Diffuse Idiopathic Skeletal Hyperostosis (DISH) is a systemic condition marked by abnormal calcification and ossification of ligaments and entheses, primarily affecting the spine but also involving peripheral sites.1 It is often diagnosed incidentally on radiographs of the axial skeleton.2 The prevalence of DISH has been reported between 2.9% and 42.0% depending on the classification criteria used and the presence of risk factors in the studied population.3,4

Clinically, DISH may present with a wide spectrum of manifestations ranging from asymptomatic radiographic findings to significant musculoskeletal symptoms. The most common presentations include back pain, stiffness, and reduced spinal mobility. Cervical spine involvement may cause dysphagia, dyspnea, hoarseness, and rarely, airway obstruction or neurologic deficits due to mechanical compression. Thoracic and lumbar involvement can result in pain and functional decline, with a risk of unstable spinal fractures even after minor trauma.5 Extraspinal manifestations include peripheral joint pain, enthesopathies, and restricted motion, with hip involvement—often mistaken for osteoarthritis—being common and linked to extensive ossification.6 These musculoskeletal features highlight that DISH is not merely an incidental radiographic finding but a condition with potential clinical consequences.

Radiographically, DISH is defined by flowing anterior spinal ossifications across at least four vertebrae with preserved disk spaces, and peripheral changes frequently involve the pelvis, hips, knees, elbows, and hands, contributing to structural enlargement, joint narrowing, and impaired function.6,7

The etiology of DISH is poorly understood and the exact mechanisms and factors that trigger the development of calcification are not well defined. DISH is often associated with hyperinsulinemia and related metabolic diseases such as glucose intolerance, type 2 diabetes mellitus (DM) and obesity.8 Insulin appears to induce differentiation of mesenchymal cells into chondrocytes and stimulate bone differentiation.8,9 Further complicating the picture, DISH is also associated with an increased risk of fragility fractures, especially in the spine. This increased bone fragility can be caused by both mechanical (e.g. abnormal trauma energy dissipation) and metabolic factors, including dysregulation of bone metabolism.10

Prediabetes is a high-risk condition for DM. Prediabetes is defined as a blood glucose level higher than normal but lower than the diagnostic value for DM.11 Prediabetes is a public health problem affecting approximately 720 million people worldwide. In addition, it has been observed that it affects one in every 3 adults in the USA. Insulin hypersecretion, insulin resistance and impaired incretin effect have an important role in the pathophysiology of prediabetes.12

It has been shown in the literature that the incidence of DISH increases in individuals with type 2 DM.8,13,14 However, to our knowledge, there is no study investigating the relationship between prediabetes and DISH development. The aim of this study was to determine the frequency of DISH in patients with prediabetes.

The study included 166 patients with prediabetes who were followed up at the Endocrinology and Metabolic Diseases outpatient clinic. Data were obtained from the form created by the researcher by questioning sociodemographic information (e.g. age, gender), duration of the disease, comorbidities, smoking, alcohol use, body mass index (BMI), medications used, and symptoms that may be related to DISH. Symptoms suggestive of DISH were defined as chronic back pain, spinal stiffness, and/or reduced spinal mobility on clinical examination, consistent with prior studies; however, no standardized questionnaire was applied.2,10

All of these patients met the following inclusion criteria: (a) age≥18 years; (b) glucose-lowering therapy with diet alone or in combination with oral agents; (c) HbA1c≤6.5% (including values≥5.7%), with a previous diagnosis of prediabetes, fasting plasma glucose between 100 and 125mg/dl, 2h plasma glucose between 140 and 199mg/dl in a 75g OGTT; (d) not pregnant; and (e) no history of self-reported osteoporosis, osteoporotic fractures, treatment with bisphosphonates and other anti-osteoporotic agents, steroids or hormone replacement therapy.

To assess the presence of DISH, all radiographs were independently evaluated by a musculoskeletal radiologist (with >5 years of experience in musculoskeletal radiology) who was blinded to patients’ clinical and laboratory data. The presence of DISH was determined according to the criteria proposed by Resnick and Niwayama3: (1) a ‘flowing’ bony bridge of at least four adjacent vertebrae, (2) relative preservation of the intervertebral disk, and (3) relative preservation of the intervertebral disk, fusion or erosion of the sacroiliac and apophyseal joints.

Of the 166 patients, 67 (40.3%) reported symptoms suggestive of DISH and underwent radiographic evaluation. DISH was diagnosed in 9 of 67 symptomatic patients (13.4%, 95% CI: 6.4–23.5). This corresponds to a minimum prevalence of 5.4% (95% CI: 2.5–10.0) in the overall cohort of 166 prediabetic patients. Baseline characteristics are shown in Table 1, and comparisons between patients with and without DISH are presented in Table 2.

