Obesity, type 2 diabetes, chronic kidney disease, and heart disease present distinct challenges for health care professionals, particularly when treating their patients with type 2 diabetes. Sadiya S. Khan, MD, a cardiologist with a focus on the influence of obesity on heart disease, discusses the connections among these conditions—recently defined in an American Heart Association (AHA) presidential advisory as Cardiovascular-Kidney-Metabolic (CKM) syndrome—and how type 2 diabetes can worsen heart and kidney disease, and vice versa.

Q: How do obesity, type 2 diabetes, kidney disease, and heart disease interact and influence each other? How does obesity affect this interaction?

A: One of the key things that we’ve learned about how these conditions develop is that they are connected. Obesity—also called excess or dysfunctional adiposity—is a source of inflammation and oxidative stress. Through this and other mechanisms, obesity contributes to the risk for high blood pressure, type 2 diabetes, and impaired kidney function, all of which often cluster and occur together and lead to heart disease.

Q: How does this interaction affect people with type 2 diabetes, particularly? Why is heart failure an especially common outcome?

A: People with type 2 diabetes have a high risk for developing heart disease, particularly heart failure. In fact, even when diabetes is well-managed, risk for heart failure persists. Risk of heart failure in people with type 2 diabetes has been underappreciated and less recognized due to our early focus on heart problems caused by clogged arteries, or coronary artery disease. Among people with type 2 diabetes, those who also have chronic kidney disease have an even higher risk of heart disease, heart failure, and death.

Q: How are newer medicines such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors used to manage these conditions?

A: One of the most positive things is that we now have medicines such as GLP-1 receptor agonists, SGLT2 inhibitors, and nonsteroidal mineralocorticoid receptor agonists that can treat all these conditions—obesity, type 2 diabetes, heart disease, and kidney disease. Some of these medicines were originally approved to treat type 2 diabetes, but we now know these medicines have the potential to also treat obesity, improve kidney function or kidney health, and prevent heart disease.

For people who have both type 2 diabetes and chronic kidney disease—and thus the highest risk of dying and developing heart disease and heart failure—these medicines can be lifesaving.

However, many people taking these medicines stop within a year. There are important unanswered questions about whether the short-term use of these medicines has any long-term benefit, and even the potential for harm. For example, once people stop taking GLP-1 receptor agonists, they often regain any weight they lose. In fact, regaining weight may lead to harmful changes in body makeup, especially if someone has lost lean muscle mass.

Q: The AHA recently defined these connected conditions as CKM syndrome. How does this help to test, treat, and manage these conditions as a group?

A: The AHA scientific statement and presidential advisory bring together, for the first time, a way to consider testing for, treating, and managing these conditions in a holistic way. As part of these considerations, the advisory identifies five stages that are defined by the presence or absence of risk factors.

The AHA created these stages to focus on preventing health problems earlier. If we aren’t identifying people earlier and we’re just waiting until they have signs and symptoms of type 2 diabetes, kidney disease, or heart disease and heart failure, then we’re missing the boat. The goal is to enhance health for people and make sure they understand that these stages are gradual, but also reversible.

Q: How can we encourage health care professionals to manage these as connected, rather than isolated, conditions? What are the most significant challenges and barriers that we can address now?

A: It’s important that we focus on how to improve overall health, quality of life, and outcomes for patients. We should think about the whole person rather than just how to treat diabetes or kidney disease or manage weight. I think we’re getting there. Defining CKM syndrome is a helpful step forward, but we’re not there yet.

One of the key challenges is to provide the kind of team-based care that the AHA advisory recommends. A team-based approach including physicians, physician assistants, nurse practitioners, pharmacists, nurses, social workers, and other health care professionals is critical to manage this group of connected conditions.

We’re seeing some success now with emerging cardiometabolic clinics that enable high-quality and timely access to care, particularly among patients with type 2 diabetes. Creating some standards across these types of clinics will be essential. Other challenges include how people access health care and food.

Q: What questions do we still have about treating these conditions? Have we identified areas for future research?

A: There are still many questions about the best way to treat these conditions, including which medicines to start and when. We are fortunate that advances in science have given us many options for treating patients. However, we should consider which is the right medicine for the right patient at the right time.

We also must figure out how to help people stick with their treatments, especially people taking GLP-1 receptor agonists. Early estimates suggest between 50% and 75% of people taking these medicines stop after a year, often due to cost and access issues. But we need to understand what other factors make people stop taking the medicines and how to address them. Stopping these medicines can reverse their benefits. One of the important things to recognize is that these are chronic disease medicines and are not meant to be short-term treatments.

One of the most pressing areas for research is how type 2 diabetes affects the heart muscle or the heart tissue itself, leading to the most common type of heart failure, heart failure with preserved ejection fraction. We know that in this type of heart failure, the heart pumps normally but struggles to relax fully, leading to symptoms. Unfortunately, we have very few treatments to help these people live longer. Improving our understanding of how type 2 diabetes leads to heart disease—what some people call diabetic cardiomyopathy—is important to improve quality of life and survival in people with type 2 diabetes.

What have you learned about managing the care of patients with heart, kidney, and metabolic conditions? Share below in the comments.