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[Possible genetic causes for late complications of diabetes mellitus]
Background:
Hyperglycemia occurs in every patient with diabetes mellitus. It is the most important factor in the development of diabetic complications. However, the onset, intensity and the progression of complications show large interindividual variations. Manifestation in families and the lack of complications in some diabetics with poor metabolic control indicate a genetic predisposition to develop diabetic complications like nephropathy, neuropathy and angiopathy.
Nephropathy:
Diabetic nephropathy occurs only in 25 to 40% of the diabetic patients. Therefore a genetic risk factor for this complication is very likely. Various variations in genes like ACE-gene and angiotensinogen-gene have been described, which could be associated with the development of diabetic nephropathy.
Neuropathy:
Peripheral diabetic neuropathy occurs in up to 66% of all diabetics. Therefore and because of the possible pathological mechanisms genetic risk factors like variations in the Na/K-ATPase-gene and in the aldose reductase-gene are discussed.
Retinopathy:
An association between diabetic retinopathy and polymorphisms in the ACE-gene and the aldose reductase-gene seems very unlikely, because up to 75% of the diabetic patients suffer from retinopathy after 15 years of diabetes.
Macroangiopathy:
A large number of studies show an association between diabetic macroangiopathy and genetic variations in the ACE-gene (I/D-variant) and the paraoxonase-gene (2 isoforms).
Conclusion:
Based on the current evidence for associations of genetic markers with diabetic complications, the generation of an individual risk profile based on genetic markers seems to be possible. In addition to near euglycemia genetic markers could direct therapeutic strategies and lead to new therapeutic approaches.