Diabetes affects approximately 6% of the population, with 20% developing foot ulcers. Gout affects about 3% of the population, but <40% receive sufficient urate-lowering therapy to prevent or dissolve urate crystal (tophi) deposition in the feet, which can ulcerate and become infected. Among patients with diabetes, 20% also have gout. This study aimed to assess adherence to recommended gout treatment in patients with diabetes and to compare usual care with initial care provided by a nurse-led gout care program. In patients with diabetes, gout is frequently undertreated, particularly when not initially managed in a nurse-led gout care program.
Key Points
Most patients with gout receive suboptimal urate-lowering treatment to prevent or dissolve urate deposits (tophi).
In this study, among patients with diabetes and gout, 67% maintained urate levels to prevent tophi. However, 50% of patients with diabetes presented with tophi, and after 2 years, only 45% achieved the lower urate level necessary to dissolve tophi.
Gout in patients with diabetes is often inadequately managed, leading to the persistence of tophi, which may mimic foot ulcers.
Diabetes is a prevalent disease, affecting ∼6% of the population (1). About 20% of individuals with diabetes develop foot ulcers. Foot ulcers are the primary cause of nontraumatic foot amputations and are associated with a 5-year mortality rate >50% (2).
Gout is similarly common, with a prevalence ranging from 2 to 3%. It occurs more frequently in people with reduced kidney function, hypertension, obesity, and heart disease and in those using diuretics—all common in people with diabetes (3–5). Among patients with gout, 10–37% have diabetes, and among patients with diabetes, 17–22% have gout (6–10). These proportions may be even higher, as population studies indicate that >30% of cases of both gout and diabetes are undiagnosed (1,11).
Gout often results in the formation of urate deposits, known as tophi, in the feet, which may ulcerate or mimic infection. Left untreated, gout can perpetuate urate deposition, hindering ulcer healing and leading to new or recurrent foot ulcers with an increased risk for amputation (Figure 1) (6,12).
Photo of the feet of a 64-year-old man with diabetes, atrial fibrillation, reduced renal function, and hypertension who had gout for 20 years without ULT.
Photo of the feet of a 64-year-old man with diabetes, atrial fibrillation, reduced renal function, and hypertension who had gout for 20 years without ULT.
Since 2006, the European Alliance of Associations for Rheumatology has recommended a treat-to-target strategy for every patient with gout, aiming to maintain the plasma urate (p-urate) level at <0.36 mmol/L (equivalent to serum urate <6 mg/dL), which is below the saturation point for monosodium urate crystal deposition (13). The Nordic Reference Interval Project 2000 compared plasma and serum urate level measurements and found equivalent results (14). For tophaceous gout, reflecting a high crystal load, it is recommended to reduce the p-urate level to <0.30 mmol/L (<5 mg/dL) until total crystal dissolution has occurred (15). Once dissolution of crystals is achieved, the p-urate level should be monitored and maintained throughout life at <0.36 mmol/L by continued urate-lowering therapy (ULT) to avoid the formation of new urate crystals and future flares (13,16). Discontinuation of recommended ULT is known to result in frequent recurrence of gout flares and urate depositions (16).
ULT is an effective, safe, and affordable treatment option that can prevent and dissolve tophi (17). However, <40% of patients with gout receive sufficient ULT to reach and maintain target p-urate levels as recommended (4,8,9). In those who do receive ULT, the dose is usually fixed without titration to achieve the necessary target p-urate concentration, and adherence is poor, especially if no significant comorbidity is present (10,18,19).
The diagnosis of gout can be challenging and is frequently overlooked or inadequately examined (11,20). The gold standard for diagnosis of gout is the detection of urate crystals by microscopy of joint fluid or tophaceous material (21). Even after a definite gout diagnosis by microscopy in patients referred to a hospital, adherence to recommended treatment is poor, especially if initial treatment is not offered in a dedicated clinic (e.g., a nurse-led gout clinic) (4,8,9).
