Glucose homeostasis influences the risk of incident knee osteoarthritis: Data from the osteoarthritis initiative

Abstract

We aimed to determine if serum measures of impaired glucose homeostasis (glucose concentrations or glycated serum protein, GSP) or systemic inflammation (high-sensitivity C-reactive protein, CRP) are related to incident typical knee osteoarthritis (KOA) or incident accelerated KOA. We conducted a case-control study using the Osteoarthritis Initiative's baseline and first 4 annual visits. All participants had no radiographic KOA at baseline (Kellgren-Lawrence [KL]<2). We classified 3 groups: 1) incident accelerated KOA: ≥1 knee developed advance-stage KOA (KL Grade 3 or 4) within 48 months, 2) incident typical KOA: ≥1 knee increased in radiographic scoring within 48 months (excluding those with accelerated KOA), and 3) No KOA: no change in KL grade by 48 months. We matched on sex. A laboratory blinded to group assignment used baseline serum samples to conduct assays for CRP, GSP, and glucose. Due to nonlinear relationships, we used 3 piece-wise multinomial logistic regression models to determine if baseline CRP, GSP, or glucose were associated with incident typical KOA or accelerated KOA compared with no KOA. We adjusted for age, body mass index, and sex. We analyzed 54 adults/group. Lower and higher GSP concentrations were associated with incident typical KOA compared with adults with concentrations (log) closer to 5.7 (lnGSP<5.7: OR=0.28, 95%CI=0.08-0.93; lnGSP>5.7: OR=3.21, 95%CI=1.07-9.62). Glucose, GSP, and CRP were not significantly associated with incident accelerated KOA. Glucose homeostasis may predict individuals at risk of incident typical KOA but not accelerated KOA, which may indicate accelerated KOA is a distinct disorder from typical KOA.

Risk factors can classify individuals who develop accelerated knee osteoarthritis: Data from the osteoarthritis initiative

“…However, the CART analysis enabled us to look at possible interactions that would be infeasible with other statistical analyses because of the limited sample size. For example, we previously found no relationship between glucose concentrations and incident accelerated KOA but the small sample size prevented us from assessing this relationship among older adults, where the CART analysis suggests it may be an important factor . Based on these findings, it may be fruitful to explore the association between fasting glucose levels and incident accelerated KOA among adults over 63.5 years of age.…”

“…While accelerated KOA represents 22% of incident cases of KOA in the Osteoarthritis Initiative cohort, the small sample size makes it is challenging to study complex interactions among risk factors. Furthermore, the nonlinear association between some risk factors and incident KOA makes this even more challenging with common statistical methods (e.g., multinomial logistic regression). Classification and regression tree (CART) analysis overcomes these issues by using a non‐parametric and nonlinear method to identify the most discriminating risk factor and associated cut point to differentiate two groups (e.g., accelerated KOA or no accelerated KOA) and then continue to find the next best risk factor and cut point .…”

A single recent injury is a potent risk factor for the development of accelerated knee osteoarthritis: data from the osteoarthritis initiative

“…While numerous studies have evaluated AKOA with data from the OAI [1,5,6,3,2,4,10,11] they have all focused on the first four years of the cohort. By studying people with AKOA after the 48-month visit of the OAI, we could explore which modifiable risk factors are consistently present and which risk factors are unique to the timing of incident AKOA.…”

Glucose enhances aggrecan expression in chondrocytes via the PKCα/p38‐miR141‐3p signaling pathway

“…In this study, we show that glucose upregulates aggrecan expression and induces cartilage formation, suggesting that glucose treatment not only restores cartilage function but also stimulates chondrogenesis. Epidemiological evidence indicates that diabetes is an independent risk factor for OA (Courties & Sellam, ; Driban et al, ). Our previous study also showed that high glucose upregulates VEGF‐A expression in human synovial fibroblast cells (Tsai et al, ), a hallmark of angiogenesis that is essential for the development, growth, and progression of OA (Ashraf & Walsh, ).…”