Pharmacokinetic Comparison of Chitosan-Derived and Biofermentation-Derived Glucosamine in Nutritional Supplement for Bone Health.

Glucosamine and chondroitin sulfate have been used as nutritional supplementation for joint tissues and osteoarthritis (OA). Biofermented glucosamine is of great interest in the supplement industry as an alternative source of glucosamine. The purpose of this study is to compare the pharmacokinetics of chitosan-derived glucosamine and biofermentation-derived glucosamine as nutritional supplementation. In a randomized, double-blind and cross-over study design, we recruited subjects of healthy men and women. The pharmacokinetics of glucosamine were examined after a single dose of glucosamine sulfate 2KCl (1500 mg) with two different sources of glucosamine (chitosan-derived glucosamine and biofermentation-derived glucosamine) to male and female subjects fitted with intravenous (iv) catheters for repeated blood sampling up to 8 h. According to plasma concentration-time curve of glucosamine after an oral administration of 1500 mg of glucosamine sulfate 2KCl, AUC0-8h and AUC0-∞ values of glucosamine following oral administration of chitosan-derived and biofermentation-derived glucosamine formulations were within the bioequivalence criteria (90% CI of ratios are within 0.8-1.25). The mean Cmax ratios for these two formulations (90% CI of 0.892-1.342) did not meet bioequivalence criteria due to high within-subject variability. There were no statistically significant effects of sequence, period, origin of glucosamine on pharmacokinetic parameters of glucosamine such as AUC0-8h, AUC0-∞, Cmax. Our findings suggest that biofermentation-derived glucosamine could be a sustainable source of raw materials for glucosamine supplement.

The Relation of Questionnaire and Performance-Based Measures of Executive Functioning With Type 1 Diabetes Outcomes Among Late Adolescents.

OBJECTIVE: Successfully managing Type 1 diabetes involves adherence to a complex daily medical regimen, requiring self-regulatory skills that rely on neurocognitive processes known as executive functioning (EF). Adolescents with poorer rated EF abilities display poorer diabetes outcomes. The purpose of this study was to examine the relationship of EF questionnaire and performance measures with adherence and glycemic control, after controlling for IQ and general questionnaire response style. METHOD: Adolescents with Type 1 diabetes (M age = 17.74, SD = .38 years) and their mothers (N = 196) completed a self/mother-report questionnaire assessing adolescents' ratings of EF abilities (Behavior Rating Inventory of Executive Functioning-Self-Report). Adolescents also completed performance-based tests of EF (Delis-Kaplan Executive Function System) and intellectual functioning (Wechsler Adult Intelligence Scale, 4th ed., Vocabulary). Adherence was indexed via 2 self-report inventories and the number of daily blood glucose checks, and glycemic control via HbA1c obtained from assay kits. RESULTS: Self/mother-reports of EF ability were associated with self/mother-reported adherence. Both questionnaire and performance-based measures of EF were associated with glycemic control. However, once IQ was taken into consideration, performance-based EF was no longer associated with glycemic control; IQ independently shared variance with glycemic control. CONCLUSION: Our findings suggest that self-reports of EF may be useful in identifying late adolescents who need assistance in managing diabetes in daily life. The finding that performance-based EF measures were not related to glycemic control independent of underlying intellectual capacity raises questions about the specific role of EF in diabetes outcomes. (PsycINFO Database Record

Bone health nutraceuticals alter microarray mRNA gene expression: A randomized, parallel, open-label clinical study.

BACKGROUND AND OBJECTIVE: Dietary intake of fruits and vegetables has been suggested to have a role in promoting bone health. More specifically, the polyphenols they contain have been linked to physiological effects related to bone mineral density and bone metabolism. In this research, we use standard microarray analyses of peripheral whole blood from post-menopausal women treated with two fixed combinations of plant extracts standardized to polyphenol content to identify differentially expressed genes relevant to bone health. METHODS: In this 28-day open-label study, healthy post-menopausal women were randomized into three groups, each receiving one of three investigational fixed combinations of plant extracts: an anti-resorptive (AR) combination of pomegranate fruit (Punica granatum L.) and grape seed (Vitis vinifera L.) extracts; a bone formation (BF) combination of quercetin (Dimorphandra mollis Benth) and licorice (Glycyrrhiza glabra L.) extracts; and a fixed combination of all four plant extracts (AR plus BF). Standard microarray analysis was performed on peripheral whole blood samples taken before and after each treatment. Annotated genes were analyzed for their association to bone health by comparison to a gene library. RESULTS: The AR combination down-regulated a number of genes involved in reduction of bone resorption including cathepsin G (CTSG) and tachykinin receptor 1 (TACR1). The AR combination also up-regulated genes associated with formation of extracellular matrix including heparan sulfate proteoglycan 2 (HSPG2) and hyaluronoglucosaminidase 1 (HYAL1). In contrast, treatment with the BF combination resulted in up-regulation of bone morphogenetic protein 2 (BMP-2) and COL1A1 (collagen type I α1) genes which are linked to bone and collagen formation while down-regulating genes linked to osteoclastogenesis. Treatment with a combination of all four plant extracts had a distinctly different effect on gene expression than the results of the AR and BF combinations individually. These results could be due to multiple feedback systems balancing activities of osteoblasts and osteoclasts. CONCLUSION: In summary, this ex-vivo microarray study indicated that the pomegranate, grape seed, quercetin and licorice combinations of plant extracts modulated gene expression for both osteoclastic and osteogenic processes.

