Association of Insulin-like Growth Factor-1 with Bone Mineral Density in Survivors of Childhood Acute Leukemia.

In this study, we investigated bone mineral deficits in children who survived childhood acute leukemia and explored the association between the insulin-like growth factor-1 (IGF-1) level and bone mineral density (BMD). This retrospective analysis enrolled 214 patients treated for acute leukemia, measuring various factors including height, weight, body mass index (BMI), and lumbar spine BMD after the end of treatment. The study found an overall prevalence of low BMD in 15% of participants. Notably, IGF-1 levels were significantly different between patients with low BMD and those with normal BMD, and correlation analyses revealed associations of the IGF-1 level and BMI with lumbar spine BMD. Regression analyses further supported this relationship, suggesting that higher IGF-1 levels were associated with a decreased risk of low BMD. The study findings suggest that IGF-1 may serve as a valuable tool for evaluating and predicting osteoporosis in survivors of childhood acute leukemia.

Factors Affecting Bone Mineral Density in Children and Adolescents with Systemic Lupus Erythematosus.

Purpose: Patients with juvenile-onset systemic lupus erythematosus (JSLE) are at a high risk of entering adulthood with disease-related morbidities such as reduced bone mass and osteoporosis. This study aimed to evaluate the clinical characteristics of JSLE and to analyze the factors associated with low bone mineral density (BMD) in these patients. Methods: Children and adolescents diagnosed with JSLE at a single hospital in Korea were included. Demographic, clinical, and laboratory data and use of glucocorticoids and disease-modifying anti-rheumatic drugs were collected. Lumbar spine BMD Z-score was measured using dual energy x-ray absorptiometry, and lumbar spine radiographic data were collected. Results: A total of 29 patients with JSLE were included in this study. Of these patients, seven had a lumbar spine Z-score of -2.0 or lower and were designated as the low BMD group. The differences in the clinical parameters and treatment variables between the low BMD and non-low BMD groups were compared. Higher cumulative glucocorticoid dose, longer glucocorticoid exposure, and higher cumulative hydroxychloroquine dose were associated with low BMD; the main factor was the duration of exposure. There was no significant correlation between BMD and clinical profile, SLE disease activity, or bone metabolism markers. Conclusion: The duration of glucocorticoid exposure, cumulative glucocorticoid dose, and cumulative hydroxychloroquine dose were risk factors for low BMD in patients with JSLE, with the main factor being duration of glucocorticoid exposure. Thus, patients with JSLE should be routinely monitored for low BMD and potential fracture risks, and glucocorticoid-sparing treatment regimens should be considered.

Risk Factors of Low Bone Mineral Density in Newly Diagnosed Pediatric Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with an increasing worldwide incidence. IBD is frequently diagnosed during childhood in the adolescent period of ongoing growth and development, and it can affect patients' linear growth, puberty, nutrition, and bone health. Therefore, its treatment and monitoring are critical to prevent secondary outcomes. However, few studies have highlighted the association between pediatric IBD and skeletal outcomes in Asian populations. We aimed to identify the prevalence and risk factors for low bone mineral density (BMD) in Korean children and adolescents with newly diagnosed IBD. Patients aged 10-18 years diagnosed with either Crohn's disease (CD) or ulcerative colitis (UC) who underwent lumbar spine bone mineral density (LSBMD) and femoral bone mineral density (FBMD) analyses via dual-energy X-ray absorptiometry at the time of IBD diagnosis were included. Low BMD was considered when the age- and sex-matched BMD Z-score was <-1.0. The LSBMD and FBMD Z-scores were correlated with clinical parameters, including general characteristics, anthropometry, and IBD-associated laboratory markers. Regression analyses were performed to identify the risk factors for low BMD. Although the general characteristics between CD (n = 42) and UC (n = 9) groups did not differ, the mean Z-scores of LSBMD and FBMD of the 51 subjects were -0.11 ± 1.24 and -0.58 ± 1.38, respectively. Furthermore, 7.8% and 18% of the study subjects had LSBMD and FBMD Z-scores < -2.0, whereas more than 50% had scores of 0--1.0. Among the clinical factors, body mass index (BMI) Z-score, duration of clinical manifestations, and serum alanine aminotransferase and selenium levels were associated with LSBMD Z-scores in the final multivariate regression analyses. Odds ratios of BMI < -2.0 standard deviation for low LSBMD and FBMD Z-scores were 31.97 and 41.45, respectively. A BMI Z-score < -0.93 was determined as the best cut-off for predicting low BMD. In newly diagnosed pediatric IBD, a substantial number of children are likely to have low BMD in prior to initial treatment while lower BMI, longer duration of clinical manifestation, and higher selenium concentration could affect initial BMD status. Routine bone health surveillance from initial IBD diagnosis throughout the treatment's completion is recommended for preventing the early development of secondary osteoporosis.

