The Effect of Combined Training with Canagliflozin on Lipocalin-2 and Omentin in Type 2 Diabetic Men

Recent findings suggest that type 2 diabetes is associated with abnormal production of adipokines (2). Impaired circulating levels of adipokines are associated with multiple cardiovascular complications in diabetes (3). Lipocalin-2 is one of the adipokines that increases in diabetic patients and its secretion is associated with insulin resistance and hyperglycemia in these patients (4). also, Omentin-1 concentrations have been reported to decrease in patients with type 2 diabetes (11).Many efforts are being made to develop a drug that improves metabolism and prevents the complications of diabetes. Canagliflozin is an SGLT2 inhibitor drug that acts by inhibiting glucose reabsorption by the body, lowers plasma glucose levels, and improves insulin resistance (13). Prescribing this drug to type 2 diabetes can help improve blood glucose control and reduce body weight in these patients (14, 15).On the other hand, exercise has been used as an adjunct in drug therapy in the management of diabetes complications. Resistance training has been reported to be associated with significant increase in lipocalin-2 concentration in men with type 2 diabetes (16). However, the results of Hosseini et al showed that eight weeks of combined training did not have significant effect on lipocalin 2 in diabetic women (18). Also, significant increase (19) and no change (20, 21) of omentin-1 has been reported in patients with type 2 diabetes after exercise.Since no research has been done on the effect of combined exercise with medication on adipokines in type 2 diabetics, Therefore, the aim of this study was to investigate the effect of combined training with Canagliflozin on lipocalin-2 and omentin-1 in type 2 diabetic men.

This is a semi-experimental study. The statistical population of this study consisted of all patients with type 2 diabetes in the Tehran city in 2019. 44 men with type 2 diabetes (mean age 25-40 years) were randomly divided into four groups (n=11) of control, drug, exercise and exercise-drug groups. Subjects were given 200 mg of canagliflozin for 12 weeks (25). Combined exercises were performed 3 sessions per week, 45 minutes for 12 weeks (26). Blood samples and anthropometric characteristics were obtained before and 24 hours after the intervention at 12-hour fasting. Data were analyzed using two-way ANOVA with repeated measures, t-test and Tukey post hoc test at P<0.05.
 

The results showed that combined training and combined training with canagliflozin significantly reduced lipocalin-2 and significantly increased omentin-1 in type 2 diabetic men (P=0.001). Also, after the combined training intervention, canagliflozin and combined training with canagliflozin, the levels of lipocalin-2 and omentin-1 were lower and higher than the pretest, respectively (P=0.001).

The findings of the present study show that combined training and combined training with canagliflozin significantly reduced lipocalin-2 and significantly increased omentin-1 in type 2 diabetic men. The findings of this study were consistent with the results of Previous research (19, 26-28, 33). Various studies have examined the mechanisms of change in lipocalin-2 induced by exercise. Perhaps one of the reasons for the decrease in lipocalin-2 levels in the present study is the intensity of exercise. also, exercise has been reported to reduce the activity of the NF-κB and inflammatory markers such as TNF-α, IFN-γ, and interleukin-1 beta, which activate lipokalin-2 expression (31), therefore It is possible that combined training in this study reduced lipocalin-2 by reducing the above factors. Some studies have reported that the reduction of lipocalin-2 is highly correlated with the reduction of adipose tissue, so that with the reduction of adipose tissue after exercise, the amount of lipocalin-2 decreases (28). also, Omentin-1 changes are largely a function of changes in body composition, including weight loss, fat mass, and body mass index and adipocyte size (35). In addition, in a study, changes in inflammatory levels have been reported to be an influential factor in regulating the expression of omentin-1 (36). Therefore, it is possible that in the present study, combined training increased the amount of omentin-1 in patients with type 2 diabetes by improving the composition of the body and inflammatory agents. The pharmacological effects of canagliflozin in the produced doses cause a significant increase in urinary glucose excretion and a decrease in hyperglycemia. Therefore, in explanation the results obtained in the present study, it can be said that canagliflozin with exercise, by lowering fasting blood glucose and also increasing insulin, may significantly improve the levels of adipokines in type 2 diabetic men. combined training was the strengths of the present study; because this type of exercise can have different responses and adaptations than other exercise programs. There were some limitations in the present study, such as the lack of measurement of other adipokines. According to the results, it seems that diabetics can benefit from combined exercise with canagliflozin to improve adipokines levels.