Metabolic Control Research Articles

The Relationship Between Age at Diabetes Onset and Clinical Outcomes in Newly Diagnosed Type 2 Diabetes: A Real-World Two-Center Study.

This study was developed with the goal of clarifying whether there is any relationship between type 2 diabetes mellitus (T2DM) age of onset and clinical outcomes for patients in National Metabolic Management Centers (MMC). From September 2017 - June 2022, 864 total T2DM patients were recruited in MMC and assigned to those with early-onset and late-onset diabetes (EOD and LOD) based on whether their age at disease onset was ≤ 40 or > 40 years. All patients received standardized management. Baseline and 1-year follow-up data from these two groups of patients were assessed. Associations between onset age and other factors were evaluated with a multivariate linear regression approach, adjusting for appropriate covariates. Outcomes in particular subgroups were also assessed in stratified analyses. Markers of dysregulated glucose metabolism and BMI values were significantly higher among EOD patients as compared to LOD patients. Subjects in both groups exhibited significant improvements in several disease-related parameters on 1-year follow-up after undergoing metabolic management. EOD patients exhibited significantly greater percentage reductions in HbA1c levels (-28.49 (-44.26, -6.45)% vs -13.70 (-30.15,-1.60)%, P =0.017) relative to LOD patients following adjustment for confounders. Significant differences were also detected between these groups when focused on subgroups of patients who were male, exhibited a BMI ≥ 25, an HbA1c ≥ 9, or had a follow-up frequency < 2. Data from a 1-year follow-up time point suggest that a standardized metabolic disease management model can promote effective metabolic control in newly diagnosed T2DM patients, particularly among individuals with EOD.

Current Advances and Material Innovations in the Search for Novel Treatments of Phenylketonuria.

Phenylketonuria (PKU) is a genetically inherited disease caused by a mutation of the gene encoding phenylalanine hydroxylase (PAH) and is the most common inborn error of amino acid metabolism. A deficiency of PAH leads to increased blood and brain levels of phenylalanine (Phe), which may cause permanent neurocognitive symptoms and developmental delays if untreated. Current management strategies for PKU consist of early detection through neonatal screening and implementation of a restrictive diet with minimal amounts of natural protein in combination with Phe-free supplements and low-protein foods to meet nutritional requirements. For milder forms of PKU, oral treatment with synthetic sapropterin (BH4), the cofactor of PAH, may improve metabolic control of Phe and allow for more natural protein to be included in the patient's diet. For more severe forms, daily injections of pegvaliase, a PEGylated variant of phenylalanine ammonia-lyase (PAL), may allow for normalization of blood Phe levels. However, the latter treatment has considerable drawbacks, notably a strong immunogenicity of the exogenous enzyme and the attached polymeric chains. Research for novel therapies of PKU makes use of innovative materials for drug delivery and state-of-the-art protein engineering techniques to develop treatments which are safer, more effective, and potentially permanent.

Efficacy of continuous glucose monitoring for finding unusual causes of hyperglycemia: a clinical case

Diabetes is a chronic condition that requires constant blood glucose self-monitoring. The carbohydrate metabolism compensation is usually assessed by the level of glycated hemoglobin. But it does not always help reveal the true cause of poor glycemic control. The devices for continuous glucose monitoring allows to assess blood glucose level in real time and find unusual causes of hyper- and hypoglycemia. Achieving target glycemic levels is influen­ced by many factors: age of patients, duration of diabetes, eating habits and eating disorders, level of education, patient’s understan­ding of the diabetes course. One of the reasons for not reaching the target levels of glycemia can be hyperphagic eating disorders, such as night eating syndrome. According to the American Psychiatric Association classification, night eating syndrome belongs to the category of “Other specified eating disorders”. Diagnostic criteria in this syndrome include consumption of &gt; 25 % of food from the daily diet after dinner or at least 2 cases per week of food consumption at night; awareness of these episodes; and at least 3 of the following: morning anorexia, uncontrollable desire to eat between dinner and sleep or at night, conviction that eating will help you fall asleep or return to sleep, insomnia and/or bad mood in the morning. The prevalence of night eating syndrome in the general population is 1.1 %, and in those who refer to metabolic surgery specialists, it is 2–20 %. The presence of night eating syndrome in diabetes adversely affects metabolic control and complicates the management of these patients, in particular, they have higher levels of HbA1c, blood pressure and body mass index compared to individuals without such eating disorder. In this case report, we describe a patient with poor glycemic control who used continuous glucose monitor and was diagnosed with night eating syndrome that helped change management and achieve normoglycemia in the evening and nighttime.

