Serum Levels of Osteocalcin and Insulin Resistance in Patients with Impaired Glucose Tolerance or New-Onset Diabetes Mellitus After Liver Transplantation.

Liver transplantation (LT) patients are at high risk of developing new-onset diabetes after transplantation (NODAT). Osteocalcin has been proposed as a mediator between bone tissue and glucose metabolism, but its role in the pathogenesis of diabetes is not defined yet. Our objective was to assess the relationship between serum osteocalcin and glucose metabolism parameters in liver transplantation recipients. A total of 187 liver transplantation patients were cross-sectionally studied, 54 of them developed NODAT. None had been diagnosed of diabetes mellitus prior to transplant. In 133 nondiabetic patients, a 75 g oral glucose tolerance test (OGTT) was performed to assess blood glucose, insulin, and C-peptide levels at baseline and 120 min. Serum total osteocalcin was measured at baseline in all patients.After OGTT, 10.5% of LT patients had NODAT criteria, 51.9% showed impaired glucose tolerance, and 37.6% had normal glucose tolerance. Overall, NODAT prevalence was 36.3%. HOMA-IR was significantly higher in NODAT compared with impaired glucose tolerance and normal glucose tolerance groups (p<0.001). Osteocalcin was inversely correlated to HOMA-IR (r=- 0.16, p=0.05), BMI (r=- 0.27, p=0.000) and waist circumference (r=- 0.21, p=0.005). Patients in the lowest osteocalcin tertile (< 16.5 ng/ml) had significantly higher fasting plasma glucose and HOMA-IR index (p=0.029 and 0.037, respectively) than those in medium or highest tertiles. In multiple linear regression analysis, osteocalcin was negatively associated with fasting plasma glucose (standardized ß coefficient-0.16; p=0.041) and 2-h insulin (standardized ß coefficient-0.21; p=0.028). Prevalence of NODAT/impaired glucose tolerance is high in liver transplantation patients and is associated with insulin resistance. In these patients total osteocalcin is inversely associated with plasma glucose level and insulin resistance indexes.

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis.

UNLABELLED: Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. INTRODUCTION: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. METHODS: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 µg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. RESULTS: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. CONCLUSIONS: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.

Serum visfatin and vaspin levels in prepubertal children: effect of obesity and weight loss after behavior modifications on their secretion and relationship with glucose metabolism.

OBJECTIVE: To investigate the impact of obesity, weight loss and oral glucose ingestion on serum visfatin and vaspin levels in prepubertal children. SUBJECTS AND METHODS: A total of 100 prepubertal obese Caucasian children (OB) and 42 controls (C) were studied. The OB group was studied at baseline and after moderate (n=46) and extensive (n=14) body mass index (BMI) reduction by conservative treatment, undergoing body composition studies (dual-energy X-ray absorptiometry) and oral glucose tolerance tests (OGTTs). Serum visfatin and vaspin levels were studied throughout the OGTT, as were their relationships with insulin, leptin, leptin soluble receptor (sOB-R), adiponectin (total and high molecular weight), resistin, interleukin-6 (IL-6) and tumor necrosis factor-α levels at every time point. RESULTS: OB had higher visfatin (P<0.001), but similar vaspin than C. BMI reduction decreased visfatin levels (P<0.001), with BMI, waist circumference and the surrogate markers of body fat (leptin and sOB-R) showing significant correlations (P<0.05) with this peptide, but not with vaspin. Visfatin and vaspin decreased during the OGTT (P<0.001). Weight reduction did not alter visfatin dynamics in the OGTT, but decreased the area under the curve (AUC) for vaspin (P<0.001), with a correlation between the AUCs for vaspin and insulin after weight loss (P<0.05). Visfatin levels were positively correlated with resistin and IL-6, after controlling for BMI and HOMA (homeostatic model assessment) index at every time point in the study. CONCLUSION: Serum visfatin, but not vaspin, levels are influenced by body fat content in obese children, whereas both adipokines are modulated by glucose intake in a BMI-dependent manner.

Acylated ghrelin levels in pre-pubertal obese children at diagnosis and after weight reduction: effect of oral glucose ingestion.

