Understanding cardiovascular-kidney-metabolic syndrome in diabetes
November 14, 2025
5 min read
Key takeaways:
- The term cardiovascular-kidney-metabolic (CKM) syndrome highlights the link between metabolic and renal conditions that drive risk for CVD.
- The CKM treatment algorithm stresses lifestyle management.
Susan Weiner
In this Diabetes in Real Life column, Susan Weiner, MS, RDN, CDN, CDCES, FADCES, talks with Colleen Dawkins, FNP-C, RD, CSOWM, about the clinical significance of cardiovascular-kidney-metabolic syndrome and its impact on diabetes care.
Weiner: What is cardiovascular-kidney-metabolic syndrome?
Dawkins: The American Heart Association (AHA) introduced cardiovascular-kidney-metabolic (CKM) syndrome in 2023. Cardiovascular, kidney and metabolic diseases share symptoms and biology, including elevated waist circumference and BMI, blood pressure and lab values such as glucose, lipids, kidney, liver and cardiac biomarkers. These symptoms clustered together occur frequently due to the underlying pathophysiology.
Weiner: How does CKM syndrome affect people with diabetes?
Dawkins: Inflammation drives changes in glucose metabolism. In people with diabetes, hyperglycemia and inflammation occur on a spectrum. When inflammation and hyperglycemia are on the higher end of the spectrum, the risk for CKM syndrome increases because they cause damage to the heart and kidneys.
Improving the management of diabetes helps reduce this risk and preserve organ function.
Weiner: What are the stages of CKM syndrome? What are the current treatment guidelines?
Dawkins: CKM syndrome ranges from stage 0 (no disease and no elevation in markers) to stage 4 (clinical cardiovascular disease with excess/dysfunctional adipose tissue, chronic kidney disease stage 4 or higher, other CKM risks). Metabolic markers and stage of CKD drive stage progression.
A study by Aggarwal and colleagues published in JAMA in 2024 estimated that 90% of U.S. adults are in at least stage 1 (excess/dysfunctional adipose tissue, impaired glucose tolerance).
Treatment guidelines are forthcoming. The treatment algorithm, as outlined in Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory from the AHA published in 2023, provides a starting point for risk reduction, delaying progression or reversing the disease process.
Lifestyle is the cornerstone of the algorithm for each stage of CKM syndrome. The AHA recommends using Life’s Essential 8, including managing glucose, blood pressure and weight.
Screening and early detection are keys to active interventions to improve or preserve health and quality of life. The AHA has an online risk calculator, PREVENT, which uses several data points to help clinicians educate patients and allow for shared decision-making.
Weiner: Is there an association between advancing stages of CKM syndrome and increased mortality? In what population?
Dawkins: Yes, research has shown that as the stages of CKM syndrome progressed, risk for all-cause mortality also increased. This association was observed in a 15-year prospective study by Li and colleagues published in Atherosclerosis in 2024. Interestingly, the association between advanced stages of CKM syndrome and all-cause mortality was most pronounced in those younger than 60 years.
Research by Gao and colleagues published in Scientific Reports in 2024 also highlighted worse outcomes in those with chronic kidney disease. They observed that the body can adapt to increased and sustained inflammation; however, the kidneys show no compensatory response to inflammation and, therefore, continue to decline functionally.
Weiner: How do inflammation, oxidative stress and cardiometabolic conditions intersect with diabetes?
Dawkins: Inflammation alters the metabolism of glucose and free fatty acids, resulting in hyperglycemia and hypertriglyceridemia. Inflammation and hyperglycemia cause a harmful positive feedback cycle for one another. The spiral of worsening inflammation and oxidative stress is fueled by hyperglycemia. This results in increased uric acid levels, further release of inflammatory cytokines and sustained hyperglycemia. This not only impacts mitochondrial function, but it also impacts insulin sensitivity and beta-cell function. Diabetes begins developing early in this cycle, even when biomarkers appear to be in range.
From a pathophysiology perspective, they are all so closely intertwined that it is difficult to say that one event is happening separately from another. This highlights the need for integrated, comprehensive care that an interdisciplinary team provides.
Weiner: Let’s talk about what the SELECT trial showed. Are there practical applications, based on the current research, to improve the lives of persons living with diabetes?
Dawkins: The SELECT trial was a randomized clinical trial with more than 17,000 participants followed on average for almost 3 years. All participants were older than 45 years, had a BMI of 27 kg/m2 or higher and had a history of myocardial infarction, stroke or symptomatic peripheral artery disease but without diabetes. Participants received weekly semaglutide 2.4 mg (Wegovy, Novo Nordisk) or placebo. In participants assigned semaglutide, there was a 20% reduction in major CV events, including nonfatal MI and all-cause mortality. Interestingly, the positive effects occurred soon after initiating semaglutide and persisted even if significant weight loss was not achieved.
McGuire and colleagues published outcomes from the SOUL trial this year. This trial looked at oral semaglutide 14 mg (Rybelsus, Novo Nordisk) and CV outcomes in people living with diabetes. The risk of major adverse CV events (MACE) were reduced by 14%, with an increase in risk reduction among those with higher baseline HbA1c levels.
Marso and colleagues published findings in 2016 from the SUSTAIN-6 trial that evaluated semaglutide 0.5 and 1 mg weekly doses and CVD outcomes in people living with diabetes and found a 26% lower risk for MACE compared with placebo.
The practical application is that GLP-1 receptor agonists have significant benefits beyond glucose control and weight reduction. Given that this medication class allows people to engage in the lifestyle changes they have been working on, sometimes for decades, and improves health outcomes, clinicians should consider this as part of a prevention or treatment plan.
Weiner: What are the implications for use of anti-obesity medications?
Dawkins: The CKM treatment algorithm stresses lifestyle management as the starting point for each stage. The goal is to reduce excess adipose tissue, thus reducing risk for the onset or progression of CKM syndrome. Reducing excess adipose tissue, measured by at least 5% weight loss, directly improves multiple metabolic markers.
It is important to remember that there are treatment options other than incretin medications, such as semaglutide and tirzepatide (Mounjaro/Zepbound, Eli Lilly). While the other options, including phentermine/topiramate (Qsymia, Vivus) and bupropion/naltrexone (Contrave, Currax), do not have the same mechanisms of action, they can be more accessible and practical. When therapy is selected, it is essential to understand how the person can benefit, including minimizing adverse side effects, controlling appetite and cravings, and supporting the accompanying lifestyle changes. It is important to consider contraindications and other risks associated with medications. Regardless of the treatment chosen, it is imperative that the person has support for making lifestyle changes and ongoing monitoring. Referrals to a registered dietitian nutritionist, an exercise specialist and a mental health professional, among others, should be considered sooner rather than later in the treatment plan.
For more information:
Colleen Dawkins, FNP-C, RD, CSOWM, is a board-certified nurse practitioner, registered dietitian nutritionist and certified specialist in obesity and weight management in private practice. Dawkins can be reached at [email protected].
Susan Weiner, MS, RDN, CDN, CDCES, FADCES, is co-author of The Complete Diabetes Organizer and Diabetes: 365 Tips for Living Well. She is the owner of Susan Weiner Nutrition PLLC and is the Healio | Endocrine Today Diabetes in Real Life column editor. She can be reached at [email protected], on X @susangweiner or on Instagram @susanweinernutrition.
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Disclosures:
Dawkins and Weiner report no relevant financial disclosures.
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