The Role of the Gut Microbiome in Youth with Polycystic Ovary Syndrome: A Systematic Review.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age and female adolescents. The diagnosis of PCOS is difficult during puberty due to overlapping of the criteria with normal variations of menstruation during this age period. There are insufficient data on the gut microbiome and PCOS and potential mechanisms linking the two. The present systematic review aimed to detect dysbiosis patterns in youth with PCOS, compared with healthy controls. METHODS: One hundred seventy-eight studies were identified by a databases search and sixty-eight by a full-text assessment for eligibility; four were included in the systematic review and underwent quality control. RESULTS: The results of the study were controversial in accordance to findings from the literature. A change in gut microbiome α diversity was found in PCOS adolescents, with no significant alterations in ß diversity. Almost all studies found Firmicutes, Bacteroidetes, and Actinobacteria in abundance in both groups, with changes in family composition and fluctuations at the phylum level. A statistically significant association between these changes and clinical or biochemical features of the syndrome was described. CONCLUSIONS: This systematic review confirmed gut microbiota dysbiosis in youth with PCOS. However, further data are needed to clarify these changes and to build a strategy to prevent the syndrome.

The association of serum vitamin D concentrations in paediatric migraine.

INTRODUCTION: Migraine is a neurologic condition characterized by hypersensitivity to auditory, olfactory, visual, and cutaneous stimuli; vomiting and nausea; and severe headache. It is the most frequent headache syndrome in children and can be categorized in chronic and/or episodic. Multiple dietary supplements have been inaugurated for the management of migraine, the most prevalent of which is vitamin D. BACKGROUND: In recent years, vitamin D deficiency has been a global public health problem, with 30-80% of the worldwide population having vitamin D deficiency. The significant role of vitamin D in neurological disorders is underlined by its key role in the brain function of the central nervous system (CNS). Current approaches in paediatric neurology include nonsteroidal anti-inflammatory drugs (NSAID) for the treatment of paediatric migraine, among others. Vitamin D is one of the dietary factors that has been linked to migraine, however, this association has mostly been examined in the adult population. OBJECTIVE: The aim of this study is to investigate the association between serum vitamin D and paediatric migraine by conducting a review of existing literature. The main question is described with the PICO format (population, intervention, control, and outcomes), while the assessment of the present research is under the PRISMA guidelines for systematic reviews. RESULTS/CONCLUSION: A systematic review of the literature reveals a remarkable association between vitamin D and migraine presentation in the paediatric population, affecting the frequency and duration of the episodes. That being the case, vitamin D supplementation could potentially improve the quality of life of paediatric patients suffering from migraine headaches.

Efficacy and safety of faster aspart in insulin pumps in children and adolescents with type 1 diabetes mellitus: A single-center study with real-world data.

AIMS: To assess the efficacy and safety of faster aspart (FIAsp) in paediatric population with type 1 diabetes mellitus (T1DM) and insulin pumps in real-world settings. METHODS: Of 44 patients, 20 used FIAsp, 16 of which switched from aspart to FIAsp and 24 used aspart/lispro. We performed within-groups and between-groups analyses in three time points for anthropometric data, % of 24-h time in range of 70-180 mg/dl (TIR), time < 70 mg/dl and <54 mg/dl and time > 180 mg/dl and >250 mg/dl, bolus and basal insulins doses (units/kg/day and %), total daily dose (TDD, units/kg/day), glycaemic variability, frequency of set changes, sensor wear per week and meals per day. RESULTS: Use of FIAsp over time increased TIR (P = 0.002) and TDD (P = 0.008 and P = 0.004, respectively for three months after the switch and recent use) and decreased time in hyperglycaemia (>180 P = 0.003 and > 250 mg/dl, P = 0.004). Frequency of set changes differ in the first 3 months (P = 0.042). Patients with FIAsp consumed more meals per day compared to those with aspart/lispro (P = 0.032). CONCLUSION: Real-world data confirm that use of FIAsp in insulin pumps in paediatric populations improves glycaemic control long-term.

Puberty in boys with type 1 diabetes mellitus: What has changed?

