Application of the HOMA Index in Diabetic Dogs and Cats: A Systematic Review of Current Evidence

Featured Application

The application of the HOMA index in diabetic companion animals offers veterinarians a practical tool to assess insulin resistance and β-cell function. This approach can enhance early diagnosis, guide individualized treatment strategies, and improve metabolic monitoring in diabetic dogs and cats.

Abstract

The use of the HOMA (Homeostatic Model Assessment) index in veterinary medicine is emerging as a promising and valuable method for evaluating insulin resistance and beta-cell function in companion animals, particularly in dogs and cats. Originally developed for use in human medicine, HOMA enables a minimally invasive assessment of glucose and insulin homeostasis, offering clinicians a practical tool for diagnosing and monitoring diabetes mellitus in animals. Its application in veterinary practice brings several advantages, including cost-effectiveness, ease of use, and the potential for early detection of metabolic disturbances before clinical symptoms appear. Nonetheless, important limitations persist, such as inter-individual variability, the effects of stress and comorbidities on glucose and insulin values, and the absence of standardized, species-specific reference ranges. These factors highlight the need for methodological refinement and the establishment of validated protocols tailored to the unique physiological characteristics of dogs and cats. Despite these challenges, HOMA represents a promising avenue for advancing the understanding of diabetes pathophysiology in veterinary patients. Future longitudinal studies and controlled trials are essential to confirm its reliability and enhance its clinical relevance. With further development, the HOMA index could become an essential tool in improving diagnostic accuracy and optimizing the management of diabetes in companion animal practice.

1. Introduction

Diabetes mellitus (DM) is a complex endocrine and metabolic disorder with an alarmingly increasing incidence in companion animals, mirroring epidemiological trends observed in humans [1,2,3].

This pathology is characterized by chronic hyperglycemia resulting from absolute or relative insulin deficiency, insulin resistance, or a combination of both [4]. Understanding the distinct pathophysiological mechanisms, together with the use of accurate diagnostic tools, is essential for effective clinical management and for the establishment accurate prognostic indicators.

According to the veterinary classification proposed by the ALIVE Project [5], canine diabetes mellitus most frequently presents as insulin-deficient diabetes (IDD), usually resulting from immune-mediated destruction or loss of pancreatic β-cells. This leads to an absolute insulin deficiency and necessitates lifelong insulin therapy. In contrast, the predominant form in cats is insulin-resistant diabetes (IRD), often accompanied by concurrent β-cell dysfunction. This form is typically associated with risk factors such as obesity, physical inactivity, chronic inflammation, and glucolipotoxicity, all of which contribute to the progressive exhaustion of β-cells.

While insulin-deficient diabetes (IDD) in dogs generally follows an irreversible course, insulin-resistant diabetes (IRD) in cats can, in some cases, enter remission—particularly when diagnosed early and managed appropriately through interventions such as insulin therapy, dietary modification, and weight control [6,7]. Regardless of species, diabetes complications can be severe, ranging from diabetic ketoacidosis to neuropathy, cataracts, nephropathy, and increased susceptibility to infections [2,8].

A detailed metabolic evaluation is therefore essential and should go beyond simple blood glucose measurement [9,10,11]. Biomarkers such as glycated hemoglobin (HbA1c), fructosamine, cholesterol, and lipid profiles provide a broader picture of glucose homeostasis, insulin secretion, and metabolic risk [4,12].

In this context, the Homeostasis Model Assessment (HOMA) indices offer a non-invasive mathematical approach for evaluating insulin sensitivity (HOMA-IR) and β-cell function (HOMA-β) [13,14]. These indices are based on fasting plasma glucose and insulin concentrations and model the feedback relationship between insulin production and tissue sensitivity under steady-state conditions [15].

Veterinary studies have shown that HOMA indices can provide practical insights into the early identification of insulin resistance (particularly in cats in early-stage disease) and the monitoring of treatment response [16,17]. Although the constants used in the original HOMA formulas were derived from human data, the method has shown promising applicability in dogs and cats, with potential for species-specific adaptation [18,19].

Longitudinal monitoring of HOMA indices is particularly valuable for guiding treatment adjustments, anticipating disease progression, and identifying high-risk patients—even before clinical signs appear [20,21]. When used alongside traditional markers, HOMA indices contribute to a more nuanced understanding of diabetes pathophysiology and allow for personalized treatment planning [5,22]. This integrated approach can improve glycemic control, prevent complications, and enhance the quality of life of diabetic companion animals [9,23].

