Abstract:
:Obesity and its comorbidities, such as type 2 diabetes, are pressing worldwide health concerns. Available anti-obesity treatments include weight loss pharmacotherapies and bariatric surgery. Whilst surgical interventions typically result in significant and sustained weight loss, available pharmacotherapies are far less effective, typically decreasing body weight by no more than 5-10%. An emerging class of multi-agonist drugs may eventually bridge this gap. This new class of specially tailored drugs hybridizes the amino acid sequences of key metabolic hormones into one single entity with enhanced potency and sustained action. Successful examples of this strategy include multi-agonist drugs targeting the receptors for glucagon-like peptide-1 (GLP-1), glucagon and the glucose-dependent insulinotropic polypeptide (GIP). Due to the simultaneous activity at several metabolically relevant receptors, these multi-agonists offer improved body weight loss and glucose tolerance relative to their constituent monotherapies. Further advancing this concept, chimeras were generated that covalently link nuclear acting hormones such as oestrogen, thyroid hormone (T3 ) or dexamethasone to peptide hormones such as GLP-1 or glucagon. The benefit of this strategy is to restrict the nuclear hormone action exclusively to cells expressing the peptide hormone receptor, thereby maximizing combinatorial metabolic efficacy of both drug constituents in the target cells whilst preventing the nuclear hormone cargo from entering and acting on cells devoid of the peptide hormone receptor, in which the nuclear hormone might have unwanted effects. Many of these multi-agonists are in preclinical and clinical development and may represent new and effective tools in the fight against obesity and its comorbidities.
journal_name
J Intern Medjournal_title
Journal of internal medicineauthors
Brandt SJ,Müller TD,DiMarchi RD,Tschöp MH,Stemmer Kdoi
10.1111/joim.12837subject
Has Abstractpub_date
2018-12-01 00:00:00pages
581-602issue
6eissn
0954-6820issn
1365-2796journal_volume
284pub_type
杂志文章,评审abstract:OBJECTIVES:The efficacy of octreotide was studied in a group of patients with biochemical evidence of insulinoma. DESIGN:A phase-II study. SETTING:A university department of internal medicine. SUBJECTS:Seven patients with biochemical evidence of insulinoma and without metastatic lesions. INTERVENTION:Daily treatmen...
journal_title:Journal of internal medicine
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2796.1994.tb01067.x
更新日期:1994-03-01 00:00:00
abstract:BACKGROUND:Epidemiological and clinical features of patients with COVID-19 have been reported, but none of them focused on medical staff, and few predictors of the duration of viral shedding have been reported. It is urgent to help healthcare workers prevent and recover quickly from the coronavirus disease 2019 (COVID-...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/joim.13160
更新日期:2020-12-01 00:00:00
abstract::Coeliac disease (CD) and noncoeliac wheat or gluten sensitivity (NCWS/NCGS) are common gluten-related disorders. Both conditions can present with gastrointestinal and extraintestinal manifestations, which can be a challenge for physicians to discern between. Whilst coeliac serology and histological assessment are requ...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/joim.13120
更新日期:2020-11-01 00:00:00
abstract::Mucosal surfaces of the body serve as the major portal of entry for human immunodeficiency virus (HIV). These tissues also house a majority of the body's lymphocytes, including the CD4(+) T cells that are the major cellular target for HIV infection. Mucosal surfaces are defended by innate and adaptive immune mechanism...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2796.2008.02042.x
更新日期:2009-01-01 00:00:00
abstract::Commonly recorded blood analyses as indicators of low- and-high risk patients with lung cancer were studied by comparing symptom- and survey-detected patients. During the period 1976-1985, in 41 of 189 non-small-cell lung cancer patients in Western Norway, lung cancer was detected by chest X-ray survey performed in th...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1991.tb00356.x
更新日期:1991-04-01 00:00:00
abstract:OBJECTIVES:To compare foreign- and Swedish-born diabetic subjects regarding health care utilization, complications, clinical and socio-economic characteristics. DESIGN:Cross-sectional study. SETTING:All known diabetic patients living in six defined primary health care districts. SUBJECTS:Of 1861 identified subjects ...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.1997.00161.x
更新日期:1997-08-01 00:00:00
abstract::We investigated skeletal involvement in five male and two female patients with ochronosis, aged 26-82 years. The main parameters of mineral metabolism, together with biochemical markers of bone resorption (urinary N-telopeptides of type I collagen) and formation (serum bone isoenzyme of alkaline phosphatase and serum ...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.2003.01145.x
更新日期:2003-09-01 00:00:00
