Insulin resistance is recognized as impaired biological insulin response with normal concentrations that correlate with a cluster of disorders such as cardiovascular disease (CVD), obesity, hypertension, type 2 diabetes . Up to now, numerous methods have been suggested for the measurement of IR in clinical practice . Some techniques such as a hyperinsulinemic - euglycemic clamp, as the gold standard method of IR, are difficult for use in clinical practices and population-based studies . Among them, HOMA-IR index is proposed as a simple surrogate for wider use in everyday clinical practice [18, 19]. HOMA-IR is a well-established index that assesses insulin resistance status based on comparing fasting glucose and circulating insulin levels that higher HOMA-IR indicates more insulin resistance . The reference value of HOMA-IR has been assessed in several human studies [13, 14, 16, 17]. To the best of our knowledge, data regarding reference value and accurate threshold of HOMA-IR are limited in the Iranian healthy population. Therefore, this study sought to report values of the HOMA-IR index regarding age and gender in healthy Iranian individuals. In this study, the mean value of HOMA-IR was 2.11 ± 0.99 in the total population. As noted earlier, mean values of HOMA-IR were reported regarding gender and age differences. The findings of the present study showed higher mean values of HOMA-IR in the men group compared to female subjects. In addition, the HOMA-IR mean values were increased in higher ages in both female and male groups.
Previous literature have evaluated HOMA-IR values in various pathological conditions with different ethnicities and clinical backgrounds [1, 4, 7, 8, 18]. One study by Esteghamati et al. investigated 1276 non-diabetic and non-hypertensive subjects in the Iranian population . The authors indicated that the normal value of HOMA-IR was 1.8 ± 1.13 in the whole population and the lower limit of the top quintile of HOMA-IR distribution values in normal subjects was 1.78 (1.69 for men and 1.81 for women). In another study, Yamada et al reported mean value of 2.0 for HOMA-IR in non-obese Japanese individuals [12, 18]. Nakai et al. reported the mean value of 1.7 (90th percentile) for IR in Japanese subjects . It has been noted that the optimal cut-off point for HOMA-IR was 1.77 in non-diabetic and 3.87 in diabetic Iranian subjects . Gayoso et al investigated 2459 random Spanish population samples . They proposed the mean value of 2 ± 1.1 in the total population and 1.9 ± 1 for women and 2.1 ± 1.2 for men. In another multicenter cross-sectional survey, Vilela et al indicated the mean value of 1.7 (1.1–2.7) for HMA-IR in 1061 non-diabetic Brazilian individuals .
In the present study, the mean values of HOMA-IR were higher than previous investigations. One reason for the inconsistency of our results with previous studies could be different clinical methods of insulin and glucose measurement. It has been argued that various insulin assays reflect different insulin levels and ultimately result in different HOMA-IR values . Another possible explanation for this discrepancy may be population diversity in terms of ethnicity. It is noteworthy that previous studies applied different inclusion criteria for defining and measurement of insulin resistance. It has been noted that both ethnic differences and gender variations can affect the reference range of HOMA-IR in different populations . In this study, the mean values of HOMA-IR in the women group were slightly lower than the male group. In accordance with these results, Isokuortti et al. reported that after adjustment for age and BMI, men had slightly higher HOMA-IRs than women . Previous population-based studies including healthy individuals have not reported HOMA-IRs separately for men and women [17, 20]. Even though Individuals in the present study were non-obese with normal glucose and lipid metabolism, these differences between two genders may be related to sexual maturity and adipose tissue accumulation pattern in adolescent population. It has been argued that in Indian the adolescents HOMA-IR scores increased with sexual maturity and with progression from normal to obese and a HOMA-IR cut-off of 2.5 provided the maximum sensitivity and specificity in diagnosing .
In conclusion, the current results showed the mean value of 2.49 ± 1.28 for HOMA-IR in the Iranian healthy population. In addition, the finding revealed a higher HOMA-IR value in men compared to females. As noted in the current study, we reported different reference values of HOMA-IR in healthy subjects compared to previous literature. Considering the large sample size in our study, more clinical investigations in terms of ethnicity should be done to provide a precise standardized HOMA-IR index in Iranian population. Reference values for HOMA-IR, even in healthy individuals may be population-specific and every laboratory should establish its own reference value for HOMA-IR, or at least understand how its insulin assay compares with other laboratories.