2. Materials and Methods

This review was conducted in full compliance with the PRISMA 2020 guidelines. The PRISMA checklist and flow diagram are provided in the Supplementary Materials. This review was not registered in a database (e.g., PROSPERO), and no review protocol was prepared. It was conducted following the PRISMA 2020 guidelines to identify, evaluate, and synthesize available evidence on the use of the HOMA index (Homeostasis Model Assessment) in the diagnosis and monitoring of diabetes mellitus in companion animals.

A comprehensive literature search was performed using multiple international databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search covered articles published between 1932 and 2024, using combinations of keywords such as “HOMA index”, “insulin resistance”, “HOMA-IR”, “HOMA-β”, “β-cell function”, “canine diabetes”, “feline diabetes”, and “companion animals”. Additional references were identified by examining the bibliographies of relevant studies.

Studies were included based on the following eligibility criteria: (1) original research articles or case series; (2) conducted on companion animals (dogs or cats); (3) involving the use of the HOMA index (HOMA-IR and/or HOMA-β); and (4) reporting relevant clinical, metabolic, or diagnostic data. Exclusion criteria were as follows: (1) studies on laboratory animals or humans; (2) review articles, editorials, or opinion pieces; and (3) articles lacking original data or sufficient methodological clarity.

Two independent reviewers screened all identified titles and abstracts, followed by full-text review of potentially eligible studies. Discrepancies were resolved by consensus. Data were extracted on species studied, study design, method of glucose and insulin measurement, HOMA calculation formulas used, and the clinical context (diagnosis, monitoring, or therapeutic evaluation).

The quality and relevance of included studies were assessed based on their methodological rigor, statistical validity, and clinical applicability. Risk of bias was considered through a qualitative appraisal of study design, sample size, and data reporting transparency. Additionally, potential publication bias was considered by assessing whether studies reported only favorable or expected outcomes and by screening reference lists for missing or unpublished studies.

Extracted data were synthesized narratively due to expected heterogeneity in study designs, species studied, and outcome measures. Comparative interpretations were supported by descriptive tables and figures illustrating HOMA-IR and HOMA-β values across species, age groups, and metabolic states.

This approach aimed to consolidate current evidence on the veterinary application of HOMA indices and to identify knowledge gaps, methodological limitations, and directions for future research.

The selection process of studies is summarized in the PRISMA 2020 flow diagram (Figure 1).

The diagram illustrates the selection process of studies included in this systematic review. It details the number of records identified, screened, assessed for eligibility, excluded, and ultimately included in the synthesis, according to PRISMA 2020 guidelines.

Software and Tools: Figures and basic statistical analyses were prepared using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) and GraphPad Prism version 9.0 (GraphPad Software, San Diego, CA, USA).

Equipment: Biochemical measurements reported in the reviewed studies were obtained using standard clinical laboratory equipment (Spectrophotometer UV-1800, Shimadzu, Kyoto, Japan; ELISA reader, Thermo Fisher Scientific, Waltham, MA, USA).

AI Tools: Artificial intelligence tools (ChatGPT, OpenAI, GPT-5, accessed in September 2025) were used for figure preparation and English editing, under author supervision. The scientific content and interpretation were entirely developed and verified by the authors.

3. Results and Discussions

3.1. The Concept of HOMA and Its Relevance in Veterinary Medicine

In the study of diabetes mellitus (DM) in companion animals, the use of the HOMA (Homeostasis Model Assessment) index could become an essential tool for evaluating insulin sensitivity and pancreatic β-cell function. This mathematical model, based on fasting glucose and insulin determinations, allows for a rapid analysis of glycemic homeostasis, facilitating both diagnosis and monitoring of disease progression [15,16,24,25]. Given that DM is an increasingly common endocrine disorder in dogs and cats, characterized by chronic hyperglycemia [1,2,16,23,26,27], the identification of efficient and accessible methods for assessing metabolic status has become a pressing necessity in modern veterinary medicine [28,29] The HOMA index, through its simplicity and accuracy, offers valuable insight into the delicate balance between insulin production and tissue response [17,30,31].

According to the updated veterinary classification proposed by the ALIVE Project [5], canine diabetes mellitus most commonly manifests as insulin-deficient diabetes (IDD), typically caused by immune-mediated destruction of pancreatic β-cells, leading to absolute insulin deficiency and the need for lifelong insulin therapy. Conversely, feline diabetes is predominantly insulin-resistant diabetes (IRD), frequently accompanied by concurrent β-cell dysfunction, often associated with obesity, physical inactivity, chronic inflammation, and glucolipotoxicity and even iatrogenic steroid administration, [1,5,7,32,33], which has been shown to induce insulin resistance in cats [32]. This distinction is essential for accurate interpretation of HOMA indices in veterinary patients, as the underlying pathophysiology directly influences insulin sensitivity and β-cell performance.

