Metabolic Effects of Weight Loss on a Very-Low-Carbohydrate Diet Compared With an Isocaloric High-Carbohydrate Diet in Abdominally Obese Subjects

ABSTRACT Background Longer-term feeding studies suggest that a low-carbohydrate diet increases energy expenditure, consistent with the carbohydrate-insulin model of obesity. However, the validity of methodology utilized in these studies, involving doubly labeled water (DLW), has been questioned. Objective The aim of this study was to determine whether dietary energy requirement for weight-loss maintenance is higher on a low- compared with high-carbohydrate diet. Methods The study reports secondary outcomes from a feeding study in which the primary outcome was total energy expenditure (TEE). After attaining a mean Run-in weight loss of 10.5%, 164 adults (BMI ≥25 kg/m2; 70.1% women) were randomly assigned to Low-Carbohydrate (percentage of total energy from carbohydrate, fat, protein: 20/60/20), Moderate-Carbohydrate (40/40/20), or High-Carbohydrate (60/20/20) Test diets for 20 wk. Calorie content was adjusted to maintain individual body weight within ± 2 kg of the postweight-loss value. In analyses by intention-to-treat (ITT, completers, n = 148) and per protocol (PP, completers also achieving weight-loss maintenance, n = 110), we compared the estimated energy requirement (EER) from 10 to 20 wk of the Test diets using ANCOVA. Results Mean EER was higher in the Low- versus High-Carbohydrate group in models of varying covariate structure involving ITT [ranging from 181 (95% CI: 8–353) to 246 (64–427) kcal/d; P ≤0.04] and PP [ranging from 245 (43–446) to 323 (122–525) kcal/d; P ≤0.02]. This difference remained significant in sensitivity analyses accounting for change in adiposity and possible nonadherence. Conclusions Energy requirement was higher on a low- versus high-carbohydrate diet during weight-loss maintenance in adults, commensurate with TEE. These data are consistent with the carbohydrate-insulin model and lend qualified support for the validity of the DLW method with diets varying in macronutrient composition. This trial was registered at clinicaltrials.gov as NCT02068885.

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Effects of Dietary Carbohydrate Content on Circulating Metabolic Fuel Availability in the Postprandial State

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa062 ◽

2020 ◽

Vol 4 (7) ◽

Author(s):

Kim J Shimy ◽

Henry A Feldman ◽

Gloria L Klein ◽

Lisa Bielak ◽

Cara B Ebbeling ◽

...

Keyword(s):

Fatty Acids ◽

Weight Loss ◽

Free Fatty Acids ◽

High Carbohydrate Diet ◽

Carbohydrate Content ◽

Dietary Carbohydrate ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

High Carbohydrate ◽

Low Carbohydrate

Abstract Context According to the carbohydrate-insulin model of obesity, an elevated insulin-to-glucagon ratio in response to a high-carbohydrate diet directs metabolic fuels toward storage, resulting in lower circulating energy. Objective To determine differences in total circulating energy post-meal related to dietary carbohydrate. Design Ancillary study within the Framingham State Food Study. Setting University community. Participants 29 adults (aged 20 to 65 years) with overweight or obesity (body mass index ≥25 kg/m2) Intervention After achieving 10% to 14% weight loss on a run-in diet, participants were randomized to weight-loss-maintenance test diets varying in carbohydrate content (high-carbohydrate, 60% of total energy, n = 11; moderate-carbohydrate, 40%, n = 8; low-carbohydrate, 20%, n = 10) and controlled for protein (20%). During 24-hour metabolic ward admissions between 10 and 15 weeks on the test diets, metabolic fuels and hormones were measured. Main Outcome Measure Energy availability (EA) based on energy content of blood glucose, beta-hydroxybutyrate, and free fatty acids, in the late postprandial period (180 to 300 minutes). Insulin at 30 minutes into the test meal (Meal Insulin-30) was measured as an effect modifier. Results Insulin-to-glucagon ratio was 7-fold higher in participants on the high- vs low-carbohydrate diet (2.5 and 0.36, respectively). Late postprandial EA was 0.58 kcal/L lower on the high- vs low-carbohydrate diet (P < 0.0001), primarily related to suppression of free fatty acids. Early postprandial EA (30 to 180 minutes) declined fastest in the high-carbohydrate group, and Meal Insulin-30 modified this diet effect. Conclusions During weight-loss maintenance on a high-carbohydrate diet, late postprandial EA is reduced, consistent with the carbohydrate-insulin model.

