Glucagon-like peptide-1 analogues in monogenic syndromic obesity: Real-world data from a large cohort of Alström syndrome patients.

Aim: To examine the real-world efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in monogenic obesity in patients with Alström syndrome (ALMS).

Methods: We screened 72 UK adult patients with ALMS and offered treatment to 34 patients meeting one of the following criteria: body mass index of 25 kg/m or higher, insulin resistance, suboptimal glycaemic control on antihyperglycaemic medications or non-alcoholic fatty liver disease.

Results: In total, 30 patients, with a mean age of 31 ± 11 years and a male to-female ratio of 2:1, completed 6 months of treatment with GLP-1 RAs either in the form of semaglutide or exenatide.

Body weight, diabetes incidence vascular events and survival 15 years after very low calorie diet in community medical clinics in the UK.

Objective: To assess weight loss maintenance, diabetes status, mortality and morbidity 15 years after a very low calorie diet programme (VLCD) in patients with obesity.

Design: General practice data bases were interrogated for subjects coded for group therapy with VLCD in the 1990s. Causes of death, occurrence of vascular disease and remission or development of diabetes were ascertained from patient records and national stroke and cardiovascular disease data bases.

Service user and community clinician design of a partially virtual diabetic service improves access to care and education and reduces amputation incidence.

Introduction: Design of an integrated diabetes service based on needs of service users (persons living with diabetes) and community clinicians in a semirural low-income health district of the UK.

Research Design And Methods: One hundred and eighty-five service users engaged through public meetings, questionnaires and focus groups. General practice staff contributed views through workshops and questionnaires.

Consensus clinical management guidelines for Alström syndrome.

Alström Syndrome (ALMS) is an ultra-rare multisystem genetic disorder caused by autosomal recessive variants in the ALMS1 gene, which is located on chromosome 2p13. ALMS is a multisystem, progressive disease characterised by visual disturbance, hearing impairment, cardiomyopathy, childhood obesity, extreme insulin resistance, accelerated non-alcoholic fatty liver disease (NAFLD), renal dysfunction, respiratory disease, endocrine and urologic disorders. Clinical symptoms first appear in infancy with great variability in age of onset and severity.

Defining renal phenotype in Alström syndrome.

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.

Refining genotype-phenotype correlation in Alström syndrome through study of primary human fibroblasts.

Background: Alström syndrome (AS), featuring retinal dystrophy, neuronal deafness, cardiomyopathy, metabolic syndrome, and diffuse fibrosis, is caused by biallelic mutations in the centrosomal protein ALMS1. Genotype-phenotype correlation has been suggested without assessment of ALMS1 expression.

Methods: ALMS1 expression (real-time PCR and immunocytochemistry) and cilia formation (immunocytochemistry) were assessed in fibroblasts from deeply phenotyped volunteers diagnosed with AS recruited from a dedicated AS Service.

Monogenic diabetes syndromes: Locus-specific databases for Alström, Wolfram, and Thiamine-responsive megaloblastic anemia.

We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease-associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alström, and Thiamine-responsive megaloblastic anemia syndromes, respectively; and included 23 previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1. We then investigated genotype-phenotype relations for the WFS1 gene.

Advanced non-alcoholic fatty liver disease and adipose tissue fibrosis in patients with Alström syndrome.

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.

Diffuse left ventricular interstitial fibrosis is associated with sub-clinical myocardial dysfunction in Alström Syndrome: an observational study.

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.

Duration of Diabetes Predicts Aortic Pulse Wave Velocity and Vascular Events in Alström Syndrome.

Context: Alström syndrome is characterized by increased risk of cardiovascular disease from childhood.

Objective: To explore the association between risk factors for cardiovascular disease, aortic pulse wave velocity, and vascular events in Alström syndrome.

Design: Cross-sectional analyses with 5-year follow-up.

Modification of severe insulin resistant diabetes in response to lifestyle changes in Alström syndrome.

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.

Coronary artery disease in Alström syndrome.