A significant challenge in the extended application of this index in veterinary medicine lies in interspecies physiological differences, which can influence the interpretation of obtained values [21,34,35]. Variations in basal metabolism, circadian rhythms of hormonal secretion, and tissue insulin sensitivity among dogs, cats, and other species may necessitate cautious adaptation of interpretive thresholds [16,17,36,37]. Nevertheless, recent advancements in veterinary research have demonstrated that the HOMA index can be successfully utilized to evaluate metabolic risk and treatment efficacy in companion animals [19,38].

In dogs, this index contributes to the early identification of insulin resistance—a key factor in diabetes development—thereby allowing for timely therapeutic interventions before the onset of severe complications [39,40]. In cats, the HOMA model enhances the understanding of how carbohydrate metabolism is influenced by factors such as diet, genetic predisposition, or the animal’s general health status [18,31,41]. This provides a solid basis for personalized management strategies, considering the potential for remission of feline type 2 diabetes in early stages [1,7].

Another important aspect of using the HOMA index in veterinary medicine is its potential to reduce the need for invasive and costly tests, such as the glucose tolerance test (GTT) or the euglycemic-hyper insulinemic clamp [9,15]. While these tests are considered the gold standard for evaluating insulin sensitivity, they are difficult to perform under typical clinical conditions, requiring extensive manipulation and constant monitoring and often inducing high levels of stress in animals [4,20] These logistical and financial constraints limit their widespread applicability in current veterinary practice [11,12]. In contrast, the HOMA index offers a much more practical alternative, providing relevant information about the patient’s metabolic status based on simple, routine blood tests [13,14].

The adaptation and validation of this index for various veterinary species contribute significantly to improving prevention, diagnosis, and treatment strategies [42,43]. By correlating HOMA values with other essential metabolic markers—such as glycated hemoglobin (HbA1c), fructosamine, lipid profiles, and hormonal levels—veterinarians can obtain a more detailed and nuanced picture of the pathophysiological mechanisms underlying DM [9,12]. This holistic approach allows for the individualization of therapies according to each patient’s specific needs, thus optimizing treatment response [12,44].

3.2. The Origin and Purpose of the HOMA Index

According to the updated veterinary classification proposed by the ALIVE Project [5], canine diabetes mellitus most commonly manifests as insulin-deficient diabetes (IDD), typically caused by immune-mediated destruction of pancreatic β-cells, leading to absolute insulin deficiency and the need for lifelong insulin therapy. Conversely, feline diabetes is predominantly insulin-resistant diabetes (IRD), frequently accompanied by concurrent β-cell dysfunction, associated with obesity, physical inactivity, chronic inflammation, and glucolipotoxicity [1,45]. This distinction is essential in interpreting HOMA indices, as the underlying pathophysiology directly influences insulin sensitivity (HOMA-IR) and β-cell function (HOMA-β).

The Homeostasis Model Assessment (HOMA) index was developed in the 1980s as a non-invasive and practical method for evaluating glucose homeostasis [13]. Its primary purpose was to provide an accessible alternative to invasive and costly methods, such as the euglycemic-hyperinsulinemic clamp, for estimating two fundamental metabolic parameters: insulin sensitivity (HOMA-IR) and pancreatic β-cell function (HOMA-β) [14,15,30,42]. The model is based on the premise that in the fasting state, a dynamic equilibrium exists between insulin secretion and tissue responsiveness, allowing these parameters to be estimated from basal glucose and insulin concentrations [19].

HOMA-IR quantifies the degree of insulin resistance, an indicator of the efficiency with which tissues [muscle, adipose, and hepatic] utilize glucose. Elevated HOMA-IR values suggest increased resistance, a finding particularly relevant in the pathogenesis of IRD in cats and in secondary forms of insulin resistance in dogs [19,39,46]. HOMA-β estimates the functional capacity of β-cells to secrete insulin, reflecting their health status and compensatory ability; low values indicate dysfunction or insufficiency, as seen in IDD in dogs and advanced stages of IRD in cats [12].

In veterinary medicine, the applicability of the HOMA index has been validated for assessing metabolic risk in companion animals. In dogs, HOMA-IR is valuable for early detection of insulin resistance in obese patients or those with endocrine disorders, enabling early intervention before the onset of overt hyperglycemia [39,47,48]. In cats, both HOMA-IR and HOMA-β are important for understanding how diet, genetic predisposition, and overall health influence carbohydrate metabolism—information essential for personalized management and for identifying patients with remission potential in the early stages [31,45].

