Childhood studies of the fat-bone relationship are conflicting, possibly reflecting the influence of metabolic abnormalities in some but not all obese children. Bone mass was compared between prepubertal overweight children with (n=41) and without (n=99) pre-diabetes. Associations of bone mass with measures of total and central adiposity, glucose intolerance, insulin sensitivity, lipid profile, systemic inflammation, and osteocalcin were also determined. In 140 overweight children aged 7–11 y, an oral glucose tolerance test was used to identify those with pre-diabetes and for determination of glucose, 2-h glucose, glucose AUC, insulin, 2-hr insulin, and insulin AUC. Blood samples were also assessed for lipids, C-reactive protein, and osteocalcin. Total body bone mineral content (BMC), fat-free soft tissue mass (FFST), and fat mass (FM) were measured by DXA. Visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAAT) were assessed using MRI. Total body BMC was 4% lower in overweight children with pre-diabetes than those without pre-diabetes, after controlling for sex, race, height, and weight (P=0.03). In the total sample, FM was positively related with BMC (β=0.16, P=0.01), after adjusting for sex, race, height, and FFST. However, VAT (β=−0.13, P=0.03) and SAAT (β=−0.34, P=0.02) were inversely associated with BMC, after controlling for sex, race, height, FFST, FM, and SAAT or VAT. No significant associations were found between BMC and the biochemical measurements. Prepubertal overweight children with pre-diabetes may be at risk for poor skeletal development. In addition, it appears that greater levels of central, rather than total, adiposity may be deleterious for developing bone.

Objective To compare bone mass between overweight adolescents with and without cardiometabolic risk factors (CMR). Associations of bone mass with CMR and adiposity were also determined. Study design Overweight adolescents (aged 14–18 years) were classified in Healthy (n=55), 1CMR (n=46) or ≥2CMR (n=42). CMR were measured using standard methods and defined according to pediatric definitions of metabolic syndrome. Total body bone mass, fat mass and fat-free soft tissue mass (FFST) were measured by DXA. Visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAAT) were assessed using MRI. Results After controlling for age, sex, race, height and FFST, Healthy group had 5.4% and 6.3% greater bone mass than the 1CMR and ≥2CMR groups, respectively (both P<0.04). Multiple linear regression, adjusting for same covariates, revealed that VAT (β=−0.22), waist circumference (β= −0.23), homeostasis model assessment of insulin resistance (β= −0.23) and HDL-cholesterol (β=0.22) were associated with bone mass (all P<0.04). There was a trend towards a significant inverse association between bone mass and fasting glucose (P=0.056). No relations were found between bone mass and fat mass, SAAT, BP or triglycerides. Conclusion Being overweight with metabolic abnormalities, particularly insulin resistance, low HDL-cholesterol and visceral adiposity, may adversely influence adolescent bone mass.

Amphiphilic gadolinium complexes were investigated as potential magnetic resonance imaging (MRI) contrast agents. A series of complexes was synthesized in order to study the effect of hydrophilic phosphodiester groups on albumin binding, relaxivity, and blood half-life in rats. Thus, compound 11a, a diethylenetriaminepentaacetato aquo gadolinium(III) (Gd-DTPA) derivative with an octyl substituent, was synthesized and compared to 5b, the analogous octyl derivative containing a phosphodiester linkage between the gadolinium chelate and the alkyl chain. Likewise, 11b, a naphthyl Gd-DTPA derivative, was compared to the naphthyl phosphodiester derivative 5c. A direct comparison is not available for 5a, a 4,4-diphenylcyclohexyl phosphodiester Gd-DTPA derivative; however, its pharmacokinetic properties mirror those of the other phosphodiester derivatives. Although the introduction of the phosphodiester moiety decreased log P by approximately 1.7 units, albumin binding data obtained in 4.5% human serum albumin (HSA) indicated that derivatives containing the phosphodiester group exhibited somewhat higher albumin affinity than their alkyl analogues (54 +/- 5 and 44 +/- 4% for 5b and 11a, respectively; 40 +/- 4 and 30 +/- 3% for 5c and 11b, respectively). Both classes of agents were characterized by enhanced relaxivity in the presence of 4.5% HSA (r1 = 16-42 mM(-1) s(-1) at 20 MHz and 37 degrees C) as compared with the relaxivity values measured in phosphate-buffered saline (PBS) alone (r1 = 4.6-6.6 mM(-1) s(-1) at 20 MHz and 37 degrees C). Pharmacokinetic data indicated that compound 5b had a half-life of 14.3 +/- 1.8 min in the rat as compared with a half-life of 6.20 +/- 0.04 min for the non-phosphodiester analogue 11a. Similarly, the half-life obtained for the phosphodiester 5c was 14.3 +/- 1.7 min as compared with a half-life of 6.80 +/- 0.03 min for 11b. The percent biliary excretion was significantly lower for the phosphodiester compounds than for non-phosphodiester analogues (17.7 +/- 4.0 and 66.9 +/- 3.4% for 5b and 11a, respectively; 17.0 +/- 1.6 and 64.3 +/- 9.0% for 5c and 11b, respectively). The percent biliary excretion (15.8 +/- 4.4%) and plasma half-life in the rat (23.1 +/- 2.9 min) for 5a are consistent with the extended plasma half-life of the other phosphodiester derivatives. Taken together, the enhanced relaxivity and extended blood half-life of the phosphodiester derivatives support the concept of using endogenous albumin binding to achieve blood pool-like properties for small-molecule magnetic resonance imaging (MRI) contrast agents.

Though adolescents consume more fructose than any other age group, the relationship between fructose consumption and markers of cardiometabolic risk has not been established in this population. We determined associations of total fructose intake (free fructose plus one-half the intake of free sucrose) with cardiometabolic risk factors and type of adiposity in 559 adolescents aged 14-18 y. Fasting blood samples were measured for glucose, insulin, lipids, adiponectin, and C-reactive protein. Diet was assessed with 4-7 24-h recalls and physical activity (PA) was determined by accelerometry. Fat-free soft tissue (FFST) mass and fat mass were measured by DXA. The s.c. abdominal adipose tissue (SAAT) and visceral adipose tissue (VAT) were assessed using MRI. Multiple linear regression, adjusting for age, sex, race, Tanner stage, FFST mass, fat mass, PA, energy intake, fiber intake, and socioeconomic status, revealed that fructose intake was associated with VAT (β = 0.13; P = 0.03) but not SAAT (P = 0.15). Significant linear upward trends across tertiles of fructose intake were observed for systolic blood pressure, fasting glucose, HOMA-IR, and C-reactive protein after adjusting for the same covariates (all P-trend < 0.04). Conversely, significant linear downward trends across tertiles of fructose intake were observed for plasma HDL-cholesterol and adiponectin (both P-trend < 0.03). When SAAT was added as a covariate, these trends persisted (all P-trend < 0.05). However, when VAT was included as a covariate, it attenuated these trends (all P-trend > 0.05). In adolescents, higher fructose consumption is associated with multiple markers of cardiometabolic risk, but it appears that these relationships are mediated by visceral obesity.

These data suggest that the lower uncarboxylated osteocalcin concentrations found in children with prediabetes may be associated with β-cell dysfunction. In addition, our findings between carboxylated osteocalcin and insulin sensitivity suggest that carboxylated osteocalcin plays a role in human glucose homeostasis.