Background/Purpose

Osteoarthritis (OA) is reported to be more prevalent in individuals with diabetes mellitus (DM).  Potential etiologies include advanced glycation endproducts, which reduce cartilage integrity, and obesity which increases the mechanical load on the knee.  We further explored the relationship of abnormal glucose metabolism and incident knee OA in a community based cohort with 84 months of follow up.

Methods

The Multicenter Osteoarthritis Study Group (MOST) is an NIH-funded longitudinal study of risk factors for knee OA in people age 50-79 years, with or at high risk of knee OA.  Subjects were eligible for this ancillary study if they did not have RKOA at baseline (Kellgren and Lawrence (KL) grade <2 bilaterally).  Subjects were excluded if they lacked follow up knee radiographs or if their baseline blood sample was not available.  A random sample diverse in baseline body mass index (BMI) of 1000 subjects (out of 1280 eligible subjects) was selected.  Fasting glucose (Unical DxC 800 Auto-analyser (Beckman Coulter, Fullerton, CA, USA) and free insulin (Luminex Milliplex Analyzer Model XYP 100/200 S, Austin, Texas) levels at baseline were measured on all subjects.  Subjects were categorized as DM based on any of the following: self-report DM, use of anti-diabetic medications or a fasting glucose at baseline of > 126 mg/dL.  The outcome was the cumulative incidence of RKOA between baseline and the 84-month follow-up visit, defined by either a KL grade > 2 or total knee replacement.  Knee-level pooled binary regression analysis was performed in men and women separately.  GEE (to account for within-subject correlation) was used to obtain risk ratios (95% CI) for incidence of RKOA predicted by: fasting glucose, insulin resistance (measured by homeostatic model assessment – insulin resistance (HOMA-IR)) and diabetes status.  Subjects who were taking insulin were excluded from models in which insulin resistance was analyzed. 

Results

Among the 1000 subjects (mean age 61+/-7.8 years, 58% women, mean BMI at baseline 29.1+/-4.9 kg/m²), there were 107 subjects with DM.  DM subjects were more likely to be male, non-white and have higher BMI.  Over the 84 months of follow-up, incidence of RKOA did not differ between diabetics compared to non-diabetics. In men, both elevated fasting glucose and HOMA-IR were associated with an increased risk of incident RKOA, but this effect did not persist after adjustment for BMI.  In women, HOMA-IR levels were associated with a decreased risk of incident RKOA after adjustment for BMI.  (Table) 

Conclusion

DM at baseline was not associated with incident RKOA in this cohort.  However, insulin resistance in women may be protective against the development of RKOA once the effect of high BMI is accounted for.  This finding needs to be replicated in additional studies.

TABLE: Risk Ratio for Incident Knee Osteoarthritis, stratified by sex   WOMEN 580 subjects/1160 knees/278 events MEN 420 subjects/840 knees/137 events   Risk Ratio (95% CI) and p-values Risk Ratio (95% CI) and p values Baseline Predictor Unadjusted Model BMI-Adjusted Modela Unadjusted Model BMI-Adjusted Modela Fasting glucose (per 1SD)   1.09 (0.96-1.23) 0.2 0.93 (0.81-1.07) 0.3 1.21 (1.04-1.42) 0.01 1.04 (0.88-1.23) 0.7 HOMA-IR (per 1SD)   1.05 (0.93-1.19) 0.4 0.81 (0.71-0.93) <0.01 1.26 (1.05-1.51) 0.01 1.03 (0.84-1.27) 0.8 Diabetes   0.92 (0.59-1.45) 0.7 0.63 (0.38-1.06) 0.08 1.49 (0.96-2.30) 0.08 1.10 (0.69-1.75) 0.7 aAdjusted for age, race, clinic site, visit, and body mass index

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hyperglycemia-and-risk-of-osteoarthritis/