Insulin sensitivity and secretion in normal children related to size at birth, postnatal growth, and plasma insulin-like growth factor-I levels

Abstract

Aims/hypothesis. Type 2 diabetes risk is associated with low birth weight, rapid weight gain during childhood, and shorter stature and lower circulating IGF-I levels in adults. The largest variations in growth rates occur during the first postnatal years. We hypothesised that early postnatal variations in height and weight gain and IGF-I levels may be associated with risk markers for adult disease. Methods. We measured the fasting insulin sensitivity (Homeostasis model) and insulin secretion post-oral glucose (insulinogenic index 0-30 min) in 851 normal 8-year-old children from a prospective birth cohort. We examined associations between size at birth, postnatal weight gain and circulating IGF-I levels with insulin sensitivity and secretion at 8 years of age. Results. Fasting insulin sensitivity at 8 years was closely related to current BMI (r=−0.33, p<0.0005). Lower insulin sensitivity and higher BMI and waist circumference were all predicted by greater weight gain between birth to 3 years of age (all p<0.0005); lower birth weight was associated with reduced insulin sensitivity only in the highest current BMI tertile (r=0.17, p=0.006). In contrast, lower insulin secretion was related to smaller size at birth (p=0.01), independent of postnatal weight gain and insulin sensitivity. Lower insulin secretion was also independently related to shorter stature at 8 years of age relative to parental height (p=0.047) and with lower plasma IGF-I levels at 5 years of age (n=252, p=0.004). Conclusions/interpretation. Associations between lower birth weight and insulin resistance may be dependent on rapid weight gain during the early postnatal years. However, irrespective of postnatal weight gain, smaller size at birth, lower IGF-I levels and lower childhood height predicted reduced compensatory insulin secretion.

Critical periods and growth patterns from fetal life onwards associated with childhood insulin levels

“…However, it is possible that associations of fetal growth with insulin or glucose metabolism become apparent later in life. Furthermore, the widely described associations of low birthweight with increased risk of type 2 diabetes may be explained by beta cell dysfunction, which we were unable to assess in this study [34]. If our findings are confirmed by other studies with directly measured fetal growth data, detailed childhood growth data and more detailed measures of childhood glucose and insulin metabolism, including measures of beta cell function, our results underline the importance of strategies aimed at preventing rapid weight gain throughout childhood to improve insulin metabolism in later life.…”

Preterm birth and later insulin resistance: effects of birth weight and postnatal growth in a population based longitudinal study from birth into adult life

“…However, in 1-year-old infants born SGA, catch-up growth in weight until age 1 year was associated with higher fasting insulin levels [3]. Similarly, in children aged 8 years, rapid weight gain between birth and age 3 years was related to insulin resistance [36]. Also in prematurely born subjects aged 13-16 years, effects of early postnatal weight gain on later insulin resistance have been reported.…”

“…To date, a number of studies have investigated the effect of infancy weight gain on later type 2 diabetes [3,11,35,36]. In middle-aged subjects, low weight at birth and at age 1 year were associated with type 2 diabetes, but the rate of weight gain in the first year of life was unrelated to type 2 diabetes [35].…”

Free triiodothyronine plasma concentrations are positively associated with insulin secretion in euthyroid individuals

“…Glucotoxicity and lipotoxicity (2), cellular nutrient overload (3), inflammatory/immune mechanisms (4), in utero exposure to a diabetic environment (5), low weight at birth (6), and genetic factors (5,7) contribute to this insulin secretory dysfunction. Furthermore, a reduction in b-cell mass may be a characteristic of subjects with impaired fasting glucose and T2DM (8,9).…”