BACKGROUND: Ghrelin isoforms are involved in energy homeostasis and carbohydrate metabolism. AIM: To determine the influence of oral glucose ingestion and weight reduction on acylated ghrelin (AG) serum levels and on the AG to total ghrelin (TG) ratio (AG/TGr) in obese pre-pubertal children. SUBJECTS AND METHODS: Seventy obese children were studied at diagnosis (D) and after reduction of their body mass index (BMI) of over 1 (-1; no.=51) and 2 SD score (-2; no.=21). Body composition was analyzed and serum levels of glucose, insulin, TG and AG, and the AG/TGr were determined at every time-point in an oral glucose tolerance test (OGTT) at D and at -2. The control group consisted of 32 lean children. RESULTS: At D AG and TG levels were lower in obese children and negatively correlated with BMI. TG levels were negatively correlated with the homeostasis model assessment (HOMA) index in the whole cohort, as with the body fat content (BFC) in the obese patients. Weight loss exclusively reduced BFC and improved HOMA, increasing AG transiently and TG sustainedly, with AG/TGr exclusively decreasing at -2. Glucose ingestion caused a sustained increase in AG and decrease in TG, thus increasing the AG/TGr throughout the entire OGTT; this remained unaltered after weight reduction. CONCLUSIONS: TG and AG levels are influenced by BMI, showing an impairment in childhood obesity that can be improved through weight loss. The different fractions of ghrelin appear to play different roles in carbohydrate metabolism and the calculation of AG/TGr could be useful in the follow up of childhood obesity.

Effect of alendronate in elderly patients after low trauma hip fracture repair.

SUMMARY: One year of once weekly alendronate, when given shortly after the surgical repair of a hip fracture, produces reductions in bone markers and increases proximal femoral bone density. The therapy was well tolerated. INTRODUCTION: Hip fracture is the most devastating type of osteoporotic fracture and increases notably the risk of subsequent fractures. The aim of this paper was to evaluate the effects of 1 year therapy with a weekly dose of alendronate in the bone mineral density and bone markers in elderly patients after low trauma hip fracture repair. METHODS: Two hundred thirty-nine patients (81 +/- 7 years; 79.8% women) were randomized to be treated either with calcium (500 mg/daily) and vitamin D(3) (400 IU/daily; Ca-Vit D group) or with alendronate (ALN, 70 mg/week) plus calcium and vitamin D(3) (500 mg/daily and 400 IU/daily, respectively; ALN + Ca-Vit D group). RESULTS: One hundred forty-seven (61.5%) patients completed the trial. Alendronate increased proximal femoral bone mineral density (BMD) in the intention-to-treat analysis (mean difference (95% confidence interval); total hip 2.57% (0.67; 4.47); trochanteric 2.96% (0.71; 5.20), intertrochanteric 2.32% (0.36; 4.29)), but the differences were not significant in the BMD of the femoral neck (0.47%; (-2.03; 2.96) and the lumbar spine (0.69%; (-0.86; 2.23)). Bone turnover markers decreased during alendronate treatment. CONCLUSION: The present study demonstrates for the first time the anti-resorptive efficacy of alendronate given immediately after surgical repair in an elderly population with recent hip fracture. This effect should positively affect the rate of subsequent fractures.

Sexual and reproductive health in HIV-positive women: a dedicated clinic improves service.

We run a one-stop clinic for HIV-positive women, offering sexually transmitted infection screening, cervical cytology and family planning. We completed an audit cycle, and showed that all aspects of our care had improved since the introduction of this integrated service.

Lack of preferential transmission of diabetic HLA alleles by healthy parents to offspring in Spanish diabetic families.

HLA-DR3 or -DR4 segregation distortion to normal or insulin-dependent (ID) diabetic offspring of 108 Spanish families whose parents were healthy was not observed; however, DR3 or DR4 ID offspring is significantly increased in the present study, since parents were chosen after tracing ID children. These results are discrepant with those found by others in families with diabetic parents in other ethnic groups. These conflicting data could be due to sampling errors or segregation distortion. Thus, ethnic group differences in a genetic (T/t-like) or metabolic mechanism might confer advantages to DR3- or DR4-bearing gametes from ID diabetic parents, but segregation distortion might only affect certain HLA DR3 or DR4 extended haplotypes which are frequent and characteristic for certain ethnic groups (i.e. B8-DR3-BfS-C4AQOB1 and Bw62-DR3-BfS-C4A383 in most caucasians) but not for other haplotypes in other ethnic groups (Spaniards; B18-DR3-BfF1-C4A3BQO and BwX-DR4-BfX-C4AXBX).

Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socio-economic impact and health status. Collaborative ODA (Observational GH Deficiency in Adults) Group.