The main advantages of HOMA in veterinary practice include its non-invasive nature, reduced stress and physiological alterations compared to complex procedures, accessibility and cost-effectiveness, and usefulness in repeated monitoring and longitudinal studies [9,49]. HOMA is also valuable for assessing the impact of therapeutic interventions on animal metabolism.

However, the method has limitations: it depends on strict adherence to fasting protocols and can be influenced by acute or chronic conditions. Establishing species-specific reference intervals and exploring the influence of external factors [diet, physical activity, chronic inflammation, medications] are necessary to refine its clinical utility [21,50]. Integrating HOMA values with other metabolic biomarkers—such as glycated hemoglobin (HbA1c), fructosamine, lipid profile, or C-peptide—can provide a holistic view of the metabolic status and guide therapeutic decision-making.

Thus, the HOMA index represents a significant advancement in both veterinary endocrinology and comparative diabetology, offering a simple, reliable, and efficient method for evaluating metabolic status. It facilitates early diagnosis, optimizes personalized therapeutic strategies, and improves prognosis and quality of life for animals affected by metabolic disorders [51,52].

3.3. Calculation Methodology [HOMA-IR and HOMA-β]

The HOMA (Homeostatic Model Assessment) index has become an essential tool for evaluating and monitoring metabolic disorders, particularly insulin resistance and pancreatic β-cell function [12,30,53]. Its applications extend beyond human medicine and are increasingly used in veterinary medicine, offering an accessible and efficient method for diagnosing and managing various endocrine and metabolic diseases, such as diabetes mellitus [54,55,56]. HOMA-IR (for insulin resistance) and HOMA-β (for β-cell function) are straightforward formulas that allow the assessment of these parameters using only fasting plasma glucose and insulin concentrations, eliminating the need for invasive or costly tests—making these methods especially useful in veterinary practice [25,57,58].

The calculation methodology for evaluating insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β) involves two simple mathematical formulas based on plasma glucose and insulin concentrations measured under fasting conditions [13,59,60,61,62].

Originally developed for humans, these formulas have been adapted for dogs and cats through species-specific parameter adjustments [19,30,63,64]. For example, in dogs, [39] demonstrated that HOMA-IR can facilitate early diagnosis of insulin resistance, while [63] identified a threshold of 2.4 for classifying obese dogs as insulin-resistant. In cats, [19] proposed a reference interval of 0.1–3.0 for lean individuals and reported a positive correlation with body fat percentage. [64] showed that HOMA remains useful even in diabetic cats in remission, revealing persistent insulin resistance.

The formula for HOMA-IR, used to calculate insulin resistance, is as follows:

HOMA-IR = (Glu × Ins)/22.5

(1)

where Glu is the plasma glucose concentration (in mmol/L) and Ins is the insulin concentration (in μU/mL) [65,66]. This formula enables a rapid and non-invasive assessment of insulin resistance, a critical factor in diagnosing diabetes and other metabolic disorders [62,65,66].

Similarly, the formula for HOMA-β, used to evaluate pancreatic β-cell function, is as follows:

HOMA-β = (20 × Ins)/(Glu − 3.5)

(2)

This calculation reflects the pancreas’s ability to secrete insulin in response to plasma glucose and insulin levels [14,67,68]. The method is useful for assessing the health status of β-cells, with significant applications in the diagnosis and therapeutic monitoring of diabetes mellitus [14,67,69], as illustrated in Figure 2.

The graph highlights the nonlinear relationships between these parameters. In the early stages of insulin resistance, β-cells compensate by increasing insulin secretion, resulting in elevated HOMA-β values. Over time, this compensatory capacity declines, leading to reduced insulin secretion and a progressive deterioration of β-cell function, even in the presence of persistent hyperglycemia—a hallmark of type 2 diabetes mellitus.

Interpretation of HOMA values must take into account factors such as species, physiological status, diet, and comorbidities [42,70,71]. For example, hypertriglyceridemia in Miniature Schnauzers is associated with elevated HOMA-IR values [70], while in obese dogs, HOMA-β may reflect compensatory hyperinsulinemia [71].

This figure illustrates the interrelation between plasma glucose levels, insulin secretion, and pancreatic β-cell function, as described by the HOMA-β index. Together, these trajectories demonstrate the physiological basis of the HOMA-β model and emphasize its utility in estimating the secretory capacity of β-cells under varying glycemic conditions.

It is important to note that although HOMA-IR and HOMA-β are rapid and accessible methods for assessing metabolic risks, careful interpretation of the results is required according to the species and physiological conditions of each patient to avoid diagnostic errors [57,72,73].

