Psychosocial Care for People With Diabetic Neuropathy: Time for Action Free

Diabetes adversely affects multiple organ systems and is an important contributor to chronic complications and increased mortality rates. Recent estimates suggest that worldwide, 537 million people are affected by diabetes (1). In the U.S., 11.3% of the population has diagnosed or undiagnosed diabetes (2), a figure expected to nearly triple by 2060 (3), with devastating implications for diabetes complications. Economically, diabetes is also extremely costly with $327 billion in direct and indirect medical expenditures annually in the U.S. (4), rendering it one of the most expensive chronic diseases (5).

The most common chronic complications include diabetic neuropathies (DN), which affect up to 50% of people with diabetes (6). Distal symmetric polyneuropathy (DSPN) and autonomic neuropathies are the best studied of the DN. The commonest of the DN is DSPN, which is caused by damage to small and large peripheral nerve fibers (7). DSPN is characterized by distal to proximal sensory nerve dysfunction with a multitude of symptoms including numbness, tingling, loss of protective sensation, and poor balance (6). Additionally, one-third of those with DSPN often experience debilitating neuropathic pain symptoms (6). DSPN is also the leading cause of diabetic foot ulceration, Charcot neuroarthropathy (CN), and lower limb amputations (6). Similarly, diabetic autonomic neuropathy may also have a broad spectrum of clinical manifestations including cardiovascular autonomic neuropathy, gastrointestinal autonomic dysfunction, and urinogenital manifestations such as male and female sexual dysfunction. Whether present alone or in combination, these symptoms and signs have been shown to be associated with elevated risk for serious cardiovascular outcomes, higher mortality rates, impaired psychological well-being, and lower quality of life (QoL) (7).

Disappointingly, neither Section 5, “Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes” (8), nor Section 12, “Retinopathy, Neuropathy, and Foot Care” (9), of the recently published American Diabetes Association (ADA) 2023 Standards of Care in Diabetes, nor a recent consensus statement by the ADA/European Association for the Study of Diabetes regarding the care of people with type 1 diabetes (10), contains specific recommendations that can support the psychological care of people with DN. Visits to the clinic for screening or monitoring efforts for microvascular complications such as retinopathy and neuropathy could well be combined with assessments of psychological problems including depression, elevated diabetes distress, poor sleep quality, and perceived treatment barriers.

The biological risk factors of DN are well defined and include glycemic exposure (HbA_1c, age, and diabetes duration) in addition to height and cardiometabolic factors (obesity, dyslipidemia, hypertension, and smoking) (11,12). However, far less is known about the role of social determinants of health in DN development. So far, epidemiological studies have shown that race/ethnicity disparities (13), socioeconomic status (14), education, and insurance gaps (15) have also been implicated in DN development in several observational studies in type 1 or type 2 diabetes. Although the Behavioral Risk Factor Surveillance System showed that self-reported racial or ethnic discrimination was associated with less optimal diabetes care and more diabetes complications, but not self-care behaviors (16), a recent narrative review concluded significant associations between structural racism and worse self-care behaviors (diet and physical activity), poorer clinical outcomes (HbA_1c and blood pressure), lower standards of care, higher mortality, and more years of life lost for adults with diabetes (17). Racism still is a key social determinant of health that is a systemic, structural, intergenerational, and cyclical problem (18). Several leading organizations have already clearly stated that racism is a key public health issue and that this social injustice issue is a root cause of health inequities (18). This complex problem requires firm governmental policy interventions that lead to structural improvements (18). Social determinants of health also include the neighborhood/physical environment, food environment, access to health care, health care affordability and quality of health care, and social context (social capital and social cohesion) (Fig. 1).

Mental health factors also play an important role. For example, depression is common in diabetes, and those with diabetes complications have a doubled risk for depression compared with those without these complications (19). Depression not only is associated with a substantially impaired QoL but also is a key determinant of poor health outcomes in diabetes (19). Meta-analytic reviews of longitudinal studies have shown that individuals who are affected by both diabetes and depression have a 38% higher risk of incident macrovascular complications and a 33% increased risk of developing microvascular diseases, with a 46% higher risk of all-cause mortality and 39% higher cardiovascular mortality (20,21). The notion that depression is associated with adverse future health outcomes has also been confirmed in those with diabetes foot complications. A systematic review of 15 studies with >12,000 participants showed that in individuals without a history of a foot ulcer diagnosis, depression was associated with a 68% higher risk for foot ulcer per Hospital Anxiety and Depression Scale (HADS) standard unit (22).

