Abstract:
AIMS/HYPOTHESIS:As glycaemia and the incidence of microvascular diabetes complications follow a log-linear relationship, it becomes increasingly difficult to demonstrate a microvascular benefit of glucose-lowering when the HbA1c level is close to normal. METHODS:The Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial randomised 12,537 people with diabetes, impaired glucose tolerance or impaired fasting glucose to receive standard glycaemic care or standard care with the addition of basal insulin glargine (A21Gly,B31Arg,B32Arg human insulin), targeting a fasting plasma glucose level ≤5.3 mmol/l. Microvascular outcomes during a median follow-up of 6.2 years were examined in participants whose baseline HbA1c was above or below the median of 6.4% (46.4 mmol/mol). RESULTS:Allocation to the insulin glargine group reduced the incidence of the primary microvascular composite outcome of kidney and eye disease in participants whose baseline HbA1c level was ≥6.4% (46.4 mmol/mol; HR 0.90 [95% CI 0.81, 0.99]) but not in participants with a lower baseline HbA1c (HR 1.07 [95% CI 0.95, 1.20]; p value for interaction 0.031). In people whose baseline HbA1c level was ≥6.4% (46.4 mmol/mol), the median post-randomisation change in HbA1c was -0.65% (interquartile range -0.16, -0.91%) after allocation to insulin glargine and -0.33% (-0.83, 0.13%) after allocation to standard care (median HbA1c difference 0.33%; p < 0.0001). A smaller median difference of 0.22% was noted in people whose baseline HbA1c was <6.4% (p < 0.0001). CONCLUSIONS/INTERPRETATION:In patients with dysglycaemia, intervention targeting normal fasting glucose levels reduced HbA1c and attenuated the risk of microvascular outcomes in participants with a baseline HbA1c level ≥6.4% (46.4 mmol/mol). A neutral effect was seen in those with a lower baseline HbA1c level. TRIAL REGISTRATION:ClinicalTrials.gov NCT00069784.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
ORIGIN trial investigators.,Gilbert RE,Mann JF,Hanefeld M,Spinas G,Bosch J,Yusuf S,Gerstein HCdoi
10.1007/s00125-014-3238-4subject
Has Abstractpub_date
2014-07-01 00:00:00pages
1325-31issue
7eissn
0012-186Xissn
1432-0428journal_volume
57pub_type
杂志文章,随机对照试验相关文献
DIABETOLOGIA文献大全abstract:AIMS/HYPOTHESIS:Peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 (PPARGC1), a coactivator regulating the transcription of genes involved in oxidative metabolism, is downregulated in patients with type 2 diabetes and in their first-degree relatives. Whether this downregulation is a cause or effect o...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0369-2
更新日期:2006-10-01 00:00:00
abstract::The concentration of biologically active insulin was measured by the isolated fat cell method in serum and urine from healthy subjects and compared with the concentration of immunoreactive insulin. In both urine and serum the values obtained by the two methods correlated closely; In addition, there was a close correla...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01219518
更新日期:1976-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:Our aim was to assess regression of albuminuria and its clinical consequences in type 1 diabetes. METHODS:The analysis included 3642 participants from the Finnish Diabetic Nephropathy (FinnDiane) Study with a 24 h urine sample and a history of albuminuria available at baseline. A total of 2729 individu...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-018-4564-8
更新日期:2018-05-01 00:00:00
abstract::Oral (o.GTT) and intravenous glucose tolerance tests (i.v. GTT) were carried out on 492 patients of both sexes, aged from 5 to 78 years. Three hundred and fifty-nine non-diabetics in all were suspected clinically of reduced carbohydrate tolerance leaving 133 patients for comparison (controls). In 102 obesity was noted...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01257910
更新日期:1966-04-01 00:00:00
abstract::We studied the effect of chronic exposure to high glucose on the glucose transport regulation in hamster pancreatic Beta cells in permanent culture (HIT). Cells were exposed to either 5.5 mmol/l or 16.7 mmol/l glucose for 48 h and then glucose transport was studied by measuring the (3H)-2-deoxyglucose uptake for 5 and...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00405011
更新日期:1991-05-01 00:00:00
abstract::Non-insulin-dependent diabetic (NIDDM) patients were studied during a modified euglycaemic state when fasting hyperglycaemia was normalized by a prior (-210 to -150 min)--and later withdrawn (-150-0 min)--intravenous insulin infusion. Glucose metabolism was assessed in NIDDM patients (n = 10) and matched control subje...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00400638
更新日期:1995-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:The aim of this study was to investigate molecular mechanisms of glucose-induced changes in islets of Langerhans by analysing global changes in protein patterns of islets exposed to elevated glucose concentrations. METHODS:Islets were isolated from C57BL/6J mice and used either directly or after exposu...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1661-7
