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Copyright © 2022 Faculty of Health Science UKM. All right reserved Artikel Ulasan/Review Article
Diabetes induced Osteoarthritis: A Narrative Review on Key Concepts and its Implications
Osteoartritis-teraruh-Diabetes: Ulasan Naratif ke atas Konsep Utama dan Implikasinya
SUMAIYAH MAT, SEOW SHI RUI, TEOH JUN JIE, AMYRA MOHD YUSUP, NOR FADILAH RAJAB, SUZANA SHAHAR & DEVINDER KAUR AJIT SINGH
ABSTRACT
Diabetes mellitus (DM) is a metabolic syndrome demonstrated with metabolic components imbalance upon insulin resistance, insulin insufficiency and hyperglycaemia. Meanwhile, osteoarthritis (OA) is a joint degenerative condition resulting in chronic inflammation. As the prevalence of diabetes rises, so does the risk of OA, as it has been demonstrated that DM is strongly linked to OA. This review aimed to summarise the key concept of patho-physiological of diabetes-induce-OA. Studies involving OA patients with and without diabetes were included in this narrative review to look at the impact of diabetes on OA in terms of physical performance, psychological status, physical activity, and social participation. Literature review suggests, DM may lead to OA via numerous pathways, with the most common one is inflammation. We also found that DM may influence OA patients by increasing pain intensity due to aberrant nociceptive fibre activity, reducing walking speed, increasing the rate of depression, and isolating them socially. While the pathophysiology of diabetes-induced osteoarthritis remains unknown, this study may raise public knowledge about how diabetes affects OA and assist healthcare providers in better understanding the condition for a better interventions planning.
Keywords: Osteoarthritis, diabetes, pain, physical performance
ABSTRAK
Diabetes mellitus (DM) merupakan sejenis sindrom metabolisme di mana ketidakseimbangan komponen metabolik berlaku atas kerintangan insulin, kekurangan insulin dan hiperglisemia, manakala osteoarthritis (OA) merupakan degenerasi sendi akibat keradangan kronik dan penjejasan biomekanik. Apabila prevalen DM meningkat, penyakit sendi iaitu OA juga dijangka meningkat, disebabkan perkaitan rapat antara DM dengan OA.
Tinjauan naratif ini bertujuan untuk mengkaji konsep utama patofisiologi diabetes-induced-OA. Kajian-kajian lepas yang melibatkan pesakit OA dengan dan tanpa DM telah dimasukkan dalam tinjauan naratif ini untuk melihat kesan DM terhadap OA dari segi prestasi dan kecergasan fizikal, status psikologi, aktiviti fizikal dan penyertaan sosial. Sorotan literatur menunjukkan bahawa DM boleh meningkatkan risiko OA melalui pelbagai cara terutamanya inflamasi. Kami juga mendapati bahawa DM mempunyai kesan signifikan ke atas pesakit OA dengan meningkatkan intensiti kesakitan akibat aktiviti serat nosiseptif yang menyimpang, memberi kesan kepada keupayaan berjalan, meningkatkan kadar kemurungan, dan mengganggu aktiviti sosial mereka.
Walaupun patofisiologi OA yang disebabkan oleh DM masih tidak diketahui, kajian ini dapat meningkatkan pengetahuan umum tentang risiko OA dalam kalangan pesakit DM dan membantu pakar bidang kesihatan untuk memahami dengan lebih baik tentang bagaimana penyakit ini menyebabkan OA dan seterusnya dapat merancang intervensi yang lebih baik.
Kata kunci: Osteoartritis, diabetes, sakit, prestasi fizikal
INTRODUCTION
As the global population is ageing rapidly, the prevalence of age and lifestyle related diseases such arthritis and diabetes are expected to rise.
