Limitation of the validity of the homeostasis model assessment as an index of insulin resistance in Korea

Homeostasis model assessment of insulin resistance (HOMA-IR) is a less invasive, inexpensive, and less labor-intensive method to measure insulin resistance (IR) as compared with the glucose clamp test. The aim of this study was to evaluate the validity of HOMA-IR by comparing it with the euglycemic clamp test in determining IR. We assessed the validity of HOMA-IR by comparing it with the total glucose disposal rate measured by the 3-hour euglycemic-hyperinsulinemic clamp in subjects with type 2 diabetes (n = 47), impaired glucose tolerance (n = 21), and normal glucose tolerance (n = 22). There was a strong inverse correlation (r = -0.558; P < .001) between the log-transformed HOMA-IR and the total glucose disposal rate. There was moderate agreement between the 2 methods in the categorization according to the IR (weighted kappa = 0.294). The magnitude of the correlation coefficients was smaller in the subjects with a lower body mass index (BMI <25.0 kg/m2 , r = -0.441 vs BMI > or =25.0 kg/m2 , r = -0.615; P = .032), a lower HOMA-beta cell function (HOMA- beta <60.0, r = -0.527 vs HOMA- beta > or =60.0, r = -0.686; P = .016), and higher fasting glucose levels (fasting glucose < or =5.66 mmol/L, r = -0.556 vs fasting glucose >5.66 mmol/L, r = -0.520; P = .039). The limitation of the validity of the HOMA-IR should be carefully considered in subjects with a lower BMI, a lower beta cell function, and high fasting glucose levels such as lean type 2 diabetes mellitus with insulin secretory defects.     

Short-term exercise improves beta-cell function and insulin resistance in older people with impaired glucose tolerance

BACKGROUND: There is a high prevalence of diabetes and impaired glucose tolerance (IGT) in the older population. Normal aging is associated with insulin resistance and impaired insulin secretion, with greater defects in people with IGT. Short-term exercise has been found to increase insulin sensitivity, but little is known about acute exercise effects on beta-cell function in older people with IGT. METHODS: We assessed the effects of 7 consecutive days of supervised aerobic exercise (1 h/d at 60-70% heart rate reserve) in 12 sedentary older people with IGT. Screening included oral glucose tolerance test, stress/maximal O(2) uptake test, and dual-energy x-ray absorptiometry scan. Participants had a frequently sampled iv glucose tolerance test at baseline and 15-20 h after the seventh exercise session. Insulin sensitivity (S(I)), glucose disappearance constant (Kg, a measure of iv glucose tolerance), acute insulin response to glucose (AIRg), and disposition index (AIRg x S(I)), a measure of beta-cell function in relation to insulin resistance, were calculated. RESULTS: Exercise was well tolerated. Body weight, fasting glucose, fasting insulin, and iv glucose tolerance were unchanged with exercise. S(I) increased by 59%, AIRg decreased by 12%, and disposition index increased by 31%. There was no significant change in fasting lipid, catecholamine, leptin, or adiponectin levels. CONCLUSIONS: Short-term exercise not only improved insulin resistance but also significantly enhanced beta-cell function in older people with IGT. These effects of short-term exercise on beta-cell function cannot be explained by changes in body weight or circulating levels of lipids, leptin, adiponectin, or catecholamines.     

Targeting insulin resistance and beta-cell dysfunction: the role of thiazolidinediones

Insulin resistance and beta-cell dysfunction are fundamental defects that contribute to the development of type 2 diabetes, and as such are targets for primary prevention of disease progression. The two parameters are linked by several factors, including glucotoxicity and lipotoxicity, and recent research has enlightened understanding of the molecular mechanisms underlying the development and progression of the disease. Historically, type 2 diabetes has been managed by controlling hyperglycemia, using agents that increase insulin levels or reduce hepatic glucose production, as exemplified by the United Kingdom Prospective Diabetes Study. The thiazolidinediones control hyperglycemia by targeting the fundamental defects of the disease, and have shown well-documented improvements in insulin sensitivity and beta-cell function, both in monotherapy and in combination with other oral antidiabetic agents. TRoglitazone In the Prevention Of Diabetes (TRIPOD) has demonstrated the potential for thiazolidinediones to delay progression to type 2 diabetes. Prospective studies such as Diabetes REduction Approaches with ramipril and rosiglitazone Medications (DREAM) are currently evaluating the long-term effects of thiazolidinediones on metabolic status and disease progression.     