A targeted approach for evaluating preclinical activity of botanical extracts for support of bone health.

Using a sequential in vitro/in vivo approach, we tested the ability of botanical extracts to influence biomarkers associated with bone resorption and bone formation. Pomegranate fruit and grape seed extracts were found to exhibit anti-resorptive activity by inhibiting receptor activator of nuclear factor-κB ligand (RANKL) expression in MG-63 cells and to reduce IL-1ß-stimulated calvarial (45)Ca loss. A combination of pomegranate fruit and grape seed extracts were shown to be effective at inhibiting bone loss in ovariectomised rats as demonstrated by standard histomorphometry, biomechanical and bone mineral density measurements. Quercetin and licorice extract exhibited bone formation activity as measured by bone morphogenetic protein-2 (BMP-2) promoter activation, increased expression of BMP-2 mRNA and protein levels, and promotion of bone growth in cultured mouse calvariae. A combination of quercetin and licorice extract demonstrated a potential for increasing bone mineral density in an intact female rat model as compared with controls. The results from this sequential in vitro/in vivo research model yielded botanical extract formulas that demonstrate significant potential benefits for bone health.

Individual differences and day-to-day fluctuations in perceived self-regulation associated with daily adherence in late adolescents with type 1 diabetes.

OBJECTIVE: To examine whether individual differences and intraindividual (within-person day-to-day) fluctuations in late adolescents' self-regulation were associated with daily adherence to the type 1 diabetes regimen. METHODS: 110 school seniors (M age = 17.78 years) and their mothers assessed adolescents' skills underlying self-regulation (executive function, attention, self-control, behavioral inhibition and activation, emotion regulation) and adherence, with glycosylated hemoglobin from medical records. Teens completed daily diaries reporting self-regulation failures surrounding monitoring blood glucose, adherence, and number of blood glucose checks each day for 14 days. RESULTS: Hierarchical Linear Models indicated that better daily adherence was associated with teen and mother reports of better self-regulation skills and teens' reports of fewer daily self-regulation failures. Daily adherence was unrelated to temperamental differences in behavioral inhibition and activation. CONCLUSIONS: Results indicate that both individual and intraindividual differences in self-regulation contribute to daily adherence highlighting the importance of daily self-regulatory challenges to adherence.

Analysis of radiographic characteristics of anterolateral bowing of the leg before fracture in neurofibromatosis type 1.

BACKGROUND: Anterolateral leg bowing is associated with neurofibromatosis type 1 (NF1) frequently leading to fracture and nonunion of the tibia. The objective of the study was to characterize the radiographic findings of tibial dysplasia in NF1. METHODS: This study is a retrospective review of radiographs of tibial dysplasia obtained within 52 years, between 1950 and 2002, from the Shriners Hospitals for Children, Salt Lake City, and of peripheral quantitative computed tomographic images of 3 individuals with anterolateral bowing of the leg without fracture compared with age- and sex-matched controls. RESULTS: Individuals with NF1 with bowing of the leg have the appearance of thicker cortices with medullary narrowing on plain film radiographs. The peripheral quantitative computed tomographic images of individuals with NF1 with anterolateral bowing show an unusual configuration of the tibia. CONCLUSIONS: Anterolateral bowing of the leg in NF1 is associated with the appearance of thicker cortices with medullary narrowing rather than thinning of the long bone cortex on plain film radiographs as currently used as a qualifier in the sixth diagnostic criterion for the clinical diagnosis of NF1. Individuals with NF1 who have anterolateral bowing of the leg have differences in tibial geometry compared with age- and sex-matched controls. CLINICAL RELEVANCE: The characterization of the radiographic findings of long bone bowing in NF1 helps clarify the NF1 clinical diagnostic criteria.