Patients with diabetes are expected to have more frequent contact for routine diabetes care and might therefore have higher awareness of necessary treatment of common comorbidities such as gout (22); however, this has not been studied before. The aim of this study was to assess adherence to recommended gout treatment to prevent and dissolve urate deposition in patients with diabetes 2 years after a gout diagnosis was verified by microscopy. A graphical summary of the study and its findings and implications is available in the Supplementary Material.
Research Design and Methods
Setting, Diagnosis, and Patients
A detailed description of the whole cohort of patients with gout and subsequent interventions was published elsewhere, with a focus on the comparison of nurse-led gout care versus usual care (8). Briefly, this prospective cohort study was conducted at the Clinic of Rheumatology at North Denmark Regional Hospital in Hjørring, Denmark, which serves a population of 290,000 individuals. We formed a consecutive cohort of all patients diagnosed with gout in the clinic by microscopy in the period from 4 February 2015 to 1 June 2021 and having follow-up 24 months after the date of microscopy.
The clinic’s microscopy service provided all joint fluid or tophaceous material examination for crystals for the entire hospital and its catchment area. The microscopy results could simply indicate whether crystals were detected (yes/no) or could be accompanied by a brief explanation focusing on the treatment of the actual flare.
Baseline information was collected from patients’ medical records. All prescribed treatments regarding ULT and diabetes were confirmed in the Shared Medicine Card national database. At baseline, a prescribed ULT (after 2009) was regarded as ongoing even if it was discontinued. At the 2-year follow-up, both the dose and redeemed prescriptions for ULT were confirmed. All patients with urate crystals were included in the study, including those with malignant diseases or severe kidney disease, with no exclusions.
Vital status was retrieved from the civil registry. All Danish citizens are assigned a unique identification number, which allows us to access patient information across all registries and information technology systems. All eligible patients participated in the study, including follow-ups for all patients who survived the first year.
The diagnosis of diabetes was confirmed in hospital files or by use of prescribed antidiabetic drugs, insulins, and/or peroral antidiabetic agents at the time of microscopy. We did not register who was responsible for patients’ long-term diabetes care (e.g., general practitioner [GP] clinic, diabetes outpatient clinic, combined care, or care delivered elsewhere). We could not obtain reliable information on foot ulcers, which frequently were treated outside of the hospital registration system (e.g., in municipal home care, a GP clinic, or a podiatry clinic).
Nurse-led gout care included consultations, provision of an educational leaflet, telephone contacts, allopurinol titration, and laboratory monitoring until patients were transferred back to their GP after 1 year with a detailed letter advocating lifelong ULT and annual checks of p-urate levels. Allopurinol was the primary choice of treatment for most patients, typically starting at a daily dose of 100 mg and gradually titrating to reach the target p-urate concentration. The initial dose and escalation were lower in patients with reduced renal function. During the study, the nurses commonly treated flares and provided temporary prophylaxis using colchicine in agreement with the national and international guidelines.
Patients in the usual care cohort received standard care in other departments such as orthopedic surgery, emergency wards, or internal medicine, including the diabetes outpatient clinic and general practice clinics. Diabetes status was not considered as a selection criterion for nurse-led care or usual care.
The primary outcome measure assessed the percentage of patients who achieved p-urate <0.36 mmol/L (<6 mg/dL) 2 years after the microscopy. Secondary outcome measures included the percentage of patients who continued ULT at the 2-year mark and the percentage of patients with tophi who achieved p-urate <0.3 mmol/L (<5 mg/dL). Outcomes were assessed only in patients who survived the first year after microscopy to allow time for treatment delay, dose titration, exclusion of terminally ill patients unable to visit the nurse-led care clinic, and transfer to GP care. For patients who died between 12 and 24 months after microscopy, the latest monitored p-urate level after 12 months was considered the 2-year outcome. For patients receiving ULT but without monitored p-urate at 2 years, the p-urate <0.36 mmol/L (<6 mg/dL) determination was extrapolated based on the ULT dose. For patients with neither ongoing ULT nor measured p-urate, the urate levels at 2 years were considered ≥0.36 mmol/L (≥6 mg/dL).
