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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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Pretreatment Fasting Glucose and Insulin as Determinants of Weight Loss on Diets Varying in Macronutrients and Dietary Fibers-The POUNDS LOST Study.
Hjorth, MF, Bray, GA, Zohar, Y, Urban, L, Miketinas, DC, Williamson, DA, Ryan, DH, Rood, J, Champagne, CM, Sacks, FM, et al
Nutrients. 2019;11(3)
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During the past 30 years, there has been a great deal of controversy about the composition of the optimal diet for weight loss and maintenance. The aim of this study was to analyse data from the POUNDS LOST trial, to investigate whether fasting plasma glucose (FPG) and fasting insulin (FI) are prognostic markers for long-term weight loss in four diets differing in carbohydrate, fat, and protein content, and assess the role of dietary fibre intake. This study was an analysis of the original trial for which baseline FPG levels were used to stratify subjects as being normoglycemic (FPG < 100 mg/dL) or prediabetic. Six hundred thirty-nine subjects were included of which 61% were women. Results show that subjects with normoglycemia lost the most body weight when randomized to the low-fat/high-protein diet, and that subjects with insulin resistance (high HOMA-IR) lost the most on the high-fat/high-protein diet. Furthermore, participants with the highest intake of dietary fibre lost more body weight during the 24-month dietary intervention period. Authors conclude that although modest differences in diet-specific weight loss between glycaemic phenotypes were identified, these findings need to be confirmed in randomised trials with this aim as a primary end-point.
Abstract
Efforts to identify a preferable diet for weight management based on macronutrient composition have largely failed, but recent evidence suggests that satiety effects of carbohydrates may depend on the individual's insulin-mediated cellular glucose uptake. Therefore, using data from the POUNDS LOST trial, pre-treatment fasting plasma glucose (FPG), fasting insulin (FI), and homeostatic model assessment of insulin resistance (HOMA-IR) were studied as prognostic markers of long-term weight loss in four diets differing in carbohydrate, fat, and protein content, while assessing the role of dietary fiber intake. Subjects with FPG <100 mg/dL lost 2.6 (95% CI 0.9;4.4, p = 0.003) kg more on the low-fat/high-protein (n = 132) compared to the low-fat/average-protein diet (n = 136). Subjects with HOMA-IR ≥4 lost 3.6 (95% CI 0.2;7.1, p = 0.038) kg more body weight on the high-fat/high-protein (n = 35) compared to high-fat/average-protein diet (n = 33). Regardless of the randomized diet, subjects with prediabetes and FI below the median lost 5.6 kg (95% CI 0.6;10.6, p = 0.030) more when consuming ≥35 g (n = 15) compared to <35 g dietary fiber/10 MJ (n = 16). Overall, subjects with normal glycemia lost most on the low-fat/high-protein diet, subjects with high HOMA-IR lost most on the high-fat/high protein diet, and subjects with prediabetes and low FI had particular benefit from dietary fiber in the diet.
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Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes: Assessment of Causal Relations.
Livesey, G, Taylor, R, Livesey, HF, Buyken, AE, Jenkins, DJA, Augustin, LSA, Sievenpiper, JL, Barclay, AW, Liu, S, Wolever, TMS, et al
Nutrients. 2019;11(6)
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It is generally accepted that certain diet and lifestyle choices contribute to a person’s risk of developing type 2 diabetes (T2D). In this meta-analysis, researchers set out to review previous studies and assess whether there is any evidence that the amount and type of carbohydrate (measured by Glycaemic Index (GI) and Glycaemic Load (GL)) in a person’s diet has a direct influence on their risk of developing T2D. The authors concluded with a high level of confidence that eating high GI and GL foods can lead to a higher risk of developing T2D. They suggest that nutrition advice that favours low GI and GL foods could produce significant cost savings for public healthcare.
