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A<\/span>my Bies was recovering in the hospital from injuries inflicted during a car accident in May 2007 when routine laboratory tests showed that her blood glucose and cholesterol were both dangerously high. Doctors ultimately sent her home with prescriptions for two standard drugs, metformin for what turned out to be type 2 diabetes and a statin to control her cholesterol levels and the heart disease risk they posed.<\/p>\n The combo, however, didn\u2019t prevent a heart attack in 2013. And by 2019 she was on 12 different prescriptions to manage her continued high cholesterol and her diabetes and to reduce her heart risk. The resulting cocktail left her feeling so terrible that she considered going on medical leave from work. \u201cI couldn\u2019t even get through my day. I was so nauseated,\u201d she said. \u201cI would come out to my car in my lunch hour and pray that I could just not do this anymore.\u201d<\/p>\n Medical researchers now think Bies\u2019s conditions were not unfortunate co-occurrences. Rather they stem from the same biological mechanisms. The medical problem frequently begins in fat cells and ends in a dangerous cycle that damages seemingly unrelated organs and body systems: the heart and blood vessels, the kidneys, and insulin regulation and the pancreas. Harm to one organ creates ailments that assault the other two, prompting further illnesses that circle back to damage the original body part.<\/p>\n If you’re enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.<\/p>\n Diseases of these three organs and systems are \u201ctremendously interrelated,\u201d says Chiadi Ndumele, a preventive cardiologist at Johns Hopkins University. The ties are so strong that in 2023 the American Heart Association grouped the conditions under one name: cardio-kidney-metabolic syndrome (CKM), with \u201cmetabolic syndrome\u201d referring to diabetes and obesity.<\/p>\n The good news, says Ndumele, who led the heart association group that developed the CKM framework, is that CKM can be treated with new drugs. The wildly popular GLP-1 receptor agonists, such as Wegovy, Ozempic and Mounjaro, target common pathology underlying CKM. \u201cThe thing that has really moved the needle the most has been the advances in treatment,\u201d says Sadiya Khan, a preventive cardiologist at Northwestern University. Although most of these drugs come only in injectable forms that can cost several hundred dollars a week, pill versions of some medications are up for approval, and people on Medicare could pay just $50 a month for them under a new White House pricing proposal. The appearance of these drugs on the scene is fortunate because researchers estimate that 90 percent of Americans have at least one risk factor for the syndrome.<\/p>\n More than a century before Bies entered the hospital, doctors had noticed that many of the conditions CKM syndrome comprises often occur together. They referred to the ensemble by terms such as \u201csyndrome X.\u201d People with diabetes, for instance, are two to four times more likely to develop heart disease than those without diabetes. Heart disease causes 40 to 50 percent of all deaths in people with advanced chronic kidney disease. And diabetes is one of the strongest risk factors for developing kidney conditions.<\/p>\n At present, around 59 million adults worldwide have diabetes, about 64 million are diagnosed with heart failure, and approximately 700 million live with chronic kidney disease.<\/p>\n The first inkling of a connection among these disparate conditions came as far back as 1923, when several lines of research started to spot links among high blood sugar, high blood pressure and high levels of uric acid\u2014a sign of kidney disease and gout.<\/p>\n Then, several decades ago, researchers identified the first step in these tangled disease pathways: dysfunction in fat cells. Until the 1940s, scientists thought fat cells were simply a stash for excess energy. The 1994 discovery of leptin, a hormone secreted by fat cells, showed researchers a profound way that fat could communicate with and affect different body parts.<\/p>\n Since then, researchers have learned that certain kinds of fat cells release a medley of inflammatory and oxidative compounds that can damage the heart, kidneys, muscles, and other organs. The inflammation they cause impairs cells\u2019 ability to respond to the pancreatic hormone insulin, which helps cells absorb sugars to fuel their activities. In addition to depriving cells of their primary energy source, insulin resistance causes glucose to build up in the blood\u2014the telltale symptom of diabetes\u2014further harming blood vessels and the organs they support. The compounds also reduce the ability of kidneys to filter toxins from the blood.