Anni Larnkjær

Does vitamin D supplementation of healthy Danish Caucasian girls affect bone turnover and bone mineralization

INTRODUCTION A high peak bone mass may be essential for reducing the risk of osteoporosis later in life and a sufficient vitamin D level during puberty may be necessary for optimal bone accretion and obtaining a high peak bone mass. Dietary intake and synthesis during winter of vitamin D might be limited but the effect of vitamin D supplementation in adolescence on bone mass is not well established. OBJECTIVE To investigate the effect of supplementation with 5 and 10 microg/day vitamin D(3) for 12 months in 11- to 12-year-old girls on bone mass and bone turnover as well as the possible influence of VDR and ER genotype on the effect of the supplementation. METHODS The girls (n=221) were randomized to receive either 5 microg or 10 microg vitamin D(3) supplementation per day or placebo for 12 months. Whole body and lumbar spine bone mass measured by DXA and pubertal status were determined at baseline and after 12 months whereas physical activity and dietary intake of calcium and vitamin D were assessed at baseline. Serum (S) 25-hydroxyvitamin D (25OHD), S-osteocalcin, S-parathyroid hormone, S-calcium, S-inorganic phosphate, urinary (U) pyridinoline (Pyr) and deoxpyridinoline (Dpyr) were measured at baseline and after 6 and 12 months. RESULTS The S-25OHD concentration increased (p<0.001) relative to the baseline values in the groups receiving either 5 microg/day (mean+/-SD; 11.0+/-10.3 nmol/l, baseline 41.9+/-17.6 nmol/l) or 10 microg/day (13.3+/-11.8 nmol/l, baseline 44.4+/-16.6 nmol/l) vitamin D(3) for 12 months compared to placebo (-3.1+/-9.8 nmol/l, baseline 43.4+/-17.1 nmol/l). There was no effect of vitamin D-supplementation on biomarkers for bone turnover or on whole body or spine bone mineral augmentation. However, vitamin D supplementation increased whole body bone mineral density (BMD) (p=0.007) and bone mineral content (BMC) (p=0.048) in the FF VDR genotype but not in the Ff or ff VDR genotypes. CONCLUSION Supplementation with vitamin D (5 or 10 microg/day) over 12 months increased the S-25OHD concentration but there was no effect on indices of bone health in the entire group of girls. However, there was an effect on BMD for a subgroup with the FF VDR genotype indicating an influence of genotype.

Secular change in adult stature has come to a halt in northern Europe and Italy

AIM To investigate whether the increase in adult stature in European countries is continuing. METHODS The secular trend in growth after 1990 for various European countries was assessed by national conscript data. RESULTS In Scandinavia and the Netherlands, the height has reached a plateau at 179-181 cm, and in Italy a plateau at 174 cm. In Belgium, Portugal and Spain, height continued to increase. CONCLUSION Only in the northern European countries and Italy height has ceased to increase.

Early programming of the IGF-I axis: negative association between IGF-I in infancy and late adolescence in a 17-year longitudinal follow-up study of healthy subjects.

BACKGROUND IGF-I is a major regulator of growth, influenced primarily by diet in infancy and primarily by GH in childhood. Breastfed infants have lower IGF-I levels compared to formula fed and tend to be shorter. The higher protein content of infant formula has a stimulatory effect on IGF-I production. Conversely, studies suggest that later in childhood, those breastfed are taller and have higher IGF-I levels. Therefore, it has been suggested that the IGF-I axis may be programmed by diet during infancy. The association between IGF-I in infancy and later life is not known. OBJECTIVE To examine the association between IGF-I in infancy and adolescence. DESIGN Infants (109) from the observational Copenhagen cohort study. METHODS Serum-IGF-I was measured during infancy (2, 6, and 9 months) and at follow-up at 17 years. Associations were examined by correlation tests and linear regression controlling for gender, breastfeeding, and other covariates. Likelihood ratio test based on residual log likelihood was applied for analysis including all measurements during infancy. RESULTS There was an inverse association between IGF-I at 9 months and 17 years (r=-0.39, P=0.014, and n=40). A 1 ng/ml higher IGF-I concentration at 9 months corresponded to 0.95 ng/ml lower IGF-I concentration at 17 years. IGF-I levels at 2 and 6 months were not significantly associated with IGF-I at 17 years, but the estimated directions were negative. These associations were not changed when adjusted for breastfeeding and other covariates except IGF-I at 2 months which was significantly negatively associated with IGF-I at 17 years (P=0.030) corresponding to a 0.96 ng/ml lower IGF-I concentration at 17 years per ng/ml IGF-I at 2 months. Inclusion of all measurements during infancy showed a negative association with 17-year values (r=-0.26, P=0.043, and n=109). CONCLUSION The results support the hypothesis that the IGF-I axis can be programmed early in life.

