Increased cell susceptibility to oxidative stress in siblings of insulin-dependent type 1 (IDDM) probands.

Oxidative stress has a role in the genesis and progression of tissue damage in IDDM. Since we observed kidney and metabolic abnormalities in non diabetic siblings of type 1 diabetics (heavier if the proband had diabetic nephropathy), we sought evidence of impaired endogenous defences against oxidants. Eighteen siblings of diabetic probands (8 with and 10 without nephropathy) and 13 healthy controls were studied. Were measured: erythrocyte glutathione content and cell response to oxygen radicals (xanthine+xanthine oxidase for 3h); serum albumin, lipids, electrolytes, iron, transferrin, ferritin, copper, ceruloplasmin, uric acid, bilirubin, SGGT, SGOT, SGPT; urinary outputs of glucose, uric acid, albumin, electrolytes, enzymes (UGGT, UNAG, UAAP). Siblings vs controls had lower serum HDL cholesterol and apoA1 (p<0.05) as well as urine glucose (p<0.01) and uric acid (p<0.05) outputs. Siblings of nephropathic probands vs siblings of non-nephropathic had higher serum total cholesterol and apoB (p<0.01), GOT (p<0.01), ceruloplasmin (p<0.05) and urine GGT output (p<0.05); serum HDL cholesterol and urine glucose excretion were lower (p<0.05); red cell methemoglobin content after oxidative stress was higher (p<0.05). Urinary GGT output was related to red cell methemoglobin content after stress, glycemia and total cholesterol (p<0.001); serum ceruloplasmin with 3h-hemolysis, methemoglobin content, triglycerides, apoB, SGGT, copper (p<0.001); serum apoB with hepatic enzymes (p<0.001); urine sodium excretion rate with glucose and uric acid outputs (p<0.001). Our findings suggest that: 1) non-diabetic siblings of nephropathic diabetics are more susceptible to oxidative stress; 2) indices of cell damage correlate with indices of oxidation, ceruloplasmin and low-density lipoproteins; 3) renal handling of molecules (glucose, uric acid) and ions (natrium) is abnormal; the supposed association of nephron transport abnormalities with insulin-resistance could explain the observed dyslipidaemia in otherwise healthy subjects