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Food intake and gastric emptying in rats with streptozotocin-induced diabetes

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1984.247.6.r1054 ◽

1984 ◽

Vol 247 (6) ◽

pp. R1054-R1061 ◽

Cited By ~ 4

Author(s):

J. G. Granneman ◽

E. M. Stricker

Keyword(s):

Gastric Emptying ◽

Food Intake ◽

Glucose Absorption ◽

Diabetic Rats ◽

High Carbohydrate Diet ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

High Carbohydrate ◽

Low Carbohydrate ◽

Streptozotocin Induced Diabetes

Recent studies suggest that the rate of nutrient transit through the upper gastrointestract may provide cues that are important to the control of food intake. We examined gastrointestinal function in rats with streptozotocin-induced diabetes and related these findings to concomitant changes in food intake. Control and diabetic rats were adapted to one of two isocaloric diets either high in carbohydrate or fat. Control rats ate similar amounts of each diet. In contrast, diabetic animals fed high-carbohydrate diet were hyperphagic, whereas those fed low-carbohydrate diet ate normal amounts of food. Gastric emptying, intestinal mass, disaccharidase activity, and glucose absorption were increased in normophagic diabetic rats fed a low-carbohydrate diet. Feeding diabetic rats high-carbohydrate diet potentiated each of these effects, and food intake was highly correlated with rate of gastric emptying. These and other results indicate that diabetes enhances gastric emptying and intestinal carbohydrate digestion and absorption, even in the absence of hyperphagia. Consequently, the hyperphagia of diabetic rats may be in part a behavioral response to a greatly accelerated clearance of nutrients from the upper gastrointestinal tract that occurs when these animals are fed diets rich in carbohydrate.

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Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial

BMJ ◽

10.1136/bmj.k4583 ◽

2018 ◽

pp. k4583 ◽

Cited By ~ 72

Author(s):

Cara B Ebbeling ◽

Henry A Feldman ◽

Gloria L Klein ◽

Julia M W Wong ◽

Lisa Bielak ◽

...

Keyword(s):

Weight Loss ◽

Energy Expenditure ◽

Total Energy ◽

Total Energy Expenditure ◽

Carbohydrate Diet ◽

Intention To Treat ◽

Low Carbohydrate Diet ◽

High Carbohydrate ◽

Low Carbohydrate ◽

Treat Analysis

AbstractObjectiveTo determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure.DesignRandomized trial.SettingMulticenter collaboration at US two sites, August 2014 to May 2017.Participants164 adults aged 18-65 years with a body mass index of 25 or more.InterventionsAfter 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose).Main outcome measuresThe primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate. Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin.ResultsTotal energy expenditure differed by diet in the intention-to-treat analysis (n=162, P=0.002), with a linear trend of 52 kcal/d (95% confidence interval 23 to 82) for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ). Change in total energy expenditure was 91 kcal/d (95% confidence interval −29 to 210) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d (91 to 326) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis (n=120, P<0.001), the respective differences were 131 kcal/d (−6 to 267) and 278 kcal/d (144 to 411). Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis (P<0.004). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol).ConclusionsConsistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion.Trial registrationClinicalTrials.govNCT02068885.

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Beneficial Effects of an 8-Week, Very Low Carbohydrate Diet Intervention on Obese Subjects

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/760804 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Yunjuan Gu ◽

Haoyong Yu ◽

Yuehua Li ◽

Xiaojing Ma ◽

Junxi Lu ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Body Composition ◽

Metabolic Profile ◽

Whole Body ◽

Carbohydrate Diet ◽

Beneficial Effects ◽

Low Carbohydrate Diet ◽

Low Carbohydrate ◽

Obese Subjects

Aim. To investigate the effects of weight loss during an 8-week very low carbohydrate diet (VLCD) on improvement of metabolic parameters, adipose distribution and body composition, and insulin resistance and sensitivity in Chinese obese subjects.Methods. Fifty-three healthy obese volunteers were given an 8-week VLCD. The outcomes were changes in anthropometry, body composition, metabolic profile, abdominal fat distribution, liver fat percent (LFP), and insulin resistance and sensitivity.Results. A total of 46 (86.8%) obese subjects completed the study. The VLCD caused a weight loss of−8.7±0.6 kg (mean ± standard error (SE),P<0.0001) combined with a significant improvement of metabolic profile. In both male and female, nonesterified fatty acid (NEFA) significantly decreased (−166.2±47.6 μmol/L,P=0.001) andβ-hydroxybutyric acid (BHA) increased (0.15±0.06 mmol/L,P=0.004) after eight weeks of VLCD intervention. The significant reductions in subcutaneous fat area (SFA), visceral fat area (VFA), and LFP were−66.5±7.9 cm2,−35.3±3.9 cm2, and−16.4±2.4%, respectively (allPvaluesP<0.0001). HOMA IR and HOMAβsignificantly decreased while whole body insulin sensitivity index (WBISI) increased (allPvaluesP<0.001).Conclusion. Eight weeks of VLCD was an effective intervention in obese subjects. These beneficial effects may be associated with enhanced hepatic and whole-body lipolysis and oxidation.

