-
1.
High-Protein or Low Glycemic Index Diet-Which Energy-Restricted Diet Is Better to Start a Weight Loss Program?
Waliłko, E, Napierała, M, Bryśkiewicz, M, Fronczyk, A, Majkowska, L
Nutrients. 2021;(4)
Abstract
BACKGROUND To date, no crossover studies have compared the effects of high-protein (HP) and low glycemic index (LGI) diets applied as starting energy-restricted diets. METHODS Thirty-five overweight or obese volunteers with sedentary lifestyles aged 41.4 ± 11.0 years, with body mass index (BMI) of 33.6 ± 4.2 kg/m2, without diabetes, completed an 8-week randomized crossover study of an energy-restricted diet (reduction of 30%; approximately 600 kcal/day). The anthropometric parameters, body composition, 24 h blood pressure, and basic metabolic profile were measured at baseline and after completing the two 4-week diets; i.e., the HP (protein at 30% of the daily energy intake) or LGI diet, followed by the opposite diet. All subjects maintained food diaries and attended six counselling sessions with a clinical dietitian. RESULTS The final weight loss was not significantly different when the HP diet was used first but was associated with a greater loss of fat mass: 4.6 kg (5.8; 3.0 kg) vs. 2.2 (4.5; 0.8); p < 0.025, preserved muscle mass, and reduced LDL-cholesterol. CONCLUSIONS A short-term HP diet applied as a jump-start diet appeared to be more beneficial than an LGI diet, as indicated by the greater fat mass loss, preservation of muscle mass, and better effects on the lipid profile.
-
2.
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial.
Rubino, D, Abrahamsson, N, Davies, M, Hesse, D, Greenway, FL, Jensen, C, Lingvay, I, Mosenzon, O, Rosenstock, J, Rubio, MA, et al
JAMA. 2021;(14):1414-1425
-
-
Free full text
-
Abstract
IMPORTANCE The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown. OBJECTIVE To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or ≥27 with ≥1 weight-related comorbidity) and without diabetes. INTERVENTIONS A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups. MAIN OUTCOMES AND MEASURES The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version [SF-36]). RESULTS Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 [SD, 12] years; 634 [79%] women; mean body weight, 107.2 kg [SD, 22.7 kg]), 787 participants (98.0%) completed the trial and 741 (92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo (difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001). Waist circumference (-9.7 cm [95% CI, -10.9 to -8.5 cm]), systolic blood pressure (-3.9 mm Hg [95% CI, -5.8 to -2.0 mm Hg]), and SF-36 physical functioning score (2.5 [95% CI, 1.6-3.3]) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%). CONCLUSIONS AND RELEVANCE Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03548987.
-
3.
Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial.
Heymsfield, SB, Coleman, LA, Miller, R, Rooks, DS, Laurent, D, Petricoul, O, Praestgaard, J, Swan, T, Wade, T, Perry, RG, et al
JAMA network open. 2021;(1):e2033457
-
-
Free full text
-
Abstract
IMPORTANCE Antibody blockade of activin type II receptor (ActRII) signaling stimulates skeletal muscle growth. Previous clinical studies suggest that ActRII inhibition with the monoclonal antibody bimagrumab also promotes excess adipose tissue loss and improves insulin resistance. OBJECTIVE To evaluate the efficacy and safety of bimagrumab on body composition and glycemic control in adults with type 2 diabetes and overweight and obesity. DESIGN, SETTING, AND PARTICIPANTS This double-masked, placebo-controlled, 48-week, phase 2 randomized clinical trial was conducted among adults with type 2 diabetes, body mass index between 28 and 40, and glycated hemoglobin (HbA1c) levels between 6.5% and 10.0% at 9 US and UK sites. The trial was conducted from February 2017 to May 2019. Only participants who completed a full treatment regimen were included in analysis. INTERVENTIONS Patients were randomized to intravenous infusion of bimagrumab (10 mg/kg up to 1200 mg in 5% dextrose solution) or placebo (5% dextrose solution) treatment every 4 weeks for 48 weeks; both groups received diet and exercise counseling. MAIN OUTCOMES AND MEASURES The primary end point was least square mean change from baseline to week 48 in total body fat mass (FM); secondary and exploratory end points were lean mass (LM), waist circumference (WC), HbA1c level, and body weight (BW) changes from baseline to week 48. RESULTS A total of 75 patients were randomized to bimagrumab (n = 37; 23 [62.2%] women) or placebo (n = 38; 12 [31.6%] women); 58 (77.3%) completed the 48-week study. Patients at baseline had a mean (SD) age of 60.4 (7.7) years; mean (SD) BMI of 32.9 (3.4); mean (SD) BW of 93.6 (14.9) kg; mean (SD) FM of 35.4 (7.5) kg; and mean (SD) HbA1c level of 7.8% (1.0%). Changes at week 48 for bimagrumab vs placebo were as follows: FM, -20.5% (-7.5 kg [80% CI, -8.3 to -6.6 kg]) vs -0.5% (-0.18 kg [80% CI, -0.99 to 0.63 kg]) (P < .001); LM, 3.6% (1.70 kg [80% CI, 1.1 to 2.3 kg]) vs -0.8% (-0.4 kg [80% CI, -1.0 to 0.1 kg]) (P < .001); WC, -9.0 cm (80% CI, -10.3 to -7.7 cm) vs 0.5 cm (80% CI, -0.8 to 1.7 cm) (P < .001); HbA1c level, -0.76 percentage points (80% CI, -1.05 to -0.48 percentage points) vs -0.04 percentage points (80% CI, -0.23 to 0.31 percentage points) (P = .005); and BW, -6.5% (-5.9 kg [80% CI, -7.1 to -4.7 kg]) vs -0.8% (-0.8 kg [80% CI, -1.9 to 0.3 kg]) (P < .001). Bimagrumab's safety and tolerability profile was consistent with prior studies. CONCLUSIONS AND RELEVANCE In this phase 2 randomized clinical trial, ActRII blockade with bimagrumab led to significant loss of FM, gain in LM, and metabolic improvements during 48 weeks in patients with overweight or obesity who had type 2 diabetes. ActRII pathway inhibition may provide a novel approach for the pharmacologic management of excess adiposity and accompanying metabolic disturbances. TRIAL REGISTRATION ClinicalTrials.gov number: NCT03005288.
