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Background: Little is known about the mechanisms underlying the association of the serum phospholipid lipophilic index (LI) with atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes (T2D). Therefore, we investigated whether the LI is associated with glucometabolic control, meta-inflammation, thrombin generation, fibrin clot properties, endothelial function and platelet activation in T2D patients with angiographically documented ASCVD. Methods: We studied 74 T2D patients with ASCVD, aged 65.6 ± 6.8 years, with a median diabetes duration of 10 years and median HbA1c of 7.0%. Serum phospholipid fatty acids (FAs) were measured by gas chromatography. The serum phospholipid LI was calculated as the sum of the products of the proportion (% of total FAs) with the melting points (°C) of each individual FA, divided by the sum of the proportions of all FAs. Levels of HbA1c, insulin, leptin, adiponectin, lipid profiles, inflammatory markers (hsCRP, interleukin-6, TNF-α), Lp-PLA2 (a biomarker of vascular inflammation), endothelial function (sICAM-1, sVCAM-1, FMD, NMD), thrombin generation, fibrin clot properties and platelet activation, measured by light transmission aggregometry with arachidonic acid [AA] and adenosine diphosphate [ADP], were assessed. Results: Patients with LI > 16.9 °C (median) had higher HbA1c concentrations by 5.9% compared to the remaining subjects (p = 0.035). In this group, HbA1c levels ≥ 7.0% were found more often than in individuals with LI ≤ 16.9 °C (62.2 vs. 35.1%; p = 0.020). Subjects with LI > 16.9 °C had higher levels of TCh by 17.1% (p = 0.012), LDL-Ch by 29.4% (p = 0.003), interleukin-6 by 22.2% (p = 0.031) and Lp-PLA2 by 32.4% (p = 0.040), compared to the remaining patients. Moreover, they had increased maximal platelet aggregation induced by AA (p = 0.045), but not by ADP. Serum phospholipid LI correlated with HbA1c (r = 0.24; p = 0.037), TCh (r = 0.36; p = 0.002), LDL-Ch (r = 0.38; p < 0.001), interleukin-6 (r = 0.27; p = 0.020) and Lp-PLA2 (r = 0.26; p = 0.026). There were no intergroup differences in endothelial function, thrombin generation and fibrin clot properties. Regression analysis showed that HbA1c ≥ 7.0% and serum levels of LDL-Ch, interleukin-6 and Lp-PLA2 were predictors of LI > 16.9 °C in adjusted models. Conclusions: In well-controlled T2D patients with ASCVD, the higher serum phospholipid LI is associated with worse glucometabolic control, enhanced vascular inflammation and higher platelet reactivity during aspirin treatment at cyclooxygenase-1-selective doses. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion The long‐term prognosis of treated phenylketonuria (PKU) is a controversial issue. A controlled long‐term study was performed to assess the neuropsychological outcome in adult patients with early treated PKU.We investigated 27 patients aged 34–55 years (median age: 47 years) and 19 healthy controls, matched for age and socio‐economic status. Patients and controls were assessed for their full‐scale IQ (FSIQ), attention and information‐processing abilities. Magnetic resonance imaging (MRI) of the brain was performed in all patients. Neuropsychological assessments and MRI were repeated at a 15‐year follow‐up.In the entire interval of 15 years, cognitive performance of patients and controls remained unchanged. Older adult patients showed poorer cognitive performance at all assessment times compared to young adult patients and controls. Cognitive performance showed no correlation to MRI results. FSIQ, however, was significantly correlated with blood phenylalanine levels in the adolescent years of adult patients older than 47 years.Cognitive performance in adult patients with early treated PKU does not seem to deteriorate in a 15 years interval. Neuropsychological assessment revealed constant modest neurocognitive impairment in patients older than 47 years. This seems to refer to an early relaxation of diet that was recommended when the older patients were adolescents. [ABSTRACT FROM AUTHOR]

Robot engagement in healthcare has the potential to alleviate medical personnel workload while improving efficiency in managing various health conditions. This study evaluates the impact of robot-assisted education on knowledge acquisition and metabolic control in children with Type 1 Diabetes Mellitus (T1DM) compared to traditional education methods. A randomized controlled trial was conducted at the pediatric diabetes clinic of the University of Tabuk Medical Center, Saudi Arabia. Thirty children aged 5–15 years with T1DM were randomly divided into two groups: the robot education (intervention) group and the control education group. Both groups participated in six weekly one-hour educational sessions, with the intervention group interacting with a Pepper robot assistant and the control group receiving education from a qualified diabetes educator nurse. Knowledge was assessed using a 12-item questionnaire before and after the intervention, while metabolic control was evaluated through weekly mean home blood glucose measurements and HbA1c levels before and three months post intervention. The intervention group demonstrated a significantly greater improvement in knowledge scores compared to the control group (p < 0.05). Weekly mean blood glucose levels were consistently lower in the intervention group throughout the study period (p < 0.05 for all samples). Both groups showed a reduction in HbA1c levels after three months, with the intervention group exhibiting a greater mean decrease. The engagement of the Pepper robot in T1DM education for children resulted in improved knowledge acquisition and better metabolic control compared to traditional education methods. This approach may establish a foundation for "learning by interacting with robots" in long-term diabetes management. Further research with larger sample sizes and longer follow-up periods is warranted to confirm these findings and explore the long-term benefits of robot-assisted education in pediatric diabetes care. [ABSTRACT FROM AUTHOR]

Abstract Background Little is known about the mechanisms underlying the association of the serum phospholipid lipophilic index (LI) with atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes (T2D). Therefore, we investigated whether the LI is associated with glucometabolic control, meta-inflammation, thrombin generation, fibrin clot properties, endothelial function and platelet activation in T2D patients with angiographically documented ASCVD. Methods We studied 74 T2D patients with ASCVD, aged 65.6 ± 6.8 years, with a median diabetes duration of 10 years and median HbA1c of 7.0%. Serum phospholipid fatty acids (FAs) were measured by gas chromatography. The serum phospholipid LI was calculated as the sum of the products of the proportion (% of total FAs) with the melting points (°C) of each individual FA, divided by the sum of the proportions of all FAs. Levels of HbA1c, insulin, leptin, adiponectin, lipid profiles, inflammatory markers (hsCRP, interleukin-6, TNF-α), Lp-PLA2 (a biomarker of vascular inflammation), endothelial function (sICAM-1, sVCAM-1, FMD, NMD), thrombin generation, fibrin clot properties and platelet activation, measured by light transmission aggregometry with arachidonic acid [AA] and adenosine diphosphate [ADP], were assessed. Results Patients with LI > 16.9 °C (median) had higher HbA1c concentrations by 5.9% compared to the remaining subjects (p = 0.035). In this group, HbA1c levels ≥ 7.0% were found more often than in individuals with LI ≤ 16.9 °C (62.2 vs. 35.1%; p = 0.020). Subjects with LI > 16.9 °C had higher levels of TCh by 17.1% (p = 0.012), LDL-Ch by 29.4% (p = 0.003), interleukin-6 by 22.2% (p = 0.031) and Lp-PLA2 by 32.4% (p = 0.040), compared to the remaining patients. Moreover, they had increased maximal platelet aggregation induced by AA (p = 0.045), but not by ADP. Serum phospholipid LI correlated with HbA1c (r = 0.24; p = 0.037), TCh (r = 0.36; p = 0.002), LDL-Ch (r = 0.38; p 16.9 °C in adjusted models. Conclusions In well-controlled T2D patients with ASCVD, the higher serum phospholipid LI is associated with worse glucometabolic control, enhanced vascular inflammation and higher platelet reactivity during aspirin treatment at cyclooxygenase-1-selective doses.

