Association Between Colchicine and Risk of Diabetes Among the Veterans Affairs Population With Gout

Wang, Liya; Sawhney, Monika; Zhao, Yingnan; Carpio, Gandahari; Fonseca, Vivian; Shi, Lizheng

doi:10.1016/j.clinthera.2015.03.010

Cited by 20 publications

(17 citation statements)

References 24 publications

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“…35,36 However, more recent retrospective studies of individuals with chronic inflammatory conditions found that long-term colchicine use did not have negative effects on insulin secretion or glycaemic control, 37 and might potentially have metabolic benefits. 17 Similarly, our results confirmed that chronic colchicine use does not impair first-phase insulin response or insulin sensitivity. Other markers of metabolic health such as HbA1c and cholesterol were not significantly changed by colchicine versus placebo treatment.…”

Section: Discussionsupporting

confidence: 81%

“…One mechanism by which colchicine exerts its anti‐inflammatory effects is by inhibiting NLRP3 inflammasome formation and activation . A recent retrospective study suggested that among patients with gout, long‐term colchicine treatment may have glycaemic benefit; however, to date no randomized controlled trial (RCT) has investigated colchicine's long‐term effects on glucose metabolism in adults with obesity and metabolic syndrome (MetS) . We hypothesized that administration of colchicine to adults with MetS, but who had not yet developed type 2 diabetes, would improve their obesity‐associated metabolic and inflammatory dysregulation.…”

Section: Introductionmentioning

confidence: 99%

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Effects of colchicine in adults with metabolic syndrome: A pilot randomized controlled trial

Demidowich

Levine

Onyekaba

et al. 2019

Diabetes Obesity Metabolism

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Aim To evaluate the efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in people with obesity and metabolic syndrome (MetS). Materials and methods Adults with obesity and MetS, but who did not have diabetes, were randomized to colchicine 0.6 mg or placebo capsules twice daily for 3 months. The primary outcome was change in insulin sensitivity (SI) as estimated by insulin‐modified frequently sampled intravenous glucose tolerance tests. Secondary outcomes included changes in other metabolic variables and inflammatory markers. Results Of 40 participants randomized (21 colchicine, 19 placebo), 37 completed the trial. Compared with placebo, colchicine significantly reduced C‐reactive protein (P <0.005), erythrocyte sedimentation rate (P <0.01), white blood cell count (P <0.005), and absolute neutrophil count (P <0.001). Change in SI was not significantly different between colchicine and placebo arms (difference: +0.21 × 10−5; CI −1.70 to +2.13 × 10−5 min−1 mU−1 mL; P = 0.82). However, changes in some secondary outcomes, including homeostatic model assessment of insulin resistance (P = 0.0499), fasting insulin (P = 0.07) and glucose effectiveness (P = 0.08), suggested metabolic improvements in the colchicine versus placebo group. Adverse events were generally mild and similar in both groups. Conclusions This pilot study found colchicine significantly improved obesity‐associated inflammatory variables and showed a good safety profile among adults with obesity and MetS who did not have diabetes. These results suggest a larger, adequately powered study should be conducted to determine whether colchicine improves insulin resistance and other measures of metabolic health in at‐risk individuals.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Effects of colchicine in adults with metabolic syndrome: A pilot randomized controlled trial

Demidowich

Levine

Onyekaba

et al. 2019

Diabetes Obesity Metabolism

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“…In the present study we observed that colchicine confirmed its role as a hypoglycemic drug lowering plasma glucose levels [ 42 , 43 ], as can be noticed in the CD + Col group. Concerning the lipid profile of the rabbits, we observed that cholesterol enriched food increased total plasma cholesterol and LDL-C in both treatment groups, whereas TG levels were reduced in the end of the experiment in a statistically significant manner for the CD + Col group.…”

