The observation that some patients with diabetes have limited joint mobility in the hand was first made by Rosenbloom et al. in 1974 (1). The spectrum of hand manifestations that occur within diabetes, termed “diabetic cheiroarthropathy” or “diabetic hand,” now includes limited joint mobility (LJM), flexor tenosynovitis (FT) including stenosing FT or trigger finger, Dupuytren’s contracture (DC), and carpal tunnel syndrome (CTS) (2).

The clinical correlates of these hand syndromes with other organ manifestations within diabetes are unclear. While some reports show an increased prevalence of hand disorders in patients with microvascular complications of diabetes mellitus (3), others do not (4). Despite their heterogeneity, at least three of these manifestations (LJM, FT, and DC) share the common pathophysiologic process of profibrotic inflammation, demonstrated on histopathology (5). CTS may be secondary to fibrotic thickening of the other structures in the carpal tunnel but may also be partly microvascular (6). We previously hypothesized that these easily accessible manifestations may reflect a global profibrotic trajectory in internal organs and could potentially serve as a clinical biomarker (7).

One hurdle in establishing such correlations is the lack of a clinical tool that can serve as a proxy measure of the amount of inflammation-fibrosis in the hand, unifying all these manifestations. The Duruöz Hand Index (DHI) is a functional score that has been validated for use in diabetes (8). However, barring early FT and CTS, these conditions are rarely painful and are functionally limiting only when they produce severe mobility restriction (9). In this situation, a clinical metric that banks on the biology of fibrosis (resistance to stretch) rather than on perceived clinical and functional effects (functional limitation, pain) is likely to be more useful. In LJM, FT, and DC, profibrotic inflammation occurs in one or more of the structures on the flexor aspect of the palm. In severe cases of LJM, contractures ensue, leading to the classical “prayer sign” (10). However, finger extension is likely to be limited much earlier than this state.

We hypothesized that such limitation would reflect in a reduced angle of maximum passive extension at the metacarpophalangeal (MCP) joint, when the hand is approximated on a flat surface. In a type 1 diabetes cohort, we showed that the mean of the angles of passive extension at the MCP joint of the second to fifth fingers (henceforth, mean MCP extension) was reduced in those with hand manifestations (9). Mean MCP extension is easy to calculate at the community level and does not need expensive equipment nor extensive training. Furthermore, this metric correlated with the presence of fibrotic tissue thickening on MRI in the type 1 diabetes patients studied.

In this study, we evaluate the performance of MCP extension as a measure of hand manifestations in an expanded population that includes type 2 diabetes, prediabetes, and non-diabetic controls in addition to type 1 diabetes. We use COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology to describe validity, reliability, and responsiveness, using separate cohorts for different aims, which add credibility to its potential use as a clinical metric of fibro-inflammatory flexor hand involvement in these conditions (11).

Diabetes-related inflammatory-fibrotic manifestations of the hands are common. A lack of a unifying and simple methodology to measure these manifestations clinically may have precluded examining whether they are biomarkers of a global multiorgan profibrotic trajectory. We show that mean MCP extension is an easy and quantitative measurement that picks up most of these hand manifestations, even in asymptomatic stages. Using COSMIN methodology, we show that it is a valid and reliable metric on a large, heterogenous prospective cohort with varying manifestations. We lay grounds for its use in both assessing and describing the severity of hand problems themselves, as well as establishing correlations with internal organ fibrosis or serological biomarkers of ongoing profibrotic processes.

In our study, individuals with diabetes-related hand manifestations exhibited a 20° reduction in mean MCP angle as compared with those without, a difference we believe is clinically significant and possible to ascertain to the eye. Although grip strength also differed statistically between the groups (45 vs. 49 mm Hg in LJM versus normal), it would not be considered clinically significant. MCP extension was also reduced in LJM, skin thickening, and DD, which are all painless conditions. This finding contrasted with DHI, which was not significantly higher in these three conditions and thus could pick up only CTS and FT, which affect hand function due to neuropathy or pain respectively. We did find a low prevalence of CTS in our cohort (≈2%), which contrasts with higher rates reported in diabetes cohorts evaluated using nerve conduction studies. In our study, CTS was identified solely through clinical symptoms and signs in an unselected outpatient population. These methodological differences likely account for the lower observed prevalence and represent an acknowledged limitation of our dataset.

The Wilson and Cleary conceptual model (1995) links biological and physiological variables to health outcomes through a continuum that includes symptom status, functional status, general health perceptions, and overall quality of life (14). (Figure 2) Applied to the diabetic hand, most existing scores focus on functional status or pain, assessing how patients manage daily activities or experience discomfort. To our knowledge, no instrument attempts to quantify the biology of the condition, specifically inflammation and collagen deposition, and resultant resistance to stretch. Symptom status and functional status are both influenced by patient-related factors such as the patients’ pain tolerance, symptom amplification, and environmental factors such as social and psychological support. Due to the variation that these influences would bring, they might not be good candidates for measures to correlate with other similar, biological processes.