Abstract
While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant relations but consideration of causality has been minimal. Here, the results of our recent meta-analyses of prospective cohort studies of 4 to 26-y follow-up are interpreted in the context of the nine Bradford-Hill criteria for causality, that is: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biological Gradient, (6) Plausibility, (7) Experimental evidence, (8) Analogy, and (9) Coherence. These criteria necessitated referral to a body of literature wider than prospective cohort studies alone, especially in criteria 6 to 9. In this analysis, all nine of the Hill's criteria were met for GI and GL indicating that we can be confident of a role for GI and GL as causal factors contributing to incident T2D. In addition, neither dietary fiber nor cereal fiber nor wholegrain were found to be reliable or effective surrogate measures of GI or GL. Finally, our cost-benefit analysis suggests food and nutrition advice favors lower GI or GL and would produce significant potential cost savings in national healthcare budgets. The high confidence in causal associations for incident T2D is sufficient to consider inclusion of GI and GL in food and nutrient-based recommendations.
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Men and women respond differently to rapid weight loss: Metabolic outcomes of a multi-centre intervention study after a low-energy diet in 2500 overweight, individuals with pre-diabetes (PREVIEW).
Christensen, P, Meinert Larsen, T, Westerterp-Plantenga, M, Macdonald, I, Martinez, JA, Handjiev, S, Poppitt, S, Hansen, S, Ritz, C, Astrup, A, et al
Diabetes, obesity & metabolism. 2018;20(12):2840-2851
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Overweight and obesity are major risk factors for developing type 2 diabetes mellitus. Men and women respond differently to weight loss programmes, with men typically losing more weight and more abdominal fat, whilst women lose more subcutaneous fat. The aim of this large multinational study was to compare the effects of weight loss induced by an 8‐week low energy diet on metabolic outcomes in overweight men and women with prediabetes. Study participants followed the Cambridge Weight Plan which is based on four formula meals, with a total of approximately 810kcal, per day, for eight weeks. Small amounts of non-starchy vegetables were allowed, as were psyllium husks in case of digestive problems. Men lost significantly more weight than women, 11.8% versus 10.3%. Insulin resistance improved similarly in men and women, but metabolic syndrome score improved more in men than in women. Men lost more fat than women and generally had more beneficial metabolic changes. Women had higher reductions in fat-free mass, bone mineral content and HDL cholesterol than men, raising the question whether rapid weight loss may have negative longer term effects for women.
Abstract
AIMS: The PREVIEW lifestyle intervention study (ClinicalTrials.gov Identifier: NCT01777893) is, to date, the largest, multinational study concerning prevention of type-2 diabetes. We hypothesized that the initial, fixed low-energy diet (LED) would induce different metabolic outcomes in men vs women. MATERIALS AND METHODS All participants followed a LED (3.4 MJ/810 kcal/daily) for 8 weeks (Cambridge Weight Plan). Participants were recruited from 8 sites in Europe, Australia and New Zealand. Those eligible for inclusion were overweight (BMI ≥ 25 kg/m2 ) individuals with pre-diabetes according to ADA-criteria. Outcomes of interest included changes in insulin resistance, fat mass (FM), fat-free mass (FFM) and metabolic syndrome Z-score. RESULTS In total, 2224 individuals (1504 women, 720 men) attended the baseline visit and 2020 (90.8%) completed the follow-up visit. Following the LED, weight loss was 16% greater in men than in women (11.8% vs 10.3%, respectively) but improvements in insulin resistance were similar. HOMA-IR decreased by 1.50 ± 0.15 in men and by 1.35 ± 0.15 in women (ns). After adjusting for differences in weight loss, men had larger reductions in metabolic syndrome Z-score, C-peptide, FM and heart rate, while women had larger reductions in HDL cholesterol, FFM, hip circumference and pulse pressure. Following the LED, 35% of participants of both genders had reverted to normo-glycaemia. CONCLUSIONS An 8-week LED induced different effects in women than in men. These findings are clinically important and suggest gender-specific changes after weight loss. It is important to investigate whether the greater decreases in FFM, hip circumference and HDL cholesterol in women after rapid weight loss compromise weight loss maintenance and future cardiovascular health.
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Effect of weight loss on the cardiovascular risk profile of obese patients with psoriasis.
