Journal Of Pediatric Endocrinology & Metabolism[JOURNAL]
Sun
5 papers
Perinatal metabolic inflammation in the hypothalamus impairs the development of homeostatic feeding circuitry.
Ullah R, Shen Y, Zhou YD … +1 more , Fu J
Metabolism · 2023 Oct · PMID 37543245 · Publisher ↗
Over the past few decades, there has been a global increase in childhood obesity. This rise in childhood obesity contributes to the susceptibility of impaired metabolism during both childhood and adulthood. The hypothala...
Over the past few decades, there has been a global increase in childhood obesity. This rise in childhood obesity contributes to the susceptibility of impaired metabolism during both childhood and adulthood. The hypothalamus, specifically the arcuate nucleus (ARC), houses crucial neurons involved in regulating homeostatic feeding. These neurons include proopiomelanocortin (POMC) and agouti-related peptide (AGRP) secreting neurons. They play a vital role in sensing nutrients and metabolic hormones like insulin, leptin, and ghrelin. The neurogenesis of AGRP and POMC neurons completes at birth; however, axon development and synapse formation occur during the postnatal stages in rodents. Insulin, leptin, and ghrelin are the essential regulators of POMC and AGRP neurons. Maternal obesity and postnatal overfeeding or a high-fat diet (HFD) feeding cause metabolic inflammation, disrupted signaling of metabolic hormones, netrin-1, and neurogenic factors, neonatal obesity, and defective neuronal development in animal models; however, the mechanism is unclear. Within the hypothalamus and other brain areas, there exists a wide range of interconnected neuronal populations that regulate various aspects of feeding. However, this review aims to discuss how perinatal metabolic inflammation influences the development of POMC and AGRP neurons within the hypothalamus.
Effect of bariatric surgery on cardio-psycho-metabolic outcomes in severe obesity: A randomized controlled trial.
Koschker AC, Warrings B, Morbach C … +11 more , Seyfried F, Jung P, Dischinger U, Edelmann F, Herrmann MJ, Stier C, Frantz S, Malzahn U, Störk S, Fassnacht M, WAS study group
Metabolism · 2023 Oct · PMID 37393945 · Publisher ↗
OBJECTIVE: Randomized evidence comparing the cardiovascular effects of surgical and conservative weight management is lacking. PATIENTS & METHODS: In this single-center, open-label randomized trial, obese patients with i...
OBJECTIVE: Randomized evidence comparing the cardiovascular effects of surgical and conservative weight management is lacking. PATIENTS & METHODS: In this single-center, open-label randomized trial, obese patients with indication for Roux-en-Y gastric bypass (RYGB) and able to perform treadmill cardiopulmonary exercise testing (CPET) were included. After a 6-12 month run-in phase of multimodal anti-obesity treatment, patients were randomized to RYGB or psychotherapy-enhanced lifestyle intervention (PELI) and co-primary endpoints were assessed 12 months later. Thereafter, PELI patients could opt for surgery and patients were reassessed 24 months after randomization. Co-primary endpoints were mean change (95 % confidence intervals) in peak VO (ml/min/kg body weight) in CPET and the physical functioning scale (PFS) of the Short Form health survey (SF-36). RESULTS: Of 93 patients entering the study, 60 were randomized. Among these (median age 38 years; 88 % women; mean BMI 48·2 kg/m), 46 (RYGB: 22 and PELI: 24) were evaluated after 12 months. Total weight loss was 34·3 % after RYGB vs. 1·2 % with PELI, while peak VO increased by +4·3 ml/min/kg (2·7, 5·9) vs +1·1 ml/min/kg (-0·2, 2·3); p < 0·0001. Respective improvement in PFS score was +40 (30, 49) vs +10 (1, 15); p < 0·0001. 6-minute walking distance also favored the RYGB group: +44 m (17, 72) vs +6 m (-14, 26); p < 0·0001. Left ventricular mass decreased after RYGB, but not with PELI: -32 g (-46, -17) vs 0 g (-13,13); p < 0·0001. In the non-randomized follow-up, 34 patients were assessed. Favorable changes were sustained in the RYGB group and were repeated in the 15 evaluated patients that opted for surgery after PELI. CONCLUSIONS: Among adults with severe obesity, RYGB in comparison to PELI resulted in improved cardiopulmonary capacity and quality of life. The observed effect sizes suggest that these changes are clinically relevant.
Diagnosis, treatment-monitoring and follow-up of children and adolescents with X-linked hypophosphatemia (XLH).
Rothenbuhler A, Schnabel D, Högler W … +1 more , Linglart A
Metabolism · 2020 Feb · PMID 30928313 · Publisher ↗
Early diagnosis, optimal therapeutic management and regular follow up of children with X-linked hypophosphatemia (XLH) determine their long term outcomes and future quality of life. Biochemical screening of potentially a...