When comparing baseline characteristics between patients with and without DISH, no significant association was observed with gender (p=0.407). However, the mean age of patients diagnosed with DISH was significantly higher compared to those without DISH (p=0.004). Although the mean BMI was numerically higher in the DISH group, the difference did not reach statistical significance (p=0.254). Similarly, fasting glucose levels were higher among DISH-positive patients (109mg/dL vs. 97.8mg/dL), yet the difference was not statistically significant (p=0.100). HbA1c levels were comparable between groups (5.92±0.17 vs. 5.94±0.22, p=0.867). Regarding smoking habits, 4 out of 9 patients with DISH (44.4%) were current smokers, but this distribution was not statistically significant (p=0.169). None of the DISH patients reported alcohol consumption.

Interestingly, hypertension was detected in 6 of 9 patients with DISH (66.7%), compared to 18 of 58 patients (31%) in the non-DISH group. This difference was statistically significant (p=0.047), suggesting a potential link between hypertension and DISH in prediabetic individuals. Other metabolic parameters did not demonstrate statistically significant differences between the two groups.

In this study, DISH was diagnosed in 5.4% of patients with prediabetes. This finding provides preliminary evidence that prediabetes may be linked to DISH, in line with reports linking metabolic conditions such as DM and obesity with higher prevalence of the disease. Previous studies have consistently shown an increased frequency of DISH among individuals with impaired glucose tolerance or established DM compared to normoglycemic populations.2,3

DM has been observed to be significantly more common in patients with DISH than in patients without DISH according to many studies.15–17 Although the quality of these studies varies, there is a general theme that patients with DM or abnormal glucose tolerance have a higher prevalence of DISH than those with normal glucose tolerance. There is an increased prevalence of DISH in patients with DM recruited from hospital clinics, possibly reflecting bias due to comorbidity factors. However, when non-diabetic people aged 60–69 years were compared with diabetic people of the same age, the prevalence of DISH increased from 4% to 21% [p<0.001].18 Both excess body weight and type 2 DM are usually accompanied by hyperinsulinemia, and this has also been reported in patients with DISH. In particular, metabolic changes such as increased insulin resistance and hyperinsulinemia are thought to contribute to the development of DISH.

Prediabetes is defined by a fasting glucose level of 100–125mg/dL, a glucose level of 140–199mg/dL measured 2h after a 75g oral glucose load, or a glycated hemoglobin level (HbA1C) of 5.7–6.4% or 6.0–6.4%.18 Prediabetes indicates an increased risk of diabetes and a high likelihood of developing type 2 DM in the future. Our findings suggest that patients with prediabetes may also have an elevated frequency of DISH, supporting the concept of an intermediate metabolic risk state.

The correlation between increasing age and the presence of DISH has been described in many studies explaining the prevalence and associations of DISH.3,12,19,20 In our study, the age of patients with DISH was statistically significantly higher than those without DISH.

Gender-related findings remain inconsistent across studies. While many reports describe male gender as significantly associated with higher DISH prevalence,17,19–21 some studies, including ours, did not confirm this difference.22,23 In our sample, no significant gender association was found, although females were more numerous overall.

Several studies have demonstrated a robust association between DISH and metabolic syndrome. In a study of 327 subjects, the prevalence of metabolic syndrome was significantly higher in the DISH group compared to the non-DISH group (28.9% vs. 16.0%), with an odds ratio of 2.0 (95% CI: 1.0–3.7; p=0.004), independent of diabetes status, indicating that metabolic syndrome itself constitutes a strong risk factor for DISH.24 This association has been further confirmed in a large-scale population-based study of more than 5000 elderly individuals, which reported an odds ratio of 2.12 (95% CI: 1.69–2.64; p=3.9×10−11), particularly driven by insulin resistance and elevated BMI, regardless of age and sex.25 Obesity alone has also been identified as a significant risk factor for DISH, with high BMI consistently observed among affected patients.4,23,26 Notably, among young adults (≤50 years) with severe obesity (BMI≥35), the prevalence of DISH reached 18%, far exceeding the <5% expected in this age group and the general population, suggesting that obesity, independent of diabetes, plays a major role in early-onset DISH.27 Additional studies have confirmed this relationship, reporting prevalence rates of 19.1% in general adult populations and even higher rates among older individuals.28 In our cohort, although BMI was higher in the DISH group, the difference did not reach statistical significance.

Hypertension has been described as more common in individuals with DISH, although findings vary across studies.4 Two studies reported significantly higher systolic blood pressure in DISH populations compared to controls.3,26 Similarly, hypertension was significantly more frequent in DISH patients in our cohort.

In addition, the association of external factors such as current smoker and alcohol intake with DISH has been investigated. In the study by Kagotani et al. the number of regular smokers was higher in the DISH group (21.1%) compared to the non-DISH group (11.9%).29 In contrast, two studies identified a significantly lower percentage of current smokers in the DISH group (3.3–57.7%) compared with the control group (7.2–65.9%).21,26 In two studies, regular alcohol consumption was not associated with the presence of DISH.26,29 Regarding alcohol use, most studies—including ours—have not demonstrated a significant association with DISH.