3.4. Reference Parameters for HOMA-IR and HOMA-β

Reference values for HOMA-IR and HOMA-β in humans are well established, are largely based on extensive clinical research, and serve as diagnostic standards for evaluating insulin sensitivity and pancreatic β-cell function [13,14], as shown in Table 1.

Generally, normal values for HOMA-IR are below 2.5, while HOMA-β values typically range between 100% and 150%, indicating adequate β-cell function [71,74]. These human-based thresholds are often used as reference points in translational studies.

When comparing these reference values to those observed in dogs and cats, notable differences emerge [19,30], as illustrated in Figure 3. For instance, overweight dogs and cats exhibited elevated HOMA-IR values (3.1 and 3.5, respectively), which surpass the typical human threshold for insulin resistance. Similarly, HOMA-β values were markedly increased in overweight dogs (180%) and moderately in overweight cats (160%), suggesting compensatory β-cell activity in response to insulin resistance [64].

Although the HOMA-IR and HOMA-β reference ranges are well established in humans, species-specific thresholds for dogs and cats are still under investigation. Therefore, the values illustrated in Figure 3 should be interpreted in a comparative context rather than against absolute human clinical cut-offs.

In veterinary studies, ref. [19] identified a HOMA-IR reference interval of 0.1–3.0 for lean cats, with significantly higher levels in overweight individuals (p < 0.0001). For dogs, ref. [39] suggested a HOMA-IR cutoff around 2.5 in the linear model and >4.4 in the nonlinear model, consistent with findings by [50] who proposed species-appropriate reference intervals for both HOMA-IR and HOMA-β. These results reinforce the concept that obesity-induced metabolic disturbances, including insulin resistance, are shared across species but must be evaluated within species-specific physiological frameworks (Figure 4).

These parameters are essential for monitoring the risk of developing type 2 diabetes and for identifying metabolic problems associated with insulin resistance [19,53,71]. When HOMA-IR exceeds the value of 2.5, it is considered indicative of significant insulin resistance, an important marker in the diagnosis of diabetes [47,71], as shown in Table 1 and Table 2.

Table 1. HOMA-IR and HOMA-β values in humans and the associated degree of diabetes [16,57,68,75].

HOMA-IR Value	Degree of Diabetes [Insulin Sensitivity]	HOMA-β Value	β-Cell Function
Below 1.0	Normal insulin sensitivity	100–150%	Normal β-cell function
1.0–2.5	Normal/moderate insulin sensitivity	100–150%	Normal β-cell function.
2.5–3.0	Mild insulin resistance	Below 100%	Slightly compromised β-cell function.
Above 3.0	Severe insulin resistance	Below 100%	Compromised β-cell function.

Table 1. HOMA-IR and HOMA-β values in humans and the associated degree of diabetes [16,57,68,75].

HOMA-IR Value	Degree of Diabetes [Insulin Sensitivity]	HOMA-β Value	β-Cell Function
Below 1.0	Normal insulin sensitivity	100–150%	Normal β-cell function
1.0–2.5	Normal/moderate insulin sensitivity	100–150%	Normal β-cell function.
2.5–3.0	Mild insulin resistance	Below 100%	Slightly compromised β-cell function.
Above 3.0	Severe insulin resistance	Below 100%	Compromised β-cell function.

Table 2. HOMA-IR and HOMA-β values in companion animals (dogs and cats) [19,53,71].

Species	HOMA-IR Value	Degree of Insulin Resistance	HOMA-β Value	β-Cell Function
Dogs	0.5–3.0	Normal–mild insulin resistance	100–150%	Normal–slightly compromised function.
Cats	0.5–2.5	Normal–mild insulin resistance	100–150%	Normal–slightly compromised function.
Overweight Dogs	2.5–3.0	Moderate insulin resistance	Below 100%	Compromised β-cell function.
Overweight Cats	2.0–2.5	Moderate insulin resistance	Below 100%	Compromised β-cell function.

Table 2. HOMA-IR and HOMA-β values in companion animals (dogs and cats) [19,53,71].

Species	HOMA-IR Value	Degree of Insulin Resistance	HOMA-β Value	β-Cell Function
Dogs	0.5–3.0	Normal–mild insulin resistance	100–150%	Normal–slightly compromised function.
Cats	0.5–2.5	Normal–mild insulin resistance	100–150%	Normal–slightly compromised function.
Overweight Dogs	2.5–3.0	Moderate insulin resistance	Below 100%	Compromised β-cell function.
Overweight Cats	2.0–2.5	Moderate insulin resistance	Below 100%	Compromised β-cell function.

