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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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Timing of daily calorie loading affects appetite and hunger responses without changes in energy metabolism in healthy subjects with obesity.
Ruddick-Collins, LC, Morgan, PJ, Fyfe, CL, Filipe, JAN, Horgan, GW, Westerterp, KR, Johnston, JD, Johnstone, AM
Cell metabolism. 2022;34(10):1472-1485.e6
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Recent research has shown that the time of the day when a larger meal is consumed may influence energy utilisation, positively affecting weight loss. This randomised, crossover, isocaloric and eucaloric controlled feeding trial compared morning-loaded calorie intake with evening-loaded calorie intake to assess its effects on weight and metabolism. Thirty healthy, overweight, or obese individuals participated in this study for four weeks and assessed their energy intake and energy expenditure. Based on the findings of this study, there were no discernible variations in either resting metabolic rate or total energy expenditure based on the timing of energy intake. Morning loaded diet can significantly lower hunger and improve satiety compared to the evening-loaded diet. Because of these effects, a morning-loaded diet may aid weight loss through behavioural adaptations. Healthcare professionals can use the results of this study to understand the benefits of morning-loaded calorie intake in terms of hunger suppression and increased satiety which may promote weight loss through behavioural change. Further robust studies are required to evaluate the metabolic outcomes and energy metabolism followed by morning-loaded energy intake and evening-loaded energy intake.
Abstract
Morning loaded calorie intake in humans has been advocated as a dietary strategy to improve weight loss. This is also supported by animal studies suggesting time of eating can prevent weight gain. However, the underlying mechanisms through which timing of eating could promote weight loss in humans are unclear. In a randomized crossover trial (NCT03305237), 30 subjects with obesity/overweight underwent two 4-week calorie-restricted but isoenergetic weight loss diets, with morning loaded or evening loaded calories (45%:35%:20% versus 20%:35%:45% calories at breakfast, lunch, and dinner, respectively). We demonstrate no differences in total daily energy expenditure or resting metabolic rate related to the timing of calorie distribution, and no difference in weight loss. Participants consuming the morning loaded diet reported significantly lower hunger. Thus, morning loaded intake (big breakfast) may assist with compliance to weight loss regime through a greater suppression of appetite.
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Effect of a Personalized Diet to Reduce Postprandial Glycemic Response vs a Low-fat Diet on Weight Loss in Adults With Abnormal Glucose Metabolism and Obesity: A Randomized Clinical Trial.
Popp, CJ, Hu, L, Kharmats, AY, Curran, M, Berube, L, Wang, C, Pompeii, ML, Illiano, P, St-Jules, DE, Mottern, M, et al
JAMA network open. 2022;5(9):e2233760
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Postprandial glycaemic response (PPGR) to foods can be different from person to person. This could be the reason why people experience different weight loss outcomes with standardised diets such as a low glycaemic index diet, low-fat diet or a low carbohydrate diet. In this single-centre, population-based, randomised, blinded clinical trial, 204 participants with irregular glucose metabolism and obesity were randomised to consume either a low-fat or personalised diet for six months in combination with fourteen behavioural change counselling sessions. The participants in the personalised diet group received a colour-coded meal score to indicate their estimated PPGR for different foods. The results of this study showed no significant weight reduction in the personalised diet group compared to the low-fat diet. Further robust studies are required to develop appropriate precision nutrition interventions for weight loss and energy balance. However, healthcare professionals can use the results of this study to understand that both a low-fat diet and a personalised diet, coupled with behavioural counselling, may be effective in promoting weight loss in obese populations with irregular glucose metabolism.
