Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Sustained elevation of blood glucose levels leads to a wide spectrum of systemic complications that significantly contribute to morbidity and reduced quality of life¹. Chronic hyperglycemia adversely affects cellular function through multiple mechanisms, including non-enzymatic glycation of proteins, increased oxidative stress, and activation of inflammatory pathways.² These processes result in structural and functional alterations of connective tissue by modifying extracellular matrix components such as collagen, proteoglycans, and elastin, ultimately leading to tissue stiffness, reduced elasticity, and impaired repair mechanisms. Such pathological changes form the basis for many long-term complications observed in individuals with diabetes.^3,4While vascular complications of diabetes, including retinopathy, nephropathy, neuropathy, and macrovascular disease, have been extensively studied and well documented, musculoskeletal (MS) manifestations of diabetes have received comparatively little attention. Musculoskeletal disorders in diabetes encompass a broad range of conditions such as adhesive capsulitis, limited joint mobility, diabetic cheiroarthropathy, Dupuytren’s contracture, trigger finger, carpal tunnel syndrome, osteoarthritis, and diabetic muscle infarction.⁵ These conditions can lead to chronic pain, joint stiffness, functional limitation, and disability, thereby substantially affecting daily activities and overall well-being of diabetic patients.^6,7 Despite their clinical relevance, MS disorders are often underdiagnosed and undertreated, as they may be overshadowed by more commonly recognized vascular complications⁸. Importantly, there is a striking paucity of data from the Indian subcontinent, where the burden of diabetes is rapidly increasing and poses a major public health challenge. India is home to one of the largest populations of individuals with diabetes globally, with unique demographic, genetic, lifestyle, and socioeconomic factors that may influence the pattern and prevalence of diabetic complications.^9-13 Differences in occupational activities, physical workload, nutritional status, healthcare access, and health-seeking behaviour may further modify the clinical spectrum of musculoskeletal disorders in Indian diabetic patients. The lack of region-specific data limits awareness among clinicians and hampers the development of targeted screening and management strategies for these conditions.

AIM

To examine the musculoskeletal manifestations in patients with diabetes mellitus and their correlation with disease duration, microvascular and macrovascular complications, and other associated factors at a tertiary care center in Northwest Rajasthan.

This cross-sectional study was conducted at the Diabetic Research Centre, Bikaner over a period of 1 yr from jan 2024 to dec 2024. The study population comprised patients with diabetes mellitus attending the outpatient department (OPD) of the Diabetic Research Centre during the study period. All consecutive diabetic patients who fulfilled the eligibility criteria were approached and screened for participation. Patients aged 14 years and above, with a known diagnosis of diabetes mellitus (either type 1 or type 2), and who were willing to participate in the study were included after obtaining informed consent. Patients who refused to provide consent were excluded from the study. In addition, patients with active COVID-19 infection, those suffering from infectious diseases known to affect the musculoskeletal system such as tuberculosis, chikungunya, or brucellosis, and those with previously diagnosed rheumatic or connective tissue disorders including rheumatoid arthritis and systemic lupus erythematosus were excluded to avoid confounding. Patients receiving long-term steroid therapy or other medications known to affect bone and muscle metabolism were also excluded. Eligible participants were enrolled and evaluated according to the study protocol to assess the prevalence of musculoskeletal manifestations in diabetic patients and to analyze associated factors.

Table 1 Age Wise distribution of cases

The age-wise distribution showed that the largest proportion of patients were in the 46–60 years age group (39.4%), followed by those aged 61–80 years (23.71%). Younger age groups of 31–45 years and 18–30 years accounted for 20% and 16.8% of the study population, respectively.

Table 2: Distribution of BMI among patients in our study

The BMI distribution indicated that the majority of patients were in the 23–24.9 kg/m² category, constituting 63.14% of the study population. Normal BMI and overweight categories accounted for smaller proportions, while underweight and obese individuals formed a minimal percentage of cases.

Table 3: Distribution of study patients according to duration of diabetes , type of microvascular and  macrovascular complication among patients

Most patients had a disease duration of 1–5 years (58%), followed by 6–10 years (20%), while longer durations were less frequent. Among complications, neuropathy (25%) was the most common microvascular complication, and coronary artery disease (16.57%) was the predominant macrovascular complication, with fewer cases of stroke and peripheral arterial disease.

Table 4: Distribution of Musculo skeleton complication among patients in our study

Musculoskeletal complications were present in 36.5% of patients, with osteoarthritis being the most frequent (13.1%), followed by shoulder capsulitis (9%) and limited joint mobility (5%). Other complications such as Charcot joint, Dupuytren’s contracture, carpal tunnel syndrome, and miscellaneous conditions were observed less commonly.

