pancreatitis is more frequent in FCS. A panel of European experts provided guidance on the diagnostic strategy surrounding FCS and proposed an algorithm-based diagnosis tool for identification of these patients, which can be readily translated into practice. Features included in this FCS score comprise: severe elevation of plasma TGs (fasting TG levels >10â¯mmol/L [885â¯mg/dL] on multiple occasions), refractory to standard TG-lowering therapies, a young age at onset, the lack of secondary factors (except for pregnancy and oral oestrogens) and a history of episodes of acute pancreatitis. Considering 53 FCS patients from three cohorts and 52 MCS patients from three cohorts, the overall sensitivity of the FCS score (≥10) was 88% (95% confidence interval [CI]: 0.76, 0.97) with an overall specificity of 85% (95% CI: 0.75, 0.94). Receiver operating characteristic curve area was 0.91. Pragmatic clinical scoring, by standardising diagnosis, may help differentiate FCS from MCS, may alleviate the need for systematic genotyping in patients with severe HTG and may help identify high-priority candidates for genotyping.
Assuntos
Quilomícrons/sangue , Técnicas de Apoio para a Decisão , Hiperlipoproteinemia Tipo I/diagnóstico , Lipase Lipoproteica/genética , Mutação com Perda de Função , Triglicerídeos/sangue , Idade de Início , Algoritmos , Biomarcadores/sangue , Consenso , Diagnóstico Diferencial , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo I/sangue , Hiperlipoproteinemia Tipo I/tratamento farmacológico , Hiperlipoproteinemia Tipo I/genética , Hipolipemiantes , Lipase Lipoproteica/metabolismo , Pancreatite/diagnóstico , Pancreatite/genética , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Regulação para CimaRESUMO
BACKGROUND: Risk stratification algorithms for coronary artery bypass grafting (CABG) do not include a weighting for preoperative mild renal impairment defined as a serum creatinine 130 to 199 micromol/L (1.47 to 2.25 mg/dL), which may impact mortality and morbidity after CABG. METHODS AND RESULTS: We reviewed prospectively collected data between 1997 and 2004 on 4403 consecutive patients undergoing first-time isolated CABG with a preoperative serum creatinine <200 micromol/L (2.26 mg/dL)] in a single institution. The in-hospital mortality was 2.5% (112 of 4403), the need for new dialysis/hemofiltration was 1.3% (57 of 4403), and the stroke rate was 2.5% (108 of 4403). There were 458 patients with a serum creatinine 130 to 199 micromol/L or 1.47 to 2.25 mg/dL (mild renal dysfunction group) and 3945 patients with a serum creatinine <130 micromol/L (<1.47 mg/dL). Operative mortality was higher in the mild renal dysfunction group (2.1% versus 6.1%; P<0.001) and increased with increasing preoperative serum creatinine level. New dialysis/hemofiltration (0.8%versus 5.2%; P<0.001) and postoperative stroke (2.2% versus 5.0%; P<0.01) were also more common in the patients with mild renal impairment. Multivariate analysis adjusting for known risk factors confirmed preoperative mild renal impairment (creatinine 130 to 199 micromol/L or 1.47 to 2.25 mg/dL; odd ratio, 1.91; 95% CI, 1.18 to 3.03; P=0.007) or glomerular filtration rate estimates <60 mL/min per 1.73 m2, derived using the Cockroft-Gault formula, (odds ratio, 1.98; 95% CI, 1.16 to 3.48; P=0.015) as independent predictors of in-hospital mortality. Preoperative mild renal dysfunction adversely affected the 3-year survival probability after CABG (93% versus 81%; P<0.001). CONCLUSIONS: Mild renal dysfunction is an important predictor of outcome in terms of in-hospital mortality, morbidity, and midterm survival in patients undergoing CABG.