Early diagnosis, optimal therapeutic management and regular follow up of children with X-linked hypophosphatemia (XLH) determine their long term outcomes and future quality of life. Biochemical screening of potentially affected newborns in familial cases and improving physician's knowledge on clinical signs, symptoms and biochemical characteristics of XLH for de novo cases should lead to earlier diagnosis and treatment initiation. The follow-up of children with XLH includes clinical, biochemical and radiological monitoring of treatment (efficacy and complications) and screening for XLH-related dental, neurosurgical, rheumatological, cardiovascular, renal and ENT complications. In 2018, the European Union approved the use of burosumab, a humanized monoclonal anti-FGF23 antibody, as an alternative therapy to conventional therapy (active vitamin D analogues and phosphate supplements) in growing children with XLH and insufficiently controlled disease. Diagnostic criteria of XLH and the principles of disease management with conventional treatment or with burosumab are reviewed in this paper.
Use of BMI as the marker of adiposity in a metabolic syndrome severity score: Derivation and validation in predicting long-term disease outcomes.
Gurka MJ, Filipp SL, Musani SK … +2 more , Sims M, DeBoer MD
Metabolism · 2018 Jun · PMID 29410278 · Full text
BACKGROUND: Estimates of adiposity in evaluating the metabolic syndrome (MetS) have traditionally utilized measures of waist circumference (WC), whereas body mass index (BMI) is more commonly used clinically. Our objecti...
BACKGROUND: Estimates of adiposity in evaluating the metabolic syndrome (MetS) have traditionally utilized measures of waist circumference (WC), whereas body mass index (BMI) is more commonly used clinically. Our objective was to determine if a MetS severity Z-score employing BMI as its measure of adiposity (MetS-Z-BMI) would perform similarly to a WC-based score (MetS-Z-WC) in predicting future disease. METHODS: To formulate the MetS-Z-BMI, we performed confirmatory factor analysis on a sex- and race/ethnicity-specific basis on MetS-related data for 6870 adult participants of the National Health and Nutrition Survey 1999-2010. We then validated this score and compared it to MetS-Z-WC in assessing correlations with future coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM) using Cox proportional hazard analysis of 13,094 participants of the Atherosclerosis Risk in Communities study and Jackson Heart Study. RESULTS: Loading factors, which represent the relative contribution of each component to the latent MetS factor, were lower for BMI than for WC in formulating the two respective scores (MetS-Z-BMI and MetS-Z-WC). Nevertheless, MetS-Z-BMI and MetS-Z-WC exhibited similar hazard ratios (HR) toward future disease. For each one standard-deviation-unit increase in MetS-Z-BMI, HR for CHD was 1.76 (95% confidence interval [CI]: 1.65, 1.88) and HR for T2DM was 3.39 (CI 3.16, 3.63) (both p < 0.0001). There were no meaningful differences between the MetS-Z-WC and MetS-Z-BMI scores in their associations with future CHD and T2DM. CONCLUSIONS: A MetS severity Z-score utilizing BMI as its measure of adiposity operated similarly to a WC-based score in predicting future CHD and T2DM, suggesting overall similarity in MetS-based risk as estimated by both measures of adiposity. This indicates potential clinical usefulness of MetS-Z-BMI in assessing and following MetS-related risk over time.
Effects of prolonged administration of ultralente insulin on fasting and postbreakfast beta-cell function in normal adults.
Coutant R, Carel JC, Aubry V … +4 more , Lahlou N, Krokowski M, Boitard C, Bougnères PF
Metabolism · 2000 Oct · PMID 11079810 · Publisher ↗
Treatment with small doses of subcutaneous insulin is being investigated as a possible approach to prevent type 1 diabetes in humans. The mechanism of prophylactic insulin therapy could involve the inhibition of beta-cel...
Treatment with small doses of subcutaneous insulin is being investigated as a possible approach to prevent type 1 diabetes in humans. The mechanism of prophylactic insulin therapy could involve the inhibition of beta-cell secretory activity and/or the initiation of an active immunoregulatory process. To evaluate the pure metabolic effect of exogenous insulin, the present study assessed whether daily subcutaneous administration of ultralente insulin alters beta-cell function in normal adults. Fourteen healthy adults were randomized to receive 0.2 U/kg x d ultralente insulin (Ultratard; Novo Nordisk, Bagsvaerd, Denmark) or placebo subcutaneously once daily for 30 days. Plasma glucose, C-peptide, and insulin concentrations were measured in the fasting state and 1 hour after a standardized breakfast, during treatment and during a recovery period of 10 days. Insulin administration induced a 15% to 40% decrease of fasting plasma C-peptide. In contrast, postbreakfast plasma C-peptide increased by 40% to 90% in subjects receiving insulin. Fasting and postbreakfast C-peptide concentrations were significantly different between groups during the injection period after adjustment for baseline concentrations (P < .05, ANOVA with repeated measures). These alterations disappeared 3 days after cessation of insulin treatment. The present regimen of exogenous insulin alters endogenous insulin secretion in normal subjects. Instead of the expected beta-cell rest, the effect appeared to be dual, with insulin secretion decreasing in the basal state and increasing after meals.
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