Case Report and Literature Review: Bisphosphonate, Sirolimus, and Atenolol Treatment in a 4-Year-Old Child Diagnosed with Gorham-Stout Disease.

We report a 4-year-old with Gorham-Stout disease (GSD) who was treated with a combination of bisphosphonate, sirolimus, and atenolol. A previously healthy 4-year-old girl presented with back pain after falling on her back 2 months prior. Thoracolumbar spine X-ray revealed diffuse compression spinal fractures in T9-L2. Magnetic resonance imaging (MRI) confirmed multiple compression fractures at T9-L5 and revealed a paraspinal mass along the T1-L1 level. Based on clinical, radiological, and histopathological findings, Gorham-Stout disease was diagnosed. Treatment with sirolimus (0.5 mg twice daily, 1.6 mg/m2) was initiated and intravenous bisphosphonate (pamidronate, 1 mg/kg for 3 days, total 3 mg/kg every 4 months) was added for back pain; she had immediate improvement in back pain. After 9 months with this treatment, she had a mild increase in paraspinal lymphangiomatosis and aggravation in T9-L5 compression fractures; atenolol was administered. The patient underwent 11 months of combination treatment with bisphosphonate, sirolimus, and atenolol, and MRI showed mild degree of reduction in the paraspinal lesions at L1-L5. The patient is currently in stable condition with no back pain or side effects. The triple combination treatment with bisphosphonate, sirolimus, and atenolol may be helpful in stabilizing the disease course of GSD.

Continuous Glucose Monitoring: A Possible Aid for Detecting Hypoglycemic Events during Insulin Tolerance Tests.

The combined pituitary function test evaluates the anterior pituitary gland, while the insulin tolerance test evaluates growth hormone deficiencies. However, successful stimulation requires achieving an appropriate level of hypoglycemia. Close medical supervision for glucose monitoring is required during hypoglycemia induction and the test is often very tedious. In addition, a capillary blood sugar test (BST) and serum glucose levels may differ greatly. An alternative approach may be utilizing a continuous glucose-monitoring (CGM) system. We provide three cases in which CGM was successfully used alongside a standard BST and serum glucose levels during the combined pituitary function test to better detect and induce hypoglycemia. Three participants who were diagnosed with multiple pituitary hormone deficiencies during childhood were re-evaluated in adulthood; a Dexcom G6 CGM was used. The CGM sensor glucose and BST levels were simultaneously assessed for glycemic changes and when adequate hypoglycemia was reached during the combined pituitary function test. The CGM sensor glucose, BST, and serum glucose levels showed similar glucose trends in all three patients. A Bland-Altman analysis revealed that the CGM underestimated the BST values by approximately 9.68 mg/dL, and a Wilcoxon signed-rank test showed that the CGM and BST measurements significantly differed during the stimulation test (p = 0.003). Nevertheless, in all three cases, the CGM sensor mimicked the glycemic variability changes in the BST reading and assisted in monitoring appropriate hypoglycemia nadir. Thus, CGM can be used as a safe aid for clinicians to use during insulin tolerance tests where critical hypoglycemia is induced.

Front-Line Tyrosine Kinase Inhibitors in Pediatric Chronic Myeloid Leukemia: A Study on Efficacy and Safety.

We conducted a retrospective study on 51 pediatric patients with newly diagnosed chronic myeloid leukemia chronic phase or accelerated phase. The patients were classified into the IMA group (N = 33), treated with imatinib, and the DSA group (N = 18), treated with dasatinib, as front-line tyrosine kinase inhibitors (TKIs). At 12 months, the rates of complete cytogenetic response were similar between the IMA group (92.3%) and DSA group (100%) (p = 0.305). However, the rate of early molecular response was higher in the DSA group than in the IMA group (100.0% vs. 80.0%, p = 0.043). By 12 and 24 months, the DSA group showed faster and higher cumulative rates of both major (DSA group: 72.2% and 100%, respectively; IMA group: 41.2% and 68.7%, respectively; p = 0.002) and deep molecular responses (DSA group: 26.0% and 43.6%, respectively; IMA group: 13.8% and 17.5%, respectively; p = 0.004). Both TKIs were well tolerated. Although the height standard deviation scores decreased in both groups, the height decline was greater in the DSA group between one and two years from the start of TKI therapy. In this study, dasatinib achieved faster and higher molecular responses with an acceptable safety profile. Further follow-up is necessary to assess the long-term outcomes of TKI treatment in children.