Bone marrow mesenchymal stem cell and mononuclear cell combination therapy in patients with type 2 diabetes mellitus: a randomized controlled study with 8-year follow-up.

To investigate the long-term effects of combining bone marrow mesenchymal stem cells (MSCs) with mononuclear cells (MCs) in the treatment of type 2 diabetes mellitus (T2DM). T2DM patients were divided into the combination group (Dual MSC + MC, n = 33), the mononuclear cell group (MC-Only, n = 32) and the control group (Control, n = 31). All groups were treated with insulin and metformin. The Dual MSC + MC group additionally received MSC and MC infusion and the MC-Only group additionally received MC infusion. The patients were followed up for 8 years. The primary endpoint was the C-peptide area under the curve (C-p AUC) at 1 year. This study was registered with clinicaltrial.gov (NCT01719640). A total of 97 patients were included and 89 completed the follow-up. The area under the curve of C-peptide of the Dual MSC + MC group and the MC-Only group was significantly increased (50.6% and 32.8%, respectively) at 1 year. After eight years of follow-up, the incidence of macrovascular complications was 13.8% (p = 0.009) in the Dual MSC + MC group and 21.4% (p = 0.061) in the MC-Only group, while it was 44.8% in the Control group. The incidence of diabetic peripheral neuropathy (DPN) was 10.3% (p = 0.0015) in the Dual MSC + MC group, 17.9% (p = 0.015) in the MC-Only group, and 48.3% in the Control group. The combination of MSC and MC therapy can reduce the incidence of chronic diabetes complications and improves metabolic control with mild side effects in T2DM patients.

EFFECTIVENESS OF CONTINUOUS GLUCOSE MONITORING IN UNCONTROLLED TYPE-2 DIABETICS IN TERTIARY HEALTHCARE CENTRE

Long term diabetic complications can be prevented or reduced by achieving good metabolic control, reflected by HbA1c &lt;6.5–7.0%.1-3 Glucose excursions might also contribute to the development of diabetic complications.4,5 Fear of hypoglycemia limits the ability to reach strict glycemic control, because it is usually accompanied by reluctance of the patient to intensify insulin therapy. Indeed, the goal of intensive therapy is to normalize HbA1c and control fasting and postprandial glycemia, while concurrently limiting the number and severity of hypoglycemic events. To reach tight glycemic control, frequent self- monitoring of blood glucose (SMBG) must be performed.6 SMBG devices provide the patient with accurate but discreet blood glucose levels. They do not provide trend information nor do they reflect glycemic fluctuations, which is possible by using continuous glucose monitoring (CGM) systems. Thus, implementation of strict glycemic control may be facilitated by a CGM device. This manuscript critically reviews the proposed benefits and indications of CGM and the current evidence of CGM on health outcomes in diabetic patients.

Why is it necessary to screen for periodontal disease in diabetic patients?

Periodontal diseases include gingivitis (inflammation of gingiva caused by the bacterial biofilm) and periodontitis involving loss of the supporting structures around the teeth, respectively cementum, periodontal ligament and alveolar bone. Diabetes increases the risk of periodontal diseases; the plausible mechanisms are: alterations in the immunoinflammatory response of bacteria, increased bone loss, the decrease in matrix-producing cells to maintain the periodontium, microvascular changes and alteration in collagen synthesis and metabolism. Treatment of periodontitis influence glycemic control in diabetic patients and intervention trial suggests that this can generate a reduction of circulating inflammatory markers and improves metabolic control in diabetic patients. International forums recommend oral examination as a component of medical care for diabetic patients. Our review summarizes current information on the association of diabetes with periodontal disease.