<\/p>\n Insulin resistance and persistently high levels of glucose trigger a further cascade of events. Too much glucose harms mitochondria\u2014tiny energy producers within cells\u2014and nudges them to make unstable molecules known as reactive oxygen species that disrupt the functions of different enzymes and proteins. This process wrecks kidney and heart tissue, causing the heart to enlarge and blood vessels to become stiffer, impeding circulation and setting the stage for clots. Diabetes reduces levels of stem cells that help to fix this damage. High glucose levels also prod the kidneys to release more of the hormone renin, which sets off a hormonal cascade critical to controlling blood pressure and maintaining healthy electrolyte levels.<\/p>\n At the same time, cells that are resistant to insulin shift to digesting stored fats. This metabolic move releases other chemicals that cause lipid molecules such as cholesterol to clog blood vessels. The constriction leads to spikes in blood pressure and heightens a diabetic person\u2019s risk of heart disease.<\/p>\n The circular connections wind even tighter. Just as diabetes can lead to heart and kidney conditions, illnesses of those organs can increase a person\u2019s risk of developing diabetes. Disruption of the kidneys\u2019 renin-angiotensin system\u2014named for the hormones involved, which regulate blood pressure\u2014also interferes with insulin signaling. Adrenomedullin, a hormone that increases during obesity, can also block insulin signaling in the cells that line blood vessels and the heart in humans and mice. Early signs of heart disease such as constricted blood vessels can exhaust kidney cells, which rely on a strong circulatory system to filter waste effectively.<\/p>\n The year before Bies\u2019s car accident, when she was in her early 30s, her primary care doctor diagnosed her with prediabetes\u2014part of metabolic syndrome\u2014and recommended changes such as a healthier diet and more exercise. But at the time, the physician didn\u2019t mention that this illness also increased her risk of heart disease.<\/p>\n Not seeing these connections creates dangers for patients like Bies. \u201cWhat we\u2019ve done to date is really look individually across one or two organs to see abnormalities,\u201d says nephrologist Nisha Bansal of the University of Washington. And those narrow views have led doctors to treat the different elements of CKM as separate, isolated problems.<\/p>\n For instance, doctors have often used clinical algorithms to figure out a patient\u2019s risk of heart failure. But in a 2022 study, Bansal and her colleagues found that one common version of this tool does not work as well in people with kidney disease. As a result, those who had kidney disease\u2014who are twice as likely to develop heart disease as are people with healthy kidneys\u2014were less likely to be diagnosed and treated in a timely manner than those without kidney ailments.<\/p>\n In another study, researchers found that among people with type 2 diabetes\u2014one in three of whom are likely to develop chronic kidney disease\u2014fewer than one quarter were receiving the kidney disease screening recommended by the American Diabetes Association and KDIGO, a nonprofit group that provides guidelines for global improvements in kidney health.<\/p>\n At present, around 59 million adults worldwide have diabetes, about 64 million are diagnosed with heart failure, and approximately 700 million live with chronic kidney disease. Collectively, these illnesses are the leading cause of death in dozens of countries; the evidence for CKM indicates that the several epidemics may in fact be one.<\/p>\n One of the first pushes for treating these diseases together came in the late 2000s. That\u2019s when Cleveland Clinic cardiologist Steven Nissen was scouring a database from a pharmaceutical company that listed its drug tests, in search of clinical trials of a diabetes drug named rosiglitazone. Across 42 trials, Nissen found, the data revealed a clear increase in heart attacks with the use of the drug. If the drug reduced diabetes, accompanying heart trouble should have gone down, not up, he thought.<\/p>\n A Senate investigation followed this vein of evidence and led to a 2007 advisory panel convened by the U.S. Food and Drug Administration. The discussions brought about a transformational change in how diabetes drugs were approved: It was no longer enough to simply show an improvement in blood glucose. Pharmaceutical companies would also need to demonstrate that the drugs were not linked to increased chances of developing heart health issues. Clinical trials to test the drugs would need to include people at high risk of heart or blood vessel diseases, including older adults.