The family of an elderly man with Barrett's esophagus was examined for gastroesophageal reflux and development of Barrett's esophagus. All five living children have gastroesophageal reflux or esophagitis, or both, and three have unequivocal Barrett's esophagus. Two third-generation descendents have gastroesophageal reflux. This pattern suggests autosomal dominant transmission of the gastroesophageal reflux trait. The family also has a high prevalence of cancer, which may represent the cancer family syndrome.

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From animal and in vitro studies, it has been suggested that high environmental glucose, ketone, or insulin concentrations and low glucose or insulin concentrations may be etiologic factors for congenital malformations (CMs) in infants of diabetic mothers (IDMs). Transplacental passage of antibody-bound insulin has been demonstrated in humans. Controversy exists regarding the pathophysiology of CMs in human insulin-dependent diabetes mellitus (IDDM) pregnancies. We hypothesized that CMs in IDMs are associated with maternal vasculopathy, poor first-trimester glycemic control (i.e., hyper- and/or hypoglycemia), advanced White class, and high insulin requirements. We studied 165 first pregnancies of women with IDDM from 1978 to 1986. The goals of glucose control were a fasting blood glucose of less than 100 mg/dl and a 90-min postprandial blood glucose of less than 140 mg/dl. Insulin requirements, body weight, and pre- and postprandial blood glucose were recorded at weekly clinic visits. Maternal blood HbA1 was measured on entry and every 4 wk to confirm that adequate glycemic control was achieved. Women who enrolled in the project were interviewed during gestation by a geneticist/dysmorphologist who obtained genetic and environmental histories using a standard questionnaire. All live-born infants and stillbirths were examined. Each live-born infant was assessed systematically by two independent examiners, a neonatologist and a geneticist/dysmorphologist; examination with standardized checklists was performed in the newborn nursery as soon after birth as was practical. In first pregnancies in the study, there were 13 IDMs with major CMs (7.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Abtract. We hypothesized that adrenergic mechanisms support the postabsorptive plasma glucose concentration, and prevent hypoglycemia when glucagon secretion is deficient. Accordingly, we assessed the impact of glucagon deficiency, produced by infusion of somatostatin with insulin, without and with pharmacologic a-and f-adrenergic blockade on the postabsorptive plasma glucose concentration and glucose kinetics in normal human subjects. During somatostatin with insulin alone mean glucose production fell from 1.5±0.05 to 0.7±0.2 mg/kg per min and mean plasma glucose declined from 93±3 to 67±4 mg/dl over 1 h; glucose production then increased to base-line rates and plasma glucose plateaued at 64-67 mg/dl over 2 h. This plateau was associated with, and is best attributed to, an eightfold increase in mean plasma epinephrine. It did not occur when adrenergic blockade was added; glucose production remained low and mean plasma glucose declined progressively to a hypoglycemic level of45±4 mg/dl, significantly (P < 0.001) lower than the final value during somatostatin with insulin alone. These data provide further support for the concept that maintenance of the postabsorptive plasma glucose concentration is a function ofinsulin and glucagon, not of insulin alone, and that adrenergic mechanisms do not normally play a critical role. They indicate, however, that an endogenous adrenergic agonist, likely adrenomedullary epinephrine, compensates for deficient glucagon secretion and prevents hypoglycemia in the Address reprint requests to Dr. Cryer.