Common Hyperglycemia Susceptibility Loci in Metabolic Syndrome Patients from Karachi, Pakistan: A Cross Sectional Study

Background: More than 75 genetic susceptibility loci have been implicated with hyperglycemia. SNPs in genes linked with satiety, insulin sensitivity, BMR (Adiponectin, FTO, and MC4R), and inflammation and autoimmunity (TNF-a) have been shown to have a relationship with metabolic syndrome. Objectives: To measure the frequency of ADIPOQ, FTO, MCR4, and TNF SNPs in metabolic syndrome patients and controls, and to assess the association of these with hyperglycemia and adiposity status. Methods: A cross-sectional study was conducted. Baseline investigations including lipid profiles, blood glucose levels, and BMI calculation were conducted for n=113 Metabolic Syndrome and n=47 healthy controls. Tetra ARMS PCR and gel electrophoresis were conducted for Adiponectin rs266729, Adiponectin rs1501299, FTO rs9939609, MCR4 rs1297013, and TNF rs1800629. Statistical analysis was performed using SPSS version 26. Results: Difference was observed in lipid profiles (including LDL, triglycerides, and cholesterol but not HDL), body fat percentage (p= 0.034), and both fasting (p=0.000) and random (p=0.000) blood glucose levels among metabolic syndrome patients versus controls. Adiponectin rs1501299, FTO rs9939609, and MCR4 rs1297013 showed genotype frequency differences between groups. Spearman’s correlation was applied to test any association of risk allele with study variables and MCR4 rs1297013 showed an independent association with Fasting Blood Glucose Level (r=0.238; p=0.024) irrespective of age, weight, or gender. Conclusion: MCR4 rs1297013 polymorphism is an independent risk factor leading to hyperglycemia in the study population, however, no other SNPs were identified to carry a significant risk. Large-scale genome-wide studies are required to identify the unique set of risk genes for the Pakistani population

Insulin Signaling Pathway Mediates FoxO-Pepck Axis Regulation of Glucose Homeostasis in Drosophila suzukii.

The agricultural pest Drosophila suzukii exhibits a strong preference for feeding on fresh fruits, demonstrating high adaptability to sugary environments. Meanwhile, high sugar levels stimulate insulin secretion, thereby regulating the steady state of sugar metabolism. Understanding the mechanisms related to sugar metabolism in D. suzukii is crucial due to its adaptation to these specific environmental conditions. The insulin signaling pathway is an evolutionarily conserved phosphorylation cascade with significant roles in development and metabolism. We observed that the activation of the insulin signaling pathway inhibited FoxO activity and downregulated the expression of Pepck, thereby activating glycolysis and reducing glucose levels. By contrast, inhibiting insulin signaling increased the FoxO activity and upregulated the expression of Pepck, which activated gluconeogenesis and led to increased glucose levels. Our findings demonstrated the crucial role of the insulin signaling pathway in mediating glucose metabolism through the FoxO-Pepck axis, which supports the ecological adaptation of D. suzukii to high-sugar niches, thereby providing insights into its metabolic control and suggesting potential strategies for pest management. Elucidating these molecular processes is important for understanding metabolic regulation and ecological specialization in D. suzukii.

Polycystic ovary syndrome and type 1 diabetes - the current state of knowledge.

Type 1 diabetes mellitus (T1DM) is characterized by an increased prevalence of polycystic ovary syndrome (PCOS) with its negative metabolic consequences, including increased cardiovascular risk. Both diseases affect patients, significantly deteriorating the quality of life. During the treatment of patients with T1DM and PCOS, lifestyle modification and increased physical activity resulting in weight reduction should always be recommended. Pharmacological treatment should be applied in accordance with the current standards. In most of these patients metformin alone or with combined oral contraceptive pills could be considered for cycle regulation. In obese patients with T1DM and PCOS glucagon-like peptide-1 receptor agonists (GLP-1 Ras) (liraglutide, semaglutide) and dual glucose-dependent insulinotropic polypeptides (GIP)/GLP-1 RAs (tirzepatide) are regarded as a safe approach. Anti-androgens could also be considered especially to treat hirsutism and hyperandrogenism in women with PCOS. There are relatively limited evidence on anti-androgens in PCOS and we should consider use them in only selected cases. Some other substances may have a positive effect on patients with T1DM and PCOS include inositol, alpha-lipoic acid, folic acid, vitamins (B1, B6, B12, D, K, E, A), chromium and selenium compounds, as well as omega-3 fatty acids. The gut microbiome is also considered as a critical modulator of the predisposition to PCOS and T1DM and may be the future goal of the treatment. The proper treatment of PCOS will translate into a reduction in the severity of typical symptoms and also into the improvement in the metabolic control of diabetes and the patients' quality of life.