Abstract This study aimed to analyze whether early‐treated adults with phenylketonuria (PKU) can subjectively sense high phenylalanine (Phe) concentrations and whether a possible impact of Phe on objective measures of cognitive performance and mood reflects patients' self‐perception. Data from the PICO study, a randomized, placebo‐controlled, double‐blind, crossover trial, were analyzed. Twenty‐eight adults with PKU received either Phe capsules or placebo in two 4‐week intervention periods in a randomized order, with a 4‐week washout in between. The median Phe level increased from 852 μmol/L (interquartile range: 345) to 1455 μmol/L (interquartile range: 369). Neuropsychological assessments were performed at four study visits. At the end of the last study visit, patients were asked whether they could discern the Phe intervention period. Seven of 28 (25%) patients stated that they could not discern between the Phe and the placebo period. Twenty‐one of 28 (75%) patients subjectively thought to sense high Phe levels. Of the 21 patients, 12 (57%) correctly identified the Phe period, whereas 9 (43%) received placebo at the time when they thought they would receive the high Phe load. Binomial tests showed that the probability of 12 out of 21 is p = 0.140, and 12 out of 28 is p = 0.113. The “Right‐Guess” group showed significantly higher Phe changes than the “Wrong‐Guess” group. Cognitive performance and standardized mood assessment did not significantly differ, and both groups reported similar subjective negative impact on cognition and mood. In conclusion, adults with early‐treated PKU cannot effectively identify high Phe levels, although some individuals may be able to perceive more pronounced increases in Phe levels.

Objectives - Type 1 Diabetes Mellitus (DM1) requires demanding treatment in order to achieve good metabolic control. Our aim was to assess whether either method of insulin administration (multiple daily administrations of insulin analogues (MDIA) or continuous subcutaneous insulin infusion (CSII)) is associated with better health-related quality of life (HRQoL). Methods - We conducted a cross-sectional study. Patients aged 10-18 years with a disease duration of at least six months were included. HRQoL was assessed by having patients and their caregivers complete the DISABKIDS-37 questionnaire. Results - Of the 40 patients included, 22 (55%) had CSII. There were no statistically significant differences between subscale scores and overall HRQoL between patients or between parents of patients with CSII or MDIA. CSII patients and parents scored better on all subscales and on the total scale, although without statistically significant differences. There were no statistically significant differences in the subscale scores and overall HRQoL reported by the patients and their parents, but there was a strong correlation between the children's and parents' scores (R=0.770; P<0.01), which was similar in patients with CSII or MDIA (R=0.735 vs R=0.790). Conclusion - Although we did not identify statistically significant differences, there was a trend towards a better HRQoL associated with the use of CSII, both from the perspective of the adolescents and their parents. This could influence therapeutic choice. Consistency between the assessments of adolescents and their carers was observed. The choice between MDIA and CSII should be based on individual preferences in order to optimize the HRQoL of adolescents with DM1. [ABSTRACT FROM AUTHOR]

Aim: To synthesize the evidence on the effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in adolescents with overweight or obesity. Materials and 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. [ABSTRACT FROM AUTHOR]

Aims: To compare glycemic control and maternal–fetal outcomes of women with type 1 diabetes (T1D) using hybrid closed loop (HCL) versus multiple daily insulin injections (MDI) plus continuous glucose monitoring. Methods: Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c and time spent within (TIR), below (TBR), and above (TAR) the pregnancy-specific glucose range of 3.5–7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes, including baseline maternal characteristics and center. Results: One hundred twelve women were included (HCL n = 59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There was no between-group difference in HbA1c in any trimester. However, in the second trimester, MDI users had a greater decrease in HbA1c (−6.12 ± 9.06 vs. −2.16 ± 7.42 mmol/mol, P = 0.031). No difference in TIR (3.5–7.8 mmol/L) and TAR was observed between HCL and MDI users, but with a higher total insulin dose in the second trimester [+0.13 IU/kg·day)]. HCL therapy was associated with increased maternal weight gain during pregnancy (βadjusted = 3.20 kg, 95% confidence interval [CI] 0.90–5.50). Regarding neonatal outcomes, newborns of HCL users were more likely to have higher birthweight (βadjusted = 279.0 g, 95% CI 39.5–518.5) and macrosomia (ORadjusted = 3.18, 95% CI 1.05–9.67) compared to MDI users. These associations disappeared when maternal weight gain or third trimester HbA1c was included in the models. Conclusions: In a real-world setting, HCL users gained more weight during pregnancy and had larger newborns than MDI users, while achieving similar glycemic control in terms of HbA1c and TIR. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this review is to comprehensively assess the association between a gluten-free diet (GFD) and metabolic control of type 1 diabetes mellitus (T1DM) in children and adolescents with T1DM and with T1DM plus coeliac disease (CD). PubMed, Embase, Cochrane Library, and Web of Science were searched until June 19, 2023. Primary outcomes were hemoglobin A1c (HbA1c), insulin dose, insulin dose adjusted A1c (IDAA1c), blood glucose (B-glu) at 90 min during Mixed Meal Tolerance Test (MMTT), C-peptide area under the curve (AUC), and C-peptide. Seven studies involving 355 T1DM patients were included. Three studies involving 141 patients compared a GFD to a standard diet in children and adolescents with T1DM without CD. Additionally, two studies with 164 patients examined the same diet comparison in those with T1DM and concurrent CD. A comparison between T1DM with CD and T1DM alone, using a GFD, was conducted in two studies encompassing 50 patients. Patients with T1DM alone had similar HbA1c [pooled weighted mean difference (WMD) = −0.5, 95% confidence interval (CI): −1.0 to 0.1, P = 0.079] and IDAA1c (pooled WMD = −0.4, 95%CI: −0.9 to 0.1, P = 0.095) levels after a GFD and a standard diet. In children and adolescents with T1DM and CD, a GFD was associated with a significantly lower HbA1c compared with a standard diet (pooled WMD = −0.64, 95%CI: −1.22 to −0.05, P = 0.034). Insulin dose was significantly lower in T1DM combined with CD patients having a GFD vs a standard diet (pooled WMD = −0.34, 95%CI: −0.66 to −0.03, P = 0.032). Our study suggests that a GFD may offer significant benefits for children and adolescents with both T1DM and CD over a standard diet. While the evidence indicates improved glycemic control with a GFD, the quality of this evidence is low, highlighting the need for rigorous, randomized trials to confirm these preliminary findings. In the interim, enhancing dietary awareness and providing tailored nutritional guidance could be pivotal for optimizing glucose management in this patient population.