Alström syndrome (ALMS) is a rare autosomal recessive condition, caused by mutations in the ALMS1 gene located on the short arm of chromosome 2. This gene codes for a protein linked with the centrosome, whose precise function is unknown. This condition was first described by Alström in 1959.

The progression from obesity to type 2 diabetes in Alström syndrome.

Background: Alström syndrome (ALMS) is a rare autosomal recessive monogenic disease associated with obesity, hyperinsulinemia, and alterations of glucose metabolism that often lead to the development of type 2 diabetes at a young age.

Objective: To study the relationship between weight and metabolism in a group of ALMS patients and matched controls.

Research Design And Methods: Fifteen ALMS patients (eight males, seven females; aged 3-51) were compared in a cross-sectional study with an age- and weight-matched control population.

New insights and therapies for the metabolic consequences of Alström syndrome.

Purpose Of Review: Recent studies have begun to evaluate the heterogeneity of insulin resistance in syndromes associated with type 2 diabetes, dyslipidaemia and associated cardiac, renal and hepatic consequences. These insights are of particular importance in Alström syndrome in which all of these conditions coexist from a young age with considerable morbidity and reduction in life expectancy. Clear definition of the phenotype in the syndrome may clarify biochemical pathways of crucial importance in propensity to diabetic complications and heart disease in the general population.

Cardiac magnetic resonance imaging in Alström syndrome.

Background: A case series of the cardiac magnetic resonance imaging findings in seven adult Alström patients.

Methods: Seven patients from the National Specialist Commissioning Group Centre for Alström Disease, Torbay, England, UK, completed the cardiac magnetic resonance imaging protocol to assess cardiac structure and function in Alström cardiomyopathy.

Results: All patients had some degree of left and right ventricular dysfunction.

Alström syndrome and cecal volvulus in 2 siblings.

Alström syndrome (ALMS1, MIM 203800) is a rare, autosomal recessively inherited monogenic condition caused by mutations in the ALMS1 gene located on the short arm of chromosome 2. ALMS1 is a multisystem condition characterized by childhood onset of blindness, dilated cardiomyopathy, sensorineural hearing loss, renal failure, fibrotic lung disease, and metabolic abnormalities, including hypertriglyceridemia, liver steatosis, insulin resistance, type 2 diabetes mellitus, and obesity. We describe 2 siblings with ALMS who presented with the potentially life-threatening condition of acute cecal volvulus, an association not previously reported.

Protection from clinical peripheral sensory neuropathy in Alström syndrome in contrast to early-onset type 2 diabetes.

Objective: Alström syndrome, with type 2 diabetes, and blindness could confer a high risk of foot ulceration. Clinical testing for neuropathy in Alström syndrome and matched young-onset type 2 diabetic subjects was therefore undertaken.

Research Design And Methods: Fifty-eight subjects with Alström syndrome (18 insulin-resistant nondiabetic and 40 diabetic; aged 8-43 years) and 30 young-onset diabetic subjects (aged 13-35 years) were studied.

Threshold for detection of diabetic peripheral sensory neuropathy using a range of research grade monofilaments in persons with Type 2 diabetes mellitus.

Aims: To identify the threshold of reduced sensory perception in Type 2 diabetes mellitus (Type 2 DM) using a range of research grade monofilaments.

Methods: Three groups of participants were recruited into a between subject, cross-sectional study. Group 1(NEW), persons with Type 2 DM diagnosed for less than 2 years (n = 80); Group 2 (EST) persons with Type 2 DM diagnosed for more than 2 years (n = 91), and Group 3, a Comparison group without Type 2 DM (n = 73), resulted in a total study population, n = 244.

Characterization of the IGF system in 15 patients with Alström syndrome.

Background: Alström syndrome (ALMS) is a rare recessively inherited progressive disease (OMIM 203800). Among its diverse spectrum of clinical features are phenotypes associated with deficiencies of the GH/IGF-I axis, including short stature, obesity, insulin resistance, hypertriglyceridaemia and heart failure.

Patients And Measurements: To characterize the IGF system in ALMS, we evaluated a subset of 15 young adults with ALMS for hepatic, renal and thyroid function.