Characteristics of people with type 1 diabetes influence the educational process for starting insulin pump therapy: an observational study.

Limited data exist on educational programs for people using insulin pump (IP) therapy or those considering its initiation, and the influence of individual characteristics on their educational pathway remains unclear. Our aim was to analyze the characteristics of people with type 1 diabetes (T1D) referred for IP therapy and how these characteristics may influence their educational process. A retrospective descriptive observational study was carried out on people with T1D referred for participation in a structured pre-IP educational program in a hospital setting. Educational, sociodemographic and clinical variables were collected and analyzed. Participants were followed up 5 years after IP placement. Seventy-one people finalized the educational program, of whom 10 experienced major barriers to completing it. People with lower educational level required more sessions and weeks to complete it compared to those with higher educational levels. People referred due to suboptimal metabolic control and hypoglycemia also required more time to complete the process. It is essential for diabetes educators to recognize the diversity of characteristics, needs and challenges among the participants in an educational program. Based on this, they must adapt strategies to provide more effective, person-centered diabetes education and support, fostering positive and sustained outcomes and engagement for participants.

Carbohydrate Counting: A Bibliometric Analysis with a Focus on Research.

Diabetes is a metabolic disease characterized by hyperglycemia due to impaired insulin secretion, activity, or both. Carbohydrate counting, known for optimal metabolic control, plays in the therapeutic strategy in diabetes. In the last decade, an increasing amount of research has been conducted on carbohydrate counting, and the literature on this topic has been published in academic journals. This bibliometric analysis aimed to comprehensively review and analyze publications from this period, shedding light on trends, developments, and key contributors. The Expanded Science Citation Index published by the Institute for Scientific Information Web of Science, which covers English-language articles published from 1993 to 2024, was used. We selected "carbohydrate counting", "carbohydrate count", "carbohydrate counts", "carbohydrate counts", and similar words as "TOPIC" to search for related articles. All basic information about each article were collected, including authors, countries, citations, and keywords. The findings emphasized the need for continued research in this area and to learn more about studies showing the relationship between carbohydrate counting and the pathophysiology of diabetes, treatment, complications, and technologies. This analysis summarizes the general trends and key findings of research on carbohydrate counting over the past years and provides guidance for future research.

Protein Extraction Methods Suitable for Muscle Tissue Proteomic Analysis.

Muscle tissue is one of the most dynamic and plastic tissues of the mammalian body and covers different roles, such as force generation and metabolic control. Muscular proteomics provides an important opportunity to reveal the molecular mechanisms behind muscle pathophysiology. To ensure successful proteomic analysis, it is necessary to have an efficient and reproducible protein extraction method. This study aimed to evaluate the efficacy of two different extraction protocols of muscle samples for two-dimensional gel electrophoresis. In particular, mouse muscle proteins were extracted by an SDS-based buffer (Method A) and by a UREA/CHAPS/DTE/TRIS solution (Method B). The efficacies of the methods were assessed by performing an image analysis of the 2DE gels and by statistical and multivariate analyses. The 2DE gels in both preparations showed good resolution and good spot overlapping. Methods A and B produced 2DE gels with different means of total spots, higher for B. Image analysis showed different patterns of protein abundance between the protocols. The results showed that the two methods extract and solubilize proteins with different chemical-physical characteristics and different cellular localizations. These results attest the efficacy and reproducibility of both protein extraction methods, which can be parallelly applied for comprehensive proteomic profiling of muscle tissue.