Abstract
IMPORTANCE Interindividual variability in postprandial glycemic response (PPGR) to the same foods may explain why low glycemic index or load and low-carbohydrate diet interventions have mixed weight loss outcomes. A precision nutrition approach that estimates personalized PPGR to specific foods may be more efficacious for weight loss. OBJECTIVE To compare a standardized low-fat vs a personalized diet regarding percentage of weight loss in adults with abnormal glucose metabolism and obesity. DESIGN, SETTING, AND PARTICIPANTS The Personal Diet Study was a single-center, population-based, 6-month randomized clinical trial with measurements at baseline (0 months) and 3 and 6 months conducted from February 12, 2018, to October 28, 2021. A total of 269 adults aged 18 to 80 years with a body mass index (calculated as weight in kilograms divided by height in meters squared) ranging from 27 to 50 and a hemoglobin A1c level ranging from 5.7% to 8.0% were recruited. Individuals were excluded if receiving medications other than metformin or with evidence of kidney disease, assessed as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration equation, to avoid recruiting patients with advanced type 2 diabetes. INTERVENTIONS Participants were randomized to either a low-fat diet (<25% of energy intake; standardized group) or a personalized diet that estimates PPGR to foods using a machine learning algorithm (personalized group). Participants in both groups received a total of 14 behavioral counseling sessions and self-monitored dietary intake. In addition, the participants in the personalized group received color-coded meal scores on estimated PPGR delivered via a mobile app. MAIN OUTCOMES AND MEASURES The primary outcome was the percentage of weight loss from baseline to 6 months. Secondary outcomes included changes in body composition (fat mass, fat-free mass, and percentage of body weight), resting energy expenditure, and adaptive thermogenesis. Data were collected at baseline and 3 and 6 months. Analysis was based on intention to treat using linear mixed modeling. RESULTS Of a total of 204 adults randomized, 199 (102 in the personalized group vs 97 in the standardized group) contributed data (mean [SD] age, 58 [11] years; 133 women [66.8%]; mean [SD] body mass index, 33.9 [4.8]). Weight change at 6 months was -4.31% (95% CI, -5.37% to -3.24%) for the standardized group and -3.26% (95% CI, -4.25% to -2.26%) for the personalized group, which was not significantly different (difference between groups, 1.05% [95% CI, -0.40% to 2.50%]; P = .16). There were no between-group differences in body composition and adaptive thermogenesis; however, the change in resting energy expenditure was significantly greater in the standardized group from 0 to 6 months (difference between groups, 92.3 [95% CI, 0.9-183.8] kcal/d; P = .05). CONCLUSIONS AND RELEVANCE A personalized diet targeting a reduction in PPGR did not result in greater weight loss compared with a low-fat diet at 6 months. Future studies should assess methods of increasing dietary self-monitoring adherence and intervention exposure. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03336411.
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Diverging metabolic effects of 2 energy-restricted diets differing in nutrient quality: a 12-week randomized controlled trial in subjects with abdominal obesity.
Schutte, S, Esser, D, Siebelink, E, Michielsen, CJR, Daanje, M, Matualatupauw, JC, Boshuizen, HC, Mensink, M, Afman, LA
The American journal of clinical nutrition. 2022;116(1):132-150
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Energy restriction (ER) diets are considered an effective strategy for managing obesity and preventing or reducing the risk of associated comorbidities. However, there are very few previous studies comparing the quality of energy restriction diets and their effect on maximising the health benefits. Therefore, this 12-week, parallel-designed, randomised controlled trial compared the effects of a 25% high-quality ER diet with a 25% low-quality ER diet and a habitual diet on cardiometabolic risk factors of 110 participants with abdominal obesity. Both ER diets were nutritionally balanced. The high-quality ER diet had added Monounsaturated fatty acids (MUFAs), Omega-3 Polyunsaturated fatty acids (n-3 PUFAs), fibre, and plant protein and had less fructose in it. The low-quality ER diet contained Saturated fatty acids (SFAs) and monosaccharides such as fructose. At the end of the 12-week trial, participants on the 25% high-quality diet showed more promising results in weight loss, reduction in cholesterol and triglycerides, and adipose tissue gene expression of energy metabolism pathways compared to the 25% low-quality ER diet. Insulin-sensitive participants with abdominal obesity on a 25% high-quality diet lost more weight compared to the rest of the participants. Further robust studies are required to evaluate the findings due to the limitations of this study. However, healthcare professionals can use the results of this study to understand the beneficial effects of an ER diet when it is enriched with specific nutrients.