Jensen, P, Zachariae, C, Christensen, R, Geiker, NR, Schaadt, BK, Stender, S, Astrup, A, Hansen, PR, Skov, L
Acta dermato-venereologica. 2014;94(6):691-4
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Psoriasis is a chronic inflammatory skin disease. It is characterised by a systemic immunological response which is mainly elicited by activated T-helper (Th)1 and Th17 lymphocytes. Like psoriasis, atherosclerosis is characterised by Th1-driven inflammation both systemically and locally in arterial walls and atherosclerotic plaques. The aim of this study was to examine the effect of weight reduction on traditional cardiovascular risk factors and on endothelial function. This study is a prospective randomised trial. The participants were randomised to either low-energy diet (n=30) providing 800–1,000 kcal/day for 8 weeks followed by 8 weeks of reduced food intake reaching 1,200 kcal/day or normal healthy foods (n=30) for 16 weeks. Results indicate that after 16 weeks, obese patients with psoriasis following the low-energy diet lost significantly more weight compared to controls encouraged to eat normal healthy foods. This resulted in significant reductions of several endpoints associated with increased cardiovascular risk. Authors conclude that certain components of the cardiovascular risk profile of obese patients with psoriasis can be effectively reduced by weight reduction.
Abstract
Psoriasis is associated with obesity and other cardiovascular risk factors including endothelial dysfunction. We aimed to investigate the effects of weight loss on the cardiovascular risk profile of obese patients with psoriasis. A randomised controlled study was conducted in which we measured the microvascular endothelial function with peripheral arterial tonometry (PAT), selected plasma markers of endothelial function, and traditional cardiovascular risk factors in 60 obese patients with psoriasis. The participants were randomised to either low-energy diet (n = 30) providing 800-1,000 kcal/day for 8 weeks followed by 8 weeks of reduced food intake reaching 1,200 kcal/day or normal healthy foods (n = 30) for 16 weeks. The intervention group lost significantly more weight than controls, which resulted in significant reductions of diastolic blood pressure, resting heart rate, total cholesterol, VLDL cholesterol, triglyceride, plasma glucose, glycated haemoglobin, and tissue plasminogen activator inhibitor. Microvascular endothelial function assessed by PAT remained unchanged. We conclude that certain components of the cardiovascular risk profile of obese patients with psoriasis can be significantly improved by weight reduction.
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Metabolic syndrome, circulating RBP4, testosterone, and SHBG predict weight regain at 6 months after weight loss in men.
Wang, P, Menheere, PP, Astrup, A, Andersen, MR, van Baak, MA, Larsen, TM, Jebb, S, Kafatos, A, Pfeiffer, AF, Martinez, JA, et al
Obesity (Silver Spring, Md.). 2013;21(10):1997-2006
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Metabolic syndrome (MetS) is a cluster of conditions including increased blood pressure, high blood sugar, excess body fat around the waist and abnormal cholesterol or triglyceride levels, leading to an increased risk of heart disease and type 2 diabetes. Weight loss helps to reduce MetS in the obese, but most people who lose weight regain it again, possibly due to changes in hormones and cell signalling proteins produced by fat cells, known as adipokines. The aim of this study was to examine the changes in sex hormones and adipokines and their role as predictors of weight regain in men. The study consisted of a weight-loss phase of 8 weeks on a low-calorie diet, followed by a follow-up phase of 6 months on one of four diets differing in protein content and glycaemic index. From each diet group, the researchers selected 6 men who had regained weight and 6 who had continued to lose weight during the follow-up period, and compared metabolic and hormonal markers between them. The researchers found that men who had MetS at the start of the study were nearly 3 times more likely to regain weight after the initial weight loss. A tendency to regain weight was correlated with high levels of retinol-binding protein, and low levels of both sex hormone binding globulin (SHBG) and testosterone. Among the hormones and proteins tested, SHBG showed the strongest correlation with obesity and MetS. The authors concluded that the hormones and proteins studied may play roles in the link between MetS and weight regain.
