Adiponectin, a collagen-like plasma protein produced and secreted exclusively by adipose tissue, has been shown to have compelling anti-atherogenic, anti-inflammatory and insulin-sensitizing properties. Adiponectin has been linked to insulin resistance in obesity and diabetes. The aim of the study is to measure serum adiponectin concentration in type II obese diabetic patients with various micro and macrovascular complications, as adiponectin seems to be an important modulator for metabolic and vascular diseases. The study was carried out on 60 obese patients with type II diabetes (30 patients with macrovascular complications and 30 patients with various microvascular complications). The control group consisted of 20 healthy subjects of matched age and sex. For all subjects participated in the study, Body Mass Index (BMI), fasting (FBG) and postprandial (PPBG) blood glucose, creatinine, sodium, potassium, lipid profile and adiponectin were measured. We found a highly significant decrease in serum adiponectin levels in diabetic patients compared with control group. There was a significant negative correlation between adiponectin levels and BMI, FBG, PPBG, creatinine, sodium, potassium, triglyceride, total cholesterol and LDL-C, with significant positive correlation between adiponectin serum levels and duration of diabetes and HDL-C in diabetic patients. These results support the hypothesis that low circulating levels of adiponectin are an important determinant of risk of cardiovascular disease and that increased adiponectin levels might be associated with better glycemic control, better lipid profile and reduced inflammation in diabetic subjects. Thus, therapeutic approaches aimed at increasing concentrations or adiponectin tissue sensitivity and action could represent a novel treatment strategy for insulin resistance in type II diabetes and might have therapeutic implications as an anti-obesity drug or as anti-atherogenic plasma protein.
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Adiponectin is emerging as an important protein in the etiology of obesity and related metabolic disorders (Hanley et al., 2003). Adiponectin, predominantly synthesized in the adipose tissue, seems to have substantial anti-inflammatory properties and to be a major modulator of insulin resistance and dyslipidemia, mechanisms that are associated with an increased atherosclerotic risk in diabetic patients (Schulz et al., 2005). Adiponectin, an adipocyte-derived peptide with anti-inflammatory and anti-atherogenic effects, is known to protect against the initiation and progression of atherosclerosis (Chen et al., 2005).
Low plasma adiponectin concentration is associated with a decrease in whole body insulin sensitivity (Tschritter et al., 2003) and has been shown to be predictive of future development of diabetes in a few studies (Daimon et al., 2003).
Adiponectin is a novel-adipocyte specific protein, although it circulates in high concentrations, adiponectin levels are lower in obese subjects than in lean subjects (Lihn et al., 2005). Apart from negative correlations with measures of adiposity, adiponectin levels are also reduced in association with insulin resistance and type II diabetes, visceral adiposity has been shown to be an independent negative predictor of adiponectin (Lihn et al., 2005).
The aim of the study is to measure serum adiponectin concentration in type II obese diabetic patients with various micro and macrovascular complications, as adiponectin seems to be an important modulator for metabolic and vascular diseases.
MATERIALS AND METHODS
The study was carried out on 60 obese patients with type II diabetes with microvascular and macrovascular complications selected from outpatient clinics, at Kasr EL-Aini Hospital, Cairo University. They were divided into 2 groups: Group I consisted of 30 patients with type II diabetes with macrovascular complications (ischemic heart disease, cerebrovascular disease) with mean age of 54.3±10.7 years (12 males and 18 females). Group II consisted of 30 patients with type II diabetes with various microvascular complications (diabetic nephropathy, neuropathy and retinopathy) with mean age of 53.3±9.8 years (19 males and 11 females). Group III consisted of 20 healthy subjects of matched age and sex (52.8±11.4 years, 9 males and 11 females).
All subjects participated in the study were subjected to the following:
|•||Detailed clinical examination including Body Mass Index (BMI).|
|•||Routine laboratory investigations: Fasting and Postprandial Blood Glucose (FBG and PPBG, respectively), lipid profile and kidney function.|
|•||Adiponectin in fasting sample.|
Ten milliliter of fasting venous blood samples (12 h fast) were taken from each subject participating in the study, the blood was left to clot, centrifuged at approximately 2000-3000 xg for 15 min at 4°C, the fasting blood glucose was determined immediately and the rest of the serum was stored at -20°C for the routine investigations and adiponectin determination. Two hours after meal, a venous blood sample (about 2 mL) were taken on fluoride for the determination of postprandial blood glucose.
