Strong associations between low birth weight and insulin resistance have been described. However, most of these studies have been retrospective. We aimed to determine whether infants born small for gestational age (SGA: birth weight <5th percentile for gestational age) have decreased insulin sensitivity, compared with appropriate for gestational age (AGA: birth weight >10th percentile) at 1 yr of age. We studied blood lipids, fasting insulin levels, other markers of insulin sensitivity, and insulin secretion during an iv glucose tolerance test in a cohort of 85 SGA and 23 AGA 1-yr-old infants. In addition, SGA infants were stratified according to catch-up growth (CUG) in weight (WCUG) or length (LCUG) during the first year of life. At 1 yr, SGA infants had a clear tendency to higher triglycerides. Fasting insulin was significantly higher in SGA infants with WCUG, compared with those who did not catch up and AGA infants (mean +/- SEM, 32.6 +/- 4.6 vs. 14.9 +/- 2.3 vs. 21.4 +/- 3.3 pM, respectively; P < 0.05). Length increment (in SD score) was the principal determinant of postload insulin secretion (R(2) = 0.1, P < 0.01). We conclude that insulin secretion and sensitivity are closely linked to patterns of rapid WCUG and LCUG during early postnatal life. Fasting insulin sensitivity is more related to WCUG and current body mass index, whereas insulin secretion seems to be directly related to LCUG.

Aims/hypothesis: Insulin resistance and type 2 diabetes risk in human subjects who were small-for-gestationalage (SGA) at birth may be a consequence of rapid early postnatal weight gain. Materials and methods: We prospectively studied early changes in fasting insulin sensitivity and insulin secretion, assessed by a short intravenous glucose tolerance test that was conducted several times from birth to 3 years of age in 55 SGA (birthweight below fifth percentile) newborns and in 13 newborns with a birthweight appropriate for gestational age (AGA). Results: Most SGA infants showed postnatal upward weight centile crossing and by 3 years were similar in size to AGA infants. SGA infants had lower pre-feed insulin levels at postnatal age 48 h than AGA infants (median 34.4 vs 59.7 pmol/l, p<0.05), but by the age of 3 years they had higher fasting insulin levels (median 38.9 vs 23.8 pmol/l, p<0.005), which were related to rate of weight gain between 0 and 3 years (r=0.47, p=0.0003). First-phase insulin secretion did not differ between SGA and AGA infants, but SGA infants had a lower glucose disposition index (beta cell compensation) (median 235 vs 501 min mmol, p=0.02), which persisted after allowing for postnatal weight gain (p=0.009). Conclusions/interpretation: SGA infants showed a marked transition from lower pre-feed insulin and increased insulin sensitivity at birth to insulin resistance over the first 3 years of life. This transition was related to rapid postnatal weight gain, which could indicate a propensity to central fat deposition. The additional observation of reduced compensatory beta cell secretion underlines the need for long-term surveillance of glucose homeostasis in all SGA subjects, whether or not they show postnatal catch-up growth.

A high frequency of hyperandrogenism, PCOM, and PCOS is observed in DM1, which appears to be associated with intensive insulin treatment.

Adiponectin, a novel adipocytokine with insulin sensitizing properties, is inversely related to obesity and insulin resistance in adults. We recently reported large variations in weight gain and insulin sensitivity during the first year in infants born small for gestational age (SGA) or appropriate for gestational age (AGA). We now determined whether adiponectin levels were related to postnatal growth and insulin sensitivity in a prospective cohort followed from birth to two years old (n = 85) (55 female/30 male, 65 SGA/20 AGA). Serum adiponectin levels at one year and two years were higher compared to reported levels in adults and older children, and decreased from one year (21.6 +/- 0.6 microg/ml) to two years (15.7 +/- 0.7 microg/ml) (p < 0.05). At two years adiponectin levels were lower in females (15.3 +/- 0.4 microg/ml) than males (16.4 +/- 0.6 microg/ml) (p < 0.05), but no gender difference was seen in leptin or insulin levels. No differences in adiponectin levels were seen between SGA and AGA infants at one or two years. However, in SGA infants changes in adiponectin between one to two years old were inversely related to weight gain (r = -0.310, p < 0.05). Changes in leptin levels between one to two years were positively related to weight gain in both SGA and AGA infants (r = 0.450 and r = 0.500 respectively, both p < 0.05). Adiponectin levels were unrelated to insulin levels at one or two years, nor to change in insulin levels between one to two years. In multiple regression analysis, adiponectin levels were related only to postnatal age; omitting age from the model, the determinants of higher adiponectin levels were male gender (p = 0.03), lower postnatal body weight (p < 0.001), and higher birth weight SD score (p = 0.004). In conclusion, fall in serum adiponectin levels during the first two years of life were related to increasing age and greater weight gain SGA infants, but were unrelated to insulin sensitivity.

