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Abstract & Commentary
Synopsis: Measures that increase adiponectin levels might be valuable targets for decreasing the risk of atherosclerosis present in patients with diabetes.
Source: Schulze MB, et al. Diabetes Care. 2004;27:1680-1687.
Patients with diabetes have a markedly increased risk of fatal coronary artery disease. This risk has mainly been attributed to hyperglycemia, dyslipidemia, and inflammatory mechanisms. Adiponectin, which is synthesized in adipose tissue, appears to play a role in all of these pathways. It has been found to be a major modulator of insulin action and resistance, have inflammatory properties, and influence lipid metabolism. Previous studies, however, have not evaluated the relationship between adiponectin and an array of complex metabolic abnormalities observed in diabetes.
This study examined the association between plasma levels of adiponectin and HbA1c, blood lipids, and inflammatory markers. Blood samples were obtained from 741 participants in the Health Professionals Follow-up Study with a diagnosis of type 2 diabetes.
Plasma adiponectin levels were positively correlated with HDL cholesterol and negatively correlated with triglycerides, apoprotein-B100, C-reactive protein (CRP), and fibrinogen. These associations were not appreciably altered after controlling for lifestyle exposures, and obesity associated variables. A 10 mg/mL higher level of adiponectin was associated with significantly lower level of HbA1c, triglycerides, apoB-100, CRP, and fibrinogen and higher HDL cholesterol. Associations between adiponectin and inflammatory markers were independent of HbA1c and HDL cholesterol suggesting that the inflammatory properties are not mediated by effects of glycemic control and blood lipids. The results were consistent among obese and non-obese men.
The study supports the hypothesis that increased adiponectin levels might be associated with better glycemic control, better lipid profiles, and reduced inflammation in diabetic subjects. Further, measures that increase adiponectin levels might be valuable targets for decreasing the atherosclerotic risks in patients with diabetes.
Comment by Ralph R Hall, MD, FACP
In a comprehensive review of "Adipose Tissue as an Endocrine Organ" Kershaw and Flier note that, in the past, we viewed adipose tissue as a depot for the storage of energy.1 Subsequently we found that fat was a major site for steroid metabolism and in 1994, the identification and characterization of leptin established adipose tissue as an endocrine organ. We now know that adipose tissue expresses and secretes a variety of bioactive peptides that act at both local and systemic sites. Excesses and as well as deficiencies in adipose tissue stores, like those seen in HIV patients after treatment with antiviral therapy, have harmful and metabolic consequences.1
Kershaw’s and Flier’s review points out that besides adipocytes, adipose tissue contains connective tissue matrix, nerve tissue, stromovascular cells and immune cells. Many of the peptides that are secreted by adipose tissue are derived from the non-adipocyte fraction. There are at least 18 adipocyte-derived proteins with endocrine function. In addition there are receptors for the traditional endocrine hormones such as insulin, glucagon, growth hormone, thyroid hormone, androgens, estrogens, etc.
Adiponectin is present in different isoforms and has different receptors in muscle and liver. The effects are modified by the plasma concentrations, and by the different isoforms and tissue-specific receptors. Administration of adiponectin to primates corrects insulin resistance, improves dyslipidemia, and decreases inflammatory markers. Blood levels increase with weight loss and the administration of insulin sensitizing drugs. Plasma adiponectin levels decline before the onset of obesity and insulin resistance. This suggests that adiponectin contributes to the pathogenesis of these conditions.
As the study by Schultz and colleagues suggests, modulating adiponectin levels is a promising approach to the management of the complications of type 2 diabetes and the metabolic syndrome.
Dr. Hall, Emeritus Professor of Medicine University of Missouri- Kansas City School of Medicine, is Associate Editor of Internal Medicine Alert.
1. Kershaw EE, Flier JS. J Clin Endocrinol Metab. 2004;89:2548-2556.