AIMS: To study the age of pubertal onset and secular trend in boys with Type 1 diabetes mellitus (T1DM) followed in two centers in North Greece. METHODS: Boys with T1DM visited the Outpatient Clinics of the 1st and 2nd Department of Paediatrics of Aristotle University of Thessaloniki from March until June 2022 were enrolled. Recent anthropometric data were recorded during the follow-up visit whereas previous anthropometric data and demographic data were collected from medical files. A volume of testis > 3 ml was indicative for the onset of puberty. RESULTS: A total of 46 boys with T1DM with documented pubertal onset after the diagnosis of T1DM were included in the study. Precocious puberty (<9 years old) was recorded in 5 boys (10.2 %), early puberty (<10 years but >9 years) in 10 (20.4 %) and 34 (69.4 %) entered puberty normally. The duration of T1DM was inversely correlated to the likelihood of earlier puberty (P < 0.001). However, no notable year predominance was observed suggesting no COVID-19 effect. CONCLUSION: A considerable number of Greek boys with T1DM appear to develop precocious and early puberty, raising thoughts regarding diabetes management and other possible cofactors.

Association Between Adipokine Profile, Systemic Inflammation, Muscle and Protein Energy Wasting in Children With Chronic Kidney Disease.

OBJECTIVES: This cross-sectional study explores the association of adipokines and interleukin-6 (IL-6) with muscle and protein energy wasting (PEW) in children with chronic kidney disease (CKD). METHODS: We measured serum adiponectin, leptin, resistin and IL-6 in 53 patients with CKD stage 3-5. Lean tissue (LTI) and fat tissue index (FTI) were estimated by bioimpedance analysis spectroscopy. PEW was defined as muscle wasting [LTI adjusted to height age (LTI HA) z-score < -1.65 SD) and at least 2 of the following: reduced body mass [body mass index adjusted to height age (BMI HA) z-score < -1.65 SD), poor growth [height z-score < -1.88 SD], questionnaire-based decreased appetite, and serum albumin ≤3.8 g/dL. RESULTS: PEW, observed in 8 (15.1%) patients, was more prevalent in CKD stage 5 (P = .010). Among the adipokines, adiponectin, and resistin levels were significantly higher in CKD stage 5 (P < .001, P = .005). Adiponectin was correlated to LTI HA z-score (Rs = -0.417, P = .002), leptin to FTI z-score (Rs = 0.620, P < .001), while no correlation was observed between resistin and body composition parameters. Resistin was the only adipokine correlated to IL-6 (Rs = 0.513, P < .001). After adjustment for CKD stage and patient age, PEW was associated with adiponectin and IL-6 rise by 1 µg/mL and 10 pg/mL respectively (odds ratio (OR) 1.240, 95% confidence interval (CI) 1.040, 1.478 and OR 1.405, 95% CI 1.075-1.836) but not with leptin, while resistin association with PEW lost its significance. CONCLUSIONS: In pediatric CKD, adiponectin is associated with muscle wasting, leptin with adiposity and resistin with systemic inflammation. Adiponectin and cytokine IL-6 may serve as PEW biomarkers.

The efficacy of automated insulin delivery systems in children and adolescents with type 1 diabetes Mellitus: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Insulin administration is the treatment of choice for people with type 1 diabetes mellitus (T1D). Technological advances have led to the development of automated insulin delivery (AID) systems, aiming to optimize the quality of life of patients with T1D. We present a systematic review and meta-analysis of the current literature about the efficacy of AID systems in children and adolescents with T1D. METHODS: We conducted a systematic literature search for randomized controlled trials (RCTs) until August 8th, 2022, investigating the efficacy of AID systems in the management of patients < 21 years of age with T1D. A priori subgroup and sensitivity analyses based on different settings (free-living settings, type of AID system, parallel group or crossover design) were also conducted. RESULTS: In total, 26 RCTs reporting a total of 915 children and adolescents with T1D were included in the meta-analysis. AID systems revealed statistically significant differences in the main outcomes, such as the proportion of time in the target glucose range (3.9-10 mmol/L) (p < 0.00001), in hypoglycemia (<3.9 mmol/L) (p = 0.003) and mean proportion of HbA1C (p = 0.0007) compared to control group. CONCLUSIONS: According to the present meta-analysis, AID systems are superior to insulin pump therapy, sensor-augmented pumps and multiple daily insulin injections. Most of the included studies have a high risk of bias because of allocation, blinding of patients and blinding of assessment. Our sensitivity analyses showed that patients < 21 years of age with T1D can use AID systems, after proper education, following their daily activities. Further RCTs examining the effect of AID systems on nocturnal hypoglycemia, under free-living settings and studies examining the effect of dual-hormone AID systems are pending.

