Background:Intrauterine growth restriction (IUGR) has been linked to adult heart disease. The IUGR heart is vulnerable to diabetic heart disease. The aim was to examine the effect of induction of type 1 diabetes on myocardial collagen deposition and cardiac function in IUGR adult rat offspring when blood glucose levels were controlled.Methods:IUGR was induced by maternal protein restriction. At 24 weeks of age, diabetes was induced in male IUGR and non-IUGR offspring by streptozotocin; insulin injections maintained blood glucose levels at a mild (7-10mmol/l; n=8 per group) or moderate level (10-15mmol/l; n=8 per group). Echocardiography and cardiac morphology were examined at 32 weeks of age.Results:IUGR offspring exhibited cardiac hypertrophy at 32 weeks, including a thicker posterior wall and increased interstitial fibrosis in the left ventricle. Hyperglycemia led to an increase in heart size and myocardial fibrosis. The response to hyperglycemia was not different between IUGR and non-IUGR rats however, cardiac fibrosis was greatest when diabetes was combined with IUGR. Maintaining blood glucose levels at a mild hyperglycemic level, in general, attenuated the adverse effects of hyperglycemia but did not reverse the fibrosis.Conclusion:Exacerbated fibrosis in hyperglycemic IUGR hearts may lead to long-term cardiac dysfunction.