Statistics
Categorical data were compared using χ2 or Fisher exact tests. The significance level was set at 5%. The analyses were conducted using the Social Science Statistics website (https://www.socscistatistics.com; accessed in July 2024).
Ethics
The study was determined by the North Denmark Region Committee on Health Research Ethics to be a quality assurance project and was subsequently approved by the region’s data protection office (study ID 2018-62 and amendment K2023-014). According to Danish regulations for this type of study, informed consent was not required.
The photo included as Figure 1 in this article was taken with the patient’s consent for de-identified use in medical journals. Deidentified patient datasets generated during and/or analyzed in this study are available from the corresponding author upon reasonable request.
Results
We diagnosed 286 consecutive patients with confirmed gout, of whom 49 (17%) also had diabetes at baseline (Table 1). Use of diuretics and the presence of hypertension or heart disease were all significantly more common in patients with diabetes (P <0.0001 to P <0.002).
Baseline Clinical Data at the Time of Gout Diagnosis by Microscopy, Puncture Sites, and Mortality Data
| All (n = 286) | With Diabetes (n = 49) | Without Diabetes (n = 237) | |
|---|---|---|---|
| Age, years | 70 (20–98) | 71 (34–85) | 68 (20–98) |
| Age >70 years | 135 | 57% | 45% |
| Tophi | 111 | 49% | 37% |
| eGFR <60 mL/min/1.73 m2 | 113 | 61% | 61% |
| eGFR <30 mL/min/1.73 m2 | 20 | 10% | 6% |
| Hypertension | 181 | 86% | 59% |
| Atrial fibrillation and/or ischemic heart disease | 117 | 61% | 37% |
| Use of diuretics | 119 | 73% | 35% |
| Cancer | 21 | 14% | 6% |
| Ongoing ULT | 53 | 20% | 18% |
| P-urate >0.50 mmol/L (>8 mg/dL) | 187 | 73% | 64% |
| Anatomical puncture site Knee Ankle Elbow Wrist Tophus finger or toe Other or unknown | 109 42 6 14 103 12 | 31% 12% 4% 6% 45% 2% | 40% 15% 2% 5% 34% 5% |
| Mortality Died <1 year after microscopy Alive for 2-year follow-up Died <2 years after microscopy | 30 256 43 | 12% 88% 14% | 10% 90% 15% |
| All (n = 286) | With Diabetes (n = 49) | Without Diabetes (n = 237) | |
|---|---|---|---|
| Age, years | 70 (20–98) | 71 (34–85) | 68 (20–98) |
| Age >70 years | 135 | 57% | 45% |
| Tophi | 111 | 49% | 37% |
| eGFR <60 mL/min/1.73 m2 | 113 | 61% | 61% |
| eGFR <30 mL/min/1.73 m2 | 20 | 10% | 6% |
| Hypertension | 181 | 86% | 59% |
| Atrial fibrillation and/or ischemic heart disease | 117 | 61% | 37% |
| Use of diuretics | 119 | 73% | 35% |
| Cancer | 21 | 14% | 6% |
| Ongoing ULT | 53 | 20% | 18% |
| P-urate >0.50 mmol/L (>8 mg/dL) | 187 | 73% | 64% |
| Anatomical puncture site Knee Ankle Elbow Wrist Tophus finger or toe Other or unknown | 109 42 6 14 103 12 | 31% 12% 4% 6% 45% 2% | 40% 15% 2% 5% 34% 5% |
| Mortality Died <1 year after microscopy Alive for 2-year follow-up Died <2 years after microscopy | 30 256 43 | 12% 88% 14% | 10% 90% 15% |
Data are median (range), n, or %.
The primary outcome of p-urate <0.36 mmol/L (<6 mg/dL) was assessed in the 256 patients who survived the first year after microscopy, including 43 in the group with diabetes and 213 in the group without diabetes (Table 2). Sixty-seven percent (29 or 43) of those with diabetes achieved the primary outcome, including 47% (8 of 17) receiving usual care and 81% (21 of 26) receiving nurse-led care (P = 0.02) (Table 3).
