Maternal diabetes alters birth weight in glucokinase-deficient (MODY2) kindred but has no influence on adult weight, height, insulin secretion or insulin sensitivity

Abstract

Altered fetal insulin secretion caused by fetal or maternal glucokinase mutations influence birth weight. Here, we attempt to answer two additional questions: firstly, whether this variation in birth weight (from low birth weight to macrosomia) has an effect on adult height or weight. Secondly, whether maternal hyperglycaemia during fetal life has an effect on metabolic phenotypes of the adult offspring. We studied 447 family members from 37 MODY2 kindred, divided into four groups according to the presence or absence of a glucokinase mutation in the subject (S+ or S-, respectively) and his/her mother (M+ or M-). Birth weight data were obtained from a questionnaire sent to the mothers. Birth weight was reduced in the presence of a fetal mutation (M-S+) and increased in the presence of a maternal mutation (M+ S-). These effects are additive as similar birth weights were observed in M+ S+ and M-S- offspring. Adult height, weight or body mass index (weight/height2) were, however, similar in the four groups of subjects. Non-diabetic adult offspring, regardless of the glycaemic status of the mothers (M+ S- or M-S-), had similar insulin secretion, insulin sensitivity, blood pressures and lipid profiles. These variables as well as the severity of hyperglycaemia were similar in adult M+ S+ and M-S+ MODY2 subjects. Maternal environment and fetal genotypes could alter growth in utero by changing fetal insulin secretion but these effects do not result in a persistent programming in latter life.