First metatarsophalangeal joint synovial hypertrophy associated with vitamin D status in type 2 diabetes mellitus: An ultrasound-graded study

Abstract

BACKGROUND

The existing semi-quantitative ultrasound grading system inadequately evaluates synovial hypertrophy at the dorsal recess of the first metatarsophalangeal joint (MTPJ). Vitamin D deficiency is prevalent in type 2 diabetes mellitus (T2DM) and may influence joint inflammation. This study hypothesizes that serum 25-hydroxyvitamin D [25(OH)D] levels are inversely associated with synovial hypertrophy severity of the first MTPJ in patients with T2DM.

AIM

To refine ultrasound grading for the first MTPJ synovial hypertrophy and investigate its association with vitamin D in T2DM.

METHODS

This cross-sectional study included 56 patients (112 MTPJs) with T2DM from Shenzhen Traditional Chinese Medicine Hospital. Synovial hypertrophy was evaluated using a refined semi-quantitative ultrasound grading system focusing on the dorsal recess overlying the metatarsal bone. Serum 25(OH)D levels were measured. Logistic regression and threshold analyses assessed associations between vitamin D status and hypertrophy severity.

RESULTS

Of 112 joints assessed, 98 exhibited synovial hypertrophy (grade 1: 40; grade 2: 50; grade 3: 8). The refined grading system demonstrated strong intra- and inter-observer reliability (intraclass correlation coefficients = 0.79 and 0.73, respectively). Lower serum 25(OH)D (< 24.3 ng/mL) was independently associated with moderate-to-severe hypertrophy [odds ratio (OR) = 0.83; P = 0.0163]. Vitamin D deficiency significantly increased the likelihood of moderate-to-severe hypertrophy compared with non-deficiency (OR = 3.86; P = 0.0422). Threshold analysis identified 23.8 ng/mL as a critical serum 25(OH)D level, below which each increment reduced moderate-to-severe hypertrophy risk by 21% (OR = 0.79; P = 0.0078).

CONCLUSION

The refined ultrasound grading system demonstrated strong reliability. Serum 25(OH)D may serve as a protective factor against the severity of synovial hypertrophy in T2DM patients with lower 25(OH)D levels.

Key Words: Vitamin D; Synovial hypertrophy; Type 2 diabetes mellitus; Metatarsophalangeal joint; Serum 25-hydroxyvitamin D

Core Tip: This study refines a semi-quantitative ultrasound grading system for first metatarsophalangeal joint synovial hypertrophy by introducing a novel subtype that specifically classifies cases of dorsal recess overlying the metatarsal bone, demonstrating high reliability (intra-observer intraclass correlation coefficient = 0.79; inter-observer intraclass correlation coefficient = 0.73). We identified a significant inverse, non-linear correlation between serum 25-hydroxyvitamin D levels and synovial hypertrophy severity, with a threshold effect at 23.8 ng/mL. These findings suggest that vitamin D deficiency may contribute to synovial inflammation in type 2 diabetes mellitus patients and that targeted screening and supplementation could help mitigate joint complications.

INTRODUCTION

Osteoarthritis (OA) is a leading cause of disability worldwide, affecting an estimated 606.5 million people as of 2021[1,2]. The first metatarsophalangeal joint (MTPJ) is one of the foot joints most severely affected by OA[3], contributing to increased foot pain, difficulty in weight-bearing activities, and a higher risk of falls[4,5]. According to the 11^th edition of the IDF Diabetes Atlas, it is estimated that 589 million adults aged 20-79 years were living with diabetes in 2024, and this figure is projected to increase by 45% by 2050. Type 2 diabetes mellitus (T2DM) is now recognized as an independent risk factor for OA, challenging the traditional view that considers OA solely as a degenerative disease[6,7]. Insulin resistance plays an important role in the cause of T2DM[8]. Research has demonstrated that individuals with OA exhibit reduced insulin sensitivity compared to those without OA, irrespective of whether they also have diabetes[9]. Furthermore, OA-related symptoms correlate significantly with the extent of insulin resistance[10]. Interestingly, studies have demonstrated the potential therapeutic efficacy of hypoglycemic agents in treating OA[11,12].

