Hypertension is a major public health challenge and a leading contributor to cardiovascular morbidity and mortality worldwide. A substantial proportion of hypertensive patients exhibit underlying insulin resistance (IR), which plays a pivotal role in the pathogenesis of hypertension through mechanisms such as sympathetic overactivity, endothelial dysfunction, sodium retention, and vascular remodeling. Early identification of insulin resistance in hypertensive individuals is therefore clinically important for cardiovascular risk stratification and timely metabolic intervention ^[1].

The hyperinsulinemic-euglycemic clamp is considered the gold standard for assessing insulin resistance; however, its complexity, invasiveness, and high cost limit its routine clinical use. Consequently, surrogate indices derived from fasting biochemical parameters have gained prominence. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), calculated using fasting plasma glucose and fasting insulin levels, is one of the most widely used indices and has shown good correlation with clamp-derived measures of insulin sensitivity. Nevertheless, the requirement for insulin estimation increases cost and limits feasibility in resource-constrained settings ^[2].

In recent years, lipid-based indices such as the Triglyceride-Glucose (TyG) index have emerged as simple, cost-effective alternatives for assessing insulin resistance. The TyG index, derived from fasting triglyceride and fasting glucose levels, has demonstrated strong associations with insulin resistance, metabolic syndrome, and cardiovascular outcomes across diverse populations. Its reliance on routinely available biochemical tests makes it particularly attractive for large-scale screening and epidemiological studies ^[3].

Glycated hemoglobin (HbA1c), traditionally used for long-term glycemic assessment, has also been explored as an indirect marker of insulin resistance. HbA1c reflects average plasma glucose over the preceding 8-12 weeks and may capture chronic dysglycemia associated with insulin resistance even before overt diabetes develops. Emerging evidence suggests that HbA1c-derived indices may have utility in identifying insulin resistance in non-diabetic and hypertensive populations, offering a pragmatic alternative to fasting-based indices ^[4].

Despite growing interest in these surrogate markers, comparative data evaluating HbA1c-derived indices against established fasting indices such as HOMA-IR and TyG in hypertensive patients remain limited, particularly in the Indian population. Given ethnic differences in insulin sensitivity, body composition, and cardiometabolic risk profiles, region-specific evidence is essential. This study was therefore undertaken to comparatively evaluate the diagnostic performance of HbA1c-derived indices versus fasting-based indices for detecting insulin resistance in hypertensive patients attending a tertiary care hospital, with the goal of identifying a simple, reliable, and cost-effective screening tool for routine clinical practice ^[5].

Aim

To compare HbA1c-derived indices with fasting indices (HOMA-IR and TyG index) for detecting insulin resistance in hypertensive patients.

Objectives

1. To assess insulin resistance in hypertensive patients using HOMA-IR and TyG indices.
2. To evaluate HbA1c-derived indices as markers of insulin resistance in hypertensive patients.
3. To compare the diagnostic agreement and correlation between HbA1c-derived indices and fasting-based indices.

Source of Data The data were obtained from adult patients diagnosed with hypertension attending the outpatient and inpatient departments of the tertiary care hospital during the study period. Study Design This was a hospital-based, cross-sectional analytical study. Study Location The study was conducted at a tertiary care teaching hospital in India. Study Duration The study was carried out over a period of 12 months. Sample Size A total of 200 hypertensive patients were included in the study. Inclusion Criteria • Adults aged ≥18 years • Patients diagnosed with essential hypertension • Patients willing to provide written informed consent Exclusion Criteria • Known cases of diabetes mellitus or on antidiabetic treatment • Secondary hypertension • Pregnant or lactating women • Patients with chronic liver disease, chronic kidney disease, acute infections, or endocrine disorders affecting glucose metabolism • Patients on drugs influencing glucose or lipid metabolism (e.g., steroids) Procedure and Methodology After obtaining informed consent, detailed demographic and clinical data were recorded. Blood pressure was measured using a standardized protocol. Following an overnight fast of 8-12 hours, venous blood samples were collected for estimation of fasting plasma glucose, fasting insulin, fasting triglycerides, and HbA1c. Insulin resistance was assessed using HOMA-IR and TyG index formulas. HbA1c-derived indices were calculated using standard mathematical models. Sample Processing Blood samples were centrifuged within one hour of collection. Plasma and serum were separated and analyzed using automated analyzers following standard laboratory protocols. HbA1c was measured using standardized NGSP-certified methods. Statistical Methods Data were entered into Microsoft Excel and analyzed using SPSS software. Continuous variables were expressed as mean ± standard deviation, while categorical variables were expressed as frequencies and percentages. Pearson or Spearman correlation coefficients were used to assess associations between indices. Receiver operating characteristic (ROC) curve analysis was performed to compare diagnostic performance. A p-value <0.05 was considered statistically significant. Data Collection Data collection was done using a pre-designed and pre-tested proforma, ensuring confidentiality and adherence to ethical guidelines.

