Signe M. Jensen

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.

Automatic needle insertion diminishes pain during growth hormone injection

Non‐compliance in children receiving growth hormone (GH) treatment is often caused by pain on injection and difficulties in administration of GH. It has been suggested that automatic needle insertion diminishes pain perception. We quantitatively measured pain intensity on injection with two prototype pens for GH administration, providing either manual or automatic sc needle insertion, using a combined visual analogue/facial scale and a five‐item scale in 18 children. With the automatic pen there was a significantly lower maximum pain score compared with the manual pen (median 28.5 versus 52.0mm) as well as a lower mean pain score (mean 13.7 versus 23.5 mm). The five‐item scale revealed that automatic needle insertion was significantly less painful than manual insertion and 13 patients chose to continue treatment with the automatic pen. In conclusion, pain during GH injection can be significantly diminished by automatic needle insertion, which may improve compliance in long‐term GH treatment.

Obesity, inflammation and metabolic syndrome in Danish adolescents.

Aim:  To describe biomarkers of inflammation and markers related to the metabolic syndrome (MS) in healthy obese Danish adolescent and compare to a normal‐weight group.

Diabetes is associated with lower tuberculosis antigen-specific interferon gamma release in Tanzanian tuberculosis patients and non-tuberculosis controls

Abstract Background: Diabetes is increasingly common in TB endemic regions and plays a role as a possible risk factor for increased progression from latent TB infection (LTBI) to active TB disease. Although the pathophysiological mechanisms are not fully understood, the immune system is weakened in diabetes patients and therefore the validity of interferon gamma release assays (IGRA) may be compromised. The aim of the present study was to assess the association between diabetes and Mycobacterium tuberculosis (Mtb) antigen-specific interferon gamma (IFN-γ) release in a TB endemic area among culture-confirmed TB patients and non-TB controls. Methods: Culture-confirmed pulmonary TB patients (n = 187) and healthy non-TB neighbourhood controls (n = 190) from Mwanza, Tanzania were tested for the presence of circulating T cells recognizing Mtb antigens using an IGRA. The diabetes status of all participants was assessed using a standard oral glucose tolerance test. The impact of diabetes on the performance of the IGRA was estimated using robust linear and logistic regression. Results: Compared to normal glucose tolerance, diabetes was associated with reduced levels of Mtb-specific IFN-γ. Increasing levels of fasting blood glucose (B − 0.3, 95% confidence interval − 0.6 to − 0.03, p = 0.033) was negatively associated with IFN-γ. Although TB patients had higher specific and lower unspecific mitogen IFN-γ responses compared to non-TB controls, the association between diabetes and IFN-γ did not depend on TB status. Conclusion: Diabetes is associated with lower levels of Mtb antigen-specific IFN-γ, and the validity of IFN- γ tests for LTBI may be questionable in individuals with diabetes.

Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes

Aims/hypothesisNormal glucose metabolism depends on pancreatic secretion of insulin and glucagon. The bihormonal hypothesis states that while lack of insulin leads to glucose underutilisation, glucagon excess is the principal factor in diabetic glucose overproduction. A recent study reported that streptozotocin-treated glucagon receptor knockout mice have normal glucose tolerance. We investigated the impact of acute disruption of glucagon secretin or action in a mouse model of severe diabetes by three different approaches: (1) alpha cell elimination; (2) glucagon immunoneutralisation; and (3) glucagon receptor antagonism, in order to evaluate the effect of these on glucose tolerance.MethodsSevere diabetes was induced in transgenic and wild-type mice by streptozotocin. Glucose metabolism was investigated using OGTT in transgenic mice with the human diphtheria toxin receptor expressed in proglucagon producing cells allowing for diphtheria toxin (DT)-induced alpha cell ablation and in mice treated with either a specific high affinity glucagon antibody or a specific glucagon receptor antagonist.ResultsNear-total alpha cell elimination was induced in transgenic mice upon DT administration and resulted in a massive decrease in pancreatic glucagon content. Oral glucose tolerance in diabetic mice was neither affected by glucagon immunoneutralisation, glucagon receptor antagonism, nor alpha cell removal, but did not deteriorate further compared with mice with intact alpha cell mass.Conclusions/interpretationDisruption of glucagon action/secretion did not improve glucose tolerance in diabetic mice. Near-total alpha cell elimination may have prevented further deterioration. Our findings support insulin lack as the major factor underlying hyperglycaemia in beta cell-deficient diabetes.

Validity of anthropometric measurements to assess body composition, including muscle mass, in 3‐year‐old children from the SKOT cohort

Nutritional status of children is commonly assessed by anthropometry both in under and overnutrition. The link between anthropometry and body fat, the body compartment most affected by overnutrition, is well known, but the link with muscle mass, the body compartment most depleted in undernutrition, associated with infections, remains unknown. In this study, we examined the relationship between common anthropometric indices and body composition measured by dual-energy X-ray absorptiometry (DEXA) in a sample of 121 healthy 3-year-old Danish children. Appendicular (arms and legs) lean mass was used to estimate muscle mass. Overall, anthropometric measures were more effective to measure absolute size of fat, lean and muscle mass than their relative sizes. Proportion of the variance explained by anthropometry was 79% for lean mass, 76% for fat mass and 74% for muscle mass. For fat mass and lean mass expressed as percentage of total body mass, this proportion was 51% and 66%, respectively; and for muscle mass as percentage of lean mass it was 34%. All the best reduced multivariate models included weight, skinfold and gender except the model estimating the proportion of muscle mass in lean body mass, which included only mid-upper arm circumference and subscapular skinfold. The power of height in the weight-to-height ratio to determine fat mass proportion was 1.71 with a 95% confidence interval (0.83-2.60) including the value of 2 used in body mass index (BMI). Limitations of anthropometry to assess body composition, and especially for muscle mass as a proportion of lean mass, should be acknowledged.