Accumulating evidence indicates that synovitis plays a crucial role in the progression of OA[13], and its prevalence is higher in individuals with T2DM compared to those without diabetes. Chronic hyperglycemia and advanced glycation end products induce oxidative stress, trigger inflammatory response, and increase synovial vascular leakage and immune cell infiltration, all contributing to synovitis and joint degeneration[14-17]. Prior research has shown that synovitis in OA is associated with severe pain, radiographic progression, and greater joint dysfunction, particularly in weight-bearing joints like the knee[13,18]. Notably, inflammation of the foot joints may serve as a prognostic indicator for the development of diabetic foot[19]. However, research focusing on synovial inflammation in the MTPJ, particularly in the context of diabetes, remains scarce.

Vitamin D has been implicated in various musculoskeletal and inflammatory conditions[20]. Furthermore, vitamin D deficiency is highly prevalent among patients with T2DM[21]. Studies have demonstrated an association between low vitamin D levels and radiographic progression of knee OA, increased joint pain, and higher diabetic foot severity scores[22,23]. However, most of these studies have focused on clinical symptoms or radiographic changes in joint structure rather than directly assessing synovitis. Synovitis may manifest earlier than other structural changes in OA and could serve as a potential predictive factor of cartilage degeneration and disease progression[24,25]. Despite these findings, the direct relationship between serum vitamin D levels and synovitis in patients with T2DM remains underexplored.

Musculoskeletal ultrasound is highly recommended by the European Society of Musculoskeletal Radiology for detecting synovial inflammation[26]. It provides sensitivity that is comparable to that of magnetic resonance imaging[27,28]. OMERACT studies on hand OA have revealed that synovial hypertrophy is more prevalent (45%) than Doppler signals (6%), suggesting that reliance solely on Doppler signals might lead to underestimation of OA-related synovitis[29]. OMERACT defines synovitis as the presence of hypoechoic synovial hypertrophy, regardless of joint effusion or Doppler activity, emphasizing the need for semi-quantitative grading[30]. To our knowledge, the dorsal recess of the MTPJ frequently extends proximally and overlies the metatarsal bone[31]. For synovial hypertrophy of the dorsal recess located over the metatarsal bone, the existing semi-quantitative grading system originally developed for rheumatic metacarpophalangeal arthritis may provide less reliable assessments in cases where there is a significant height discrepancy between the apices of the articular surfaces (Figure 1).

Figure 1 Schematic diagram of ultrasonographic semi-quantitative grading of synovial hypertrophy of the metatarsophalangeal joint. M: Metatarsal head; P: Proximal phalanx; SH: Synovial hypertrophy; A: The line connecting the apices; B: The horizontal line of the metatarsal head apex; a: The region between the articulating bones apices; b: The region from metatarsal head apex to diaphysis. For synovial hypertrophy (thickness 0.88 mm) in region b, using line A as the reference line, synovial hypertrophy will be judged as grade 2, and using line B as the reference line, it will be judged as grade 1.

This study aims to develop a refined semi-quantitative ultrasound grading system for MTPJ synovial hypertrophy and explore the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and the severity of synovial hypertrophy in T2DM patients.

MATERIALS AND METHODS

Study design and participants

This cross-sectional study was conducted between March 2023 and January 2024 at Shenzhen Traditional Chinese Medicine Hospital. Ethical approval was obtained from the Shenzhen Traditional Chinese Medicine Hospital Ethics Committee (No. K2023/098/02), and all participants provided written informed consent. Inclusion criteria included patients diagnosed with T2DM according to World Health Organization and American Diabetes Association guidelines. The exclusion criteria were as follows: (1) Patients with gout, hyperuricemia, rheumatoid arthritis, or psoriatic arthritis; (2) A history of trauma or surgery involving the MTPJ; (3) Other types of diabetes; and (4) Those with severe cardiac, hepatic, or renal failure. The sample size was determined based on the exploratory nature of this study, considering the limited availability of similar studies in the existing literature. Statistical significance was defined as P < 0.05. In this study, a total of 72 in patients with T2DM were recruited from the Department of Endocrinology and Metabolism. Following the application of exclusion criteria, 16 participants were excluded, resulting in a final sample size of 56 participants (comprising 112 first MTPJs) for analysis.

