Variants and Haplotypes of<i>TCF7L2</i>Are Associated with β-Cell Function in Patients with Newly Diagnosed Type 2 Diabetes: The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 1

Bonetti, Sara; Trombetta, Maddalena; Malerba, Giovanni; Boselli, Linda; Trabetti, Elisabetta; Muggeo, Michele; Stoico, Vincenzo; Negri, Carlo; Pignatti, Pierfranco; Bonora, Enzo; Bonadonna, Riccardo C.

doi:10.1210/jc.2010-1677

Cited by 33 publications

(34 citation statements)

References 19 publications

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“…The analysis of the glucose and C-peptide curves was performed as previously described (16,17). Further details can be found in the Supplementary Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Effects of Aerobic Training and Resistance Training in Type 2 Diabetic Subjects

et al. 2012

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OBJECTIVETo assess differences between the effects of aerobic and resistance training on HbA1c (primary outcome) and several metabolic risk factors in subjects with type 2 diabetes, and to identify predictors of exercise-induced metabolic improvement.RESEARCH DESIGN AND METHODSType 2 diabetic patients (n = 40) were randomly assigned to aerobic training or resistance training. Before and after 4 months of intervention, metabolic phenotypes (including HbA1c, glucose clamp–measured insulin sensitivity, and oral glucose tolerance test–assessed β-cell function), body composition by dual-energy X-ray absorptiometry, visceral (VAT) and subcutaneous (SAT) adipose tissue by magnetic resonance imaging, cardiorespiratory fitness, and muscular strength were measured.RESULTSAfter training, increase in peak oxygen consumption (VO2peak) was greater in the aerobic group (time-by-group interaction P = 0.045), whereas increase in strength was greater in the resistance group (time-by-group interaction P < 0.0001). HbA1c was similarly reduced in both groups (−0.40% [95% CI −0.61 to −0.18] vs. −0.35% [−0.59 to −0.10], respectively). Total and truncal fat, VAT, and SAT were also similarly reduced in both groups, whereas insulin sensitivity and lean limb mass were similarly increased. β-Cell function showed no significant changes. In multivariate analyses, improvement in HbA1c after training was independently predicted by baseline HbA1c and by changes in VO2peak and truncal fat.CONCLUSIONSResistance training, similarly to aerobic training, improves metabolic features and insulin sensitivity and reduces abdominal fat in type 2 diabetic patients. Changes after training in VO2peak and truncal fat may be primary determinants of exercise-induced metabolic improvement.

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“…The analysis of the glucose and C-peptide curves was performed as previously described (16,17). Further details can be found in the Supplementary Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Effects of Aerobic Training and Resistance Training in Type 2 Diabetic Subjects

et al. 2012

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“…This locus was discovered following a linkage peak fine-mapping study on chromosome 10 [41]. TCF7L2 diabetes risk variants, either as SNPs or as haplotypes, detrimentally influencecell function and might play a role in determining the metabolic phenotype of patients with newly diagnosed T2DM [42]. A recent meta-analysis demonstrates that four variants of TCF7L2 gene are all associated with T2DM and indicates a multiplicative genetic model for all the four polymorphisms, as well as suggests that the TCF7L2 gene in almost 1/5 of all T2DM [43].…”

Section: Genetic Polymorphisms Associated With Risk Of Type 2 Diabetesmentioning

confidence: 99%

Genome-Wide Association Studies: Is there a Genotype for Cognitive Decline in Older Persons with Type 2 Diabetes?

Abbatecola¹,

Olivieri²,

Corsonello³

et al. 2011

Current Pharmaceutical Design

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There is a dramatic increase in the number of elderly persons on a worldwide scale with an increase in chronic comorbidities, especially type 2 diabetes (T2DM) and dementia. Although cognitive faculties commonly deteriorate in non-diabetic persons as they age, several studies have concluded that diabetes is uniquely associated with cognitive decline and is associated with a two-fold risk of Alzheimer's Disease (AD). Studies have also suggested that good glycemic has shown to improve cognitive status, however whether the use of specific anti-diabetic oral agents may play an additional role in controlling against cognitive deterioration is unknown. In addition, excitotoxicity from the overstimulation of glutamate receptors is considered a major cause of neuron death in AD and statins may be promising agents for protecting against memory loss. Possible pathophysiologic mechanisms common to both T2DM and AD are glucose toxicity and a direct effect of insulin on amyloid metabolism. In fact, AD and T2DM have comparable pathological features in the islet and brain (amyloid derived from amyloid β protein (β-amyloid) in the brain in AD and islet amyloid derived from islet amyloid polypeptide in the pancreas in T2DM). Evidence is growing linking precursors of amyloid deposition in the brain and pancreas to the pathogenesis of AD and T2DM, respectively. Indeed, the need to identify agents capable of correcting such pathological features may in turn significantly protect against the accumulation of β-amyloid in the brain, known to interfere with correct cognitive function. Cholesterol may also be directly involved in β-amyloid aggregation: abnormal oxidative metabolites such as cholesterol-derived aldehydes can modify β-amyloid, firstly promoting Schiff base formation, then accelerating the early stages of amyloidogenesis. At the moment, genome-wide association studies (GWAS) have begun to elucidate the genetic architecture of chronic diseases including, T2DM and AD. Thus, one of the challenges for a successful GWAS in the future will be to identify a genotype in older persons with T2DM for good drug response, which in turn may protect against cognitive decline and AD. The literature has suggested that the use of insulin sensitizers and statins is correlated with a lower rate of cognitive decline in older persons. In this paper, we will explore recent findings regarding diverse single nucleotide polymorphisms from GWAS on T2DM, AD and both. We will also shed light on future pathways, as the basis of improving drug and diagnostics development for a better integration of genetic studies for precise drug-development focusing on the role of genetic variation in maintaining metabolic control and cognitive performance.

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“…Out of 228 potentially relevant articles retrieved from electronic databases and reference lists, 19 studies met the inclusion criteria[14,19,[24][25][26][27][31][32][33][34][35][36][37][38][39][40][41][42]. A flow diagram of search and selection was shown in Supporting Information S2.…”

mentioning

confidence: 99%

Polymorphism in the transcription factor 7-like 2 (TCF7L2) gene is associated with impaired proinsulin conversion—A meta-analysis

Shen

Fang

2015

Diabetes Research and Clinical Practice

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Variants and Haplotypes ofTCF7L2Are Associated with β-Cell Function in Patients with Newly Diagnosed Type 2 Diabetes: The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 1

Abstract: TCF7L2 diabetes risk variants, either as single-nucleotide polymorphisms or as haplotypes, detrimentally influence β-cell function and might play a role in determining the metabolic phenotype of patients with newly diagnosed type 2 diabetes.

Cited by 33 publications

References 19 publications

Metabolic Effects of Aerobic Training and Resistance Training in Type 2 Diabetic Subjects

Metabolic Effects of Aerobic Training and Resistance Training in Type 2 Diabetic Subjects

Genome-Wide Association Studies: Is there a Genotype for Cognitive Decline in Older Persons with Type 2 Diabetes?

Polymorphism in the transcription factor 7-like 2 (TCF7L2) gene is associated with impaired proinsulin conversion—A meta-analysis

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