A Causality between Thyroid Function and Bone Mineral Density in Childhood: Abnormal Thyrotropin May Be Another Pediatric Predictor of Bone Fragility.

Low bone mass can occur in children and adolescents with numerous chronic conditions; however, the influence of abnormal thyroid hormone and thyroid-stimulating hormone (TSH) levels on low bone mineral density (BMD) in children and adolescents remains controversial. Investigating the effects of excessive or deficient thyroid hormone and TSH levels on the risk of childhood bone fragility may provide a better understanding of the role of thyroid function on bone density in the pediatric population. The triiodothyronine (T3), thyroxine (T4), and TSH levels and BMD of 619 children diagnosed with various underlying conditions and whose treatment was completed were simultaneously assessed. The T3, free thyroxine (FT4), and TSH levels were subcategorized based on the age-matched reference range, and the lumbar spine BMD (LSBMD) data were compared. The mean LSBMD z-score was 0.49 ± 1.28, while T3, FT4, and TSH levels were 1.25 ± 0.29 ng/mL, 1.28 ± 0.19 ng/dL, and 2.76 ± 1.87 µU/mL, respectively. Both lumbar and femoral BMD z-scores were lower in children with abnormal TSH levels. TSH abnormality was the strongest risk factor for decreased LSBMD z-scores, and thus could be an early indicator of low BMD in children and adolescents with various underlying conditions.

Short-term effect of growth hormone treatment in childhood leukemia survivors with growth hormone deficiency.

PURPOSE: Survivors of childhood leukemia are at risk of growth impairment due to intensive chemotherapy and radiation treatments. This study investigated the auxological and biochemical characteristics of childhood leukemia survivors diagnosed with growth hormone deficiency (GHD) and the changes in these parameters after 1 year of growth hormone (GH) treatment. METHODS: A total of 24 children diagnosed with GHD after leukemia treatment was analyzed. Clinical and biochemical data were collected retrospectively at leukemia diagnosis, GHD diagnosis, and 1 year after GH treatment. Standard deviation score (SDS) was calculated based on the age- and gender-adjusted population. RESULTS: Of the 24 children included in this study, 19 received GH treatment. The median age at GHD diagnosis was 12.3 years, and the median delay in bone age was 1.46 years. Height SDS decreased from -0.69 at leukemia diagnosis to -2.58 at GHD diagnosis (P<0.001). The change in height SDS with and without GH for 1 year was 0.35 and -0.21, respectively (P=0.044). In regression analyses, higher height SDS at GHD diagnosis and a smaller decrease of the height SDS between leukemia and GHD diagnoses were positively correlated with height SDS after GH treatment. CONCLUSION: GH treatment could be beneficial and safe for improving height in childhood leukemia survivors with GHD. Height SDS at GHD diagnosis and reduction of height SDS between leukemia and GHD diagnosis could be potential factors in predicting the therapeutic effects. Close auxological monitoring is recommended for any childhood leukemia survivors who experience posttreatment height decline.

Factors affecting bone mineral density in children and adolescents with secondary osteoporosis.

PURPOSE: This study aimed to investigate the clinical factors associated with bone mineral density (BMD) among children and adolescents with osteoporosis secondary to treatment for underlying clinical conditions. METHODS: We retrospectively reviewed the medical records of patients aged 10-18 years and evaluated them for lumbar spine BMD (LSBMD) after treatment for underlying diseases, including hemato-oncologic, rheumatologic system, and inflammator y bowel diseases. LSBMD measured by dual-energy x-ray absorptiometry (DXA) performed from March 2019 to March 2021 was evaluated. We analyzed 117 patients who underwent initial DXA after treatment for underlying diseases. RESULTS: Subjects in this study had multiple underlying diseases: hemato-oncologic (78.6%), rheumatologic (11.1%), and inflammatory bowel diseases (10.3%). There was no significant association between the z-score and bone metabolic markers (P>0.05). However, higher cumulative glucocorticoid (GC) dose significantly reduced LSBMD z-score (P=0.029). Moreover, the association between cumulative dose of GC and initial z-score of LSBMD was significant in logarithmic regression analysis (P=0.003, R2=0.149). GC accumulation was a significant risk factor for vertebral fracture when the initial BMD was evaluated after treatment (P=0.043). Bone metabolic markers did not significantly influence the risk of vertebral fracture. CONCLUSION: Initial bone mass density of the lumbar spine evaluated after long-term GC use for underlying diseases is a predictor of further vertebral fractures.

