1 Introduction

Diabetes mellitus (DM) is recognized as one of the century's major health challenges, having a significant impact on individuals, the healthcare system, and communities globally.^1–3 With an alarming rise in the prevalence rate, diabetes has transcended the boundaries and affected populations across the globe. The International Diabetes Federation (IDF) reported in 2021 that 537 million adults worldwide have diabetes, a figure that might climb to 643 million by 2030.³ DM leads to disabling vascular and non-vascular complications.⁴ Persistent hyperglycemia in type 2 DM predisposes an individual to stiffness and musculoskeletal pain due to the accumulation of glycation end-products.^5–7

In general, pain mechanisms have been categorized as nociceptive, neuropathic, nociplastic, and idiopathic.⁸ Musculoskeletal pain (MSK) is a common yet frequently neglected complication of diabetes mellitus, presenting significant challenges for diagnosis and management. Musculoskeletal pain (MSK) may be either primary (predominantly nociplastic) or secondary (predominantly nociceptive).⁷ The International Statistical Classification of Diseases and Related Health Problems (ICD-11) codes define chronic primary MSK pain as pain that lasts longer than three months and causes significant emotional distress or functional disability that cannot be explained by another condition.

Four clinical criteria were put forth by Kosek et al.⁹ to identify nociplastic pain that affects the musculoskeletal system: 1) The pain is not discrete; it is regional. 2) Pain duration: more than 3 months. 3) Its cause cannot be fully explained by a nociceptive or neuropathic mechanism. 4) Clinical signs of pain hypersensitivity are present in the region of pain.

Diabetes mellitus is an endocrine disorder, affecting multiple systems. Diabetes-related diseases and comorbidities significantly lower patients' quality of life.¹⁰ Musculoskeletal pain is one of the obstacles to maintaining adequate physical activity.¹¹ Because diabetic neuropathy and musculoskeletal conditions are linked to persistent hyperglycemia, comorbid chronic pain is a common symptom of type 2 diabetes mellitus (T2DM).^7,12,13 We hypothesized that chronic musculoskeletal pain is more prevalent in people with diabetes as compared to the general population. In addition, we also hypothesized that participants who reported multiple regional pains had higher HbA1c levels than those who reported pain localized to one region.

The study aimed to evaluate the prevalence of cMSK pain and its association with diabetes and glycaemic control and to evaluate comorbid conditions of chronic MSK pain.

2 Methods and material

A prospective case-control study was conducted at a level 1 tertiary care facility from April to July 2024. The approval of the ethical committee was acquired (Ref no: IRB/TA/GH/ORTHO/2024/015). Patients with type-2 diabetes mellitus above 30 years of age who visited our hospital's outpatient department participated in the study (study group).

3 Results

Demographic details of the study population have been mentioned in Table 1. The overall prevalence of chronic musculoskeletal (cMSK) pain in our study was 23.3 % (140 out of 600). Our study group (Group-1/Diabetic Group) includes 300 diabetic patients, of whom 83 (27.7 %) have a history of cMSK pain, and among the control group (Group-2/Healthy Cohort), 57 (19 %) out of 300 have a history of cMSK pain (Fig. 1). On comparative analysis between diabetic group and cohort group, we found that there is a significant association between diabetes mellitus and chronic musculoskeletal pain (P = 0.012), and the odds ratio between the groups was found to be 1.6.

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Fig. 1 Image demonstrating a bar chart for comparing the prevalence of chronic musculoskeletal (cMSK) pain between group 1 (diabetic group) and group 2 (healthy cohort).

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Among the 600 individuals, we found that 330 were males and 270 were females, and cMSK pain was reported by 140 patients out of which 77 were females (28.5 % females had MSK pain) and 63 were males (19.1 % males had MSK pain). We analyzed the association of gender with musculoskeletal pain and found that females have a significantly higher association with MSK pain compared to males (P = 0.007) (Table 2).

Group-1 (diabetic group): We had 300 diabetic mellitus patients in Group-1 with a mean age of 54 ± 12.1 years, with 171 males and 129 females. The mean random blood sugar levels were 158.5 ± 69.5 and the mean HbA1c level was 8.4 ± 2.3 (range: 5.2 to 18.2). On the age-wise distribution of the study population, we found that most of the population belonged to the 5th decade (35.4 %) of age. Among these 300 patients, 73 % (219 of 300) of diabetic patients were on oral hypoglycemic agents (OHA) alone, 4.6 % (14 of 300) were taking insulin alone, and 21.4 % (64 of 300) were on a combination of OHA and insulin; however, 1 % (3 out of 300) of the study population maintained only diet control (Table 1).