Toxin-mediated depletion of NAD and NADP drives persister formation in a human pathogen

Toxin–antitoxin (TA) systems are widespread in bacteria and implicated in genome stability, virulence, phage defense, and persistence. TA systems have diverse activities and cellular targets, but their physiological roles and regulatory mechanisms are often unclear. Here, we show that the NatR–NatT TA system, which is part of the core genome of the human pathogen Pseudomonas aeruginosa, generates drug-tolerant persisters by specifically depleting nicotinamide dinucleotides. While actively growing P. aeruginosa cells compensate for NatT-mediated NAD+ deficiency by inducing the NAD+ salvage pathway, NAD depletion generates drug-tolerant persisters under nutrient-limited conditions. Our structural and biochemical analyses propose a model for NatT toxin activation and autoregulation and indicate that NatT activity is subject to powerful metabolic feedback control by the NAD+ precursor nicotinamide. Based on the identification of natT gain-of-function alleles in patient isolates and on the observation that NatT increases P. aeruginosa virulence, we postulate that NatT modulates pathogen fitness during infections. These findings pave the way for detailed investigations into how a toxin–antitoxin system can promote pathogen persistence by disrupting essential metabolic pathways.

Unique Characteristics of Adipocytes in Metabolic Health: Insights and Implications

Adipocytes secrete a wide range of bioactive peptides known as adipokines. These factors play a crucial role in the complex network of metabolic control that connects adipose tissue activity with systemic metabolic balance. The intricacy of adipokine signalling networks and their relationships with other bodily metabolic regulators is also highlighted in this study. Although adipokines are necessary for healthy metabolism, the pathophysiology of various metabolic illnesses, such as obesity, type 2 diabetes, and cardiovascular diseases, are associated with their dysregulation. We explored the effects of changes in adipokine function and levels that affect various disorders, providing a detailed picture of the pathophysiology. This review also delves into the potential of adipokine as a metabolic illness biomarker, including its prognostic and diagnostic potential. Moreover, it assesses the potential therapeutic benefits of regulating adipokine activity and explores present and upcoming approaches to target these molecules to enhance metabolic health. Overall, This study emphasizes the many functions of adipokines in several metabolic processes, such as insulin sensitivity, lipid metabolism, glucose regulation, and inflammation. Additionally, it offers a comprehensive and insightful understanding of adipokines, emphasizing their pivotal role in metabolic well-being and disease.

Maternal diet during pregnancy and adaptive changes in the maternal and fetal pancreas have implications for future metabolic health.

Fetal and neonatal development is a critical period for the establishment of the future metabolic health and disease risk of an individual. Both maternal undernutrition and overnutrition can result in abnormal fetal organ development resulting in inappropriate birth size, child and adult obesity, and increased risk of Type 2 diabetes and cardiovascular diseases. Inappropriate adaptive changes to the maternal pancreas, placental function, and the development of the fetal pancreas in response to nutritional stress during pregnancy are major contributors to a risk trajectory in the offspring. This interconnected maternal-placental-fetal metabolic axis is driven by endocrine signals in response to the availability of nutritional metabolites and can result in cellular stress and premature aging in fetal tissues and the inappropriate expression of key genes involved in metabolic control as a result of long-lasting epigenetic changes. Such changes result is insufficient pancreatic beta-cell mass and function, reduced insulin sensitivity in target tissues such as liver and white adipose and altered development of hypothalamic satiety centres and in basal glucocorticoid levels. Whilst interventions in the obese mother such as dieting and increased exercise, or treatment with insulin or metformin in mothers who develop gestational diabetes, can improve metabolic control and reduce the risk of a large-for-gestational age infant, their effectiveness in changing the adverse metabolic trajectory in the child is as yet unclear.

Control of tuberal hypothalamic development and its implications in metabolic disorders.

The tuberal hypothalamus regulates a range of crucial physiological processes, including energy homeostasis and metabolism. In this Review, we explore the intricate molecular mechanisms and signalling pathways that control the development of the tuberal hypothalamus, focusing on aspects that shape metabolic outcomes. Major developmental events are discussed in the context of their effect on the establishment of both functional hypothalamic neuronal circuits and brain-body interfaces that are pivotal to the control of metabolism. Emerging evidence indicates that aberrations in molecular pathways during tuberal hypothalamic development contribute to metabolic dysregulation. Understanding the molecular underpinnings of tuberal hypothalamic development provides a comprehensive view of neurodevelopmental processes and offers a promising avenue for future targeted interventions to prevent and treat metabolic disorders.