Usefulness of glycated albumin level as a glycemic index complementing glycosylated hemoglobin in diabetic children and adolescents.

PURPOSE: Glycated albumin (GA) is a glycemic marker reflecting the average serum glucose of the previous 2 weeks. This study aimed to evaluate the usefulness of GA as a glycemic index to complement glycosylated hemoglobin (HbA1c) in children and adolescents. METHODS: Fifty-four children and adolescents with diabetes mellitus (DM) and 97 children and adolescents without DM (NDM) were enrolled. The correlation between mean blood glucose (MG) and GA compared to HbA1c was investigated in the DM group. The correlation between fasting glucose (FG) and GA compared to HbA1c was investigated in the NDM group. Factors affecting GA, HbA1c, and GA/HbA1c were analyzed. RESULTS: In the DM group, positive correlations were observed between MG and GA (P=0.003), between MG and HbA1c (P=0.001), and between GA and HbA1c (P<0.001). The correlation coefficient between MG and GA did not differ from that between MG and HbA1c in the DM group (P=0.811). Among patients with DM, those whose standardized body mass index standard deviation score (BMI SDS) was ≥2 had a lower GA/HbA1c compared with those whose BMI SDS was <2 (P=0.001). In the NDM group, there were no significant correlations between FG and GA, between FG and HbA1c, or between GA and HbA1c. The NDM subjects whose BMI SDS was ≥2 had a lower GA/HbA1c than did the NDM subjects whose BMI SDS was <2 (P=0.003). CONCLUSION: GA is comparable with HbA1c in reflecting glycemic control in children and adolescents with DM. GA is affected by obesity in children and adolescents with or without DM.

The association of serum irisin with anthropometric, metabolic, and bone parameters in obese children and adolescents.

Background: Irisin is an adipomyokine secreted by muscle and adipose cells, and it plays a role in glucose, fat, and bone metabolism. This study aimed to determine the correlation of serum irisin levels with anthropometric, metabolic, and bone parameters in obese children and adolescents. Methods: This single-center study included 103 Korean children and adolescents: 54 (52.4%) obese participants with a body mass index (BMI) ≥95th percentile and 49 (47.6%) healthy controls with BMI within the 15th to 85th percentile. Various parameters were measured, including fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride and glucose (TyG) index, lipid profile, alkaline phosphatase (ALP), osteocalcin, and 25(OH)-Vitamin D levels. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA) in 33 healthy subjects. Results: Serum irisin was significantly higher in the obese group than in the control group (mean 18.1 ± 3.5 vs. 16.2 ± 2.0 ng/mL; p = 0.001). Serum irisin level was positively correlated with chronological age (r = 0.28; p = 0.004), height SDS (r = 0.24; p = 0.02), BMI SDS (r = 0.37; p < 0. 001), fasting glucose (r = 0.27; p = 0.007), fasting insulin (r = 0.23; p = 0.03), HOMA-IR (r = 0.21; p = 0.04), osteocalcin (r = 0.27; p = 0.006) and negatively correlated with HDL cholesterol (r = -0.29; p = 0.005). All these correlations were evident in obese subjects but not in healthy subjects. ALP and 25(OH)-Vitamin D were unrelated to irisin levels. Among 33 healthy subjects, total body-less head (TBLH) BMD Z-score was positively correlated with serum irisin (r = 0.39; p = 0.03), osteocalcin (r = 0.40; p = 0.02), fasting insulin (r = 0.39; p = 0.04), and HOMA-IR (r = 0.38; p = 0.047). Conclusion: This study demonstrated an association between irisin levels and glucose, lipid, and bone parameters in children and adolescents. Our findings suggest that irisin has a potential role in metabolic disorders and bone health in obese children and adolescents.

High Glycated Hemoglobin Instead of High Body Mass Index Might Increase the Urine N-Acetyl-ß-D-glucosaminidase Con-Centration in Children and Adolescents with Diabetes Mellitus.

