Body composition in adults born preterm with very low birth weight.

BACKGROUND: Studies on body composition in preterm very low birth weight (VLBW < 1500 g) survivors are inconsistent and trajectories later in life unknown. We assessed body composition and its change from young to mid-adulthood in VLBW adults. METHODS: We studied 137 VLBW adults and 158 term-born controls from two birth cohorts in Finland and Norway at mean age 36 years. Body composition was assessed by 8-polar bioelectrical impedance. We compared results with dual-energy x-ray absorptiometry measurements at 24 years. RESULTS: In mid-adulthood, VLBW women and men were shorter than controls. Fat percentage (mean difference in women 1.1%; 95% CI, -1.5% to 3.5%, men 0.8%; -2.0% to 3.6%) and BMI were similar. VLBW women had 2.9 (0.9 to 4.8) kg and VLBW men 5.3 (2.7 to 8.1) kg lower lean body mass than controls, mostly attributable to shorter height. Between young and mid-adulthood, both groups gained fat and lean body mass (p for interaction VLBW x age>0.3). CONCLUSION: Compared with term-born controls, VLBW adults had similar body fat percentage but lower lean body mass, largely explained by their shorter height. This could contribute to lower insulin sensitivity and muscular fitness previously found in VLBW survivors and predispose to functional limitations with increasing age. IMPACT: In mid-adulthood, individuals born preterm with very low birth weight had similar body fat percentage but lower lean body mass than those born at term. This was largely explained by their shorter height. First study to report longitudinal assessments of body size and composition from young to mid-adulthood in very low birth weight adults. Lower lean body mass in very low birth weight adults could contribute to lower insulin sensitivity and muscular fitness and lead to earlier functional limitations with increasing age.

A 1-year pilot study of intralymphatic injections of GAD-alum in individuals with latent autoimmune diabetes in adults (LADA) with signs of high immunity: No safety concerns and resemblance to juvenile type 1 diabetes.

AIMS: To test, for the first time in latent autoimmune diabetes in adults (LADA), the effects of autoantigen-specific immunotherapy by intralymphatic administration of aluminium-formulated recombinant human glutamic acid decarboxylase 65 (GAD-alum); specifically, to test if this treatment is safe, to test whether it induces a strong immunological response akin to a similar protocol in type 1 diabetes and to look for associations with preserved beta-cell function. MATERIALS AND METHODS: Three GAD-alum injections, 4 µg each, were administered 1 month apart into an inguinal lymph node in 14 people with newly diagnosed LADA (age 30-62 years) presenting with high levels of antibodies against glutamic acid decarboxylase (GADA). Adverse effects, immunological variables and beta-cell function were monitored, with detailed measurements at 5 and 12 months from baseline. RESULTS: Clinical adverse effects were minor and transient and measured laboratory variables were unaffected. All participants completed the study. Treatment raised levels of GADA, elicited strong effects on reactivity of peripheral blood mononuclear cells to GAD and raised cytokine/chemokine levels. Beta-cell function appeared stable preferentially in the seven participants carrying human leukocyte antigen (HLA) haplotypes DR3DQ2, as assessed by C-peptide glucagon tests (P < 0.05 vs. seven non-carriers). CONCLUSION: Intralymphatic treatment with GAD-alum in LADA is without clinical or other safety concerns over a 12-month period. As in a similar protocol used in type 1 diabetes, treatment exerts a strong immunological impact and is compatible with protection of beta-cell function preferentially in HLA-DR3DQ2 LADA patients. These findings pave the way for a randomized controlled trial in this important subgroup of LADA patients.

Maternal serum retinol, 25(OH)D and 1,25(OH)2D concentrations during pregnancy and peak bone mass and trabecular bone score in adult offspring at 26-year follow-up.

BACKGROUND: Vitamin A and D deficiency is prevalent in pregnant women worldwide. Both vitamins are involved in fetal skeletal development. A positive association between maternal vitamin D levels and offspring bone mineral density (BMD) at adulthood has been observed. The impact of maternal vitamin A status in pregnancy on offspring peak bone mass remains unclear. METHOD AND FINDINGS: Forty-one mother-child pairs were recruited from a population-based prospective cohort study in Trondheim, Norway, where pregnant women were followed from gestational week 17. Their term-born infants were followed from birth (1986-88). Regression analyses were performed for vitamin A (retinol), 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in maternal serum (gestational weeks 17, 33, 37) and cord blood. Offspring BMD and spine trabecular bone score (TBS), a measure of bone quality, were analyzed by dual x-ray absorptiometry at 26 years. Average levels during pregnancy of retinol, 25(OH)D and 1,25(OH)2D were 1.66 (0.32) µmol/L, 59.0 (20.6) nmol/L, and 251.3 (62.4) pmol/L, respectively. 1,25(OH)2D levels were similar in those with 25(OH)D levels <30 and >75 nmol/L. After adjustment for maternal age, BMI, smoking, and education, and offspring birth weight, maternal serum retinol was positively associated with offspring spine BMD [mean change 30.8 (CI 7.6, 54.0) mg/cm2 per 0.2 µmol/L retinol], and with offspring TBS, although non-significant (p = 0.08). No associations were found between maternal 25(OH)D and 1,25(OH)2D levels and offspring bone parameters. Vitamin levels in cord blood were not associated with offspring BMD or TBS. CONCLUSIONS: This is the first study to show an association between maternal vitamin A status and offspring peak bone mass. Our findings may imply increase future risk for osteoporotic fracture in offspring of mothers with suboptimal vitamin A level. No associations were observed between 25(OH)D and 1,25(OH)2D and offspring BMD.