IGF-1 and IGF-binding proteins and bone mass, geometry, and strength: relation to metabolic control in adolescent girls with type 1 diabetes.

Children and adolescents with poorly controlled type 1 diabetes mellitus (T1DM) are at risk for decreased bone mass. Growth hormone (GH) and its mediator, IGF-1, promote skeletal growth. Recent observations have suggested that children and adolescents with T1DM are at risk for decreased bone mineral acquisition. We examined the relationships between metabolic control, IGF-1 and its binding proteins (IGFBP-1, -3, -5), and bone mass in T1DM in adolescent girls 12-15 yr of age with T1DM (n = 11) and matched controls (n = 10). Subjects were admitted overnight and given a standardized diet. Periodic blood samples were obtained, and bone measurements were performed. Serum GH, IGFBP-1 and -5, glycosylated hemoglobin (HbA(1c)), glucose, and urine magnesium levels were higher and IGF-1 values were lower in T1DM compared with controls (p < 0.05). Whole body BMC/bone area (BA), femoral neck areal BMD (aBMD) and bone mineral apparent density (BMAD), and tibia cortical BMC were lower in T1DM (p < 0.05). Poor diabetes control predicted lower IGF-1 (r(2) = 0.21) and greater IGFBP-1 (r(2) = 0.39), IGFBP-5 (r(2) = 0.38), and bone-specific alkaline phosphatase (BALP; r(2) = 0.41, p < 0.05). Higher urine magnesium excretion predicted an overall shorter, lighter skeleton, and lower tibia cortical bone size, mineral, and density (r(2) = 0.44-0.75, p < 0.05). In the T1DM cohort, earlier age at diagnosis was predictive of lower IGF-1, higher urine magnesium excretion, and lighter, thinner cortical bone (r(2) >or=0.45, p < 0.01). We conclude that poor metabolic control alters the GH/IGF-1 axis, whereas greater urine magnesium excretion may reflect subtle changes in renal function and/or glucosuria leading to altered bone size and density in adolescent girls with T1DM.

Peripheral quantitative computed tomography of the tibia: pediatric reference values.

Peripheral quantitative computed tomography (pQCT) has been used in a number of pediatric studies. Reference data for children are primarily limited to the radius. The purpose of this study was to establish normal reference ranges for pQCT measurements of the tibia for children. A cross-sectional sample of healthy, white, non-Hispanic children aged 5-18 years (n=416; 197 boys) was measured at the distal tibia metaphysis and diaphysis by pQCT to assess trabecular and cortical bone, respectively. Differences were determined between and within genders by height for bone geometry, density, and strength. Height-specific normal ranges were calculated, and gender-specific centile curves were generated. A positive, linear relationship was found between tibia cortical bone geometry and strength parameters and height (r2 >or=0.58, p<0.001), with mean values greater for boys than girls (p

Randomized controlled trial evaluating response to metformin versus standard therapy in the treatment of adolescents with polycystic ovary syndrome.

OBJECTIVE: We evaluated the hypothesis that metformin would improve signs and symptoms of polycystic ovary syndrome (PCOS) in adolescents as compared to oral contraceptive pills (OCP) and have a favorable effect on obesity. STUDY DESIGN: Thirty-five obese, post-menarchal, non-sexually active adolescents aged 12-21 years with PCOS and hyperinsulinism were randomly assigned to receive either OCP or metformin for 6 months. RESULTS: There was a significant decrease in BMI in the two groups over time, from 40.1 to 38.6 in the OCP group, and 37.3 to 36.3 in the metformin group, p = 0.0026, but no significant difference in the degree of change between the two groups. Both groups had decreased free testosterone (OCP: 1.8 pg/ml to 0.96 pg/ml; metformin: 2.1 pg/ml to 1.6 pg/ml), p < 0.0001, and improvements in insulin resistance as evidenced by increased glucose/insulin (G/I) ratio (p < 0.005) and increased QUICK1 scores (p < 0.0005). No significant differences in response to treatment were found between the metformin and OCP groups in outcome variables. CONCLUSION: Adolescents with PCOS treated with metformin or OCP experienced similar beneficial outcomes including reduction in androgen levels, weight loss, and increased insulin sensitivity. The choice of a treatment agent for long-term use will depend on safety profiles, therapeutic goals and patient adherence.

Bone mineral acquisition in adolescents with type 1 diabetes.