Modifications of the homeostasis model assessment of insulin resistance index with age

The aim of the study was to analyze the association between aging and insulin resistance estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). This work involved two studies: (1) the Di@bet.es study is a cross-sectional study including 4,948 subjects, comprising a representative sample of the adult Spanish population; (2) the Pizarra study is a population-based cohort study undertaken in Pizarra (Spain), in which 1,051 subjects were evaluated at baseline and 714 completed the 6-year follow-up study. Study variables included a clinical and demographic structured survey, a lifestyle survey, a physical examination, and an oral glucose tolerance test in subjects without diabetes. In the Di@bet.es study overall, an increase occurred in blood glucose until the age of 50, after which it remained stable (data adjusted for gender, body mass index, abnormal glucose regulation [AGR]). The HOMA-IR increased significantly with age (p = 0.01), due to a higher prevalence of obesity (p < 0.0001) and AGR (p < 0.001). In non-obese subjects without AGR, HOMA-IR values were not modified with age (p = 0.30), but they were with body mass index (p < 0.001). In the Pizarra study, the HOMA-IR was significantly lower after 6-year follow-up in the whole study population. Subjects with a HOMA-IR level higher than the 75th percentile at baseline were more likely to develop diabetes (OR 2.2, 95 % CI 1.2–3.9; p = 0.007) than subjects with a lower HOMA-IR. We concluded that age per se did not increase HOMA-IR levels, changes that might be related to higher rates of obesity and AGR in older subjects. The HOMA-IR was associated with an increased risk of developing type 2 diabetes 6 years later.     

Clinical significance of the insulin resistance index as assessed by homeostasis model assessment

To examine the clinical significance of the insulin resistance index as determined by homeostasis model assessment (HOMA-IR), we investigated the relationship between HOMA-IR and the insulin resistance estimated by the euglycemic-hyperinsulinemic clamp method in various subgroups and compared the significance of HOMA-IR with that of fasting plasma insulin levels (FIRI). HOMA-IR was significantly correlated to the inverse of the glucose infusion rate (1/GIR) in both diabetic and non-diabetic subjects (r=0.747, P<0.0001 and r=0.419, P<0.002, respectively). In the diabetic patients, treatment with sulfonylureas did not weaken this correlation (r=0.833, P<0.0001). HOMA-IR was found to be closely related to FIRI (r=0.932, P<0.0001), but HOMA-IR was more closely associated with 1/GIR than FIRI was. HOMA-IR as well as 1/GIR was correlated with the visceral fat area (VFA) more closely than with the subcutaneous fat area (SFA), while FIRI was correlated almost equally with both of them. In conclusion, HOMA-IR is a convenient and beneficial method for evaluating insulin resistance, especially in subjects with visceral fat accumulation, and reflects insulin resistance obtained by euglycemic clamp more accurately than FIRI alone.     

The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes

The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes have been debated extensively. The concept that a feedback loop governs the interaction of the insulin-sensitive tissues and the beta cell as well as the elucidation of the hyperbolic relationship between insulin sensitivity and insulin secretion explains why insulin-resistant subjects exhibit markedly increased insulin responses while those who are insulin-sensitive have low responses. Consideration of this hyperbolic relationship has helped identify the critical role of beta-cell dysfunction in the development of Type 2 diabetes and the demonstration of reduced beta-cell function in high risk subjects. Furthermore, assessments in a number of ethnic groups emphasise that beta-cell function is a major determinant of oral glucose tolerance in subjects with normal and reduced glucose tolerance and that in all populations the progression from normal to impaired glucose tolerance and subsequently to Type 2 diabetes is associated with declining insulin sensitivity and beta-cell function. The genetic and molecular basis for these reductions in insulin sensitivity and beta-cell function are not fully understood but it does seem that body-fat distribution and especially intra-abdominal fat are major determinants of insulin resistance while reductions in beta-cell mass contribute to beta-cell dysfunction. Based on our greater understanding of the relative roles of insulin resistance and beta-cell dysfunction in Type 2 diabetes, we can anticipate advances in the identification of genes contributing to the development of the disease as well as approaches to the treatment and prevention of Type 2 diabetes.     

