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Effects of a low-carbohydrate diet on insulin-resistant dyslipoproteinemia-a randomized controlled feeding trial.
Ebbeling, CB, Knapp, A, Johnson, A, Wong, JMW, Greco, KF, Ma, C, Mora, S, Ludwig, DS
The American journal of clinical nutrition. 2022;115(1):154-162
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Diets high in carbohydrates and particularly processed carbohydrates can increase the risk for developing a dysfunction in the body’s ability to take up sugar from the blood, known as insulin resistance. However how this relates to insulin resistance can contribute to the development of many diseases such as type 2 diabetes, heart disease and stroke, which highlights the importance in preventing this dysfunction. This randomised control trial of 148 individuals aimed to determine the role of low, medium, and high carbohydrate diets with varying saturated fat content on measures for insulin resistance. The results showed that regardless of the fat content, it was the level of carbohydrate that determined the effect on measures of insulin resistance. High saturated fat and low-carbohydrate diets improved insulin resistance and low saturated fat high carbohydrate diets worsened insulin resistance. Improvements were also observed in blood lipids with a high fat low carbohydrate diet. It was concluded that a diet low in carbohydrates, but high in saturated fat improved insulin resistance and blood lipid levels. This study could be used by healthcare professionals to understand that a diet, which replaces fat with carbohydrates may be worsening insulin resistance and that low carbohydrate diets may be of benefit.
Abstract
BACKGROUND Carbohydrate restriction shows promise for diabetes, but concerns regarding high saturated fat content of low-carbohydrate diets limit widespread adoption. OBJECTIVES This preplanned ancillary study aimed to determine how diets varying widely in carbohydrate and saturated fat affect cardiovascular disease (CVD) risk factors during weight-loss maintenance. METHODS After 10-14% weight loss on a run-in diet, 164 participants (70% female; BMI = 32.4 ± 4.8 kg/m2) were randomly assigned to 3 weight-loss maintenance diets for 20 wk. The prepared diets contained 20% protein and differed 3-fold in carbohydrate (Carb) and saturated fat as a proportion of energy (Low-Carb: 20% carbohydrate, 21% saturated fat; Moderate-Carb: 40%, 14%; High-Carb: 60%, 7%). Fasting plasma samples were collected prerandomization and at 20 wk. Lipoprotein insulin resistance (LPIR) score was calculated from triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P). Other outcomes included lipoprotein(a), triglycerides, HDL cholesterol, LDL cholesterol, adiponectin, and inflammatory markers. Repeated measures ANOVA was used for intention-to-treat analysis. RESULTS Retention was 90%. Mean change in LPIR (scale 0-100) differed by diet in a dose-dependent fashion: Low-Carb (-5.3; 95% CI: -9.2, -1.5), Moderate-Carb (-0.02; 95% CI: -4.1, 4.1), High-Carb (3.6; 95% CI: -0.6, 7.7), P = 0.009. Low-Carb also favorably affected lipoprotein(a) [-14.7% (95% CI: -19.5, -9.5), -2.1 (95% CI: -8.2, 4.3), and 0.2 (95% CI: -6.0, 6.8), respectively; P = 0.0005], triglycerides, HDL cholesterol, large/very large TRL-P, large HDL-P, and adiponectin. LDL cholesterol, LDL-P, and inflammatory markers did not differ by diet. CONCLUSIONS A low-carbohydrate diet, high in saturated fat, improved insulin-resistant dyslipoproteinemia and lipoprotein(a), without adverse effect on LDL cholesterol. Carbohydrate restriction might lower CVD risk independently of body weight, a possibility that warrants study in major multicentered trials powered on hard outcomes. The registry is available through ClinicialTrials.gov: https://clinicaltrials.gov/ct2/show/NCT02068885.
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Multi-scale mechanistic modelling of the host defence in invasive aspergillosis reveals leucocyte activation and iron acquisition as drivers of infection outcome.
Ribeiro, HA, Vieira, LS, Scindia, Y, Adhikari, B, Wheeler, M, Knapp, A, Schroeder, W, Mehrad, B, Laubenbacher, R
Journal of the Royal Society, Interface. 2022;(189):20210806
Abstract
Aspergillus species are ubiquitous environmental moulds, with spores inhaled daily by most humans. Immunocompromised hosts can develop an invasive infection resulting in high mortality. There is, therefore, a pressing need for host-centric therapeutics for this infection. To address it, we created a multi-scale computational model of the infection, focused on its interaction with the innate immune system and iron, a critical nutrient for the pathogen. The model, parameterized using published data, was found to recapitulate a wide range of biological features and was experimentally validated in vivo. Conidial swelling was identified as critical in fungal strains with high growth, whereas the siderophore secretion rate seems to be an essential prerequisite for the establishment of the infection in low-growth strains. In immunocompetent hosts, high growth, high swelling probability and impaired leucocyte activation lead to a high conidial germination rate. Similarly, in neutropenic hosts, high fungal growth was achieved through synergy between high growth rate, high swelling probability, slow leucocyte activation and high siderophore secretion. In summary, the model reveals a small set of parameters related to fungal growth, iron acquisition and leucocyte activation as critical determinants of the fate of the infection.
