The Link Between Type 2 Diabetes and Heart Failure

A Mendelian Randomization found a correlation between type 2 diabetes and heart failure, utilizing genetic markers.

Type 2 diabetes and heart failure are two common chronic conditions that coincide in 40% of patients. However, the correlation is often unclear. Risk factors for heart failure in patients with T2DM are coronary artery disease and arterial hypertension, which directly affect the myocardium. While the symptoms of T2DM are often masked and unrecognizable in patients with heart failure, diabetes treatment, specifically SGLT2 inhibitors, has shown a reduction in heart failure hospitalization¹. Farxiga is an SGLT2 inhibitor used for diabetes and has gained FDA approval as a new treatment option for heart failure, highlighting the significance of the association between T2DM and heart failure. In addition, observational studies have shown a two to four increased risk in patients with heart failure and diabetes, as opposed to those who do not have diabetes^2,3. Poor glycemic control, older age, retinopathy, duration of diabetes, and hypertension have all increased the risk of heart failure⁴. Previous observational studies have failed to show the causality between T2DM and heart failure and show inconsistent effects on the prevalence of heart failure.

A Mendelian randomization study⁵ was recently conducted to estimate the relationship between metabolic risk factors and T2DM and heart failure. Two samples of MR were performed to analyze data from primarily European individuals utilizing genome-wide association summaries. These data sets included T2DM and heart failure patients and looked at HbA1C, fasting insulin, and fasting glucose parameters. The researchers used an older T2DM genome-wide association study from the DIAGRAM consortium consisted of 74,124 cases and 234 variants associated with T2DM. Heart failure variants were studied utilizing 47,309 cases in the HERMES consortium. In addition, 10,149 patients with T2DM were studied to find the association between T2DM and heart failure in the GoDARTS study. Cox proportional hazards regression was utilized to look at BMI, age, systolic blood pressure, sex, and history of myocardial infarction. A multivariable MR analysis was also conducted to consider the association of variants with other exposures.

The GoDARTS observational analysis showed a higher incidence of heart failure in patients with T2DM (13.4%) than those without T2DM (3.9%). Genetic liability to T2DM was shown to be in correlation with having a higher risk for heart failure ( [OR] 1.13 per 1-log unit higher risk of T2D; 95% CI 1.11–1.14; P < 0.001). The association between T2DM and heart failure was slightly reduced when coronary disease, BMI, blood pressure, and LDL were adjusted in the multivariable MR. However, there were no significant associations between fasting glucose or insulin, hemoglobin, and risk of heart failure. This analysis shows that the association between heart failure and T2DM could be lower when coronary heart disease is included in the research, suggesting the need to educate patients about preventing CHD. This MR study has also shown a pleiotropy between genetic variants and T2DM with heart failure.

This study might have been underpowered to detect a more negligible effect, as genetic variants were only accounted for a small proportion. Although previous studies have failed to show causality between T2DM and heart failure, this MR showed a relationship between genetic variants and T2DM with heart failure. Additionally, this relationship can show shared pathophysiology between T2DM, heart failure, and coronary heart disease. T2DM genetic variants were previously associated with coronary heart disease, while CHD genetic variants were correlated with heart failure. The authors did not report a relationship between HbA1C and fasting insulin or glucose with heart failure, indicating that an abnormality in glycemic levels alone should not be attributed to heart failure in patients with T2DM. A few limitations of this MR include a limited ability to use subgroup analysis such as sex or age, a lack of heart failure subgroup data such as preserved vs. reduced ejection fraction, and ischemic vs. nonischemic. Furthermore, the risk of coronary heart disease could potentially be elevated before developing T2DM, as the authors have shown that patients with prediabetes were at an increased cardiovascular risk. However, this study has notably identified the genetic and pathophysiology relationship of T2DM in heart failure and how coronary heart disease can intervene.

Practice Pearls:

• T2DM and heart failure often occur together and are each associated with morbidity and mortality.
• This MR found an association between T2DM and heart failure. However, the risk was lower with the association of coronary heart disease.
• Further studies analyzing the sequential incidence of time of disease onset between T2DM, heart failure, and CHD will help evaluate the correlation between the three conditions.

1. Seferović, Petar M, et al. “Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology.” European journal of heart failure
2. Kannel, W B, and D L McGee. “Diabetes and cardiovascular disease. The Framingham study.” JAMA
3. Gottdiener, J S et al. “Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study.” Journal of the American College of Cardiology
4. Nichols, Gregory A et al. “The incidence of congestive heart failure in type 2 diabetes: an update.” Diabetes care
5. Mordi, Ify R, et al. “Type 2 Diabetes, Metabolic Traits, and Risk of Heart Failure: A Mendelian Randomization Study.” Diabetes care,

Dalia Elabed, PharmD Candidate 2022, University of South Florida Taneja College of Pharmacy

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