BACKGROUND: Intrauterine growth restriction (IUGR) has been linked to heart disease in adulthood. Hence the IUGR heart is likely to be vulnerable to diabetic heart disease. The aim of this study was to examine the effect of induction of type 1 diabetes on myocardial collagen deposition and cardiac function in adult rats with a history of IUGR, after controlling blood glucose levels. METHODS: IUGR was induced by protein restriction in the pregnant female rat. When the offspring were 24 wk of age, diabetes was induced in male IUGR and non-IUGR rats by means of streptozotocin; insulin injections were used to maintain blood glucose levels at a mild (7-10 mmol/l; n = 8 per group) or moderate level (10-15 mmol/l; n = 8 per group). Echocardiography and cardiac morphology analyses were carried out when the rats were 32 wk of age. RESULTS: IUGR offspring exhibited cardiac hypertrophy at 32 wk, 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 present along with a history of IUGR. In general, maintaining blood glucose levels at a mildly hyperglycemic level attenuated the adverse effects of hyperglycemia but did not reverse the fibrosis. CONCLUSION: Exacerbated fibrosis in hyperglycemic hearts of IUGR offspring may lead to long-term cardiac dysfunction.