Neither homeostasis model assessment nor quantitative insulin sensitivity check index can predict insulin resistance in elderly patients with poorly controlled type 2 diabetes mellitus

To clarify whether homeostasis model assessment (HOMA IR) and quantitative insulin sensitivity check index (QUICKI) may be indicators of insulin resistance in elderly patients with type 2 diabetes mellitus, their relationship with the glucose infusion rate during the euglycemic hyperinsulinemic clamp study (clamp IR) was assessed. This study comprised 56 Japanese patients with type 2 diabetes mellitus; of these, 28 were 70 yr of age or older (group 1) and 28 were less than 70 yr of age (group 2). Their blood sugars were in poor control (fasting plasma glucose levels: group 1, 9.0 +/- 2.6 mmol/liter; group 2, 8.9 +/- 2.3 mmol/liter; hemoglobin A1c: group 1, 9.5 +/- 2.0%; group 2, 9.2 +/- 1.7%). Log-transformed HOMA IR was significantly correlated with the clamp IR in group 2 patients (r = -0.51, P < 0.01), but not in group 1 patients (r = -0.28, P = 0.15). There was a significant positive correlation between QUICKI and clamp IR in group 2 patients (r = 0.50, P < 0.01). However, no significant correlation was observed between QUICKI and clamp IR in group 1 patients (r = 0.31, P = 0.12). There was a significant correlation between log-transformed HOMA IR (r = -0.37, P < 0.01) or QUICKI (r = 0.37, P < 0.01) and clamp IR when both groups were combined. In conclusion, neither HOMA IR nor QUICKI should be used as an index of insulin resistance in elderly patients with poorly controlled type 2 diabetes mellitus. The results of this study suggest the need for developing a new noninvasive method for evaluating insulin resistance in those patients.     

Relative role of insulin resistance and beta-cell dysfunction in the progression to type 2 diabetes--The Kinmen Study

This study compared the relative role of insulin resistance and beta-cell dysfunction (both assessed using the HOMA method) with glucose intolerance conditions in the progression to type 2 diabetes among a high risk group of subjects with fasting plasma glucose (FPG) 5.6-7.0 mmol/l in Kinmen, Taiwan. Data were collected during a continuing prospective study (1998-99) of a group of Taiwanese subjects at high-risk of developing type 2 diabetes who had fasting hyperglycemia (5.6-7.0 mmol/l) and exhibited 2-h postload glucose concentrations <11.1 mmol/l from 1992-94 to 1995-96. Among 644 non-diabetic subjects at baseline, 79.8% (514/644) had at least one follow-up examination. There were 107 new cases of diabetes diagnosed by 1999 WHO criteria in 2918.7 person-years of follow-up. The incidence rate was 3.67%/year (107/2918.7). After adjustment for other possible associative variables, including gender, age, BMI, waist circumference, insulin resistance, and beta-cell dysfunction, Cox's hazard model showed that those individuals with isolated IFG (impaired fasting glucose) and those individuals with isolated IGT (2-h glucose impairment) exhibited similar risk of developing diabetes. Those individuals with isolated IFG and isolated IGT showed a comparable impairment of basal or hepatic insulin sensitivity, but those individuals with isolated IFG had a greater beta-cell dysfunction by the HOMA method.     

Optimal reference interval for homeostasis model assessment of insulin resistance in a Japanese population

The aim of the present study was to establish a reference interval for homeostasis model assessment of insulin resistance (HOMA‐IR) in a Japanese population based on the C28‐A3 document from the Clinical and Laboratory Standards Institute (CLSI). We selected healthy subjects aged 20–79 years, with fasting plasma glucose < 100 mg/dL, body mass index < 25 kg/m² and alanine aminotransferase < 31 U/L. HOMA‐IR values were log transformed, values beyond mean ± 3 standard deviations (SD) were truncated, and the mean ± 2 SD of log HOMA‐IR values were taken as the upper and lower reference limits of HOMA‐IR. We selected 2173 subjects as reference individuals, and 2153 subjects were used for analysis. The reference interval for HOMA‐IR was established as between 0.4 and 2.4. This represents the first reference interval study for HOMA‐IR that applies the stringent CLSI C28‐A3 document. HOMA‐IR ≥ 2.5 should be considered a reasonable indicator of insulin resistance in Japanese. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00113.x, 2011)     

Cystic fibrosis-related diabetes: the role of peripheral insulin resistance and beta-cell dysfunction.