abstract::It is now well recognized that cardiovascular events (CVE) occur quite commonly, both in the acute phase and in the long-term, in patients with community-acquired pneumonia (CAP). CVE have been noted in up to 30% of patients hospitalized with all-cause CAP. One systematic review and meta-analysis of hospitalized patie...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/joim.12875
更新日期:2019-06-01 00:00:00
abstract::The prevalence of coronary heart disease (CHD) was determined in a population survey in Mauritius where the prevalence of non-insulin dependent diabetes and mortality from CHD are amongst the highest in the world. Men and women aged 35-74 years of all major ethnic groups were included: Asian Indians (Hindus and Muslim...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1993.tb00672.x
更新日期:1993-02-01 00:00:00
abstract::Neuroendocrine tumour of the small intestine (SI-NET), formerly known as midgut carcinoid tumour, is the most common small intestinal malignancy. The incidence is rising, with recent reports of 0.67 per 100 000 in the USA and 1.12 per 100 000 in Sweden. SI-NETs often present a challenge in terms of diagnosis and treat...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/joim.12526
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Benefit from endovascular thrombectomy (EVT) for large-vessel occlusion (LVO) acute ischaemic stroke (AIS) is well demonstrated. Furthermore, emerging evidence supports efficacy in appropriately selected patients treated beyond current recommendations of 6 h. We evaluated clinical outcomes in ...
journal_title:Journal of internal medicine
pub_type: 杂志文章,多中心研究
doi:10.1111/joim.12680
更新日期:2017-12-01 00:00:00
abstract::A 42-year-old man presented with a mediastinal tumour. On histological examination, tuberculosis was evoked, but no definitive conclusion could be drawn. The patient thereafter developed throat ulcerations and rapidly progressing renal insufficiency due to necrotizing glomerulonephritis. After reviewing the histologic...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1990.tb00146.x
更新日期:1990-03-01 00:00:00
abstract:OBJECTIVES:the results of experimental studies suggest that vitamin D deficiency activates the renin-angiotensin system and predisposes to hypertension. Results of previous epidemiological studies investigating the association between 25-hydroxyvitamin D [25(OH)D] status and hypertension have not been consistent, perha...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2010.02309.x
更新日期:2011-02-01 00:00:00
abstract::Serum creatine kinase (CK) is an important adjunct in the diagnosis of myocardial infarction or in monitoring for the side-effects of drugs. We report elevation of CK in patients with untreated heterozygous familial hypercholesterolaemia (FH) with no evidence of myocardial infarction. Of a group of 30 patients, 60% ha...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1990.tb00268.x
更新日期:1990-11-01 00:00:00
abstract::Hyponatraemia (HN) can result from a wide range of mechanisms, and therapy must be individualized. Two theories of the origin of HN in acute brain disease have prevailed. The first is the cerebral salt wasting syndrome (CSWS), where excessive natriuresis caused by some unknown cerebral natriuretic factor lowers the to...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2796.1992.tb00588.x
更新日期:1992-10-01 00:00:00
abstract::Apart from being an acute phase reactant, fibrinogen appears to play an important although not widely recognized role in athero-/thrombogenesis. Arteriosclerotic diseases are associated with elevated levels of plasma fibrinogen. Strategies that lower the cardiovascular risk also lower fibrinogen levels. Virtually all ...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2796.1990.tb00174.x
更新日期:1990-06-01 00:00:00
abstract:OBJECTIVE:Patients undergoing bariatric surgery present long-term metabolic improvements and reduced type 2 diabetes risk, despite long-term weight regain. We hypothesized that part of these protective effects could be linked to altered gene expression in white adipose tissue (WAT). METHODS:Transcriptomic profiling by...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/joim.13066
更新日期:2020-08-01 00:00:00
abstract::Hepatitis C virus infection is now one of the most important causes of chronic liver disease. Primary care physicians play an important role in the diagnosis and initial work-up of patients infected with this virus. Understanding which patients may be at risk is the first step. By understanding the correct use of hepa...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2796.2001.00781.x
更新日期:2001-02-01 00:00:00
abstract::Calcium is important for bone health. It has been customary to focus on dietary calcium intake, but of central importance for the body needs in the individual patient is the actual calcium absorption. This absorption consists of an active vitamin D-mediated component and a passive diffusional component. A number of di...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2796.1992.tb00519.x
更新日期:1992-02-01 00:00:00
abstract::Forty-one patients with hyperprolactinaemia and suspected prolactinomas were studied. Growth hormone (GH) and thyrotropin (TSH) secretory patterns after thyrotropin releasing hormone (TRH) were affected in the majority of patients. The disturbances were observed regardless of tumour size as indicated by the radiologic...
