The long-term efficacy and use of phenylalanine-free infant amino acid formula (PFIF) is understudied. This retrospective, longitudinal study evaluated PFIF (PKU Start: Vitaflo International) in children with phenylketonuria, collecting data on metabolic control, growth, dietary intake, and symptoms and the child\'s experience with PFIF. Twenty-five children (12 males, 48%) with a median age of 3.6 years (2.0-6.2 years) were included. During 24 months follow-up, children maintained normal growth and satisfactory metabolic control. The protein intake from protein substitutes increased from 2.7 at 6 months to 2.8 g/kg/day at 24 months, while natural protein decreased from 0.6 to 0.4 g/kg/day. By 24 months, most children (n = 16, 64%) had stopped PFIF, while nine (36%) continued with a median intake of 450 mL/day (Q1:300 mL, Q3: 560 mL). Children who continued PFIF after 24 months of age had higher energy and fat intakes with higher weight/BMI z-scores compared with those who stopped earlier (p < 0.05). Constipation was reported in 44% of infants but improved with age. Initial difficulty with PFIF acceptance was reported in 20% of infants but also improved with time. Prolonged use of PFIF in pre-school children may contribute to poor feeding patterns and overweight; thus, replacing the majority of the protein equivalent provided by PFIF with a weaning protein substitute by 12 months and discontinuing PFIF before 2 years is recommended.

BACKGROUND: Due to newborn screening and early treatment, patients with phenylketonuria (PKU) and mild hyperphenylalaninemia (mHPA) develop largely normal, in terms of IQ testing and academic attainment. However, the impact of metabolic control in various stages of development on more complex cognitive abilities, i.e. executive functions (EF), is still unclear.
METHODS: EFs were tested in 28 patients with PKU/mHPA, aged 8-17 years, identified by newborn screening and continuously treated. The relation to current (testing day & past 10 phenylalanine (Phe) values) and long-term metabolic control (age periods: childhood <6, 6-10, adolescence >10 years, lifetime Phe) was analyzed.
RESULTS: EFs were in the lower normative range (IQR of T-values: 47.35-51.00). Patients reaction time was significantly slower than the population mean (divided attention/TAP: median 40, p < 0.01). Both, long-term and current metabolic control correlated with performance in EF tests: Higher current Phe impaired reaction times (Go/No-Go, r = -0.387; working memory, r = -0.425; p < 0.05) and performance in planning ability (ToL r = -0.465, p < 0.01). Higher long-term Phe values both in childhood and adolescence mainly affected attention (omissions/TAP r = -0.357 and - 0.490, respectively, both p < 0.05) as well as planning ability (ToL r = -0.422 and - 0.387, adolescence and lifetime, p < 0.05).
CONCLUSIONS: Current and long-term metabolic control in PKU/mHPA, including the adolescent period, influence EFs, especially affecting reaction time and planning abilities. This should be taken into account in patient counselling.

OBJECTIVE: To synthesize the evidence on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adolescents with overweight or obesity.
METHODS: For this systematic review and network meta-analysis, we searched five databases and registries until 2 March 2024 for eligible randomized controlled trials (RCTs). The primary outcome was weight change. We did a pairwise meta-analysis to compare GLP-1RAs and placebo, followed by a drug-wise network meta-analysis (NMA) to compare GLP-1RAs against each other.
RESULTS: We screened 770 records to include 12 RCTs with 883 participants. The evidence suggests that GLP-1RAs reduced weight (mean difference -4.21 kg, 95% confidence interval [CI] -7.08 to -1.35) and body mass index (BMI; mean difference -2.11 kg/m2, 95% CI -3.60 to -0.62). The evidence on waist circumference, body fat percentage and adverse events (AEs) was very uncertain. The results remained consistent with subgroup analyses for coexisting type 2 diabetes. Longer therapy duration led to a greater reduction in weight and BMI. In the NMA, semaglutide led to the greatest weight reduction, followed by exenatide, liraglutide and lixisenatide.
CONCLUSIONS: The evidence suggests that GLP-1RAs reduce most weight-related outcomes in adolescents, with semaglutide being the most efficacious. There is uncertain evidence on body fat and serious AEs, probably due to fewer studies and low incidence, respectively. Larger RCTs with head-to-head comparisons, pragmatic design, adiposity-related outcomes, and economic evaluation can further guide the use and choice of GLP-1RAs.