AIMS: The goal of this study was to identify the glycaemic status and investigate the roles of peripheral insulin resistance (IR) and pancreatic -cell dysfunction in the pathogenesis of cystic fibrosis-related diabetes (CFRD) in adult cystic fibrosis (CF) patients with no previous history of glycaemic disturbances. METHODS: The glucose tolerance status of 68 CF patients was determined using 2-h oral glucose tolerance tests (OGTTs). Peripheral IR was measured using the homeostasis model assessment for insulin resistance (HOMA-IR) in the CF group and 46 normal healthy control subjects. Pancreatic -cell function, calculated as the ratio between the 30-min increment in plasma insulin and the corresponding 30-min post-OGTT plasma glucose concentration, was also measured in a subset of 30 CF patients and 16 normal healthy controls. Extended 180-min OGTTs, with frequent plasma glucose and insulin sampling, were also undertaken in 24 CF patients and eight normal healthy controls to determine glucose-induced insulin response. RESULTS: Of the 68 CF patients studied, 41, 18 and nine were found to have normal, impaired and diabetic glucose tolerances, respectively. The mean HOMA-IR values (mU/mmol) in the CF patients, as a whole, were not significantly different compared with the normal healthy controls (CF 2.2 +/- 1.1 vs. control 1.8 +/- 0.9; NS). Within the CF group, glycaemic status had no impact on HOMA-IR (mU/mmol): 2.2 +/- 1.2 (normal glucose tolerance); 2.0 +/- 1.0 (impaired glucose tolerance); and 2.3 +/- 1.1 (diabetic glucose tolerance). -cell function (mU/mmol) was not only significantly lower in the CF group (CF 1.65 +/- 1.8; P < 0.001) but also in the CF group with normal glucose tolerance (2.25 +/- 2.10; P < 0.01) compared with healthy control (4.98 +/- 2.38). Mean plasma glucose concentrations were generally higher and mean plasma insulin concentrations lower in the CF group as a whole when compared with normal healthy controls. Within the CF group, there was a progressive decline in glucose-induced insulin release with worsening glycaemic status. CONCLUSIONS: A lack of difference in peripheral IR, measured using HOMA-IR, in the CF group and healthy controls or within the CF group with differing glycaemic status suggests that IR does not have a significant role in the pathogenesis of CFRD. Pancreatic -cell function, already subnormal in CF patients with OGTT-defined normal glucose tolerance status, deteriorated further with worsening glycaemic status. This suggests that insulinopenia plays a prominent role in the pathogenesis of glucose intolerance and subsequent development of CFRD.     

Longitudinal assessment of insulin sensitivity in pregnancy. Validation of the homeostasis model assessment

OBJECTIVE: To validate the use of the homeostasis model assessment (HOMA) for measurement of insulin sensitivity in obese women during gestation and the postpartum period. DESIGN: Three consecutive measurements of insulin resistance (IR) were performed during and after pregnancy to compare the homeostasis model assessment insulin sensitivity index (HOMA-IR) to glucose utilization rates obtained during hyperinsulinaemic euglycaemic clamps (G(Rd)). PATIENTS: Six obese women (mean second trimester BMI = 30.4 kg/m(2)) with normal glucose tolerance were studied during the second and third trimesters of pregnancy and once in the postpartum period. Thus, there were a total of 18 measurements for analysis. RESULTS: Correlations between the rate of glucose disappearance (G(Rd)) (the gold standard) and the HOMA-derived metabolic parameters of insulin sensitivity were significant, with a multiple R(2) of 43.5% (P = 0.003). However, when controlling for variations between patients using dummy variables, we observed that one patient differed from the other five in the relationship between G(Rd) and HOMA-IR. Applying this regression we obtained a R(2) of 72.6% (P < 0.001). When the regression constant was omitted, we observed that the individual trends during pregnancy and postpartum in two patients differed statistically from the other patients between the two assessments, and we obtained a multiple R(2) of 97.3% (< 0.001). CONCLUSIONS: HOMA estimation of insulin resistance is appropriate for use during both the second and third trimesters of pregnancy and postpartum in obese women with normal glucose tolerance. It lacks sensitivity for the evaluation of individuals, where more precise measures of insulin sensitivity should be utilized.     

