Can a Higher Protein/Low Glycemic Index vs. a Conventional Diet Attenuate Changes in Appetite and Gut Hormones Following Weight Loss? A 3-Year PREVIEW Sub-study.

Background: Previous research showed that weight-reducing diets increase appetite sensations and/or circulating ghrelin concentrations for up to 36 months, with transient or enduring perturbations in circulating concentrations of the satiety hormone peptide YY. Objective: This study assessed whether a diet that is higher in protein and low in glycemic index (GI) may attenuate these changes. Methods: 136 adults with pre-diabetes and a body mass index of ≥25 kg/m2 underwent a 2-month weight-reducing total meal replacement diet. Participants who lost ≥8% body weight were randomized to one of two 34-month weight-maintenance diets: a higher-protein and moderate-carbohydrate (CHO) diet with low GI, or a moderate-protein and higher-CHO diet with moderate GI. Both arms involved recommendations to increase physical activity. Fasting plasma concentrations of total ghrelin and total peptide YY, and appetite sensations, were measured at 0 months (pre-weight loss), at 2 months (immediately post-weight loss), and at 6, 12, 24, and 36 months. Results: There was a decrease in plasma peptide YY concentrations and an increase in ghrelin after the 2-month weight-reducing diet, and these values approached pre-weight-loss values by 6 and 24 months, respectively (P = 0.32 and P = 0.08, respectively, vs. 0 months). However, there were no differences between the two weight-maintenance diets. Subjective appetite sensations were not affected by the weight-reducing diet nor the weight-maintenance diets. While participants regained an average of ~50% of the weight they had lost by 36 months, the changes in ghrelin and peptide YY during the weight-reducing phase did not correlate with weight regain. Conclusion: A higher-protein, low-GI diet for weight maintenance does not attenuate changes in ghrelin or peptide YY compared with a moderate-protein, moderate-GI diet. Clinical Trial Registry: ClinicalTrials.gov registry ID NCT01777893 (PREVIEW) and ID NCT02030249 (Sub-study).

Urine dipsticks are not accurate for detecting mild ketosis during a severely energy restricted diet.

BACKGROUND: Detection of the mild ketosis induced by severely energy-restricted diets may be a clinically useful way to monitor and promote dietary adherence. Mild ketosis is often assessed using urine dipsticks, but accuracy for this purpose has not been tested. OBJECTIVE: To determine the accuracy of urine dipsticks to detect mild ketosis during adherence to a severely energy-restricted diet. METHODS: Two hundred and sixty three (263) fasting urine and 263 fasting blood samples were taken from 50 women (mean [standard deviation, SD] age 58.0 [4.3] years and body mass index 34.3 [2.4] kg/m2) before and at six time points during or for up to 10 weeks after 16 weeks of severe energy restriction, achieved with a total meal replacement diet. The amount of ketones (acetoacetate) in the urine was classified as '0 (Negative)', '+/- (Trace)', '+ (Weak)' or '++ (Medium)' by urine dipsticks (Ketostix, Bayer). The concentration of ketones (ß-hydroxybutyrate) in the blood was measured with our reference method, a portable ketone monitor (FreeStyle Optium, Abbott). The diagnostic accuracy of the urine dipsticks was assessed from the percent of instances when a person was actually 'in ketosis' (as defined by a blood ß-hydroxybutyrate concentration at or above three different thresholds) that were also identified by the urine dipsticks as being from a person in ketosis (the percent 'true positives' or sensitivity), as well as the percent of instances when a person was not in ketosis (as defined by the blood monitor result) was correctly identified as such with the urine dipstick (the percent 'true negatives' or specificity). Thresholds of ≥0.3mM, ≥0.5mM or ≥1.0mM were selected, because mean blood concentrations of ß-hydroxybutyrate during ketogenic diets are approximately 0.5mM. Sensitivity and specificity were then used to generate receiver operating characteristic curves, with the area under these curves indicating the ability of the dipsticks to correctly identify people in ketosis (1 = perfect results, 0.5 = random results). RESULTS: At threshold blood ß-hydroxybutyrate concentrations of ≥0.3mM, ≥0.5mM and ≥1.0mM, the sensitivity of the urine dipsticks was 35%, 52% and 76%; the specificity was 100%, 97% and 78%; and the area under the receiver operating characteristic curves was 0.67, 0.74 and 0.77, respectively. These low levels of sensitivity mean that 65%, 48% or 24% of the instances when a person was in ketosis were not detected by the urine dipsticks. CONCLUSION: Urine dipsticks are not an accurate or clinically useful means of detecting mild ketosis in people undergoing a severely energy-restricted diet and should thus not be recommended in clinical treatment protocols. If monitoring of mild ketosis is indicated (eg, to monitor or help promote adherence to a severely energy-restricted diet), then blood monitors should be used instead.

3-Year effect of weight loss via severe versus moderate energy restriction on body composition among postmenopausal women with obesity - the TEMPO Diet Trial.

We have previously shown that a severely energy-restricted diet leads to greater loss of weight, fat, lean mass and bone mineral density (BMD) at 12 months in postmenopausal women with obesity than a moderately energy-restricted diet. We now aim to evaluate whether these effects are sustained longer term (ie, at 36 months). 101 postmenopausal women were randomized to either 12 months of moderate (25 to 35%) energy restriction with a food-based diet (moderate intervention), or 4 months of severe (65 to 75%) energy restriction with a total meal replacement diet followed by moderate energy restriction for 8 months (severe intervention). Body weight and composition were measured at 0, 24 and 36 months. Participants in the severe intervention lost ~1.5 to 1.7 times as much weight, waist circumference, whole-body fat mass and visceral adipose tissue compared to those in the moderate intervention, and were 2.6 times more likely (42% versus 16%) to have lost 10% or more of their initial body weight at 36 months (P < 0.01 for all). However, those in the severe versus moderate intervention lost ~1.4 times as much whole-body lean mass (P < 0.01), albeit this was proportional to total weight lost and there was no greater loss of handgrip strength, and they also lost ~2 times as much total hip BMD between 0 and 36 months (P < 0.05), with this bone loss occurring in the first 12 months. Thus, severe energy restriction is more effective than moderate energy restriction for reducing weight and adiposity in postmenopausal women in the long term (3 years), but attention to BMD loss in the first year is required. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Reference Number: 12612000651886, anzctr.org.au.