Integration of metabolomic and transcriptomic analyses reveals novel regulatory functions of the ChREBP transcription factor in energy metabolism.

Carbohydrate Response Element-Binding Protein (ChREBP) is a transcription factor that activates key genes involved in glucose, fructose, and lipid metabolism in response to carbohydrate feeding, but its other potential roles in metabolic homeostasis have not been as well studied. We used liver-selective GalNAc-siRNA technology to suppress expression of ChREBP in rats fed a high fat/high sucrose diet and characterized hepatic and systemic responses by integrating transcriptomic and metabolomic analyses. GalNAc-siChREBP-treated rats had lower levels of multiple short-chain acyl CoA metabolites compared to rats treated with GalNAc-siCtrl containing a non-targeting siRNA sequence. These changes were related to a sharp decrease in free CoA levels in GalNAc-siChREBP treated-rats, accompanied by lower expression of transcripts encoding enzymes and transporters involved in CoA biosynthesis. These activities of ChREBP likely contribute to its complex effects on hepatic lipid and energy metabolism. While core enzymes of fatty acid (FA) oxidation are induced by ChREBP knockdown, accumulation of liver acylcarnitines and circulating ketones indicate diversion of acetyl CoA to ketone production rather than complete oxidation in the TCA cycle. Despite strong suppression of pyruvate kinase and activation of pyruvate dehydrogenase, pyruvate levels were maintained, likely via increased expression of pyruvate transporters, and decreased expression of lactate dehydrogenase and alanine transaminase. GalNAc-siChREBP treatment increased hepatic citrate and isocitrate levels while decreasing levels of distal TCA cycle intermediates. The drop in free CoA levels, needed for the 2-ketoglutarate dehydrogenase reaction, as well as a decrease in transcripts encoding the anaplerotic enzymes pyruvate carboxylase, glutamate dehydrogenase, and aspartate transaminase likely contributed to these effects. GalNAc-siChREBP treatment caused striking increases in PRPP and ZMP/AICAR levels, and decreases in GMP, IMP, AMP, NaNM, NAD(P), and NAD(P)H levels, accompanied by reduced expression of enzymes that catalyze late steps in purine and NAD synthesis. ChREBP suppression also increased expression of a set of plasma membrane amino acid transporters, possibly as an attempt to replenish TCA cycle intermediates. In sum, combining transcriptomic and metabolomic analyses has revealed regulatory functions of ChREBP that go well beyond its canonical roles in control of carbohydrate and lipid metabolism to now include mitochondrial metabolism and cellular energy balance.

Greater urinary calcium excretion is associated with diminished bone accrual in youth with type 1 diabetes

Abstract Context The adverse skeletal effects of type 1 diabetes (T1D) include deficient bone accrual and lifelong increased fracture risk. The contributors to impaired bone accrual in people with T1D are incompletely understood. Objective To determine if urinary calcium excretion is associated with impaired bone accrual in youth with T1D and to characterize the contribution of glycemic control and markers of bone mineral metabolism to urinary calcium excretion. Design Observational study. Participants 50 participants with T1D aged 6-20 years completed a 12-month longitudinal study of bone accrual. A second cohort of 99 similarly aged participants with T1D completed cross-sectional 24-hr urine and blood collections. Main Outcome Measure Whole body less head bone mineral content (WBLH BMC) velocity Z-score and fractional excretion of calcium (FeCa). Results Participants in the bone accrual cohort had lower WBLH BMC velocity compared to a healthy reference dataset (Z-score −0.3 ± 1.0, p=0.03). FeCa was negatively associated with WBLH BMC velocity Z-score, ρ= −0.47, p=0.001. In the urinary calcium excretion cohort, intact parathyroid hormone (β= −0.4, p=0.01), beta c-telopeptide (β=0.35, p=0.007), and either hemoglobin A1c (HbA1c, β=0.08, p=0.03) or urine fractional glucose excretion (β=0.07, p=0.03) were associated with FeCa in multivariable regression models that included known determinants of urinary calcium excretion. Conclusions Urinary calcium excretion was negatively associated with bone accrual in this cohort of youth with T1D. Mechanistic studies are needed to determine if interventions to reduce urinary calcium excretion could increase bone accrual and reduce skeletal fragility in people with T1D.

