Mechanisms and evidence for CGM’s impact on mental health in individuals with diabetes

From a physiological point of view, it is known that both peripheral and central metabolic states play significant roles in the etiopathogenesis of MDD and other common psychiatric conditions, such as generalized anxiety disorder (GAD). In fact, high glycemic variability and persistent hyperglycemia have been associated with an increased incidence of MDD and GAD.Reference Kwon, Lee and Kim² Although the underlying mechanisms remain unclear, several prominent theories offer explanations. One theory posits that central and peripheral inflammation, mediated by cytokines released from adipocytes and immune cells, contributes to psychiatric symptoms in individuals with metabolic syndrome.Reference Chan, Cathomas and Russo³ In the same vein, Pistis et al.Reference Pistis, Strippoli and van Dalfsen¹ found that disturbances in metabolic networks—eg, insulin-glucose homeostasis, immuno-inflammatory processes, adipokine synthesis and secretion, intracellular signaling cascades, and mitochondrial respiration—are implicated in the pathophysiology, brain volumetric changes, symptomatic expression (eg, neurocognitive decline), and medical comorbidity in depressive disorders.

The central nervous system, similar to the pancreas, is a critical modulator of the metabolic milieu and is endangered by chronic abnormalities in metabolic processes. Others suggest hormonal disruptions, such as elevated cortisol levels or impaired insulin and glucagon-like peptide (GLP) function, may also play a role.Reference Mersha, Tollosa, Bagade and Eftekhari⁴ Additionally, alterations in the gut microbiome and glial cell function may be involved, as metabolic disturbances can disrupt the gut-brain axis and impair neuroinflammation.Reference Zhuang, Shen and Ji⁵ While the underlying mechanisms continue to be investigated, one can hypothesize based on current evidence that stabilizing glucose levels through CGM use may improve mood, reduce diabetes-related distress, and potentially alleviate depressive symptoms, thereby decreasing the prevalence of psychiatric conditions, such as MDD and GAD.

The use of CGM has been shown to improve patient-reported outcomes in individuals with diabetes, with benefits likely stemming from both the reduction in illness management burden and the biological effects of physiological glucose stabilization.Reference Ssemmondo, Deshmukh and Wilmot⁶ On one hand, CGMs reduce the daily hassles of diabetes management, including frequent finger pricks, manual glucose logging, and the anxiety associated with unpredictable blood sugar fluctuations. This reduction in management burden likely contributes to lower diabetes-related distress and improved quality of life, as shown by Ssemmondo et al.Reference Ssemmondo, Deshmukh and Wilmot⁶ Moreover, growing evidence suggests that glucose stabilization itself provides biological benefits that positively impact mental health. For example, stable glucose levels reduce the formation of advanced glycation endproducts (AGEs), mitigate oxidative stress, and prevent inflammation—factors known to adversely affect brain function and mood regulation.Reference Wątroba, Grabowska and Szukiewicz⁷ Additionally, hyperglycemia and glycemic variability have been linked to increased pro-inflammatory cytokine release, which disrupts the blood–brain barrier and impairs neuroplasticity in brain regions involved in mood regulation, such as the hippocampus and prefrontal cortex.Reference Wątroba, Grabowska and Szukiewicz⁷

Metabolic disorders, such as obesity and diabetes mellitus (DM), may further affect brain cellular integrity and functional connectivity, potentially leading to cognitive and mood disturbances. This phenomenon has been termed “metaboptosis,” due to the finding that chronic metabolic dysregulation can lead to premature cellular aging and neuronal dysfunction, which may contribute to psychiatric conditions.Reference McIntyre, Young and Haddad⁸ The role of glucose in brain function, and by extension, poor mental health symptoms, is also well-documented. By maintaining tighter glucose control, CGMs may also help preserve neuronal and glial cell function, support healthy neurotransmitter signaling, and thus reduce the risk of mood disturbances. These effects are particularly relevant for individuals with metabolic disorders, where altered glucose metabolism exacerbates psychological symptoms.Reference Zhang, Lachance, Mattson and Jia⁹

The bidirectional relationship between metabolic disorders, such as type 2 diabetes mellitus (T2DM), and mental health conditions like MDD is defined not only by shared biological mechanisms but also by how each condition exacerbates the other. It is important to recognize that this interaction extends beyond the biological pathways—such as inflammation, insulin resistance, and neuroplasticity impairment—since each disorder can influence the severity and progression of the other. For instance, metabolic dysregulation in diabetes can worsen mood and cognitive function, while the emotional distress and psychological stress associated with MDD can destabilize glucose regulation, creating a feedback loop that complicates both management and treatment. This bidirectional nature underscores the importance of innovative therapeutic interventions, such as CGM, which provide an opportunity to address both conditions simultaneously. By breaking the cycle of metabolic and psychiatric exacerbation, CGMs can play a pivotal role in integrated treatment approaches, enhancing overall patient outcomes and offering a more holistic solution to the comorbidity between metabolic and psychiatric disorders.

