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

https://doi.org/10.1016/j.diabres.2006.10.005Get rights and content

Abstract

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 > 8.0 mmol/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.

Introduction

Insulin resistance, as well as impaired pancreatic β-cell function, is the principal cause of glucose intolerance and type 2 diabetes. Insulin resistance is also well-correlated with central obesity, lipid abnormality, and hypertension, and accumulation of these metabolic abnormalities, so called metabolic syndrome, results in severe atherosclerosis. Treatment of insulin resistance with thiazolidine diones or metformin improves mortality and decreases cardiovascular events. It is therefore important to evaluate the extent of insulin resistance in obese and type 2 diabetic patients, and to treat them with improvement of life styles and/or medication.

Several techniques are used to evaluate insulin resistance in humans, and among them, the M-value determined by the euglycemic hyperinsulinemic clamp technique is considered the gold standard [1]. Since this method is complicated and expensive to be utilized in epidemiological studies, the homeostasis model assessment index (HOMA-IR) [2], calculated from fasting glucose and insulin levels, has been mainly applied in clinical studies. However, several studies demonstrated that HOMA-IR failed to detect insulin resistance in individuals with normal and impaired glucose tolerance [3], [4]. In addition, this index may be inadequate in diabetic subjects with moderate hyperglycemia, where insulin secretory ability fails to compensate for the impaired homeostasis of glucose [5]. Therefore, a more accurate index is necessary for determining insulin resistance especially in diabetic patients.

Adiponectin, the most abundant of adipose-specific proteins, is known to modulate the action of insulin via activation of AMP-activated protein kinase in the muscle and the liver [6]. Serum adiponectin levels were found to correlate directly with whole-body insulin sensitivity in patients with obesity and type 2 diabetes [7]. Therefore, in this study, we examined the correlation between adiponectin levels and HOMA-IR and M-values, and established a novel index of insulin resistance, which can be used even for individuals with hyperglycemia by modifying HOMA-IR by taking into account adiponectin levels.

Section snippets

Materials and methods

A total of 117 Japanese subjects with various degrees of glucose tolerance, including individuals with type 2 diabetes (T2DM; n = 89, 54.7 ± 10.8 years, BMI 26.2 ± 18.5), impaired glucose tolerance (IGT; n = 5, 43.2 ± 19.8 years, BMI 25.3 ± 3.2), and normal glucose tolerance (NGT; n = 23, 49.7 ± 10.2 years, BMI 25.5 ± 4.3) were enrolled in this study carried out in Osaka University Hospital, Osaka City University Hospital, and Ryukyu University Hospital. The study was approved by the Ethical Committee for Human

Results

Fasting glucose levels were significantly higher in T2DM (7.4 ± 1.7) than NGT and IGT (5.1 ± 0.6 and 5.9 ± 1.2 mmol/L, P < 0.001). Fasting insulin and adiponectin levels were similar among three groups (NGT, 48.0 ± 20.4, 5.8 ± 2.2; IGT, 46.8 ± 18.0, 6.8 ± 3.3; T2DM, 56.7 ± 51.6 pmol/L, 6.1 ± 2.8 μg/mL). HOMA-IR was significantly higher in T2DM (3.1 ± 2.6) than NGT and IGT (1.8 ± 0.8, 2.1 ± 0.9, P < 0.05). The M-values were significantly higher in NGT (6.0 ± 2.5 mg/kg/min) than T2DM and IGT (4.6 ± 2.3, 4.9 ± 1.9 mg/kg/min, P < 0.05).

Discussion

In the present study, the M-value significantly correlated with fasting plasma glucose and fasting serum insulin and adiponectin levels in Japanese subjects. Therefore, we generated a modified index of HOMA-IR (HOMA-AD) by taking account into adiponectin levels; found that this index is a more accurate indicator for assessing insulin resistance than HOMA-IR. This index is simply based on glucose, insulin, and adiponectin levels in fasting blood sample.

Although HOMA-IR is easy to calculate,

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