RESUMEN
Although the destruction of pancreatic islet Beta cells is the defining characteristic of autoimmune diabetes, the precise cellular and molecular mechanisms effective for beta cell death have yet to be defined as we are still rather ignorant about the events directly responsible for this death. Markers of apoptosis [lL-1beta and NO], antiapoptotic marker [s-Fas], glutamic acid decarboxylase antibodies [GADA] and albuminuria were studied in 60 insulin dependent diabetic children and in 17 age and sex matched healthy children. Patients were classified into two groups according to the duration of diabetes into: group "A" included insulin dependent diabetics with disease duration < 5 years and group " B" insulin dependent diabetics with disease duration of 5 years or more. When glycemic control was taken into account the diabetic patients were further classified into metabolically controlled diabetics and non metabolically controlled ones according to the level of glycated hemoglobin. Our results revealed that the mean serum levels of IL-1 beta, NO, GADA and urinary albumin excretion rate were significantly higher, while serum levels of s-Fas were significantly lower in all diabetics than in controls, in diabetics with disease duration of 5 years or more than in those with disease duration <5 years and in non metabolically controlled diabetics than metabolically controlled ones. Significant positive correlations were detected between GADA serum levels with each at apoptotic markers, lL-1beta and NO and patients' age, between serum levels of IL-1Beta and NO, as well as between urinary albumin excretion and each of glycated hemoglobin, apoptotic markers [lL-1beta, NO] and GADA. Statistically significant negative correlations were detected between anti apoptotic marker, s-Fas and each of apoptotic markers, GADA and urinary albumin excreted in urine. Sixty four percent of diabetics with disease duration <5 years were normoalbuminuric [n= 28/44] and 36.36 % were microalbuminuric [stage 1 nephropathy] [n=16/44]. While 25% of diabetics with disease duration of 5 years or more were normoalbuminuric [n=4/16], 56.25 % were microalbuminuric [stage 1 nephropathy] [n=9/16] and 18.75 % were macroaibuminuric [stage 2 nephropathy][n=3/16]. No significant increase in the mean levels of blood urea and serum creatinine was detected in all studied diabetic groups when compared with controls and with each other
Conclusion: The present study clearly indicates the role of both lL-beta cytokine and NO as apoptotic markers, s-Fas as antiapoptotic marker and GADA in mediating islet B-celi damage in insulin dependent diabetics as well as their prognostic values. ? albuminuria is an early indicator of early diabetic nephropathy. The levels of apoptotic markers, GADA and excreted urinary albumin predict progression to overt nephropathy. Routine monitoring of all diabetic children for micro albuminuria must be done as it is a simple and reliable technique identifying insulin dependent diabetics at high risk for nephropathy. Apoptotic markers, GADA and albumin excretion rate are aggravated with prolongation of the disease duration and deterioration of glycemic control. Good glycemic control and novel strategies aimed at modifying the apoptotic process or inducing immune tolerance to antigens may arrest or reverse the process of beta-cell death, thereby preventing the onset of IDDM or lessening its clinical severity