This study assessed the association of serum adipokine and leptin levels with glycemic control and dyslipidemia in Sudanese patients with type 2 diabetes mellitus.
In this study, adiponectin levels were significantly lower among patients when compared with control group. The findings of the study agreed with previous studies suggesting that adiponectin may play a role in glucose metabolism and low adiponectin levels are frequently reported in type 2 diabetes in different ethnic groups [42, 43]. Higher serum adiponectin levels were reported to be associated with lower risk of diabetes among Japanese, Mexicans, Asian Indians Kashmiri and other populations [44, 45, 46]. The low levels of adiponectin seen in diabetic patients are believed to be associated with the disorder of glucose and lipid metabolism [47,48], and this explains the presence of insulin resistance in type 2 DM patients. The explanation of the association between diabetes and adiponectin could be related to the anti-diabetic effects of adiponectin. Adiponectin has been reported to promote pancreatic beta-cell function, increase insulin sensitivity by stimulating hepatic insulin signaling by enhancing Insulin receptor substrate 2 expression . Adiponectin also increases glucose uptake by stimulating the translocation of the glucose transporter 4 (GLUT4) to the cell surface . Adiponectin has also been reported to modulates the interaction between hepatic and skeletal muscle insulin receptors by activation of 5 adenosine monophosphate-activated protein kinase (AMPK) pathway . Other potential mechanisms of the glucose lowering effect of adiponectin include; suppression of hepatic gluconeogenesis, stimulation of fatty acid oxidation in the liver, stimulation of glucose uptake and fatty acid oxidation in skeletal muscle . This result demonstrates a clear significant relationship between plasma adiponectin concentration and Type 2DM. Thus, adiponectin has increasingly been considered a potential biomarker for type 2DM.
In this study, adiponectin was inversely correlated with HbA1c levels similar to previous studies [53,54], indicating that adiponectin could be used as a marker for evaluation of glycemic control and disturbance of glucose metabolism in diabetic patients. The reduction of serum adiponectin in patients was independent of their body mass indices. In contrast with the previous studies that have shown adiponectin levels negatively correlated with BMI and insulin resistance in diabetic patients [55,56,57]. However, other previous reports agreed with this study that there was no correlation between adiponectin and BMI in diabetic patients [58,59]. It could be explained by the fact that adiponectin concentrations were mostly linked with insulin sensitivity rather than insulin resistance in type 2 diabetic patients.
Leptin levels were high in the patients with type 2 diabetes compared with controls, and positively correlated with HbA1c levels in the patients. This could explain the role of leptin in glucose homeostasis. The insulin sensitizing effects of leptin have been related to increased fatty acid oxidation and decreased triglyceride storage in muscle [60,61]. It has been identified as an important regulator of pancretic b-cell mass and inhibition of insulin gene expression , mediation of direct inhibitory effects of leptin on insulin secretion may be disrupted under conditions of increased leptin levels such as type 2DM and obesity [62, 63].
The study results showed no significant difference in BMI between diabetic patients and healthy controls, in agreement with previous reports , serum leptin levels were not correlated with BMI in diabetic patients. In relation to this aspect, a previous study found an association between diabetes and leptin levels when BMI was adjusted in the regression model . It is probable that factors other than increased body fat content also contribute to the elevated leptin levels in diabetic patients. There were some studies that have shown positive correlation between leptin and BMI in patients with type 2DM [66, 67]. In agreement with a previous study , serum adiponectin and leptin levels did not vary significantly between genders although significant differences were observed in patients and controls.
Adiponectin was found to be correlated with various parameters of lipids profile, it is especially associated with HDL and TG. Adiponectin induces an increase in serum HDL and, in addition, it lowers serum TG through the enhanced catabolism of TG-rich lipoproteins .The findings of the current study showed that, serum lipid profile of type 2 diabetic patients was abnormal compared with those of the controls whose lipid profiles were mostly within normal values. This confirmed the well-known association of dyslipidemia with type 2 diabetes . In this study the positive correlation between serum adiponectin and HDL levels in the patients, is in agreement with previous studies that reported positive correlation between HDL and adiponectin that was independent of BMI and insulin resistance in type 2 diabetic patients [71 72, 73, 74].It could be explained by the fact that decreased adiponectin levels have been related to increased hormone sensitive lipase activity, which may be responsible for the decreased levels of HDL cholesterol [75,76]. Several studies have investigated the relationship between adiponectin, LDL and TC levels, but the results were controversial, previous studies showed that the level of adiponectin has an inverse relationship with LDL and TG [72, 73, 74], another study showed no significant correlation between serum adiponectin level, LDL cholesterol and total cholesterol in type 2 diabetic patients . In the current study there were inverse correlations between serum adiponectin with LDL and TC in the patients, a similar study conducted in Japan showed a negative correlation between serum adiponectin levels and LDL, TC, levels in type 2 diabetics . The negative correlation was explained to be due to low levels of adiponectin which is associated with reduced activation of peroxisome proliferator activator receptor-alpha (PPAR-α) receptors in the liver and decreased expression of LDL receptors in body tissues . A Previous study reported inverse correlation between serum adiponectin and TG level in the type 2 diabetic patients .
It has been explained by the hypothesis that adiponectin may increase the production and activation of lipoprotein lipase and the expression of VLDL receptors by activation of PPAR αin liver which will reduce the storage of triglycerides in adipose tissue and their uptake by the hepatocytes and increase concentration of triglyceride in the blood (hypertriglyceridemia) . In contrast, this study showed there was no correlation between serum adiponectin and TG level in the type 2 diabetic patients.
The association between leptin and lipid metabolism has been reported in animal studies, leptin deficiency has been observed to be associated with hyperglycemia, hyperlipidemia, and insulin resistance . There are contradictions between the relations of serum leptin levels and lipids profile. Some studies reported that there was no relationship between leptin and the parameters of a lipid profile [82,83]. Other study showed a significant positive correlation between leptin and lipid profile (HDL, TG) .
In current study leptin levels seem to correlate only with selected lipid profile parameters (TC and LDL), in agreement with previous study the results showed positive correlation between leptin level and total cholesterol . A study on Japanese showed that there was a significant relationship between serum leptin level and LDL in diabetic patients , these results are consistent with this study and another study conducted showed a positive correlation between serum leptin level and LDL in white subjects . Despite the link between serum leptin levels and lipid metabolism and the indication that high leptin levels are biomarkers of obesity , this study did not demonstrate a correlation between leptin level, TG and HDL, in agreement with a previous study .