Adapting these values for companion animals is more complex due to significant physiological differences between species [31,39,40,71]. Studies conducted on dogs suggest that an upper HOMA-IR threshold of 3.0 is associated with insulin resistance, while in cats, this threshold is usually lower, reflecting the metabolic particularities of each species [47,53]. For example, older or overweight dogs may develop insulin resistance even at higher HOMA-IR values, making the evaluation of this parameter essential for early diagnosis of metabolic issues [47,71,76]. In cats, studies show that diet can significantly influence HOMA values, with cats on low-carbohydrate diets exhibiting a different metabolic response compared to those on standard diets [77,78,79]. Additionally, adapting HOMA values according to the animal’s age and weight is crucial, as older animals or those with increased body weight have a higher risk of developing insulin resistance, as shown in Table 2 [30,43,80,81].

The physiology of insulin differs significantly between dogs and cats, highlighting the importance of adjusting reference values according to the respective species [9,16,55]. For example, dogs tend to develop insulin resistance more readily as they age or gain weight, making it necessary to consider these variables when interpreting HOMA-IR values [39,47]. Cats, on the other hand, may exhibit greater variability in HOMA values due to differences in insulin metabolism, and conditions such as obesity or chronic inflammation can significantly alter the results [30,31].

Factors such as obesity, chronic inflammation, and other metabolic disorders can significantly influence HOMA-IR and HOMA-β values, and these conditions are often correlated with an increased risk of developing diabetes or other metabolic diseases [60,71,82,83].

The interpretation of HOMA-IR and HOMA-β values should therefore be species-specific and aligned with the ALIVE classification. For example, elevated HOMA-IR in an IRD (insulin-resistant diabetes) cat suggests a potentially reversible stage if early intervention is initiated, whereas similar values in a dog with IDD usually indicate concurrent insulin resistance superimposed on an irreversible β-cell loss, requiring different therapeutic priorities.

Therefore, the interpretation of HOMA values in companion animals must take into account a variety of physiological and clinical factors, including age, weight, general health status, and diet [30,49,84]. These variable constants can significantly affect the results; thus, a reference framework adapted for each species is necessary [30,84]. The validation and adjustment of HOMA values for dogs and cats represent an essential step in developing an effective diagnostic and monitoring tool in veterinary practice [9,30,85].

3.5. Differences in the Use of HOMA Between Humans and Companion Animals

The use of HOMA indices (HOMA-IR and HOMA-β) in veterinary medicine requires significant adaptations due to physiological and metabolic differences between humans, dogs, and cats [16,18,19,50,71]. It is important to note that the original HOMA models were designed and validated exclusively for use in humans, and their direct application to other species may violate the model’s core assumptions [14]. This is further complicated by the absence of standardized insulin immunoassays for dogs and cats, which results in considerable variability between analytical methods and limits cross-study comparability. Therefore, while HOMA-derived indices can offer valuable insights in veterinary contexts, they must be interpreted cautiously, in conjunction with species-specific validation data and complementary metabolic markers (e.g., fructosamine, HbA1c, lipid profile, C-peptide).

In human studies, these indices have been validated on well-characterized physiological models, with established clinical thresholds for diagnosing insulin resistance and assessing β-cell function [14], as illustrated in Figure 5.

In humans, the mechanisms by which insulin regulates glucose concentrations and the ways in which imbalances occur in type 1 and type 2 diabetes are well understood [14,74]. In contrast, in companion animals, insulin physiology is influenced by a broader set of variables, and the types of diabetes differ significantly. According to the updated veterinary classification proposed by the ALIVE Project [5], canine diabetes mellitus most frequently manifests as insulin-deficient diabetes (IDD), typically caused by immune-mediated destruction of pancreatic β-cells, leading to absolute insulin deficiency and the need for lifelong insulin therapy. Conversely, feline diabetes is predominantly insulin-resistant diabetes (IRD), often accompanied by concurrent β-cell dysfunction, associated with obesity, physical inactivity, chronic inflammation, and glucolipotoxicity [32,86]

The use of the HOMA index to evaluate diabetes risk in companion animals faces additional challenges due to variability in basal blood glucose levels. In dogs, glucose values are generally more stable but can still be affected by stress, concurrent diseases, or medications [1]. In cats, stress-induced hyperglycemia is a well-known phenomenon that can significantly overestimate HOMA-IR [31]. Dietary composition, feeding patterns, and differences in carbohydrate metabolism between species can also influence both glucose and insulin dynamics [16,18].

Moreover, concurrent endocrine disorders such as hypothyroidism or hyperadrenocorticism can significantly alter HOMA values, impacting the correct interpretation of test results [5]. These conditions complicate the accurate assessment of insulin resistance and β-cell function in dogs and cats, often requiring species-specific reference ranges or even alternative diagnostic approaches.