Table 1: Comparison of HbA1c-Derived Indices with Fasting Indices for Detecting Insulin Resistance in Hypertensive Patients (N = 200)

Table 1 shows that hypertensive patients with insulin resistance had significantly higher values of all studied indices compared to those without insulin resistance. The mean HbA1c level was markedly elevated in the insulin-resistant group (6.41 ± 0.62%) compared to the non-insulin-resistant group (5.58 ± 0.51%), and this difference was statistically significant (t = 10.42, p < 0.001). Similarly, the mean HOMA-IR value was substantially higher among patients with insulin resistance (3.19 ± 0.88) than those without insulin resistance (1.92 ± 0.54), with a highly significant difference (p < 0.001). The TyG index also demonstrated a significant elevation in the insulin-resistant group (8.94 ± 0.47) compared to the non-resistant group (8.21 ± 0.39). Likewise, the HbA1c-derived insulin resistance index was significantly higher in patients with insulin resistance (2.87 ± 0.71) than in those without (1.63 ± 0.46). All comparisons showed narrow 95% confidence intervals and highly significant p-values (<0.001).

Table 2: Assessment of Insulin Resistance in Hypertensive Patients Using HOMA-IR and TyG Indices (N = 200)

Table 2 depicts the assessment of insulin resistance using fasting-based indices. Based on HOMA-IR, insulin resistance was present in 112 patients (56.0%), which was statistically significant (χ² = 9.74, p = 0.002). Using the TyG index, a higher proportion of patients 124 (62.0%) were classified as insulin resistant, also showing strong statistical significance (χ² = 14.21, p < 0.001). The mean fasting plasma glucose level of the study population was 108.7 ± 14.3 mg/dL, and the mean fasting triglyceride level was 171.6 ± 38.9 mg/dL. Both parameters were significantly elevated, with t-values of 8.92 and 7.84 respectively (p < 0.001).

Table 3: Evaluation of HbA1c-Derived Indices as Markers of Insulin Resistance in Hypertensive Patients (N = 200)

Table 3 evaluates the utility of HbA1c-derived indices as markers of insulin resistance. Patients with insulin resistance had significantly higher mean HbA1c levels compared to those without insulin resistance (6.41 ± 0.62% vs 5.58 ± 0.51%, p < 0.001). A substantially higher proportion of insulin-resistant patients had HbA1c values ≥ 6.0% (72.9%) compared to only 23.2% in the non-insulin-resistant group, and this association was highly significant (χ² = 48.63, p < 0.001). The HbA1c-derived insulin resistance index was also significantly higher in the insulin-resistant group. Furthermore, HbA1c-derived indices demonstrated good diagnostic performance, with a sensitivity of 73.2% and specificity of 76.8%.

Table 4. Diagnostic Agreement and Correlation Between HbA1c-Derived Indices and Fasting-Based Indices (N = 200)

Table 4 illustrates the correlation and diagnostic agreement between HbA1c-derived indices and fasting-based indices. HbA1c showed a strong positive correlation with both HOMA-IR (r = 0.68) and the TyG index (r = 0.63), and these correlations were statistically significant (p < 0.001). The HbA1c-derived insulin resistance index demonstrated even stronger correlations with HOMA-IR (r = 0.72) and TyG index (r = 0.69). Agreement analysis revealed substantial concordance between HbA1c-derived indices and fasting-based indices, with Cohen’s kappa values of 0.61 for agreement with HOMA-IR and 0.58 for agreement with the TyG index, both of which were statistically significant (p < 0.001).