Children with diabetes, and particularly those with obesity, have poor glycemic control. They are thus at higher risk of early microvascular complications. Renal tubulointerstitial markers are integral to evaluating diabetic nephropathy. Various biomarkers have been proposed, but their role in the obese pediatric population is uncertain. We investigated renal injury markers in children with diabetes, according to obesity, and determined their role as early predictors of diabetic nephropathy. Fifty-three children and adolescents, diagnosed with either type 1 or 2 diabetes mellitus, and 43 control children, aged 7-18 years, were included. Clinical and laboratory characteristics, including six renal injury markers, were compared among subjects according to body mass index and presence of diabetes mellitus. Urine neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and N-acetyl-ß-D-glucosaminidase (NAG) showed significant difference between controls and diabetic children, whereas urine NAG was the only biomarker that was significantly lower either in non-obese or obese controls as compared to diabetic children. Urine NGAL, KIM-1, and NAG showed significant correlations with both HbA1c and urine ACR, whereas only urine NAG was significantly correlated with HbA1c even when groups were subdivided based on the presence of either obesity or diabetes. After adjusting for age, sex, body mass index, duration of known diabetes, and urine albumin-to-creatinine ratio, HbA1c remained a significant risk factor for elevated urine NAG. Urine NAG could be a useful indicator of tubulointerstitial damage in children with diabetes in the pre-albuminuric state. Tighter glycemic control appears to be crucial for avoiding early progression to diabetic nephropathy.

Metabolic Impacts of Discontinuation and Resumption of Recombinant Human Growth Hormone Treatment during the Transition Period in Patients with Childhood-Onset Growth Hormone Deficiency.

BACKGROUND: Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period. METHODS: This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption. RESULTS: Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates. CONCLUSION: GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.

Association between Stress Hyperglycemia and Adverse Outcomes in Children Visiting the Pediatric Emergency Department.

Stress hyperglycemia (SH) is often identified in patients visiting the pediatric emergency department (PED), and SH in adults has been associated with adverse outcomes, including mortality. In this retrospective study, we determined the adverse outcomes according to blood glucose (BG) levels of children visiting the PED of tertiary hospitals. Data were collected from the electronic medical records of children aged <18 years between 1 January 2011 and 31 December 2020. A total of 44,905 visits were included in the analysis. SH was identified in 1506 patients, with an incidence rate of 3.4%. Compared to those without SH, patients with SH had significantly higher ward admission rates (52.6% vs. 35.9%, p < 0.001), intensive care unit admission rates (2.6% vs. 0.7%, p < 0.001), and mortality rates (2.7% vs. 0.3%, p < 0.001). Compared to the normoglycemic group of 45 ≤ BG < 150 mg/dL, the odds ratios (95% CI) for mortality were 5.61 (3.35−9.37), 27.96 (14.95−52.26), 44.22 (17.03−114.82), and 39.94 (16.31−97.81) for levels 150 ≤ BG < 200, 200 ≤ BG < 250, 250 ≤ BG < 300 and ≥300 mg/dL, respectively. This suggests that SH is common in children visiting the PED and is associated with higher adverse outcomes. Thus, there is a need to quickly identify its cause and take prompt intervention to resolve it.

Effect of Growth Hormone Therapy on a 4-Year-Old Girl with Pfeiffer Syndrome and Short Stature: A Case Report.

Fibroblast growth factor receptors (FGFRs) are expressed in epiphyseal cartilage cells of developing bones and regulate endochondral bone formation with interdependent signaling pathways. Gene mutation in FGFRs disrupts the formation of endochondral bony structure by reducing the number of proliferating chondrocytes. Among the syndromes caused by mutation in the FGFR gene, Pfeiffer syndrome is a rare inherited disease characterized by acrocephalosyndactyly related to hypertelorism, broad pollex, and hallux. We describe the case of a 4-year-old girl with short stature, advanced bone age, wide thumbs and great toes. The patient was diagnosed with partial growth hormone deficiency and an identified mutation in the FGFR2 gene. Standard deviation score of her height increased after starting growth hormone therapy. This report will raise awareness of the growth hormone provocation test regardless of bone age in patients with short stature founded FGFR gene mutation.

Adrenocortical carcinoma and a sporadic MEN1 mutation in a 3-year-old girl: a case report.

