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.
In early postnatal life, SGA infants display an increased insulin sensitivity with respect to glucose disposal but not with respect to suppression of lipolysis, ketogenesis, and hepatic production of IGFBP-1. It will be important to determine how these differential sensitivities to insulin vary with increasing age.
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.
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