Gestational diabetes leads to the development of diabetes in adulthood in the rat.

We have developed a model of gestational diabetes in the rat to determine whether an altered metabolic intrauterine milieu is directly linked to the development of diabetes later in life. Uteroplacental insufficiency is induced in the pregnant rat on day 19 of gestation. Sham-operated animals serve as controls. Offspring are growth retarded at birth; however, they catch up by 5-7 weeks of age. At approximately 8 weeks of age, they are bred to normal males. During pregnancy, these animals develop progressive hyperglycemia and hyperinsulinemia accompanied by impaired glucose tolerance and insulin resistance. Offspring, designated as infants of a diabetic mother (IDMs), are heavier at birth and remain heavy throughout life. IDMs are insulin resistant very early in life, and glucose homeostasis is progressively impaired. Defects in insulin secretion are detectable as early as 5 weeks of age. By 26 weeks of age, IDMs are overtly diabetic. These data demonstrate that the altered metabolic milieu of the diabetic pregnancy causes permanent defects in glucose homeostasis in the offspring that lead to the development of diabetes later in life.

Congenital diaphragmatic hernia in 120 infants treated consecutively with permissive hypercapnea/spontaneous respiration/elective repair.

BACKGROUND/PURPOSE: Poor prognosis (approximately 50% survival rate and significant morbidity) traditionally has been associated with congenital diaphragmatic hernia (CDH). The authors reviewed a single institution experience and challenged conventional wisdom in the context of a care strategy based on permissive hypercapnea/spontaneous respiration/elective repair. METHODS: From August 1992 through February 2000, all infants with CDH and (1) respiratory distress requiring mechanical ventilation, (2) in-born or (3) transferred preoperatively within hours of birth are reported. All respiratory care strategy used permissive hypercapnea/spontaneous respiration and combined with elective repair. Arterial blood gas values and concomitant ventilator support were recorded. Outcome markers were (1) need for extracorporeal membrane oxygenation ECMO, (2) discharge to home, (3) supplemental oxygen need at discharge, and (4) influence of non-ECMO ancillary therapies (surfactant, nitric oxide, high-frequency oscillatory ventilation). RESULTS: One hundred twenty consecutive infants were reviewed. Overall survival rate was 75.8%, but, excluding 18 of 120 not treated (6 lethal anomalies, 10 overwhelming pulmonary hypoplasia, 3 prerepair ECMO-related neurocomplications), 84.4% survived to discharge. A total of 67/120 were inborn. Non-ECMO ancillary treatments had no impact on survival rate. ECMO was used in 13.3%. Surgery was transabdominal; prosthetics were used in 7%. Tube thoracostomy was rare. Every inborn patient (n = 11) requiring a chest tube for pneumothorax died. Respiratory support before surgery was peak inspiratory pressure (PIP), 22, FIO(2),.43 with PaO(2), 66 torr; PaCO(2), 41 torr; and pH, 7.32. The survivors discharged on oxygen (n = 2) died at 4 and 7 months. CONCLUSIONS: The majority of infants with life-threatening CDH treated with permissive hypercapnea/spontaneous respiration/elective surgery survive to discharge with minimal pulmonary morbidity.