更新日期:2005-03-01 00:00:00
abstract::An in vitro method for detecting IgE insulin antibody using the principle of the radioallergosorbent test (RAST) is described. In six patients with insulin allergy, the RAST values were higher than in normal persons or insulin-treated diabetics without insulin-allergy. No differences were observed between normal perso...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00429705
更新日期:1978-01-14 00:00:00
abstract:AIMS/HYPOTHESIS:Diabetic retinopathy is characterised by morphological lesions related to disturbances in retinal blood flow. It has previously been shown that the early development of retinal lesions temporal to the fovea may predict the development of treatment-requiring diabetic maculopathy. The aim of this study wa...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-017-4424-y
更新日期:2017-12-01 00:00:00
abstract::We compared urinary albumin excretion during and after pregnancy in 30 insulin-dependent diabetic (IDDM) women with normoalbuminuria and in 12 IDDM women with microalbuminuria (> 15 micrograms.min-1) prior to conception. There was a 6.7-fold increase in the urinary albumin excretion up until the third trimester in the...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章
doi:10.1007/BF00400946
更新日期:1994-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:High sodium (HS) effects on hypertension are well established. Recent evidence implicates a relationship between HS intake and insulin resistance, even in the absence of hypertension. The aim of the current study was to determine whether loss of the vascular actions of insulin may be the driving factor ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-014-3373-y
更新日期:2014-12-01 00:00:00
abstract:AIMS/HYPOTHESIS:Microvascular endothelial hyperpermeability, mainly caused by claudin-5 deficiency, is the initial pathological change that occurs in diabetes-associated cardiovascular disease. The ketone body β-hydroxybutyrate (BHB) exerts unique beneficial effects on the cardiovascular system, but the involvement of ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05305-2
更新日期:2021-01-01 00:00:00
abstract::The human insulin receptor exists in two isoforms (HIR-A alpha-subunit 719 amino acids and HIR-B alpha-subunit 731 amino acids) which are generated by alternative splicing of a small exon and display distinct patterns of tissue-specific expression. Using the polymerase chain reaction we have recently shown that skelet...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00404072
更新日期:1993-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:Glucagon-like peptide-1 (GLP-1) lowers glucose levels by potentiating glucose-induced insulin secretion and inhibiting glucagon release. The question of whether GLP-1 exerts direct effects on the liver, independently of the hormonal changes, is controversial. We tested whether an exogenous GLP-1 infusio...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章
doi:10.1007/s00125-012-2738-3
更新日期:2013-01-01 00:00:00
abstract::[Nepsilon-palmitoyl Lys (B29)] human insulin is a fatty acid-acylated derivative of insulin with extended action compared to unmodified insulin when infused intravenously (i.v.) secondary to its binding to circulating albumin. The duration and activity profile of the acylated (A) and NPH (B) insulins were assessed fol...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050876
更新日期:1998-01-01 00:00:00
abstract:AIMS/HYPOTHESIS:Currently, three categories of cardiovascular autonomic nervous function measures are used: classic Ewing-test measures, measures of heart-rate variability (HRV), and measures of baroreflex sensitivity (BRS). Little is known about the agreement between these measures, and reference and reproducibility v...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章
doi:10.1007/s00125-003-1032-9
更新日期:2003-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:Mesenchymal stem cells (MSCs) can exert an immunosuppressive effect on any component of the immune system, including dendritic cells (DCs), by direct contact, the release of soluble markers and extracellular vesicles (EVs). We evaluated whether MSCs and MSC-derived EVs have an immunomodulatory effect on...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-015-3808-0
更新日期:2016-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:Abnormal gut microbiota and blood metabolome profiles have been reported both in children and adults with uncomplicated type 1 diabetes as well as in adults with type 1 diabetes and advanced stages of diabetic nephropathy. In this study we aimed to investigate the gut microbiota and a panel of targeted ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05260-y
更新日期:2020-12-01 00:00:00
