COVID-19 triggered encephalopathic crisis in a patient with glutaric aciduria type 1

Objectives The impact of coronavirus disease-19 (COVID-19) on metabolic outcome in patients with inborn errors of metabolism has rarely been discussed. Herein, we report a case with an acute encephalopathic crisis at the course of COVID-19 disease as the first sign of glutaric aciduria type 1 (GA-1). Case presentation A 9-month-old patient was admitted with encephalopathy and acute loss of acquired motor skills during the course of COVID-19 disease. She had lethargy, hypotonia, and choreoathetoid movements. In terms of COVID-19 encephalopathy, the reverse transcription-polymerase chain reaction assay test for COVID-19 was negative in cerebral spinal fluid. Brain imaging showed frontotemporal atrophy, bilateral subcortical and periventricular white matter, basal ganglia, and thalamic involvement. Elevated glutarylcarnitine in plasma and urinary excretion of glutaric and 3-OH-glutaric acids was noted. A homozygote mutation in the glutaryl-CoA dehydrogenase gene led to the diagnosis of GA-1. Conclusions With this report, neurological damage associated with COVID-19 has been reported in GA-1 patients for the first time in literature.

Multidisciplinary Approach for Hypothalamic Obesity in Children and Adolescents: A Preliminary Study

Hypothalamic obesity (HO) is delineated by an inexorable weight gain in subjects with hypothalamic disorder (congenital or acquired). The aim of the present study was to evaluate the effect of a multidisciplinary approach on weight trend and metabolic outcome in children and adolescents with hypothalamic disease who were overweight or obese. Thirteen patients (aged 8.1–16.1 years) received a personalized diet, accelerometer-based activity monitoring, and psychological assessment. Height, weight, body mass index (BMI), and serum metabolic parameters were assessed at baseline (T0) and after six months (T1). Metformin was introduced at T1 in four subjects who were then re-evaluated after six months (T2). At T1, weight gain was significantly reduced compared with T0 (0.29 ± 0.79 kg/month vs. 0.84 ± 0.55 kg/month, p = 0.03), and weight standard deviation score (SDS) and BMI SDS did not change significantly, as serum metabolic parameters. The four subjects treated with metformin showed a reduction of weight SDS and BMI SDS at T2. In conclusion, patients treated with our multidisciplinary approach showed, after 6 months, favorable results characterized by decreased weight gain and stabilization of weight SDS and BMI SDS in a condition usually characterized by inexorable weight gain. However, further analysis, larger cohorts, and longer follow-up are needed to confirm these preliminary data.

Metabolic outcome analysis of patients with and without diabetes mellitus undergoing cardiac rehabilitation for ischaemic heart disease

Funding Acknowledgements Type of funding sources: None. Introduction Patients with T2DM have reduced benefit from cardiac rehabilitation compared to non-diabetics. Additionally, diabetics are less likely to follow up after rehab completion. The European Society of Cardiology (ESC) recommend the use of SGLT2 inhibitors and GLP-1 analogues for T2DM with coronary artery disease. Both classes reduce all-cause mortality, improve HbA1C and obesity. Purpose We analysed our cardiac rehab population, comparing outcomes of patients with T2DM to those without; additionally, we appraised outcomes of new agents compared to prior standard care. Methods 180 patients were analysed, 90 diabetics and 90 non-diabetics. Data from 2016-2020 was reviewed. Sub-analysis was performed on those treated with SGLT2 inhibitors or GLP-1 analogues. Statistics performed on IBM SPSS v.26. Results Data points are displayed in Table 1. Patients on GLP-1/SGLT2 therapy comprised 14.44% (n = 13) of diabetics. Prescription of these agents increased from 0% in 2016 to 45% in 2020. Mean BMI loss in this group was comparable to non-diabetics, at 0.3615 kg/m2. Conclusions HTN and obesity was higher in diabetics, with lower total cholesterol - possibly explained by earlier recognition and treatment. BMI loss for non-diabetics was 2.13 times that of diabetics (0.362 kg/m2 vs 0.171 kg/m2, p = 0.2), but comparable to those on SGLT2 or GLP-1 therapy (0.3615 kg/m2). Use of these agents increased significantly as robust data became available. Table 1CategoryNon-Diabetics (Mean)Diabetics (Mean)P-ValueAge (Years)66.1 (SD +/- 8.73)67.73 (SD +/- 8.88)0.21Sex (Male)58%54%0.41Smoker or Ex25%27.7%0.52PCI (% of total)78%82%0.48CABG (% of total)22%18%0.74Cholesterol (mmol/L)4.21 (SD +/- 1.29)3.57 (SD +/- 0.9)<0.001BMI (kg/m2)- Prior27.56 (SD +/- 3.11)31.76 (SD +/- 5.89)<0.001BMI (kg/m2)- Post27.19 (SD +/- 3.13)30.98 (SD +/- 6.16)<0.001Change in BMI0.363 (SD +/- 0.525)0.171 (SD +/- 1.33)0.21Resting Heart Rate - Prior73.32 (SD +/- 10.75)76.94 (SD +/- 13.22)0.059Resting Heart Rate - Post69.46 (SD +/- 10.01)75.29 (SD +/- 11.21)<0.001Systolic BP (mmHg) - Prior141.9 (SD +/- 18.89)150.5 (SD +/- 18.87)0.0026Systolic BP (mmHG) - Post135.2 (SD +/- 17.65)140 (SD +/- 19.26)0.07Comparison of baseline demographics and metabolic data of those with diabetes mellitus to those without.