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Changes in the lipidome in type 1 diabetes following low carbohydrate diet: a randomized crossover trial

10.1101/2020.09.17.20196394 ◽

2020 ◽

Author(s):

Naba Al-Sari ◽

Signe Schmidt ◽

Tommi Suvitaival ◽

Min Kim ◽

Kajetan Trost ◽

...

Keyword(s):

Type 1 Diabetes ◽

Hdl Cholesterol ◽

High Carbohydrate Diet ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

High Carbohydrate ◽

Lipid Species ◽

Low Carbohydrate ◽

Before And After

Aims/hypothesis: Lipid metabolism might be compromised in type 1 diabetes and the understanding of their physiology is critically important. This study aimed to compare the change in plasma lipid concentrations during carbohydrate dietary changes in individuals with type 1 diabetes and identify predictive biomarkers and early-stage pathophysiology for dyslipidaemia. We hypothesized that: (1) the lipidomics profiles before and after ingesting low or high carbohydrate diet for 12 weeks would be different; and (2) specific annotated lipid species would have significant associations with metabolic outcomes. Methods: Ten adults with type 1 diabetes (mean+/-SD: age 43.6+/-13.8 years, diabetes duration 24.5+/-13.4 years, BMI 24.9+/-2.1 kg/m2, HbA1c 57.67+/-2.6 mmol/mol) using insulin pumps participated in a randomized 2-period crossover study with a 12-week intervention period of low carbohydrate diet (< 100 g carbohydrates/day) or high carbohydrate diet (> 250 g carbohydrates/day) respectively, separated by a 12-week washout period. A large-scale non-targeted lipidomics was performed with mass spectrometry for fasting plasma samples obtained before and after each diet intervention. Logitudinal lipid levels were analysed using linear mixed-effects models. Results: In total, 289 lipid species were identified from 14 major lipid classes (triacylglycerides, phosphatidylcholines, phosphatidylethanolamines, hexosyl-ceramide, sphingomyelins, lyso-phosphatidylcholines, ceramides, lactosyl-ceramide, lyso-phoshatidylethanolamine, free fatty acids, phosphatidylinositols, phosphatidylglycerols, phosphatidylserines and sulfatides). Comparing the two diets, 11 lipid species belonging to sphingomyelins, phosphatidylcholines and LPC(O-16:0) were changed. All the 11 lipid species were significantly elevated during low carbohydrate diet. Two lipid species were most differentiated between diets, namely SM(d36:1) (B+/-SE: 1.44+/-0.28, FDR = 0.010) and PC(P-36:4)/PC(O-36:5) (B+/-SE: 1.34+/-0.25, FDR = 0.009) species. Poly-unsaturated PC(35:4) was inversely associated with BMI and positively associated with HDL-cholesterol (p < 0.001). Conclusion/interpretation: Lipidome-wide outcome analysis of a randomized cross-over trial of individuals with type 1 diabetes following a low carbohydrate diet showed an increase in sphingomyelins and phosphatidylcholines which are thought to reduce dyslipidaemia. The poly-unsaturated phosphatidylcholine 35:4 was inversely associated with BMI and positively associated with HDL-cholesterol (p < 0.001). Results from this study warrant for more investigation on the long-term effect of PC(35:4) lipid-species in lipid homeostasis in type 1 diabetes. Trial registration Clinicaltrials.gov NCT02888691 Keywords Biomarker ∙ Cardiovascular disease ∙ Dyslipidaemia ∙ Lipidomics ∙ Low carbohydrate diet ∙ Randomized trial ∙ Type 1 diabetes.

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THE EFFECT OF DIETARY PROTEIN ON THE COURSE OF NEPHROTOXIC NEPHRITIS IN RATS

Journal of Experimental Medicine ◽

10.1084/jem.70.6.615 ◽

1939 ◽

Vol 70 (6) ◽

pp. 615-627 ◽

Cited By ~ 75

Author(s):

Lee E. Farr ◽

Joseph E. Smadel

Keyword(s):

Dietary Protein ◽

Rat Kidney ◽

High Carbohydrate Diet ◽

Acute Renal Injury ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

High Carbohydrate ◽

Low Protein ◽

Low Carbohydrate ◽

Nephrotoxic Nephritis

Acute nephritis of medium severity, affecting both glomeruli and tubules, was produced in rats by injections of anti-rat-kidney serum, given on 3 consecutive days. The course of the nephritis was markedly influenced by the type of diet which was fed. Rats tended to recover promptly from the induced nephritis when a low protein-high carbohydrate diet was given. On the other hand, in nephritic rats maintained on a medium protein diet the nephritis almost invariably became chronic and half the animals died of renal insufficiency during the 10½ months of observation. Finally none of the rats which received a high protein-low carbohydrate diet recovered from the acute renal injury; all developed chronic progressive nephritis and the majority died of renal failure after some months.

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