As previously discussed, the association between T2DM and MDD is mediated by both shared biological mechanisms (e.g., inflammatory pathways). Dysregulated blood glucose, particularly hyperglycemia, triggers a cascade of damaging effects that impact both metabolic and psychiatric health. Hyperglycemia promotes the formation of AGEs, which activate receptors for AGEs (RAGE), leading to systemic inflammation and the release of pro-inflammatory cytokines such as IL-6, TNF-α, and C-reactive protein (CRP). This inflammatory response increases oxidative stress by raising the production of reactive oxygen species (ROS) and depleting antioxidant defenses, which in turn damages cellular structures, including lipids, proteins, and DNA. In the brain, these processes disrupt neuroplasticity, impair brain-derived neurotrophic factor (BDNF) signaling, and alter mood regulation.Reference Pistis, Strippoli and van Dalfsen^1, Reference Wątroba, Grabowska and Szukiewicz⁷

Furthermore, hyperglycemia-induced oxidative stress and inflammation contribute to endothelial dysfunction, compromising the blood–brain barrier and allowing inflammatory mediators to infiltrate the central nervous system.Reference Liu, Leone and Ludvigsson¹⁰ This cascade activates microglia, amplifying neuroinflammation and exacerbating mood disturbances, thus creating a vicious cycle where metabolic dysregulation worsens psychiatric symptoms and vice versa.

Conversely, chronic psychological stress and trauma activate the body’s “fight or flight” response, which disrupts immune function and the gut microbiome, further impairing glucose regulation.Reference Liu, Leone and Ludvigsson¹⁰ The overlapping biological mechanisms between mental health and metabolic dysregulation—such as inflammation, insulin resistance, and neuroplasticity impairment—form a reciprocal relationship where each condition exacerbates the other. This bidirectional dynamic highlights the complexity of managing comorbid T2DM and psychiatric disorders like MDD. For instance, while metabolic dysfunction in T2DM worsens mood and cognitive function, the emotional stress associated with MDD can destabilize glucose regulation, complicating both management and treatment.Reference Possidente, Fanelli, Serretti and Fabbri¹¹

The aforementioned shared biological mechanisms are further supported by research identifying common genetic and molecular pathways. Liu et al.Reference Liu, McIntyre and Li¹² demonstrated that both T2DM and MDD involve dysregulation in immune system signaling, tau protein formation, and neuronal apoptosis. Both conditions also exhibit hormonal imbalances, such as hypercortisolemia and insulin resistance, autonomic nervous system dysfunction, systemic inflammation, and disruptions in the gut-brain axis—all contributing to neurodegeneration and impaired emotional regulation. Farzi et al.Reference Farzi, Hassan, Zenz and Holzer¹³ highlighted the role of oxidative stress and mitochondrial dysfunction in these processes, further underlining the biological overlap between T2DM and MDD. The co-occurrence of these disorders elevates the risk of cardiovascular complications and other comorbidities, as emphasized by Subba et al.Reference Subba, Sandhir, Singh, Mallick and Mondal¹⁴, reinforcing the need for integrated treatment approaches.

In this context, CGM presents a promising tool for addressing both T2DM and MDD simultaneously. By providing real-time data on glucose fluctuations, CGMs offer valuable insights into the metabolic processes that contribute to psychiatric symptoms. By stabilizing glucose levels, CGMs not only improve metabolic control but also help mitigate mood disturbances, cognitive impairments, and emotional dysregulation commonly seen in individuals with both T2DM and MDD. Notably, CGMs reduce the burden of diabetes management, eliminating the need for frequent finger pricks and manual glucose logging, which alleviates diabetes-related distress and improves quality of life.Reference Ssemmondo, Deshmukh and Wilmot⁶ This stabilization of glucose levels can reduce the anxiety and stress associated with unpredictable blood sugar fluctuations, which in turn may lead to improved mental health outcomes. CGMs could be especially beneficial for individuals with trauma-related disorders, who are at increased risk for developing T2DM due to shared biological mechanisms.Reference Zhuang, Shen and Ji⁵ Ultimately, CGMs offer an integrated, non-pharmacological approach to managing the comorbidities of metabolic and psychiatric health, targeting both the metabolic and psychological aspects of these disorders and providing a holistic solution that may improve overall patient well-being.

CGM offers several potential benefits for psychiatric symptom management beyond the traditional approaches used in diabetes care. By allowing for real-time stabilization of glucose levels, especially when paired with an insulin pump, CGMs help individuals approximate the physiological glucose homeostasis seen in individuals without diabetes. One can postulate that the greater alignment of glucose levels with normal physiological ranges could lead to reductions in mood disturbances and improvements in mental health outcomes from a psychological and physiological perspective.

A summary of key clinical findings is provided in the table below.

As seen in Table 1, Hermanns et al.Reference Hermanns, Ehrmann and Shapira¹⁵ found that elevated depression and diabetes-related distress were significantly associated with higher glucose levels. The authors suggested that personalized symptom profiles informed by glucose data could improve the precision of diabetes symptom monitoring, ultimately enhancing mental health outcomes. Similarly, Ssemmondo et al.Reference Ssemmondo, Deshmukh and Wilmot⁶ demonstrated that intermittently scanned CGM (isCGM) significantly reduced diabetes-related distress and improved HbA1c levels in individuals with high baseline levels of distress. These findings further indicate that CGM can address both the psychological burden of diabetes management and its physiological manifestations, potentially reducing psychiatric symptoms and improving overall wellbeing.