Clinical and laboratory assessments

Participants completed standardized questionnaires to collect demographic information, including age, gender, body mass index (BMI), and duration of diabetes. BMI was calculated by dividing the participants’ weight (kg) by the square of their height (m²). Fasting blood samples were collected in the morning for laboratory measurements of serum levels of 25(OH)D, fasting blood glucose, glycated hemoglobin, albumin, and uric acid. The total serum 25(OH)D levels were measured using an electrochemiluminescence immunoassay (Roche Cobas e601 analyzer). According to the Endocrine Society Clinical Practice Guidelines[32], vitamin D deficiency was defined as serum levels below 20 ng/mL in this study.

Ultrasound examination

A Canon Aplio i900 ultrasound machine (Canon Medical Systems, Shimoishigami, Japan) with an 8-24 MHz multifrequency linear transducer was used. Scans were performed with patients in a supine position and the first MTPJ in a neutral position. Synovial hypertrophy was assessed in longitudinal and transverse planes, with grading performed in the longitudinal plane. The grading system was expanded upon EULAR-OMERACT classifications: Grade 0: No synovial hypertrophy; Grade 1: Mild synovial hypertrophy, 1a: Between the apices of the articulating bones without extending beyond the line connecting the apices; 1b: In the region from metatarsal head apex to diaphysis without extending beyond the horizontal line of the metatarsal head apex; Grade 2: Moderate synovial hypertrophy, 2a: Between the apices of the articulating bones, extending beyond the line connecting the apices but with a flat or concave surface; 2b: In the region from metatarsal head apex to diaphysis, extending beyond the horizontal line of the metatarsal head apex but with a flat or concave surface; Grade 3: Severe synovial hypertrophy, 3a: Between the apices of the articulating bones, extending beyond the line connecting the apices but with a convex surface; 3b: In the region from metatarsal head apex to diaphysis, extending beyond the horizontal line of the metatarsal head apex but with a convex surface (Figures 1 and 2).

Figure 2 Ultrasound characteristics of semi-quantitative grading of metatarsophalangeal joint synovial hypertrophy located in the region from metatarsal head apex to diaphysis. A: Mild synovial hypertrophy (1b); B: Moderate synovial hypertrophy (2b); C: Severe synovial hypertrophy (3b). M: Metatarsal head; P: Proximal phalanx; SH: Synovial hypertrophy; Dashed line: The horizontal line of the metatarsal head apex.

Ultrasound evaluations were performed by a musculoskeletal ultrasound expert (QSL, 12 years of experience) blinded to clinical and laboratory data. Intra- and inter-observer reliability was assessed using intraclass correlation coefficients (ICCs), with results indicating strong reproducibility [intra-observer ICC = 0.79, 95% confidence interval (CI): 0.70-0.85; inter-observer ICC = 0.73, 95%CI: 0.63-0.80].

Statistical analysis

Data was analyzed using R (http://www.R-project.org) and Empower Stats (XY Solutions, Boston, MA, United States). Continuous variables were presented as mean ± SD for normally distributed data or median interquartile range (IQR) for non-normally distributed data. Categorical variables were reported as percentages. Group comparisons were conducted using t-tests for normally distributed data, Kruskal-Wallis tests for non-normally distributed data, and χ² tests for categorical variables. Logistic regression models were employed to investigate the associations between serum 25(OH)D levels and the severity of synovial hypertrophy, adjusting for potential confounders. Threshold effects were assessed using segmented logistic regression. Statistical significance was determined at P < 0.05.