Dichotomous Primary 2-Year Outcome for 256 Patients With Gout Who Survived First Year After Microscopy
| Total, n | With Diabetes (n = 43) | Without Diabetes (n = 213) | |
|---|---|---|---|
| All patients | 256 | 67% | 60% |
| Nurse-led gout care | 112 | 81% | 81% |
| Age >70 years | 111 | 50% | 65% |
| eGFR <60 mL/min/1.73 m2 | 93 | 68% | 60% |
| P-urate >0.50 mmol/L (>8 mg/dL) at baseline | 165 | 65% | 62% |
| Female sex | 45 | 73% | 59% |
| Use of diuretics at baseline | 100 | 67% | 59% |
| P-urate <0.30 mmol/L (<5 mg/dL) if tophi at baseline | 88 | 45% | 47% |
| Ongoing ULT at 2 years | 216 | 76% | 69% |
| Allopurinol use (mean dose) | 205 | 98% (305 mg/day) | 76% (270 mg/day) |
| Total, n | With Diabetes (n = 43) | Without Diabetes (n = 213) | |
|---|---|---|---|
| All patients | 256 | 67% | 60% |
| Nurse-led gout care | 112 | 81% | 81% |
| Age >70 years | 111 | 50% | 65% |
| eGFR <60 mL/min/1.73 m2 | 93 | 68% | 60% |
| P-urate >0.50 mmol/L (>8 mg/dL) at baseline | 165 | 65% | 62% |
| Female sex | 45 | 73% | 59% |
| Use of diuretics at baseline | 100 | 67% | 59% |
| P-urate <0.30 mmol/L (<5 mg/dL) if tophi at baseline | 88 | 45% | 47% |
| Ongoing ULT at 2 years | 216 | 76% | 69% |
| Allopurinol use (mean dose) | 205 | 98% (305 mg/day) | 76% (270 mg/day) |
Primary outcome was achieved if p-urate was <0.36 mmol/L; for the 88 patients with tophi at baseline, the 2-year outcome was achieved if p-urate was <0.30 mmol/L.
Dichotomous Primary 2-Year Outcome for 43 Patients With Diabetes and Gout Who Survived First Year After Microscopy, by Type of Gout Intervention
| Total, n | Receiving Nurse-Led Gout Care (n = 26) | Receiving Usual Care (n = 17) | |
|---|---|---|---|
| Alive >1 year after microscopy | 43 | 100% | 74% |
| Male sex | 32 | 73% | 76% |
| Age >70 years | 28 | 73% | 53% |
| P-urate <0.36 mmol/L (<6 mg/dL) | 29 | 81% | 47% |
| P-urate <0.30 mmol/L (<5 mg/dL) if tophi at baseline | 20 | 50% | 33% |
| P-urate <0.36 mmol/L if eGFR <60 mL/min/1.73 m2 at baseline | 17 | 79% | 43% |
| P-urate not measured | 3 | 0% | 18% |
| ULT ongoing at 2 years | 38 | 100% | 71% |
| Allopurinol use (mean dose) | 35 | 96% (354 mg/day) | 59% (214 mg/day) |
| Febuxostat use (mean dose) | 3 | 4% (40 mg/day) | 12% (60 mg/day) |
| Total, n | Receiving Nurse-Led Gout Care (n = 26) | Receiving Usual Care (n = 17) | |
|---|---|---|---|
| Alive >1 year after microscopy | 43 | 100% | 74% |
| Male sex | 32 | 73% | 76% |
| Age >70 years | 28 | 73% | 53% |
| P-urate <0.36 mmol/L (<6 mg/dL) | 29 | 81% | 47% |
| P-urate <0.30 mmol/L (<5 mg/dL) if tophi at baseline | 20 | 50% | 33% |
| P-urate <0.36 mmol/L if eGFR <60 mL/min/1.73 m2 at baseline | 17 | 79% | 43% |
| P-urate not measured | 3 | 0% | 18% |
| ULT ongoing at 2 years | 38 | 100% | 71% |
| Allopurinol use (mean dose) | 35 | 96% (354 mg/day) | 59% (214 mg/day) |
| Febuxostat use (mean dose) | 3 | 4% (40 mg/day) | 12% (60 mg/day) |
Primary outcome was achieved if p-urate was <0.36 mmol/L; for those with tophi at baseline, the 2-year outcome was achieved if p-urate was <0.30 mmol/L.