Painful DN (PDN) is likely the most disabling neuropathic symptoms, affecting up to 30% of all individuals with DN (6). A consequence of its negative impact on QoL is that PDN remains challenging to treat, as clinicians continue to rely heavily on pharmacological treatments, the effectiveness of which is limited and hampered by serious dose-related side effects. Thus, the number of people with PDN achieving clinically relevant pain reduction remains unacceptably low (6). Consequently, inadequate pain control in people with PDN results in severe sleep deprivation, anxiety, depression, and impaired physical and mental functioning (6,7). Moreover, the inadequate pain control leads to decreased work productivity and even loss of employment or early retirement (6,7).

In a systematic review of 66 studies investigators highlighted the negative impact of painful neuropathy on QoL and recommended continuous monitoring of pain management strategies and their impact on QoL (23). More detailed data regarding the specific domains impacted by PDN were recently provided from Multicentre, double-blind, crossover trial to identify the Optimal Pathway for TreatIng neurOpathic paiN in Diabetes Mellitus (OPTION-DM) (24). This large trial from 13 U.K. centers included individuals with PDN who reported a mean daily pain numerical rating of ≥4. Health status, assessed with the RAND 36-item short-form survey (SF-36), with scores ranging from 0 to 100 (most optimal score), indicated that the most impacted domains by PDN were role limitations due to physical health (21.9), pain (33.4), physical functioning (34.9), and energy level (36.9) (24).

Pain catastrophizing and psychological flexibility are central psychological constructs hypothesized to impact individuals’ adaptation to PDN (25). Pain catastrophizing is a negative cognitive set consisting of several domains along which individuals process their pain experience (rumination, magnification, and helplessness). Pain catastrophizing is an independent contributor to emotional distress in people with PDN and is associated with increased disability and decreased QoL through a perceived decline in physical activity (26). Selvarajah et al. (27) found that catastrophic thinking was a key contributor to higher levels of anxiety and depression. Psychological flexibility includes several related processes: acceptance, committed action, cognitive defusion, or the ability to separate one’s thoughts from events as they are directly experienced, and self-as-context, i.e., not based on self-evaluations and separate from one’s thoughts and feelings. In the regression analyses, psychological flexibility accounted for significant variance in PDN experience and was associated with less functional impairment and less depression (28). Kioskli et al. (28) reported that higher acceptance of pain was associated with lower pain intensity, lower pain distress, lower functional impairment, and lower depression severity and impact in a cross-sectional sample of people with PDN. In the same study, pain intensity accounted for 32% of variance of functional impairments, while psychological flexibility accounted for an additional 7% of the variance.

Investigators of a systematic review concluded that in individuals with PDN, the prevalence of anxiety ranged between 7.8% and 60% and that of depression between 13.6% and 50.6% (28). It is well-known that depression and anxiety often coexist: 26%–31% of those with PDN suffered from both depression and anxiety; the prevalence of sleep disorders was found to range between 42% and 44% (29). Findings of a Dutch study identified a series of specific fears experienced by people with PDN suffering from pain: fear of pain increase, of physical injury, of falling, of loss of identity, of negative evaluation by others (30). In regression models, including potential confounders and a set of fears, as identified in a qualitative study, pain intensity, pain duration, and fear of falling were significantly associated with pain-related disability and reduced QoL (31). The predominance of fear of falling in individuals suffering from PDN is an interesting finding that requires further investigation. It is plausible that people with PDN are also experiencing DN–postural instability resulting in fear of falling. It could also be possible that medications used to alleviate pain are negatively impacting balance through their recognized central nervous system side effects. A study by Vileikyte et al. (32) showed that pain unpredictability and the lack of pain control, along with PDN-related limitations in activities of daily living, mediated the association between PDN and depression. In an Italian study, PDN was a strong determinant of depression, compared with other diabetes-related complications and comorbidities (33).

Sleep quality is important for successful PDN management. Results of a study with comparison of the analgesic efficacy of pregabalin, amitriptyline, and duloxetine, and its effect on sleep, daytime functioning, and QoL in patients with PDN, showed no significant differences in analgesic efficacy between the treatments. However, there was a significant treatment effect on measures of sleep, with pregabalin demonstrating improved sleep continuity, while duloxetine was associated with increased wake and reduced total sleep time (34). These data suggest that the presence of comorbid sleep disturbance in persons with PDN could, in part, predict substantial pain relief in response to pregabalin treatment.