RESULTS

Among the 112 assessed joints, 14 displayed no synovial hypertrophy, whereas 98 exhibited varying degrees of hypertrophy (grade 1: 40, grade 2: 50, grade 3: 8). Synovial hypertrophy involving the region from the metatarsal head apex to diaphysis was observed in 43 joints (43.9%), distributed as grade 1 in 18 joints, grade 2 in 19 joints, and grade 3 in 6 joints.

Clinical characteristics of different synovial hypertrophy groups

The clinical characteristics of the participants were stratified based on the severity of synovial hypertrophy, as shown in Table 1. The median age of the participants was 56 years (IQR: 51.0-64.8), with 63.3% being male. The median BMI was 24.1 kg/m² (IQR: 22.5-26.3). Additionally, the median duration of diabetes among participants was 10 years (IQR: 4.0-15.0), and the median glycated hemoglobin level was 8.2% (IQR: 7.4-9.9). The median 25(OH)D level of the participants was 24.3 ng/mL (IQR: 20.0-29.5). Participants were categorized according to their vitamin D levels [low (< 24.3 ng/mL) vs high (≥ 24.3 ng/mL), deficiency (< 20 ng/mL) vs non-deficiency (≥ 20 ng/mL)]. Compared to the group with mild hypertrophy, patients with moderate-to-severe synovial hypertrophy were younger and demonstrated higher albumin levels (P < 0.05). Notably, within the low 25(OH)D group, patients exhibiting moderate-to-severe synovial hypertrophy exhibited lower 25(OH)D levels compared to those with mild synovial hypertrophy (P < 0.05). In addition, a lower proportion of patients in the 25(OH)D deficiency group presented with mild synovial hypertrophy (P < 0.05).

Table 1 Study population characteristics based on the degree of synovial hypertrophy, mean ± SD/n (%).

Variable	Total	Mild	Moderate-severe	P value
Number	98	40	58
Gender				0.896
Male	62 (63.3)	25 (62.5)	37 (63.8)
Female	36 (36.7)	15 (37.5)	21 (36.2)
Age (year), median IQR	56.0 (51.0-64.8)	58.5 (55.0-66.2)	55.0 (47.0-63.8)	0.0221
DD (year), median IQR	10.0 (4.0-15.0)	8.0 (4.0-15.0)	10.0 (3.2-16.5)	0.9421
UA (μmol/L), median IQR	314.5 (275.8-365.0)	314.5 (269.0-393.0)	314.5 (280.0-356.0)	0.3901
FPG (μg/dL), median IQR	6.9 (6.1-9.3)	6.9 (6.2-8.3)	6.5 (6.1-9.7)	0.9911
HbA1c (%), median IQR	8.2 (7.4-9.9)	8.0 (7.3-10.0)	8.2 (7.5-9.6)	0.8511
ALB (g/L)	41.3 ± 3.5	40.3 ± 3.2	42.0 ± 3.6	0.014
BMI (kg/m2), median IQR	24.1 (22.5-26.3)	24.1 (22.6-27.2)	23.9 (22.2-25.4)	0.5011
25(OH)D (ng/mL), median IQR	24.3 (20.0-29.5)	24.6 (22.6-28.4)	22.55 (19.1-29.4)	0.1161
25(OH)D dichotomous
Low, median IQR	19.8 (17.3-22.0)	21.70 (19.4-22.6)	19.1 (15.9-20.2)	0.014
High, median IQR	27.9 (25.3-33.0)	27.3 (25.4-30.9)	30.7 (25.2-36.0)	0.187
25(OH)D status				0.009
Non-deficiency	75 (76.5)	36 (90.0)	39 (67.24)
Deficiency	23 (23.5)	4 (10.00)	19 (32.76)

¹P if the variable is continuous, it is obtained by the Kruskal Wallis rank sum test. If the counting variable has a theoretical number < 10, it is obtained by Fisher’s exact probability test.