Effect of restoration of euthyroidism on visfatin concentrations and body composition in women

Dysregulation of thyroid function has known impact on body metabolism, however, data regarding metabolic outcome after restoration of thyroid function is limited. Therefore, the aim of the study was to investigate the effect of restoration of euthyroidism on serum visfatin, and its associations with insulin resistance and body composition. This is an observational study with consecutive enrollment. Forty-nine hyperthyroid (median age of 34 years) and 44 hypothyroid women (median age of 46 years) completed the study. Laboratory parameters and body composition analysis were assessed before and after the therapy. In the hyperthyroid group, visfatin concentrations increased (P < 0.0001), while glucose concentrations decreased (P < 0.0001). Total body mass and fat mass in the trunk and limbs significantly increased during the treatment. In the hypothyroid group, significant weight loss resulted from decrease of fat and muscle masses in trunk and limbs. Visfatin serum concentrations positively correlated with total fat mass (r = 0.19, P = 0.01) and insulin concentrations (r = 0.17, P = 0.018). In conclusion, restoration of thyroid function is not associated with beneficial changes in body composition, especially among hyperthyroid females.

Gut-derived Flavonifractor species variants are differentially enriched during in vitro incubation with quercetin

Flavonoids are a common component of the human diet with widely reported health-promoting properties. The gut microbiota transforms these compounds affecting the overall metabolic outcome of flavonoid consumption. Flavonoid-degrading bacteria are often studied in pure and mixed cultures but the multiple interactions between quercetin-degraders and the rest of the community have been overlooked. In this study, a comparative metataxonomic analysis of fecal communities supplemented with the flavonoid quercetin led us to identify a potential competitive exclusion interaction between two sequence variants related to the flavonoid-degrading species, Flavonifractor plautii, that belong to the same genus but different species. During incubation of fecal slurries with quercetin, the relative abundance of these two variants was inversely correlated; one variant, ASV_65f4, increased in relative abundance in half of the libraries and the other variant, ASV_a45d, in the other half. This pattern was also observed with 6 additional fecal samples that were transplanted into germ-free mice fed two different diets. Mouse’s diet did not change the pattern of dominance of either variant, and initial relative abundances did not predict which one ended up dominating. Potential distinct metabolic capabilities of these two Flavonifractor-related species were evidenced, as only one variant, ASV_65f4, became consistently enriched in complex communities supplemented with acetate but without quercetin. Genomic comparison analysis of the close relatives of each variant revealed that ASV_65f4 may be an efficient utilizer of ethanolamine which is formed from the phospholipid phosphatidylethanolamine that is abundant in the gut and feces. Other discordant features between ASV_65f4- and ASV_a45d-related groups may be the presence of flagellar and galactose-utilization genes, respectively. Overall, we showed that the Flavonifractor genus harbors variants that present a pattern of negative co-occurrence and that may have different metabolic and morphological traits, whether these differences affect the dynamic of quercetin degradation warrants further investigation.

Sugar causes obesity and metabolic syndrome in mice independently of sweet taste

Intake of sugars, especially the fructose component, is strongly associated with the development of obesity and metabolic syndrome, but the relative role of taste versus metabolism in driving preference, intake, and metabolic outcome is not fully understood. We aimed to evaluate the preference for sweet substances and the tendency to develop metabolic syndrome in response to these sugars in mice lacking functional taste signaling [P2X2 (P2X purinoreceptor 2)/P2X3 (P2X purinoreceptor 3) double knockout mice (DKO)] and mice unable to metabolize fructose (fructokinase knockout mice). Of interest, our data indicate that despite their inability to taste sweetness, P2X2/3 DKO mice still prefer caloric sugars (including fructose and glucose) to water in long-term testing, although with diminished preference compared with control mice. Despite reduced intake of caloric sugars by P2X2/3 DKO animals, the DKO mice still show increased levels of the sugar-dependent hormone FGF21 (fibroblast growth factor 21) in plasma and liver. Despite lower sugar intake, taste-blind mice develop severe features of metabolic syndrome due to reduced sensitivity to leptin, reduced ability to mobilize and oxidize fats, and increased hepatic de novo lipogenesis. In contrast to P2X2/3 DKO and wild-type mice, fructokinase knockout mice, which cannot metabolize fructose and are protected against fructose-induced metabolic syndrome, demonstrate reduced preference and intake for all fructose-containing sugars tested but not for glucose or artificial sweeteners. Based on these observations, we conclude that sugar can induce metabolic syndrome in mice independently of its sweet properties. Furthermore, our data demonstrate that the metabolism of fructose is necessary for sugar to drive intake and preference in mice.