Recent systematic reviews of psychosocial factors related to PDN indicate that QoL, along with depression, anxiety, and sleep quality, are the most studied variables and are consistently associated with pain intensity. Thus, there is abundant evidence supporting the notion that psychological problems are common and that many of these factors can amplify pain experience (Fig. 1 [35]).

Studies with longitudinal data in this area are scarce, with an exception of that by Rohde et al. (36), who reported data from a large population-based cohort to determine whether individuals with DN have higher risk of developing a psychiatric disorder in comparison with those without DN. Using the nationwide Danish registers, they identified all people who were diagnosed with DN between 1996 and 2019, who were then matched with five control subjects with diabetes who were not diagnosed with DN and had comparable duration of diabetes. In a next step, a Cox proportional hazards model was used to compare incidence rates of mental disorders between individuals with DN and the diabetes duration–matched individuals (36). Those with diagnosed DN had a higher risk of developing any mental disorder (age- and sex-adjusted hazard rate ratio 1.40, 95% CI 1.31–1.48) as well as all specific mental disorders (unipolar depression, anxiety disorder, bipolar disorder, psychotic disorder) compared with diabetes duration–matched control subjects (36).

Postural instability and falls are seldom mentioned among the complications of diabetes, even though they are common and threaten physical and psychological well-being. We have shown that DN-related postural instability is strongly associated with depression, poor self-rated health, and nonadherence to off-loading in people with active diabetic foot ulcers (DFUs) (32,37–40).

People with diabetes have a substantially higher risk of falls, which may be up to ∼20 times higher compared with the general population without diabetes (39). DSPN has been identified as an independent risk factor for unsteadiness and loss of balance linked to falls (41). Likewise, individuals with a DFU had an increased risk of falls compared with those without an active foot ulcer (42). It is important to note that medications used to alleviate pain are negatively impacting balance through their recognized central nervous system side effects (43). Direct physical injuries linked to PDN-related unsteadiness and falls are an overt concern, with increased falls risk also carrying an increased mortality risk (44–46).

People with diabetes have a greater fear of falling compared with people without diabetes (47). Although was shown that fear-associated activity restriction may provide short-term protection against falls (48), presumably in reducing “exposure” to fall risk situations, in the long-term fear of falling leads to further declines in physical function and increased falls (49). More research therefore is needed to determine the role of fear of falling in the relationship between risk factors and falls. Fear of falling has been shown to significantly associate with several gait parameters, including a slower stride velocity and shorter stride lengths, indicating the direct effect on gait and relation to PDN-related unsteadiness (50). In another study investigators examined the impact of self-perceived unsteadiness on gait characteristics and balance in individuals with DN and compared this measure against laboratory assessment of walking (51). The study findings demonstrated that subjective perceptions of unsteadiness reported prior to laboratory tests correlated with objective measures of balance impairment during walking. Moreover, individuals with DN not only were aware of themselves as being unsteady but also attempted to self-regulate their unsteadiness by altering specific gait parameters, such as walking more slowly and taking shorter steps.

The sensorimotor impairment attributable to DN affects not only gait but also control of the gas pedal during driving (52,53). Drivers with DN have been shown to have lower maximal ankle plantar flexor muscle strength and impaired ankle proprioception, resulting in alterations of the accelerator pedal control while driving (52,53). This use of the gas pedal with DN was found to adversely influence driving performance, but potential for improvement with targeted practice remains possible. Driving is an important part of leading an independent life to many people, and cessation of this activity may have important psychosocial consequences that we currently do not understand due to the lack of research. There is potential for adaptive technologies and interventions to help keep people driving more safely for longer, but again more research is needed to confirm and understand the psychosocial implications.

Recent research therefore highlights two important points in relation to DN-related unsteadiness: 1) although many changes to gait can be seen before the onset of significant peripheral neuropathy, marked unsteadiness during gait is only present in people with diabetic peripheral neuropathy; 2) objective gait laboratory measures and subjective feelings of unsteadiness agree very well in terms of unsteadiness and falls risk, underlining the close interrelationship of physical and psychological factors.

Several group-based interventions (e.g., gait and balance training, tai chi, yoga) have shown some benefits in reducing fear of falling and improving balance confidence in this population (54–56). Improvements in balance have been reported following exercise training programs in people with DN (37,57). In most successful studies in improving balance and important aspects of motor function underpinning balance investigators have used elements of resistance exercise and balance‐type exercises (58,59). There is still limited evidence for the efficacy of exercise programs on DN–postural instability. Surprisingly, there is a complete absence of evidence for the impact of psychosocial interventions on DN–postural instability, despite strong evidence, outlined above, for the relationship between psychological factors and DN–postural instability. Thus, randomized controlled trials evaluating interventions targeting psychological factors associated with this burdensome complication are needed.