Metabolic Outcomes in Adults Born Preterm With Very Low Birthweight or Small for Gestational Age at Term: A Cohort Study.

Context and Objectives: Low birthweight (LBW) has emerged as a risk factor of metabolic syndrome (MetS). Whether adults with very low birthweight (VLBW) born preterm are at higher risk than individuals who were term-born small for gestational age (tb-SGA) is not established. We assessed metabolic outcomes, including relation with skeletal parameters, in these two LBW categories. Design, Participants, and Outcomes: This follow-up cohort study included 189 individuals (females 51%), aged 25 to 28 years; 55 were preterm VLBW (≤1500 g), 59 were tb-SGA (<10th percentile), and 75 were controls (≥10th percentile). Outcomes were indices of MetS: blood pressure (BP), waist circumference, fasting glucose, lipid profile, and association between calculated MetS score and bone mineral density (BMD) and trabecular bone score (TBS), a measure of bone quality. Results: Compared with controls, individuals with VLBW displayed higher systolic [mean (SD), 126 (13.3) vs 119 (12.3) mm Hg; 95% CI, 1.27 to 11.48 mm Hg] and diastolic [71.9 (7.6) vs 68.6 (7.1) mm Hg; 95% CI, 0.3 to 6.2 mm Hg] BP, higher glycated hemoglobin, higher C-peptide, increased insulin resistance (Homeostatic Model Assessment 2), and lower high-density lipoprotein cholesterol [1.34 (0.3) vs 1.50 (0.4); 95% CI, 0.32 to 0.01]. Substantial differences were mainly seen between control females and females with VLBW. The adults who were tb-SGA had higher waist circumference and higher total and low-density lipoprotein cholesterol compared with controls. In males, MetS score correlated positively with BMD and inversely with TBS. Conclusions: The LBW groups and preferentially females in the VLBW group displayed a less favorable metabolic profile than did controls. The inverse association between MetS score and bone quality suggests enhanced future fracture risk.

Hyperoxia reduces insulin release and induces mitochondrial dysfunction with possible implications for hyperoxic treatment of neonates.

We previously showed that hyperoxia in vitro negatively affects beta cells of the rat. Here, we tested for possible clinical significance as well as mitochondrial interactions by hyperoxia, using human islets (function and viability), INS-1 832/13 cells (mitochondrial metabolism), and mouse neonates (effects in vivo). Lastly, we assessed relevant parameters in a cohort of individuals born preterm and then exposed to hyperoxia. Human islets and INS-1 832/13 cells were exposed to 24 h of hyperoxia (90-92% oxygen). Mouse neonates were subjected to 5 days of continuous hyperoxia. Individuals born preterm were evaluated in terms of glucose homeostasis and beta cell function by HbA1c and the HOMA2 formula. In human islets, hyperoxia significantly reduced glucose-stimulated insulin secretion by 42.2 ± 5.3% and viability assessed by MTT by 22.5 ± 5.4%. Hyperoxia down-regulated mitochondrial complex II by 21 ± 5% and upregulated complex III by 26 ± 10.1% and complex IV by 37 ± 10.6%. Partly similar effects on mitochondrial complexes were found in hyperoxia-exposed INS-1 832/13 cells. Exposure to hyperoxia swiftly reduced oxygen consumption in these cells and increased mitochondrial uncoupling. Hyperoxia transiently but significantly reduced insulin release in mouse neonates. Individuals born preterm displayed higher HbA1c versus controls, as well as insulin resistance. Thus, hyperoxia exerts negative effects in vitro on human beta cells and results indicate inhibitory effects on insulin secretion in vivo in mouse neonates. Negative effects may be lessened by the demonstrated swift and profound mitochondrial adaptability. Our findings open the possibility that hyperoxia could negatively affect beta cells of preterm human neonates.

Peak Bone Mass and Bone Microarchitecture in Adults Born With Low Birth Weight Preterm or at Term: A Cohort Study.

Context and Objectives: Peak bone mass (PBM) is regarded as the most important determinant of osteoporosis. Growing evidence suggests a role of intrauterine programming in skeletal development. We examined PBM and trabecular bone score (TBS) in adults born preterm with very low birth weight (VLBW) or small for gestational age (SGA) at term compared with term-born controls. Design, Setting, Participants, and Outcomes: This follow-up cohort study included 186 men and women (25 to 28 years); 52 preterm VLBW (≤1500 g), 59 term-born SGA (<10th percentile), and 75 controls (>10th percentile). Main outcome was bone mineral density (BMD) by dual x-ray absorptiometry. Secondary outcomes were bone mineral content (BMC), TBS, and serum bone markers. Results: VLBW adults had lower BMC and BMD vs controls, also when adjusted for height, weight, and potential confounders, with the following BMD Z-score differences: femoral neck, 0.6 standard deviation (SD) (P = 0.003); total hip, 0.4 SD (P = 0.01); whole body, 0.5 SD (P = 0.007); and lumbar spine, 0.3 SD (P = 0.213). The SGA group displayed lower spine BMC and whole-body BMD Z-scores, but not after adjustment. Adjusted odds ratios for osteopenia/osteoporosis were 2.4 and 2.0 in VLBW and SGA adults, respectively. TBS did not differ between groups, but it was lower in men than in women. Serum Dickkopf-1 was higher in VLBW subjects vs controls; however, it was not significant after adjustment for multiple comparisons. Conclusions: Both low-birth-weight groups displayed lower PBM and higher frequency of osteopenia/osteoporosis, implying increased future fracture risk. The most pronounced bone deficit was seen in VLBW adults.