OBJECTIVE: To track bone mineral acquisition in adolescents with type 1 diabetes (DM). STUDY DESIGN: Subjects were adolescents, ages 12 to 18 years, with DM (n=42) and a healthy regional reference (n=199). Measurements of tibia bone characteristics by peripheral quantitative computed tomography (pQCT) and spine and whole body (WB) by dual-energy x-ray absorptiometry (DEXA), anthropometrics, and lifestyle questionnaires were obtained during a 12-month period. Disease duration, insulin dose, renal function, and glycosylated hemoglobin (HbA1c) values for the previous 12 months were recorded. RESULTS: Body size and maturation were similar between groups. DM had lower tibia, spine, and WB bone characteristics but greater muscle mass (LBM) and lower bone mineral content (BMC)/LBM at baseline and 12 months. Annual gains for tibia cortical bone and WB BMC/LBM were lower and inversely related to HbA1c levels (R=-0.36 to -0.51), whereas spine area and density and WBLBM were greater and were predicted by pubertal-driven growth. Overall, the DM cohort had 8.5% less WB BMC/LBM, suggesting that bone mineral deposition was not adequately adapted to muscle gains. CONCLUSIONS: Adolescents with type 1 diabetes continue to have smaller bone mass and bone size despite normal growth and maturation. Poor metabolic control appears to negatively influence bone mineral acquisition.

Alterations in bone characteristics associated with glycemic control in adolescents with type 1 diabetes mellitus.

OBJECTIVE: To determine whether bone characteristics in adolescents with type 1 diabetes mellitus (DM) are influenced by blood glucose regulation and disease duration. The subjects were adolescents with type 1 DM (n=55) recruited from the University of Utah's Primary Children's Pediatric Diabetes Treatment Center. A reference database consisting of 95 healthy adolescents from the same geographic area was used for comparison.Study design Measurements of the tibia by peripheral quantitative computed tomography were made to assess cortical and trabecular bone characteristics. Hip, spine, and whole body characteristics were measured by dual-energy x-ray absorptiometry. Height, weight, health histories, Tanner stage, disease duration, insulin regimen, and glycosylated hemoglobin values were recorded. RESULTS: Age, maturation, and body size and composition values were similar between the subjects with type 1 DM and reference. Subjects with type 1 DM had lower tibia trabecular and femoral neck density and whole body mineral content and density. The mean glycosylated hemoglobin value was inversely related to tibia trabecular bone density (R(2)=-0.30) and whole body bone mineral content (R(2)=-0.25) and accounted for 3.0% to 8.9% of the variance. CONCLUSIONS: Altered bone mineral acquisition in adolescents with type 1 DM may limit peak bone mass acquisition and increase the risk of osteoporosis in later life.

Personnel costs and perceived benefit of telephone care in the management of children with type 1 diabetes.

Intensive management of patients with type 1 diabetes improves control and reduces rates of long-term complications. Telephone care as an adjunct to office visits is important in the management of children with type 1 diabetes in pediatric endocrine practices in the USA. The goal of this project was to assess the personnel costs and patients' perceptions of telephone care in a moderately sized pediatric diabetes care center (301 patients with a diagnosis of type 1 diabetes). There were two parts to this study. First, telephone logs were kept by three pediatric endocrine nurses (2.2 full-time equivalents [FTEs]) and three pediatric endocrinologists (2.0 FTEs) for two 1-wk blocks. Computerized databases were used to determine the number of clinic visits in 1998. Second, a survey assessing the frequency, perceived value and consequences of phone contact with the diabetes team was distributed to 40 families at clinic visits. Mean nurse/certified diabetes educator (CDE) time spent on the phone was 12.1 h/wk, with an additional 9.7 h/wk spent preparing and documenting. Physicians spent 6.4 h/wk on the phone, and 6.1 h/wk preparing/supervising/documenting. For our 301 patients with diabetes, the weekly personnel cost for telephone care at our institution was 1367 US dollars or 236 US dollars/patient/yr. Of the families surveyed, 80% reported that they had used the phone to obtain care for their child with diabetes and 55% had paged the doctor on call in the previous 6 months. Seven patients reported that phone contact prevented a total of 13 emergency department (ED) visits and 35 office visits. Using a cost estimate of 550 US dollars per ED visit, and 103 US dollars per office visit, the cost of prevented visits was 232 US dollars/patient/yr in our center. These data indicate that telephone care is effective in reducing the cost of reimbursable care via the ED and office visits, as well as avoiding hospitalization. However, the cost of providing this telephone care is not reimbursable to providers.