journal_title:Journal of internal medicine
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2796.1990.tb00260.x
更新日期:1990-11-01 00:00:00
abstract::The incidence of obesity and metabolic disease, such as type 2 diabetes mellitus (T2D), is rising globally. Dietary lipid over supply leads to lipid accumulation at ectopic sites, such as skeletal muscle. Ectopic lipid storage is highly correlated with insulin resistance and T2D, likely due to a loss of metabolic flex...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/joim.12729
更新日期:2018-11-01 00:00:00
abstract::In healthy individuals, insulin resistance is associated with physiological conditions such as pregnancy or body weight gain and triggers an increase in beta cell number and insulin secretion capacity to preserve normoglycaemia. Failure of this beta cell compensation capacity is a fundamental cause of diabetic hypergl...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/joim.12096
更新日期:2013-09-01 00:00:00
abstract::Primary adrenal insufficiency (PAI), or Addison's disease, is a rare, potentially deadly, but treatable disease. Most cases of PAI are caused by autoimmune destruction of the adrenal cortex. Consequently, patients with PAI are at higher risk of developing other autoimmune diseases. The diagnosis of PAI is often delaye...
journal_title:Journal of internal medicine
pub_type: 杂志文章,实务指引,评审
doi:10.1111/joim.12162
更新日期:2014-02-01 00:00:00
abstract::The introduction of targeted biological therapies has revolutionised the management of immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, ankylosing spondylitis, psoriasis and inflammatory bowel disease. Following treatment with these therapies, many patients experience significant improvement...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/joim.12432
更新日期:2016-01-01 00:00:00
abstract::Millions of people worldwide receive agents targeting the renin-angiotensin system (RAS) to treat hypertension or statins to lower cholesterol. The RAS and cholesterol metabolic pathways in the brain are autonomous from their systemic counterparts and are interrelated through the cholesterol metabolite 27-hydroxychole...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/joim.12838
更新日期:2018-12-01 00:00:00
abstract:OBJECTIVES:To analyse whether there is an association between country of birth in first-generation immigrants and first hospitalization for or death from coronary heart disease (CHD) and to analyse whether this association remains in second-generation immigrants. DESIGN:In this follow-up study, the MigMed database at ...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.2006.01630.x
更新日期:2006-04-01 00:00:00
abstract::The first unifying definition for the metabolic syndrome was proposed by WHO in 1998. In accordance to this, patients with type 2 diabetes mellitus or impaired glucose tolerance have the syndrome if they fulfil two of the criteria: hypertension, dyslipidaemia, obesity/abdominal obesity and microalbuminuria. Persons wi...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2796.2001.00864.x
更新日期:2001-08-01 00:00:00
abstract::A total of 4401 subjects admitted to the Medical Division of St Camillo Hospital in Comacchio (Ferrara, Italy) over a period of 7 years were prospectively evaluated in order to determine whether the heterozygous beta-thalassaemic (HBT) could be considered as a protective factor against the occurrence of acute myocardi...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1111/j.1365-2796.1991.tb00416.x
更新日期:1991-08-01 00:00:00
abstract::Hypertriglyceridaemia, as defined by fasting triglyceride levels of greater than 2.8 mmol l-1, is a prevalent dyslipoproteinaemia in our population. The underlying pathophysiological mechanisms that result in elevations of plasma triglycerides are heterogeneous and, in most cases, incompletely understood. However, in ...
journal_title:Journal of internal medicine
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2796.1992.tb01256.x
更新日期:1992-06-01 00:00:00
abstract:BACKGROUND:As reported by major clinical series in the literature, about 2% of patients receiving unfractionated heparin (UFH) develop immune-mediated (type II) heparin-induced thrombocytopenia (HIT) that may be complicated in 30-75% of cases by a paradoxical thrombotic syndrome (HITTS), either arterial or venous. HITT...
journal_title:Journal of internal medicine
pub_type: 杂志文章
doi:10.1046/j.1365-2796.2002.01021.x
更新日期:2002-08-01 00:00:00