DD: Duration of diabetes; UA: Serum uric acid; FPG: Fasting plasma glucose; HbA1c: Glycated hemoglobin; ALB: Albumin; BMI: Body mass index; IQR: Interquartile range; 25(OH)D: 25-hydroxyvitamin D.

Association between vitamin D levels and synovial hypertrophy

Table 2 presents the univariate logistic regression analysis results. No significant correlation was observed between 25(OH)D levels and the severity of synovial hypertrophy when 25(OH)D was analyzed as a continuous variable. However, 25(OH)D level was significantly negatively associated with moderate-to-severe synovial hypertrophy in the low 25(OH)D group [odds ratio (OR) = 0.85, 95%CI: 0.75-0.98, P = 0.0229]. In contrast, no significant correlation was observed in the high 25(OH)D group (OR = 1.01, 95%CI: 0.93-1.10, P = 0.8308). Furthermore, individuals with vitamin D deficiency were significantly more likely to exhibit moderate-to-severe synovial hypertrophy than those without deficiency (OR = 4.38, 95%CI: 1.36-14.12, P = 0.0132). Age was significantly negatively associated with moderate-to-severe synovial hypertrophy (OR = 0.95, 95%CI: 0.91-0.99, P = 0.0146), whereas albumin was positively associated (OR = 1.16, 95%CI: 1.03-1.32, P = 0.0183).

Table 2 Univariate analysis for first metatarsophalangeal joint synovial hypertrophy across different degrees.

Variable	OR (95%CI)	P value
Gender
Male	Reference
Female	0.95 (0.41, 2.18)	0.8962
Age (year)	0.95 (0.91, 0.99)	0.0146
DD (year)	1.00 (0.95, 1.06)	0.9327
UA (μmol/L)	1.00 (0.99, 1.01)	0.7669
FPG (μg/dL)	1.06 (0.88, 1.27)	0.5511
HbA1c (%)	0.97 (0.79 1.20)	0.7817
ALB (g/L)	1.16 (1.03, 1.32)	0.0183
BMI (kg/m2)	0.94 (0.83, 1.07)	0.3633
25(OH)D (ng/mL)	0.96 (0.91, 1.02)	0.2169
25(OH)D (dichotomous)
Low	0.85 (0.75, 0.98)	0.0229
High	1.01 (0.93, 1.10)	0.8308
25(OH)D status
Non-deficiency	Reference
Deficiency	4.38 (1.36, 14.12)	0.0132

DD: Duration of diabetes; UA: Serum uric acid; FPG: Fasting plasma glucose; HbA1c: Glycated hemoglobin; ALB: Albumin; BMI: Body mass index; 25(OH)D: 25-hydroxyvitamin D; OR: Odds ratio; CI: Confidence interval.

Table 3 presents the results of the multivariate logistic regression model. According to the results of the univariate analysis, age and albumin level were identified as confounding variables. In addition, considering the potential influence of sex, BMI, and diabetes mellitus[33-35] on OA, the analyses included sex, BMI, and duration of diabetes as confounding variables. In model I (adjusted for age and albumin) and model II (adjusted for age, albumin, sex, BMI, and duration of diabetes), multivariate logistic regression analysis revealed that 25(OH)D levels in the low 25(OH)D group were independently associated with moderate-to-severe synovial hypertrophy, and it was a protective factor against moderate-to-severe synovial hypertrophy (model I: OR = 0.83, 95%CI: 0.72-0.97, P = 0.0152; model II: OR = 0.83, 95%CI: 0.71-0.97, P = 0.0163). Patients with vitamin D deficiency exhibited a significantly higher likelihood of developing moderate-to-severe synovial hypertrophy compared to those without vitamin D deficiency (model I: OR = 3.68, 95%CI: 1.01-13.39, P = 0.0484; model II: OR = 3.86, 95%CI: 1.05-14.20, P = 0.0422).

Table 3 Multivariate analysis of serum 25-hydroxyvitamin D in the degree of first metatarsophalangeal joint synovial hypertrophy.

