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Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial.
Thomsen, MN, Skytte, MJ, Samkani, A, Carl, MH, Weber, P, Astrup, A, Chabanova, E, Fenger, M, Frystyk, J, Hartmann, B, et al
Diabetologia. 2022;65(3):506-517
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The carbohydrate restricted diet has been shown to be beneficial for Type 2 diabetes (T2D) management and reducing cardiovascular disease risk. This open-label, parallel randomised controlled trial involved Type 2 diabetic patients taking antidiabetic medications who restricted their energy intake by following either a carbohydrate-reduced high protein diet or a conventional diabetic diet. Participants in both groups had a 5.9% reduction in body weight, similar changes in fasting NEFA, apoB, apoA-1, total cholesterol, LDL-cholesterol, HDL-cholesterol, and non-HDL cholesterol, and a significant reduction in fasting glucose, insulin, C-peptide, and HOMA2-IR after 6 weeks of intervention. Carbohydrate-reduced high protein diet group showed a greater reduction in HbA1c and diurnal mean glucose, glycaemic variability, fasting triacylglycerol concentration and liver fat content. Carbohydrate-reduced high protein diet caused an adverse reaction in some patients, and those following a carbohydrate-reduced high protein diet excreted more urea than those eating a conventional diabetic diet. To confirm the results of this study, long-term robust studies are needed. This study can assist healthcare professionals in understanding the benefits of following a carbohydrate-reduced high protein diet in improving glycaemic control, triglyceride levels, and reducing body weight in Type 2 diabetes patients.
Abstract
AIMS/HYPOTHESIS Lifestyle modification and weight loss are cornerstones of type 2 diabetes management. However, carbohydrate restriction may have weight-independent beneficial effects on glycaemic control. This has been difficult to demonstrate because low-carbohydrate diets readily decrease body weight. We hypothesised that carbohydrate restriction enhances the beneficial metabolic effects of weight loss in type 2 diabetes. METHODS This open-label, parallel RCT included adults with type 2 diabetes, HbA1c 48-97 mmol/mol (6.5-11%), BMI >25 kg/m2, eGFR >30 ml min-1 [1.73 m]-2 and glucose-lowering therapy restricted to metformin or dipeptidyl peptidase-4 inhibitors. Participants were randomised by a third party and assigned to 6 weeks of energy restriction (all foods were provided) aiming at ~6% weight loss with either a carbohydrate-reduced high-protein diet (CRHP, percentage of total energy intake [E%]: CH30/P30/F40) or a conventional diabetes diet (CD, E%: CH50/P17/F33). Fasting blood samples, continuous glucose monitoring and magnetic resonance spectroscopy were used to assess glycaemic control, lipid metabolism and intrahepatic fat. Change in HbA1c was the primary outcome; changes in circulating and intrahepatic triacylglycerol were secondary outcomes. Data were collected at Copenhagen University Hospital (Bispebjerg and Herlev). RESULTS Seventy-two adults (CD 36, CRHP 36, all white, 38 male sex) with type 2 diabetes (mean duration 8 years, mean HbA1c 57 mmol/mol [7.4%]) and mean BMI of 33 kg/m2 were enrolled, of which 67 (CD 33, CRHP 34) completed the study. Body weight decreased by 5.8 kg (5.9%) in both groups after 6 weeks. Compared with the CD diet, the CRHP diet further reduced HbA1c (mean [95% CI] -1.9 [-3.5, -0.3] mmol/mol [-0.18 (-0.32, -0.03)%], p = 0.018) and diurnal mean glucose (mean [95% CI] -0.8 [-1.2, -0.4] mmol/l, p < 0.001), stabilised glucose excursions by reducing glucose CV (mean [95% CI] -4.1 [-5.9, -2.2]%, p < 0.001), and augmented the reductions in fasting triacylglycerol concentration (by mean [95% CI] -18 [-29, -6]%, p < 0.01) and liver fat content (by mean [95% CI] -26 [-45, 0]%, p = 0.051). However, pancreatic fat content was decreased to a lesser extent by the CRHP than the CD diet (mean [95% CI] 33 [7, 65]%, p = 0.010). Fasting glucose, insulin, HOMA2-IR and cholesterol concentrations (total, LDL and HDL) were reduced significantly and similarly by both diets. CONCLUSIONS/INTERPRETATION Moderate carbohydrate restriction for 6 weeks modestly improved glycaemic control, and decreased circulating and intrahepatic triacylglycerol levels beyond the effects of weight loss itself compared with a CD diet in individuals with type 2 diabetes. Concurrent differences in protein and fat intakes, and the quality of dietary macronutrients, may have contributed to these results and should be explored in future studies. TRIAL REGISTRATION ClinicalTrials.gov NCT03814694. FUNDING The study was funded by Arla Foods amba, The Danish Dairy Research Foundation, and Copenhagen University Hospital Bispebjerg Frederiksberg.
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Elucidation of Prebiotics, Probiotics, Postbiotics, and Target from Gut Microbiota to Alleviate Obesity via Network Pharmacology Study.
