One such complex web of interconnections exists between the heart, kidneys, and type 2 diabetes. As healthcare professionals at the forefront of patient care, pharmacists play a crucial role in recognising and managing the intricate relationship between these three vital organs. 

Type 2 diabetes, a chronic metabolic disorder affecting millions worldwide, not only poses a significant threat to blood sugar regulation but also exerts profound effects on various organ systems. Two vital organs that face particular vulnerability are the heart and the kidneys. Research over the years has revealed that these three entities are intrinsically linked, forming a triad of conditions that can exacerbate one another and complicate overall patient management. 

Cardiovascular renal metabolic (CVRM) disorderare a complex combination of different health diseases including cardiovascular diseases (CVDs), chronic kidney disease (CKD), and type 2 diabetes (T2D). These diseases are interlinked, meaning a change in one of the disease outcomes will affect the other diseases’ outcomes. Risk factors for these diseases are also the same. Treatment and management should be planned in a holistic manner. This can be done by understanding the underlying causes and the interplay between them. 

THE HEART CONNECTION 

Cardiovascular diseases (CVDs) include coronary artery disease (CAD), heart failure (HF), and acute coronary syndrome. CVDs are interconnected with diabetes and renal diseases and share common risk factors. 

CAD results from atherosclerotic plaques that accumulate in the coronary arteries leading to hypercholesterolaemia resulting in a decrease of oxygen to the heart muscles. This may in turn lead to hypertension which can worsen kidney damage and raise the risk for a heart attack/stroke. 

Approximately 1:3 patients with CAD are estimated to have T2D. Patients with both CAD and T2D have almost double the risk for a major CV event compared to people living with T2D who only have risk factors for CVDs. ^1,2 

It is also important to note that the more risk factors (eg diabetes, multivessel disease, or CKD) a patient has prior to a heart attack, the greater their chance is of experiencing a CV event. ³ 

In the US, about 33-46% of the patients with end-stage renal disease have CVDs and about 28-44% have HF.⁴

THE KIDNEY CONNECTION 

Chronic kidney disease (CKD) is caused by diabetes and hypertension which are also interlinked. The main causes of CKD are diabetes, high blood pressure and glomerulonephritis.⁵ 

Kidney disease is a common complication of T2D. If a patient has T2D and kidney disease, there is a 3x higher risk of dying from a CV event such as heart attack or stroke. Heart disease is the most common cause of death among people who have CKD. 

When a patient suffers from hypertension it can damage the small blood vessels situated in the kidney. This results in the kidneys failing to filter the blood as they should. In turn, having kidneys that do not function optimally can lead to hypertension, indicating an interlink between the two diseases. 

Patients with CKD also face an increased risk of developing other complications like anaemia or hyperkalaemia. Hyperkalaemia is associated with an increased risk of CV events and death.^6,7,8 

THE DIABETES CONNECTION 

Type 2 diabetes (T2D) is associated with metabolic disorder within CVRM diseases. This makes it important for people living with T2D to be aware that both their kidneys and heart are at risk due to diabetes. Diabetes can damage blood vessels in the kidneys, which can eventually lead to CKD and, over time, kidney failure. 

Hyperglycaemia damages blood vessels over time and having hyperglycaemia for an extensive period can lead to damage of the heart and kidneys. Treatment with a SLGT-2 inhibitor (e.g., dapagliflozin) may be useful for targeting CVRM diseases.

By gaining a deeper understanding of the complex relationship between the heart, kidney, and type 2 diabetes, pharmacists can provide holistic care, optimise therapeutic outcomes, and improve the quality of life for their patients. 

REFERENCES 

1. Bartnik M, et al. The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe. The Euro Heart Survey on diabetes and the heart. Eur Heart J. 2004;25(21):1880–90. 
2. Cavender MA, et al. Impact of Diabetes Mellitus on Hospitalization for Heart Failure, Cardiovascular Events, and Death: Outcomes at 4 Years from the Reduction of Atherothrombosis for Continued Health (REACH) Registry. Circulation. 2015;132(10):923–31. 
3. Lindholm D, et al. Association of key risk factors and their combinations on ischemic outcomes in patients with invasively managed myocardial infarction in Sweden. Presented at: ESC Congress 2018, 2018 Aug 25-29, Munich, Germany. 
4. United States Renal Data System. 2018 USRDS annual data report: Epidemiology of kidney disease in the United States National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases: Chapter 9: Cardiovascular Disease in Patients With ESRD; 2018. Available from: URL: https://www.usrds.org/2018/view/v2_08.aspx. 
5. National Kidney Foundation. Kidney Disease: Causes; 2020 [cited 16 Oct 2020]. Available from: URL: https://www.kidney.org/atoz/content/kidneydiscauses. 
6. Hoppe LK et al. Association of Abnormal Serum Potassium Levels with Arrhythmias and Cardiovascular Mortality: A Systematic Review and Meta-Analysis of Observational Studies. Cardiovasc Drugs Ther2018; 32(2):197–212. 
7. Dunn JD et al. The Burden of Hyperkalemia in Patients With Cardiovascular and Renal Disease. The American Journal of Managed Care 2015; 21(15):S307-15. 
8. Einhorn LM et al. The Frequency of Hyperkalemia and Its Significance in Chronic Kidney Disease. Arch Intern Med 2009; 169(12):1156-1162. 

WEBSITES: 

• American Heart Association (AHA) and the American Diabetes Association (ADA). KnowDiabetesbyHeart. Diabetes, your heart and kidneys: A Triangle of Risk. Available at: https://www.knowdiabetesbyheart.org/articles/diabetes-your-heart-and-kidneys-triangle-of-risk/ - accessed: 23 May 2023 
• American Heart Association (AHA) and the American Diabetes Association (ADA). KnowDiabetesbyHeart. Webinars. Available at: https://kdbh2022stg.wpengine.com/professional/professional-resources/webinar-series/  accessed: 23 May 2023 
• American Heart Association (AHA) and the American Diabetes Association (ADA). KnowDiabetesbyHeart. Heart Health: The link between Type 2 Diabetes and Chronic Kidney Disease. Available at: https://www.knowdiabetesbyheart.org/wp-content/uploads/2022/12/89159_KDBH_Kidney_HeartHealth.pdf - accessed: 24 May 2023  
• National Institute of Diabetes and Digestive and Kidney Diseases. Available at: https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease - accessed: 21 May 2023 
• Organs Talk. About the interconnectivity of organ systems. Available at: https://www.organs-talk.com/ - accessed: 23 May 2023