Musculoskeletal pain was reported by 27.7 % of diabetics (83 out of 300). The shoulder (32.5 %) was the most involved region, followed by the knee (29 %), and the least involved region was the elbow joint (4.8 %) (Table 3, Fig. 2). Among diabetics, 22.3 % (67 out of 300) reported sensory problems such as pricking, burning, numbness, or a combination of these in either the upper or lower limbs. Details of pain distribution and regions involved based on body segment have been mentioned in Table 3. Among our study population, we analyzed other associated co-morbidities and their relationship with chronic musculoskeletal pain. We found that along with DM, 79 patients had hypertension (P = 0.5), 53 had dyslipidemia (P = 0.191), and 16 of them had hypothyroidism (P = 0.133). None of these co-morbidities showed statistically significant association with chronic musculoskeletal pain (P > 0.05) (see Table 4).

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Fig. 2 Image demonstrating the distribution of chronic musculoskeletal (cMSK) pain in one or more of the body regions among group 1 (diabetic group) and group 2 (healthy cohort).

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Based on HbA1c levels, we divided the study population into three subgroups: group-1A (HbA1c of less than 8), group-1B (HbA1c of 8–12), and group-1C (HbA1c level of more than 12). Out of 300 patients, 148 were in group 1A, 130 were in group 1B, and 22 were in group 1C (Fig. 3). On subgroup analysis, we found that there is a significant association between chronic musculoskeletal pain and HbA1c levels (p < 0.005). and we also found that the group-1C individuals reported involvement in multiple regions (more than two regions involved) compared to those with group-1B and group-1A individuals, and the difference was found to be statistically significant (p = 0.002) (Fig. 4).

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Fig. 3 Image demonstrating the Distribution of population based on HbA1c levels: group 1A (HbA1c of less than 8), group 1B (HbA1c level between 8 and 12), group 1C (HbA1c of more than 12) and their association with chronic musculoskeletal pain.

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Fig. 4 Image demonstrating the number of body regions involved with chronic musculoskeletal (cMSK) pain based on HbA1c levels: group 1A (HbA1c of less than 8), group 1B (HbA1c level between 8 and 12), group 1C (HbA1c of more than 12).

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Group-2 (Healthy Cohort): We included 300 healthy non-diabetic cohorts in Group 2 with a mean age of 47.2 ± 11 years; males were 159 and females were 141. The mean random blood sugar levels were 97.5 ± 23. On the age-wise distribution of the study population, we found that most of the population belonged to the 5th decade (33.7 %) (Table 1).

Musculoskeletal pain in one or more regions was reported by 19 % of healthy non-diabetic cohorts (57 out of 300); among these 57 patients, the pain was most reported in the knee joint (36.8 %), followed by low back pain (30 %), and the least involved region was the wrist joint (3.5 %) (Fig. 2, Table 3).

4 Discussion

Diabetes mellitus causes alterations in the peri-articular system, skeletal systems, and connective tissues in a variety of ways.¹⁵ Hyperglycaemia leads to low pain thresholds in individuals with diabetes mellitus.¹⁶ Advanced glycation end products (AGEs) accumulation and their crosslinking of collagen may contribute to the development of musculoskeletal complications.^16,17 Pain is a frequent comorbidity in patients with diabetes and can arise from various sources. Musculoskeletal pain is particularly common, with recent data indicating that individuals with diabetes are 1.7–2.1 times more likely to experience chronic musculoskeletal pain compared to those without the condition.^{7,12,16,18,19} With this study, we report the overall prevalence of chronic musculoskeletal pain to be 23.3 %. However, the incidence of cMSK pain is higher in patients with diabetes mellitus compared to the non-diabetic population, 27.7 % and 19 %, respectively. The odds ratio between the groups was analyzed and found to be 1.6.

Studies have shown an association between gender and MSK pain, where women are more prone to musculoskeletal pain compared to men.^20–23 Similarly, our study found that females have a significantly higher association with cMSK pain than males (P = 0.007). Pai et al.,²⁴ in their study, found that the 10-year cumulative incidence of musculoskeletal pain for both the diabetic and non-diabetic groups was higher in females than males. Studies also concluded that pain thresholds were lower in females than males.