Table 5: correlation of musculoskeletal complication with micro and macro vascular complication

Musculoskeletal complications showed a statistically significant association with microvascular complications (p = 0.0001), with a higher proportion of musculoskeletal involvement among patients having microvascular disease. In contrast, the association between musculoskeletal and macrovascular complications was not statistically significant (p = 0.051).

Figure 1,2,3: Association of musculoskeletal manifestation with type to diabetes, micro vascular and macro vascular complication

The majority of patients were aged 41–50 years, followed by 31–40 and >50 years, with the least in 18–30 years. Overall, middle-aged adults formed the largest proportion of the study population. Musculoskeletal complications were common among patients with retinopathy, nephropathy, and neuropathy, with Dupuytren contracture and limited joint mobility being the most frequent. The differences in prevalence across these groups were statistically significant (p = 0.0001). Musculoskeletal complications were observed in patients with stroke, CAD, and PAD, with limited joint mobility and osteoarthritis being the most common. However, the differences among these groups were not statistically significant (p > 0.05).

Table 6: Association of musculoskeletal manifestation with biochemical investigations

Patients with musculoskeletal complications exhibited significantly higher levels of HbA1c, HsCRP, and ESR, and significantly lower levels of vitamin D compared to those without musculoskeletal complications. However, no significant differences were observed for uric acid and ferritin levels

The age-wise distribution of the study population is shown in the table. The largest proportion of patients belonged to the 46–60 years age group, accounting for 39.4% of cases. This was followed by patients aged 61–80 years, who constituted 23.71% of the study population. The 31–45 years age group represented 20% of the patients. Younger adults aged 18–30 years comprised 16.8% of the total population. Overall, middle-aged and elderly individuals formed the majority of the study cohort. Similarly Mahamane Aminou Mahamane Sani et al. (2022)¹⁴ found that out of one hundred (100) diabetic patients with osteoarticular diseases were collected, the average age was 56 years with extremes of 21 and 90 years.

The BMI distribution of the study population showed that the majority of patients were in the 23–24.9 kg/m² category, accounting for 63.14%. Normal BMI (18.5–22.9 kg/m²) was observed in 18% of patients. Overweight individuals (25–29.9 kg/m²) constituted 14.28% of the study population. Underweight patients (<18.5 kg/m²) formed a small proportion at 3.14%.Obesity (>30 kg/m²) was rare, seen in only 1% of cases. Overall, most patients fell within the normal to overweight BMI range. Also RP Agrawal et al. (2013)¹⁵ found that among various risk factors BMI (odd ratio: 7.429) were common risk factors.

The majority of patients had a disease duration of 1–5 years, accounting for 58% of the study population. This was followed by a duration of 6–10 years in 20% of patients. Longer disease durations of 11–15 years and more than 15 years were observed in 7% and 14% of cases, respectively. Among microvascular complications, neuropathy was the most common, affecting 25% of patients. Retinopathy and nephropathy were seen in 17% and 16.2% of patients, respectively. Regarding macrovascular complications, coronary artery disease was the most frequent (16.57%), while stroke and peripheral arterial disease were less common.

Musculoskeletal complications were observed in 128 patients, accounting for 36.5% of the study population. Osteoarthritis was the most common manifestation, seen in 13.1% of patients. Shoulder capsulitis was the next most frequent complication, affecting 9% of cases. Limited joint mobility was noted in 5% of patients, while Charcot joint was present in 3.4%. Dupuytren’s contracture (2.8%) and carpal tunnel syndrome (1.43%) were less commonly observed. Other musculoskeletal conditions together contributed to 2.5% of the cases.

Musculoskeletal complications were analyzed in relation to both microvascular and macrovascular complications. Among patients with musculoskeletal involvement, a higher number had associated microvascular complications compared to those without. This association between musculoskeletal and microvascular complications was found to be statistically significant (p = 0.0001). In contrast, the distribution of macrovascular complications was comparable between patients with and without musculoskeletal involvement. The association between musculoskeletal and macrovascular complications did not reach statistical significance (p = 0.051). Similarly Mahamane Aminou Mahamane Sani et al. (2022)¹⁴ observed that the presence of one or more degenerative complications of diabetes (nephropathy, retinopathy, nephropathy) was the most frequent factor associated with musculo skeletal complication in diabetic patients.

The study included a total of 350 participants with varying ages. The majority of patients, 138 (39.4%), were between 46 and 60 years old. Participants aged 61–80 years accounted for 83 (23.71%), while 70 (20%) were between 31 and 45 years. Younger adults aged 18–30 years comprised 59 (16.8%) of the study population. The data indicates that middle-aged and older adults formed the bulk of the cohort. This distribution is important for understanding age-related trends in the studied condition.Also RP Agrawal et al. (2013)¹⁵ observed that the manifestations were more common in type 1 diabetes (62.7%).