Abstract
OBJECTIVE Weight loss helps reduce the symptoms of the metabolic syndrome (MetS) in the obese, but weight regain after active weight loss is common. The changes and predictive role of circulating adipokines and sex hormones for weight regain in men during dietary intervention, and also the effect of basal MetS status on weight regain, were investigated. DESIGN AND METHODS Twenty-four men who continued to lose weight (WL) and 24 men who regained weight (WR) during the 6-month follow-up period after weight loss were selected from the Diogenes Study. Their circulating concentrations of leptin, adiponectin, retinol-binding protein 4 (RBP4), luteinizing hormone, prolactin, progesterone, total and free testosterone, and sex hormone-binding globulin (SHBG) were measured at baseline, after 8-week low-calorie diet-induced active weight loss, and after a subsequent 26-week ad libitum weight maintenance diet, and analyzed together with anthropometrical and physiological parameters. RESULTS Overweight and obese men with MetS at baseline had higher risk to regain weight (odds ratio = 2.8, P = 0.015). High baseline RBP4, low total testosterone, and low SHBG are predictors of weight loss regain (different between WR and WL with P = 0.001, 0.038, and 0.044, respectively). CONCLUSIONS These variables may play roles in the link between MetS and weight loss regain.
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Diets with high or low protein content and glycemic index for weight-loss maintenance.
Larsen, TM, Dalskov, SM, van Baak, M, Jebb, SA, Papadaki, A, Pfeiffer, AF, Martinez, JA, Handjieva-Darlenska, T, Kunešová, M, Pihlsgård, M, et al
The New England journal of medicine. 2010;363(22):2102-13
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The recommended diet composition for best preventing and managing obesity has remained inconclusive. The aim of this trial is to test the efficacy of moderate fat diets that vary in protein content and glycaemic index for preventing weight regain after weight loss. After completing an 8-week low calorie diet, participants were assigned to a low protein and low-glycaemic-index diet, a low-protein and high-glycaemic-index diet, a high-protein and low-glycaemic index diet, a high-protein and high-glycaemic-index diet or a control diet. A total of 548 participants adhered to and completed the 26-week intervention following the 8-week intensive weight loss programme. This study found that participants assigned to the high-protein and low-glycaemic index diet maintained the initial weight loss and had a higher rate of completion compared with the other diets. The authors conclude that this diet composition appears to be ideal for prevention of weight regain in obese patients following successful weight loss.
Abstract
BACKGROUND Studies of weight-control diets that are high in protein or low in glycemic index have reached varied conclusions, probably owing to the fact that the studies had insufficient power. METHODS We enrolled overweight adults from eight European countries who had lost at least 8% of their initial body weight with a 3.3-MJ (800-kcal) low-calorie diet. Participants were randomly assigned, in a two-by-two factorial design, to one of five ad libitum diets to prevent weight regain over a 26-week period: a low-protein and low-glycemic-index diet, a low-protein and high-glycemic-index diet, a high-protein and low-glycemic-index diet, a high-protein and high-glycemic-index diet, or a control diet. RESULTS A total of 1209 adults were screened (mean age, 41 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 34), of whom 938 entered the low-calorie-diet phase of the study. A total of 773 participants who completed that phase were randomly assigned to one of the five maintenance diets; 548 completed the intervention (71%). Fewer participants in the high-protein and the low-glycemic-index groups than in the low-protein-high-glycemic-index group dropped out of the study (26.4% and 25.6%, respectively, vs. 37.4%; P=0.02 and P=0.01 for the respective comparisons). The mean initial weight loss with the low-calorie diet was 11.0 kg. In the analysis of participants who completed the study, only the low-protein-high-glycemic-index diet was associated with subsequent significant weight regain (1.67 kg; 95% confidence interval [CI], 0.48 to 2.87). In an intention-to-treat analysis, the weight regain was 0.93 kg less (95% CI, 0.31 to 1.55) in the groups assigned to a high-protein diet than in those assigned to a low-protein diet (P=0.003) and 0.95 kg less (95% CI, 0.33 to 1.57) in the groups assigned to a low-glycemic-index diet than in those assigned to a high-glycemic-index diet (P=0.003). The analysis involving participants who completed the intervention produced similar results. The groups did not differ significantly with respect to diet-related adverse events. CONCLUSIONS In this large European study, a modest increase in protein content and a modest reduction in the glycemic index led to an improvement in study completion and maintenance of weight loss. (Funded by the European Commission; ClinicalTrials.gov number, NCT00390637.).