DFUs have detrimental effects on individuals’ health status and QoL, caused by limitations of physical functioning and activities of daily living, thereby negatively affecting important social and family roles (60–62). In a recent meta-analysis investigators examining QoL of individuals with DFUs (63) concluded that QoL is diminished on four of eight SF-36 subscales: physical functioning, role physical, general health, and vitality. QoL for individuals with DFUs is worse than for those who either healed primarily without amputation or underwent minor amputation (64). Furthermore, studies have also demonstrated significantly worse health status among individuals affected by CN as compared with those with diabetes without CN (65). However, the presence of DFUs did not appear to have an additional negative impact on health status in people with CN in comparison with those with CN but without DFUs (66).

Impaired mobility caused by non-weight-bearing DFU treatments is a key issue, especially for those with preexisting postural instability due to DN (38). This results in situations where the off-loading device is not optimally used, which results in delayed DFU healing (38). Therefore, in selecting an off-loading device, it is important to inquire about this DN symptom, especially as self-reported balance issues appear to correspond with the objective tests of postural instability (51). In a recent systematic scoping review regarding use of a foot off-loading device investigators confirmed that postural instability and abnormal gait are important determinants of dissatisfaction with the footwear exterior, stigma, and embarrassment of wearing foot off-loading in public (67). Therefore, interventions to promote adherence to recommended foot off-loading should not overlook taking the time to carefully explore and discuss user perceptions, regarding the “pros and cons” of using an off-loading device.

Several psychological factors are important in relation to DFU. First, being diagnosed with a DFU can evoke a range of emotions, with fear of amputation being a predominant one (68); patient beliefs regarding DFU risk in turn can impact preventive foot self-care (69). Another key factor is depression, which is also a common mental health problem in people with DFUs that appeared to be associated with negative health outcomes (70). For example, in a study of individuals presenting with their first DFU, investigators found that one-third of the sample was affected by clinical depression (70). Both minor and major depressive disorder were associated with a twofold increased mortality risk at a 5-year follow up in comparison with no depression (70). This was later confirmed by results of a study by Iversen et al. (71), who also reported increased risk of mortality among those depressed, over and beyond the increased risk associated with an HFU. Several other large-scale epidemiological investigations showed that depression is associated with incident first DFUs. Results of the first study demonstrated that major depression had a twofold increase in risk of incident DFUs, which is in line with the results describe above, linking depression with poor health outcomes (72). These observations were further solidified by an epidemiological investigation demonstrating a link between depression and increased DFU risk in a dose-response manner during an 11‐year follow‐up (73). Similarly, another prospective study of a clinically well‐defined DN population showed that both foot self-care and depression, while having no impact on the development of recurrent DFUs, play a substantial role in incident first DFUs (74). However, research into the role of depression in DFU healing produced inconsistent results. A study of elderly individuals with DFUs showed that geriatric depression is predictive of DFU nonhealing (75), while findings of a subsequent investigation showed that confrontational coping and not depression is predictive of DFU nonhealing (76). More recently, another study with a small sample size also showed no association between depression and DFU healing (77). That depression, like foot self-care, was associated with DFU risk only in those without prior DFU clearly warrants further investigation (22).

Similarly, in two recently conducted systematic reviews of psychological interventions for treating and preventing DFU recurrence investigators were unable to determine whether psychological interventions are of any benefit in terms of achieving DFU healing or preventing recurrence (78,79). This is for two main reasons: only a few trials included testing of psychological interventions and there was poor-quality assessment of the outcomes of interest. It was therefore concluded that randomized controlled trials of theoretically informed interventions, which assess clinical outcomes, are urgently required.

A growing body of evidence indicates that digital health technologies are effective in secondary DFU prevention (80). The introduction of smart technologies, where plantar foot temperatures and pressures can be monitored and feedback provided in real time, not only represents a paradigm shift in DFU risk screening and monitoring but, crucially, also transforms foot care education. In allowing people to visualize their personal DFU risk, digital technologies are likely to enhance individuals’ active participation in foot self-care. Moreover, as recently demonstrated by Chatwin et al. (81), continuous plantar pressure feedback modifies patients’ behavior so that they preemptively off-load high-pressure areas, thereby reducing reulceration risk. While promising, digital technologies introduce additional layers of complexity to foot care. Yet, there is a paucity of research examining determinants of patient and provider acceptance of digital technology (82).