Abstract
BACKGROUND Despite the established relation between energy restriction (ER) and metabolic health, the most beneficial nutrient composition of a weight-loss diet is still a subject of debate. OBJECTIVES The aim of the study was to examine the additional effects of nutrient quality on top of ER. METHODS A parallel-designed, 12-week 25% ER dietary intervention study was conducted (clinicaltrials.gov: NCT02194504). Participants aged 40-70 years with abdominal obesity were randomized over 3 groups: a 25% ER high-nutrient-quality diet (n = 40); a 25% ER low-nutrient-quality diet (n = 40); or a habitual diet (n = 30). Both ER diets were nutritionally adequate, and the high-nutrient-quality ER diet was enriched in MUFAs, n-3 PUFAs, fiber, and plant protein and reduced in fructose. Before and after the intervention, intrahepatic lipids, body fat distribution, fasting and postprandial responses to a mixed-meal shake challenge test of cardiometabolic risk factors, lipoproteins, vascular measurements, and adipose tissue transcriptome were assessed. RESULTS The high-nutrient-quality ER diet (-8.4 ± 3.2) induced 2.1 kg more weight loss (P = 0.007) than the low-nutrient-quality ER diet (-6.3 ± 3.9), reduced fasting serum total cholesterol (P = 0.014) and plasma triglycerides (P < 0.001), promoted an antiatherogenic lipoprotein profile, and induced a more pronounced decrease in adipose tissue gene expression of energy metabolism pathways than the low-quality ER diet. Explorative analyses showed that the difference in weight loss between the two ER diets was specifically present in insulin-sensitive subjects (HOMA-IR ≤ 2.5), in whom the high-nutrient-quality diet induced 3.9 kg more weight loss than the low-nutrient-quality diet. CONCLUSIONS A high-nutrient-quality 25% ER diet is more beneficial for cardiometabolic health than a low-nutrient-quality 25% ER diet. Overweight, insulin-sensitive subjects may benefit more from a high- than a low-nutrient-quality ER diet with respect to weight loss, due to potential attenuation of glucose-induced lipid synthesis in adipose tissue.
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Consuming a Protein and Fiber-Based Supplement Preload Promotes Weight Loss and Alters Metabolic Markers in Overweight Adults in a 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial.
Glynn, EL, Fleming, SA, Edwards, CG, Wilson, MJ, Evans, M, Leidy, HJ
The Journal of nutrition. 2022;152(6):1415-1425
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One of the challenges of reduced-calorie diets is the inability to control appetite. Reductions in food intake can lead to the activation of neurological pathways that increase hunger and food cravings. Adjusting nutrient intake has the potential to serve as an effective strategy for increasing feelings of satiety, which can lead to improved appetite control. The aim of this study was to determine if greater weight loss and greater changes in body composition and metabolic outcomes could be achieved following a 12-wk energy-restricted diet that included twice-daily consumption of a protein and fibre-based multi-ingredient nutritional supplement shake (HPF) compared with an isocaloric low-protein/lower-fibre placebo (LPF) in adults with overweight and obesity. This study is a double-blind randomised placebo-controlled study. Two hundred and six healthy adults were recruited and randomly assigned to intervention groups in a 1:1 ratio. Results show that the habitual consumption of an HPF preload 30 min before breakfast and lunch resulted in greater weight loss compared with an isocaloric LPF preload in overweight/obese adults. In addition, improved metabolic outcomes were observed in the HPF group throughout the 84-d randomized controlled trial. Authors conclude that diet composition rather than energy reduction alone may influence the success of a weight-loss regimen, potentially including protein and fibre content.