Osteoarthritis (OA) and diabetes mellitus (DM) commonly co-exist due to their high prevalence and shared risk factors (Veronese et al. 2019). DM affected more than 470 million people worldwide (Lin et al. 2020). According to the National Health
and Morbidity Survey (NHMS) in the year 2019 by the Ministry of Health (MOH), 18.3% Malaysian adults aged 18 and above suffered diabetes. The prevalence of DM has quadrupled in 13 years, from 16% in year 1996 with a spike to 43.4% in the year 2019 among individuals age 65-68 years old (Institute for Public Health 2020). This indicates that nearly one in five Malaysians has diabetes and high prevalence among older people. While osteoarthritis (OA) is one of the significant
contributors for the global disability burden which Years Lived with Disability (YLDs) increased with Disability Adjusted Life Years (DALYs) increased from 0.42% (1990) to 0.69% (2010) worldwide (Cross et al. 2014). The incidence of OA peaks at an advanced age of 70 – 79 years old, contributing to disease burden and lower quality of life especially in older adults (Vos et al. 2017). In Malaysia, a study among older people aged 55 and above showed that over 33.3% reported to have knee pain where 27% reported to have symptoms of knee OA which include stiffness (Mat et al.
2019).
According to epidemiological research, the prevalence of OA among individuals with DM was 29.5±1.2% while the prevalence of DM with OA was 14.4±0.1% which indicates coexistence.
Moreover, OA and DM were significantly associated, high overall risk was found when the odd ratio of OA in people with DM was 1.46 (1.08 to 1.96) and that of DM in people with OA was 1.41 (1.21 to 1.65) (Louati et al. 2015).
In contrast, a recent meta-analysis on 295,100 participants, it was suggested that diabetes is not the significant risk factor for OA but emphasized the role of obesity as the confounding factor (Khor et al. 2020). This indicates that the existing evidence on the independent associations between DM and OA is conflicting and remains unclear.
This review will summarise the key concepts and studies related to diabetes-induced-osteoarthritis from the literature which can serve as a reference for healthcare professionals for further understanding.
PATHOPHYSIOLOGY OF DIABETES- INDUCED-OSTEOARTHRITIS
The key idea that links DM to OA is the disrupted metabolism. It is suggested that metabolic components that builds up abnormally has negative consequences on the joint homeostasis, potentially inducing chronic inflammation in the joint (Berenbaum, 2011). DM is part of metabolic syndrome (MetS). Based on the studies by (Baker et al. 2009) and (Alberti & Zimmet 1998), MetS is a term to describe a collection of disease that occur at the same time such as hypertension, insulin resistance, dyslipidaemia, obesity which may lead to development of heart disease and type 2 diabetes mellitus. In correlation to MetS, a study by (Puenpatom & Victor 2009) outlined how MetS can be one of the risk factors to increase the severity of OA. This study consisted of 7714 sample based on the data from National Health and Nutrition Examination Survey III representing the general US population, out of which 975 of them had OA (Puenpatom & Victor 2009). MetS was found to be prevalent in 59% of the people with
OA, with 30% of them having hyperglycaemia (Puenpatom & Victor 2009). In addition, in younger age group (average 45 years old), OA and MetS were demonstrated to be strongly associated, thus concluding that OA will develop earlier and in more severe form among people with MetS (Puenpatom & Victor 2009).
Considering that hyperglycemia is a key feature of DM and is one of the components of MetS, it suggests that DM may affect people with OA due to this high glucose levels. This will lead to systemic inflammation response because of the increased reactive oxygen species (ROS) production by glycation reaction and electron transport chain in the mitochondria (Kaneto et al.
2010). High glucose level also enhances the accumulation of advanced glycation end products (AGE) in the cartilage, AGE accumulates by time in chondrocytes and synovial cells, then through its receptor namely the receptor for advanced glycation end products (RAGE), deposits inflammation risks (Mendes et al. 2015). RAGE activation induces various signalling pathways and promotes pro-inflammatory and pro-degradative mediator (Loeser et al. 2005). For instance, RAGE signalling upregulates MAP kinase, NF-kappa B activity and MMP-13 production that causes cartilage damage (Loeser et al. 2005). Moreover, alteration in glucose transporter function further reinforces the deleterious process (Berenbaum, 2011). This has been demonstrated in vitro that high glucose transporter 1 (GLUT1) expression stimulated by high glucose condition enhances AGE, endoplasmic reticulum stress, and inflammatory factors (Li et al. 2021). The hypothetical framework of the associations between diabetes and osteoarthritis is as summarised in Fig. 1.
CLINICAL PRESENTATION OF DIABETES-INDUCED-
OSTEOARTHRITIS
Presence of diabetes mellitus significantly increases pain intensity of joints with OA. There was higher pain intensities found in patients with diabetes based on both Knee Injury and Osteoarthritis Outcome Score (KOOS) and a numeric rating scale (NRS) (Eitner et al. 2021).
