Investigating the Link Between Atrial Fibrillation and Type 2 Diabetes

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Based on epidemiologic evidence, it can be assumed that the major factor in the development of atrial fibrillation in patients with type 2 diabetes is metabolic syndrome.
Based on epidemiologic evidence, it can be assumed that the major factor in the development of atrial fibrillation in patients with type 2 diabetes is metabolic syndrome.

Endocrinologists are not fully aware of the risks for atrial fibrillation in patients with type 2 diabetes, according to David S. H. Bell, MB, retired Professor of Medicine at the University of Alabama at Birmingham School of Medicine and lead author of a review on atrial fibrillation and type 2 diabetes published in Diabetes, Obesity & Metabolism.1 Dr Bell firmly believes endocrinologists should actively screen for the condition. “Physicians need to know that it's not just heart attacks and strokes in the patient [with diabetes],” he told Endocrinology Advisor. “There's an increase in heart failure in [those with diabetes], and there's an increase in cardiac arrhythmias.”

Atrial fibrillation is the most common cardiac arrhythmia, carrying an estimated lifetime risk of 22% to 26%.2 It is a risk factor for ischemic stroke, systemic thromboembolism, transient ischemic attack, dementia, and death.3,4 In 2010, atrial fibrillation was estimated to affect 5.2 million individuals in the United States, a figure projected to more than double to 12.1 million people by 2030 with the aging of the population.5 Symptoms of atrial fibrillation include fatigue, palpitations, dizziness, and chest tightness, but the condition is often silent and diagnosed only after the occurrence of thromboembolism, stroke, or heart failure.6,7

In patients with diagnosed atrial fibrillation, comorbid diabetes is associated with more severe symptoms of atrial fibrillation, lower quality of life, and increased risk for stroke, mortality, and hospitalizations.6,8 Compared with the general population, patients with type 2 diabetes are at a 35% to 60% greater risk for atrial fibrillation.1

The exact mechanisms that account for the elevated risk for atrial fibrillation in patients with type 2 diabetes have not been fully elucidated. In a 2007 review on the topic of diabetes and atrial fibrillation, Marijana Tadic, MD, PhD of the Faculty of Medicine at the University of Belgrade in Belgrade, Serbia, and colleagues stated, “it is difficult to determine whether diabetes directly affects the atrial tissue or whether different pathways are involved, including hypertension, coronary artery disease, and abnormal activity of the autonomic nervous system.”9 In contrast, Dr Bell and his co-author Edison Goncalves, MD, were more definitive, writing, “Based on the epidemiological evidence it can be assumed that the major factor in the development of [atrial fibrillation] in the [person with] type 2 [diabetes] is the metabolic syndrome. The metabolic syndrome and its associations with hypertension, inflammation, endothelial dysfunction, [and] myocardial steatosis in addition to hyperglycemia (particularly fluctuations in glucose levels…) leads to left atrial fibrosis and structural remodeling accompanied by left atrial dilatation.”1

Dr Bell and Dr Goncalves reject the idea that hyperglycemia is a major factor in atrial fibrillation, writing, “If the degree of glycemic control was a factor for developing atrial fibrillation, the incidence and prevalence of [atrial fibrillation] would be increased in [patients] with type 1 diabetes.”1 However, a 2017 analysis of records from the Swedish National Patient Registry indicated that the risk for atrial fibrillation in men with type 1 diabetes was slightly greater than in patients without the disease, and for women with type 1 diabetes, risk for atrial fibrillation was 50% higher. The risk for atrial fibrillation in people with type 1 diabetes increased significantly with severity of renal complications. Study investigators also found a greater risk for atrial fibrillation in patients with deteriorating glycemic control.10 In another population-based study, risk for atrial fibrillation was correlated with higher levels of blood glucose, suggesting that poor glucose control also plays a role in risk for the condition.11 Despite this, Dr Bell and Dr Goncalves concluded in their review that renal hypertension — not hyperglycemia — was responsible for the increased rate of atrial fibrillation in the 2017 study.1

