Reduced Gluconeogenesis due to Hyperinsulinism: Hormonal and Metabolic Studies in an Infant with Hypoglycemia

Abstract

Summarygenesis in vivo in man, however, is still a matter of controversy ( 5 , 11). This paper presents evidence for a much reduced An infant with a of h~~o g l~c e m i a suffered from g l~c o n e~g e n~s i s in an infant with hyperinsulinism, The hypoglyh~~o g l~c e m i a caused h~~erinsulinism. G1ucagon se-cemia was best counteracted by injections of long acting glucacretion was normal. The in vivo incorporation of 14C from gon. alanine into glucose was much reduced, but the key gluconeogenic enzymes revealed normal to high activities in vitro, with normal intracellular distributions. The glucogenic amino acids in CASE REPORT plasma tended to be high, especially proline. A n alanine load revealed a normal glucagon secretion pattern, whereas the BRB, a boy, was born at term On February 16, l Y 7 j , after a insulin secretion was inappropriately strong. The insulin re-normal Pregnancy. Birthweight was 2800 g, length 48 cm, and sponse to glucagon, however, was subnormal. The alanine load the neonatal period was uneventful. b he ~a t i e n t has two sisters, caused a paradoxic drop in plasma pyruvate. Serial determina-One of whom suffered from hypoglycemia from the age of 2 tions of the fasting values of plasma alanine and free fatty acids months. the and the @FA) disclosed a highly significant negative correlation. had suffered from hypoglycemia. The sister and the mother The best therapeutic effect was obtained with long acting recovered s~ontaneously at 4-5 years of age, and are now in glucagon sc twice daily, but hypoglycemia before the next good health, except that the sister is slightly mentally retarded. injection of glucagon could not be avoided. Glucagon treatment Studies of the other members were refused. caused a marked drop in the plasma amino acids, including the The patient first experienced symptoms of hypoglycemia at branched-chained, and a highly significant decrease in plasma 4.5 months of age, when he got attacks with loss of tonus, eyetriglycerides and increase in FFA, whereas glycerol did not rolling, smacking of the lips, and, occasionally, convulsions. H e change. Dipheuylhydantoin caused a significant increase in Was first admitted to our hospital at 7 months of age, with a blood glucose, but therapeutic serum levels of the drug were glucose of 0.83 mmol/liter. Routine laboratory difficult to achieve. investigations were normal, except for moderate elevations of ~~~i~~ glucagon treatment an oral glucose tolerance test was alanine aminotransferase and aspartate aminotransferase in senormal, with a normal increase in insulin, whereas an iv glucose rum. These values later normalized, but intermittently alanine tolerance test was diabetic (KG = 1.0), and there was n o rise in aminotransferase, alkaline phosphatase, and y-glutam~l transinsulin.peptidase were elevated. The liver was not enlarged, and It is concluded that the reduced in viva incorporation of 1 4~ appeared normal by laparotomy for liver biopsy. ~i s t o l o~i c a l l~, into glucose from alanine reflected a reduced gluconeogenesis, ...