Fibroblast growth-factor 23 and vitamin D are associated with iron deficiency and anemia in children with chronic kidney disease.

BACKGROUND: This cross-sectional study investigates the association of fibroblast growth-factor 23 (FGF23) and other bone mineral parameters with iron status and anemia in pediatric chronic kidney disease (CKD). METHODS: Serum calcium, phosphorus, 25-hydroxyvitamin D (25(OH)D), intact parathormone, c-terminal FGF23, a-Klotho, iron (Fe), ferritin, unsaturated iron-binding capacity, and hemoglobin (Hb) were measured in 53 patients from 5 to 19 years old with GFR < 60 mL/min/1.73 m2. Transferrin saturation (TSAT) was calculated. RESULTS: Absolute (ferritin ≤ 100 ng/mL, TSAT ≤ 20%) and functional iron deficiency (ferritin > 100 ng/mL, TSAT ≤ 20%) were observed in 32% and 7.5% of patients, respectively. In CKD stages 3-4 (36 patients), lnFGF23 and 25(OH)D were correlated with Fe (rs = - 0.418, p = 0.012 and rs = 0.467, p = 0.005) and TSAT (rs = - 0.357, p = 0.035 and rs = 0.487, p = 0.003) but not to ferritin. In this patient group, lnFGF23 and 25(OH)D were correlated with Hb z-score (rs = - 0.649, p < 0.001 and rs = 0.358, p = 0.035). No correlation was detected between lnKlotho and iron parameters. In CKD stages 3-4, in multivariate backward logistic regression analysis, including bone mineral parameters, CKD stage, patient age, and daily alphacalcidol dose as covariates, lnFGF23 and 25(OH)D were associated with low TSΑΤ (15 patients) (OR 6.348, 95% CI 1.106-36.419, and OR 0.619, 95% CI 0.429-0.894, respectively); lnFGF23 was associated with low Hb (10 patients) (OR 5.747, 95% CI 1.270-26.005); while the association between 25(OH)D and low Hb did not reach statistical significance (OR 0.818, 95% CI 0.637-1.050). CONCLUSIONS: In pediatric CKD stages 3-4, iron deficiency and anemia are associated with increased FGF23, independently of Klotho. Vitamin D deficiency might contribute to iron deficiency in this population. A higher resolution version of the Graphical abstract is available as Supplementary information.

Efficacy and safety of ultra-rapid insulin analogues in insulin pumps in patients with Type 1 Diabetes Mellitus: A systematic review and meta-analysis.

AIMS: To assess the efficacy and safety of ultra-rapid insulin analogues used with continuous subcutaneous insulin infusion systems (CSII) in adults with type 1 diabetes (T1DM). METHODS: We searched MEDLINE and Cochrane Library up to May 2022 for randomized controlled trials comparing ultra-rapid with rapid-acting insulin analogues (RAIAs) used with CSII. We performed random effects meta-analyses for % of 24-h time in range of 70-180 mg/dl (TIR), time in hypoglycaemia (<70 mg/dl) and hyperglycaemia (>180 mg/dl), 1- and 2-hour post-prandial glucose [PPG] increment after a meal test, HbA1c and average insulin dose at endpoint, unplanned infusion set changes and severe hypoglycaemia. RESULTS: Nine studies (1,156 participants) were included. Ultra-rapid insulins were superior to RAIAs on TIR (mean difference [MD] 1.1 %, 95 % CI 0.11-2.11), time spent in hypoglycaemia (MD -0.47 %, 95 % CI -0.63 to -30), and 1- and 2-hour PPG (MD -12.20 mg/dl, 95 % CI -19.85 to -4.54 and MD -17.61 mg/dl, 95 % CI -28.55 to -6.66, respectively). Ultra-rapid insulins increased odds of unplanned infusion set changes (odds ratio 1.60, 95 % CI 1.26-2.03). CONCLUSION: Ultra-rapid acting insulins provided better PPG control compared to RAIAs but their use might result in more infusion set changes.