Assuntos
Ponte de Artéria Coronária , Doença das Coronárias/cirurgia , Nefropatias/complicações , Idoso , Biomarcadores , Estudos de Coortes , Doença das Coronárias/complicações , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Hemofiltração , Mortalidade Hospitalar , Humanos , Rim/fisiopatologia , Nefropatias/sangue , Nefropatias/fisiopatologia , Nefropatias/terapia , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Diálise Renal , Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
This consensus statement addresses the current three main modalities of treatment of homozygous familial hypercholesterolaemia (HoFH): pharmacotherapy, lipoprotein (Lp) apheresis and liver transplantation. HoFH may cause very premature atheromatous arterial disease and death, despite treatment with Lp apheresis combined with statin, ezetimibe and bile acid sequestrants. Two new classes of drug, effective in lowering cholesterol in HoFH, are now licensed in the United Kingdom. Lomitapide is restricted to use in HoFH but, may cause fatty liver and is very expensive. PCSK9 inhibitors are quite effective in receptor defective HoFH, are safe and are less expensive. Lower treatment targets for lipid lowering in HoFH, in line with those for the general FH population, have been proposed to improve cardiovascular outcomes. HEART UK presents a strategy combining Lp apheresis with pharmacological treatment to achieve these targets in the United Kingdom (UK). Improved provision of Lp apheresis by use of existing infrastructure for extracorporeal treatments such as renal dialysis is promoted. The clinical management of adults and children with HoFH including advice on pregnancy and contraception are addressed. A premise of the HEART UK strategy is that the risk of early use of drug treatments beyond their licensed age restriction may be balanced against risks of liver transplantation or ineffective treatment in severely affected patients. This may be of interest beyond the UK.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Benzimidazóis/uso terapêutico , Remoção de Componentes Sanguíneos/métodos , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Homozigoto , Hiperlipoproteinemia Tipo II/terapia , Mutação , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/efeitos adversos , Benzimidazóis/efeitos adversos , Biomarcadores/sangue , Remoção de Componentes Sanguíneos/efeitos adversos , Doenças Cardiovasculares/genética , Terapia Combinada , Consenso , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Inibidores de PCSK9 , Fenótipo , Pró-Proteína Convertase 9/metabolismo , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Reino UnidoRESUMO
The relationship between antiretroviral treatment of HIV infection, body fat distribution, insulin resistance, and very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) apolipoprotein-B (apoB) kinetics was investigated in 55 HIV-infected patients taking two nucleoside analogs plus either a protease inhibitor (n = 15) or a nonnucleoside reverse transcriptase inhibitor (n = 25), 15 antiretroviral therapy-naive patients, and 12 HIV-negative controls. Compared with the controls, high-density lipoprotein cholesterol was reduced in all groups (P < 0.01). Plasma triglyceride was increased in patients taking protease inhibitors (P < 0.05). VLDL and IDL apoB fractional catabolic rate (FCR) was lower in all treatment groups (P < 0.05) compared with controls. Trunk fat, VLDL apoB absolute secretion rate, and insulin resistance were not different between groups. Peripheral fat was lower in the treated patients (P < 0.05) and correlated with duration of therapy (r = -0.55; P < 0.001). There was a positive correlation between peripheral fat and VLDL apoB FCR (P = 0.002) and IDL apoB FCR (P = 0.002) and a negative correlation with VLDL apoB pool size, VLDL cholesterol, and triglyceride (P < 0.03; P < 0.01; P < 0.002). These results suggest that mild dyslipidemia resulting from antiretroviral therapy is caused by a decrease in VLDL and IDL apoB FCR, which is associated with a loss of peripheral fat.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Hiperlipidemias/complicações , Lipoproteínas VLDL/sangue , Lipoproteínas/sangue , Adulto , Terapia Antirretroviral de Alta Atividade , Estudos Transversais , Etnicidade , Feminino , Inibidores da Protease de HIV/uso terapêutico , Humanos , Hiperlipidemias/sangue , Lipoproteínas/efeitos dos fármacos , Lipoproteínas VLDL/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/uso terapêuticoRESUMO
BACKGROUND: Alström syndrome is a rare inherited ciliopathy with progressive multisystem involvement. Dilated cardiomyopathy is common in infancy and recurs or presents de novo in adults with high rates of premature cardiovascular death. Although Alström syndrome is characterised by fibrosis in solid organs such as the liver, the pathogenesis of related cardiomyopathy are not clear. To date it is not known whether diffuse interstitial myocardial fibrosis is present before the onset of heart failure symptoms or changes in conventional parameters of left ventricular function. METHODS: In this observational study, 26 patients with Alström syndrome (mean age 27 ± 9 years, 65 % male, 24 h ABPM 130 ± 14 / 77 ± 9 mmHg) without symptomatic cardiovascular disease were recruited from a single centre and compared to matched healthy controls. All subjects underwent cardiac MRI (1.5 T) to assess ventricular function, diffuse interstitial myocardial fibrosis by measurement of extracellular volume on T1-mapping (MOLLI) and coarse replacement fibrosis using standard late gadolinium enhancement imaging. RESULTS: Global extracellular volume was increased in Alström syndrome with wider variation compared to controls (0.30 ± 0.05 vs. 0.25 ± 0.01, p < 0.05). Left ventricular long axis function and global longitudinal strain were impaired in Alström syndrome without change in ejection fraction, ventricular size or atrial stress (NT-proBNP) (p < 0.05). Global extracellular volume was associated with reduced peak systolic longitudinal strain (r = -0.73, p < 0.01) and strain rate (r = -0.57, p < 0.01), increased QTc interval (r = 0.49, p < 0.05) and serum triglycerides (r = 0.66, p < 0.01). Nine (35 %) patients had diffuse mid-wall late gadolinium enhancement in a non-coronary artery distribution. CONCLUSION: Diffuse interstitial myocardial fibrosis is common in Alström syndrome and is associated with impaired left ventricular systolic function. Serial studies are required to determine whether global extracellular volume may be an independent imaging biomarker of vulnerability to dilated cardiomyopathy and heart failure.