BACKGROUND: In 2011, a European phenylketonuria (PKU) survey reported that the blood phenylalanine (Phe) levels were well controlled in early life but deteriorated with age. Other studies have shown similar results across the globe. Different target blood Phe levels have been used throughout the years, and, in 2017, the European PKU guidelines defined new targets for blood Phe levels. This study aimed to evaluate blood Phe control in patients with PKU across Europe.
METHODS: nine centres managing PKU in Europe and Turkey participated. Data were collected retrospectively from medical and dietetic records between 2012 and 2018 on blood Phe levels, PKU severity, and medications.
RESULTS: A total of 1323 patients (age range:1-57, 51% male) participated. Patient numbers ranged from 59 to 320 in each centre. The most common phenotype was classical PKU (n = 625, 48%), followed by mild PKU (n = 357, 27%) and hyperphenylalaninemia (HPA) (n = 325, 25%). The mean percentage of blood Phe levels within the target range ranged from 65 ± 54% to 88 ± 49% for all centres. The percentage of Phe levels within the target range declined with increasing age (<2 years: 89%; 2-5 years: 84%; 6-12 years: 73%; 13-18 years: 85%; 19-30 years: 64%; 31-40 years: 59%; and ≥41 years: 40%). The mean blood Phe levels were significantly lower and the percentage within the target range was significantly higher (p < 0.001) in patients with HPA (290 ± 325 μmol/L; 96 ± 24%) and mild PKU (365 ± 224 μmol/L; 77 ± 36%) compared to classical PKU (458 ± 350 μmol/L, 54 ± 46%). There was no difference between males and females in the mean blood Phe levels (p = 0.939), but the percentage of Phe levels within the target range was higher in females among school-age children (6-12 years; 83% in females vs. 78% in males; p = 0.005), adolescents (13-18 years; 62% in females vs. 59% in males; p = 0.034) and adults (31-40 years; 65% in females vs. 41% in males; p < 0.001 and >41 years; 43% in females vs. 28% in males; p < 0.001). Patients treated with sapropterin (n = 222) had statistically significantly lower Phe levels compared to diet-only-treated patients (mean 391 ± 334 μmol/L; percentage within target 84 ± 39% vs. 406 ± 334 μmol/L; 73 ± 41%; p < 0.001), although a blood Phe mean difference of 15 µmol/L may not be clinically relevant. An increased frequency of blood Phe monitoring was associated with better metabolic control (p < 0.05). The mean blood Phe (% Phe levels within target) from blood Phe samples collected weekly was 271 ± 204 μmol/L, (81 ± 33%); for once every 2 weeks, it was 376 ± 262 μmol/L, (78 ± 42%); for once every 4 weeks, it was 426 ± 282 μmol/L, (71 ± 50%); and less than monthly samples, it was 534 ± 468 μmol/L, (70 ± 58%).
CONCLUSIONS: Overall, blood Phe control deteriorated with age. A higher frequency of blood sampling was associated with better blood Phe control with less variability. The severity of PKU and the available treatments and resources may impact the blood Phe control achieved by each treatment centre.

Background: Type 2 diabetes mellitus (T2DM) often leads to cardiac autonomic neuropathy (CAN), a severe complication affecting cardiovascular health. Exercise training is a proven intervention for improving metabolic control and cardiovascular health in T2DM, but the effects of concurrent exercise training (CET), combining aerobic and resistance exercises, on CAN are not fully understood. Objective: This randomized controlled trial investigates the impact of a structured CET program on cardiac autonomic modulation, metabolic profile, body composition, cardiorespiratory fitness (CRF), and quality of life (QoL) in individuals with T2DM and CAN. Methods: A total of 96 participants, aged 35-70 years, with T2DM and CAN, were randomized into CET (n = 48) and control (n = 48) groups. The CET group engaged in combined aerobic and resistance training three times per week for 13 weeks, while the control group received standard care. Primary outcomes included heart rate variability (HRV) and heart rate recovery (HRR). Secondary outcomes were metabolic profile, body composition, CRF, and QoL, which were assessed using standardized protocols and validated questionnaires. The trial was registered with the Clinical Trials Registry-India (CTRI/2021/09/036711). Results: Significant improvements were noted in the CET group compared to controls. HRV metrics (SDNN, RMSSD, pNN50, TP, LF power, HF power, and LF/HF ratio) and HRR metrics (HRR30s, HRR1, HRR2, and HRR3) all showed significant enhancements (p < 0.01). The CET group also exhibited substantial reductions in fasting blood glucose, postprandial blood glucose, HbA1c, waist circumference, hip circumference, and percentage body fat (p < 0.01). Improvements were observed in lipid profile markers and CRF (VO2max) (p < 0.01). QoL scores improved significantly in the CET group as per the ADDQoL-19 (p < 0.01). Conclusions: CET significantly enhances cardiac autonomic modulation, metabolic profile, body composition, CRF, and QoL in individuals with T2DM and CAN. These findings support the integration of CET into standard T2DM management to improve clinical outcomes and QoL. Further research is needed to explore the long-term benefits and broader applicability of CET in diverse diabetic populations.