Kidney function tests: Colorimetric techniques were used for the determination of creatinine using alkaline picrate method (Höuöt, 1985) and sodium and potassium were measured using flame emission spectrophotometry (Velapoldi et al., 1978). Blood glucose was carried out by glucose oxidase method (Siest et al., 1981).
Lipid profile: Total cholesterol was carried out using Trinder`s reaction (Allian et al., 1974). Triglyceride was carried out using enzymatic hydrolysis of glycerol (Fossati and Prencipe, 1982). High Density Lipoprotein Cholesterol (HDL-C) was determined using phosphotungestic acid precipitation (Lopes-Virella et al., 1977). Low Density Lipoprotein Cholesterol (LDL-C) was determined according to the method described by Steinberg (1981)
All the above kits were supplied by Sentinel CH (Principe Eugenio 5-20155 Milan- Italy).
Adiponectin determination: By quantitative sandwich enzyme immunoassay technique and the kit was supplied by LINCO Research Inc. (6 Research Park Drive, St Charles, Missouri, USA) (Faraj, 2003).
The results were expressed as mean±SD. Data was statistically analyzed using SPSS package for windows, version 7.5 (f-test and r-coefficient).
There was a highly significant increase in the BMI of diabetic patients compared with control group Table 1.
There was a highly significant increase in fasting and postprandial blood glucose, triglyceride, total cholesterol and low-density lipoprotein cholesterol serum levels with highly significant decrease in high-density lipoprotein cholesterol concentration in diabetic patients compared with control group. A significant increase was found in serum creatinine, with significant decrease in sodium and potassium serum levels in diabetic patients compared with control group Table 2.
Table 3 revealed that there was a highly significant decrease in serum adiponectin level in diabetic patients in comparison to control group.
In-group I and II diabetic patients, there was a significant negative correlation between serum adiponectin level and BMI, FBG, PPBG, creatinine, sodium, potassium, triglyceride, total cholesterol and LDL-C with significant positive correlation between serum adiponectin and duration of diabetes and HDL-C Table 4.
|Table 1:||The different clinical parameters of all studied group (mean±SD)|
|p*<0.05: Significant, p<0.01: Highly significant, Group I: Type II diabetic patients with macrovasculr complications, Group II: Type II diabetic patients with microvascular complications, Group III: Control group|
|Table 2:||The different biochemical parameters of all studied groups (mean±SD)|
|Table 3:||The mean level of serum adiponectin in different studied groups (mean±SD)|
|Table 4:||The correlation between serum adiponectin and different clinical and biochemical parameters of diabetic patients|
Adiponectin is a novel and important member of the adipokine family, which has regulatory functions in the glucose and lipid metabolism (Palomer et al., 2005).
Adiponectin stimulates fatty acid oxidation, reduces triglycerides and improve glucose metabolism by increasing the insulin sensitivity, in addition, adiponectin inhibits the inflammatory process that accompanies atherogenesis, as it reduces expression of endothelial adhesion molecules, macrophage to foam cell transformation, tumor necrosis factor expression in macrophage and adipocyte and smooth muscle cell proliferation (Palomer et al., 2005).
The aim of the study is to measure serum adiponectin concentration in type II obese diabetic patients with various micro and macrovascular complications, as adiponectin seems to be an important modulator for metabolic and vascular diseases. The study was done on two groups of diabetic obese patients, group I (those with macrovascular complications) and group II (those with microvascular complications) and a control group (group III). The results of this study showed a highly significant decrease in adiponectin levels in diabetic patients compared with control group (p<0.001), with lower levels in-group I compared to group II patients. These results agreed with several researchers, Chen et al. (2005) measured plasma adiponectin concentrations in patients with ischemic cerebrovascular disease with and without type II diabetes and they found statistically lower levels of plasma adiponectin in those patients especially with type II diabetes.
