ABSTRACT
Type-1 diabetes mellitus is a disease that results from autoimmune destruction of insulin producing beta-cells. The autoimmune response against beta-cells is believed to result from a disorder of immune regulation. According to this concept tumor necrosis factor alpha [TNF-alpha], interleukin-10 [IL-10], nitric oxide [NO], urinary albumin excretion rate [UAER] and HbAIc in addition to serum glucose, kidney and liver function tests as well as lipogram were studied in sixty eight type-1 diabetic patients. Twelve healthy subjects were included as a control group According to disease duration patients were classified into three groups: group I [30 cases] patients with disease duration less than 5 years, group II [22 cases] patients with disease duration 5-10 years and group III [16 cases] patients with disease duration > 10 years. Also patients were classified according to UAER into 3 groups: group A [30 cases] normoalbuminuric patients UAER < 20 micro g/min. group B [35 cases] microalbuminuric patients UAER 20-200 micro g/min. group C [3 cases] macroalbuminuric patients UAER > 200 micro g/min. According to HbAIc levels, patients were classified into controlled group [HbALc < 6%] 20 patients and uncontrolled group [HbAIc > 6%] 48 patients. In whole patients group mean values of HbAIc, TNF-alpha and UAER showed significant elevations compared to controls [P <0.001, 0.001 and 0.05 respectively], while IL-10 revealed significant reduction. [P < 0.001]: NO mean value showed statistically insignificant elevation. Mean values of HbAIc in groups I, II, III, A, B revealed significant elevations compared to controls [P < 0.001 for all] also in group III versus group I [P < 0.05] and in group B versus A [P<0.05]. TNF-alpha showed significant elevation in groups I, II, III in comparison with controls [P < 0.001 for all]. While mean value of IL-10 showed significant reduction in groups I, III compared to controls [P < 0.01, P < 0.001 respectively] also in group III versus group I, II [P < 0.01 for both]. NO and UAER showed significant elevations in group III compared to controls [P < 0.05 and P < 0.01 respectively]. NO levels showed significant elevation in groups I and III compared to group II [P < 0.05 for both]. UAER in group III revealed significant elevation versus groups I and ii [P < 0.01, P < 0.001 respectively]. In normoalbuminuric and microalbuminuric groups [A, B] TNF-alpha showed significant elevation compared to controls [P < 0.001 for both]. IL-10 mean value showed significant reduction in groups A and B compared to controls [P < 0.001 for both]. NO levels revealed no significant differences. In uncontrolled group, level of IL-10 was significantly low, while UAER was significantly high [p < 0.05 for both]. TNF-alpha and NO showed no signifigant difference between controlled and uncontrolled groups. Positive correlations were found between TNF-alpha and serum glucose and HbAIc, also negative correlations were found between IL-10 and serum glucose, HBAIc, cholesterol, triglycerides and LDL-c. NO showed positive correlation with UAER level. From this study we concluded that increased TNF-a [proinflammatory cytokine of Th1] and decreased IL-10 levels [type 2 cytokine of Th2] may play a role in the pathogenesis of type-1 diabetes mellitus. TNF-alpha and IL-10 may be a predictor of glycemic control. Increased NO level may play a role in the pathogenesis and complications of diabetes