Oh, KK, Gupta, H, Min, BH, Ganesan, R, Sharma, SP, Won, SM, Jeong, JJ, Lee, SB, Cha, MG, Kwon, GH, et al
Cells. 2022;11(18)
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The prevalence of obesity and associated comorbidities, such as diabetes, heart attack, hypertension, and cancer, is increasing worldwide. Microbes in the gut may play a significant role in the management of obesity by fermenting dietary fibres and producing metabolites such as short-chain fatty acids and flavonoids. In this meta-analysis, data were retrieved about gut microbial metabolites from the gutMGene database to evaluate the beneficial effects of prebiotics, probiotics, and postbiotics on key targets of obesity. Tryptophan was converted into beneficial metabolites such as indole by Escherichia coli, and isoflavones were converted into equol by Lactobacillus paracasei JS1. A positive effect may be exerted by these metabolites on the treatment of obesity. According to this meta-analysis, equol can reduce the levels of Interleukin-6, one of the inflammatory cytokines associated with obesity. Prebiotic isoflavone is fermented by probiotic Lactobacillus paracasei JS1 to produce equol, a postbiotic that inhibits the action of interleukin-6 and exerts a beneficial effect on obesity. In addition to understanding the relationship between prebiotics, probiotics, and postbiotics, healthcare professionals can use the results of this study to modulate the pathophysiology of obesity. It is necessary to conduct further rigorous research in order to evaluate the pharmacological value of the elements.
Abstract
The metabolites produced by the gut microbiota have been reported as crucial agents against obesity; however, their key targets have not been revealed completely in complex microbiome systems. Hence, the aim of this study was to decipher promising prebiotics, probiotics, postbiotics, and more importantly, key target(s) via a network pharmacology approach. First, we retrieved the metabolites related to gut microbes from the gutMGene database. Then, we performed a meta-analysis to identify metabolite-related targets via the similarity ensemble approach (SEA) and SwissTargetPrediction (STP), and obesity-related targets were identified by DisGeNET and OMIM databases. After selecting the overlapping targets, we adopted topological analysis to identify core targets against obesity. Furthermore, we employed the integrated networks to microbiota-substrate-metabolite-target (MSMT) via R Package. Finally, we performed a molecular docking test (MDT) to verify the binding affinity between metabolite(s) and target(s) with the Autodock 1.5.6 tool. Based on holistic viewpoints, we performed a filtering step to discover the core targets through topological analysis. Then, we implemented protein-protein interaction (PPI) networks with 342 overlapping target, another subnetwork was constructed with the top 30% degree centrality (DC), and the final core networks were obtained after screening the top 30% betweenness centrality (BC). The final core targets were IL6, AKT1, and ALB. We showed that the three core targets interacted with three other components via the MSMT network in alleviating obesity, i.e., four microbiota, two substrates, and six metabolites. The MDT confirmed that equol (postbiotics) converted from isoflavone (prebiotics) via Lactobacillus paracasei JS1 (probiotics) can bind the most stably on IL6 (target) compared with the other four metabolites (3-indolepropionic acid, trimethylamine oxide, butyrate, and acetate). In this study, we demonstrated that the promising substate (prebiotics), microbe (probiotics), metabolite (postbiotics), and target are suitable for obsesity treatment, providing a microbiome basis for further research.
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Food Exclusion Based on IgG Antibodies Alleviates Symptoms in Ulcerative Colitis: A Prospective Study.
Jian, L, Anqi, H, Gang, L, Litian, W, Yanyan, X, Mengdi, W, Tong, L
Inflammatory bowel diseases. 2018;24(9):1918-1925
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Ulcerative Colitis (UC) is a chronic debilitating inflammatory bowel disease that may need lifetime management. Dietary management of UC by eliminating food antigens that may be causing a delayed immune response is one of the approaches used widely to manage the disease. Food intolerance, mediated by immunoglobulin G antibodies in response to food antigens that are otherwise harmless, could be one cause of UC. Low levels of digestive enzymes may result in poor digestion of glucose, amino acids, and glycerol, followed by an immune reaction that leads to food sensitivities. Ninety-seven UC patients were enrolled in this open-label, stratified, prospective, randomised controlled trial to evaluate the effect of an elimination diet versus a sham diet (a normal healthy diet). Following an IgG-specific exclusion diet for six months resulted in the alleviation of UC symptoms and an improvement in health-related quality of life. Further studies are needed to confirm the effectiveness of the exclusion diet since the intervention group did not show a significant reduction in IgG antibody levels. These results can be used by healthcare professionals to understand the potential role of exclusion diets in the management of UC.
Abstract
BACKGROUND Most patients with ulcerative colitis (UC) rely predominantly on medication for disease control. Diet interventions can reduce pharmaceutical expenditures and prolong remission. We designed a prospective study to evaluate whether an immunoglobulin G (IgG)-guided exclusion diet would improve symptoms and quality of life (QoL) in patients with UC. METHODS The 6-month diet intervention included 97 patients with UC, who were randomly divided into an intervention group (n = 49) and a control (n = 48) group. Individual diet plans were created for the intervention group according to IgG titers; the control group ate a healthy diet as normal. Observational indices included disease activity, extraintestinal manifestations, nutritional status, and QoL. Relationships between food-specific IgG antibodies and these indices were also analyzed. RESULTS At baseline, there were no significant differences between the groups. Food-specific IgG antibodies were detected in 70.10% of participants. After intervention, the Mayo score was significantly lower in the intervention group than in the control group (2.41 ± 0.89 vs 3.52 ± 1.15, P < 0.05). The number of patients with extraintestinal manifestations decreased from 7 to 2 in the intervention group and from 6 to 5 in the control group. As for nutritive indices, the intervention group had higher mean body mass index and albumin than the control group (23.88 ± 3.31 vs 21.50 ± 6.24 kg/m2, respectively, P < 0.05; 48.05 ± 6.39 vs 45.72 ± 5.48 g/L, respectively, P < 0.05), whereas prealbumin and transferrin were not significantly different between the groups. QoL improved after food exclusion (P < 0.05). CONCLUSIONS An IgG-guided exclusion diet ameliorated UC symptoms and improved QoL. Interactions between IgG-based food intolerance and UC warrant further study.