Results of a systematic review with a meta-analysis demonstrated a low accuracy of depression recognition by nonpsychiatrist physicians (83). Similar results were found in an outpatient setting, where recognition rates of an elevated level of anxiety, depression, or diabetes distress by diabetes nurse specialists ranged between 20 and 29% (84). Currently it is unknown how often psychological problems remain undiscussed and/or untreated in people with DN. Yet, many health care providers express a need to be better supported in providing optimal psychological care. For example, results of the second Diabetes Attitudes, Wishes and Needs (DAWN2) study, which included health care professionals from 17 countries, showed that although psychosocial support was considered a key aspect of diabetes care, health care professionals also stated that they lacked adequate resources and reimbursement to provide optimal care for psychological problems (85). Of all health care providers, 59% reported that they wanted more training in the management of psychological problems related to diabetes (85). Furthermore, patients often do not talk about their balance concerns during medical consultations, as they may perceive these as aging rather than illness-related disability (62,86). As a result of this, clinicians may also overlook balance deficits. Therefore, it is important to emphasize that problems with imbalance should be discussed during consultations, as these patients have ∼20-fold greater risk of falling compared with age-matched control subjects (87). Several surveys of people with PDN and their health care providers highlighted important differences between the physician and patient perceptions of PDN, which may impact on its diagnosis and treatment: physicians considered the diagnosis and treatment of PDN a low priority, which may be reflected in the generally low incidence of screening (range 12–65%) and a lack of awareness of PDN (88). Similarly, a study by Vileikyte et al. (69) demonstrated that people have common sense misconceptions about DN as a risk factor for DFUs, which, if not attended to, may result in a lack of preventive foot self-care.

The ADA has advocated that psychosocial care should be provided to all people with diabetes, with the goal of optimizing health-related QoL and health outcomes. Such care should be integrated with routine medical care and delivered by trained health care professionals using a collaborative, person-centered, culturally informed approach. When indicated and available, qualified mental health professionals should provide additional targeted mental health care (89). The guidelines also mention that psychosocial screening should be implemented, and it is essential that screening efforts do not become tokenistic, i.e., to “tick a box.” Screening results should be discussed with the patient with diabetes and adequate referral opportunities to psychological care should be in place; otherwise, screening can become unethical. Preferably, the diabetes care team should include a mental health professional (psychiatrist, psychologist, and/or social worker) to advise the team and consult with people with diabetes in need of psychosocial support (89). Stepped care for depression in diabetes had a net economic benefit of the intervention of almost $1,000 per patient treated (90). However, the cost-effectiveness of psychological interventions in people with DN has not been investigated yet.

An empathic approach is essential in the care of patients, as well as for communicating with their family members. The goal is to appreciate how patients feel, explore their experience of their symptoms, and provide assurance that treatments are available to help alleviate their symptoms. Many patients feel terribly misunderstood because their severely painful feet do not appear abnormal and they believe that family members or others do not fully understand their predicament. In responding to these patients the whole health care team must speak with the same voice, as conflicting information can be extremely counterproductive. The holistic management of a patient with DN involves treatment of symptoms (such as neuropathic pain, comorbid mood disorders, insomnia, comorbid autonomic symptoms, and unsteadiness/falls) on top of the existing evidence-based strategies aimed at the prevention of foot complications (91). The biopsychosocial model of pain proposes that biological factors are important in the appraisal and perception of abnormal sensations generated by damaged nerves. These appraisals and behavioral responses are, in turn, influenced by social or environmental factors. The management of chronic pain, therefore, requires use of a biopsychosocial approach with appreciation that persistent pain is a disease rather than a symptom and that all influencing factors must be addressed (92). Although the first point of consultation might be with a general practitioner, internal medicine specialist, endocrinologist, neurologist, or pain specialist, ideally a multimodal/multidisciplinary team approach, with tailored involvement of psychologists, specialist nurses, podiatrists, physical therapists, orthotists, and pain specialists, is recommended to provide personalized and enhanced patient care (10,89).

