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BERNARD PORTHA AN. R. ACAD. NAC. FARM.

subjects have been also described including the arteriosclerosis,
deposition of amyloid associated fibrosis and fat infiltrations (4, 5).

The genetic basis of beta-cell dysfunction in this form of diabetes
(the most frequent one) is certainly more complex than in subjects
with MODY or mitochondrial diabetes: it involves both multiple
interacting genes and environmental factors, which determine
whether diabetes will develop and at what age.

The clustering of T2D in families and the high concordance rates
noted for identical vs. fraternal twins implies a genetic etiology.
However, after years of intensive work by many laboratories, there
has been little success identifying T2D susceptiblity genes in humans
(review in 6).

A role for maternal inheritance in T2D was first suggested
by epidemiological studies. Adult patients described as having
maturity-onset diabetes had a higher prevalence of T2D in the
maternal side over two generations compared to the paternal side
suggesting a higher maternal transmission (7). In addition, in
patients with gestational diabetes, higher frequency of diabetes
in mothers than in fathers was reported (8). The maternal influence
in the development of T2D has been reported in the majority of
studies (9). Although a few studies did not find a maternal effect,
none reported a higher paternal transmission. Foetal exposure to
T2D as an environmental factor that may explain the maternal
transmission of T2D, was first demonstrated in Pima Indians, a
population with the highest prevalence of T2D reported around the
world (10). In order to negate the confounding effect of genetic
factors related to T2D, the effect of in utero exposure to type 1
diabetes was recently studied in a group of adult offspring free from
immunological markers of type 1 diabetes: a 33% prevalence of IGT
was reported in offspring of mothers compared to none of the
offspring of fathers (control group) (11). Taken together, these
findings strongly suggest that in utero exposure to diabetes is
associated with abnormal glucose homeostasis in offspring of
diabetic mothers and may participate in the excess of maternal
transmission in T2D.

To sum-up, now that the reduction in beta-mass has been
repeatedly established in humans with T2D, the debate focuses on

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