Abstract:
AIMS/HYPOTHESIS:We investigated the association of variants of the transcription factor 7-like 2 (TCF7L2) gene with: (1) incident diabetes in the Finnish Diabetes Prevention Study (DPS, Study I); (2) type 2 diabetes and impaired glucose regulation (i.e. IGT or IFG) in a cross-sectional study (Study II); and (3) insulin secretion, insulin sensitivity and adipose tissue expression of TCF7L2 in offspring of type 2 diabetic probands (III). SUBJECTS AND METHODS:Study I (the DPS) included 507 individuals with IGT who were randomly allocated to control and intervention groups and followed for an average of 3.9 years to monitor for progression to diabetes. Study II was a population-based cross-sectional study of 1,766 men, aged 50-70 years, randomly selected from the population of Kuopio, eastern Finland. Study III included 238 non-diabetic offspring of patients with type 2 diabetes. Genotyping of rs12255372 and rs7903146 of TCF7L2 was carried out. RESULTS:In the DPS, the TT genotype of rs12255372 was significantly associated with an adjusted 2.85-fold risk (95% CI 1.17-6.95, p = 0.021) of incident diabetes in the control group, but not in the intervention group. In Study II, the adjusted odds ratio in subjects with the TT genotype was 3.40 (1.45-7.97, p = 0.005) for the comparison of diabetic subjects with normoglycaemic subjects. The T allele of rs12255372 was significantly associated with decreased insulin secretion (Studies II, III). Expression of TCF7L2 in adipose tissue tended to be lower in subjects with the TT risk genotypes of rs12255372 and rs7903146. CONCLUSIONS/INTERPRETATION:The variant of rs12255372 of TCF7L2 was associated with incident type 2 diabetes in the DPS and in a separate population-based cross-sectional study. Impaired insulin secretion is likely to be the main cause for our findings.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Wang J,Kuusisto J,Vänttinen M,Kuulasmaa T,Lindström J,Tuomilehto J,Uusitupa M,Laakso Mdoi
10.1007/s00125-007-0656-6subject
Has Abstractpub_date
2007-06-01 00:00:00pages
1192-200issue
6eissn
0012-186Xissn
1432-0428journal_volume
50pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract:AIM/HYPOTHESIS:Although mitochondrial oxidative phosphorylation (OxPhos) dysfunction is believed to be responsible for beta cell dysfunction in insulin resistance and mitochondrial diabetes, the mechanisms underlying progressive beta cell failure caused by defective mitochondrial OxPhos are largely unknown. METHODS:We...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-015-3506-y
更新日期:2015-04-01 00:00:00
abstract::Data are discussed which demonstrate that insulin plays an important role in sodium metabolism. The primary action of insulin on sodium balance is exerted on the kidney. Increases in plasma insulin concentration within the physiological range stimulate sodium reabsorption by the distal nephron segments and this effect...
journal_title:Diabetologia
pub_type: 杂志文章,评审
doi:10.1007/BF00252649
更新日期:1981-09-01 00:00:00
abstract:AIMS/HYPOTHESIS:Augmented oxidative stress induced by hyperglycaemia possibly contributes to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine to 8-oxo, 2'-deoxyguanosine in DNA. To investigate the possible contribution of oxidative DNA damage to the path...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250051258
更新日期:1999-08-01 00:00:00
abstract::Non-diabetic first degree relatives of non-insulin-dependent diabetic (NIDDM) families are at increased risk of developing diabetes mellitus, and have been studied to identify early metabolic abnormalities. Hormone concentrations measured by specific enzyme immunoassays were assessed in non-diabetic relatives of North...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050805
更新日期:1997-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:The aim of this study was to assess whether the diabetogenicity of areca nut (Areca catechu or 'betel-nut'), which has previously been demonstrated experimentally in mice, independently contributes to the risk of hyperglycaemia or type 2 diabetes in men in Taiwan, where the habit has become established ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1532-2
更新日期:2004-10-01 00:00:00
abstract:AIMS/HYPOTHESIS:Increased NEFA levels, characteristic of type 2 diabetes mellitus, contribute to skeletal muscle insulin resistance. While NEFA-induced insulin resistance was formerly attributed to decreased glycolysis, it is likely that glucose transport is the rate-limiting defect. Recently, the plant-derived sugar a...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2527-z
更新日期:2012-06-01 00:00:00
abstract:AIMS/HYPOTHESIS:Bariatric surgery consistently induces remission of type 2 diabetes. We tested whether there are diabetes-specific mechanisms in addition to weight loss. METHODS:We studied 25 morbidly obese patients (BMI 51.7 ± 1.5 kg/m(2) [mean ± SEM]), 13 with non-insulin-treated type 2 diabetes (HbA(1c) 7.1 ± 0.5% ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-011-2193-6