For those with DN, clinicians should also consider using DN-specific instruments that tap into DN-specific QoL (62) or pain catastrophizing (93). Self-report questionnaires can be completed online before the consultation, either at home or in a waiting room (10). Furthermore, there is no consensus statement yet that guides clinicians and researchers in choosing the best patient-reported outcome measures (PROMs) for DN. Investigators conducted a systematic review with the aim of retrieving and comparing PROMs that were specifically evaluated among cohorts with DN (94). The search yielded 299 studies, 19 of which were focused on measuring symptoms or impact of PDN with use of patient-reported outcomes, and 12 of these included descriptions of validation studies of PROMs among subjects with PDN (94). The review did not comprise a systematic evaluation of the psychometric quality of the included PROMs, but measures used to assess PDN include Brief Pain Inventory for patients with Painful Diabetic Neuropathy (BPI-DPN), Neuropathic Pain Scale (NPS), Neuropathy Total Symptom Score-6 (NTSS6), Neuropathic Pain Symptom Inventory (NPSI), and the following measures tap into PDN-related QoL and symptoms: Norfolk Quality of Life Questionnaire–Diabetic Neuropathy (QOL-DN), Neuropathy and foot ulcer–specific Quality of Life instrument (NeuroQoL), Patient Interpretation of Neuropathy scale (PIN), and Diabetic Peripheral Neuropathic Pain Impact measure (DPNPI) (94). Investigators of future studies should evaluate the measurement properties of these tools using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines for systematic reviews of PROMs (95).

The recent American Academy of Neurology guideline reported that there are limited studies on nonpharmacological interventions for PDN (96). A range of psychological interventions have been designed to help individuals cope with chronic pain. The first relevant study is a systematic review (based on n = 75 studies) summarizing the results of trials testing the effectiveness of psychological treatments in a number of chronic pain conditions, including chronic low back pain, fibromyalgia, and rheumatoid arthritis (97). Investigators had tested cognitive behavioral therapy (CBT) in n = 59 studies, behavioral therapy in n = 8 studies, and determined the effectiveness of acceptance and commitment therapy (ACT) in n = 5 studies (97). In this systematic review, Williams et al. (97) concluded that individuals treated with CBT reported significantly lower pain levels, less distress, and less disability after treatment and also at 6- to 12-month follow-up, in comparison with control subjects—with relatively small effect sizes, however. Results also showed that, in comparison with nonpsychological interventions (such as exercise programs or education on pain management), CBT reduced pain, disability, and distress, although with small effect sizes. The quality of evidence was moderate. Large effects on pain were found for ACT, but the number of studies and quality of these studies was low (97).

Racaru et al. (98) studied the effectiveness of psychological interventions on pain and related outcomes in diabetic peripheral neuropathy in another systematic review showing that that psychological therapies had large positive short-term effects on the severity of pain and small short-term effects on pain interference (98). A moderate effect was found on depression. For medium-term outcomes, they confirmed a large effect on pain severity and interference and a moderate impact on depression (98). For the long-term, significant decreases in pain interference, mood, and self-care behaviors were described (98).

After the publication of the review, results of three new RCTs were published. A small RCT included comparison of CBT with diabetes education among individuals with PDN (99). The authors concluded that CBT reduced neuropathic pain intensity at 12 weeks compared with education and also after 36 weeks; CBT was superior to education and improved pain interference and mental health functioning compared with diabetes education (99).

ACT is a new intervention that has received less attention but has the potential to help individuals cope with PDN. In ACT intervention, a key goal is to increase psychological flexibility in the presence of pain and accomplish improvements to functioning. ACT interventions focus on six central processes: 1) acceptance of problems that cannot be changed such as pain, 2) values-based action, 3) contact with the present moment, 4) cognitive defusion (thoughts are not facts and can be observed), 5) developing an observer self that can change dependent on the context, and 6) committed action in line with important values (100). Thus, ACT can be considered as a potentially promising approach that requires further testing in PDN and that has already been investigated in other patient groups with chronic pain. Significant, medium-to-large effect sizes were reported for pain acceptance and psychological flexibility, which are typically considered processes of ACT, and small-to-medium effects for daily functioning, anxiety, and depression (100).

DN is common and has a negative impact on psychological functioning and QoL. Although psychological research in still scarce in DN, it has become clear that psychological factors such as depression are associated with poor future health outcomes. The beliefs of individuals with DN regarding the prescribed therapies are understudied, and it is unclear whether successful treatment of emotional problems such as comorbid depression leads to better health outcomes in DN. As medication for PDN is not effective enough in a substantial number of people, and has considerable side effects, in new well-designed randomized trials investigators should test effects of the most promising psychological interventions such as CBT and ACT. Validation and standardization of PROMs in DN is urgently needed for use in the clinical setting and in research.

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

R.P.-B. is an editor of Diabetes Care but was not involved in any of the decisions regarding review of the manuscript or its acceptance.