Abstract 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). Discussion 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. Trial registration ISRCTN registry ISRCTN11967109 . Registered on 9 May 2024.

Abstract Background The aim was to evaluate the effect of metabolic control on bone biomarkers in children with type I diabetes. Materials and methods The children were divided into two groups according to their glycated hemoglobin (HbA1c) (%) levels: 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% (p %8). Conclusion HbA1c and serum TOS levels had an effect on bone turnover biomarkers in individuals with type I diabetes.

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. [ABSTRACT FROM AUTHOR]

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). Discussion: 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. Trial registration: ISRCTN registry ISRCTN11967109. Registered on 9 May 2024. [ABSTRACT FROM AUTHOR]

The relationship between metabolic changes occurring in the developing internodes of sugarcane and the final yield and sugar characteristics is poorly understood due to the lack of integration between phenotypic and metabolic data. To address this issue, a study was conducted where sugarcane metabolism was modeled based on the measurement of cellular components in the top internodes, at two stages of crop development. The study also looked at the effects of Trinexapac-ethyl (Moddus®) on growth inhibition. The metabolome was measured using GC-analysis, while LC-MS/MS was used to measure proteome changes in the developing internodes. These data were then integrated with the metabolic rates. Regardless of the growth rate, internode elongation was restricted to the top five internodes. In contrast, sucrose and lignin accumulation was sensitive to the growth rate. Crossover plots showed that sucrose accumulation only occurred once the cell wall synthesis had slowed down. These data suggest that sucrose accumulation controlled a reduction in sucrose breakdown for metabolic activity and a reduction in demand for carbon for cell wall polysaccharide synthesis. This study also found that nucleotide sugar metabolism appears to be a key regulator in regulating carbon flow during internode development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The aim was to evaluate the effect of metabolic control on bone biomarkers in children with type I diabetes. Materials and 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). Conclusion: HbA1c and serum TOS levels had an effect on bone turnover biomarkers in individuals with type I diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Efficacy and safety of the fixed ratio combination of insulin degludec and liraglutide (IDegLira) has been largely documented. However, long-term data are limited. This study aimed at describing persistence in therapy and the effectiveness at 48 months of IDegLira. Methods: We conducted an observational study based on retrospective chart review. All patients treated with IDegLira during 2018–2022 were included. Data on treatment approaches and clinical outcomes were collected at the first prescription of IDegLira (T0) and after 6, 12, 24, 36, and 48 months. Results: Overall, 156 patients (mean age 68 years, 64.1% men) started IDegLira, of whom 88 (56.4%) were previously treated with basal-oral therapy (BOT) and 68 (43.6%) with basal-bolus schemes (BB). Before starting IDegLira, 23.8% were treated with ≥ 2 oral antihyperglycemic agents in association with insulin; at T0, the proportion decreased to 3.2%. Short-acting insulin was discontinued after the first week. After 48 months, levels of HbA1c were significantly reduced by 1.34% in the BOT group and 1.07% in the BB group (p < 0.0001 in both groups). In the BOT group, FBG levels decreased by about 50 mg/dl and body weight was unchanged. In the BB group, FBG levels decreased by about 40 mg/dl and body weight was significantly reduced by an average of 7.7 kg. Five patients (3.2%) interrupted therapy with IDegLira during 48 months, and no severe hypoglycemia occurred. Conclusions: Our study emphasizes the important role of IDegLira in maintaining a good metabolic control while minimizing the risk of major hypoglycemia and weight gain in the long term. The substantial simplification of treatment schemes can increase adherence. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the relationship between metabolic control factors, socio-demographic characteristics, personality traits, and self-perceived health status in diabetes. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Abstract Background The SARS-CoV-2 pandemic brought a radical shift in the healthcare system and suboptimal care for vulnerable patients, such as those with Type 2 Diabetes Mellitus (T2D). Therefore, we compared metabolic control and macro/microvascular complications of patients with T2D before and throughout the three-year SARS-CoV-2 pandemic. Research design and methods A retrospective observational cohort of subjects with T2D studied from 2018 to 2022 in Northern Mexico was treated by a dynamic multidisciplinary team. Levels of Glycated hemoglobin (HbA1c), fasting serum glucose (FG), LDL-Cholesterol (LDL-C), blood pressure (BP), albuminuria, triglycerides, Body Mass Index (BMI), and FIB-4 score, micro and macrovascular complications were evaluated. Results A total of 999 patients were studied, 51.7% males with a mean (SD) age of 60.1 (12.7) years. Adequate glycemic control based on HbA1c increased by 15.2% and 42.3% in FSG (p

Abstract Objective The simultaneous presence of celiac disease and type 1 diabetes (T1DM) is coupled with more hazards of comorbidities and complications. This current study aimed to screen for celiac disease in Egyptian children with type 1 diabetes and evaluate its impact on glycemic control. Methods A cross-sectional study was verified with 200 Egyptian children diagnosed with T1DM and having a diabetic duration of less than five years. Testing for anti-tissue transglutaminase IgA (tTG-IgA), anti-tissue transglutaminase IgG (tTG-IgG), anti-Endomysial IgA (EMA), and Hb A1c levels were done. Results The serological screening revealed that 11 cases (5.5%) tested positive; 8 children with T1DM (4.0%) showed tTG-IgA antibodies ≥ 10 times the upper limit of normal (ULN) with at least one symptom; and 3 cases (1.5%) had levels between 20 and 50 IU/ml (considering a cut-off point of 10 U/ML for positive results). Intestinal biopsy was performed for these three cases, with one case detected to have subtotal villous atrophy, resulting in an overall prevalence of celiac disease in T1DM as 4.5%. Children with positive screening exhibited a higher insulin dose, a higher HbA1c, an increased frequency of hypoglycemic attacks, and recurrent DKA compared to negative cases. A negative correlation was detected between tTG-IgA antibodies with height Z score and hemoglobin level, while a positive correlation was found between tTG-IgA antibodies and HbA1c level. Conclusion Undiagnosed celiac disease in children with T1DM negatively impacted metabolic control and affected their general health.