The impact of COVID-19 vaccination on glycaemic control in children and adolescents with type 1 diabetes mellitus on continuous glucose monitoring.

AIMS: To investigate the impact of SARS-COV-2 vaccination on the glycaemic control in children and adolescents with T1DM wearing continuous glucose monitoring (CGM). METHODS: Caregivers of children and adolescents with T1DM were questioned regarding SARS-CoV-2 vaccination during their regular visits at the Pediatric Diabetes Outpatient Clinic. Data regarding Time in Range (TIR) (glucose levels: 70-180 mg/dl) 7 days prior and 7 days after a vaccination dose were collected in patients wearing CGM and data regarding insulin daily doses were also obtained for the insulin pump users. RESULTS: From a total of 135 patients eligible for SARS-CoV-2 vaccination, 70 (51.9%) children (37 boys, 52.9%) were vaccinated with at least one dose. Seven patients received only one dose, whereas two children received a third booster shot. No statistically significant difference was observed in either TIR (64.19% post vs. 65.53% pre, p = 0.158) or total daily insulin dose (40.08 U/day post vs. 39.32 U/day pre, p = 0,282). Additionally, in ten patients on Hybrid Closed-Loop System the percentage of the automated insulin boluses given post-vaccination was not statistically significant different compared to the boluses given pre-vaccination (15.80% vs. 16.90%, p = 0,491). CONCLUSIONS: Vaccination against SARS-CoV-2 in children and adolescents with T1DM is safe and is not associated with immediate glucose imbalance.

Arterial stiffness indices in children and adolescents with type 1 diabetes mellitus: A meta-analysis.

AIMS: Cardiovascular disease (CVD) represents the most frequent cause of morbidity and mortality among patients with type 1 diabetes mellitus (T1DM). Our aim was to review the evidence and conduct a meta-analysis assessing measures of arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx) in children and adolescents with T1DM compared to healthy controls. METHODS: PubMed and the Cochrane Library were searched for relevant studies published up to 10 May 2021. RESULTS: Twenty-one studies were finally included in the meta-analysis. The T1DM group had significantly higher carotid to femoral PWV levels than that of the control group (mean difference [d]: 0.53 CI: 0.35-0.71, P < 0.00001) but with a fair heterogeneity (I 2:73%). By omitting one study with marked heterogeneity, mean difference in cfPWV remained significantly increased in the T1DM group compared to the control group (mean difference [d]: 0.37 CI: 0.27-0.48, P < 0.00001) but with improved heterogeneity (I2 = 26%). Regarding Aix, the T1DM group had a significantly higher AI@75 index than that of the control group (mean difference [d]: 0.28 CI: 0.17-0.39, P < 0.00001) and with no heterogeneity (I 2 = 8%). CONCLUSIONS: Youths with T1DM show increased arterial stiffness, either as increased carotid-femoral pulse wave velocity or increased augmentation index, early in their course of life compared to healthy controls. PROSPERO REGISTRATION NUMBER: CRD42021253236.

Comparison of Insulin Dose Adjustments Made by Artificial Intelligence-Based Decision Support Systems and by Physicians in People with Type 1 Diabetes Using Multiple Daily Injections Therapy.

