Recent advances in molecular genetics have allowed the identification of genetic anomalies associated with some monogenic forms of NIDDM, such as maturity-onset diabetes of the young (MODY) or maternally inherited diabetes associated with deafness (MIDD). However, these genes do not account for a great part of the genetic determinism of the common forms of NIDDM. A candidate gene approach studying the genes or chromosomal areas involved in syndromes associated with diabetes, such as ataxia telangiectasia (1) or Friedreich's ataxia (FRDA)(2), may contribute to the identification of susceptibility genes for NIDDM.

FRDA is an autosomal recessive disorder characterized by a progressive degeneration of the central and peripheral nervous systems. In most cases, it is caused by an expansion of a GAA triplet (in general, from 200 to [is greater than] 900 GAA repeats) in the first intron of the X25 gene located on chromosome 9q13, encoding the protein frataxin. The frataxin gene is a good candidate gene for NIDDM for several reasons. First, diabetes or impaired glucose tolerance is present in 30% of FRDA subjects. Several alterations in insulin secretion and insulin sensitivity have been described in FRDA. A reduced insulin response to arginine stimulation was reported in FRDA patients whatever their glucose tolerance, while FRDA patients with diabetes, as well as first degree relatives, showed insulin resistance (3, 4). Second, frataxin plays a crucial role in mitochondrial metabolism and mitochondrial DNA stability. FRDA gene mutations cause a multiple Fe-S-dependent respiratory chain enzyme deficiency, probably triggered by an oxidative stress secondary to an iron overload in the mitochondrial matrix (5). Based on knowledge of the role of mitochondrial oxidative phosphorylation in the [Beta]-cell metabolism,[Beta]-cell function may be abnormal in FRDA, as in other mitochondrial diseases. Third, a recent study showed that although the clinical features of FRDA are correlated with the size of the GAA repeat expansion, this was not the case for diabetes (6). Thus, it could be possible that small GAA expansions in the frataxin gene contribute to the development of diabetes in subjects free from FRDA. Furthermore, in a recent study, Ristow et al.(7) reported an association between NIDDM and the GAA repeat length in the FRDA gene in German and US populations.