Aims/hypothesis: This register-based study aimed to describe autoimmune comorbidity in children and young adults from type 1 diabetes onset, and to investigate whether such comorbidity was associated with a difference in HbA1c or mortality risk compared with children/young adults with type 1 diabetes without autoimmune comorbidity. Methods: A total of 15,188 individuals from the Swedish National Diabetes Register, registered with type 1 diabetes before 18 years of age between 2000 and 2019, were included. Five randomly selected control individuals from the Swedish population (Statistics Sweden) were matched to each individual with type 1 diabetes (n=74,210 [346 individuals with type 1 diabetes were not found in the Statistics Sweden register at the date of type 1 diabetes diagnosis, so could not be matched to control individuals]). The National Patient Register was used to attain ICD-10 codes on autoimmune diseases and the Cause of Death Register was used to identify deceased individuals. Results: In the total type 1 diabetes cohort, mean±SD age at onset of type 1 diabetes was 9.5±4.4 years and mean disease duration at end of follow-up was 8.8±5.7 years. Of the individuals with type 1 diabetes, 19.2% were diagnosed with at least one autoimmune disease vs 4.0% of the control group. The HRs for comorbidities within 19 years from onset of type 1 diabetes were 11.6 (95% CI 10.6, 12.6) for coeliac disease, 10.6 (95% CI 9.6, 11.8) for thyroid disease, 1.3 (95% CI 1.1, 1.6) for psoriasis, 4.1 (95% CI 3.2, 5.3) for vitiligo, 1.7 (95% CI 1.4, 2.2) for rheumatic joint disease, 1.0 (95% CI 0.8, 1.3) for inflammatory bowel disease, 1.0 (95% CI 0.7, 1.2) for systemic connective tissue disorder, 1.4 (95% CI 1.1, 1.9) for uveitis, 18.3 (95% CI 8.4, 40.0) for Addison's disease, 1.8 (95% CI 0.9, 3.6) for multiple sclerosis, 3.7 (95% CI 1.6, 8.7) for inflammatory liver disease and 19.6 (95% CI 4.2, 92.3) for atrophic gastritis. Autoimmune disease in addition to type 1 diabetes had no statistically significant effect on HbA1c or mortality risk. Conclusions/interpretation: To our knowledge, this is the first comprehensive study where young individuals with type 1 diabetes were followed regarding development of a wide spectrum of autoimmune diseases, from onset of type 1 diabetes. In this nationwide and population-based study, there was already a high prevalence of autoimmune diseases in childhood, especially coeliac and thyroid disease. The presence of autoimmune comorbidity did not have a statistically significant effect on metabolic control or mortality risk. [ABSTRACT FROM AUTHOR]

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK) are two enzymes of the Calvin Benson cycle that stand out for some peculiar properties they have in common: (i) they both use the products of light reactions for catalysis (NADPH for GAPDH, ATP for PRK), (ii) they are both light-regulated through thioredoxins and (iii) they are both involved in the formation of regulatory supramolecular complexes in the dark or low photosynthetic conditions, with or without the regulatory protein CP12. In the complexes, enzymes are transiently inactivated but ready to recover full activity after complex dissociation. Fully active GAPDH and PRK are in large excess for the functioning of the Calvin-Benson cycle, but they can limit the cycle upon complex formation. Complex dissociation contributes to photosynthetic induction. CP12 also controls PRK concentration in model photosynthetic organisms like Arabidopsis thaliana and Chlamydomonas reinhardtii. The review combines in vivo and in vitro data into an integrated physiological view of the role of GAPDH and PRK dark complexes in the regulation of photosynthesis. • Calvin-Benson cycle regulation involves the formation of protein complexes in the dark or low light conditions. • GAPDH and PRK change their activity while changing their oligomerization state. • GAPDH and PRK activities are regulated at multiple levels in a light-dependent manner. • Thioredoxin redox state and metabolites coordinate the activation of PRK and GAPDH. • While activated GAPDH and PRK are in large excess for the Calvin-Benson cycle, complexed forms may limit RuBP regeneration. [ABSTRACT FROM AUTHOR]

Clinical scenarios have risen where females with Type 1 diabetes mellitus (T1-DM), whose demographics are similar to their male counterparts, have sustained bone injuries, whereas the males with T1-DM have not. These scenarios bring into question the effect of T1-DM on various aspects of bone health and injury risk in females. The purpose of this study was to investigate the impact of T1-DM in females on their fracture risk, glycemic control abilities, and bone mineral density when compared to their male counterparts. Results were consistent across all studies, indicating that individuals with T1-DM had poor glycemic control abilities during ages within peak bone accrual, had significantly lower bone mineral density, and had a greater fracture incidence. Given these results, there is a need for future education to emphasize the importance of glycemic management, future research to investigate differences in physically active populations, and for clinicians to recognize their at-risk patients and take the necessary measures to prevent injury. [ABSTRACT FROM AUTHOR]

Background: To achieve a normal nutritional status, patients suffering from phenylketonuria (PKU) are typically prescribed amino acid (AA) supplements with low or no phenylalanine (Phe) content. Studies evaluating patient preferences regarding the intake modalities of AA supplements are limited. This study aimed to collect real-world data regarding prescription adherence and intake modalities of AA supplements reported by PKU patients while monitoring metabolic control. Methods: This cross-sectional study included 33 PKU patients (16 female and 17 male) with a mean age of 27.2 years. Questionnaires were provided to assess information on AA supplement intake, such as prescription adherence rate, frequency and timing of administration, supplement formulation, and combination with food or drinks. Plasma phenylalanine levels were monitored during the study period. Results: 51.5% (n = 17) of patients reported to lay within an adherence range of 75–100%. The majority of patients consumed AA supplements twice daily, with breakfast (87.9%) and afternoon snacks (51.5%). Powder supplements were most commonly used (72.7%) and often combined with milk and/or fruit juices (45.4%). Conclusions: Despite the known concerns related to treatment compliance among PKU adolescents and adults, most of the study participants reported a high level of adherence to AA supplement prescription. The personalized dietary regimens followed by the patients included in the current study represent a treatment approach that might be worth trying in non-compliant patients. [ABSTRACT FROM AUTHOR]

Context: The condition when a person's gender identity does not match the sex assigned at birth is called gender incongruence (GI). Numbers of GI people seeking medical care increased tremendously over the last decade. Diabetes mellitus is a severe and lifelong disease. GI combined with diabetes may potentiate into a burdensome package for affected people. Objective: The study aimed to characterize people with GI and diabetes from an extensive standardized registry, the Prospective Diabetes Follow-up Registry (DPV), and to identify potential metabolic and psychological burdens. Methods: We compared demographic and clinical registry data of persons with type 1 or type 2 diabetes and GI to those without GI and used propensity score matching (1:4) with age, diabetes duration and treatment year as covariates. Results: 75 persons with GI, 49 with type 1 and 26 with type 2 diabetes were identified. HbA1c values were similar in matched persons with type 1 or 2 diabetes and GI compared to those without GI. Lipid profiles showed no difference, neither in type 1 nor in type 2 diabetes. Diastolic blood pressure was higher in the type 1 and GI group than in those without, whereas systolic blood pressure showed comparable results in all groups. Depression and anxiety were significantly higher in GI people (type 1 and 2). Non-suicidal self-injurious behaviour was more common in type 1 and GI, as was suicidality in type 2 with GI. Conclusion: Mental health issues are frequent in people with diabetes and GI and need to be specially addressed in this population. [ABSTRACT FROM AUTHOR]