Abstract
BACKGROUND Higher protein and fiber diets promote weight management and metabolic health. OBJECTIVES This study aimed to determine if greater weight loss and positive changes in metabolic outcomes could be achieved with twice-daily consumption of a high-protein and fiber-based multi-ingredient nutritional shake (HPF) compared with an isocaloric low-protein, lower fiber-based placebo (LPF). METHODS Study procedures were conducted by an independent research organization under clinicaltrials.gov registration NCT03057873. Healthy overweight and obese adults [n = 206; BMI (kg/m2): 27-35; 70% female] were randomly assigned to HPF or LPF. All participants were prescribed an energy-restricted diet (500 kcal/d less than energy needs) and consumed a HPF (17 g protein, 6 g fiber) or LPF (1 g protein, 3 g fiber) shake 30 min before breakfast and lunch for 12 wk. Primary outcomes included body weight and total body fat percentage. Blood samples were collected at days (D) 0, 28, 56, and 84 for secondary analyses related to metabolic markers of health. RESULTS Although weight loss occurred in both groups, HPF had greater weight loss at D84 compared with LPF (-3.3 kg vs. -1.8 kg, P < 0.05). Percentage body fat decreased in both groups (HPF: -1.33%, LPF: -1.09%; P < 0.001) with no differences between groups. Serum total cholesterol, LDL cholesterol, and oxidized LDL decreased between -5.1% to -8.3%, whereas adiponectin increased over time in both groups; these changes occurred to a greater extent in HPF compared with LPF (all P < 0.05). CONCLUSIONS A multi-ingredient HPF nutritional supplement shake consumed as a preload before breakfast and lunch positively influenced weight management and metabolic outcomes in overweight adults compared with an LPF placebo. These findings suggest that specific nutrient factors (i.e., potentially including protein, fiber, and bioactive content) other than calorie reduction alone influence the success of a weight-loss regimen. This trial was registered at www.clinicaltrials.gov as NCT03057873.
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A high-carbohydrate diet lowers the rate of adipose tissue mitochondrial respiration.
Bikman, BT, Shimy, KJ, Apovian, CM, Yu, S, Saito, ER, Walton, CM, Ebbeling, CB, Ludwig, DS
European journal of clinical nutrition. 2022;76(9):1339-1342
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The hormone insulin plays a fundamental role in cellular nutrient signalling, including mitochondrial function. The aim of this study was to test the hypothesis that a high-carbohydrate diet would lower measures of mitochondrial respiration in adipose tissue, consistent with the carbohydrate-insulin model of obesity. This study is an ancillary study of the Framingham State Food Study, in which the primary outcome was total energy expenditure. Data of twenty-seven participants were included in this report. Results show that a high-carbohydrate diet lowers mitochondrial respiratory function. Authors conclude the study’s sample may not reflect mitochondrial activity in all body fat depots. Thus, further research is required in order to replicate the study’s findings, conduct quantitative energetic studies, examine generalizability to other populations and experimental conditions, and explore translation to the prevention and treatment of obesity.
Abstract
Adipocyte mitochondrial respiration may influence metabolic fuel partitioning into oxidation versus storage, with implications for whole-body energy expenditure. Although insulin has been shown to influence mitochondrial respiration, the effects of dietary macronutrient composition have not been well characterized. The aim of this exploratory study was to test the hypothesis that a high-carbohydrate diet lowers the oxygen flux of adipocyte mitochondria ex vivo. Among participants in a randomized-controlled weight-loss maintenance feeding trial, those consuming a high-carbohydrate diet (60% carbohydrate as a proportion of total energy, n = 10) had lower rates of maximal adipose tissue mitochondrial respiration than those consuming a moderate-carbohydrate diet (40%, n = 8, p = 0.039) or a low-carbohydrate diet (20%, n = 9, p = 0.005) after 10 to 15 weeks. This preliminary finding may provide a mechanism for postulated calorie-independent effects of dietary composition on energy expenditure and fat deposition, potentially through the actions of insulin on fuel partitioning.
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A Single Bout of Premeal Resistance Exercise Improves Postprandial Glucose Metabolism in Obese Men with Prediabetes.
Bittel, AJ, Bittel, DC, Mittendorfer, B, Patterson, BW, Okunade, AL, Abumrad, NA, Reeds, DN, Cade, WT
Medicine and science in sports and exercise. 2021;53(4):694-703
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Prediabetes is a metabolic condition defined by elevated fasting (impaired fasting glucose) and/or postprandial (impaired glucose tolerance) plasma glucose. The aim of this study was to determine the effects of a single bout of resistance exercise on postprandial glucose metabolism following a mixed meal in obese, sedentary men with prediabetes. This study is a randomised, cross-over study design which enrolled ten participants. Participants were aged 39-62 years, obese, and demonstrated insulin resistance with compensatory increases in beta cell function. Results show that a single bout of resistance exercise performed 4.5 hours before a mixed meal (as opposed to an oral glucose tolerance test) reduced total postprandial glucose appearance, increased insulin sensitivity, and reduced the glycaemic response to a mixed meal. However, it did not have effect on glucose oxidation in obese men with prediabetes. Improvements in insulin sensitivity were complemented by reduced postprandial insulin concentration. Authors conclude that further investigation is needed to elucidate how resistance exercise affects exogenous (meal) vs endogenous postprandial glucose metabolism, and if additional bouts of exercise (i.e. training) produce superior outcomes for this population.