Effect of Weight Loss via Severe vs Moderate Energy Restriction on Lean Mass and Body Composition Among Postmenopausal Women With Obesity: The TEMPO Diet Randomized Clinical Trial.

Importance: Severely energy-restricted diets are the most effective dietary obesity treatment. However, there are concerns regarding potential adverse effects on body composition. Objective: To compare the long-term effects of weight loss via severe vs moderate energy restriction on lean mass and other aspects of body composition. Design, Setting, and Participants: The Type of Energy Manipulation for Promoting Optimum Metabolic Health and Body Composition in Obesity (TEMPO) Diet Trial was a 12-month, single-center, randomized clinical trial. A total of 101 postmenopausal women, aged 45 to 65 years with body mass index (calculated as weight in kilograms divided by height in meters squared) from 30 to 40, who were at least 5 years after menopause, had fewer than 3 hours of structured physical activity per week, and lived in the Sydney metropolitan area of New South Wales, Australia, were recruited between March 2013 and July 2016. Data analysis was conducted between October 2018 and August 2019. Intervention: Participants were randomized to either 12 months of moderate (25%-35%) energy restriction with a food-based diet (moderate intervention) or 4 months of severe (65%-75%) energy restriction with a total meal replacement diet followed by moderate energy restriction for an additional 8 months (severe intervention). Both interventions had a prescribed protein intake of 1.0 g/kg of actual body weight per day, and physical activity was encouraged but not supervised. Main Outcomes and Measures: The primary outcome was whole-body lean mass at 12 months after commencement of intervention. Secondary outcomes were body weight, thigh muscle area and muscle function (strength), bone mineral density, and fat mass and distribution, measured at 0, 4, 6, and 12 months. Results: A total of 101 postmenopausal women were recruited (mean [SD] age, 58.0 [4.2] years; mean [SD] weight, 90.8 [9.1] kg; mean [SD] body mass index, 34.4 [2.5]). Compared with the moderate group at 12 months, the severe group lost more weight (effect size, -6.6 kg; 95% CI, -8.2 to -5.1 kg), lost more whole-body lean mass (effect size, -1.2 kg; 95% CI, -2.0 to -0.4 kg), and lost more thigh muscle area (effect size, -4.2 cm2; 95% CI, -6.5 to -1.9 cm2). However, decreases in whole-body lean mass and thigh muscle area were proportional to total weight loss, and there was no difference in muscle (handgrip) strength between groups. Total hip bone mineral density (effect size, -0.017 g/cm2; 95% CI, -0.029 to -0.005 g/cm2), whole-body fat mass (effect size, -5.5 kg; 95% CI, -7.1 to -3.9 kg), abdominal subcutaneous adipose tissue (effect size, -1890 cm3; 95% CI, -2560 to -1219 cm3), and visceral adipose tissue (effect size, -1389 cm3; 95% CI, -1748 to -1030 cm3) loss were also greater for the severe group than for the moderate group at 12 months. Conclusions and Relevance: Severe energy restriction had no greater adverse effect on relative whole-body lean mass or handgrip strength compared with moderate energy restriction and was associated with 2-fold greater weight and fat loss over 12 months. However, there was significantly greater loss of total hip bone mineral density with severe vs moderate energy restriction. Therefore, caution is necessary when implementing severe energy restriction in postmenopausal women, particularly those with osteopenia or osteoporosis. Trial Registration: anzctr.org.au Identifier: 12612000651886.

Less Waste on Waist Measurements: Determination of Optimal Waist Circumference Measurement Site to Predict Visceral Adipose Tissue in Postmenopausal Women with Obesity.

With obesity being a leading cause of preventable death, it is vital to understand how best to identify individuals with greater risk of metabolic disease, especially those with high visceral adipose tissue (VAT). This study aimed to determine whether three commonly used waist circumference (WC) measurement sites could provide accurate estimations of VAT, as determined by magnetic resonance imaging (MRI), which is a gold standard for measuring VAT, in postmenopausal women with obesity. VAT volume was measured by MRI of the total abdomen in 97 women aged 57.7 ± 0.4 years (mean ± SEM), mean body mass index 34.5 ± 0.2 kg/m². WC was measured at the midpoint between the lowest rib and the iliac crest (WCmid), the narrowest point of the torso (WCnarrow), and at the level of the umbilicus (WCumbilicus). WC differed significantly according to measurement site, with WCnarrow (102.1 ± 0.7 cm) < WCmid (108.3 ± 0.7 cm) < WCumbilicus (115.7 ± 0.8 cm) (p < 0.001). WCmid, WCnarrow and WCumbilicus were all significantly correlated with VAT, as measured by MRI (r = 0.581, 0.563 and 0.390, respectively; p < 0.001 for all), but the relationships between WCmid or WCnarrow and VAT determined by MRI were stronger than for WCumbilicus. Measurement of either WCmid or WCnarrow provides valid estimates of VAT in postmenopausal women with obesity, with WCnarrow being favoured in light of its greater ease and speed of measurement in this population.