<\/p>\n Nissen recalls immense opposition to the idea and concern that the bar had been set too high. Those fears were not unfounded\u2014many large pharmaceutical companies \u201cabandoned the search for diabetes drugs\u201d because the trials would take longer to complete and cost more, according to endocrinologist Daniel Drucker of the Lunenfeld-Tanenbaum Research Institute in Toronto. \u201cThe pharma industry was 100 percent worried about this,\u201d Drucker says.<\/p>\n Drucker, who at the time was studying a promising new group of drugs for diabetes, was concerned about the extra time and expense, too. But in preliminary experiments, the scrutiny for additional conditions began to pay off. In 2008, at about the same time the fda updated its guidance on diabetes drugs, Drucker and other researchers discovered that the new molecules they were investigating seemed to protect mice and rats from heart disease.<\/p>\n \u201cThere\u2019s not going to be a one-size-fits-all approach to all of this.\u201d \u2014Nisha Bansal, nephrologist<\/p>\n The new drugs mimicked a small protein named GLP-1, which normally regulates blood sugar and digestion. Small studies suggested it had wider benefits and might protect heart function in people who were hospitalized after a heart attack and angioplasty. At the time, these GLP-1 mimics were being used only as diabetes treatments. But studies in animals suggested they could do more, and subsequent trials in people showed the drugs also protected heart and kidney function. \u201cWe might not have discovered these actions of GLP-1 for some time if we hadn\u2019t been directed by the fda to really study this,\u201d Drucker says. \u201cIn hindsight, it worked out very well.\u201d<\/p>\n The regulations ended up leading to very successful multifaceted drugs. In 2013, the year that Bies had her heart attack, the fda approved the first of a group of medications that act to block a receptor known as SGLT2 in the kidneys. These so-called SGLT2 inhibitors are \u201calmost a wonder drug,\u201d says nephrologist Dominic Raj of George Washington University.<\/p>\n In a series of stunning, large trials, researchers established that these drugs lowered blood glucose, delayed the worsening of kidney disease, and were strongly correlated with reduced risk of several cardiac conditions. These studies also confirmed that cardiac, kidney and metabolic diseases are \u201cmore closely linked than we anticipated,\u201d Bansal says. \u201cThe SGLT2 trials were really a landmark in this.\u201d<\/p>\n GLP-1-mimicking drugs such as Wegovy have been similar changemakers. A clinical trial of GLP-1 medications was stopped early because the benefits were so overwhelming that it was unethical to continue giving a placebo to patients in a comparison group. In 2024 researchers compared one drug with a placebo in more than 3,500 participants with type 2 diabetes and chronic kidney disease. But instead of looking only at diabetes improvement, they examined kidney and heart conditions as well. The scientists found an 18 to 20 percent lower risk of death in those treated with the GLP-1 drug.<\/p>\n Although the GLP-1 medicines do have side effects (nausea and vomiting are some), within a few short years clinicians found that they had therapies that were designed to protect one organ but also treated others. \u201cNow we have excellent evidence to say that not only will you have better control of your diabetes, and not only will these medicines help you lose weight, but they will prevent or attenuate the risk of developing serious heart disease and serious kidney disease,\u201d Drucker says.<\/p>\n Bies\u2019s physician prescribed her the GLP-1 receptor agonist drug Ozempic in 2024. Two months after she began the treatment, her blood glucose levels dipped below the diabetic range. Her heart is healthier, too. Doctors are \u201cvery happy with where my numbers are,\u201d she says. And with fewer drugs in her system, Bies feels much better overall.<\/p>\n N<\/span>ot everyone is convinced that the CKM syndrome framework is necessary. Nissen, for one, says it is \u201ca rebranding of a very old concept.\u201d The symptoms and health risks linked to CKM overlap significantly with those of metabolic syndrome, an older term used to describe a similar constellation of health risks, he says.