Abstract
INTRODUCTION Prediabetes is a major risk factor for type 2 diabetes and cardiovascular diseases. Although resistance exercise (RE) is recommended for individuals with prediabetes, the effects of RE on postprandial glucose metabolism in this population are poorly understood. Therefore, the purpose of this study was to elucidate how RE affects postprandial glucose kinetics, insulin sensitivity, beta cell function, and glucose oxidation during the subsequent meal in sedentary men with obesity and prediabetes. METHODS We studied 10 sedentary men with obesity (body mass index, 33 ± 3 kg·m-2) and prediabetes by using a randomized, cross-over study design. After an overnight fast, participants completed either a single bout of whole-body RE (seven exercises, 3 sets of 10-12 repetitions at 80% one-repetition maximum each) or an equivalent period of rest. Participants subsequently completed a mixed meal test in conjunction with an intravenous [6,6-2H2]glucose infusion to determine basal and postprandial glucose rate of appearance (Ra) and disappearance (Rd) from plasma, insulin sensitivity, and the insulinogenic index (a measure of beta cell function). Skeletal muscle biopsies were obtained 90 min postmeal to evaluate pyruvate-supported and maximal mitochondrial respiration. Whole-body carbohydrate oxidation was assessed using indirect calorimetry. RESULTS RE significantly reduced the postprandial rise in glucose Ra and plasma glucose concentration. Postprandial insulin sensitivity was significantly greater after RE, whereas postprandial plasma insulin concentration was significantly reduced. RE had no effect on the insulinogenic index, postprandial pyruvate respiration, or carbohydrate oxidation. CONCLUSION/INTERPRETATION A single bout of RE has beneficial effects on postprandial glucose metabolism in men with obesity and prediabetes by increasing postprandial insulin sensitivity, reducing the postprandial rise in glucose Ra, and reducing postprandial plasma insulin concentration.
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Effect of time restricted eating on body weight and fasting glucose in participants with obesity: results of a randomized, controlled, virtual clinical trial.
Peeke, PM, Greenway, FL, Billes, SK, Zhang, D, Fujioka, K
Nutrition & diabetes. 2021;11(1):6
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Time-restricted eating (TRE) has been identified as an effective method of losing weight in the face of rising obesity worldwide. Fasting for at least 12 hours has a beneficial effect on weight management and cardiometabolic health. Overnight fasting longer than 12 hours may result in fat-burning or ketosis. A high-fat, low-protein, low-carbohydrate snack during a 14-hour fast is believed not to raise blood sugar levels and helps with hunger management. This 8-week virtual, pilot, randomised, comparator-controlled clinical trial evaluated the benefits of following a commercial weight loss programme combined with TRE on body weight and fasting blood glucose (FBG) levels. The commercial weight loss programme included calculated calories and macronutrient content in their customised meal plans, as well as coaching and troubleshooting sessions. The participants were randomly assigned to 14-hour fasting (14:10) or 12-hour fasting (control). The 14:10 group also consumed 200 kcal of mixed nuts as a snack at hour 12 to determine the effect on blood glucose levels. After the intervention for 8 weeks, the 14:10 group showed a significant reduction in body weight (11kg) and FBG (8mg/dl), and the 12:12 group significantly lost 9kg of body weight and showed a non-significant reduction in FBG (3mg/dl). Participants with higher baseline FBG levels showed a greater reduction in FBG, indicating potential greater improvements in people with diabetes. A comparison of the two groups did not show a statistically significant difference in intervention effects. A fasting snack at 12 hours did not affect FBG in the 14:10 group, which may help adherence. Due to the exploratory nature of this study, larger robust studies are needed to assess the effectiveness of 14:10 and 12:12 time-restricted fasting regimens with commercial weight loss programmes. However, healthcare professionals can use the results of this study to understand the beneficial effects of different time-restricted fasting regimens on cardiometabolic health.