IGF-I and IGFBP-3 in healthy 9 month old infants from the SKOT cohort: breastfeeding, diet, and later obesity.

BACKGROUND High IGF-I concentrations in infancy have been associated with later obesity but the interactions between diet, IGF-I concentrations and growth in early life are complex and involve programming of the IGF-I axis. OBJECTIVE This paper examines how IGF-I and IGFBP-3 concentrations measured at age 9 months are related to diet and growth in infancy. DESIGN In the Danish SKOT cohort healthy term infants were included at age 9 months with follow-up at age 18 months. Total 252 infants had a full data set and were included in the analysis. Measurements include weight, length, skinfold thickness, waist circumference, 7-d food records, and blood analysis of IGF-I, and IGFBP-3. RESULTS Infants not being breastfed at 9 months of age (46%) had higher median IGF-I concentration than breastfed infants (51.6 vs. 44.2 ng/mL, P=0.0005) and there was a negative dose response effect of daily numbers of breastfeedings on IGF-I concentration. IGF-I concentration was negatively associated with birth weight and positively related to increase in weight, length and BMI between birth and 9 months. Between 9 months and 18 months of age increase in length was positively and increase in BMI was negatively related to IGF-I concentration. CONCLUSION Breastfeeding has a strong negative effect on IGF-I concentrations in late infancy. Although IGF-I concentrations at 9 months of age were negatively associated with change in BMI during the following 9 months we speculate that this could reflect an early adiposity rebound and thereby an increased risk of obesity later in life.

Amount and quality of dietary proteins during the first two years of life in relation to NCD risk in adulthood

During late infancy many infants have a protein intake, which is more than three times as high as the physiological need. Several observational studies have shown an association between a high-protein intake (>15 energy %) early in life and an increased risk of developing obesity and thereby non-communicable diseases (NCDs) later in life. This effect was supported by a recent intervention study with infant formulas with two levels of protein, showing that a higher protein intake during the first year of life resulted in a higher body mass index (BMI) at age 2 years. It is also plausible that an important reason for the slower growth in breast-fed infants is the lower content of protein in breastmilk, but other qualities of breastmilk could also play a role. A high intake of protein, especially dairy protein, stimulates the growth factors insulin-like growth factor (IGF-I) and insulin, and it has been suggested that the lower risk of NCDs in breast-fed infants is mediated through a regulation of IGF-I. A low quality of protein, as in cereal-based diets with no animal foods as often seen in low-income countries, may contribute to undernutrition, which can also result in an increased risk of NCDs later in life. In conclusion, there is some evidence that a high protein intake during the complementary feeding period is associated with increased risk of NCDs and that avoidance of a high protein intake could reduce the risk of obesity. In low-income countries, emphasis should be on providing sufficient amounts of high-quality protein to improve survival, growth and development.

The effects of whole milk and infant formula on growth and IGF-I in late infancy

Background/Objectives:High protein intake has been associated with increased growth. This may be linked to increased concentrations of insulin-like growth factor I (IGF-I), which seems to be influenced by the diet, especially its protein component. The short-term effects of high protein intake in late infancy are not known. The objective was to investigate the effects of high protein intake in the form of whole milk (WM) on growth and IGF-I from 9 to 12 months of age.Subjects/Methods:Healthy infants (n=83) were randomized to receive either WM or infant formula and fish oil or no fish oil (2 × 2 design). Anthropometric variables, IGF-I concentrations, serum urea nitrogen (SUN) and diet were recorded before and after the intervention.Results:Intake of WM significantly increased the protein energy percentage (PE%; P⩽0.001) and SUN (P=0.01), whereas there was no effect on size. The milk intervention increased IGF-I in boys (P=0.034) but not in girls. Intake of fish oil had no effect on the outcomes. Including all infants in the analysis there was a significant correlation between weight and IGF-I at 12 months (r=0.316, P=0.017), and PE% was positively associated with IGF-I after adjusting for sex and breastfeeding at both 9 (r=0.329, P=0.015) and 12 months (r=0.272, P=0.044).Conclusions:Randomization to WM had no overall effect on growth. However, the positive effect of WM on IGF-I in boys and the positive association between PE% intake and IGF-I at 9 and 12 months is consistent with the hypothesis that a high milk intake stimulates growth.