Body composition in a pediatric population with type-1 diabetes – The importance of planned physical exercise

Objective and methodsThis study aimed to assess the body composition of pediatric patients with type-1 diabetes (T1D) in a Portuguese pediatric endocrinology/diabetic clinic, using the InBody 570 bioimpedance system. Preschool children (<6 years) and those recently diagnosed (<6 months) were excluded. ResultsThe study included 78 patients (53% female). Median age at assessment was 14 years, with 81% pubertal children. Eighty-seven percent were using continuous subcutaneous insulin infusion (CSII), 25% with an automated closed-loop model. Median HbA1c was 7.3%. Most had an adequate body mass index (BMI) standard deviation score (62%) and 48% engaged in regular physical exercise (PE) outside of school. Median percentage body fat (PBF) was 21.5% and was abnormal in 48%, with median visceral adiposity of 4. Despite adequate BMI, 11% had excessive PBF. PBF was significantly associated with visceral fat (r=0.79; P<0.001), female gender (P<0.001) and PE performed out of school (P=0.005). PE was associated with lower PBF (P=0.005), lower visceral fat (P=0.002), and higher muscle-to-fat ratio (P=0.006). ConclusionEngaging in physical exercise out of school correlated significantly with improved body composition, characterized by reduced PBF and diminished visceral adiposity. Considering the known benefits of physical exercise for metabolic and glycemic control, this study highlights the importance of promoting regular physical exercise in T1D patients.

A specific serum lipid signature characterizes patients with glycogen storage disease type Ia

Glycogen storage disease type Ia (GSDIa) is a rare, inherited glucose-6-phosphatase-α (G6Pase-α) deficiency-induced carbohydrate metabolism disorder. Although hyperlipidemia is a hallmark of GSDI, the extent of lipid metabolism disruption remains incompletely understood. Lipidomic analysis was performed to characterize the serum lipidome in patients with GSDIa, by including age- and sex-matched healthy controls and age-matched hypercholesterolemic controls. Metabolic control and dietary information biochemical markers were obtained from patients with GSDIa. Patients with GSDIa showed higher total serum lysophosphatidylcholine (Fold Change, (FC) 2.2, P < 0.0001), acyl-acyl-phosphatidylcholine (FC 2.1, P < 0.0001), and ceramide (FC 2.4, P < 0.0001) levels and bile acid (FC 0.7, P < 0.001), acylcarnitines (FC 0.7, P < 0.001), and cholesterol esters (FC 1.0, P < 0.001) than those of healthy controls, and higher di- (FC 1.1, P < 0.0001; FC 0.9, P < 0.01) and triacylglycerol (FC 6.3, P < 0.0001; FC 3.9, P < 0.01) levels than those of healthy controls and hypercholesterolemic subjects. Both total cholesterol and triglyceride values correlated with Cer (d16:1/22:0), Cer (d18:1/20:0), Cer (d18:1/20:0(OH)), Cer (d18:1/22:0), Cer (d18:1/23:0), Cer (d18:1/24:1), Cer (d18:2/22:0), Cer (d18:2/24:1). Total cholesterol also correlated with Cer (d18:1/24:0), Cer (d18:2/20:0), HexCer (d16:1/22:0), HexCer (d18:1/18:0), and Hex2Cer (d18:1/20:0). Triglyceridelevels correlated with Cer (d18:0/24:1). Alanine aminotransferase values correlated with Cer (d18:0/22:0), insulin with Cer (d18:1/22:1) and Cer (d18:1/24:1), and HDL with hexosylceramide (HexCer) (d18:2/23:0). These results expand on the currently known involvement of lipid metabolism in GSDIa. Circulating Cer may allow for refined dietary assessment compared with traditional biomarkers. Because specific lipid species are relatively easy to assess, they represent potential novel biomarkers of GSDIa.