Preliminary report: homeostasis model assessment of insulin resistance, an indicator of insulin resistance, is strongly related to serum insulin: practical data presentation and the mathematical basis

The homeostasis model assessment for insulin resistance (HOMA-R) is frequently used as an indicator of insulin resistance. The purpose of this study was to clarify the advantage of HOMA-R as an indicator of insulin resistance. A population of 3008 Japanese male workers (34 to 64 years old), who have no history of diabetes mellitus, hypertension, dyslipidemia, hyperuricemia, coronary and/or cerebrovascular disease and their fasting plasma glucose were under 140 mg/dL. The Spearman's rank correlation coefficient between HOMA-R and the serum insulin was 0.982. Although HOMA-R is also regulated by the plasma glucose, insulin and plasma glucose are not independent. The lower and upper 2.5%ile data of plasma glucose were prepared, which were used for mathematical basis of strong correlation between HOMA-R and serum insulin. Subjects with higher insulin had higher plasma glucose, which was resulted in higher HOMA-R. In the same manner, HOMA-R would become lower in the area of lower insulin levels. As two lines of the lower and upper 2.5%ile data of plasma glucose exists near, the correlation between HOMA-R and serum insulin became very strong. Although HOMA-R is a popular indicator of insulin resistance, we recommend that HOMA-R could be substituted simply by serum insulin. This may be valid in the general population with no remakable medical condition.     

Different contributions of insulin resistance and beta-cell dysfunction in overweight Israeli Arabs with IFG and IGT

BACKGROUND: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are both intermediate stages that exist between normal glucose tolerance and overt type 2 diabetes. Epidemiological studies demonstrated that the two categories define distinct populations. In this study, we examined the contributions of insulin resistance and beta-cell dysfunction to both states in overweight subjects of Arab origin. METHODS: Twelve subjects with isolated IFG, 10 with isolated IGT, and 20 with IFG and IGT (combined glucose in tolerance-CGT) were compared with 30 subjects with normal glucose tolerance (NGT) subjects; all were of Arab origin and were overweight or obese. Different indices for insulin resistance and beta-cell function were calculated from oral glucose tolerance (OGTT) values. RESULTS: Subjects with isolated IFG and CGT were more obese and had significantly higher values of insulin resistance than subjects with isolated IGT and NFG. There was no significant difference between the insulin resistance in subjects with isolated IGT and that in subjects with NGT. Indices of beta cell function were severely reduced among subjects with isolated IGT and CGT when compared with those with both isolated IFG and NGT, while subjects with isolated IFG had similar beta-cell indices to subjects with NGT. CONCLUSION: These data demonstrate that beta-cell dysfunction and insulin resistance contribute differently to the pathogenesis of IFG and IGT among overweight Arab subjects.     

A novel index of insulin resistance determined from the homeostasis model assessment index and adiponectin levels in Japanese subjects

Insulin resistance is the principal cause of glucose intolerance and type 2 diabetes and induces progression of severe atherosclerosis in these patients. Adiponectin, the adipose-specific proteins, is known to correlate negatively with insulin resistance in patients with obesity and type 2 diabetes. The purpose of this study was to evaluate the potential of using serum adiponectin levels as a marker of insulin resistance in various states of insulin resistance. Furthermore, we attempted to establish a modified index of the homeostasis model assessment index (HOMA-IR), calculated from the product of serum insulin and plasma glucose levels divided by serum adiponectin levels (HOMA-AD). We recruited 117 Japanese subjects with various degrees of glucose tolerance and determined serum adiponectin levels and insulin sensitivity (M-value) by using the euglycemic hyperinsulinemic clamp technique. M-value, the gold standard index of insulin resistance, correlates significantly and independently with fasting insulin (r=-0.313, P<0.001), glucose (r=-0.319, P<0.001), and adiponectin (r=0.241, P<0.002) levels. M-values were more significantly correlated with HOMA-AD (r=-0.643, P<0.001) than HOMA-IR values (r=-0.591, P<0.001). In subjects with moderate hyperglycemia (fasting glucose levels>8.0mmol/L, n=30), HOMA-AD showed a more significant correlation with the M-value than HOMA-IR (r=-0.535, P=0.005 versus r=-0.461, P=0.010). We would therefore like to propose a novel index, HOMA-AD, as a simple and adequate index for determining insulin resistance even in diabetic patients with overt hyperglycemia.     

