Browsing by Author "Kang, Amy"

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    Risk Factors for Fracture in Patients with Coexisting Chronic Kidney Disease and Type 2 Diabetes: An Observational Analysis from the CREDENCE Trial
    (Hindawi, 2022-05-27) Young, Tamara K.; Toussaint, Nigel D.; Di Tanna, Gian Luca; Arnott, Clare; Hockham, Carinna; Kang, Amy; Schutte, Aletta E.; Perkovic, Vlado; Mahaffey, Kenneth W.; Agarwal, Rajiv; Bakris, George L.; Charytan, David M.; Heerspink, Hiddo J.L.; Levin, Adeera; Pollock, Carol; Wheeler, David C.; Zhang, Hong; Jardine, Meg J.; Medicine, School of Medicine
    Background: The fracture pathophysiology associated with type 2 diabetes and chronic kidney disease (CKD) is incompletely understood. We examined individual fracture predictors and prediction sets based on different pathophysiological hypotheses, testing whether any of the sets improved prediction beyond that based on traditional osteoporotic risk factors. Methods: Within the CREDENCE cohort with adjudicated fracture outcomes, we assessed the association of individual factors with fracture using Cox regression models. We used the Akaike information criteria (AIC) and Schwartz Bayes Criterion (SBC) to assess six separate variable sets based on hypothesized associations with fracture, namely, traditional osteoporosis, exploratory general population findings, cardiovascular risk, CKD-mineral and bone disorder, diabetic osteodystrophy, and an all-inclusive set containing all variables. Results: Fracture occurred in 135 (3.1%) participants over a median 2.35 [1.88-2.93] years. Independent fracture predictors were older age (hazard ratio [HR] 1.04, confidence interval [CI] 1.01-1.06), female sex (HR 2.49, CI 1.70-3.65), previous fracture (HR 2.30, CI 1.58-3.34), Asian race (HR 1.74, CI 1.09-2.78), vitamin D therapy requirement (HR 2.05, CI 1.31-3.21), HbA1c (HR 1.14, CI 1.00-1.32), prior cardiovascular event (HR 1.60, CI 1.10-2.33), and serum albumin (HR 0.41, CI 0.23-0.74) (lower albumin associated with greater risk). The goodness of fit of the various hypothesis sets was similar (AIC range 1870.92-1849.51, SBC range 1875.60-1948.04). Conclusion: Independent predictors of fracture were identified in the CREDENCE participants with type 2 diabetes and CKD. Fracture prediction was not improved by models built on alternative pathophysiology hypotheses compared with traditional osteoporosis predictors.
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    The impact of canagliflozin on the risk of neuropathy events: A post-hoc exploratory analysis of the CREDENCE trial
    (Elsevier, 2022) Liao, Jinlan; Kang, Amy; Xia, Chao; Young, Tamara; Di Tanna, Gian Luca; Arnott, Clare; Pollock, Carol; Krishnan, Arun V.; Agarwal, Rajiv; Bakris, George; Charytan, David M.; de Zeeuw, Dick; Heerspink, Hiddo J.L.; Levin, Adeera; Neal , Bruce; Wheeler, David C.; Zhang, Hong; Zinman, Bernard; Mahaffey, Kenneth W.; Perkovic, Vlado; Jardine, Meg J.; Smyth , Brendan; Medicine, School of Medicine
    Aim: Canagliflozin reduces the risk, and progression, of diabetic kidney disease. We hypothesized that it may improve the microvascular complication of neuropathy. Methods: The CREDENCE trial randomized participants with type 2 diabetes and kidney disease to canagliflozin 100 mg daily or placebo. Neuropathy events were defined post-hoc as any reported adverse event consistent with a peripheral or autonomic neuropathy event. The effect of canagliflozin and predictors of neuropathy events were estimated using Cox regression analysis. In sensitivity analyses the endpoint was restricted to sensorimotor polyneuropathy, diabetic neuropathy, and non-autonomic neuropathy events. Results: Almost half (48.8%) of the 4401 participants had a diagnosis of neuropathy at baseline. Over a median of 2.45 years of follow up, 657 people experienced a neuropathy event (63.2 per 1000 patient-years). Independent factors associated with higher risk of experiencing neuropathy events were non-white race, younger age, higher glycated haemoglobin and lower estimated glomerular filtration rate. The incidence of neuropathy events was similar in people randomized to canagliflozin and placebo (334/2202 vs. 323/2199; HR 1.04, 95% CI 0.89 to 1.21, P = 0.66). Canagliflozin had no impact on sensorimotor polyneuropathy (HR 0.93, 95% CI 0.69 to 1.25, P = 0.63), diabetic neuropathy (HR 0.91, 95% CI 0.68 to 1.22, P = 0.52), or non-autonomic neuropathy (HR 1.03, 95% CI 0.87 to 1.21, P = 0.77). The lack of effect on neuropathy events was consistent in subgroup analyses. Conclusion: Canagliflozin did not affect the risk of neuropathy events in the CREDENCE trial. Future large randomized studies with prespecified neuropathy endpoints are required to determine the impact of sodium glucose cotransporter 2 inhibitors on diabetic neuropathy.