Infant BMI peak, breastfeeding, and body composition at age 3 y

BACKGROUND With the increasing focus on obesity, growth patterns in infancy and early childhood have gained much attention. Although the adiposity rebound has been in focus because of a shown association with adult obesity, not much has been published about the infant peak in body mass index (BMI). OBJECTIVE This study links age and BMI at infant peak to duration of breastfeeding and body composition at 3 y of age. DESIGN Frequent weight and height measurements for 311 Danish children in the SKOT (Complementary and Young Child Feeding - Impact on Short and Long Term Development and Health; in Danish) cohort were used to estimate BMI growth curves for the age span from 14 d to 19 mo by using a nonlinear mixed-effects model. BMI growth velocity before peak and age and BMI at peak were derived from the subject-specific models. Information about pregnancy and breastfeeding was assessed from background questionnaires. Assessment of body composition at age 3 y was made based on bioelectrical impedance, weight, and height. RESULTS A longer duration of exclusive breastfeeding was associated with an earlier peak in infant BMI (P = 0.0003) and a lower prepeak velocity (P < 0.0001). BMI level at peak and prepeak velocity was positively associated with fat and fat-free mass at age 3 y (all P < 0.0001), whereas a later age at peak was associated with a lower fat mass, fat mass index, and fat-free mass index at age 3 y (all P < 0.001). CONCLUSIONS BMI peak characteristics are strongly associated with both duration of exclusive breastfeeding and body composition at 3 y of age. Thus, a better knowledge of characteristics and determinants of the early BMI peak is likely to improve our understanding of early development of obesity.

Effect of milk proteins on linear growth and IGF variables in overweight adolescents.

OBJECTIVE Milk may stimulate growth acting via insulin-like growth factor-I (IGF-I) secretion but the effect in adolescents is less examined. This study investigates the effect of milk proteins on linear growth, IGF-I, IGF binding protein-3 (IGFBP-3) and IGF-I/IGFBP-3 ratio in overweight adolescents. DESIGN The trial included 193 overweight adolescents aged 12-15 years. They were randomized to drink 1L/day of: skimmed milk, whey, casein or water for 12 weeks; all milk-based drinks contained 35 g protein/L. A subgroup of 32 adolescents was examined 12 weeks before they were randomized into the groups and started the intervention (pre-test control group). Examinations included anthropometry, diet registration and blood samples which were analyzed for IGF-I and IGFBP-3 by chemiluminescence methods. The effects of milk-based drinks on linear growth, IGF-I, IGFBP-3 and IGF-I availability, calculated as the IGF-I/IGFBP-3 ratio, were compared with baseline, the pre-test control group and water. RESULTS IGF-I increased with skimmed milk (P=0.015) and tended to increase with casein (P=0.075) compared to the pre-test control group. IGFBP-3 but not IGF-I increased with skimmed milk (P=0.006) and casein (P=0.001) compared to water. There was no difference in height or height Z-score for any of the milk-based test drink groups compared to water or compared to the pre-test control group. However, height Z-score decreased within the whey group. CONCLUSIONS Skimmed milk and casein may have a stimulating effect on the IGF-I system whereas there was no positive effect on height in overweight adolescents during this 12 week intervention.

The impact of early growth patterns and infant feeding on body composition at 3 years of age

Early excessive weight gain is positively associated with later obesity, and yet the effect of weight gain during specific periods and the impact of infant feeding practices are debated. The objective of the present study was to examine the impact of weight gain in periods of early childhood on body composition at 3 years, and whether infant feeding modified the relationship between early growth and body composition at 3 years. We studied 233 children from the prospective cohort study, SKOT (in Danish: Småbørns Kost og Trivsel). Birth weight z-scores (BWZ) and change in weight-for-age z-scores (WAZ) from 0 to 5, 5 to 9, 9 to 18 and 18 to 36 months were analysed for relations with body composition (anthropometry and bioelectrical impedance) at 3 years by multivariate regression analysis. BWZ and change in WAZ from 0 to 5 months were positively associated with BMI, fat mass index (FMI) and fat-free mass index (FFMI) at 3 years. Full breastfeeding for 6 months (compared to less than 1 month) eliminated the effect of early growth (P = 0.01). Full breastfeeding for 6 months (compared to less than 1 month) also eliminated the positive relation between BWZ and FMI (P = 0.009). No effect modification of infant feeding was found for FFMI. In conclusion, high birth weight and rapid growth from 0 to 5 months were associated with increased FMI and FFMI at 3 years. Longer duration of full breastfeeding reduced the effect of birth weight and early weight gain on fat mass.

Evaluation of multi‐outcome longitudinal studies

Evaluation of intervention effects on multiple outcomes is a common scenario in clinical studies. In longitudinal studies, such evaluation is a challenge if one wishes to adequately capture simultaneous data behavior. In this situation, a common approach is to analyze each outcome separately. As a result, multiple statistical statements describing the intervention effect need to be reported and an adjustment for multiple testing is necessary. This is typically done by means of the Bonferroni procedure, which does not take into account the correlation between outcomes, thus resulting in overly conservative conclusions. We propose an alternative approach for multiplicity adjustment that incorporates dependence between outcomes, resulting in an appreciably less conservative evaluation. The ability of the proposed method to control the familywise error rate is evaluated in a simulation study, and the applicability of the method is demonstrated in two examples from the literature.