Similarly, in the study by (Alenazi et al. 2020), patients with knee OA and DM had greater pain ratings compared to those without DM. Both of these studies share a few similar limitations which included not being specific in terms of types and duration of DM, individual pain sensitivity, and previous history of knee injuries or surgeries.
FIGURE 1 Hypothetical Framework of the Associations between Diabetes and Osteoarthritis. *BCAA – branched-chain amino acids; AGEs – advanced glycation end products; TCA – tricarboxylic acid
Hyperglycaemia in DM is deduced to cause microvascular damage, release of proinflammatory cytokines and hypoxia (Fowler, 2008). DM is also known to cause changes at nerve endings such as in voltage-gated sodium channel expression and phosphorylation (Hong et al. 2004), resulting in production of abnormal activity of nociceptive fibres. This could be one of the reasons why people with OA who also have DM may present with more pain.
In addition, joint space narrowing (JSN) was approximately two times greater in people with type 2 diabetes in comparison to those without diabetes (Eymard et al. 2015). In the same study, from the subgroup analysis, it was found that there are gender differences in the associations in which type-2 diabetes was a significant predictor of JSN in males but not in females. However, a few factors that may be related to disease progression of knee OA at baseline, such as physical activity was not considered, suggesting the need for future study in this area.
IMPLICATION OF DIABETES- INDUCED-OA
To date, there are no available studies that have been conducted on population with diabetes- induced osteoarthritis due to the nature of late diagnosis in OA. Moreover, previous research have been focused on the rate of arthroplasty to measure the adverse effects of DM on OA progression (King & Rosenthal 2015). Thus, in this narrative review, studies involving OA population with and without diabetes were included to examine the impact of DM on OA in term of physical performance, psychological status, physical activity, and social participations.
PHYSICAL PERFORMANCE
In term of physical performance among people with diabetes-induced knee OA, there are a few studies as summarised in Table 1. Alenazi et al.
(2020) did a study to investigate the association between diabetes and walking speed performance (Alenazi et al. 2020). The authors found that most people with knee OA and DM had slower walking speed compared those with knee OA without diabetes. While the study by (Zaharia et al. 2021) showed that people with knee OA and type-2 DM had about 60% and 22% lower isometric knee extension strength and knee range of motion respectively compared to people with knee OA without type-2 DM. Similarly, people with knee OA and type-2 DM had lower grip strength and balance skills when compared to those with knee OA and without type-2 DM (Zaharia et al. 2021).
Generally, there is still lack of information in diabetes-induced knee OA population with objective assessments and outcome measures based on physical performance. Besides, questionnaires are considered to be subjective and may lead to different findings based on the tolerance, sensitivity, and perspective of the individuals in different geographical areas. Thus, objective assessments based on outcome measures are recommended to understand specifically the major physical components that are affected. It may consist of the prerequisites of physical performance, such as walking speed, endurance, grip strength, lower limb strength, and dynamic balance.
Based on the study by Wallis et al. (2019) people who are diagnosed with OA have restrictions in terms of social participation, namely taking public transportation. This could be explained by loading of the lower limb joints, prolonged walking, and overuse of the affected joints (Wallis et al. 2019). Apart from that, limitation in physical activity and social participation could be interlinked to the psychological issues such as social isolation (Siviero et al. 2020). In regard to correlation between OA and DM, there are also limited studies and these conditions have been addressed separately or on its own.
PSYCHOLOGICAL STATUS
In regard to the psychological status, a systematic review study on thirteen studies had suggested that people with knee OA are most likely to have psychological impact. These may include frustrations, fear of not being able to perform certain activities, depression and lower self- efficacy (Wallis et al. 2019). Hsu et al. (2015), in his study on primary family caregivers’
observations and perceptions towards their older relatives about knee OA pain and pain management, carers claimed that people with OA always easily got angry and upset due to joint pain.
The effects of osteoarthritis on psychological status have been highlighted in most prior studies, but additional pathologies connected to the co- existence of diabetes has been overlooked. A longitudinal cohort study based on the public osteoarthritis initiative (OAI) database has been conducted to see if there was a deterioration of symptoms in terms of knee pain and mental health status in patients with OA who also had diabetes (Eitner et al. 2021). In participants with OA and DM, 14.4% of them had significant depressive symptoms (CES-D ≥16) compared to those with OA only (9.1%).