OBJECTIVE: The aim of the present study was to assess the socio-economic impact at baseline and after one year of follow-up of clinical and health status characteristics and laboratory tests of adult-onset GH deficiency (AGHD), a well-known clinical entity, in a large group of Spanish hypopituitary patients with untreated AGHD. DESIGN AND METHODS: A total of 926 eligible patients with GHD (GH

Correlations between bone mineral density, insulin-like growth factor I and auxological variables.

Recent studies have shown growth-related changes in spinal bone mineral density (BMD) in children; however, there is less information available on the relationship between BMD and insulin-like growth factor I (IGF-I). The aim of this study was to relate the BMD of the spine and radius with serum IGF-I levels and auxological variables in normally growing children. We used dual X-ray absorptiometry to measure the BMD in the lumbar spine (L1-L4) and distal radius of 121 children (69 boys, 52 girls) aged 3-18 years whose growth velocity was normal. Lumbar and radial BMD increased with age (p < 0.001) and puberty (p < 0.001) and was highly correlated to age, weight, height, body surface and bone age (r = 0.70-0.89 and p < 0.001 for all variables). Partial correlation, with age held constant, was weaker but still significant for most auxological variables. Serum IGF-I concentrations increased slowly during childhood and markedly during early stages of puberty, and correlated with lumbar and radial BMD (r = 0.55 and 0.45, respectively; p < 0.001) and with the auxological variables (p < 0.001). When age was held constant, IGF-I levels still correlated significantly with the auxological variables and with BMD, except in the case of radial BMD in boys. By multiple regression analysis IGF-I, unlike auxological variables, did not reach significance in the ability to predict BMD. Therefore, in healthy children, serum IGF-I levels show a weaker relationship to BMD than do auxological variables.

Bone mineral status in prepubertal children with constitutional delay of growth and puberty.

OBJECTIVE: We wished to clarify whether the osteopenia reported in adult men with a history of constitutional delay of growth and puberty (CDGP) could be due to the delayed puberty or an independent predisposition to osteoporosis in this condition. DESIGN: Short prepubertal children with CDGP and children with familial short stature (FSS) were matched for height and other auxological variables. The FSS children served as a control group. METHODS: We measured spinal (L1-L4) bone mineral content (BMC) and bone mineral density (BMD) by dual energy X-ray absorptiometry (Hologic QDR 1000/w) in 56 children aged 5-11 years. All children had height below the 10th percentile for chronological age (CA), and bone age (BA) less than 10 years, 29 of them with clinical diagnosis of possible CDGP and 27 of them with FSS. The BMD standard deviation scores (SDS) relative to the values for normal height children were obtained. RESULTS: The mean (+/-S.D.) spinal BMD was significantly lower in the children with CDGP than in the FSS group (0.534+/-0.059 vs 0.623+/-0.060 g/cm2, P< 0.001). Both groups had negative mean lumbar BMD SDS, but in the CDGP group it was significantly lower than in the FSS group as well when the SDS was based on the CA (-1.41+/-0.61 vs -0.38+/-0.51, P< 0.001) and when it was related to BA (-0.78+/-0.64 vs -0.17+/-0.52, P< 0.01). BMC was significantly lower in the CDGP than in the FSS group, when multiple regression analysis was performed by using scanned bone area, body weight and height, sex and BA as independent variables (P = 0.0005). CONCLUSION: The finding of decreased mineralization in prepubertal children with CDGP before the age of puberty suggests that they may have an inherent predisposition to osteopenia.

Acromegaly and bronchial carcinoid. Effect of removal of the latter.

A patient with a long-standing history of bronchial carcinoid and acromegaly was studied. There was pituitary enlargement with an intrasellar mass (brain computed tomography scan), high basal GH levels, and abnormal GH and other pituitary hormones response to oral glucose and a combined test (LHRH, TRH, insulin). After resection of the bronchial carcinoid, basal GH was normal, GH was normally suppressed during OGTT, pituitary function was within expected normal range, and there was regression of the pituitary tumor together with clinical improvement. These data suggest that the patient's acromegaly was secondary to pituitary stimulation due to the bronchial carcinoid.

Study of bone loss in diabetes mellitus type 1.