Background: Visceral Adiposity Index (VAI) is a gender-specific mathematical model based on BMI, waist circumference (WC) and lipid parameters. No study has yet examined the relationship between this index and the glycemic and metabolic parameters in children and adolescents with Type 1 Diabetes Mellitus (DM). The current study aims at examining the relationship between glycemic and metabolic control and VAI in children and adolescents with Type 1 DM. Methods: A total of 150 children and adolescents aged 6–18 years with Type 1 DM were included in this study. Anthropometric, glycemic and metabolic parameters were examined. VAI was calculated using gender-specific formulas. Statistical analysis was done by SPSS version 23. Results: The average age of the participants was 12.2 ± 3.1 years (females 53.0%). The females had higher rates of VAI, microalbuminuria and hypertension than males. Participants of both gender with higher VAI quartiles had higher anthropometric measurements, insulin usage, low-density lipoprotein cholesterol (LDL-C), triglycerides and urine microalbumin and had poor glycemic control. Sex adjusted correlation analysis showed that VAI is negatively correlated with estimated glucose disposal rate (eGDR), and positively correlated with insulin dose, LDL-C, triglycerides, glycosylated hemoglobin (HbA1c) and microalbuminuria. Conclusion: The present paper is the first study examining the relationship between Type 1 DM and VAI. Higher VAI values in children and adolescents with type 1 DM may adversely affect glycemic and metabolic control. VAI can be a useful and new method in evaluating glycemic and metabolic control in children and adolescents with Type 1 DM. [ABSTRACT FROM AUTHOR]

Experimental approaches in neuroeconomics generally involve monetary utility. Utility in the health domain is relevant in diabetes because constant daily life decisions are critical for self-consequential long-term outcomes. We used fMRI to investigate self-consequent decision-making in the health and economic domains in Type 1 Diabetes Mellitus and controls (N = 50). We focused on two critical phases of decision-making: Investment and Feedback (Positive or Negative). Patients showed larger BOLD activation of limbic, and reward/dopaminergic regions in particular in the health trust game. Importantly, the worse the trajectory of metabolic control (increasing HbA1C), the higher the BOLD activity in regions of the interoceptive saliency network. This was manifested by positive correlations between brain activity during investment in anterior cingulate cortex and insula and HbA1c blood level progression. We conclude that the neural correlates of health-consequent decision-making domain involve limbic and reward related dopaminergic regions in Type 1 Diabetes Mellitus. Furthermore, the temporal trajectory of HbA1C blood levels is correlated with neural risk processing in the saliency network. Evidence for differential risk processing in the health versus the neuroeconomic context, and the discovery of a role for the saliency interoceptive network in metabolic control trajectories suggests a new perspective on the development of personalized interventions. [ABSTRACT FROM AUTHOR]

Background: Advances in treatment could mitigate the expected adverse changes in the body composition of children and adolescents with type 1 diabetes (T1D). Objectives: To examine the evolution of weight status and body composition and their association with glycaemic control and partial clinical remission in youth with T1D. Methods: Ninety‐nine participants with T1D (median age 9.5 years [interquartile range 7.3, 12.9], 59.6% boys) were longitudinally followed for 3 years since diagnosis. Data at seven pre‐determined time points were extracted from medical files. Outcome measures included body mass index (BMI) z‐scores, muscle‐to‐fat ratio (MFR) z‐scores, haemoglobin A1c (HbA1c) levels, continuous glucose monitoring metrics, and insulin dose‐adjusted HbA1c (IDAA1c) levels. Results: The BMI z‐scores increased significantly (p < 0.001) for both sexes, with no significant change in MFR z‐scores over time. The girls had higher BMI z‐scores (p < 0.001) and lower MFR z‐scores than the boys (p = 0.016). The mean HbA1c levels decreased during the first month and at 3 months since diagnosis (p < 0.001), then plateaued and achieved a median overall HbA1c of 7.1% for the entire cohort. At 12 months, 37 participants (37.6%) were in partial clinical remission, as evidenced by IDAA1c ≤ 9. The odds of partial clinical remission at 2 years increased by 2.1‐fold for each standard deviation increase in the MFR z‐score (p < 0.001). Higher MFR z‐scores were associated with better metabolic control. Conclusions: Integration of body composition assessments could mitigate adverse body changes in paediatric patients with T1D. [ABSTRACT FROM AUTHOR]

Over the past century, age-related diseases, such as cancer, type-2 diabetes, obesity, and mental illness, have shown a significant increase, negatively impacting overall quality of life. Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels, including transcriptional, translational, and post-translational processes, resulting from cellular stress and circadian derangements. The circadian clock emerges as a key regulator, sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes, such as stem-cell function, cellular stress responses, and inter-tissue communication, which become disrupted during aging. Given the crucial role of hypothalamic circuits in regulating organismal physiology, metabolic control, sleep homeostasis, and circadian rhythms, and their dependence on these processes, strategies aimed at enhancing hypothalamic and circadian function, including pharmacological and non-pharmacological approaches, offer systemic benefits for healthy aging. Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions, like the hypothalamus, while reducing side effects associated with systemic drug delivery, thereby presenting new therapeutic possibilities for diverse age-related conditions.

Abstract Background Preliminary evidence demonstrates some parameters of metabolic control, including glycaemic control, lipid control and insulin resistance, vary across the menstrual cycle. However, the literature is inconsistent, and the underlying mechanisms remain uncertain. This study aimed to investigate the association between the menstrual cycle phase and metabolites and to explore potential mediators and moderators of these associations. Methods We undertook a cross-sectional cohort study using UK Biobank. The outcome variables were glucose; triglyceride; triglyceride to glucose index (TyG index); total, HDL and LDL cholesterol; and total to HDL cholesterol ratio. Generalised additive models (GAM) were used to investigate non-linear associations between the menstrual cycle phase and outcome variables. Anthropometric, lifestyle, fitness and inflammatory markers were explored as potential mediators and moderators of the associations between the menstrual cycle phase and outcome variables. Results Data from 8694 regularly menstruating women in UK Biobank were analysed. Non-linear associations were observed between the menstrual cycle phase and total (p

Introduction: The COVID-19 pandemic has led to an island-wide lockdown in Sri Lanka, leading to restrictions in daily routines. The ensuing lifestyle changes have drastically influenced the prevalence and worsening of chronic diseases like diabetes with poor metabolic control of the disease. Objectives: To evaluate the immediate impact of the lockdown on the metabolic parameters associated with diabetes control in individuals with type-2 diabetes mellitus (T2DM). Methodology: A single center cross-sectional descriptive study was conducted on 157 T2DM patients attending a diabetes clinic in the private sector. Pre- and post-lockdown data on metabolic control of the study population was collected from patient records. Patients’ perceptions of diet/exercise and access to medication/medical care during the lockdown were collected through a telephone interview. Results: Pre- and post-lockdown data of 157 male (Females 88; mean age-58.68±SD 13.44 years) patients belonging to the age group 48-72 were evaluated. Of the patients who had a HbA1c of ≤ 7% pre-lockdown, 80% had shown to maintain their HbA1c. Of the patients with HbA1c > 7% pre-lockdown, 27.9% showed a reduction of their HbA1c below 7%. The majority of the responders had no difference in their diet (69.2%) and exercise (65.4%) during the lockdown. Among those with improved HbA1c (n=101;63% of cohort), 16.9% and 13% had better diet and exercise respectively while none in worsened HbA1c group had improved diet or exercise. Conclusions: Lockdown in Sri Lanka has not been associated with worsening of glycaemic control in the studied cohort of patients with type 2 diabetes. Adherence to the recommended diet and exercise regime during lockdown is associated with better glycaemic control in patients with type 2 diabetes.