Childhood adrenocortical carcinoma (ACC) is a rare disease that is mostly linked to familial cancer syndrome. Although the prevalence of ACC is extremely low in children, it is clinically important to diagnose ACC early because age and tumor stage are closely related to prognosis. From this perspective, understanding the underlying genetics and possible symptoms of ACC is crucial in managing ACC with familial cancer syndromes. In this report, we present the case of a 3-year-old girl who initially presented with symptoms of precocious puberty and was later found to have ACC by imaging analysis. On genetic analysis, the patient was found to have a MEN1 gene mutation. MEN1 mutations are found in patients with multiple endocrine neoplasia type 1 (MEN1), usually precipitating multiple endocrine tumors, including pituitary adenoma, parathyroid hyperplasia, and adrenal tumors. Although MEN1 mutation is usually inherited in an autosomal dominant manner, neither of the patient's parents had the same mutation, making hers a case of sporadic MEN1 mutation with initial presentation of ACC. The clinical course and further investigations of this patient are discussed in detail in this report.

Clinical Significance of the Fetuin-A-to-Adiponectin Ratio in Obese Children and Adolescents with Diabetes Mellitus.

Fetuin-A and adiponectin are inflammatory cytokines associated with obesity and insulin resistance. This study aimed to examine the fetuin-A-to-adiponectin ratio (FAR) in diabetic children and to determine the role of FAR. A total of 54 children and adolescents with diabetes mellitus (DM) and 44 controls aged 9-16 years were included in this study. Clinical characteristics, including plasma fetuin-A and adiponectin levels, were compared with respect to body mass index (BMI) and diabetes type. Of 98 children, 54.1% were obese, whereas 18.4% were obese and diabetic. FAR was higher in obese children with DM than in non-obese children and also in type 2 DM children than in type 1. FAR showed a stronger association with BMI than with fetuin-A and adiponectin individually, and its association was more prominent in diabetic children than in controls. BMI was a risk factor for increased FAR. Plasma fetuin-A was elevated in obese children, and its association with insulin resistance and ß cell function seemed more prominent in diabetic children after adjustment for adiponectin. Thus, FAR could be a useful surrogate for the early detection of childhood metabolic complications in diabetic children, particularly those who are obese.

Associations between Sclerostin and Anthropometric and Metabolic Parameters in Children and Adolescents.

(1) Background: Bone plays an important role in the regulation of the systemic glucose and energy metabolism. Sclerostin, secreted by osteocytes, is an inhibitor of the Wnt/ß-catenin bone metabolic pathway, and is involved in osteoporosis and metabolic disease. The aim of this study was to investigate the relationship between sclerostin and anthropometric and metabolic parameters in children and adolescents with obesity or who are overweight. (2) Methods: This study included 63 children and adolescents (20 obese, 11 overweight and 32 healthy control subjects). We evaluated the correlation between serum sclerostin and anthropometric parameters, metabolic parameters related to glucose (homeostasis model assessment of insulin resistance [HOMA-IR]), lipid, and bone metabolism (osteocalcin and 25-hydroxy vitamin D). (3) Results: Sclerostin and osteocalcin levels did not differ between obese and control groups. Sclerostin level was higher in boys than in girls (median 20.7 vs. 18.9 pmol/L, respectively; p = 0.04). In all subjects, sclerostin levels were negatively correlated with fasting insulin (r = -0.26; p = 0.04) and HOMA-IR (r = -0.28; p = 0.03), and positively correlated with serum concentrations of triglycerides (r = 0.29; p = 0.04), alkaline phosphatase (r = 0.41; p = 0.002), and osteocalcin (r = 0.33; p = 0.008). In obese patients, sclerostin levels were correlated negatively with fasting glucose (r = -0.49; p = 0.03) and HOMA-IR (r = -0.48; p = 0.03) and positively correlated with triglyceride levels (r = 0.53; p = 0.02). In the healthy control, sclerostin levels were correlated negatively with fasting insulin levels (r = -0.61; p < 0.001) and HOMA-IR (r = -0.36; p = 0.04). After adjusting for age, sex, and height SDS, a negative correlation between sclerostin and HOMA-IR was found (r = -0.39; p = 0.003) in all of the subjects. This association was more evident in obese patients (r = -0.60; p = 0.01) than in healthy controls (r = -0.39; p = 0.047). (4) Conclusions: Among children and adolescents with obesity, serum sclerostin was negatively correlated with HOMA-IR. Further studies are needed to clarify the mechanisms involved to understand how sclerostin affects the glucose metabolism.