ULT was continued in 100% of the patients receiving nurse-led care and 71% of the patients receiving usual care (Table 3). For patients with diabetes receiving ULT, allopurinol was used by 92% (35 of 38); in the nurse-led care group, the average administrated daily dose was 354 mg, versus 214 mg/day in the usual care group (Table 3). For patients with diabetes, the average daily dose of allopurinol was 305 mg compared with 270 mg for patients without diabetes, reflecting a higher proportion of patients with tophi and diuretic use in the diabetes group (Table 2). No cases of allopurinol hypersensitivity syndrome were observed. Febuxostat was used by three patients with an average daily dose of 53 mg.
Among the 43 patients with diabetes who were alive for the 2-year follow-up, 26 (60%) initially received nurse-led gout care compared with 86 (40%) of patients without diabetes (Table 3).
In the diabetes group, 29 (67%) achieved p-urate <0.36 mmol/L (<6 mg/dL), including 47% of those receiving usual care and 81% of those receiving nurse-led care (P <0.00001) (Table 2). In the group without diabetes, 128 (60%) achieved p-urate <0.36 mmol/L (<6 mg/dL), including 48% receiving usual care and 79% receiving nurse-led care (P <0.00001).
For the 20 patients with diabetes and tophi at baseline, 45% (9 of 20) achieved the recommended target p-urate <0.30 mol/L (<5 mg/dL), including 33% (2 of 6) in usual care and 50% (7 of 14) in nurse-led care (Tables 2 and 3). For the 68 patients without diabetes and tophi at baseline, 47% (32 of 68) achieved the recommended target p-urate <0.30 mol/L (<5 mg/dL), including 32% in usual care and 64% in nurse-led care (Table 2).
The median time from microscopy to the first visit in the nurse-led clinic was 37 days, and this intervention consisted of a median of two visits and three telephone contacts over 336 days.
Thirty patients died in the first year, and an additional 13 patients died between 12 and 24 months after microscopy, yielding a 2-year mortality rate of 14% (7 or 49) in the diabetes group compared with 15% (36 of 237) in the group without diabetes (Table 1).
Discussion
Our study demonstrated that, in a cohort of patients with both diabetes and gout, 67% maintained target p-urate levels 2 years after the gout diagnosis was confirmed by microscopy in a hospital. At the time of diagnosis, half of the patients with diabetes presented with tophi, and, after 2 years, only 45% of these reached the recommended lower p-urate level necessary to dissolve tophi. ULT was continued in 88% of patients, including 100% in the nurse-led gout clinic and 71% in usual care, where doses were often too low. Patients who were allocated to 1 year of initial nurse-led gout care before transitioning to GP care had significantly better outcomes in all measures compared with those receiving usual care only. There were no significant differences in gout-related outcomes between patients with and without diabetes.
We regard our quality assurance study with complete follow-up as a relevant representation of real-life clinical settings. This approach, despite the limitations stated below, allowed us to include and evaluate a broader and more representative group of patients, eliminating potential selection biases associated with strict inclusion criteria that are most often applied in interventional studies and thereby exclude the most relevant patients from participation. The hospital’s microscopy service was the only available site in the catchment area to examine patients for urate crystals and thus confirmed gout in all patients with and without diabetes.