Table 1. Summary of Clinical Evidence Supporting the Mental Health and Psychosocial Benefits of Continuous Glucose Monitoring

Polonsky et al.Reference Polonsky, Hessler, Ruedy and Beck¹⁶ reported that CGM use led to significant improvements in diabetes-specific quality of life, including reductions in diabetes distress, hypoglycemic fear, and greater hypoglycemic confidence. The ability to reduce these anxieties associated with blood sugar fluctuations may not only improve physical outcomes but also enhance emotional stability.Reference Polonsky, Pylov and Imberg¹⁹ These early findings provide preliminary support that CGM use can reduce both the psychological and physical burdens of diabetes management, improving overall wellbeing and reducing psychiatric symptoms.

Additionally, as previously mentioned, metabolic dysregulation is a key feature of, and clinical predictor for, mood-, stress-, and trauma-related disorders such as MDD, GAD, and post-traumatic stress disorder. Recent evidence supports the notion that fluctuations in blood sugar levels may be associated with psychiatric symptoms, suggesting that metabolic data—such as that collected through CGM—could provide valuable insights into the mind-body connection. For instance, Hermanns et al.Reference Hermanns, Ehrmann and Kulzer²⁰ reported that hyperglycemia values were negatively correlated with positive mood ratings and were associated with more negative mood ratings, suggesting that stabilization of blood glucose levels could improve mood by mitigating the intensity of glucose-related mood fluctuations.

It then stands to reason that individuals with diabetes, who regularly experience blood sugar fluctuations, may benefit from CGM not only for managing glycemic control but also for enhancing mental health on a psychological level. The use of CGM can help individuals better understand the relationship between physiological states and psychological well-being, offering real-time insights into how fluctuations in glucose levels correlate with mood and emotional regulation, in addition to the potential direct physiological benefits discussed previously. These include the aforementioned pathways of reducing systemic inflammation, oxidative stress, and the formation of AGEs—all of which are known to adversely affect brain function and mood regulation.

The psychological benefits of CGM are likely inextricably linked with the biological advantages of more stable glucose control. By reducing both the emotional distress associated with diabetes management and the physical consequences of dysregulated glucose, CGMs provide a holistic approach to improving patient well-being. From a patient perspective, the ability to more precisely track and manage glucose levels not only alleviates anxieties such as hypoglycemic fear but also fosters a greater sense of control over one’s health, leading to improved quality of life and satisfaction with care. Moreover, from a physiological standpoint, CGMs help approximate normal physiological glucose homeostasis, a key factor in mitigating the systemic inflammation, oxidative stress, and neuroplasticity impairments that contribute to psychiatric symptoms. This dual benefit—enhancing mental health while stabilizing metabolic function—supports a more comprehensive, patient-centered approach to diabetes care, emphasizing the importance of integrated treatment strategies that consider both the body and mind. By aligning with normal glucose regulation, CGMs could not only provide an effective tool for managing diabetes but also offer a powerful means of improving mental health outcomes, ultimately benefiting patients on multiple levels.

Applications of CGM in non-diabetic populations and limitations

While CGMs are primarily used by individuals with diabetes, they may also benefit those without diabetes who are interested in a personalized approach to wellness, for example, providing the function of reducing baseline distress or improving quality of life. By offering insights into an individual’s unique metabolic responses, CGMs may provide valuable data for customizing dietary and lifestyle changes, potentially alleviating psychiatric symptoms and offering additional solutions for mental health management in those with and without the formal diagnosis of a metabolic condition.

However, while CGMs offer many benefits, they are not without limitations, particularly for non-diabetic use. One major barrier is the potential need for a prescription from healthcare providers, which can make CGMs inaccessible to individuals without insurance or those in lower socioeconomic brackets. Walker et al.Reference Walker, Hood and Gurka²¹ found significant disparities in CGM use based on socioeconomic status, race, and ethnicity, highlighting inequities in healthcare access. For example, uninsured individuals and those from minority ethnic backgrounds were found to have lower odds of receiving CGM prescriptions.Reference Wallia, Agarwal and Owen²² Additionally, although CGMs are often covered by insurance for individuals with diabetes, they are not typically covered for those with prediabetes or those seeking to use CGMs for general wellness monitoring. This creates a barrier to access for those who may benefit from CGM use but do not meet the clinical criteria for coverage. Moreover, there is limited research on the optimal glucose target ranges for individuals without diabetes, which raises concerns about the potential effectiveness and safety of CGMs outside a clinical context.Reference Oganesova, Pemberton and Brown²³

It ‘is also important to note that CGMs cannot determine the root cause of the underlying symptoms. While they can provide real-time glucose data, the physiological factors contributing to psychiatric symptoms, such as inflammation, oxidative stress, or hormonal dysregulation, require a more comprehensive clinical approach to fully understand.