BACKGROUND: Social jetlag is a chronic disruption of sleep timing that is characterized by different sleep timing during workdays and free days. Social jetlag has been associated with disturbed glucose metabolism, insulin resistance, and increased risk of metabolic syndrome and type 2 diabetes. In this study, we aim to investigate whether a combination of bright light therapy in the morning, bright light reduction in the evening and sleep advance instructions for 3 weeks reduces social jetlag and if this results in improvement of glycemic and metabolic control, sleep, mood and quality of life after 3 and 12 weeks in people with prediabetes and type 2 diabetes and to assess possible mediators, compared to regular sleep habits.
METHODS: In this randomized controlled trial, 60 people with prediabetes or type 2 diabetes with > 1 h social jetlag will be recruited. The intervention consists of bright light therapy (5000 lx) emitted by Vitamine-L (Lumie, UK) for 30 min each morning, combined with the advice to follow sleep advance instructions and to wear bright light-dimming goggles every evening for a period of 3 weeks. The control group adheres to their regular sleep habits and conditions. The primary outcome is glycated hemoglobin (HbA1c) after 12 weeks comparing the intervention and control in an intention-to-treat analysis. Secondary outcomes at 3 and 12 weeks are (1) social jetlag; (2) insulin sensitivity, fasting blood glucose, glucose-lowering medication use, and frequency of perceived hypoglycemia; (3) metabolic outcomes, including body mass index (BMI), waist circumference, body fat percentage, and blood pressure; (4) mood, including depression, fatigue and anxiety (measured with questionnaires); and (5) quality of life measured using EQ5D questionnaire. To assess other factors that might play a role as possible mediators, we will measure (para)sympathetic nervous system activity assessed with ECGs and electrochemical skin conductance tests, sleep quality and sleep phase distribution assessed with a sleep measuring headband (ZMax), the Dim Light Melatonin Onset in saliva samples (in a subgroup) at 3 and 12 weeks, the feeling of satiety and satiation with a 10-cm visual analog scale (VAS), diet using a food frequency questionnaire, and physical activity using an accelerometer (ActiGraph).
CONCLUSIONS: Social jetlag can contribute to poorer glycemic control and metabolic control in those with type 2 diabetes. With this intervention, we aim to reduce social jetlag and thereby improve glycemic and metabolic control. This could offer a way to improve overall population health and to reduce the disease burden of type 2 diabetes.
BACKGROUND: ISRCTN registry ISRCTN11967109 . Registered on 9 May 2024.

UNASSIGNED: This study aimed to assess the relationship between metabolic control factors, socio-demographic characteristics, personality traits, and self-perceived health status in diabetes.
UNASSIGNED: This cross-sectional study included 318 patients with type 1 and 2 diabetes (DM). Participants completed a questionnaire-based survey, which included the NEO Personality Inventory-Revised to measure five personality dimensions and the SF-12 survey to assess self-perceived health status. Binary logistic regression was performed to analyze the data, with socio-demographic characteristics, clinical data, and nutrition status as independent variables, and self-perceived health status (categorized as poor or good condition) as the dependent variable. Unadjusted and adjusted binary logistic regression analyses were used to examine the association between personality traits (high vs. low) and metabolic control factors (good control vs. bad control) with health status scores.
UNASSIGNED: 60.7% of the participants with diabetes in the study described their health as \"good.\" The results indicated that female gender (OR: 0.314, 95%CI: 0.105-0.938, P = 0.038), age > 60 years (OR: 0.263, 95%CI: 0.117-0.592, P = 0.001), comorbidities (OR: 0.314, 95%CI: 0.178-0.556, P = 0.001), DM complications (OR: 0.531, 95%CI: 0.337-0.838, P = 0.007), diabetic neuropathy (OR: 0.562, 95%CI: 0.356-0.886, P = 0.013), and diabetic ulcer (OR: 0.130, 95%CI: 0.023-0.747, P = 0.022) were independent variables associated with a \"poor\" health status. However, regular physical activity (OR: 3.144, 95%CI: 1.209-8.175, P = 0.019) and a healthy nutritional diet (OR: 2.456, 95%CI: 1.421-4.245, P < 0.001) were associated with a higher likelihood of a \"good\" self-perceived health status.
UNASSIGNED: Preventive programs and interventions aimed at improving self-perceived health among patients with diabetes should focus on increasing regular physical activity and promoting a healthy nutritional status. These actions should be particularly targeted towards female and older patients with higher neuroticism traits.