Section: Discussionsupporting

confidence: 72%

Per os colchicine administration in cholesterol fed rabbits: Triglycerides lowering effects without affecting atherosclerosis progress

et al. 2017

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Background: Atherosclerosis is a chronic inflammatory disease that is promoted, among others, by pro-inflammatory cytokines such as IL-1β and IL-18 produced by NLRP 3 inflammasome. Development of atherosclerotic lesions is also affected by leptin. Furthermore, inflammasome's action is interfered with other inflammatory diseases, like diabetes. On the other hand, colchicine is reported to act as anti-inflammatory agent inhibiting inflammasome's action and stabilizing atherosclerotic lesions. The purpose of this study is to investigate the effect of per os colchicine on the de novo formation of atherosclerotic lesions and on the levels of IL-18, leptin and insulin in cholesterol-fed rabbits. Methods: Twenty-three male, 2 months old New Zealand White rabbits, were seperated in 3 groups and were fed with different types of diet for 7 weeks: standard, cholesterol 1% w/w and cholesterol 1% w/w plus colchicine 2 mg/kg body weight. Blood was collected for biochemical measurements and conduction of ELISA for leptin, IL-18 and insulin. Histologic examination of stained with eosin and hematoxylin aorta specimens was performed. Aortic intimal thickness was evaluated using image analysis. The statistical analysis included non-parametric tests: a) paired-sample Wilcoxon test, b) Spearman correlation coefficient and c) Kruscal-Wallis test. Results: Triglerycide levels were decreased in cholesterol plus colchicine group in the end of the experiment (p < 0.05), whereas the cholesterol group had increased levels. No statistical differences were observed in the levels of IL-18, leptin and insulin between groups. Likewise, there was neither any correlation between IL-18, leptin and intima thickness nor between IL-18 and glucose and between leptin and weight. In cholesterol and colchicine group there was a strong positive correlation between IL-18 and insulin levels in the 4th week (r s = .66, n = 10, p < 0.05), whereas in the 7th week this correlation became strong negative (r s = −.86, n = 10, p < 0.05). Finally, intima thickness in the ascending and thoracic aorta of the cholesterol and colchicine group was significantly greater than that of the other groups (p < 0.05). Conclusions: Per os administration of colchicine did not influence atherosclerosis progression in cholesterol-fed rabbits, levels of IL-18, insulin and leptin. We encountered the attenuating role of colchicine on TG levels.

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“…In a small placebo-controlled crossover study of colchicine in twelve patients with type 2 diabetes, subjects had a significantly lower glucose by oral glucose tolerance test while on colchicine [20]. In patients without diabetes, a large retrospective cohort study found that colchicine users (matched to non-users by propensity scoring) did not have a significantly lower diabetes incidence (adjusted hazard ratio 0.88; 95 % CI 0.66, 1.16) [21]. …”

Section: Diabetes-specific Effects Of Rheumatologic Immune Modulatorsmentioning

confidence: 99%

Immune-Modulating Therapy for Rheumatologic Disease: Implications for Patients with Diabetes

et al. 2016

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Immune modulators used to treat rheumatologic disease have diverse endocrine effects in patients with diabetes. Providers should be aware of these effects given that diabetes and rheumatologic disease overlap in prevalence and cardiovascular morbidity. In patients with type 1 diabetes, clinical trials have demonstrated that immune modulators used early in the disease can improve pancreatic function, though their efficacy in adults with longstanding autoimmune diabetes is unknown. In patients with type 2 diabetes, hydroxychloroquine is an effective antihyperglycemic and may be preferred for rheumatologic use in patients with difficult glycemic control. In patients without diabetes, hydroxychloroquine and tumor necrosis factor (TNF) inhibitors have been found to decrease diabetes incidence in observational studies. Additionally, dapsone and sulfasalazine alter erythrocyte survival resulting in inaccurate HbA1c values. These multifaceted effects of immune modulators create a need for coordinated care between providers treating patients with diabetes to individualize medication selection and prevent hypoglycemic events. More research is needed to determine the long-term outcomes of immune modulators in patients with diabetes.

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Association Between Colchicine and Risk of Diabetes Among the Veterans Affairs Population With Gout

Cited by 20 publications

References 24 publications

Effects of colchicine in adults with metabolic syndrome: A pilot randomized controlled trial

Effects of colchicine in adults with metabolic syndrome: A pilot randomized controlled trial

Per os colchicine administration in cholesterol fed rabbits: Triglycerides lowering effects without affecting atherosclerosis progress

Immune-Modulating Therapy for Rheumatologic Disease: Implications for Patients with Diabetes

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