<\/p>\n Ndumele, however, disagrees with that characterization. \u201cAlthough they are clearly related, CKM syndrome and metabolic syndrome have some very important differences,\u201d he says. For one, the CKM framework encompasses more disease states. And clinicians can use the concept to identify different stages of risk: very early warning signs followed by clinical conditions\u2014including but not limited to metabolic syndrome\u2014and ultimately late stages of CKM, which include full-blown heart and kidney disease. \u201cThis is meant to better support prevention across the life course,\u201d Ndumele says. Ongoing studies are testing new ways to identify those at risk of CKM early on and help with preventive care.<\/p>\n Patients such as Bies agree that combining care for the diseases that make up CKM could save lives. For decades she and countless other patients have struggled to manage different aspects of their health. Bies remembers that although all her doctors were affiliated with the same hospital, they didn\u2019t communicate with one another or see others\u2019 notes about her prescriptions.<\/p>\n A few years ago Bies joined an American Heart Association advisory committee on CKM to inform clinicians and advocate for others who deal with this complex illness, in hopes that speaking up about her own traumatic journey might help others so that \u201csomebody else won\u2019t have to wait 10 to 12 years to advocate for themselves,\u201d she says.<\/p>\n At the University of Washington, Bansal and her colleagues are testing an integrated care model in which patients meet with multiple specialists at the same time to chart out their care. It is, she says, a work in progress. \u201cHow do we actually improve the rates of screening and disease recognition and get more people who are eligible on therapies to treat CKM disease?\u201d Bansal says. \u201cAlthough there have been a lot of exciting advances, we\u2019re only at the beginning. Integrating care is always a challenge.\u201d<\/p>\n Such integrations are critical to help with early diagnosis\u2014a crucial step in squelching the rise of CKM around the world, according to Ndumele. In the future, even more specialties may need to coordinate. New research already hints at the involvement of other organs and organ systems. Cardiologist Faiez Zannad of the University of Lorraine in France suspects that as researchers glean a clearer picture, CKM syndrome will further expand to include liver disease. Zannad is investigating liver damage in heart patients because it is another common fallout of the same disease mechanisms.<\/p>\n Researchers and patients caution, however, that the move to group different diseases into CKM should not hinder efforts to understand each condition. Each person\u2019s course of disease\u2014their initial diagnosis, the complications they are at greatest risk of developing and how best to treat them\u2014can vary. \u201cIt\u2019s a very broad syndrome, and there will be nuances in terms of understanding subgroups, what the mechanisms are, and how we diagnose and treat patients,\u201d Bansal says. \u201cThere\u2019s not going to be a one-size-fits-all approach to all of this.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":" Amy Bies was recovering in the hospital from injuries inflicted during a car accident in May 2007 when routine laboratory tests showed that her blood glucose and cholesterol were both dangerously high. Doctors ultimately sent her home with prescriptions for two standard drugs, metformin for what turned out to be type 2 diabetes and a<\/p>\n","protected":false},"author":1,"featured_media":37997,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[50],"tags":[2193,737,542,3411,1713,1759,20901,20900,4259],"class_list":{"0":"post-37996","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-environment","8":"tag-diabetes","9":"tag-diseases","10":"tag-drugs","11":"tag-heart","12":"tag-illness","13":"tag-kidney","14":"tag-ozempiclike","15":"tag-treatable","16":"tag-type"},"_links":{"self":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/posts\/37996","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=37996"}],"version-history":[{"count":0,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/posts\/37996\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=\/wp\/v2\/media\/37997"}],"wp:attachment":[{"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=37996"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=37996"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/naijaglobalnews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=37996"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}On supporting science journalism<\/h2>\n