In prepubertal children, low birth weight is related to reduced insulin sensitivity, particularly if a history of rapid postnatal weight gain is present. We sought to determine whether these associations were also evident in premature, very-low-birth-weight (VLBW) children. We studied 60 VLBW prepubertal children aged 5-7 yr (mean age 5.7 +/- 0.7 yr). Birth weights ranged from 690 to 1500 g (mean 1195 +/- 31 g), with gestational ages between 25 and 34 wk (median 29 wk). A short iv glucose tolerance test was carried out to assess fasting insulin sensitivity and glucose-stimulated insulin secretion. The effects of current body mass index, birth weight (SD scores), postnatal growth rates, and indicators of postnatal morbidity were evaluated by analysis of covariance. Twenty children were born small for gestational age, and 40 were appropriate for gestational age. Ninety-eight percent of them had attained a height within target range. Children who were small for gestational age had lower insulin sensitivity than children who were appropriate for gestational age (homeostasis model assessment insulin resistance index 1.24 +/- 0.17 vs. 0.94 +/- 0.08, P < 0.05). Moreover, birth weight SD scores correlated significantly with homeostasis model assessment insulin resistance index (r = -0.326, P = 0.01). This effect persisted after adjustment for current body mass index, gestational age, and perinatal morbidity. In addition, fasting and postload insulin secretion during the short iv glucose tolerance test correlated significantly with early postnatal growth rates, independently of birth weight SD scores. Our findings in a cohort of VLBW prepubertal children indicate that growth in utero as well as postnatal growth rates are independent determinants of subsequent insulin sensitivity and secretion.

These data suggest that patients with DM1 have differences in ovarian steroidogenic response to leuprolide, compared with C girls during puberty. Future studies in young women should clarify whether these findings are related to the pathogenesis of hyperandrogenism later in life.

IGF-I levels increased rapidly from birth in SGA, but not AGA children. During the key first-year growth period, IGF-I levels were related to beta-cell function and longitudinal growth. In contrast, by 3 yr, when catch-up growth was completed, IGF-I levels were related to body mass index and IR, and these higher IGF-I levels in SGA infants might indicate the presence of relative IGF-I resistance.

Wide ranges in postnatal weight gain are seen in infants born small for gestational age (SGA); most show some catch-up growth and this may be driven by increased appetite. Ghrelin, the natural ligand of the GH secretagogue receptor, has potent orexigenic effects. In adults circulating ghrelin levels are increased in anorexia, decreased in obesity and show post prandial suppression. The aim of the present study was to test the hypothesis that rate of weight gain over the first year in SGA infants may relate to variable suppression of circulating ghrelin levels. Serum ghrelin levels were measured in 1 y old infants born SGA (n = 85) and in control infants born adequate for gestatitional age (AGA) (n = 22) fasting and 10 minutes after intravenous (iv) glucose (0.5 g/Kg of 25% dextrose). Sex- and gestational age-adjusted SD scores (SDS) for body weight were calculated at birth and at 1 y, and delta weight SDS between 0-1 y was calculated as an index of postnatal weight gain. In both SGA and AGA groups, ghrelin levels reduced from fasting (mean +/- SE: 104.4 +/- 6.4 fmol/ml) to 10 minutes post-iv glucose (82.7 +/- 5.3, p < 0.005). There were no differences in ghrelin levels between SGA and AGA infants (fasting or post-iv glucose). However, in SGA infants ghrelin levels post-glucose, but not fasting, were psitively related to current length (r = 0.28, p < 0.05), weight (r = 0.23, p < 0.05) and to change in weight SDS 0-1 y (r = 0.22, p < 0.05). SGA infants who showed poor catch-up growth showed a larger decline in ghrelin concentrations post-iv glucose. In conclusion, circulating ghrelin levels rapidly decreased after iv glucose. Higher ghrelin levels or lower reductions in circulating levels following iv glucose were seen in SGA infants who showed greater infancy weight gain, suggesting that sustained orexigenic drive could contribute to postnatal catch-up growth.