The superior results in the nurse-led gout care group strongly reaffirm the importance of initial education and engagement of patients in disease management, the usefulness of a treat-to-target strategy, and the collaborative involvement of GPs in subsequent long-term care (8,9). Although patients with diabetes were treated with higher doses of allopurinol (305 vs. 270 mg), the doses were not sufficient to achieve target p-urate levels in a portion of the population. There were no obvious reasons not to titrate the allopurinol dose adequately to reduce p-urate levels, indicating that current diabetes care providers lack sufficient awareness of the early diagnosis and effective treatment of this common and serious comorbidity.
This study had some weaknesses, as we did not examine patients with diabetes in our catchment area for gout and adherence to recommended gout management, nor did we examine all patients with gout for undiagnosed diabetes. Our study population was small and biased toward describing patients with diabetes and advanced gout who were eventually diagnosed in hospital settings. There might be a bias in selection of patients to either nurse-led or usual care for gout, but the data did not indicate significant differences in outcomes between patients with and without diabetes.
We did not examine several clinical features of diabetes, such as disease duration, type of antidiabetic medication, A1C values, and type of provider delivering diabetes care, including foot inspections. We could not retrieve data for foot ulcers because these patients are often treated in home care services or by GPs and podiatrists.
Based on a gout prevalence of 2.5% and the prescribed and redeemed sales of urate-lowering drugs in our region (medstat.dk/en), we estimate that, on average, 26% of patients with gout are treated with a daily dose of 300 mg allopurinol or 40 mg febuxostat. Based on actual incidence and prevalence data, we estimate that there were 1,400 patients with both type 2 diabetes and gout in our catchment area in the study period (1,6,7,23). However, we only diagnosed gout by microscopy in 49 patients (4%), although our clinic performs all microscopies for urate in the catchment area. This finding implies that 96% of patients with diabetes and gout are not diagnosed with definite gout by microscopy or that the gout diagnosis is made based on a less accurate assessment (i.e., symptoms and signs only or through the use of a gout calculator such as www. mdcalc.com).
The high proportion of patients with tophi indicates that many had suffered from undiagnosed or insufficiently treated gout for years before receiving a definitive diagnosis. Additionally, the patients’ age, anatomical puncture sites, and high mortality rates suggest advanced stages of gout. Mortality rates were similar in patients with and without diabetes, even though patients with diabetes were older and used more diuretics. The differences in the registered shared comorbidities between the two groups did not provide an obvious explanation. One possible explanation for this unexpected result could be that the overall severity of comorbid conditions, such as cardiovascular disease and kidney dysfunction, played a more significant role in mortality than the presence of diabetes alone. Additionally, it is possible that patients with diabetes received more intensive monitoring and management of their comorbidities, which may have mitigated the impact of diabetes on mortality rates and led to an underestimation of comorbidities in the group without diabetes.
Patients with suboptimally treated gout not only suffer because of painful flares, low quality of life, and tophi that may ulcerate, but studies indicate that flares are followed by a doubling of the risk of myocardial infarction or stroke in the following months (24,25). Achieving an average p-urate concentration <0.36 mmol/L (<6 mg/dL) is associated with an absence of gout flares and a reduction in the number of flares in the subsequent 12 months in people with gout (26). P-urate levels should also be lowered enough (<0.30 mmol/L [<5 mg/dL]) to promote dissolution of urate deposits in patients with tophaceous gout such as in the feet (27). These results support the recommended two-level treat-to-target p-urate approach in the management of gout.
Our study provides no explanation of why the awareness of gout management in routine diabetes care is suboptimal and no better than that provided by other health care providers for patients without diabetes. Patients with diabetes are on a routine basis repeatedly screened for a range of well-known comorbidities (e.g., hypertension, atrial fibrillation, hypercholesterolemia, kidney disease, and foot problems). It is surprising that awareness of gout risk seems to be missing in these surveillance programs (22,28).
