The interaction between type 2 diabetes mellitus and arterial hypertension is a risk factor for the development of primary knee osteoarthritis.

Abstract

Background

Osteoarthritis (OA) comprises a group of phenotypes that reflect different underlying causes and mechanisms. In knee osteoarthritis (KOA), six phenotypes have been described, including the metabolic phenotype, which has been linked to metabolic syndrome (MetS). Within this phenotype, components of MetS such as type 2 diabetes mellitus (DM2) and hypertension (HTN) may contribute to the risk of KOA. Although DM2 and HTN may coexist by chance, they also share common risk factors, raising the possibility of a biological interaction that increases susceptibility to KOA. While both conditions have been studied as independent risk factors for OA, their combined effect on KOA has not been clearly described.

Objective

This study aimed to evaluate the association of DM2 and HTN with primary KOA and to determine whether their interaction increases susceptibility to KOA in a Mexican population.

Methods

A case-control study was conducted using participants from a previously recruited cohort established to investigate genetic risk factors for primary KOA. Cases were adults aged 40 years or older with clinically diagnosed primary KOA, radiographic grade ≥2 according to the Kellgren-Lawrence scale, BMI ≤27 kg/m², no history of severe knee injury or surgery, and no other joint disease. Controls had no clinical evidence of KOA and a radiographic grade <2. DM2 and HTN were identified based on diagnoses documented in medical records. To analyze DM2 and HTN as independent main effects, as well as their interaction, univariate and multivariate non-conditional logistic regression models were performed, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using STATA version 15.0. Additionally, the multifactor dimensionality reduction (MDR) algorithm was applied to examine interaction effects.

Results

A total of 451 cases and 570 controls were included. Women predominated in both groups (76.0% of cases and 70.4% of controls; p = 0.04). Cases were older on average (62.7 ± 10.9 vs. 58.8 ± 11.1 years) and had a higher BMI (26.3 ± 3.5 vs. 25.4 ± 2.8; p < 0.01). DM2 and HTN were both more frequent among cases than controls (p = 0.004 and p = 0.0001, respectively). When analyzed as independent main effects, both conditions were associated with increased risk of primary KOA: DM2, OR 1.6 (95% CI, 1.2–2.2), and HTN, OR 1.7 (95% CI, 1.3–2.2). These associations remained after adjustment for age, sex, and BMI. The interaction model between DM2 and HTN showed an increased risk of primary KOA, with an OR of 2.0 (95% CI, 1.3–3.1), which also persisted after adjustment. The MDR analysis likewise identified a significant interaction between DM2 and HTN in relation to KOA.

Conclusion

These findings suggest that DM2 and HTN interact to increase the risk of primary KOA in the Mexican population.