In addition to other illnesses, patients with osteoarthritis and diabetes can feel persistent pain.
Based on American Pain Society and the International Association for the study of pain,
chronic pain can be defined as pain that persisted for a long time (beyond normal tissue healing) approximately in 3 months (Chou et al. 2009;
International Association for the Study of Pain (1986). People with chronic pain are more prone to experience psychological problems compared to those without chronic pain (Gureje et al. 1998).
This is because when chronic pain of long term conditions such as OA, the pain can be amplified
from the original pathophysiology, with increased negative consequences on both physical and psychological statuses (Chou et al. 2009). Even though there are limited studies that examined the effects of OA associated with DM towards participants’ psychological status, we can have a glimpse of the problems as people with both OA and diabetes may experience chronic pain which consequently impact their mental health.
TABLE 1 Summary of studies on Implication of Diabetes-induced-Osteoarthritis Implication Author,
Year
Study Design/Name
Sample Findings
Physical Performance
Eitner (2021)
Cross-sectional study/the Osteoarthritis Initiative.
OA+DM=202 OA-DM=2,279
Medical Outcomes Study Short Form 12 questionnaire (β = – 1.42 [95% CI = –2.57, –0.26]), physical component summary score (β = –3.49 [95% CI = – 4.73, –2.25])
Zaharia (2021)
Cross-sectional study/German Diabetes Study
OA+DM=17 OA-DM=22 (Underwent intravenous glucose tolerance and hyperinsulinemic- euglycemic clamp tests)
Patients with type 2 diabetes and osteoarthritis had lower musculoskeletal function, which included isometric knee extension strength, range of motion, balancing skills, and hand grip strength, as compared to controls with osteoarthritis.
Alenazi (2020)
Cross-sectional study/ the Osteoarthritis Initiative.
knee OA+DM = 236, knee OA-DM = 1554
Diabetes was associated with decreased walking speed (B =
−0.064; 95% CI = −0.09 to
−0.03).
Eitner (2021)
Cross-sectional study/ the Osteoarthritis Initiative.
OA+DM=202 OA-DM=2,279
The Physical Activity Scale for the Elderly: non-statistically significant.
Psychological status
Eitner (2021)
Cross-sectional study
OA+DM=202 OA-DM=2,279
Center for Epidemiological Studies-Depression
(β = 1.08 [95% CI = 0.08, 2.08])
Participants with OA and DM had significant depression symptoms compared to OA participants without DM
*OA – osteoarthritis; DM – diabetes mellitus.
CONCLUSION
This review highlighted that the pathophysiology of diabetes-induced osteoarthritis is still unclear, and more research is needed. While, only in a few studies, its effects on physical performance and psychological statuses are investigated, it is
important to note that its combined effects are possibly intensified. Future research should focus on the clinical presentation, molecular profile and physical performance of diabetes-induced osteoarthritis phenotype, which could aid in the understanding of the condition and help with tailored intervention planning.
ACKNOWLEDGEMENT
This study was supported by the Fundamental Research Grant Scheme grant from the Malaysia’s
Minister of Higher Education
(FRGS/1/2021/SKK0/UKM/02/15).
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Sumaiyah Mat Seow Shi Rui Nor Fadilah Rajab Suzana Shahar
Devinder Kaur Ajit Singh
Centre For Healthy Ageing and Wellness Faculty of Health Sciences
Universiti Kebangsaan Malaysia 50300 Jalan Raja Muda Abdul Aziz Wilayah Persekutuan Kuala Lumpur Malaysia
Teoh Jun Jie Amyra Mohd Yusup Physiotherapy programme Faculty of Health Sciences Universiti Kebangsaan Malaysia Faculty of Health Sciences Universiti Kebangsaan Malaysia 50300 Jalan Raja Muda Abdul Aziz Wilayah Persekutuan Kuala Lumpur Malaysia
Corresponding author: Sumaiyah Mat E-mail: [email protected] Tel: +603-9289 7159
Fax: +603-9289 7161 Received: 30 December 2021 Revised: 5 April 2022
Accepted for publication: 20 May 2022