更新日期:2011-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:To investigate clinical and sociodemographic predictors of birthweight in singletons born to women with type 1 or type 2 diabetes. METHODS:Normally formed singleton live births and intrapartum stillbirths, born to women with pre-conception diabetes during 1996-2008, were identified from the population-...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2721-z
更新日期:2012-12-01 00:00:00
abstract:UNLABELLED:AIMS/HYPOTHESIS; The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II (non-insulin-dependent) diabetes mellitus in subjects with impaired glucose tolerance, to evaluate the effects of the intervention programme on cardiov...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/s001250051229
更新日期:1999-07-01 00:00:00
abstract:AIMS/HYPOTHESIS:The process of islet isolation can cause chemical and mechanical injury to beta cells. In addition, hyperglycaemia after islet transplantation can compromise beta cell function. The aim of this experiment was to evaluate changes in gene expression in endogenous islets using laser-capture microdissection...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0536-5
更新日期:2007-02-01 00:00:00
abstract:AIMS/HYPOTHESIS:To assess whether self-monitoring of blood glucose (SMBG) is an independent predictor of improved outcome in a community-based cohort of type 2 diabetic patients. MATERIALS AND METHODS:We used longitudinal data from (1) 1,280 type 2 diabetic participants in the observational Fremantle Diabetes Study (F...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0581-0
更新日期:2007-03-01 00:00:00
abstract:AIMS/HYPOTHESIS:We examined the acute postprandial effects of meals containing unsaturated fatty acids on flow-mediated dilation (FMD) of the brachial artery and triacylglycerols in individuals with type 2 diabetes. We hypothesised that consumption of omega-3 fatty acids would enhance vascular function. Saturated fat r...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-004-1600-7
更新日期:2005-01-01 00:00:00
abstract:AIMS/HYPOTHESIS:Chronic hyperglycaemia in patients with Type II (non-insulin-dependent) diabetes mellitus often leads to a decline in glucose-responsive insulin secretion from pancreatic beta cells, a phenomenon called glucose toxicity. Upon hyperglycaemia, glycation reaction occurs in the beta cells and induces oxidat...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250051313
更新日期:1999-12-01 00:00:00
abstract:AIMS/HYPOTHESIS:Type 2 diabetes is characterised by progressive loss of pancreatic beta cell mass and function. Therefore, it is of therapeutic interest to identify factors with the potential to improve beta cell proliferation and insulin secretion. Bone morphogenetic protein 4 (BMP4) expression is increased in diabeti...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-015-3568-x
更新日期:2015-06-01 00:00:00
abstract::Blood glucose values close to normal reduce the microvascular complications of insulin-dependent diabetes mellitus. The Stockholm study of this effect continued after the initial 7.5-year period in order to see what happened when intensively treated patients were left to control their own treatment while treatment was...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s001250050602
更新日期:1996-12-01 00:00:00
abstract::Recent studies have reported reduced endocrine and symptomatic responses to hypoglycaemia 18-24 h after antecedent hypoglycaemia in both non-diabetic subjects and those with insulin-dependent diabetes mellitus. We examined these and peripheral physiological responses in eight non-diabetic subjects aged 23-35 years in ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00422367
更新日期:1995-10-01 00:00:00
abstract::Downregulation of insulin receptor tyrosine kinase (IRK) activity yields to impaired insulin signalling and contributes to the pathogenesis of cellular insulin resistance. Activation of protein kinase C (PKC) by different agents is associated with an inhibition of IRK activity in various cell types. There is evidence ...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050761
更新日期:1997-07-01 00:00:00
abstract::Insulin secretion from pancreatic beta cells is dependent on membrane potential changes that result from the concerted regulation of multiple ion channels. Among the distinct K+ channels known to be expressed in beta cells, large conductance Ca(2+)-activated K+ channels have been suggested to play an important role in...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00403907
更新日期:1996-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:Type 2 diabetes mellitus is associated with reduced incretin effects. Although previous studies have shown that hyperglycaemia contributes to impaired incretin responses in beta cells, it is largely unknown how hyperlipidaemia, another feature of type 2 diabetes, contributes to impaired glucagon-like pe...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2776-x
