Search

Objective: Since the offspring of gestational diabetic mothers (GD) is at increased risk to develop obesity and diabetogenic disturbances later in life, while pathophysiological mechanisms responsible are unclear, to investigate long-term consequences of neonatal hyperinsulinism occurring characteristically in GD offspring., Methods: Newborn Wistar rats received daily subcutaneous injections of a long-acting insulin from the 8th to 11th day of life (IRI), while in controls (CO) NaCl was applied. Body weight was recorded throughout life. Glucose tolerance test was performed on the 140th day of life (1.5 g/kg glucose injected i.p. after an overnight fast and blood samples were taken up to 90 min from retroorbital plexus). On the 240th day of life, the vulnerability to a single "subdiabetogenic" dose of streptozotocin (STZ; 25 mg/kg body weight) was tested. Blood samples for estimating glucose levels were taken before STZ, and subsequently on days 2, 7, 14, 21, and 28 after STZ., Results: IRI rats developed overweight during juvenile life until adulthood (P<0.001), characterized by a clear elevation of the Lee obesity index (P<0.005), and associated with basal hyperglycaemia (P<0.05), hyperinsulinaemia (P<0.05), as well as an increased insulin/glucose-ratio as a measure of insulin resistance (P<0.005). Impaired glucose tolerance occurred in early adulthood, and increased vulnerability to a "subdiabetogenic" dose of streptozotocin (see above), leading to significant hyperglycaemia (P<0.05), was evaluated in the 9th month of age. Accompanied by a transient reduction of hyperinsulinaemia during a period of 21 days, Lee obesity index and insulin/glucose-ratio decreased significantly after STZ treatment in IRI rats (P<0.01)., Conclusions: Overweight and increased diabetes susceptibility in adulthood due to temporary hyperinsulinism during a critical period of postnatal life are suggested to be a consequence of acquired dysregulation and overstimulation, respectively, of the pancreatic insulin secretion in rats.