Variable	Model I		Model II
	OR (95%CI)	P value	OR (95%CI)	P value
25(OH)D (dichotomous)
Low	0.83 (0.72, 0.97)	0.0152	0.83 (0.71, 0.97)	0.0163
High	1.01 (0.92, 1.11)	0.8054	1.02 (0.92, 1.13)	0.7081
25(OH)D status
Non-deficiency	Reference		Reference
Deficiency	3.68 (1.01, 13.39)	0.0484	3.86 (1.05, 14.20)	0.0422

Model I: Age and albumin were adjusted. Model II: Age, albumin, duration of diabetes, body mass index, and gender were adjusted. 25(OH)D: 25-hydroxyvitamin D; OR: Odds ratio; CI: Confidence interval.

Threshold analysis of vitamin D and synovial hypertrophy

Segmented logistic regression analysis (adjusted for age and albumin) revealed a non-linear inverse relationship between 25(OH)D levels and the severity of synovial hypertrophy, identifying a threshold at 23.8 ng/mL (Table 4). Below this level, each 1 ng/mL increase in 25(OH)D was associated with a 21% reduction in the likelihood of moderate-to-severe synovial hypertrophy (OR = 0.79, 95%CI: 0.67-0.94, P = 0.0078). However, above this threshold, the association was not significant (OR = 1.06, 95%CI: 0.96-1.17, P = 0.2465).

Table 4 Threshold effect of serum 25-hydroxyvitamin D on the degree of synovial hypertrophy of the first metatarsophalangeal joint using the segmentation logistic regression model.

Inflection points of 25(OH)D (ng/mL)	OR (95%CI)	P value
< 23.8	0.79 (0.67, 0.94)	0.0078
> 23.8	1.06 (0.96, 1.17)	0.2465
Log-likelihood ratio test		0.007

Adjusted: Age and albumin. 25(OH)D: 25-hydroxyvitamin D; OR: Odds ratio; CI: Confidence interval.

DISCUSSION

Compared to previous studies, our grading system for synovial hypertrophy of the first MTPJ refines the region from the metatarsal head apex to diaphysis. This study involved 43.9% of synovial hypertrophy in this region. Szkudlarek et al[36] classified synovial hypertrophy as grade 3 when it extended beyond the line linking the apices of the articular bones with extension along the bone diaphysis. However, this definition does not account for hypertrophy confined to the region from metatarsal head apex to diaphysis. Molyneux et al[37] and Terslev et al[38] used semi-quantitative ultrasound grading systems to evaluate synovitis in MTPJ OA and rheumatoid arthritis, respectively, reporting moderate inter- and intra-observer agreement (ICC = 0.65 and 0.61 for OA, kappa = 0.60 and 0.54 for rheumatoid arthritis). In contrast, our study demonstrated higher agreement (intra-observer ICC = 0.79; inter-observer ICC = 0.73), potentially due to the anatomical specificity of our grading system.

To the best of our knowledge, this is the first study to explore the relationship between ultrasound-graded synovial hypertrophy and serum 25(OH)D levels in T2DM. In our study, the multivariate logistic regression analysis revealed that 25(OH)D in the low 25(OH)D group was independently associated with moderate-to-severe synovial hypertrophy. Furthermore, the probability of moderate-to-severe synovial hypertrophy was significantly higher in the vitamin D deficiency group compared to those without deficiency, but the confidence intervals are relatively broad (model I: OR = 3.68, 95%CI: 1.01-13.39, P = 0.0484; model II: OR = 3.86, 95%CI: 1.05-14.20, P = 0.0422). Subsequently, we conducted a threshold effect analysis and identified 25(OH)D was a protective factor against moderate-to-severe synovial hypertrophy when 25(OH)D levels were below 23.8 ng/mL (OR = 0.79, 95%CI: 0.67-0.94, P = 0.0078). These findings suggest the potential benefits of vitamin D supplementation for managing synovial inflammation in T2DM patients with lower 25(OH)D levels. Wang et al[39] demonstrated that vitamin D supplementation reduced synovial effusion volume in knee OA patients with baseline 25(OH)D levels below 20 ng/mL. Similarly, Laslett et al[40] reported that correcting moderate vitamin D deficiency (5-10 ng/mL) alleviated knee pain progression in elderly individuals, though supplementation had little effect at higher 25(OH)D levels. Zhou and Hyppönen[41] also observed an inverse L-shaped relationship between serum 25(OH)D and inflammatory markers such as C-reactive protein, stabilizing at approximately 25 ng/mL. These findings align with our results, suggesting a non-linear protective effect of vitamin D on synovial hypertrophy and OA inflammation. Conversely, some studies report no significant association between vitamin D levels and OA severity. A three-year study found that vitamin D supplementation did not significantly affect joint space narrowing, osteophyte formation, or symptom progression in knee OA patients[42]. Another two-year observational study indicated that while vitamin D deficiency increased the risk of developing knee OA, serum 25(OH)D levels were not correlated with clinical or radiographic OA severity[43]. These discrepancies may stem from differences in study design, population characteristics, and the duration required for vitamin D-mediated effects to manifest in joint health.