Common misconceptions about gout, such as the belief that it is not a serious condition or that it is self-induced by lifestyle, present significant barriers to effective care (29). Worry about allopurinol toxicity in patients with renal insufficiency was also an obstacle for sufficient ULT until it was shown that the side effect could be prevented if initial allopurinol doses were reduced according to estimated glomerular filtration rate (eGFR) (30). The misinterpretation of normal p-urate values (in males 0.23–0.48 mmol/L [4–8 mg/dL] and in females 0.16–0.35 mmol/L [3–6 mg/dL]) may also counteract relevant ULT because many p-urate measurements are performed during flares, when p-urate values drop significantly. More than 40% of patients with gout have normal p-urate levels in the weeks around a flare and 10% are even <0.36 mmol/L (<6 mg/dL) (31,32).
Urate deposits and tophi are often located in the feet, especially around the first metatarsophalangeal joint (Figure 1). The tophi may ulcerate and masquerade as diabetic foot ulcers. Gout, foot ulcers, and amputations all are more prevalent among men and in the elderly (2).
Gout as the underlying cause for diabetic foot ulcers has been reported in several small case series (12,20,33–35). The International Working Group on the Diabetic Foot has been producing evidence-based guidelines on the prevention and management of diabetes-related foot disease since 1999 but does not consider gout (28).
Foot ulcers and subsequent risk of amputation are the most feared complications in patients with diabetes (36). Foot ulcers are indeed the most common cause for lower-extremity amputations in these patients. Two registry-based studies have examined the associations among gout, diabetes, and amputation (6,37,38). The largest population-based study demonstrated that patients with gout only, diabetes only, and comorbid gout and diabetes had amputation rates 4.6, 13.2, and 22.0 times higher than patients without gout or diabetes, respectively. These findings indicate that increased risks of amputation incurred by patients with diabetes and gout are independent and synergistic. Given that both conditions are associated with cardiovascular, renal, and metabolic complications, independent risk was expected, but additive risk was not (38).
Whether a proportion of amputations in gout are preventable, similar to what has been shown in diabetes, is unknown. The association of amputations with suboptimal urate control should not be interpreted as causal because p-urate control could serve as a surrogate for gout severity or other unmeasured or inadequately measured cofactors, such as severity of diabetes or renal insufficiency. The American Veteran Study did not show association between attributes of ULT administration and amputations (6). These null findings may reflect real-life health care practices, which infrequently involve ULT dose escalation, resulting in nonachievement of recommended protective p-urate levels, as indicated in our study. However, the reported cases of ulcerating tophi in the feet indicate a potential for prevention of at least some amputations in patients with diabetes. Systematic screening for gout in patients with diabetes and foot ulcers, and especially those considered for amputations, could potentially identify patients who might benefit from a diagnosis of gout as the underlying cause (6).
There are unproven methods to examine foot ulcer debris for urate crystals and support the suspected gout diagnosis by a combination of questionnaires, ultrasound, dual CT scans of the feet, and clinical examinations, which together can help to discriminate gout from its mimics (39). Whether such implementation of systematic screening for gout in patients with diabetes and foot ulcers who are being considered for amputation or education on the topic for both patients and diabetes care professionals would improve long-term outcomes is unknown and will require further study.
Conclusion
Our study indicates that the current level of awareness of gout and adherence to recommended treatment and target p-urate levels in patients with diabetes is insufficient to prevent tophi. For patients who had developed tophi, <50% achieved the p-urate level necessary to dissolve the deposits, potentially leading to foot ulcers. Treatment outcomes significantly improved when affordable nurse-led initial gout care was implemented.
Duality of Interest
No potential conflicts of interest relevant to this article were reported.
Author Contributions
C.R. conceived and designed the study, applied for approval, and trained the research nurses in gout care. C.R. and J.W.L. oversaw development of the project database and performed the data analysis and interpretation. J.W.L. provided gout care, including patients’ gout leaflet. P.C.W.H. provided input on diabetes and foot ulcer care. G.L.N. critically reviewed the manuscript and the presentation of data. All authors critically revised the work for intellectual content, approved the final version, and agreed to be accountable for the work. C.R. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
This article contains supplementary material online at https://doi.org/10.2337/figshare.28020806.