Increased HbA1c levels have associations with chronic musculoskeletal pain. It is possible that neurohormones partially mediate the relationship between pain and higher HbA1c levels. Pain triggers the release of many neurohormonal substances, including cortisol, which have been associated with higher serum glucose values in patients with diabetes. The study by Carvalho-e-Silva et al. identified shoulder, knee, and hip pain as prominent issues, consistent with the present study's findings (table). Abaraogu et al.¹² reported that individuals with Type 2 Diabetes Mellitus (T2DM) are 29 times more likely to experience chronic musculoskeletal pain in the upper back and knee compared to healthy individuals. Additionally, the study by Ramchurn et al., which had a mean HbA1c of 9.1 %, found a significant prevalence of upper limb involvement among diabetic patients with concurrent shoulder and hand problems. Singh et al.'s study on an Indian population revealed a significant association between high Body Mass Index (BMI), elevated HbA1c levels, and the prevalence of musculoskeletal manifestations in diabetic patients, with 50.7 % of the diabetic subjects exhibiting such manifestations.²⁵ In our study, we found that patients with higher HbA1c levels are more prone to cMSK pain, and the difference was found to be statistically significant (p < 0.005). We also found that significantly a greater number of patients with higher HbA1c levels reported cMSK pain in multiple regions. (p = 0.002) (table).

One of the most debated topics in the relationship between diabetes and chronic musculoskeletal issues is whether diabetes affects all musculoskeletal systems of the body equally, regardless of their location. There are differing opinions on this matter. Some argue that diabetes primarily impacts only the musculoskeletal structures of the extremities.^{16,18,26–28} However, research has shown that individuals with Type 2 Diabetes Mellitus (T2DM) also experience difficulties with trunk muscles and other postural muscles during more strenuous tasks. This impairment in postural control can lead to abnormal biomechanics within the musculoskeletal system. As a result, these abnormalities may contribute to a range of different musculoskeletal problems. In our diabetic group, the most, commonly involved region was the shoulder. Shoulder pain was reported by 35.5 % of individuals either as a single region being involved or in association with other region pain. However, in the control group of non-diabetic individuals, the majority of them reported knee involvement. Elbow joint and wrist joint pain were least reported among diabetic and non-diabetic individuals, respectively. In our study, we also analyzed the role of associated co-morbidities like hypertension, dyslipidemia, and hypothyroidism in patients with diabetes mellitus, and we found that none of these co-morbidities showed a significant association with chronic musculoskeletal pain (P > 0.05).

The major strength of our study lies in its design and methodology. Our study relied on patient-reported symptoms gathered through a questionnaire rather than on objectively measured clinical signs, and we evaluated a group of patients and compared their results with a well-matched control group using the same methodology. By doing so, we highlighted a significant clinical issue with appropriate attention. However, our study has some limitations; the questionnaire did not allow identification of any specific cause of pain, and further investigations to diagnose pathology were not done.

5 Conclusion

This study highlights the higher prevalence and significant impact of musculoskeletal pain in diabetic patients compared to non-diabetic individuals. Addressing musculoskeletal pain is crucial for improving the overall quality of life in diabetic patients. Clinicians should adopt a proactive and comprehensive approach to pain management in diabetics.

Using a simple Nordic questionnaire during routine check-ups helps with screening of joint and surrounding soft tissue pathology, preventing future complications that could lead to disability.

CRediT authorship contribution statement

Owais Ahmed: Writing – original draft, Data curation, Formal analysis, Investigation, Validation, Visualization. Suresh R Prabhu: Conceptualization, Supervision, Validation, Writing – review & editing. Ajoy Prasad Shetty: Conceptualization, Methodology, Project administration, Supervision, Validation, Writing – review & editing. A. Nousy: Data curation, Validation. Mohamed Zackariya: Supervision, Validation, Writing – review & editing. Dheenadhayalan Jayaramaraju: Writing – review & editing, Project administration, Supervision. Abishek Sivan: Data curation, Validation. Rajasekaran Shanmuganathan: Methodology, Writing – review & editing, Project administration, Supervision, Resources.

Patient consent

Verbal consents were obtained from the subjects before collecting the questionnaire and survey.

Ethical statement

No ethical concerns.

Ethical committee clearance and Institutional review board approval was obtained.

Funding statement

We authors declare that this study has not received financial support or funding.

There is no source of funding to disclose.