While people with type 1 diabetes mellitus (DM) often have bone deficiency, the relation between this deficiency and the duration or control of diabetes remains controversial. To assess the possibility of such an interrelationship, we studied parameters relating to mineral metabolism (Ca, P, alkaline phosphatase, Mg, PTH, and hydroxyproline (OHP)); bone remodeling (osteocalcin); diabetic control (HbA1c); and radiological study of the second metacarpal of the left hand and of bone age in 87 children with type 1 DM. The mineral parameters were not abnormal among the diabetics. Diabetic children had similar levels of fasting osteocalcin as normals (10.05 +/- 4.9 vs. 9.79 +/- 3.34 ng/ml, mean +/- SD); this did not differ by sex. The bone age fell within two standard deviations of the mean, and 9.5% of the diabetics had a bone mass deficit (less than the mean cortical thickness) greater than 2 SD. There was no correlation between osteocalcin and Ca, P, glycemia, HbA1c, PTH, Mg, or OHP. Our results do not support any association between bone mass loss and the severity or duration of type 1 diabetes. Bone turnover, measured by serum osteocalcin, was normal. Therefore the pathogenesis of osteopenia in type 1 DM remains unclear, and requires further investigation.

Hypoglycemic action of an oral fig-leaf decoction in type-I diabetic patients.

The effect of a decoction of fig leaves (Ficus carica), as a supplement to breakfast, on diabetes control was studied in insulin-dependent diabetes mellitus (IDDM) patients (six men, four women, age 22-38 years, body mass index (BMI): 20.8 +/- 3.0 kg/m2, HbA1c 7.6 +/- 0.9% with a mean duration of diabetes of 9 +/- 6.3 years). The patients were managed with their usual diabetes diet and their twice-daily insulin injection. During the first month, patients were given a decoction of fig leaves (FC) and during the next month a non-sweet commercial tea (TC). The patients were divided into two groups (n = 5) with random allocation and cross-over design. A standard breakfast was given at the beginning and end of each month-run. C-peptide, 2 h pre- and post-prandial glycemia, HbA1c, cholesterol, lipid fractions and hematology data, were analyzed during each visit. Glycemic profiles (7/day per week) were recorded by patients. Only two patients had intolerance dropout. Post-prandial glycemia was significantly lower during supplementation with FC 156.6 +/- 75.9 mg/dl versus TC 293.7 +/- 45.0 mg/dl (P < 0.001) without pre-prandial differences 145.0 +/- 41.5 and 196.6 +/- 43.2 mg/dl, respectively. Medium average capillary profiles were also lower in the two sub-groups of patients during FC 166.7 +/- 23.6 mg/dl, P < 0.05 and 157.1 +/- 17.0 mg/dl versus TC 245.8 +/- 14.2 mg/dl and 221.4 +/- 27.3 mg/dl. Average insulin dose was 12% lower during FC in the total group. The addition of FC to diet in IDDM could be of help to control postprandial glycemia.

Bone mass after long-term euthyroidism in former hyperthyroid women treated with (131)I influence of menopausal status.

The objective of this study was to assess bone mineral density (BMD) and bone markers in former hyperthyroid females after long-term euthyroidism (>4 yr) following (131)I therapy, as well as the potential influence of the timing of menopause. Twenty-six females ages 57 +/- 8 yr previously diagnosed with hyperthyroidism and treated with (131)I who were euthyroid for a minimum of the last 4 yr (10 +/- 5 yr) were studied. Eighteen patients (69%) were on levothyroxine (LT(4)) replacement therapy for 9 +/- 4 yr. BMD (g/cm(2) and Z-score) was measured by dual X-ray absorptiometry in the lumbar spine, femoral neck, and Ward's triangle. BMD (Z-score) was lower than the normal reference values for the Spanish population in all sites (lumbar spine: -0.65 +/- 1.13; femoral neck: -0.47 +/- 0.95; Ward's triangle: -0.37 +/- 0.88). No differences were found between BMD values according to the etiology of the hyperthyroidism or current LT(4) therapy. Current postmenopausal patients (n = 21) showed lower BMD than current premenopausal patients in the lumbar spine and femoral neck (p < 0.05). Those women who were postmenopausal at the time of the (131)I therapy (n = 15) also had lower lumbar spine BMD than premenopausal patients (p = 0.01), while no significant difference in BMD was seen according to the menopausal status when hyperthyroidism was diagnosed. Former hyperthyroid patients after long-term euthyroidism following (131)I therapy showed reduced BMD at the lumbar spine and proximal femur. Menopausal women showed a greater reduction in bone density. The menopausal status at the time of diagnosis did not seem to have long-term effects in bone density; nevertheless, an early therapeutic intervention in premenopause is suggested to reduce bone loss.

Bone mineral density in hypoparathyroid women on LT4 suppressive therapy. Effect of calcium and 1,25(OH)2 vitamin D3 treatment.