Robot engagement in healthcare has the potential to alleviate medical personnel workload while improving efficiency in managing various health conditions. This study evaluates the impact of robot-assisted education on knowledge acquisition and metabolic control in children with Type 1 Diabetes Mellitus (T1DM) compared to traditional education methods. A randomized controlled trial was conducted at the pediatric diabetes clinic of the University of Tabuk Medical Center, Saudi Arabia. Thirty children aged 5–15 years with T1DM were randomly divided into two groups: the robot education (intervention) group and the control education group. Both groups participated in six weekly one-hour educational sessions, with the intervention group interacting with a Pepper robot assistant and the control group receiving education from a qualified diabetes educator nurse. Knowledge was assessed using a 12-item questionnaire before and after the intervention, while metabolic control was evaluated through weekly mean home blood glucose measurements and HbA1c levels before and three months post intervention. The intervention group demonstrated a significantly greater improvement in knowledge scores compared to the control group (p < 0.05). Weekly mean blood glucose levels were consistently lower in the intervention group throughout the study period (p < 0.05 for all samples). Both groups showed a reduction in HbA1c levels after three months, with the intervention group exhibiting a greater mean decrease. The engagement of the Pepper robot in T1DM education for children resulted in improved knowledge acquisition and better metabolic control compared to traditional education methods. This approach may establish a foundation for “learning by interacting with robots” in long-term diabetes management. Further research with larger sample sizes and longer follow-up periods is warranted to confirm these findings and explore the long-term benefits of robot-assisted education in pediatric diabetes care.

Abstract Aims In this cross-sectional study, we aimed to evaluate metabolic control, adherence to a gluten-free diet (GFD), and quality of life (QoL) in individuals with type 1 diabetes (T1D) and celiac disease (CD). Methods We targeted individuals with T1D and CD at a major tertiary hospital in Saudi Arabia. We gathered retrospective data from medical records and prospectively assessed glycemic control using HbA1c and ambulatory glucose metrics, adherence to a GFD using the Celiac Dietary Adherence Test (CDAT), and QoL using the Celiac Disease Quality of Life survey (CD-QoL). Results Forty-eight out of 1095 patients screened (4.38%) were included. Mean age and HbA1c were 21.3 (± 6.6) and 8.3% (± 0.8%). The average time in range% and above range% were 38.5 (range 24–68) and 29.6 (± 7.4). The median hypoglycemic events/month was 8, with a median duration of 80 min. The median overall CDAT and CD-QoL scores were 20.5 and 54. No significant correlations were observed between glucose management indicator (GMI), % in target, and CDAT/CD-QoL scores (all p > 0.05). Conclusions No significant effect of GFD on QoL or glycemic control was observed. Further prospective studies are warranted to establish solid evidence of the impact of GFD on individuals with T1D and CD.

Abstract Background Phenylketonuria (PKU) is a rare inborn error of metabolism affecting the catabolism of phenylalanine (Phe). To date, findings regarding health-related quality of life (HRQoL) in adults with early-treated classical PKU are discrepant. Moreover, little is known about metabolic, demographic, and cognitive factors associated with HRQoL. Hence, we aimed to investigate HRQoL and its association with demographic, metabolic, and cognitive characteristics in a large European sample of adults with early-treated classical PKU. Results This cross-sectional study included 124 adults with early-treated classical PKU from Hungary, Italy, Spain, Switzerland, and Turkey. All participants prospectively completed the PKU quality of life questionnaire (PKU-QoL), a questionnaire specifically designed to evaluate the impact of PKU and its treatment on HRQoL in individuals with PKU. In addition, information about Phe levels (concurrent and past year), demographic (age and sex), and cognitive variables (intelligence quotient, IQ) were collected. Most domains revealed little or no impact of PKU on HRQoL and more than three-quarters of the patients rated their health status as good, very good, or excellent. Nevertheless, some areas of concern for patients were identified. Patients were worried about the guilt that they experience if they do not adhere to the dietary protein restriction and they were most concerned about high Phe levels during pregnancy. Further, tiredness was the most affected symptom, and the supplements’ taste was considered a main issue for individuals with PKU. The overall impact of PKU on HRQoL was higher in women (U = 1315.5, p = .012) and in adults with a lower IQ (r s = − 0.448, p = .005). The overall impact of dietary protein restriction was higher in adults with higher concurrent Phe levels (r s = 0.272, p = .007) and higher Phe levels during the past year (r s = 0.280, p = .009). Conclusion The impact of PKU on most domains assessed in the PKU-QoL was considered to be low. These results likely reflect the successful implementation of the newborn screening resulting in the prevention of severe adverse long-term outcomes. However, a particular clinical focus should be given to patients with lower IQ, higher Phe levels, and women, as these variables were associated with a lower HRQoL.

The association between type 1 diabetes (T1D) and coeliac disease (CD) is well known. Metabolic control of thirty-seven patients aged between 1 and 18 years, with coexisting T1D and CD were evaluated. The control group includes 37 patients affected only by diabetes. All data relating to the metabolic control of all patients were acquired through examination of medical records and CMG reports available on dedicated online platforms. Glucose variability was expressed as Coefficient of Variation (CV) and Standard Deviation of blood glucose values (SD). The formula used for CV computation is: CV (%) = 100 × SD (daily glycemia)/Mean (daily glycemia). Patients with T1D and CD showed a significant reduction in rapid pre-prandial insulin. The same reduction was present if we consider only patients using CGM. In patients without CGM, there was no difference in the doses of basal, pre-prandial and total insulin. Indicators of metabolic control were overlapping between the two groups in patients who used CGM. On the contrary, diabetic and coeliac patients without CGM had increased levels of glycaemic variability indicators and HbA1c. Finally, the percentage of target glycaemic values and >250 mg/dL glycaemic values were significantly decreased and increased, respectively in T1D and CD patients without CGM. With this study we wanted to demonstrate if CGM could improve metabolic control of patients with coexisting T1D and CD. Our data show a worse metabolic control in patients with T1D and CD who did not use CGM. Instead, patients who use CGM, regardless of the concomitant CD, manage to achieve the same glycaemic targets through an adjustment of titration of pre-prandial insulin doses.

