The incidence of peripheral, cerebro- and cardiovascular disease (CVD) in
patients with type 2 diabetes mellitus is approximately twice as high as
in the non-diabetic population. Conventional cardiovascular risk factors
such as plasma lipids, lipoproteins and hypertension only partially
explain this excessive risk of developing atherosclerosis and CVD.
Meta-analysis of studies performed in non-diabetic populations indicates
that the risk of CVD increases continuously with glucose levels above 4.2
mmol/l. The glucose hypothesis suggests that treatment which normalizes
glucose levels prevents or delays the long-term complications of diabetes
mellitus. However, the outcome of the UK Prospective Diabetes Study
demonstrates that glucose control does not completely prevent CVD.In
healthy subjects, serum IGF-I levels peak in early adulthood, after which
they gradually decrease with increasing age. Several observations suggest
that there is a premature and progressive age-related decline in serum
IGF-I bioactivity in type 2 diabetics, which eventually results in a
(relative) IGF-I deficiency. In type 2 diabetics, close relationships have
been demonstrated between glycaemic control and serum IGF-I levels, with
worse control being associated with lower IGF-I levels. Several studies
(in non-diabetics) suggest that lowered circulating IGF-I levels account
for a poor outcome of CVD. We previously observed in a population-based
study that a genetically determined lowered IGF-I expression increases the
risk of myocardial infarction with type 2 diabetes.This genetic approach
overcomes the problem tha