Several studies have reported that age, BMI, and diabetes mellitus are major risk factors for OA[17,33,44,45]. D’Agostino et al[44] conducted a prospective population-based cohort study involving knee ultrasound screenings in individuals over 60 (mean BMI of 26.33 kg/m²). They found that the prevalence of inflammatory abnormalities was high in the elderly population (68.8%, with 48.3% exhibiting synovial hypertrophy). Furthermore, their findings demonstrated a significant association between inflammatory abnormalities and diabetes mellitus despite only approximately 10% of the study population being diabetic. Conversely, another case-control study[46] did not support the hypothesis that diabetes mellitus predisposes patients to more severe OA compared to non-diabetic individuals. Zhu et al[47] drew a similar conclusion, emphasizing that BMI might confound the association between T2DM and OA. In contrast, Williams et al[48] demonstrated that T2DM is associated with both radiographic and symptomatic OA, even after adjusting for BMI and body weight. A two-sample mendelian randomization analysis further confirmed that T2DM is an independent risk factor associated with increased synovitis[49]. In our study, the median BMI (24.1 kg/m²) was near the normal range, and the median age of participants was 56 years. However, the prevalence of synovial hypertrophy (87.5%) was significantly higher than that of D’Agostino et al[44]. This discrepancy may be attributed to the characteristics of our study population, consisting of individuals with T2DM exhibiting a higher glycated hemoglobin level (8.2%) and a longer duration of diabetes (10 years).

Hyperglycemia may exacerbate synovitis, which is a central pathology in OA[7]. Salikhova et al[19] demonstrated that the primary ultrasound diagnostic criterion for assessing the risks associated with the development of diabetic foot conditions may involve a gradual progression from the phase of hyaline cartilage compaction to that of synovitis and subsequently to the phase of bone tissue necrosis related to Charcot’s foot. Thus, this provides us with a clue that the synovial hypertrophy of the MTPJ in diabetic patients may not only represent imaging manifestations of OA but could also serve as a prognostic indicator for the development of diabetic foot.

Given the cross-sectional design of our study, it is unclear if vitamin D supplementation can alleviate synovial hypertrophy in T2DM patients with low 25(OH)D levels. Longitudinal studies are required to establish causality and to identify the optimal serum vitamin D level for reducing synovial hypertrophy. Furthermore, our study was limited by its small sample size and execution at a single center. Future studies involving larger, multi-center cohorts are necessary to confirm the reliability of our semi-quantitative grading system for MTPJ synovial hypertrophy.

CONCLUSION

This study developed a refined semi-quantitative ultrasound grading system for assessing synovial hypertrophy in the first MTPJ and revealed that vitamin D may serve as a potential protective factor against the severity of synovial hypertrophy in T2DM patients with lower 25(OH)D levels. While our findings offer new insights, further longitudinal studies are required to establish causality and explore the therapeutic potential of vitamin D supplementation in managing T2DM-related joint disorders.