The validity data increase confidence that we are measuring the construct of interest. In this paper, we show that MCP correlated with a physician’s idea of fibrosis severity, even though this assessment is a far more subjective measure. We consider the correlation of −0.5 to be a reasonable indicator of convergent validity in this context. Given the inherent subjectivity of physician judgment and its ordinal nature, a moderate correlation still supports construct validity—especially when the directionality is consistent and statistically significant. A stronger testament to the validity of this metric comes from our previous work in type 1 diabetes, where mean MCP extension correlated with fibrous tissue deposition on MRI in flexor compartments (9). In addition, weak correlations with both DHI and grip strength denote that these are measuring diverging constructs. Clinically, DHI elevation in those with MCP extension <30° indicate functional impairment only in the most severely affected. This is likely because limited MCP hyperextension alone may not affect most hand functions assessed by DHI, which involve grip and dexterity. In more severe cases, associated flexor contractures of the proximal or distal interphalangeal joints may develop and contribute more directly to functional limitation. Overall, these data suggest that mean MCP extension adds additional value in the clinical armamentarium assessing diabetes hand. While no established minimal clinically important difference (MCID) exists for MCP extension in this context, our findings suggest that a difference of approximately 8°–10° is easily detectable and associated with clinical change over time. In our data, a threshold of <40°for mean MCP extension showed excellent agreement between raters in identifying restricted motion (Cohen’s κ = 0.81) and could serve as a pragmatic cutoff to define “restricted” extension. Future work should validate these thresholds in relation to patient-reported outcomes and functional measures to improve clinical decision-making and screening applicability.

Detecting an ongoing fibrotic process in its preclinical stages is useful because fibrosis, once established, is largely irreversible. Early detection may allow for timely intervention, potentially halting or slowing disease progression before irreversible tissue damage occurs. Using current diagnostic paradigms in the diabetic hand, patients will only be detected when they get the full-fledged manifestation and complain to the physician. Data suggest that end-stage phenotypes, such as the prayer sign, do correlate with stiffness in other tissues. For example, the prayer sign has been associated with difficult endotracheal intubation in surgery (15) and with increased ventilatory hours following bypass surgery (16), possibly suggesting upper respiratory and lung stiffness respectively. The prayer sign is a subjective binary sign for flexor compartment fibrosis, and such associations may benefit from quantitative measures of the same. Having a quantitative measure is also likely to help in evaluating the longitudinal course of these syndromes, which is not possible with binary outcomes. To this effect, we saw that MCP extension is sensitive to change—both in documenting a gradual decline in those with diabetes-related hand conditions and an improvement in more acute flexor tenosynovitis.

Mean MCP extension restriction before symptoms or functional deficits arise could potentially help in detecting such “preclinical” disease. We used the additional category of “skin thickening” as a possible preclinical state before the prayer sign is evident. Mean MCP extension was restricted in this state as compared with controls. It was also interesting to note that the group with prediabetes had a higher prevalence of ST whereas the fraction of LJM increased in type 1 and type 2 diabetes. This observation may suggest that the fibrotic program in the hand is set before hyperglycemia develops, which then modifies it toward increasing the severity of LJM. It will be informative to follow the group with prediabetes and skin thickening, to confirm this possibility. These data will also support a Mendelian Randomization in the UK Biobank, which showed a causal relationship between hyperglycemia and hand manifestations (17).

Reliability studies across a heterogeneous patient population increase our confidence in being able to use mean MCP extension in the clinic and community. While interrater agreement was good overall, the ability in identifying severe extension (<40°) was excellent. With proper training, mean MCP extension can potentially be measured by paramedical staff in the community.

This paper has several strengths, including a large, prospective dataset of more than 2,500 individuals, and the use of blinded clinical opinions to minimize bias. The inclusion of both types of diabetes, prediabetes, and healthy controls enhances generalizability, and the use of smaller datasets tailored to the methodological approach helps establish reliability and responsiveness. The study’s weaknesses include small numbers of patients with certain hand conditions like CTS, the absence of a gold standard imaging technique, lack of correlation with similar scores like the Hand Mobility in Scleroderma (HAMIS) score (18), and the absence of long-term follow-up in most of the cohort. We acknowledge that goniometric measurements are the established standard for assessing joint range of motion. A formal comparison with standard goniometry or digital angle measurement tools would enhance external validity and should be pursued in future studies. Nevertheless, the high inter-rater reliability observed in our study supports the reproducibility of the method with minimal training. Mean MCP extension is not specific to diabetes-related hand conditions. It may be affected by other disorders such as rheumatoid arthritis, neurological contractures, trauma, or palmar psoriasis. As such, its use should be limited to well-characterized populations unless supported by appropriate differential diagnosis. Caution should be exercised when generalizing its application beyond diabetes-related fibrosis without further validation.

Expanding the dataset to include broader hand conditions will help establish ranges.

A further limitation is the absence of imaging and systemic biomarker correlation in the present dataset. While these data would strengthen mechanistic interpretation, the aim of this study was primarily methodological, to establish validity, reliability, and responsiveness of mean MCP extension using COSMIN guidance in a large and diverse cohort. Imaging-based validation is inherently feasible only in smaller subsets. Future work will incorporate magnetic resonance imaging (MRI) as a gold standard that will add to the construct validity, as well as compare the measurement method with goniometry. Long-term follow-up studies in diabetic cheirarthropathy are few and are needed to assess the utility of detecting “preclinical” hand stiffness. Finally, it would be important to correlate mean MCP extension with markers of internal organ fibrosis including the heart, kidney, lung, and liver, to evaluate if the hand can indeed serve as a clinical biomarker (7).

In conclusion, this group of studies highlights the clinical significance of mean MCP extension as a valid indicator of flexor fibro-inflammatory hand manifestations in diabetes, despite their clinical heterogeneity. A notable 20° difference in those with hand manifestations can be easily detected in the community. The measurement can be used reliably with minimal training and is sensitive to both worsening and improvement in these conditions. The large dataset, blinded assessments, and inclusion of controls strengthen the findings and establish a proof of concept for more widespread use of this simple measure in further correlative and interventional studies.