Matsuda et al. (2004) studied the relationship between adiposity and plasma adipocytokine levels (adiponectin, leptin, resistin and tumor necrosis factor-alpha) and investigated the clinical significance of adiposity and plasma adipocytokine levels on diabetic micro- and macro-angiopathy in type II diabetic subjects, they found that plasma adiponectin levels was negatively correlated with both visceral and subcutaneous fat areas.
Also the result of this study agreed with Anthony et al. (2003), Yilmaz et al. (2004) and Schulze et al. (2005) they all demonstrated low serum adiponectin levels in type II diabetic patient with various diabetic angiopathy.
The results of this study revealed that the mean serum adiponectin levels were negatively correlated with BMI, fasting and postprandial blood glucose, creatinine, total cholesterol and LDL-C, however; adiponectin level was positively correlated with HDL-C and duration of diabetes in both diabetic groups. The mechanisms by which adiponectin may affect blood lipids are largely unknown. Effects of adiponectin on hepatic lipase activity, which is increased in central obesity and insulin resistance, are suspected (Cnop et al., 2003). Hyperglycemia acutely increases circulating cytokine concentrations (Morohoshi et al., 1996; Esposito et al., 2002), HDL-cholesterol down regulates expression of adhesive molecules on the surface of vascular endothelium (Garner et al., 1998) and inhibits platelet aggregation (Nofer et al., 1998) and thus has anti-inflammatory and antithrombotic properties.
These results agreed with Schulze et al. (2005) who found an inverse association between adiponectin and BMI in type II diabetic patients and they also suggested that increased adiponectin levels are associated with a moderately decreased coronary heart disease risk in diabetic man. This suggests that although adiponectin might in part mediate effects of body fat on lipoproteins, other unrecognized pathways controlling its production might be important as well. Furthermore, the associations were largely independent of fasting insulin concentration (Zietz et al., 2003; Valsamakis et al., 2003) and indexes of insulin resistance assessed by the homeostasis model assessment (Shand et al., 2003; Yamamoto et al., 2002), the euglycemic-hyperinsulinemic clamp and the oral glucose tolerance test (Tschritter et al., 2003). This suggests that mechanisms other than effects on insulin resistance and hepatic lipase activity most likely mediate the association between adiponectin and blood lipids.
Various authors stated that circulatory adiponectin levels are lower in obese subjects than in lean subjects (Lihn et al., 2005) and weight reduction has resulted in increases in adiponectin (Anthony et al., 2003). Also adiponectin levels are reduced in association with insulin resistance. Several insulin-resistant states such as obesity and type II diabetes or cardiovascular diseases, have been found to be associated with low levels of plasma adiponectin (Palomer et al., 2005).
Gottsater et al. (2004) had prospectively follow concentrations of plasma adiponectin and serum advanced glycation end products in relation to plasma lipids and retinopathy over 3 years in type II diabetic patients, they found that plasma adiponectin levels correlated inversely with fasting C-peptide and low density lipoprotein cholesterol and directly with high density lipoprotein cholesterol and they concluded that both plasma adiponectin and advanced glycated end products increased during the 3 years follow up study period and that this increase was explained by improvements in insulin sensitivity and dyslipidemia.
Many researchers had demonstrated the adiponectin levels were reduced prior to the development of type II diabetes and that decreased serum levels of adiponectin are a risk factor for the progression of type II diabetes (Tschritter et al., 2003; Daimon et al., 2003; Lihn et al., 2005) and they stated that administration of adiponectin has been accompanied by lower plasma glucose level as well as increased insulin sensitivity.
Furthermore, reduced expression of adiponectin has been associated with some degree of insulin resistance in animal studies indicating a role of hypoadiponectinemia in relation to insulin resistance (Lihn et al., 2005). The primary mechanism by which adiponectin enhance insulin sensitivity appears to be through fatty acid oxidation and inhibition of hepatic glucose production.
In conclusion this study showed that serum adiponectin levels were lower in type II diabetic patients with various angiopathy or vascular complications and this may indicate the possible anti-atherogenic affect for adiponectin, which appears to be an insulin enhancer with the potential use as a new pharmacological treatment for metabolic syndrome. Thus, therapeutic approaches aimed at increasing concentrations or adiponectin tissue sensitivity and action could represent a novel treatment strategy for insulin resistance in type II diabetes and might have therapeutic implications as an anti-obesity drug or as anti-atherogenic plasma protein.
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