Abstract: The modification of atmosphere composition is a strategy to prolong the storage of organisms susceptible to senescence. Atmospheres with high levels of carbon dioxide could be applied to prolong the viability of recalcitrant seeds, which are in a constant process of deterioration due to intense metabolic activity. However, there is a need to develop methods that allow the standardized generation of these modified atmospheres to isolate the effect of low oxygen from high carbon dioxide. In this study, the generation of modified atmospheres was carried out by experiments with insufflated gas (IG) or compensated vacuum (CV), on recalcitrant Inga vera embryos as an experimental model. In IG, CO2 and N2 were uninterruptedly injected into a mixing chamber, in which the gases underwent turbulence to be homogenized and subsequently applied to the flasks where the embryos were incubated. In CV, the embryos were placed in flasks, from which a fraction of the air present inside was removed, and subsequently, the gases of interest were injected in defined fractions. The CV method proved to be more efficient and it was possible to restrict the respiratory metabolism of the Inga vera embryos by reducing respiration with the increase in carbon dioxide applied exogenously.

For engineered microorganisms, the production of heterologous proteins that are often useless to host cells represents a burden on resources, which have to be shared with normal cellular processes. Within a certain metabolic leeway, this competitive process has no impact on growth. However, once this leeway, or free capacity, is fully utilized, the extra load becomes a metabolic burden that inhibits cellular processes and triggers a broad cellular response, reducing cell growth and often hindering the production of heterologous proteins. In this study, we sought to characterize the metabolic rearrangements occurring in the central metabolism of Pseudomonas putida at different levels of metabolic load. To this end, we constructed a P. putida KT2440 strain that expressed two genes encoding fluorescent proteins, one in the genome under constitutive expression to monitor the free capacity, and the other on an inducible plasmid to probe heterologous protein production. We found that metabolic fluxes are considerably reshuffled, especially at the level of periplasmic pathways, as soon as the metabolic load exceeds the free capacity. Heterologous protein production leads to the decoupling of anabolism and catabolism, resulting in large excess energy production relative to the requirements of protein biosynthesis. Finally, heterologous protein production was found to exert a stronger control on carbon fluxes than on energy fluxes, indicating that the flexible nature of P. putida 's central metabolic network is solicited to sustain energy production. • Heterologous protein production in P. putida reshuffles the periplasmic metabolism. • Increased protein production progressively decouples catabolism from anabolism. • Protein production exerts a stronger control on energy than on carbon fluxes. • Glucose is directed towards ATP production to meet the elevated energy demands. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a chronic disease that requires lifelong management and care, affecting around 422 million people worldwide and roughly 37 million in the United States. Patients newly diagnosed with diabetes must work with health care providers to formulate a management plan, including lifestyle modifications and regular office visits, to improve metabolic control, prevent or delay complications, optimize quality of life, and promote well-being. Objective: Our aim is to investigate one component of system-wide access to timely health care for people with diabetes in New York City (NYC), namely the length of time for someone with newly diagnosed diabetes to obtain an appointment with 3 diabetes care specialists: a cardiologist, an endocrinologist, and an ophthalmologist, respectively. Methods: We contacted the offices of 3 different kinds of specialists: cardiologists, endocrinologists, and ophthalmologists, by telephone, for this descriptive cross-sectional study, to determine the number of days required to schedule an appointment for a new patient with diabetes. The sampling frame included all specialists affiliated with any private or public hospital in NYC. The number of days to obtain an appointment with each specialist was documented, along with "time on hold" when attempting to schedule an appointment and the presence of online booking capabilities. Results: Of the 1639 unique physicians affiliated with (private and public) hospitals in the 3 subspecialties, 1032 (cardiologists, endocrinologists, and ophthalmologists) were in active practice and did not require a referral. The mean wait time for scheduling an appointment was 36 (SD 36.4; IQR 12-51.5) days for cardiologists; 82 (SD 47; IQR 56-101) days for endocrinologists; and 50.4 (SD 56; IQR 10-72) days for ophthalmologists. The median wait time was 27 days for cardiologists, 72 days for endocrinologists, and 30 days for ophthalmologists. The mean time on hold while attempting to schedule an appointment with these specialists was 2.6 (SD 5.5) minutes for cardiologists, 5.4 (SD 4.3) minutes for endocrinologists, and 3.2 (SD 4.8) minutes for ophthalmologists, respectively. Over 46% (158/341) of cardiologists enabled patients to schedule an appointment on the web, and over 55% (128/228) of endocrinologists enabled patients to schedule an appointment on the web. In contrast, only approximately 25% (117/463) of ophthalmologists offered web-based appointment scheduling options. Conclusions: The results indicate considerable variation in wait times between and within the 3 specialties examined for a new patient in NYC. Given the paucity of research on wait times for newly diagnosed people with diabetes to obtain an appointment with different specialists, this study provides preliminary estimates that can serve as an initial reference. Additional research is needed to document the extent to which wait times are associated with complications and the demographic and socio-economic characteristics of people served by different providers. [ABSTRACT FROM AUTHOR]

Background Individuals with chronic diseases are less often presented to hospitals due to the restrictions enforced during the pandemic period and the fear of contracting the disease. The purpose of the present study was to investigate the effects of the anxiety level associated with novel coronavirus on daily life, treatment compliance, and metabolic conditions in elderly diabetes mellitus (DM) patients. Methods This study included 263 patients diagnosed with type 2 DM aged >65 years. The researchers collected the study data through the face-to-face interview method. The Patient Information Form, Coronavirus Anxiety Scale (CAS), Morisky Medication Adherence Scale, Insomnia Severity Index, and the Depression Anxiety Stress Scales (DASS-21) were used for data collection. Results The mean CAS score was 4.25±3.76. Mean CAS scores were higher in the participants who reported a decrease in the frequency of shopping, grocery/market visits, public transport use, hospital visits, and attending routine checks, during the pandemic (p<0.05). Furthermore, a significant positive correlation was found between the mean CAS score and the DASS-21 score (p<0.05). There was a significant negative correlation between the mean CAS score and the treatment compliance score (p<0.05). Conclusion The pandemic and coronavirus anxiety have had an adverse effect on daily life, treatment compliance, and metabolic conditions in elderly DM patients. [ABSTRACT FROM AUTHOR]

