Maternal diabetes results in inverse changes of circulating fetal IGF-1 and IGFBP-1 at birth. A decrease in circulating IGFBP-1 and to a lesser extent an increase in circulating IGF-1 may present an important mechanism that contributes to increased birth weight in diabetic pregnancies.

OBJECTIVE -In genetically diabetes-prone populations, maternal diabetes during pregnancy increases the risk of their children developing diabetes and obesity (the vicious cycle of type 2 diabetes). Fetal hyperinsulinemia at birth acts as a marker of this risk. We therefore examined whether cord insulin and leptin concentrations are increased in offspring of Maori and Pacific Island mothers with type 2 and gestational diabetes mellitus (GDM) and varying degrees of glycemic control (HbA 1c ). RESEARCH DESIGNS AND METHODS -Maori and PacificIsland mothers were prospectively recruited at Middlemore Hospital, South Auckland. Cord blood was taken from umbilical vein at birth from singleton babies born after 32 weeks of gestation to 138 mothers with GDM, 39 mothers with type 2 diabetes, and 95 control mothers. , and control subjects 13 ng/ml [8 -22]; P Ͻ 0.001) in cord blood. Cord insulin concentrations Ͼ120 pmol/l were found in 29% of offspring of mothers with GDM and 31% of mothers with type 2 diabetes. Many mothers with GDM had abnormalities of glucose tolerance postpartum (20% type 2 diabetes, 34% impaired glucose tolerance or impaired fasting glucose). Higher cord insulin (57 pmol/l [40 -94]) and leptin (26 ng/ml [17-39]) concentrations were found even in offspring of GDM mothers with normal glucose tolerance postpartum. RESULTSCONCLUSIONS -Raised cord insulin and leptin concentrations are a common finding in offspring of mothers with type 2 diabetes and GDM in this population. Diabetes Care 29:1345-1350, 2006F etal hyperinsulinemia is characteristic of pregnancy complicated by maternal diabetes and underpins complications such as macrosomia (1). Cord leptin correlates with measures of adiposity at birth (2-4) and is also raised in offspring of mothers with diabetes (3,4). Assessment of insulin and leptin at birth may be a particularly useful way of monitoring whether the fetus has been exposed to abnormally high levels of glucose in utero. Fetal hyperinsulinism may also have potential prognostic implications. Several studies have suggested that the maternal intrauterine environment might result in "programming" of later disease. An increased risk of obesity (5-8) and abnormal glucose tolerance (9 -12) are observed when offspring have been exposed to maternal diabetes in utero. Fetal hyperinsulinemia acts as a marker of this increased risk, offspring of diabetic mothers with higher insulin levels in utero being at a higher risk of later metabolic complications (7,8,10).The Pacific Island and Maori peoples of New Zealand are populations at high risk of both type 2 and gestational diabetes during pregnancy. We measured concentrations of fetal insulin, insulin propeptides, and leptin, together with weight and skinfold thickness at birth, with the following hypotheses: where the mother has type 2 diabetes and gestational diabetes mellitus (GDM), fetal hyperinsulinism is common despite treatment of disease, and fetal leptin and fat mass are similarly increased; and in subgroup analysis, these effects are most pronounce...

Lactation was suppressed in rats using a combined treatment of bromocriptine (to reduce prolactin concentrations) and a specific antiserum to rat GH administered twice daily for 2 days. When milk production had ceased, as determined by litter weight loss and the absence of milk in the stomachs of pups, attempts were made to reinitiate lactation using prolactin, GH, insulin-like growth factor-I (IGF-I) precomplexed to recombinant human IGF-binding protein-3 (hIGFBP-3) or IGF-I plus IGF-II precomplexed to hIGFBP-3. Despite the fact that all treatments except prolactin led to increases in serum IGFs and IGFBP-3, only prolactin and GH provoked the reinitiation of milk production as determined by increased litter weight gain, milk in the stomach of pups and a significant increase in the weight of the mammary glands. Since the mammary gland has been shown to produce IGFBPs which may inhibit IGF action we also tested three IGF-I analogues, R3-IGF-I, Long-IGF-I and Long-R3-IGF-I. R3-IGF-I has a single amino acid substitution (Glu to Arg) at position 3 whereas Long-IGF-I has a 13 amino acid N-terminal extension. These modifications dramatically reduce the ability of these analogues to bind to IGFBPs although they remain active at the IGF-I receptor. Such IGF analogues would therefore be expected to be active irrespective of the production of inhibitory IGFBPs. However, none was effective in reinitiating lactation, even at doses which have been shown to be biologically effective in terms of nitrogen retention.(ABSTRACT TRUNCATED AT 250 WORDS)