Abstract
BACKGROUND Time restricted eating (TRE) is an emerging dietary intervention for weight loss that is hypothesized to reinforce the metabolic benefits of nightly fasting/ketosis. This pilot study investigated the effectiveness of a daily 14-h metabolic fast (14:10 TRE beginning after dinner, a "fasting snack" at hour 12, and ending with breakfast 14 h later) combined with a commercial weight management program on body weight and fasting blood glucose (FBG) in individuals with obesity. We also investigated the effect of the low-calorie, high-fat, low-carbohydrate, and low-protein "fasting snack" on blood glucose. METHODS This 8-week, randomized, controlled, clinical trial included men and women (BMI ≥ 30 kg/m2) between June and October 2020. Study procedures were conducted remotely. Participants were randomized to 14:10 or 12-h TRE (12:12, active comparator) and prescribed a diet (controlled for calories and macronutrient composition) and exercise program that included weekly customized counseling and support. The primary outcome was change from baseline in body weight in the 14:10 group. RESULTS Of the 78 randomized participants, 60 (n = 30/group) completed 8 weeks. The LS mean change from baseline in weight in the 14:10 group was -8.5% (95% CI -9.6 to -7.4; P < 0.001) and -7.1% (-8.3 to -5.8; P < 0.001) in the 12:12 group (between group difference -1.4%; -2.7 to -0.2; P < 0.05). There was a statistically significant LS mean change from baseline to week 8 in FBG in the 14:10 group of -7.6 mg/dl (95% CI -15.1 to -0.1; P < 0.05) but not in the 12:12 group (-3.1 mg/dl, -10.0 to 3.7; P = NS). Both interventions resulted in a larger reduction in FBG in participants with elevated FBG (≥100 mg/dl) at baseline (both P < 0.05). CONCLUSIONS In participants with obesity who completed 8 weeks of the 14:10 TRE schedule combined with a commercial weight loss program, there was statistically significant and clinically meaningful weight loss and improvements in FBG.
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Proteomic profiles before and during weight loss: Results from randomized trial of dietary intervention.
Figarska, SM, Rigdon, J, Ganna, A, Elmståhl, S, Lind, L, Gardner, CD, Ingelsson, E
Scientific reports. 2020;10(1):7913
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Understanding biological substances, or "biomarkers" that are present in the body of individuals with obesity, could lead to personalised dietary recommendations for weight loss. Current research on biomarkers in individuals with obesity who have undergone a weight loss intervention is lacking. This secondary analysis of a randomised control trial study of 609 healthy and obese adults over 6 months, aimed to identify biomarkers associated with obesity, determine any changes with weight loss and if these could be used to make personalised recommendations. 263 biomarkers were tested and the results showed that 102 were associated with body mass index (BMI). 88 were elevated in individuals with a higher BMI. Upon weight loss, a large number of these decreased and a small number increased. The type of diet had no influence on how these biomarkers changed and only one could be used to predict weight loss. It was concluded that many of the biomarkers were connected to BMI and many changed with weight loss, however none of the biomarkers studied could be used to individualise dietary recommendations. This study could be used by healthcare professionals to understand that the role of biomarkers in personalising recommendations is complex and more research may be needed.
Abstract
Inflammatory and cardiovascular biomarkers have been associated with obesity, but little is known about how they change upon dietary intervention and concomitant weight loss. Further, protein biomarkers might be useful for predicting weight loss in overweight and obese individuals. We performed secondary analyses in the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized intervention trial that included healthy 609 adults (18-50 years old) with BMI 28-40 kg/m2, to evaluate associations between circulating protein biomarkers and BMI at baseline, during a weight loss diet intervention, and to assess predictive potential of baseline blood proteins on weight loss. We analyzed 263 plasma proteins at baseline and 6 months into the intervention using the Olink Proteomics CVD II, CVD III and Inflammation arrays. BMI was assessed at baseline, after 3 and 6 months of dietary intervention. At baseline, 102 of the examined inflammatory and cardiovascular biomarkers were associated with BMI (>90% with successful replication in 1,584 overweight/obese individuals from a community-based cohort study) and 130 tracked with weight loss shedding light into the pathophysiology of obesity. However, out of 263 proteins analyzed at baseline, only fibroblast growth factor 21 (FGF-21) predicted weight loss, and none helped individualize dietary assignment.
