Age-dependent Insulin Secretion of the Endocrine Pancreas In Vitro from Fetuses of Diabetic and Nondiabetic Patients

Abstract

Fetal hyperinsulinemia is assumed to play a key role in the pathogenesis of diabetic fetopathy. To investigate the role of enhanced fetal B-cell mass as one cause of fetal hyperinsulinemia during diabetic pregnancy, we studied human fetal pancreatic slices from diabetic women (FDW) with poor metabolic control and nondiabetic women (FNDW) between 11 and 26 wk of pregnancy, morphometrically and by in vitro incubation experiments. Abortions had been performed due to different medical indications. We found a good correlation between the calculated B-cell mass and the gestational age in both FDW and FNDW, but the increase in FDW was much more pronounced. Such a correlation was also found in vitro regarding the insulin response to glucose and IBMX. The FDW had significantly higher values than FNDW of the same age range. In contrast to this, we found in two diabetic patients with tight metabolic control during the whole pregnancy results similar to those in FNDW. Therefore, we assume that it could be possible to prevent fetal hyperinsulinemia and perhaps even diabetic fetopathy in diabetic women by tight metabolic control during the whole pregnancy, but further investigations are necessary.

Amniotic Fluid Insulin at 14–20 Weeks’ Gestation

“…AF insulin concentration increases significantly during the 14 -20-week period (3,8) and has been associated with birth weight in female offspring (16). Though acute fetal hyperglycemia does not appear to elicit insulin release in the fetuses of nondiabetic women during this period (2), increased pancreatic insulin content and glucose-mediated insulin release can be demonstrated in the fetuses of diabetic women during the 16 -20-week period (1). The presence of AF insulin and Cpeptide before 20 weeks has been associated with maternal diabetes (6,7,15).…”

“…nsulin production by the human fetus can be identified as early as 11 weeks of gestational age (1). In the early midtrimester, an acute hyperglycemic stimulus in the human fetus does not appear to provoke insulin release in nondiabetic pregnancy (2) but may do so in the fetuses of diabetic women (1).…”

“…In the early midtrimester, an acute hyperglycemic stimulus in the human fetus does not appear to provoke insulin release in nondiabetic pregnancy (2) but may do so in the fetuses of diabetic women (1).…”

Midtrimester Amniotic Fluid Leptin and Insulin Levels and Subsequent Gestational Diabetes

“…Amniotic fluid insulin is from a fetal origin, but the gestational age during which amniotic fluid insulin predictably rises in response to maternal hyperglycemia is unknown. However, we know that insulin can be identified in pancreatic islets in the early midtrimester [17] , and that increased pancreatic insulin content has been found in the fetus of diabetic women during the 16-to 20-week period [18] . Chronic insulin administration stimulates leptin production in humans [19] and it has been reported that leptin is overexpressed in placentas of diabetic women who require chronic insulin therapy [20] , suggesting that insulin may modulate placental leptin expression.…”

Growth of fetuses of diabetic mothers

“…In particular, a poor glycemic control in the first conceptual weeks causes a high incidence of congenital malformations21 and early growth delay"g~22; later on (11 weeks to 15 weeks of menstrual age), it is responsible for the hyperfunction of the fetal pancreatic beta-cells, with the consequent accelerated growth and macrosomia at birth. 23 In all our study groups a strict glycemic control was obtained. However, in the CSII group the k coefficicnt was significantly lower than the controls for both BPD and AC.…”