abstract:AIMS/HYPOTHESIS:Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Despite recent advances, our understanding of its pathophysiology remains incomplete. The aim of this study was to provide deeper insight into the complex network of molecular and cellular c...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-020-05218-0
更新日期:2020-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:We have examined the effects of streptozotocin-induced type 1 diabetes on the expression and subcellular distribution of the classic sugar transporters (GLUT-1 to 5 and sodium-dependent glucose transporter-1 [SGLT-1]) in the endothelial cells of an en face preparation of septal coronary artery from Wist...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1583-4
更新日期:2004-12-01 00:00:00
abstract::The effect of a five day pretreatment with phenformin (3 X 50 mg daily) on hepatic metabolism was studied in six healthy volunteers. Arterial and hepatic venous concentrations of substrates and hepatic blood flow were estimated during a basal period and during a low-dose lactate infusion (0,03 mmol . kg-1 . min-1). Th...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01219423
更新日期:1978-04-01 00:00:00
abstract::Non-insulin-dependent diabetes mellitus (NIDDM) is commonly associated with hypertriglyceridaemia, low serum HDL-cholesterol concentrations, hypertension, obesity and accelerated atherosclerosis (metabolic syndrome X). Since a similar dyslipidaemia occurs with the acute-phase response, we investigated whether elevated...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050822
更新日期:1997-11-01 00:00:00
abstract::Insulin secretion rates after glucose loading were calculated from peripheral venous IRI concentrations considering half life and distribution space of exogenous insulin in normal men and dogs. The coefficients of multiple linear regression analysis between insulin secretion rates and plasma glucose (level and order a...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00290484
更新日期:1980-01-01 00:00:00
abstract:AIMS/HYPOTHESIS:Carbohydrate-free diet prevents hyperglycaemia and beta cell destruction in the New Zealand Obese (NZO) mouse model. Here we have used a sequential dietary regimen to dissociate the effects of obesity and hyperglycaemia on beta cell function and integrity, and to study glucose-induced alterations of key...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-010-1973-8
更新日期:2011-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:Few data are available about intakes and food sources of trans-fatty acids (TFAs) or their associations with cardiometabolic outcomes in Asian people who consume a prudent diet but are experiencing rapid nutritional transitions. We aimed to investigate the relationships between TFA biomarkers and type 2...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2674-2
更新日期:2012-11-01 00:00:00
abstract::An incidence of 9.0 out of 100,000 children under 19 years of age with Type 1 (insulin-dependent) diabetes was detected in Toronto during a 2 year prospective study. An increased number of cases occurred in the winter months of one of the years but not of the other during the study. The annual incidence was the same i...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00281308
更新日期:1982-04-01 00:00:00
abstract::The immune response of diabetic patients to influenza vaccination was examined in 31 patients, 10 with Type 1 (insulin-dependent) diabetes and 21 with Type 2 (non-insulin-dependent diabetes), and in 19 normal subjects. Each received a single intramuscular injection of the 3 virus strains (A/Chile,A/Philippines,B/USSR)...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00870139
更新日期:1986-12-01 00:00:00
abstract:AIMS/HYPOTHESIS:Differences in seasonality of birth patterns between the general population and the group who develop Type I (insulin-dependent) diabetes mellitus indicate that environmental factors operating around the antenatal and perinatal period could be important. We investigated whether the same unsual patterns ...
journal_title:Diabetologia
pub_type: 杂志文章,多中心研究
doi:10.1007/pl00002957
更新日期:2001-10-01 00:00:00
abstract::The past decade has resulted in multiple new findings of potential proteomic biomarkers of diabetic kidney disease (DKD). Many of these biomarkers reflect an important role in the (patho)physiology and biological processes of DKD. Situations in which proteomics could be applied in clinical practice include the identif...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/s00125-016-4001-9
更新日期:2016-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:The study aimed to investigate whether baseline physical activity protects against the occurrence of type 2 diabetes during a 28 year follow-up, after controlling for childhood environment and genetic predisposition. METHODS:At baseline in 1975 same-sex twin pairs born in Finland before 1958 were sent ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-010-1875-9
更新日期:2010-12-01 00:00:00