The interplay of insulin resistance and beta-cell dysfunction involves the development of type 2 diabetes in Chinese obeses

Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder characterized by defects in insulin secretion and action and obesity plays an important role in the deterioration of glucose metabolism. In the present study we evaluated the degree of insulin resistance and first-phase insulin secretion of β-cell in obese subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM in Chinese. A total of 220 subjects underwent standard 75 g oral glucose tolerance test (OGTT) and insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity index (S _I) was assessed by the reduced sample number (n = 12) of Bergman’s minimal model method with FSIGT. Insulin secretion capacities were determined by the insulinogenic index (I _{30 min} − I _{0 min})/(G _{30 min} − G _{0 min}) in OGTT and the acute insulin response to glucose (AIR) in FSIGT. The disposition index (DI), the product of AIR and S _I was used to determine whether AIR was adequate to compensate for insulin resistance. The S _I in healthy lean control group was significantly higher than that in NGT, IGT, and T2DM group, but there was no significant difference among NGT, IGT, and T2DM group. The AIR in NGT group was significantly greater than that in control group, but then it was progressively decreased in IGT and T2DM group. The value of DI in control group was significantly higher than that in those three abnormal groups, and was decreased from NGT to IGT and T2DM group with significant difference. It indicates that obese subjects with different glucose tolerances have a similar degree of insulin resistance but differ in insulin secretion in Chinese Han population.     

Relationship between alcohol consumption and insulin resistance measured using the homeostatic model assessment for insulin resistance: A retrospective cohort study of 280,194 people

Background and aimAlcohol consumption causes metabolic disorders and is a known risk factor for cardiovascular disease. However, some studies suggested that low level alcohol consumption improves insulin resistance. We evaluated the effects of alcohol consumption on insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR).Methods and resultsThis study included 280,194 people without diabetes who underwent comprehensive health examinations more than twice between 2011 and 2018. The levels of alcohol intake were obtained through a self-questionnaire. All subjects were divided into two groups based on the Korean standard cut-off value of HOMA-IR, 2.2. Cox proportional hazard analysis was used to assess the risk of insulin resistance according to alcohol consumption. The mean age of the study subjects was 38.2 years and 55.7% were men. During the follow-up period (median 4.13 years), HOMA-IR progressed from <2.2 to ≥2.2 in 64,443 subjects (23.0%) and improved from ≥2.2 to <2.2 in 21,673 subjects (7.7%). In the parametric survival analysis, alcohol consumption was associated with improvement of HOMA-IR (HR [95% CI], 1.09[1.03–1.14], 1.11[1.06–1.17] and 1.20[1.13–1.26], respectively). In the analysis classified according to changes in alcohol consumption amounts, increased alcohol consumption tended to prevent the progression of HOMA-IR (0.97[0.96–0.99]; p = 0.004). However, the association between the changes in alcohol consumption amounts and improvement of HOMA-IR was not statistically significant.ConclusionThis retrospective observational study has shown that alcohol consumption can improve insulin resistance and increased alcohol consumption amounts may have preventive effects on the progression of HOMA-IR compared to the baseline level.     

Insulin tolerance test is comparable to homeostasis model assessment for insulin resistance in patients with nonalcoholic fatty liver disease.

INTRODUCTION: Insulin resistance (IR) is common in patients with nonalcoholic fatty liver disease (NAFLD). We compared the performance of insulin tolerance test and the homeostasis model assessment (HOMA) for measuring IR in such patients. METHODS: In a prospective study, IR was determined using both insulin tolerance test and HOMA in 22 patients with NAFLD. Rate constant for insulin tolerance test (KITT) was calculated using the formula KITT (%/min) = 0.693/t(1/2), where t(1/2) was calculated from the slope of plasma glucose concentration during 3-15 minutes after administration of intravenous insulin. IR was assessed using HOMA as the product of fasting insulin (microU/L) and fasting plasma glucose (mmol/L) levels divided by 22.5. RESULTS: All the 22 patients had IR. Results of KITT and HOMA-IR for determining IR showed a fair correlation (r = 0.55; p = 0.03). CONCLUSIONS: Insulin tolerance test may be a useful method for assessing IR in patients with NAFLD.