aime-Casas,3 Aida Jiménez-Corona,2,4 David Rivera-De La Parra,1,2 Enrique Octavio Graue-Hernández,2 Sergio Hernández-Jiménez1 On behalf of the Group of Study CAIPaDi1Centro de Atención Integral del Paciente con Diabetes (CAIPaDi) Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 2Instituto de Oftalmología Fundación Conde de Valenciana IAP, Mexico City, Mexico; 3Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico; 4Dirección General de Epidemiología, Secretaría de Salud, Mexico City, MexicoCorrespondence: Liliana Pérez-Peralta, Centro de Atención Integral del Paciente con Diabetes, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15. Colonia Sección XVI, Tlalpan, Mexico City, 14080, Mexico, Tel +52 55 54870900 (5045), Email [email protected] Purpose: To evaluate the risk factors associated with diabetic macular edema (DME) in patients with a recent type 2 diabetes mellitus (T2DM) diagnosis.Patients and Methods: We conducted a case-control study at a third-level hospital in Mexico City. We enrolled patients ≥ 18 years old, with T2DM less than five years of diagnosis, without disabling complications, and non-smokers. The control group was patients with diabetic retinopathy and without macular edema (DR-DME). Cases were patients with DR+DME. We measured fasting glucose, creatinine, lipid profile, urinary albumin/creatinine ratio (ACR), and HbA1c. An ophthalmological examination consisted of visual acuity measurement, digital three-field fundus photography with an automatic non-mydriatic camera, slit lamp, and Optical coherence tomography (OCT) examination.Results: 183 and 61 patients with DR-DME and DR+DME, respectively, were included in the analysis. The prevalence of mild DR was higher in the DR-DME group, but the frequencies of moderate and severe retinopathy were higher in the DR+DME group. Patients in the DR-DME group had better vision than those in the DR+DME group. Logistic regression analysis revealed that age (OR, 1.07), HbA1c (OR, 1.19), and Albumin-to-Creatinine Ratio (ACR) > 30 mg/g (OR, 3.37) were associated with an increased possibility of DME compared to DR-DME.Conclusion: Our study provides insights into the association between risk factors and DME. We found a statistically strong association between HbA1c levels, age, and ACR. Patients with poor metabolic control should undergo an extensive medical examination to screen for DME, which may be related to the chronicity of DM and renal damage. [ABSTRACT FROM AUTHOR]

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In phenylketonuria (PKU), an important component of the UK dietary management system is a 50 mg phenylalanine (Phe)/1 g protein exchange system used to allocate the Phe/natural protein intakes according to individual patient tolerance. Any foods containing protein ≤ 0.5 g/100 g or fruits/vegetables containing Phe ≤ 75 mg/100 g are allowed without measurement or limit. In children with PKU, we aimed to assess the difference between the prescribed natural protein intake and their actual consumed intake, and to calculate the natural protein/Phe intake from foods given without measurement or restriction. Over a 6-month duration, three one-day diet diaries were collected every month by caregivers of children with PKU at the beginning of a follow-up study. Dietary intakes of Phe, as well as natural and total protein intakes, were calculated using Nutritics® (v5.09). Weekly blood Phe spots were collected by caregivers. The target blood Phe level was ≤360 μmol/L for ages up to 12 years and ≤600 μmol/L for ages ≥12 years. Sixteen early treated children (69% females) with PKU were recruited. The median age was 11 years (range: 9–13), and most had classical PKU (n = 14/16). A median of 18 (range 12–18) one-day diaries and 22 blood spots were analysed for each subject over 6 months. The median prescribed natural protein was 6 g/day (range: 3–27), but when calculated, the actual median intake from all foods consumed was 10 g/day (range: 4–37). The median prescribed Phe was 300 mg/day (range: 150–1350), but the actual median intake was 500 mg/day (range: 200–1850). The median difference between the prescribed and actual natural protein daily intakes was +4 g/day (range: −2.5 to +11.5), with a median percentage increase of 40% for natural protein/Phe intake (p < 0.001). The median blood Phe level was 250 μmol/L (range 20–750), with 91% of blood Phe levels within the target range. Only one patient (11 years) had less than 75% of their blood Phe levels within the target range. The UK Phe exchange system provides flexibility in the dietary management of PKU. With this method, the actual natural protein intake was 167% higher than the prescribed amount. Although this led to a variable daily protein intake, the majority of children (n = 15/16) experienced no deterioration in their metabolic control. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a prevalent chronic disease in patients who die of COVID-19. The aim of this study was to investigate the clinical and metabolic characteristics of diabetic patients with COVID-19 during the pre-vaccination phase. A retrospective cohort study was conducted from February 2020 to February 2021 to examine the clinical and metabolic profiles of unvaccinated diabetic patients affected by COVID-19. Data were collected from claim databases, hospital discharge records, and clinical records within a healthcare district located in northeastern Italy with a population of 936,000. Potential prognostic indicators including sex, age, Body Mass Index (BMI), duration and type of diabetes, metabolic control, and the use of antidiabetic, antihypertensive, lipid-lowering, and antiplatelet therapies were investigated. For hospitalized patients, additional variables were recorded, such as length of hospital stay, blood pressure at admission, comorbidities, D-dimer levels, blood glucose (BG), in-hospital insulin and corticosteroid therapies, requirement for mechanical ventilation (i.e., orotracheal or tracheostomy), admission to the Intensive Care Unit (ICU), and mortality. Diabetic patients hospitalized for COVID-19 with a poorer prognosis were characterized by advanced age, longer diabetes duration, hypertension, higher usage of sulfonylureas, and lower usage of dietotherapy alone, metformin, Glucagon-Like Peptide-1 Receptor agonists (GLP1-Ra), and Renin-Angiotensin-Aldosterone System inhibitors (RAAS-i). Considering the potential for COVID-19 to become endemic, special care should be taken in managing older diabetic patients' treatments. • Use of RAAS-i prior to COVID-19 was found to be associated with the best outcomes. • Dietotherapy alone, metformin, and GLP1-Ra were related to fewer hospitalizations. • Use of sulfonylureas and in-hospital corticosteroids were related to poor prognosis. • The COVID-19 endemic phase demands cautious therapy for older diabetic patients. [ABSTRACT FROM AUTHOR]

Hypomagnesemia and unhealthy eating patterns are associated with poor glycemic control in individuals with type 2 diabetes mellitus (T2DM). This study aimed to associate magnesium status and dietary patterns with glycemic control in T2DM individuals. This cross-sectional study included 147 individuals with T2DM, aged between 19 and 59 years, of both sexes, residents in Sergipe/Brazil. The BMI, waist circumference, %body fat, plasma magnesium, serum glucose, insulin, %HbA1c, triacylglycerol, total cholesterol, LDL-c, and HDL-c were analyzed. Eating patterns were identified using a 24-h recall method. Logistic regression models were used to verify the association of magnesium status and dietary patterns with markers of glycemic control by adjusting for sex, age, time of T2DM diagnosis, and BMI. A P value < 0.05 was considered significant. Magnesium deficiency increased the chance of elevated %HbA1c by 5.893-fold (P = 0.041). Three main dietary patterns were identified: mixed (MDP), unhealthy (UDP), and healthy (HDP). UDP also increased the chance of elevated %HbA1c levels (P = 0.034). T2DM individuals' who presented magnesium deficiency had a higher chance of elevated %HbA1c levels (8.312-fold) and those in the lowest quartile (Q) of the UDP (Q1: P = 0.007; Q2: P = 0.043) had a lower chance of elevated %HbA1c levels. However, the lower quartiles of the HDP were associated with a greater chance of alterations in the %HbA1c level (Q1: P = 0.050; Q2: P = 0.044). No association was observed between MDP and the variables studied. Magnesium deficiency and UDP were associated with a higher chance of inadequate glycemic control in T2DM individuals. [ABSTRACT FROM AUTHOR]