Diabetes mellitus and atrial fibrillation: Perspectives on epidemiological and pathophysiological links

Lip, Gregory Y.H.; Varughese, George

doi:10.1016/j.ijcard.2005.03.003

Cited by 59 publications

(41 citation statements)

References 24 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In neonatal rat cardiac myocytes, IGF1 had an impact on potassium currents that protected myocytes against arrhythmogenesis, and this protection was mediated by both PI3K-dependent and PI3K-independent mechanisms 49 . Identification of drugs that can mediate protection independently of PI3K is of further significance because risk factors for HF and AF including obesity and diabetes have also been associated with impaired PI3K-Akt signalling in the heart [23][24][25]44 . Thus, a therapy that can provide protection independent of PI3K has the potential to be valuable in a number of settings.…”

Section: Discussionmentioning

confidence: 99%

“…In brief, the model was generated by breeding a cardiac-specific Tg mouse with a failing heart because of dilated cardiomyopathy (DCM, induced with increased activity of mammalian sterile 20-like kinase 1, Mst1; a kinase activated by clinically important pathologic insults such as ischaemia/ reperfusion 21 ) with a cardiac-specific Tg mouse with reduced phosphoinositide 3-kinase (PI3K; because of expression of a dominant negative PI3K (dnPI3K) mutant 22 ). Risk factors for HF and AF, including ageing, obesity and diabetes, have been associated with insulin resistance that can lead to depressed/ defective PI3K signalling [23][24][25] , and PI3K activity was also depressed in atrial tissue from patients with AF 20 . Reducing PI3K in the mouse model with DCM accelerated the HF phenotype based on the following findings: additional systolic dysfunction, substantial atrial enlargement, increased fibrosis and elevated lung weights 20 .…”

mentioning

confidence: 99%

See 1 more Smart Citation

The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice

et al. 2014

View full text Add to dashboard Cite

Heart failure (HF) and atrial fibrillation (AF) share common risk factors, frequently coexist and are associated with high mortality. Treatment of HF with AF represents a major unmet need. Here we show that a small molecule, BGP-15, improves cardiac function and reduces arrhythmic episodes in two independent mouse models, which progressively develop HF and AF. In these models, BGP-15 treatment is associated with increased phosphorylation of the insulin-like growth factor 1 receptor (IGF1R), which is depressed in atrial tissue samples from patients with AF. Cardiac-specific IGF1R transgenic overexpression in mice with HF and AF recapitulates the protection observed with BGP-15. We further demonstrate that BGP-15 and IGF1R can provide protection independent of phosphoinositide 3-kinase-Akt and heat-shock protein 70; signalling mediators often defective in the aged and diseased heart. As BGP-15 is safe and well tolerated in humans, this study uncovers a potential therapeutic approach for HF and AF.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice

et al. 2014

View full text Add to dashboard Cite

show abstract

“…37 People with diabetes have higher levels of C-reactive protein, 3-6 a marker of systemic inflammation, which may promote myocardial fibrosis and diastolic dysfunction. Diabetes is associated with left atrial enlargement 2 which is thought to allow the development and propagation of reentrant electrical circuits.…”