OBJECTIVE: The primary aim of the study was to evaluate the differences in metabolic control and chronic microvascular complications in patients with type 3 autoimmune polyglandular syndrome (APS3), compared to type 1 diabetes mellitus (T1DM) alone. Secondary aims were to evaluate the age of autoimmune thyroid disease (AIT) onset and the effects of levothyroxine treatment on metabolic control in patients with APS3.
METHODS: We retrospectively reviewed 276 patients with T1DM alone and 214 patients with APS3 and evaluated clinical and metabolic parameters and microvascular complications.
RESULTS: Patients with T1DM showed a longer duration of diabetes (p = 0.001) and lower age of diabetes onset (p = 0.020) compared to patients with APS3. Female gender (p = 0.001) and microalbuminuria (p = 0.006) were significantly more frequent in patients with APS3 compared to T1DM. In addition, patients with APS3 showed higher AIT onset frequency in the 16-30 quartile age-range. Furthermore, APS3 patients treated with levothyroxine showed significantly better HbA1c values than non-treated patients (p = 0.001).
CONCLUSIONS: We found that patients with APS3 showed positive microalbuminuria, earlier than T1DM. Patients with APS3 showed higher frequency of AIT age of onset in the 16-30 age-range and those treated with levothyroxine had better metabolic control, than untreated ones.

BACKGROUND: The aim was to evaluate the effect of metabolic control on bone biomarkers in children with type I diabetes.
METHODS: The children were divided into two groups according to their glycated hemoglobin (HbA1c) (%) levels: a group with HbA1c levels < 8% (n = 16) and: a group with HbA1c levels > 8% (n = 18). The serum total oxidative status (TOS) (µmol/L), total antioxidant status (TAS) (mmol/L), alkaline phosphatase (ALP) (IU/L), osteocalcin (OC) (ng/ml), procollagen type-1-N-terminal peptide (P1NP) (ng/ml), and vitamin D (IU) levels and food consumption frequencies were determined.
RESULTS: When patients were classified according to HbA1c (%) levels, those with HbA1c levels < 8% were found to have lower TOS (µmol/L) values (8.7 ± 6.16, 9.5 ± 5.60) and higher serum OC (ng/mL) (24.2 ± 16.92, 22.0 ± 6.21) levels than those with HbA1c levels > 8% (p < 0.05). Regardless of the level of metabolic control, there was a statistically significant association between serum TOS (µmol/L) and P1NP (ng/ml) (p < 0.05) levels, with no group-specific relationship (HbA1c levels <%8 or HbA1c levels >%8).
CONCLUSIONS: HbA1c and serum TOS levels had an effect on bone turnover biomarkers in individuals with type I diabetes.

Introduction: Obesity (OB), type 2 diabetes mellitus (T2D), and hypertension (HTN) are health issues in Mexico linked to unhealthy behaviors. This study investigates the relationship between behavior change indicators and metabolic control in Mexican adults with OB, T2D, and HTN. Methods: We used data from the 2016 National Health and Nutrition Survey Midway (ENSANUT MC-2016), representing ∼59.5 million Mexican adults aged 20-59 with these conditions. We assessed behavior change indicators, including stages of change, self-efficacy, and perceptions of benefits and barriers. In addition, we conducted descriptive analyses and used statistical tests, such as Pearson\'s chi-squared test and logistic regression models, adjusted for multiple variables. Results: We found that adults in the action and maintenance stages of physical activity (PA) were four times more likely to have adequate HTN control than those in the precontemplation stage. Self-efficacy for PA was related to better control in T2D and HTN. Self-efficacy for reducing the consumption of sugary beverages was positively associated with control in OB and T2D. No significant association was observed with self-efficacy for consuming fruits and vegetables. Conclusion: Behavior-change indicators are significantly linked to metabolic control in adults with HTN. These results support the importance of these indicators in managing chronic diseases such as HTN and their potential use in public health strategies.