Objective: Artificial intelligence-based decision support systems (DSS) need to provide decisions that are not inferior to those given by experts in the field. Recommended insulin dose adjustments on the same individual data set were compared among multinational physicians, and with recommendations made by automated Endo.Digital DSS (ED-DSS). Research Design and Methods: This was a noninterventional study surveying 20 physicians from multinational academic centers. The survey included 17 data cases of individuals with type 1 diabetes who are treated with multiple daily insulin injections. Participating physicians were asked to recommend insulin dose adjustments based on glucose and insulin data. Insulin dose adjustments recommendations were compared among physicians and with the automated ED-DSS. The primary endpoints were the percentage of comparison points for which there was agreement on the trend of insulin dose adjustments. Results: The proportion of agreement and disagreement in the direction of insulin dose adjustment among physicians was statistically noninferior to the proportion of agreement and disagreement observed between ED-DSS and physicians for basal rate, carbohydrate-to insulin ratio, and correction factor (P < 0.001 and P ≤ 0.004 for all three parameters for agreement and disagreement, respectively). The ED-DSS magnitude of insulin dose change was consistently lower than that proposed by the physicians. Conclusions: Recommendations for insulin dose adjustments made by automatization did not differ significantly from recommendations given by expert physicians regarding the direction of change. These results highlight the potential utilization of ED-DSS as a useful clinical tool to manage insulin titration and dose adjustments.

The Effect of Various, Everyday Practices on Glucose Levels in Critically Ill Children.

BACKGROUND: To evaluate the effect of various, everyday intensive care unit (ICU) practices on glucose levels in critically ill pediatric patients with the use of a continuous glucose monitoring system. METHODS: Seventeen sensors were placed in 16 pediatric patients (8 male). All therapeutic and diagnostic interventions were recorded and 15 minutes later, a flash glucose measurement was obtained by swiping the sensor with a reader. Glucose difference was calculated as the glucose value 15 minutes after the intervention minus the mean daily glucose value for each individual patient. Additionally, the consciousness status of the patient (awake or sedated) was recorded. RESULTS: Two hundred and five painful skin interventions were recorded. The mean difference of glucose values was higher by 1.84 ± 14.76 mg/dL (95% CI: -0.19 to 3.87 mg/dL, P = .076). However, when patients were categorized regarding their consciousness level, mean glucose difference was significantly higher in awake state than in sedated patients (4.76 ± 28.07 vs -2.21 ± 15.77 mg/dL, P < .001). Six hundred forty-nine interventions involving the respiratory system were recorded. Glucose difference during washings proved to be significantly higher than the ones during simple suctions (4.74 ± 14.18 mg/dL vs 0.32 ± 18.22 mg/dL, P = .016). Finally, glucose difference in awake patients was higher by 3.66 ± 13.91 mg/dL compared to glucose difference of -2.25 ± 21.07 mg/dL obtained during respiratory intervention in sedated patients. CONCLUSIONS: Diagnostic and therapeutic procedures in the ICU, especially when performed in an awake state, exacerbate the stress and lead to a significant rise in glucose levels.

Adjustment of Insulin Pump Settings in Type 1 Diabetes Management: Advisor Pro Device Compared to Physicians' Recommendations.

AIMS: To compare insulin dose adjustments made by physicians to those made by an artificial intelligence-based decision support system, the Advisor Pro, in people with type 1 diabetes (T1D) using an insulin pump and self-monitoring blood glucose (SMBG). METHODS: This was a multinational, non-interventional study surveying 17 physicians from 11 countries. Each physician was asked to provide insulin dose adjustments for the settings of the pump including basal rate, carbohydrate-to-insulin ratios (CRs), and correction factors (CFs) for 15 data sets of pumps and SMBG of people with T1D (mean age 18.4 ± 4.8 years; eight females; mean glycated hemoglobin 8.2% ± 1.4% [66 ± 11mmol/mol]). The recommendations were compared among the physicians and between the physicians and the Advisor Pro. The study endpoint was the percentage of comparison points for which there was an agreement on the direction of insulin dose adjustments. RESULTS: The percentage (mean ± SD) of agreement among the physicians on the direction of insulin pump dose adjustments was 51.8% ± 9.2%, 54.2% ± 6.4%, and 49.8% ± 11.6% for the basal, CR, and CF, respectively. The automated recommendations of the Advisor Pro on the direction of insulin dose adjustments were comparable )49.5% ± 6.4%, 55.3% ± 8.7%, and 47.6% ± 14.4% for the basal rate, CR, and CF, respectively( and noninferior to those provided by physicians. The mean absolute difference in magnitude of change between physicians was 17.1% ± 13.1%, 14.6% ± 8.4%, and 23.9% ± 18.6% for the basal, CR, and CF, respectively, and comparable to the Advisor Pro 11.7% ± 9.7%, 10.1% ± 4.5%, and 25.5% ± 19.5%, respectively, significant for basal and CR. CONCLUSIONS: Considerable differences in the recommendations for changes in insulin dosing were observed among physicians. Since automated recommendations by the Advisor Pro were similar to those given by physicians, it could be considered a useful tool to manage T1D.

Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature.

Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the discovery of new molecules, such as micro ribonucleic acids (micro-RNAs, miRNAs), as well as their interactions with T1DM, has spurred novel prospects in the diagnosis of the disease. This review aims at summarizing current knowledge regarding miRNAs' biosynthesis and action pathways and their role as gene expression regulators in T1DM. MiRNAs follow a complex biosynthesis pathway, including cleaving and transport from nucleus to cytoplasm. After assembly of their final form, they inhibit translation or cause messenger RNA (mRNA) degradation, resulting in the obstruction of protein synthesis. Many studies have reported miRNA involvement in T1DM pathogenesis, mainly through interference with pancreatic b-cell function, insulin production and secretion. They are also found to contribute to ß-cell destruction, as they aid in the production of autoreactive agents. Due to their elevated accumulation in various biological specimens, as well as their involvement in T1DM pathogenesis, their role as biomarkers in early preclinical T1DM diagnosis is widely hypothesized, with future studies concerning their diagnostic value deemed a necessity.

Pathogenic and Low-Frequency Variants in Children With Central Precocious Puberty.

Background: Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in MKRN3, DLK1, KISS1, and KISS1R genes were investigated in patients with CPP. Methods: Fifty-four index girls and two index boys with CPP were first tested by Sanger sequencing for the MKRN3 gene. All children found negative (n = 44) for the MKRN3 gene were further investigated by whole exome sequencing (WES). In the latter analysis, the status of variants in genes known to be related with pubertal timing was compared with an in-house Cypriot control cohort (n = 43). The identified rare variants were initially examined by in silico computational algorithms and confirmed by Sanger sequencing. Additionally, a genetic network for the MKRN3 gene, mimicking a holistic regulatory depiction of the crosstalk between MKRN3 and other genes was designed. Results: Three previously described pathogenic MKRN3 variants located in the coding region of the gene were identified in 12 index girls with CPP. The most prevalent pathogenic MKRN3 variant p.Gly312Asp was exclusively found among the Cypriot CPP cohort, indicating a founder effect phenomenon. Seven other CPP girls harbored rare likely pathogenic upstream variants in the MKRN3. Among the 44 CPP patients submitted to WES, nine rare DLK1 variants were identified in 11 girls, two rare KISS1 variants in six girls, and two rare MAGEL2 variants in five girls. Interestingly, the frequent variant rs10407968 (p.Gly8Ter) of the KISS1R gene appeared to be less frequent in the cohort of patients with CPP. Conclusion: The results of the present study confirm the importance of the MKRN3-imprinted gene in genetics of CPP and its key role in pubertal timing. Overall, the results of the present study have emphasized the importance of an approach that aligns genetics and clinical aspects, which is necessary for the management and treatment of CPP.

Update on the Crosstalk Between Adipose Tissue and Mineral Balance in General Population and Chronic Kidney Disease.

Adipose tissue is nowadays considered as a major endocrine organ, which apart from controlling lipid metabolism, displays a significant role in energy expenditure, food intake and in the regulation of various systemic physiological processes. Adipose derived pro-inflammatory cytokines and adipokines, particularly leptin and adiponectin, provide inter-communication of adipose tissue with various metabolic pathways, ultimately resulting in a complex network of interconnected organ systems. Recent clinical and experimental research has been focused on exploring the direct interaction between adipokine profile and elements of mineral metabolism, including parathormone (PTH), fibroblast growth factor-23 (FGF23) and calcitriol. The emerging crosstalk between adipose tissue and calcium and phosphorus homeostasis suggests that metabolic disorders from one system may directly affect the other and vice versa. It is current knowledge that fat metabolism disturbance, commonly encountered in obese individuals, influences the expression of calciotriopic hormones in general population, while various clinical trials attempting to successfully achieve body fat loss by modulating mineral profile have been published. In chronic kidney disease (CKD) state, there is an increasing evidence suggesting that mineral disorders, influence adipose tissue and linked endocrine function. On the contrary, the impact of disturbed fat metabolism on CKD related mineral disorders has been also evocated in clinical studies. Recognizing the pathogenetic mechanisms of communication between adipose tissue and mineral balance is critical for understanding the effects of metabolic perturbations from the one system to the other and for identifying possible therapeutic targets in case of disrupted homeostasis in one of the two connected systems. To that end, this review aims to enlighten the recent advances regarding the interplay between mineral metabolism, fat mass and adipokine profile, based on in vitro, in vivo and clinical studies, in general population and in the course of CKD.