Among patients with diabetic complications, musculoskeletal disorders were common across those with retinopathy, nephropathy, and neuropathy. Dupuytren contracture was the most frequent complication in retinopathy (19%) and nephropathy (23%), while Charcot joint was predominant in neuropathy (15%). Limited joint mobility and osteoarthritis were also significant, affecting 7–18% of patients depending on the complication type. Carpal tunnel syndrome and shoulder capsulitis were less common, ranging from 3% to 10%. Other musculoskeletal issues were rare, affecting around 3% of patients. Overall, the prevalence of musculoskeletal complications was significantly higher in patients with retinopathy (70%), nephropathy (74.24%), and neuropathy (56%), with a p-value of 0.0001, indicating strong statistical significance.

The conclusion of the study highlights the significant relationship between diabetes and the prevalence of musculoskeletal manifestations. It may indicate that longer duration of diabetes correlates with an increased risk of both microvascular and macrovascular complications, which in turn contribute to various musculoskeletal issues. Additionally, the study might emphasize the importance of early detection and management of these complications to improve the quality of life for diabetic patients. It could also suggest that healthcare providers should consider musculoskeletal symptoms as integral to diabetes management, given their potential impact on mobility and overall health. Finally, the conclusion may call for further research to explore the underlying mechanisms and to develop effective interventions for managing these manifestations in diabetic patients.

1. Resnick D, Niwayama G, compilers. In: Diagnosis of bone and joint disorders. Philadelphia: WB Saunders; 1988. pp. 1563–1615.
2. Botek G, Anderson MA, Taylor R. Charcot neuroarthropathy: An often overlooked complication of diabetes. Cleve Clin J Med. 2010;77:593–599.
3. Gamstedt A, Holm-Glad J, Ohlson CG. Hand abnormalities are strongly associated with the duration of diabetes mellitus. J Intern Med. 1993;234:189.
4. Gulliford , Latinovic, Charlton Increased incidence of carpal tunnel syndrome up to 10 years before diagnosis of diabetes. Diabetes Care. 2006;29:1929.
5. Verdugo RJ, Salinas RA, Castillo J. Surgical versus non-surgical treatment for carpal tunnel syndrome. Cochrane Database Syst Rev. 2008
6. Ryzewicz M, Wolf JM. Trigger digits: principle management, and complications. J Hand Surg Am. 2006;31:135–146.
7. Owens H, compiler. In: Frozen shoulder. In: Donatelli R, Orthopedic physical therapy. New York: Churchill Livingston; 1996. pp. 257–277.
8. Mavrikakis ME, Drimis S, Kontoyannis DA. Calcific shoulder periarthritis (tendinitis) in adult onset diabetes mellitus: a controlled study. Ann Rheum Dis. 1989;48:211–214.
9. Manske RC, Prohaska D. Diagnosis and management of adhesive capsulitis. Curr Rev Musculoskelet Med. 2008;1:180–189.
10. Dacre JE, Beeney N, Scott DL. Injections and physiotherapy for stiff shoulder. Ann Rheum Dis. 1989;48:322–325.
11. Arkkila PE, Gautier JF. Musculoskeletal disorders in diabetes mellitus: An update. Best Practice and Research Clinical Rheumatology. 2003;17:945–970.
12. Fournier K, Papanas N, Compson JP. A diabetic patient presenting with stiff hand following fasciectomy for Dupuytren's Contracture. A case report. Cases J. 2008;1:277.
13. Katzman BM, Steinberg DR, Bozentka DJ. Utility of obtaining radiographs in patients with trigger finger. Am J Orthop. 1999;28:703–705.
14. Sani MAM, Daou M, Alzouma RH et al. Epidemiological Aspects of Osteoarticular and Rheumatological Diseases Related to Diabetes in Niger. Journal of Diabetes Mellitus. 2022;12:263-270.
15. Agrawal RP, Gothwal S, Tantia P, Agrawal R, Rijhwani P, Sirohi P, Meel JK. Prevalence of Rheumatological Manifestations in Diabetic Population from North-West India. J Assoc Physicians India. 2014 Sep;62(9):788-92. PMID: 26259313.
16. Majjad A, Errahali Y, Toufik H, H Djossou J, Ghassem MA, Kasouati J, et al. Musculoskeletal Disorders in Patients with Diabetes Mellitus: A Cross‑Sectional Study. Int J Rheumatology 2018;2018:3839872. doi: 10.1155/2018/3839872.
17. Jena D, Sahoo J, Barman A, Behera KK, Bhattacharjee S, Kumar S. Type 2 diabetes mellitus, physical activity, and neuromusculoskeletal complications. J Neurosci Rural Pract. 2022 Oct-Dec;13(4):705-710. doi: 10.25259/JNRP_11_2022. Epub 2022 Dec 2. PMID: 36743753; PMCID: PMC9893944.