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Oral High-Dose Vitamin D Dissolved in Oil Raised Serum 25-Hydroxy-Vitamin D to Physiological Levels in Obese Patients After Sleeve Gastrectomy-A Double-Blind, Randomized, and Placebo-Controlled Trial.
Wolf, E, Utech, M, Stehle, P, Büsing, M, Helfrich, HP, Stoffel-Wagner, B, Egert, S, Alteheld, B, Riege, R, Knapp, A, et al
Obesity surgery. 2016;(8):1821-9
Abstract
BACKGROUND Osteomalacia and cardiometabolic disorders are favored in morbidly obese patients due to an inadequate vitamin D (VD) status. Former trials supplementing orally VD (20-50 μg/day) in crystalline form after sleeve gastrectomy (SG) could not stabilize serum 25-hydroxycholecalciferol levels at predefined concentrations (≥50 nmol/l). We hypothesized that VD in an oily suspension would increase its bioavailability resulting in normal serum VD levels minimizing markers of cardiometabolic risk. METHODS Morbidly obese patients (n = 94, BMI 51.8 ± 11.5 kg/m(2)) received orally 80 μg/day VD3 dissolved in oil or placebo (pure oil) in a randomized, double-blind, parallel-group study for 12 weeks after SG. 25-hydroxycholecalciferol, parathyroid hormone, albumin, alkaline phosphatase, phosphate, magnesium, calcium, creatinine, C-reactive protein, lipids, glucose, and glycated hemoglobin were determined in serum/plasma before surgery and after 4 and 12 weeks of supplementation. Intake of energy, fat, and VD were monitored using a 3-day food record. RESULTS Seventy-nine patients were included in statistical analysis. Preoperatively, 77.2 and 40.5 % presented 25-hydroxycholecalciferol levels <75 and <50 nmol/l, respectively. After 12 weeks of supplementation, significantly more patients in the VD group exhibited levels >50 nmol/l (92 %) and >75 nmol/l (68 %) compared to the placebo group (54 and 22 %, respectively). Parameters of mineral metabolism and cardiometabolic risk were not modulated by intervention. CONCLUSION Supplementation of 80 μg/day VD3 by oil is an effective and safe measure to prevent VD deficiency and to treat a preexisting undersupply in patients after SG. Cardiometabolic risk factors were, however, not affected; probably, higher VD doses might be necessary. CLINICAL TRIAL REGISTRATION This trial was registered retrospectively on November 14, 2014, at the German Clinical Trials Register as DRKS00007143.
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Apoptosis-related gene expression in glioblastoma (LN-18) and medulloblastoma (Daoy) cell lines.
Wybranska, I, Polus, A, Mikolajczyk, M, Knapp, A, Sliwa, A, Zapala, B, Staszel, T, Dembinska-Kiec, A
Human cell. 2013;(4):137-48
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Abstract
The expression of apoptosis genes in a commercial pre-designed low-density array from Applied Biosystems was evaluated in two human brain cancer cell models, LN-18 and Daoy (HTB-186™) in comparison to the reference human primary endothelial cells under basic conditions. Analysis of the gene expression in the cancer cell lines compared to the normal control revealed features reflecting anti-apoptotic and inflammatory characteristics of the former. There was an overall downregulation of apoptosis-stimulating genes in both cancer cell lines, along with an upregulation of certain apoptosis inhibitors. A number of genes demonstrated statistically significant changes in their expressions, including BAX (BCL2-associated X protein); the CARD4/NLR family, CARD domain containing 4; CASP10 (caspase 10, apoptosis-related cysteine peptidase); DAP1 (death-associated protein kinase 1), and BIRC5 (baculoviral IAP repeat-containing 5). Anti-apoptotic potential in both cell lines was demonstrated by changes in the Bax:Bcl-2 ratio and downregulation of the APAF1 gene in LN18 cells. There was also significant downregulation of extrinsic signals and the TNF/FADD/inflammatory cascade, and upregulation of caspase inhibitors (IAPs). These results provided a novel molecular characterization of important human cancer cell lines, which might provide a useful research tool for investigating the experimental model of the CNS cell.