Prediabetes is a metabolic disorder that affects millions of people worldwide and is considered one of the most significant precursors to type 2 diabetes. It is characterized by persistently elevated blood sugar levels that do not yet meet the diagnostic thresholds for overt diabetes. Behind this seemingly moderate change, however, lies a complex biological imbalance that can affect nearly all of the body’s systems. At the core of this is increasing insulin resistance: the body’s cells respond less and less effectively to the hormone insulin, which normally ensures that glucose is transported from the blood into the cells. As a result, more sugar remains in the bloodstream, which sets harmful processes in motion over the long term. Blood vessels, the liver, the heart, and the nervous system are particularly affected.
A new large-scale study by King’s College London, published in the prestigious journal The Lancet Diabetes & Endocrinology, now provides important new insights into the dynamics of this condition. The researchers show that prediabetes is not necessarily an irreversible precursor to diabetes, but can be fully reversed to a normal metabolic state under certain conditions.
Significantly Reduced Risk of Cardiovascular Disease
In particular, the study shows that individuals whose blood sugar levels returned to normal had a more than 50 percent lower risk of serious cardiovascular events. These include heart attacks, strokes, heart failure, and deaths resulting from cardiovascular disease.
It is noteworthy that this effect occurred regardless of the original duration of prediabetes. This means that even individuals with a longer history of elevated blood sugar levels were able to significantly reduce their risk, provided they succeeded in stabilizing their metabolism again.
These findings are particularly relevant because they shift the perspective on prediabetes. While the condition was often viewed as an “intermediate stage” in the past, it is increasingly evident that it can be actively influenced—with potentially significant implications for long-term heart health.
Biological Mechanisms: Why Sugar Affects the Heart
The connection between blood sugar and the cardiovascular system is biologically complex. Chronically elevated glucose levels lead to a series of harmful processes that accumulate over the years. For one thing, they promote chronic, low-grade inflammation in the blood vessels. This inflammation damages the inner walls of the arteries, making it easier for lipids to accumulate. This is a central mechanism of atherosclerosis, or hardening of the arteries.
On the other hand, persistently elevated blood sugar leads to oxidative stress. This produces reactive oxygen species that can damage cell structures, proteins, and DNA. The endothelial cells of the blood vessels, which are crucial for regulating blood flow, are particularly sensitive to this process. Over time, this results in increasing stiffening and narrowing of the arteries, which significantly increases the risk of heart attack and stroke.
However, the new study shows that these processes are not necessarily irreversible. Returning to normal blood sugar levels appears to at least partially slow down or stabilize many of these harmful mechanisms. This suggests that human metabolism is a highly dynamic system that responds to changes in diet, exercise, and lifestyle. Even moderate improvements in insulin sensitivity appear to be sufficient to significantly reduce the risk of serious cardiovascular events.
Hormonal Regulation: Cortisol as a Key but Often Overlooked Factor
Cortisol is produced in the adrenal cortex and is one of the key hormones of the body’s so-called stress axis. Its release is regulated by a finely tuned control system in the brain, known as the hypothalamic-pituitary-adrenal axis. This system normally ensures that cortisol follows a clear daily rhythm: levels are highest in the morning to activate the body, while they decline throughout the day and are very low at night. In acute stress situations such as physical stress, anxiety, or injury, cortisol release can rise sharply for a short time, which is an important survival mechanism from an evolutionary perspective.
During this acute phase, cortisol acts as a comprehensive energy regulator. It ensures that blood sugar levels rise by releasing energy reserves stored in the liver in the form of glucose. At the same time, fat and protein metabolism are adjusted so that energy is quickly available to the body. In addition, cortisol influences the cardiovascular system by increasing the sensitivity of blood vessels to other stress hormones such as adrenaline, thereby improving circulatory stability. The immune system is also temporarily suppressed to make energy available for other vital functions during an acute stress situation.
This mechanism, which is actually protective, becomes problematic when cortisol release is no longer just short-term but remains permanently elevated. This condition, known as hypercortisolism, causes the body to remain in a sort of chronic state of alarm. Hormonal regulation loses its normal rhythm, leading to profound changes in metabolism. This is particularly evident in glucose metabolism, as cortisol continuously stimulates glucose production in the liver while simultaneously reducing the cells’ sensitivity to insulin. This can lead to the gradual development of insulin resistance, which is considered a key risk factor for prediabetes and type 2 diabetes.
At the same time, persistently elevated cortisol levels influence fat distribution in the body. A typical result is increased fat storage in the abdominal cavity—that is, visceral adipose tissue—which is metabolically active and produces pro-inflammatory signaling molecules on its own. This fat tissue is closely linked to an increased risk of cardiovascular disease, as it can exacerbate chronic, low-grade inflammatory processes in the body. Muscle mass is also broken down more rapidly with chronically elevated cortisol, leading in the long term to a decrease in muscle mass and physical performance. At the same time, bone metabolism can be impaired, causing bone density to decrease and the risk of osteoporosis to increase. Chronically elevated cortisol levels also have an adverse effect on the cardiovascular system. On the one hand, it amplifies the effects of other stress hormones; on the other hand, it influences salt and water regulation in the body, which can lead to increased blood volume. Both mechanisms contribute to an increase in blood pressure and place greater long-term strain on the blood vessels. Over the years, this increases the risk of arterial narrowing and, consequently, of heart attack and stroke.
