HLA-DQA and DQB alleles and predisposition to insulin dependent diabetes mellitus

Type I insulin-dependent diabetes mellitus [IDDM] is an autoimmune disease. Onset of the disease is attributed to interplay between genetic and environmental risk factors. It is strongly associated with the presence of arginine in position 52 of DQ alpha [alpha] chain and the absence of aspartic acid in position 57 of the DQ beta [alpha] chain. In this study we assessed the relative contribution of DQ alpha and DQ alpha chains to susceptibility to type I diabetes among the Egyptian patients. We identified those genetically at risk of development among their siblings in order to detect early development of autoantibodies allowing early application of preventive programs. Genomic DNA of forty Egyptian type I IDDM patients, 13 non diabetic siblings and 22 non diabetic controls were amplified using polymerase chain reactionamplification refractory mutation system [ARMS] and genotyped for HLA-DQA and DQB alleles. A significant high frequency of homozygous genotype for DQB1 non- Asp allele was detected in patients 50%, p=0.01, odd ratio [OR] =10 at 95% confidence interval [CI] =2.1-48.6 with susceptible results to the disease. The frequency of diabetogenic heterodimer Arg/non-Asp was significantly high in patients [82%, p=0.044, OR= 3.26, at 95% CI= 1.005-10.6]. On the other hand, a significant lower frequency of homozygous genotype for DQB1 Asp allele was detected in patients 12.5%, p=0.065; it was associated with protection from the disease. In conclusion, in Egyptian patients susceptibility and protection from type I diabetes is mainly associated with the DQ alpha chain. Siblings have potential risk to the disease. Non affected siblings should be targeted in a larger study for counselling. At risk individuals should be subjected to regular monitoring for the early development of autoantibodies which start years before the overt diabetes.

Protein C and microalbuminuria in insulin dependent diabetic children

The aim of this study was to assess one of the coagulation parameters, protein C, in insulin-dependent diabetic children and to find out its relation to the development of vascular changes manifested by microalbuminuria and to the glycemic control indices in diabetic children. The study was performed on 46 children including 24 diabetic patients with normoalbuminuria [mean age 11.2 +/- 1.9 years], 10 patients with microalbuminuria [mean age 13.5 +/- 1.23 years] and 12 healthy children of comparable age and sex with the patients as a control group. All children were subjected to full history taking, thorough physical examination, anthropometric assessment, fundus examination and laboratory investigations including a measurement of complete blood picture [CBC], fasting blood sugar [FBS], glycosylated hemoglobin [HbA1c], cholesterol [CH], triglycerides [TG], microalbuminuria and protein C [PC] levels. There was a highly significant increase in plasma PC level in diabetic children when compared with the controls and this increase was significantly more in microalbuminuric than in normoalbuminuric children. Moreover, PC level was significantly positively correlated with the duration of the disease and with other parameters and indices of diabetic control including HbA1c, CH, TG and microalbuminuria, which indicated that PC assessment could be used as a predictor of development of vascular complications as atherosclerosis and nephropathy in insulin-dependent diabetes mellitus