Association Between Secondary Hyperparathyroidism and Body Composition in Pediatric Patients With Moderate and Advanced Chronic Kidney Disease.

Objective: This single center cross-sectional study aims to investigate the association between secondary hyperparathyroidism and body composition in pediatric patients with moderate (stage 3) and advanced (stage 4-5) chronic kidney disease (CKD). Methods: 61 patients (median age: 13.4 years) were included. Body composition indices, including lean tissue index (LTI) and fat tissue index (FTI), were measured using multi-frequency bio-impedance spectroscopy. Muscle wasting was defined as LTI adjusted to height-age (HA) z-score < -1.65 SD and high adiposity as FTI z-score > 1.65 SD. Serum mineral metabolism parameters, including serum intact parathormone (iPTH), calcium, phosphorus and 25-hydroxyvitamin D, as well as serum leptin were measured in each patient. In advanced CKD patients, the mean values of serum mineral laboratory parameters of the 6 months prior to body composition assessment were recorded, and alfacalcidol index, defined as weekly alfacalcidol dose (mcg/week) per pg/ml of iPTH × 1,000, was calculated. Results: In moderate CKD (31 patients), high iPTH (>90 ng/ml) was observed in 10 (32.3%) patients and was associated with higher FTI z-score (p = 0.022). Moreover, serum iPTH was negatively correlated to LTI HA z-score (rs = -0.486, p = 0.006), and positively correlated to serum leptin levels (rs = 0.369, p = 0.041). The positive correlation between FTI z-score and iPTH (rs = 0.393, p = 0.039) lost significance after adjustment for serum leptin. iPTH was positively associated with high adiposity (12 patients, 38.7%) after adjustment for the other mineral metabolism parameters (OR 1.023, 95% CI 1.002-1.045, p = 0.028). In advanced CKD (30 patients), no significant correlation was observed between iPTH and body composition indices and serum leptin levels. Eleven (36.7%) patients with muscle wasting presented lower alfacalcidol index (p = 0.017). Alfacalcidol index ≤ 24 was strongly associated with muscle wasting after adjustment for CKD stage and other mineral metabolism parameters (OR 7.226, 95% CI 1.150-45.384, p = 0.035). Conclusion: Secondary hyperparathyroidism is associated with high adiposity in moderate but not in advanced CKD, with leptin acting as a potential contributive factor. In advanced CKD, targeting higher alfacalcidol weekly dose per each unit of serum PTH seems beneficial for preventing muscle wasting.

Subcutaneous Fat Necrosis and Hypercalcemia with Nephrocalcinosis in Infancy: Case Report and Review of the Literature.

Subcutaneous fat necrosis is an uncommon benign panniculitis affecting more commonly full-term newborns. It has been associated with birth asphyxia and meconium aspiration, as well as therapeutic hypothermia. Although the prognosis is generally favorable, complications such as hypercalcemia, thrombocytopenia, hypoglycemia and hypertriglyceridemia may complicate its course. The most serious complication is hypercalcemia that may reach life threatening levels and can be associated with nephrocalcinosis. We thereby describe a case of subcutaneous fat necrosis after therapeutic hypothermia, which presented with late-onset refractory severe hypercalcemia and persistent nephrocalcinosis during the follow up of the patient. Due to the risk of the development of chronic kidney disease, we highlight the importance of careful monitoring of hypercalcemia and review the literature of subcutaneous fat necrosis related to nephrocalcinosis.