-
4.
Efficacy and Safety of Ertugliflozin in Patients with Overweight and Obesity with Type 2 Diabetes Mellitus.
Heymsfield, SB, Raji, A, Gallo, S, Liu, J, Pong, A, Hannachi, H, Terra, SG
Obesity (Silver Spring, Md.). 2020;(4):724-732
-
-
Free full text
-
Abstract
OBJECTIVE This study aimed to evaluate ertugliflozin in patients with overweight and obesity with type 2 diabetes mellitus. METHODS Data from three placebo-controlled, randomized, Phase 3 studies were pooled. Patients with baseline BMI ≥ 25 (1,377/1,544; 89%) were assessed with a stratification by BMI subgroup. RESULTS At week 26, reductions from baseline in glycated hemoglobin A1c (HbA1c), fasting plasma glucose, body weight (BW), and systolic blood pressure (SBP) were greater with ertugliflozin versus placebo. For placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively, least squares mean change was 0.1%, -0.8%, and -0.9% for HbA1c and -1.2 kg, -3.1 kg, and -3.2 kg for BW. HbA1c reductions were consistent across BMI subgroups. For ertugliflozin 5 mg and 15 mg, least squares mean change (placebo adjusted) in absolute BW was -1.4 kg and -1.2 kg for BMI 25 to < 30, -1.8 kg and -1.9 kg for BMI 30 to < 35, and -2.5 kg and -2.9 kg for BMI ≥ 35. Percent BW changes were similar across BMI subgroups. Incidence of adverse events was 52.5%, 44.6%, and 50.1% with placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively. CONCLUSIONS Meaningful reductions in HbA1c, fasting plasma glucose, BW, and SBP were observed with ertugliflozin in patients with overweight and obesity with type 2 diabetes mellitus. Ertugliflozin improved HbA1c and SBP and reduced BW across BMI subgroups. Ertugliflozin was generally well tolerated.
-
5.
Nigella sativa and Trigonella foenum-graecum Supplemented Chapatis Safely Improve HbA1c, Body Weight, Waist Circumference, Blood Lipids, and Fatty Liver in Overweight and Diabetic Subjects: A Twelve-Week Safety and Efficacy Study.
Rao, AS, Hegde, S, Pacioretty, LM, DeBenedetto, J, Babish, JG
Journal of medicinal food. 2020;(9):905-919
-
-
Free full text
-
Abstract
In 2019, ∼ 463 million people globally had diabetes mellitus (DM), with China (25.1%), India (16.6%), and the United States (6.69%) representing nearly 50% of that total. The primary objectives of this exploratory study were to assess the safety and potential efficacy of Nigella sativa and fenugreek seed supplemented chapatis in overweight (OW) and type 2 DM subjects. Forty subjects (15/OW; 9/DM; 16/DM/OW) consumed two chapatis twice a day 6 days/week for a daily dose of 5.45 g of an N. sativa/fenugreek combination over 12 weeks with no changes in lifestyle or medications. Anthropometric, glycemic, and vascular variables were recorded at baseline and after 6 and 12 weeks. Glycated hemoglobin (HbA1c), plasma lipids, and complete metabolic profile were measured at baseline and termination. Compliance, estimated during twice-daily individual delivery of precooked chapatis, was 100%, with no significant adverse effects. At termination, body weights, body mass index, waist and hip circumferences, index of central obesity, HbA1c, fasting blood glucose, 2-h postprandial blood glucose, estimated average glucose over 12 weeks, total cholesterol (TC), non-high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL), and triglycerides (TG) were decreased (P < .05) over all subjects. Subjects with HbA1c ≥7.0 exhibited greater improvements in all glycemic variables than HbA1c <7.0 subjects. In addition, the decrease in HbA1c was positively correlated with decreases in (1) hepatic enzymes alkaline phosphatase (r = 0.301, P = .0067) and aspartate transaminase (r = 0.277, P = .0129), (2) systolic blood pressure (r = 0.388, P = .0004), and (3) number of diagnostic metabolic syndrome criteria exhibited per subject (r = 0.391, P = .0005), cardiovascular risk score (CRS) (r = 0.281, P = .0115), and hepatic steatosis index (HSI) (r = 0.223, P = .0467). Atherogenic and diabetogenic indexes TC/HDL, low density lipoprotein/HDL, VLDL/HDL, and TG/HDL were all decreased (P < .05). Among all subjects, improvement (P < .05) was seen in CRS (-10.7%), fatty liver index (-19.8%), lipid accumulation product (-13.8%), and HSI (-7.53%). N. sativa/fenugreek supplemented chapatis present a safe and seamless dietary modification to address cardiometabolic risk.