The etiology of vertebral hyperostosis remains unclear.4 However, the relationship between DISH and components of the metabolic syndrome is clear. Hypothetically, this relationship is a consequence of the extra ‘energy’ required for new bone formation and explains the high prevalence of DISH in obese patients or the absence of DISH in non-obese patients.29,30 This appears to reflect the increased prevalence of obesity and diabetes in DISH patients. Therefore, hyperinsulinemia, possibly associated with obesity, may be a factor linking metabolic parameters with the development of vertebral hyperostosis.

Beyond hyperinsulinemia, several mechanisms may underlie the association between prediabetes and DISH. Increased visceral adiposity and ectopic fat deposition, particularly in the liver, promote insulin resistance and systemic inflammation, which may contribute to abnormal bone and soft tissue remodeling characteristic of DISH.31,32 Chronic low-grade inflammation, largely driven by adipose tissue and metabolic organs, is increasingly recognized as a central mechanism in prediabetes and may stimulate osteogenic pathways in ligaments and entheses. Individuals with prediabetes exhibit elevated levels of inflammatory mediators, particularly tumor necrosis factor-alpha, with trends toward higher interleukin-8 and interleukin-1β. These inflammatory alterations are closely associated with increased BMI, waist circumference, blood pressure, triglycerides, fasting glucose, and HbA1c, underscoring the tight link between metabolic dysregulation and inflammation.32–34 In addition, dyslipidemia—manifested as elevated triglycerides and altered HDL/LDL profiles—has been implicated in both prediabetes and DISH through effects on bone metabolism and soft tissue calcification.31 Subphenotyping studies also show that certain prediabetes clusters carry higher risks of kidney, cardiovascular, and liver complications, potentially sharing mechanisms such as vascular calcification and extracellular matrix turnover with DISH. Importantly, prediabetes is a heterogeneous condition encompassing distinct metabolic and inflammatory profiles, suggesting that the overlap with DISH may be particularly pronounced in specific subgroups, rather than being solely mediated by hyperinsulinemia.31,32,35

In line with previous studies, patients with DISH showed a significantly higher age compared to those without DISH in our cohort. Hypertension was also more frequent among patients with DISH, supporting prior evidence of metabolic comorbidities contributing to disease burden. BMI was higher in patients with DISH, although this difference did not reach statistical significance. Gender-related findings remain inconsistent across the literature; while many reports describe higher prevalence in males, no significant difference was observed in our cohort. The mechanisms linking prediabetes to DISH remain speculative. Hyperinsulinemia and insulin resistance are potential contributors, and chronic low-grade inflammation in prediabetes may also play a role in abnormal ossification. Further research is required to clarify these pathways.

Our study has several limitations that should be recognized. Firstly, this study was designed as a single-center, cross-sectional study. Secondly, radiographs were obtained only in patients with symptoms suggestive of DISH. This approach was chosen for ethical and practical reasons, including radiation exposure, cost, and feasibility. However, this selection may have introduced a bias and led to an underestimation of the true prevalence, as subclinical cases of DISH could have been missed. Therefore, our findings likely reflect the frequency of clinically relevant DISH rather than the overall prevalence in the prediabetic population. Thirdly, moreover, the definition of “symptoms suggestive of DISH” was not standardized and was based on clinical judgment (e.g., chronic back pain, stiffness), which could have introduced subjectivity in patient selection. Fourth, the number of patients diagnosed with DISH was relatively small, which may have limited the statistical power of our analyses and restricts the generalizability of our findings. Finally, DISH may also affect the cervical spine and peripheral sites such as the elbows, shoulders, knees, or calcanei, which were not assessed in our study. Larger, multicentre studies including systematic imaging of all patients regardless of symptoms are warranted to validate and extend our results. In addition, we did not assess the duration of prediabetes or longitudinal markers of glucose control, which may influence the risk of developing DISH. Future prospective studies incorporating these parameters will be valuable to further elucidate the relationship between glucose metabolism and DISH.

In conclusion, a potential association between DISH and metabolic conditions such as DM is known. However, the nature of this relationship is not fully understood. It is hypothesized that factors characteristic of DM and prediabetes, such as insulin resistance and chronic low-grade inflammation, may contribute to the development or progression of DISH. However, further research is needed to fully elucidate the relationship between DISH and prediabetes.

Writing-original draft preparation and conceptualization, A.A., S.U. and T.P. Supervision, A.A., and T.P.; All authors have read and agreed to the published version of the manuscript.

Local Ethics Committee approval was given by the local medical ethics committee (Decision No: 1807) of the Celal Bayar University before starting this study. A signed, informed consent was taken from all participants.

Written informed consent has been obtained from the patients to publish this paper.

No funding.

The authors have declared no conflicts of interest.

The data that support the findings of this study are available from the corresponding author upon reasonable request.