Our aim was to study the bone mineral density (BMD) of patients with chronic hypoparathyroidism (hypoPTH) after longterm calcium and vitamin D treatment. Twenty hypoPTH women (mean-/+SD, aged 50-/+15 years, IPTH 4-/+6 pg/ml) and 20 matched euparathyroid women (euPTH) after near total thyroidectomy for thyroid cancer, completed with I-131 ablation and on suppressive therapy with L-Thyroxine (LT(4)), were studied. In addition eight hypoPTH patients who were receiving LT(4) replacement therapy after surgery for compressive goiter were simultaneously studied. The hypoPTH patients were on calcium and 1,25(OH)(2) vitamin D(3) therapy to normalize serum calcium. Bone mineral density (BMD) (DXA, at the lumbar spine [L(2)- L(4), LS], femoral neck [FN] and Ward triangle [WT]), serum and urine calcium, serum phosphorus, TOTALALP and osteocalcin were measured. Patients with hypoPTH showed greater lumbar BMD than euPTH patients on suppressive therapy (Z-score; 1.01-/+1.34 vs. -0.52-/+0.70, p<0.05). Serum osteocalcin levels were higher in hypoPTH patients on suppressive therapy compared to hypoPTH patients on replacement therapy. The LS BMD from hypoPTH patients correlated with calcium supplements (r=0.439; p=0.02), 1,25(OH)(2)D(3) dose (r=0.382; p=0.04) and LT(4) dose (r=0.374; p=0.05). Our data suggest that long-term treatment with calcium and 1,25(OH)(2) vitamin D3 supplements in hypoPTH patients on suppressive LT4 therapy results in increased BMD when compared with patients with normal PTH levels.

The parasacral approach to the rectum.

The posterior parasacral approach to the rectum is well-suited to several benign conditions and may occasionally be indicated in malignant rectal disorder. The York Mason modification of the Kraske procedure permits preservation of the sphincters and preservation of anal continence. The procedure is recommended as part of a surgeon's repertoire in operations on the rectum.

Comparison between spinal and radial bone mineral density in children measured by X-ray absorptiometry.

Several studies have analyzed the correlation between axial bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA) and growth parameters. However, little is known about the growth-related changes in appendicular BMD measured by this technique. We used DXA to measure BMD in the lumbar spine (L1-L4) and distal radius in 121 normal growing children (69 boys, 52 girls), aged 3 to 18 yr. Both lumbar and radius BMD showed a steady increase with age and a steeper increment during puberty. There was a good correlation between spinal and radial BMD (r = 0.83; p < 0.001) and both were highly correlated with growth parameters; their respective correlation coefficients did not differ significantly for chronological age (r = 0.70 vs 0.80), weight (r = 0.77 vs 0.76), height (r = 0.73 vs 0.79), body surface (r = 0.78 vs 0.80), body mass index (r = 0.54 vs 0.49) and bone age (r = 0.77 vs 0.79). By multiple regression analysis the best predictors for spinal BMD were bone age, pubertal stage and weight, while for radial BMD the best predictors were chronological age and weight. We have shown that the measurement of BMD by DXA at distal radius, an easily accessible bone, has a correlation with growth parameters as good as lumbar spine BMD measurements in children.

Evaluation of radial bone mineral content in prepubertal children with constitutional delay of growth.

We have previously reported that children with constitutionally delayed growth (CDG) have significantly lower spinal bone mineralization than children with familial short stature (FSS). The aim of the present study was to evaluate whether the decreased bone mineralization in children with CDG also affects the radius, which has a lower bone turnover than the spine. To avoid the possibility of size-related artifacts in the assessment of bone mineral data, data were corrected for bone and body size. Radial bone mineral content (RBMC) and radial bone mineral density (RBMD) were measured by dual energy X-ray absorptiometry (Hologic QDR 1000/w) in 56 short prepubertal children aged 5-11 years. All children had height below the 10th percentile for chronological age (CA), and bone age (BA) less than 10 years, 29 of them with clinical diagnosis of CDG and 27 of them with FSS. The mean (+/- SD) RBMD was significantly lower in the children with CDG than in the FSS group (0.361 +/- 0.035 vs 0.385 +/- 0.033 g/cm2, p<0.05). RBMC was significantly lower in CDG than in FSS, when multiple regression analysis was performed by using radial scanned bone area (RSBA), body weight and height, sex and BA as independent variables (p = 0.03). These data indicate that the decreased bone mineralization in children with CDG also affects peripheral bone, and that this finding is not due to bone or body size artifacts.