Assuntos
Síndrome de Alstrom/patologia , Cardiomiopatias/patologia , Ventrículos do Coração/patologia , Adolescente , Adulto , Síndrome de Alstrom/fisiopatologia , Cardiomiopatias/fisiopatologia , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Função Ventricular Esquerda/fisiologia , Adulto JovemRESUMO
BACKGROUND: Alström syndrome is a recessively inherited condition characterised by severe insulin resistance and metabolic syndrome with progression to type 2 diabetes, hepatic dysfunction and coronary artery disease. The metabolic responses to lifestyle changes in the syndrome have not been reported. CASE REPORTS: We describe the effects on glycaemia of intense cycling in two insulin treated Alström patients with diabetes, and the effects of opposite lifestyle changes over one year in two others. METHODS: After practise and clinical assessment two patients aged 21 and 39 years undertook a 380 km cycle ride over 4 days by tandem. The effects of planned reductions in insulin therapies and increased regular carbohydrate ingestion were monitored by frequent capillary blood glucose measurements. Two siblings aged 22 and 25 years underwent assessment of glycaemia, C-peptide/glucose ratio serum lipids, hepatic function and ultrasound, Enhanced Liver Fibrosis test and measures of insulin resistance. Measurements were repeated one year later after profound lifestyle changes. RESULTS: Aerobic exercise strikingly improved blood glucose control despite reduction in insulin dose and increased carbohydrate intake. Increase in exercise and exclusion of fast foods improved all aspects of the metabolic syndrome and induced remission of diabetes in one sibling. Reduction in exercise and consumption of high energy foods in the other resulted in development of type 2 diabetes, severe metabolic syndrome and fatty liver in the other. CONCLUSIONS: Despite dual sensory loss and genetic basis for insulin resistance, Alström patients can successfully ameliorate the metabolic syndrome with lifestyle changes.
Assuntos
Síndrome de Alstrom/terapia , Diabetes Mellitus Tipo 2/terapia , Resistência à Insulina , Estilo de Vida , Adulto , Síndrome de Alstrom/diagnóstico , Síndrome de Alstrom/genética , Síndrome de Alstrom/metabolismo , Biomarcadores/metabolismo , Exercício Físico , Terapia por Exercício , Feminino , Humanos , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: WHO, IDF and ADA recommend HbA(1c) ≥6.5% (48 mmol/mol) for diagnosis of diabetes with pre-diabetes 6.0% (42 mmol/mol) [WHO] or 5.7% (39 mmol/mol) [ADA] to 6.4% (47 mmol/mol). We have compared HbA(1c) from several methods for research relating glycaemic markers. RESEARCH DESIGN AND METHODS: HbA1c was measured in EDTA blood from 128 patients with diabetes on IE HPLC analysers (Bio-Rad Variant II NU, Menarini HA8160 and Tosoh G8), point of care systems, POCT, (A1cNow+ disposable cartridges and DCA 2000(®)+ analyser), affinity chromatography (Primus Ultra2) and the IFCC secondary reference method (Menarini HA8160 calibrated using IFCC SRM protocol). RESULTS: Median (IQ range) on IFCC SRM was 7.5% (6.8-8.4) (58(51-68) mmol/mol) HbA(1c) with minimum 5.3%(34 mmol/mol)/maximum 11.9%(107 mmol/mol). There were positive offsets between IFCC SRM and Bio-Rad Variant II NU, mean difference (1SD), +0.33%(0.17) (+3.6(1.9) mmol/mol), r(2)=0.984, p<0.001 and Tosoh G8, +0.22%(0.20) (2.4(2.2) mmol/mol), r(2)=0.976, p<0.001 with a very small negative difference -0.04%(0.11) (-0.4(1.2) mmol/mol), r(2)=0.992, p<0.001 for Menarini HA8160. POCT methods were less precise with negative offsets for DCA 2000(®)+ analyser -0.13%(0.28) (-1.4(3.1) mmol/mol), r(2)=0.955, p<0.001 and A1cNow+ cartridges -0.70%(0.67) (-7.7(7.3) mmol/mol), r(2)=0.699, p<0.001 (n=113). Positive biases for Tosoh and Bio-Rad (compared with IFCC SRM) have been eliminated by subsequent revision of calibration. CONCLUSIONS: Small differences observed between IFCC-calibrated and NGSP certified methods across a wide HbA(1c) range were confirmed by quality control and external quality assurance. As these offsets affect estimates of diabetes prevalence, the analyser (and calibrator) employed should be considered when evaluating diagnostic data.