Faculty Bibliography

Background/Purpose : Several studies implicate gout and/or xanthine oxidase activity as risk factors for type 2 diabetes. However, no studies have directly evaluated the effect of the xanthine oxidase inhibition on type 2 diabetes development. We therefore assessed the impact of allopurinol use on diabetes incidence in a retrospective cohort study of Veterans' Affairs patients with gout. Methods : The New York Harbor VA Computerized Patient Record System was searched to identify patients with an ICD-9 code for gout also meeting at least 4 1977 American Rheumatology Association gout diagnostic criteria. Pharmacy records were reviewed, and subjects divided into subgroups based on >30 continuous days of allopurinol prescription, versus no allopurinol. Incident diagnoses of diabetes, defined as first hemoglobin A1c <= 6.5% or physician documentation, were identified during an observation period from January 1, 2000 through December 31, 2015. Categorical variables, including the primary endpoint, were analyzed utilizing Fisher's exact test. Continuous variables were analyzed using binomial regression and the Student's T test. Results : 1032 subjects were allopurinol users, and 485 subjects were allopurinol never-users. The average duration of allopurinol use was 48.4 months. There were significantly more Black subjects in the allopurinol group, whereas there were significantly more Asian subjects and subjects with chronic kidney disease in the non-allopurinol group. Over a mean 94.3 months of follow-up, there was no significant difference in diabetes incidence between the allopurinol and non-allopurinol groups (8.0/1000 person-years versus 11.3/1000 person-years, p=0.64). There was also no significant difference in diabetes incidence when subjects were analyzed by baseline serum urate level, colchicine use, allopurinol dose, extent of urate lowering with allopurinol or achieving target urate level. When stratified into quartiles by duration of allopurinol use, a significant difference was observed between diabetes incidence in the longest and shortest quartiles among subjects in the allopurinol cohort (7.3 per 1000 person-years versus 21.3 per 1000 person-years, p=0.007). Conclusion : In this study, allopurinol use was overall not associated with reduced diabetes incidence, but longer durations of allopurinol use may have been associated with decreased diabetes. Prospective studies may further elucidate the relationship between hyperuricemia, gout, xanthine oxidase activity and diabetes, and the potential impact of gout treatments on diabetes incidence. (Figure Presented )

OBJECTIVES/OBJECTIVE:Gout patients with chronic kidney disease (CKD) accumulate the active allopurinol metabolite oxypurinol, suggesting that allopurinol may promote greater serum urate (sU) lowering in CKD patients. METHODS:We identified all patientswith gout diagnoses on either 100 mg or 300 mg of allopurinol daily, with available pre- and on-treatment sU levels, in our system in a 1-year period. Mean sU decrement by dosing per CKD groups was determined by CKD stage. RESULTS:Of 1,288 subjects with gout, 180 met entry criteria, with 83 subjects receiving 100 mg and 97 receiving 300 mg allopurinol. Subjects with CKD stage 1 experienced less sU lowering with 100 mg than 300 mg of allopurinol. Subjects with stage 4 and 5 CKD had equivalent sU decreases across the 100 mg and 300 mg allopurinol groups. However, the 100 mg group started at a higher pre-treatment sU and ended at a higher final sU than the 300 mg group. CONCLUSIONS:The strategy of titrating allopurinol to sU in patients with kidney impairment may result in greater sU lowering at lower doses than in patients without CKD but may also pose a treatment challenge from a possible drug ceiling effect.

Background/Purpose: Previous studies suggest that patients with gout are at increased risk for developing diabetes.1 One possible explanation for this increased risk is the activation of pathologic pathways common to both diabetes and gout, including IL-1b.2 Among its many mechanisms, colchicine has been found to suppress activation of the NLRP3 inflammasome, inhibiting activation of IL-1b. Colchicine may also activate AMPK, a down regulator of inflammation and gluconeogenesis.3 In the present study, we investigated whether chronic colchicine use reduces diabetes incidence among patients with gout.
Method(s): We reviewed the Computerized Patient Record System (CPRS) of the New York Harbor Veterans' Affairs Healthcare System to assess the incidence of diabetes between 2000 and 2015 among 140 randomly selected patients with gout who had taken colchicine daily for some or all of the study period. We compared the diabetes incidence among these patients with 115 randomly selected patients with gout who did not take colchicine during the same time period. At study entry, all subjects met a modified version of 1977 ARA gout classification criteria and had no diabetes diagnosis. Patients were excluded if their duration of colchicine use was <60 contiguous days. Incident diabetes was defined as a new hemoglobin A1c value of >=6.5% during the study period.
Result(s): Among gout patients who had taken colchicine, we observed no difference in diabetes incidence compared to patients not taking colchicine (17.1% versus 17.4%, OR = 0.983, p = 1.0). When patients were analyzed by duration of colchicine use, there was no significant difference in diabetes incidence between patients in the longest (36.5 to 114 months) compared to the shortest tertile (2.3 to 14 months)(27.3% versus 9.1%, p=0.24) of colchicine exposure. Among patients in the colchicine group who experienced incident diabetes during the study period (n=24), 50% (n=12) were actively taking colchicine at the time of their diagnosis and 50% (n=12) had discontinued colchicine use prior to their diabetes diagnosis.
Conclusion(s): We found no significant difference in the 15-year diabetes incidence between patients taking colchicine and those not taking colchicine, suggesting that colchicine is not beneficial to prevent incident diabetes. Larger and prospective studies will be needed to confirm this observation

Gout is characterized by the deposition of monosodium urate crystals and by acute and chronic inflammation in response to crystals so deposited. Multiple case reports and series describe the deposition of monosodium urate in the spine as a rare manifestation of gout, but the actual prevalence of spinal involvement is unknown and likely to be higher than generally anticipated. Here we review the characteristics of 131 previously reported cases of spinal involvement in gout. We focus in particular on the use of imaging modalities and the extent to which they correlate with presenting symptoms and tissue diagnoses. The recent innovation of using dual-energy computerized tomography to identify urate crystal deposition holds promise for reducing the need for surgical intervention and for establishing a true prevalence rate for spinal gout.