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Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease.
Smith, GI, Shankaran, M, Yoshino, M, Schweitzer, GG, Chondronikola, M, Beals, JW, Okunade, AL, Patterson, BW, Nyangau, E, Field, T, et al
The Journal of clinical investigation. 2020;130(3):1453-1460
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Non-alcoholic fatty liver disease (NAFLD) is a common complication of obesity and is associated with multiorgan insulin resistance, dyslipidaemia and an increased risk of diabetes and coronary heart disease. The aims of this study were to (a) determine hepatic de novo lipogenesis (DNL) [the liver’s biochemical process of synthesising fatty acids] in 3 distinct cohorts, (b) determine the relationships among hepatic DNL and intrahepatic [within the liver] triglyceride (IHTG) content, and (c) determine the effect of moderate (10%) weight loss. This study is a cross-sectional study which included a total of 67 men and women (mean age: 39 ± 1 years; 14 men and 53 women). Results highlight the importance of DNL in the pathogenesis of hepatic steatosis [build up of fats in the liver] and suggest that increases in daily 24-hour plasma glucose and insulin concentrations are major drivers of increased DNL in individuals with obesity and NAFLD. Additionally, moderate (10%) weight loss caused a marked decrease in both hepatic DNL and IHTG content. Authors conclude that increases in circulating glucose and insulin promote hepatic DNL in individuals with NAFLD. Whereas an improvement in insulin sensitivity and a decrease in hepatic DNL, are potentially important contributors to the decline in IHTG content associated with moderate weight loss.
Abstract
BACKGROUNDAn increase in intrahepatic triglyceride (IHTG) is the hallmark feature of nonalcoholic fatty liver disease (NAFLD) and is decreased by weight loss. Hepatic de novo lipogenesis (DNL) contributes to steatosis in individuals with NAFLD. The physiological factors that stimulate hepatic DNL and the effect of weight loss on hepatic DNL are not clear.METHODSHepatic DNL, 24-hour integrated plasma insulin and glucose concentrations, and both liver and whole-body insulin sensitivity were determined in individuals who were lean (n = 14), obese with normal IHTG content (n = 26), or obese with NAFLD (n = 27). Hepatic DNL was assessed using the deuterated water method corrected for the potential confounding contribution of adipose tissue DNL. Liver and whole-body insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp procedure in conjunction with glucose tracer infusion. Six subjects in the obese-NAFLD group were also evaluated before and after a diet-induced weight loss of 10%.RESULTSThe contribution of hepatic DNL to IHTG-palmitate was 11%, 19%, and 38% in the lean, obese, and obese-NAFLD groups, respectively. Hepatic DNL was inversely correlated with hepatic and whole-body insulin sensitivity, but directly correlated with 24-hour plasma glucose and insulin concentrations. Weight loss decreased IHTG content, in conjunction with a decrease in hepatic DNL and 24-hour plasma glucose and insulin concentrations.CONCLUSIONSThese data suggest hepatic DNL is an important regulator of IHTG content and that increases in circulating glucose and insulin stimulate hepatic DNL in individuals with NAFLD. Weight loss decreased IHTG content, at least in part, by decreasing hepatic DNL.TRIAL REGISTRATIONClinicalTrials.gov NCT02706262.FUNDINGThis study was supported by NIH grants DK56341 (Nutrition Obesity Research Center), DK20579 (Diabetes Research Center), DK52574 (Digestive Disease Research Center), and RR024992 (Clinical and Translational Science Award), and by grants from the Academy of Nutrition and Dietetics Foundation, the College of Natural Resources of UCB, and the Pershing Square Foundation.