Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 5 uppsatser.

Mutations in the insulin-like growth factor-I (IGF-I) receptor (IGF1R) have been associated with prenatal and postnatal growth retardation. However, little is known about potential effects of mutations in the IGF1R on carbohydrate homeostasis. Methods: We investigated clinical, endocrine and metabolic parameters in four family members carrying a novel IGF1R mutation (p.Tyr387X): an 18-year-old male (index case), his sister and two paternal aunts. Results: All family members showed a variable degree of impairment in prenatal growth, with birth weight standard deviation scores (SDS) between –1.65 and –2.37 and birth length SDS between –1.78 and –3.08. Their postnatal growth was also impaired, with height SDS between –1.75 and –4.86. The index case presented high IGF-I levels during childhood and adolescence and delayed bone age. The index case and his two paternal aunts had impaired glucose tolerance (IGT) associated with a variable degree of alterations in insulin sensitivity and secretion. In contrast, the index case’s sister, who had had IGT during pregnancy, showed normal glucose metabolism but reduced insulin sensitivity. Conclusion: This is the first study showing an association between a novel IGF1R mutation and a variable degree of alterations in prenatal and postnatal growth and in carbohydrate metabolism.

Gestational diabetes (GDM) is a disorder of glucose metabolism arising for the first time in pregnancy and spontaneously receding after birth. The issue of GDM is very topical since, according to the latest update of diagnostic criteria, up to 17% of pregnant women is threatened by this disorder. The incidence of GDM correlates with the increasing prevalence of overweight/obesity and metabolic syndrome. It is proved that women who have had gestational diabetes have an enormously increased risk of developing type 2 diabetes mellitus (DM2T). The risk accosiated with a gestational diabetes pregnancy stretches beyond the host, and can affect the fetus both directly (e. g. macrosomia development), and epigenetically (increases susceptibility to obesity, DM2T development or cardiovascular disease). Significant influence on the development of GDM (or DM2T) is a body composition that is directly related to lifestyle (nutritional intake and physical activity) and genetic role i salso involved. Early intervention may help delay the risk of developing DM2T and other metabolic complications. In this diploma thesis we monitored metabolic profiles of glucose and lipids and body composition based on anthropometric examination and questionnaires of nutritional income and physical activity. For the complex...