Dr Bell and Dr Goncalves found no evidence that dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, and the glucagon-like peptide 1 agonists had any impact on the risk for atrial fibrillation in patients with diabetes. They did conclude that both the insulin-sensitizing thiazolidine pioglitazone (but not rosiglitazone) and metformin may be protective against new-onset atrial fibrillation. “In addition, drugs that stimulate the sympathetic nervous system through hypoglycemia (insulin and secretagogues) likely increase the incidence of [new-onset atrial fibrillation],” the researchers concluded.1 This finding is supported by a nested case-control study using a national health insurance database in Taiwan in which insulin users had a higher risk for new-onset atrial fibrillation compared with nonusers.12

In a recommendation statement on screening with electrocardiography, the US Preventive Services Task Force concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening with electrocardiography for the prediction of cardiovascular disease events in asymptomatic adults at intermediate or high risk (including diabetes) for cardiovascular disease events.13 In contrast, Dr Bell stated that the increased risk for atrial fibrillation and other cardiovascular diseases in patients with diabetes warrants annual electrocardiography, a position that is echoed by some researchers.14 “Endocrinologists need to avoid being glucocentric,” he told Endocrinology Advisor. “We often think that when our patients have complaints that they must be due to their blood sugar. But we have to care for the whole patient. Diabetes affects every organ of the body. We need to be alert to the possibility that their complaints may be due to atrial fibrillation, so that we can avoid strokes.”

References

1. Bell DSH, Goncalves E. Atrial fibrillation and type 2 diabetes: prevalence, etiology, pathophysiology and effect of anti-diabetic therapies [published online August 24, 2018]. Diabetes Obes Metab. doi: 10.1111/dom.13512

2. Andrade J, Khairy P, Dobrev D, Nattel S. The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms. Circ Res. 2014;114(9):1453-1468.

3. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983-988.

4. Zakeri R, Van Wagoner DR, Calkins H, et al. The burden of proof: the current state of atrial fibrillation prevention and treatment trials. Heart Rhythm. 2017;14(5):763-782.

5. Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013;112(8):1142-1147.

6. Echouffo-Tcheugui JB, Shrader P, Thomas L, et al. Care patterns and outcomes in atrial fibrillation patients with and without diabetes: ORBIT-AF registry. J Am Coll Cardiol. 2017;70(11):1325-1335.

7. Lip GY. Stroke in atrial fibrillation: epidemiology and thromboprophylaxis. J Thromb Haemost. 2011;9 Suppl 1:344-351.

8. Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology. 2007;69(6):546-554.

9. Tadic M, Cuspidi C. Type 2 diabetes mellitus and atrial fibrillation: from mechanisms to clinical practice. Arch Cardiovasc Dis. 2015;108(4):269-276.

10. Dahlqvist S, Rosengren A, Gudbjörnsdottir S, et al. Risk of atrial fibrillation in people with type 1 diabetes compared with matched controls from the general population: a prospective case-control study. Lancet Diabetes Endocrinol. 2017;5(10):799-807.

11. Aune D, Feng T, Schlesinger S, Janszky I, Norat T, Riboli E. Diabetes mellitus, blood glucose and the risk of atrial fibrillation: a systematic review and meta-analysis of cohort studies. J Diabetes Complications. 2018;32(5):501-511.

12. Chen H-Y, Yang F-Y, Jong G-P, Liou Y-S. Antihyperglycemic drugs use and new-onset atrial fibrillation in elderly patients. Eur J Clin Invest. 2017;47(5):388-393.

13. U.S. Preventive Services Task Force. Final Recommendation Statement: Cardiovascular Disease Risk: Screening With Electrocardiography. June 2018. Accessed September 26, 2018.

14. V Bandemer S, Merkel S, Nimako-Doffour A, Weber MM. Diabetes and atrial fibrillation: stratification and prevention of stroke risks. EPMA J. 2014;5(1):17.

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