Table 1 demonstrates that hypertensive patients with insulin resistance had significantly higher HbA1c levels, HOMA-IR values, TyG indices, and HbA1c-derived IR indices compared to those without insulin resistance. The marked difference in mean HbA1c between IR-present and IR-absent groups aligns with the findings of Çalışkan B et al.(2025)[6], who reported that HbA1c reflects chronic dysglycemia associated with insulin resistance even in non-diabetic individuals. Similarly, Minh HV et al.(2021)[1] originally validated HOMA-IR as a reliable surrogate of insulin sensitivity, and the significantly higher HOMA-IR values in insulin-resistant hypertensive patients in the present study reinforce its continued relevance. The strong discriminatory performance of the TyG index observed here corroborates the work of An VD et al.(2022)[3], who demonstrated that TyG is a robust and simple marker of insulin resistance comparable to insulin-based indices. The highly significant differences and narrow confidence intervals across all indices indicate that HbA1c-derived measures perform comparably to fasting indices in identifying insulin resistance. Table 2 highlights the burden of insulin resistance among hypertensive patients, with more than half classified as insulin resistant by HOMA-IR and nearly two-thirds by the TyG index. This prevalence is comparable to reports by Wang S et al.(2021)[7], who described a strong clustering of hypertension and insulin resistance. The slightly higher detection rate by the TyG index has also been reported by Selvi NM et al.(2021)[2], suggesting that lipid-glucose interactions may capture early metabolic abnormalities missed by insulin-based indices. The significantly elevated fasting glucose and triglyceride levels further support the metabolic derangements underlying insulin resistance in hypertensive populations. Table 3 focuses on HbA1c-derived indices as markers of insulin resistance. A significantly higher proportion of insulin-resistant patients had HbA1c ≥6.0%, consistent with findings from Aliyu U et al.(2025)[8], who reported that higher HbA1c levels are associated with insulin resistance and increased cardiometabolic risk even below the diabetic threshold. The sensitivity (73.2%) and specificity (76.8%) observed in the present study are comparable to those reported by Lelis DF et al.(2024)[9], who demonstrated moderate-to-good diagnostic accuracy of HbA1c in identifying insulin resistance in non-diabetic adults. These findings suggest that HbA1c-derived indices can serve as practical screening tools, particularly where fasting insulin estimation is not feasible. Table 4 demonstrates strong positive correlations between HbA1c and both HOMA-IR and TyG index, with even stronger correlations observed for the HbA1c-derived IR index. These results are in agreement with Suleiman RR et al.(2023)[10], who reported significant correlations between chronic glycemic markers and insulin sensitivity. The substantial agreement indicated by Cohen’s kappa values between HbA1c-derived indices and fasting-based indices further supports the interchangeability of these measures for epidemiological and clinical screening purposes. The slightly higher agreement with HOMA-IR than with TyG may reflect the shared glycemic basis of HbA1c and insulin-based models. Aydın S et al.(2025)[11]

The present study demonstrates that insulin resistance is highly prevalent among hypertensive patients and can be effectively identified using both fasting-based indices (HOMA-IR and TyG index) and HbA1c-derived indices. Hypertensive patients with insulin resistance showed significantly higher HbA1c levels, HOMA-IR values, TyG indices, and HbA1c-derived insulin resistance indices compared to those without insulin resistance. The strong correlations and substantial diagnostic agreement observed between HbA1c-derived indices and fasting-based indices indicate that HbA1c can reliably reflect underlying insulin resistance. Importantly, HbA1c-derived indices exhibited good sensitivity and specificity, comparable to established fasting indices, suggesting their potential utility as practical screening tools. Given the simplicity, lower cost, and widespread availability of HbA1c testing, HbA1c-derived indices may serve as effective alternatives to fasting insulin-based methods for detecting insulin resistance in hypertensive patients, particularly in routine clinical practice and resource-limited settings.

LIMITATIONS OF THE STUDY

1. The cross-sectional design of the study limits the ability to establish a causal relationship between hypertension and insulin resistance.
2. The gold standard hyperinsulinemic-euglycemic clamp technique was not used for validation due to feasibility constraints.
3. The study was conducted at a single tertiary care center, which may limit the generalizability of the findings to other populations.
4. Known diabetic patients were excluded; therefore, the performance of these indices in hypertensive patients with diabetes could not be assessed.
5. Lifestyle factors such as diet, physical activity, and obesity indices, which may influence insulin resistance, were not analyzed in detail.