Endocrine Abstracts

Background: Diabetic nephropathy (DN) is a micro-chronic diabetic complication brought on by changes in metabolism and hemodynamics. Inflammatory cytokines, generally IL-1β, IL-6 and IL-18 are linked in the development and advancement of DN. They act as pleiotropic polypeptides regulating inflammatory and immune responses through actions on cells. Fibrinogen is the liver-synthesized protein, with different functions and responses to both acute and chronic stimuli.AimThe aim of this research work is to find the relationship of IL-1β, IL-6, IL-18 and fibrinogen in the advancement of diabetic nephropathy.MethodsThis cross sectional study was conducted on 1152 subjects selected from different cities (Lahore, Gujranwala, Multan, Islamabad, Karachi and Gharro) of Pakistan. The enrolled subjects were categorized into control group (n=384), diabetes mellitus group (DM) (n=384) and diabetic nephropathy group (DN) (n=384). The serum concentration of IL-1β, IL-6, IL-18 and fibrinogen were determined by enzyme-linked immunosorbent assay (ELISA). The expression analysis of IL-1β, IL-6, IL-18 and fibrinogen were performed by Real Time PCR.ResultsThe significant increased level of serum IL-6 (56.01 pg/ml), IL-1β (36.93 pg/ml) and decreased level of IL-18 (132.61pg/ml) and Fibrinogen (11.93 pg/ml) was observed in DN subjects as compared to control and DM subjects. The expression profile of IL-6 were increased by more than thirty three fold (n-fold =~ 33.3) and expression of IL-1β increased by more than eleven fold (n-fold =~ 11.76) in DN group. The decreased expression of IL-18 (n-fold =~ 1.92) and fibrinogen (n-fold =~ 12.03) was observed in DN group as compared to DM and control group. The uric acid, creatinine, blood sugar and GFR highly correlated with inflammatory cytokines that showed the disease severity. The predictive model by linear regression analysis concluded that age, serum creatinine, blood sugar and expression of IL-6 plays an essential role in the progression of DN. An inverse relationship between fibrinogen and blood sugar was observed in DN subjects. Differences in serum levels of IL-1β, IL-6, IL-18 and fibrinogen was observed among population of selected cities.ConclusionThe present study implicates that among pro-inflammatory cytokines, Il-6 is an important predictor of DN progression in Pakistani population. The significant variation was observed in the expression of IL-1β, IL-6, IL-18 & fibrinogen in Lahore, Gujranwala, Multan, Islamabad, Karachi and Gharro that screen the variation in different races of Pakistan.