Clustering of cardiovascular risk factors in families of type 1 diabetic patients: abnormalities are both common to all members and specific for diabetic nephropathy

A genetic predisposition to type 1 insulin-dependent diabetes mellitus (IDDM) and its microvascular complications has been suggested. To study familiar clustering of clinical and laboratory abnormalities in non-diabetic normotensive relatives of type 1 diabetics, we examined 21 IDDM patients (8 micro, 13 normoalbuminuric), their first-degree relatives (29 parents, 20 siblings) and matched healthy controls. Measurements: serum fasting glucose, HbA1c, fructosamine, insulin, lipids; urea, creatinine, electrolyte clearances; proteinuria, albuminuria and enzymuria (N-acetyl-beta-D-glucosaminidase, NAG; gamma-glutamyltransferase, GGT, alanine-aminopeptidase, AAP); erythrocyte sodium-hydrogen countertransport. Parents of diabetic patients had higher proteinuria (p<0.01) and tubular brush-border enzymuria (GGT, p<0.05; AAP, p<0.01) than controls. Parents of microalbuminuric diabetics (n=11) had heavier proteinuria (p<0.01), albuminuria (p<0.001), dyslipidemia (triglycerides, p<0.01; apolipoprotein B, p<0.05) than parents of normoalbuminuric probands (n=16). Siblings of diabetic people showed raised proteinuria (p<0.01) and albuminuria (p<0.05) than controls. Siblings of microalbuminuric probands (n=9) had higher albuminuria (p<0.05), serum total cholesterol (p<0.05), triglycerides (p<0.05) and apoB (p<0.05) than siblings of normoalbuminuric diabetics. Erythrocyte sodium-hydrogen antiport activity was elevated in IDDM patients and relatives, irrespective of probandʹs renal status. Our data support the presence of multiple cellular defects, either common to all family members (elevated proteinuria and antiport activity) and specific for families with nephropathic proband (dyslipidemia and higher albuminuria). They confirm a familiar predisposition to CVD in families with diabetic nephropathy, while doubt the role of sodium-hydrogen antiporter as candidate predictor of diabetic nephropathy.