It is important to note that the Homeostatic Model Assessment was originally developed and validated for humans [13,14]. Direct extrapolation to other species must be approached with caution. Nonetheless, several veterinary studies have investigated the potential of HOMA-derived indices as surrogate markers for insulin sensitivity in companion animals. For example, [19] reported that overweight cats had significantly higher HOMA-IR and fasting insulin concentrations compared to lean cats, with a positive correlation between HOMA-IR and body fat percentage, and proposed a tentative reference range for this species. Similarly [63] found that obese dogs with HOMA-IR > 2.4 could be classified as insulin resistant, supporting the discriminative ability of the index in clinical veterinary practice.

These findings indicate that while HOMA indices should be interpreted within the context of species-specific physiology, they remain valuable, non-invasive tools for estimating insulin sensitivity and β-cell function in both dogs and cats. When combined with additional diagnostic markers and clinical context, they can contribute to improved disease monitoring, early intervention, and individualized treatment strategies.

3.6. Protocol for Sample Collection and HOMA Determination

The protocol for blood sample collection to determine HOMA values involves measuring plasma glucose and insulin concentrations under fasting conditions [13,14,42]. This method is essential for obtaining accurate results, allowing a correct assessment of insulin sensitivity and β-cell function [16,17].

To ensure result accuracy, blood samples should be collected in the morning before feeding [20,42]. This precaution helps prevent postprandial hormonal fluctuations that could significantly alter measured values [13,20]. Standardizing the collection process is important to maintain consistency and facilitate comparisons between different studies and patients [16,20,87,88].

Plasma glucose concentrations are typically determined using enzymatic–colorimetric methods, which are recognized for their precision and efficiency in producing reliable results [13,42].

Another essential aspect of this protocol is the proper handling of blood samples immediately after collection [20,31,42,89]. It is imperative that samples be processed promptly to avoid degradation of biochemical components such as insulin, which can be affected by improper storage conditions [19,20]. Additionally, the use of appropriate materials for storage and transport helps maintain the stability of the analyzed biochemical parameters [31,40].

The entire workflow of the sampling and HOMA determination protocol, applicable to both humans and animals, is illustrated in Figure 6.

In companion animals, reference values for glucose and insulin can vary significantly depending on species, sex, and age [16,17]. Therefore, interpreting the results requires an individualized approach tailored to each patient [20,31]. By rigorously applying this protocol, an accurate evaluation of the HOMA index is ensured, thus contributing to the diagnosis and monitoring of diabetes mellitus and other metabolic dysfunctions [16,20,31].

3.7. Correlation Between HOMA-IR and Diabetes Severity

The correlation between the HOMA-IR (Homeostasis Model Assessment—Insulin Resistance) index and the severity of diabetes mellitus in companion animals represents a major area of interest in veterinary endocrinology [16,21]. Numerous studies have analyzed this relationship, highlighting the usefulness of this parameter in monitoring disease progression and optimizing therapeutic strategies [19,38]. An elevated HOMA-IR is an indicator of increased insulin resistance, a key pathophysiological factor that can negatively affect metabolic balance and often necessitates significant treatment adjustments to improve glycemic control [14]. A profound understanding of this correlation allows veterinarians to personalize therapeutic approaches and anticipate the risk of complications, contributing to a more effective management of the condition [17,23].

The severity of diabetes mellitus is defined not only by the magnitude of hyperglycemia but also by the degree of underlying metabolic dysfunction [4,8]. Insulin resistance, quantified by HOMA-IR, is a central element of this dysfunction, particularly in the context of insulin-resistant diabetes, which is prevalent in cats but also relevant in certain forms of canine diabetes [5]. At a physiological level, marked insulin resistance means that peripheral tissues [muscle, adipose tissue] and the liver respond inefficiently to the insulin signal [15]. This leads to reduced glucose uptake by cells and excessive hepatic glucose production, culminating in persistent hyperglycemia [4,21]. The pancreas initially attempts to compensate for this resistance by increasing insulin secretion (hyperinsulinemia), maintaining blood glucose within relatively normal limits. However, this compensation is often unsustainable, and pancreatic β-cells may eventually experience functional exhaustion [13,14]. As insulin resistance worsens, an increasingly larger amount of insulin is required to maintain adequate glycemic control. A high HOMA-IR, reflecting this increased insulin demand, is directly associated with poor glycemic control and difficulties in achieving therapeutic targets [31,63].