Furthermore, cortisol also plays a complex role in the immune system. While it has an anti-inflammatory effect in the short term, chronically elevated levels can paradoxically lead to a dysregulation of the immune response. Instead of clear suppression or activation, this often results in so-called “silent inflammation”—a state in which mild but persistent inflammatory processes remain active in the body. This form of chronic inflammation is now considered a major risk factor for many lifestyle-related diseases, including cardiovascular diseases, metabolic disorders, and neurodegenerative diseases.
Against this backdrop, recent research findings take on added significance. They show that elevated cortisol levels are detectable in a surprisingly high proportion of patients with difficult-to-treat hypertension. This suggests that hormonal dysregulation may play a significantly greater role in the development of cardiovascular diseases than previously assumed. Overall, this makes it clear that cortisol is not merely a classic stress hormone, but a central regulator of the entire metabolic system, whose chronic dysregulation can have far-reaching health consequences.
The MOMENTUM Study: Prevalence of Hormonal Disorders in Hypertension
A large multicenter U.S. study conducted as part of the so-called MOMENTUM program examined over 1,000 patients with resistant hypertension—that is, high blood pressure that is difficult to control despite multiple medications. Among other methods, the researchers used the dexamethasone suppression test to detect signs of impaired cortisol regulation. This test normally suppresses the body’s own cortisol production. If cortisol levels remain elevated, this suggests a possible hormonal imbalance.
The analysis showed that a significant proportion of patients exhibited signs of hypercortisolism. In addition, many of those affected had other hormonal disorders, such as primary hyperaldosteronism, which can also contribute to the development of high blood pressure. These results suggest that hormonal causes may be more common in treatment-resistant hypertension than previously assumed. At the same time, they open up new diagnostic perspectives that go beyond traditional treatment with blood pressure medications.
Sugar-free isn’t Always Better for Your Metabolism
Researchers from the Dasman Diabetes Institute presented findings from an experimental mouse study at ENDO 2026, the annual meeting of the Endocrine Society, which examined the effects of a completely sugar-free, low-fat diet. The animals were fed either a sucrose-free diet or a comparable diet with normal sugar content over a 16-week period.
Despite similar body weights, the mice fed the sugar-free diet showed changes in metabolism, including impaired glucose tolerance, signs of insulin resistance, and changes in lipid metabolism. These findings suggest that not only the amount of sugar but also the availability of certain carbohydrates plays a role in metabolic regulation. The body requires a finely tuned interplay of energy intake, hormonal responses, and microbial activity in the gut to maintain stable glucose homeostasis.
Particularly striking were the significant changes in the gut microbiome. The composition of bacterial communities in the gut is highly sensitive to changes in diet. Certain bacterial species rely on the availability of fermentable carbohydrates to produce metabolic products such as short-chain fatty acids. These substances have anti-inflammatory effects in the gut and throughout the body, strengthen the intestinal barrier, and even influence insulin sensitivity in muscle and liver tissue. If such dietary components are completely absent, the balance of the microbial community can shift, which in turn can affect overall energy metabolism. The observed signs of inflammation in the gut and liver also fit into this picture. The liver is a central metabolic organ that is closely connected to the gut via the so-called gut-liver axis. Changes in the microbiome can trigger signals there that influence fat metabolism and, in the worst case, contribute to increased fat accumulation in the liver. In the long term, such processes are associated with an increased likelihood of metabolic disorders such as fatty liver or insulin resistance.
The findings do not contradict the fundamental understanding that excessive sugar consumption can be harmful to health. However, they indicate that nutrition should not be understood merely in terms of “more or less sugar,” but rather as a complex system in which various nutrients interact with one another. Completely eliminating individual components can trigger unexpected adaptive responses in the metabolism, which can also have negative long-term effects.
The Gut Microbiome: A Key Interface Between Diet and Metabolism
Another particularly important aspect concerns the gut microbiome. The trillions of microorganisms in the human gut are not merely passive participants in digestion but are actively involved in regulating metabolism, the immune system, and energy balance. Among other things, they produce short-chain fatty acids, which have anti-inflammatory effects and stabilize the gut’s barrier function. At the same time, they influence glucose and fat metabolism as well as hormonal signaling pathways.
A complete elimination of certain carbohydrates can throw these microbial communities out of balance. This shifts the production of important metabolic products, which in turn can affect inflammatory processes and insulin sensitivity.
Whether it’s prediabetes, hormonal dysregulation, or nutrition—all three areas of research point to a common underlying principle: health is not a static state, but a dynamic system of balance. Both excessively high blood sugar levels and chronically elevated stress hormones can disrupt this balance. At the same time, animal and human studies show that even extreme diets can have unexpected metabolic consequences.
New Perspectives for Prevention and Metabolic Medicine
Current research findings paint an increasingly complex picture of human metabolic health. Prediabetes is a reversible risk condition; normalizing it can significantly reduce the risk of cardiovascular disease.
At the same time, hormonal factors such as cortisol may play a much greater role in the development of high blood pressure than previously assumed. In addition, animal research shows that not only reducing sugar intake but also completely eliminating it can influence biological systems—particularly via the gut microbiome.
Overall, it is becoming clear that heart and metabolic health are not determined by individual measures, but by the finely tuned interaction of many systems. Prevention therefore increasingly means not radical interventions, but the restoration of a stable biological balance.