更新日期:2013-02-01 00:00:00
abstract::Ciglitazone is orally active in preventing and reversing the hyperglycaemic syndrome in C57BL/6J-ob/ob mice and it is only mildly and transiently hypoglycaemic in lean littermates (C57BL/6J-+/?). Its effect on glucose disposal in vivo was estimated by injecting glucose-6-3H/14C and following the specific activity of r...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00284462
更新日期:1983-12-01 00:00:00
abstract::Analysis of the plasma from a totally pancreatectomized patient, with antiserum 30 K, has demonstrated basal glucagon immunoreactivity (GIR) levels in the normal range (80-110 pg/ml). Neither i. v. arginine nor oral glucose affected these GIR values, thus indicating the absence of functioning pancreatic or gastrointes...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF01220639
更新日期:1976-12-01 00:00:00
abstract:AIMS/HYPOTHESIS:We analysed the cost-effectiveness of intensified prevention in diabetic patients with different risks for foot ulcers and lower extremity amputations. Specifically, we examined whether the additional prevention costs associated with present recommendations would be offset by reduced costs of future foo...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250100013
更新日期:2001-11-01 00:00:00
abstract:AIMS:We compared the effects of continuous subcutaneous insulin infusion (CSII) with those of multiple daily insulin (MDI) injections on glycaemic control, risk of hypoglycaemic episodes, insulin requirements and adverse events in type 1 and type 2 diabetes mellitus. METHODS:The electronic databases MEDLINE, EMBASE an...
journal_title:Diabetologia
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00125-008-0974-3
更新日期:2008-06-01 00:00:00
abstract::It is suggested that amylin (islet associated polypeptide), co-secreted with insulin from the pancreatic beta cells acts as a circulating hormone which opposes the action of insulin on muscle and increases hepatic glucose production. We have tested the effect of amylin in human subjects on postabsorptive glucose homeo...
journal_title:Diabetologia
pub_type: 临床试验,杂志文章
doi:10.1007/s001250050088
更新日期:1994-02-01 00:00:00
abstract::The role of syntaxin 1, a protein involved in the docking of synaptic vesicles at presynaptic active zones, has been investigated in pancreatic islet cells. Using two different monoclonal antibodies we have shown that syntaxin 1 is present in the pancreatic islet cell microsomal fraction. Furthermore, functional exper...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s001250050364
更新日期:1995-07-01 00:00:00
abstract::The use of tritiated glucose tracers may result in underestimation of glucose turnover during hyperinsulinaemic clamps giving paradoxical negative endogenous glucose production rates. While mathematical modelling errors in the analysis of tracer data are major determinants of this underestimate in the non-steady state...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00400570
更新日期:1990-11-01 00:00:00
abstract::To study the effect of E. Coli L-asparaginase on glucose tolerance and insulin release, 6 patients with neoplastic disease were subjected to 3 hour oral glucose tolerance tests with simultaneous measurement of serum immunoreactive insulin (IRI) levels before and following the intravenous administration of 5000 I. U. L...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00422255
更新日期:1978-08-01 00:00:00
abstract:AIMS/HYPOTHESIS:The aim of this study was to determine the role of fatty acid signalling in islet beta cell compensation for insulin resistance in the Zucker fatty fa/fa (ZF) rat, a genetic model of severe obesity, hyperlipidaemia and insulin resistance that does not develop diabetes. MATERIALS AND METHODS:NEFA augmen...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-006-0305-5
更新日期:2006-09-01 00:00:00
abstract::The pO2 at which haemoglobin is half-saturated with oxygen (p50) was determined at fixed pCO2 (45 mmHg) and without altering the resulting pH and the level of organic phosphates in heparinized whole blood samples from 26 diabetic patients and 24 normal subjects of both sexes. Diabetic blood p50 was higher (29.79 +/- 1...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/BF00260950
更新日期:1982-11-01 00:00:00
abstract:AIMS/HYPOTHESIS:Pancreatic islet transplantation (PIT) offers a physiological treatment for type 1 diabetes, but the failure of islet engraftment hinders its application. The female hormone 17β-oestradiol (E2) favours islet survival and stimulates angiogenesis, raising the possibility that E2 may enhance islet engraftm...
journal_title:Diabetologia
pub_type: 杂志文章
doi:10.1007/s00125-012-2764-1
更新日期:2013-02-01 00:00:00