Effect of growth in infancy on body composition, insulin resistance, and concentration of appetite hormones in adolescence

BACKGROUND High infancy weight gain is associated with increased body mass index (BMI) and insulin resistance (IR) in later life, but the association with later body composition has not been well explored. Appetite regulatory hormones may be programmed in early life, but data to support this are lacking. OBJECTIVE We investigated the effect of weight gain in infancy on body composition, IR, leptin, ghrelin, and adiponectin at 17 y of age. DESIGN This was an observational study of 95 term and appropriate-for-gestational-age infants. We measured weight at birth and 9 mo of age and, for a subgroup (n = 60), at 3 and 6 mo of age. Changes in weight SD scores from 0 to 9, 0 to 3, 3 to 6, and 6 to 9 mo of age were calculated. Follow-up examinations at 10 and 17 y of age included body fat (BF) assessment by dual-energy X-ray absorptiometry scanning. We measured serum leptin, ghrelin adiponectin, and IR at 17 y of age. RESULTS Weight gain from 0 to 9 mo of age was positively associated with BMI (P < 0.003), percentage BF (P < 0.05), and percentage trunk fat (TF) (P < 0.03) but not with percentage TF relative to total BF, in childhood and adolescence, and most of these effects were explained by growth from 0 to 3 mo of age. Weight gains from 0 to 9 and 0 to 3 mo of age were not related to IR or leptin but were negatively associated with ghrelin and adiponectin corrected for BF at 17 y of age. CONCLUSION Our findings suggest that high weight gain in infancy, especially from 0 to 3 mo of age, has a role in programming both BF and concentrations of ghrelin and adiponectin in adolescence, whereas there was no effect on IR or leptin in this study.

Determinants of blood glucose and insulin in healthy 9‐month‐old term Danish infants; the SKOT cohort

Diabet. Med. 27, 1350–1357 (2010)

Skim Milk, Whey, and Casein Increase Body Weight and Whey and Casein Increase the Plasma C-Peptide Concentration in Overweight Adolescents

In adults, dietary protein seems to induce weight loss and dairy proteins may be insulinotropic. However, the effect of milk proteins in adolescents is unclear. The objective was to test whether milk and milk proteins reduce body weight, waist circumference, homeostatic model assessment, plasma insulin, and insulin secretion estimated as the plasma C-peptide concentration in overweight adolescents. Overweight adolescents (n = 203) aged 12-15 y with a BMI of 25.4 ± 2.3 kg/m(2) (mean ± SD) were randomized to 1 L/d of skim milk, whey, casein, or water for 12 wk. All milk drinks contained 35 g protein/L. Before randomization, a subgroup of adolescents (n = 32) was studied for 12 wk before the intervention began as a pretest control group. The effects of the milk-based test drinks were compared with baseline (wk 0), the water group, and the pretest control group. Diet and physical activity were registered. Outcomes were BMI-for-age Z-scores (BAZs), waist circumference, plasma insulin, homeostatic model assessment, and plasma C-peptide. We found no change in BAZ in the pretest control and water groups, whereas it was greater at 12 wk in the skim milk, whey, and casein groups compared with baseline and with the water and pretest control groups. The plasma C-peptide concentration increased from baseline to wk 12 in the whey and casein groups and increments were greater than in the pretest control (P < 0.02). There were no significant changes in plasma C-peptide in the skim milk or water group. These data suggest that high intakes of skim milk, whey, and casein increase BAZs in overweight adolescents and that whey and casein increase insulin secretion. Whether the effect on body weight is primary or secondary to the increased insulin secretion remains to be elucidated.

Early nutrition impact on the insulin-like growth factor axis and later health consequences.

Purpose of reviewThere is increasing interest in the role of insulin-like growth factor-I (IGF-I) in the relation between early growth and later risk of noncommunicable diseases (NCDs). This review presents and discusses a selection of recent publications on this topic. Recent findingsNutrition during pregnancy and in preterm infants has an influence on IGF-I. Breastfeeding is associated with lower IGF-I values and the effect of early protein intake was confirmed in a large intervention study. IGF-I levels are associated with early obesity, but the relation is complex and differs with age. Further studies and reviews support that there is a programming of the IGF axis, with higher levels during early life being associated with lower levels in adulthood, which is likely to influence the risk of NCDs later in life. SummaryRecent studies support that IGF-I plays an important role in the complex association between early diet, growth and later health, but more studies are needed to better understand the role of IGF-I, especially in the early development of obesity. Studies with data on how IGF-I is influenced by early diet in studies of preterm infants and young children with undernutrition from low-income countries will be helpful in recommending optimal diets.