In line with the ALIVE classification, most canine diabetes cases correspond to IDD [insulin-deficient diabetes], whereas feline diabetes is typically IRD (insulin-resistant diabetes) [5,90]. This categorization is more accurate than directly mapping veterinary cases to human type 1 or type 2 diabetes, as it reflects species-specific pathophysiology and aids in targeted interpretation of HOMA values. Although canine diabetes is predominantly insulin-deficient due to β-cell destruction, insulin resistance can play a significant role in certain cases or complications. A high HOMA-IR in dogs may indicate intrinsic insulin resistance or resistance induced by factors such as obesity, chronic systemic inflammation, or endocrine comorbidities like hyperadrenocorticism or hypothyroidism [42]. This resistance can complicate management even in insulin-dependent dogs, requiring higher doses of exogenous insulin to achieve satisfactory glycemic control. Similarly, in cats, steroid administration (e.g., methylprednisolone acetate) has been shown to induce significant insulin resistance, which can be detected through HOMA indices [32]. Persistently high HOMA-IR in dogs has been associated with a poor metabolic response to insulin therapy and less stable glycemia, reflected by wide glycemic fluctuations or persistent hyperglycemic episodes [39].

In cats, where insulin-resistant diabetes is the predominant form, the correlation between HOMA-IR and disease severity is of particular importance [1,7]. Insulin resistance is a central pathophysiological event in feline diabetes, often exacerbated by obesity and physical inactivity [20]. High HOMA-IR values in cats reflect a significant degree of insulin resistance, which, if left unaddressed, can lead to pancreatic β-cell exhaustion and progression towards permanent insulin dependence [19,23]. Monitoring HOMA-IR in diabetic cats allows for the evaluation of therapeutic intervention efficacy. Specific dietary interventions—such as high-protein, low-carbohydrate diets—combined with weight management and, in some cases, oral hypoglycemic agents can significantly reduce insulin resistance, manifested by a decrease in HOMA-IR [1,7]. Such reductions are often correlated with improved glycemic control and, in early-stage cases, even diabetes remission.

Analyzing the correlation between HOMA-IR and diabetes severity provides crucial information for clinical management [16,17]. A high HOMA-IR signals the need for more vigorous therapeutic adjustments, which may include intensifying insulin therapy, implementing targeted dietary modifications, managing weight, and addressing comorbidities that exacerbate insulin resistance [1]. Longitudinal monitoring of HOMA-IR enables the evaluation of treatment response and the dynamic adjustment of therapy, ensuring that interventions remain aligned with the patient’s changing metabolic needs. Beyond its diagnostic and management utility, HOMA-IR also plays a predictive role [12,15]. A rising HOMA-IR, even without major glycemic changes, can indicate worsening insulin resistance and an increased risk of disease progression or complications. This is particularly valuable in screening programs for predisposed breeds or animals in a prediabetic state, such as obese cats with transient hyperglycemia [1,20]. Early detection enables preventive measures—dietary adjustments, exercise programs—that can delay or prevent clinical diabetes, improving quality of life and reducing the economic and emotional burden of chronic disease management.

While HOMA-IR is a valuable metric, it must be interpreted within the context of a complete clinical evaluation and additional metabolic markers such as fructosamine, HbA1c, lipid profiles, and C-peptide [13,14,91]. This integrated approach provides a comprehensive understanding of the patient’s metabolic state, supporting evidence-based and personalized treatment decisions.

4. Conclusions

The use of the Homeostasis Model Assessment (HOMA) indices for evaluating insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β) in companion animals provides a non-invasive, cost-effective, and repeatable method with significant potential for improving the diagnosis, classification, and management of diabetes mellitus [13,14]. Within the ALIVE veterinary classification [5], correct interpretation of HOMA indices must be species-specific. In dogs, where insulin-deficient diabetes (IDD) predominates, elevated HOMA-IR values may indicate concurrent insulin resistance superimposed on irreversible β-cell loss, complicating glycemic control [18]. In cats, where insulin-resistant diabetes (IRD) is the predominant form, high HOMA-IR often reflects an early, potentially reversible stage of the disease, particularly when addressed promptly with dietary modification, weight control, and pharmacological intervention [1,7,35].

Despite its advantages, the application of HOMA in veterinary practice faces challenges, including interindividual variability, the influence of comorbidities, and the absence of standardized reference values for different species, sexes, and ages [16,20].

These limitations underline the need for standardized protocols and large-scale, longitudinal studies to establish clinically relevant cut-off points.

Therefore, HOMA should be used as a complementary diagnostic and monitoring tool, integrated with other metabolic markers such as fructosamine, HbA1c, lipid profiles, and C-peptide, alongside a complete clinical evaluation. This integrated approach allows for personalized therapeutic adjustments, improved glycemic control, prevention of complications, and an overall enhancement of the quality of life in diabetic companion animals [9,23].