Measurement of the High–Molecular Weight Form of Adiponectin in Plasma Is Useful for the Prediction of Insulin Resistance and Metabolic Syndrome

Abstract

OBJECTIVE -The high-molecular weight (HMW) form of adiponectin, an adipocytederived insulin-sensitizing hormone, has been reported to be the most active form of this hormone. We investigated whether measurement of plasma HMW adiponectin levels, using our newly developed enzyme-linked immunosorbent assay system for selective measurement of human HMW adiponectin level, may be useful for the prediction of insulin resistance and metabolic syndrome.RESEARCH DESIGN AND METHODS -A total of 298 patients admitted for diabetes treatment or coronary angiography served as study subjects. Receiver operator characteristic (ROC) curves for the HMW ratio (HMWR; ratio of plasma level of HMW adiponectin to that of total adiponectin) and plasma total adiponectin levels were plotted to predict the presence of insulin resistance and metabolic syndrome. CONCLUSIONS -The HMWR value has better predictive power for the prediction of insulin resistance and metabolic syndrome than plasma total adiponectin level. RESULTS Diabetes Care 29:1357-1362, 2006A diponectin (also known as ACRP30, GBP28, and AdipoQ) is a hormone secreted exclusively by adipocytes (1-4). Adiponectin replenishment has been found to ameliorate the abnormalities of metabolic syndrome, including insulin resistance, hyperglycemia, and dyslipidemia, in a murine model of obesity-linked metabolic syndrome associated with decreased adiponectin levels (5). Adiponectin-deficient mice (6,7) have been demonstrated to show features of metabolic syndrome, such as insulin resistance, glucose intolerance, dyslipidemia, and hypertension. In humans, decreased plasma adiponectin levels have been demonstrated in patients with obesity, diabetes, and coronary artery disease (8 -10), all of which are linked to insulin resistance. Moreover, the degree of hypoadiponectinemia has been reported to be correlated with the degree of insulin resistance (11,12), and hypoadiponectinemia has been shown to be closely associated with the clinical phenotype of metabolic syndrome (13,14). The gene encoding adiponectin (APM1) has been mapped to chromosome 3q27, which has been reported to be linked to type 2 diabetes and metabolic syndrome by genome-wide scans in Japanese (15), American, (16), and French-Caucasian (17) populations. A single nucleotide polymorphism in the adiponectin gene was shown to be associated with hypoadiponectinemia, insulin resistance, and increased risk of type 2 diabetes (18,19), indicating that adiponectin may play a crucial role in the regulation of insulin sensitivity and glucose and lipid metabolism and that reduced plasma adiponectin levels caused by genetic and environmental factors may lead to the development of insulin resistance, type 2 diabetes, and metabolic syndrome (20). Indeed, a recent study demonstrated that individuals with high plasma adiponectin levels had a substantially lower relative risk of developing type 2 diabetes, even after adjustment for conventional risk factors, such as BMI (21,22).We have reported that adiponectin forms multimers and is present in th...

Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases

“…21 We then developed an enzyme-linked immunosorbent assay system and showed that measurement of HMW is useful for the prediction of insulin resistance and metabolic syndrome. 24 Recently, we showed that adiponectin also centrally regulates energy expenditure and food intake. 28 We also identified AdipoRs (AdipoR1 and R2) by expression cloning, 15 and found that AdipoRs are also decreased in obesity.…”

“…23 The HMW adiponectin/total adiponectin ratio is more tightly correlated with insulin resistance than total adiponectin. The HMW adiponectin/total adiponectin ratio is more useful than total adiponectin in the diagnosis of metabolic syndrome 24 ( Figure 4). …”

Adiponectin complexes in human cerebrospinal fluid: distinct complex distribution from serum

“…A number of recent papers highlight the relevance of the HMW form for the peripheral functions of adiponectin [19,[25][26][27][28][29][30]. In light of the very large size of this complex (>500 kDa), it is not surprising that the HMW form is very inefficiently translocated across the BBB and not found in any measurable quantities in CSF.…”

Increased Muscle Mass Protects Against Hypertension and Renal Injury in Obesity

“…Plasma indexes of inflammation (tumor necrosis factor‐α) and antioxidants (interleukin‐10 and uric acid) were unchanged with myostatin deletion. Adiponectin (Table 1, plasma hormones), known to be associated with hypertension, was unchanged between the lean and obese groups 29, 30. Plasma amino acid profiles (Table 2) showed no effect of myostatin deletion in the lean mice.…”