Section: Discussionmentioning

confidence: 99%

Diabetes Mellitus, Glycemic Control, and Risk of Atrial Fibrillation

et al. 2010

View full text Add to dashboard Cite

BACKGROUND: Diabetes may be an independent risk factor for atrial fibrillation. However, results from prior studies are in conflict, and no study has examined diabetes duration or glycemic control. OBJECTIVE: To examine the association of diabetes with risk of atrial fibrillation and to describe risk according to diabetes duration and glycemic control. DESIGN: A population-based case-control study. PARTICIPANTS: Within a large, integrated healthcare delivery system, we identified 1,410 people with newlyrecognized atrial fibrillation from ICD-9 codes and validated cases by review of medical records. 2,203 controls without atrial fibrillation were selected from enrollment lists, stratified on age, sex, hypertension, and calendar year. MAIN MEASURES: Information on atrial fibrillation, diabetes and other characteristics came from medical records. Diabetes was defined based on physician diagnoses recorded in the medical record, and pharmacologically treated diabetes was defined as receiving antihyperglycemic medications. Information about hemoglobin A1c levels came from computerized laboratory data. KEY RESULTS: Among people with atrial fibrillation, 252/1410 (17.9%) had pharmacologically treated diabetes compared to 311/2203 (14.1%) of controls. The adjusted OR for atrial fibrillation was 1.40 (95% CI 1.15-1.71) for people with treated diabetes compared to those without diabetes. Among those with treated diabetes, the risk of developing atrial fibrillation was 3% higher for each additional year of diabetes duration (95% CI 1-6%). Compared to people without diabetes, the adjusted OR for people with treated diabetes with average hemoglobin A1c ≤7 was 1.06 (95% CI 0.74-1.51); for A1c >7 but ≤8, 1.48 (1.09-2.01); for A1c >8 but ≤9, 1.46 (1.02-2.08); and for A1c >9, 1.96 (1.22-3.14). CONCLUSIONS: Diabetes was associated with higher risk of developing atrial fibrillation, and risk was higher with longer duration of treated diabetes and worse glycemic control. Future research should identify and test approaches to reduce the risk of atrial fibrillation in people with diabetes.

show abstract

“…Diabetes mellitus (DM) is one of the strongest independent risk factors for subsequent AF (7,8) and has pathophysiological links with AF (9), but the exact mechanisms that underlying the relationship between DM and AF remain speculative. A recent meta-analysis (10) indicated that individuals with DM had an approximate 40% greater risk of AF compared with unaffected individuals.…”

Section: Introductionmentioning

confidence: 99%

Hyperglycemia aggravates atrial interstitial fibrosis, ionic remodeling and vulnerability to atrial fibrillation in diabetic rabbits

Liu

Fu²,

Li³

et al. 2012

Anadolu Kardiyol Derg

View full text Add to dashboard Cite

Objective: The purpose of this study was to investigate the effects of hyperglycemia on atrial interstitial fibrosis, ionic remodeling and vulnerability to atrial fibrillation (AF) in alloxan-induced diabetic rabbits. Methods: Sixty Japanese rabbits were randomly assigned to alloxan-induced diabetic group (n=30) and control group (n=30). Ten rabbits in each group were respectively used to electrophysiological and histological study, patch-clamp study and Western blotting analysis. Langendorff perfusion was used to record inter-atrial conduction time (IACT), atrial effective refractory period (AERP) and dispersion (AERPD) and vulnerability to AF. Histological study was measured by Sirius-red stain. Patch-clamp technique was used to measure action potential duration (APD) and atrial ionic currents (INa and ICaL). Western blotting was applied to assess atrial protein expression of transforming growth factor beta 1 (TGFβ1). Results: Compared with control group, electrophysiological studies showed IACT was prolonged (37.91±6.81 vs. 27.43±1.63ms, p<0.01), AERPD was increased (30.37±8.33 vs. 14.70±5.16ms, p<0.01) in diabetic group. Inducibility of AF in diabetic group was significantly higher than in controls (8/10 vs. 1/10 of animals, p<0.01). Collagen volume fraction was increased (6.20±0.64% vs. 2.15±0.21%, p<0.01) in diabetic group. Patch-clamp studies demonstrated APD90 and APD50 were prolonged in diabetic rabbits (p<0.05 vs. control). The densities of INa were reduced and the densities of ICaL were increased (p<0.01 vs. control). Protein expression of TGFβ1 was increased in diabetic group (p<0.001 vs. control). Conclusion: Our study suggests that hyperglycemia contributes to atrial interstitial fibrosis, ionic remodeling and vulnerability to AF in diabetic rabbits, resulting in atrial structural remodeling and electrical remodeling for the development and perpetuation of AF. (Anadolu Kardiyol Derg 2012; 12: 543-50)

show abstract

Diabetes mellitus and atrial fibrillation: Perspectives on epidemiological and pathophysiological links

Cited by 59 publications

References 24 publications

The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice

The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice

Diabetes Mellitus, Glycemic Control, and Risk of Atrial Fibrillation

Hyperglycemia aggravates atrial interstitial fibrosis, ionic remodeling and vulnerability to atrial fibrillation in diabetic rabbits

Contact Info

Product

Resources

About