GENETICS OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Non insulin-dependent diabetes mellitus (NIDDM) is a genetic disorder with an epidemic development in the westernized civilisations. The knowledge of genetic factors would help in screening those individuals susceptible to develop diabetes, to prevent overfeeding, overweight and sedentarity ; these environmental factors can reveal or worsen diabetes. NIDDM is a clinically and genetically heterogeneous disorder, probably due to the alteration of several genes. The collection of numerous and large families with several diabetic subjects and the sorting in clinically homogeneous subgroups are necessary to identify the susceptibility genes. It has been recently shown that glucokinase (enzyme that phosphorylates glucose in pancreatic beta-cell and liver) was the cause of MODY (maturity onset diabetes of the young), a NIDDM subtype characterized by an autosomic dominant mode of inheritance and an early age of onset. Glucokinase mutations are responsible for a mild hyperglycemia with onset during childhood or during pregnancy; in addition, diabetes can be due to mutations in mitochondrial DNA in families where the disease is maternally transmitted and often associated with hearing loss. These two genetic defects can account for about 2 % to 5 % of NIDDM patients each. Screening for these mutations is feasible.