-
6.
Phase 1 Study of the Pharmacology of BTI320 Before High-Glycemic Meals.
Luke, DR, Lee, KKY, Rausch, CW, Cheng, C
Clinical pharmacology in drug development. 2019;(3):395-403
-
-
Free full text
-
Abstract
BTI320 is a proprietary fractionated mannan polysaccharide being studied for attenuation of postprandial glucose excursion. The apparent blood glucose-lowering effect of this compound is effective in lowering postprandial hyperinsulinemia, participating in the metabolic regulation of other lipid molecules; the consequence of this activity is yet to be validated with BTI320 with respect to the risk of cardiovascular disease. The primary objective of the study was to determine the postprandial glucose and insulin responses to 3 test meals containing rice alone or consumed with BTI320 (study A) or 3 test meals (SpriteTM ) alone or consumed with BTI320 (study B). Twenty overweight but otherwise healthy volunteers, 4 female and 6 male (mean age 29 years, BMI 27-28 kg/m2 ) in study A and 6 female and 4 male (mean age 32 years, BMI 25-32 kg/m2 ) in study B participated in the BTI320 evaluations. Standardized postprandial response methodology was utilized. In study A the addition of 6- and 12-g BTI320 tablets reduced postprandial glucose responses to white rice by 19% and 32% and reduced postprandial insulin responses by 16% and 24%, respectively (P ≤ .05). In study B 2.6 and 5.2 g BTI320 reduced the glycemic index by 10% and 14%, respectively, and led to 14% and 18% decreases in the insulinemic index of the soft drink (P ≤ .05). These 2 studies demonstrated that the consumption of BTI320 before carbohydrate food or sugary beverage significantly reduced postprandial glucose levels and insulin responses to that meal or beverage in a dose-dependent manner.
-
7.
Effects of a dietary supplement on inflammatory marker expression in middle-aged and elderly hypertensive patients.
Wang, J, Hong, Z, Wang, N, Wu, L, Ding, B, Ge, Z, Bi, Y, Li, W
Clinics (Sao Paulo, Brazil). 2019;:e890
Abstract
OBJECTIVES We aimed to explore the effects of diet on the inflammatory response in middle-aged and elderly people with hypertension. METHODS Thirty overweight or obese patients with stage one hypertension (age range, 45-75 years) were allocated to either the intervention or control group (n=15 per group; age- and sex-matched). Patients in the intervention group consumed a food powder supplement (100 g) instead of a regular meal. The control group maintained their normal dietary habits. This study lasted for six weeks. Blood pressure, inflammatory marker levels, and energy intake were measured before and after the study. RESULTS After 6 weeks, the diet composition of the intervention group changed significantly (p<0.05). The intake of proteins, dietary fibre, monounsaturated fat, and polyunsaturated fat increased significantly (p<0.05), while the total energy intake trended towards an increase (p>0.05). In the control group, the total energy intake decreased significantly (p<0.05). The levels of nuclear factor-κB (NF-κB), soluble intercellular adhesion molecule-1 (sICAM-1) and high sensitivity C-reactive protein (hs-CRP) decreased, and adiponectin increased significantly in the intervention group (p<0.05); however, no significant changes were observed in the inflammatory marker levels of the control group. In the intervention group, systolic blood pressure decreased significantly (p<0.05), and diastolic blood pressure also exhibited a decreasing trend. No significant change in blood pressure was observed in the control group. CONCLUSION The consumption of a food powder supplement can improve diet composition, decrease blood pressure and reduce inflammation in middle-aged and elderly overweight or obese hypertensive patients. The food powder supplement may also have an anti-atherosclerotic effect in hypertensive patients.
-
8.
Application of Machine Learning to Predict Dietary Lapses During Weight Loss.
Goldstein, SP, Zhang, F, Thomas, JG, Butryn, ML, Herbert, JD, Forman, EM
Journal of diabetes science and technology. 2018;(5):1045-1052
-
-
Free full text
-
Abstract
BACKGROUND Individuals who adhere to dietary guidelines provided during weight loss interventions tend to be more successful with weight control. Any deviation from dietary guidelines can be referred to as a "lapse." There is a growing body of research showing that lapses are predictable using a variety of physiological, environmental, and psychological indicators. With recent technological advancements, it may be possible to assess these triggers and predict dietary lapses in real time. The current study sought to use machine learning techniques to predict lapses and evaluate the utility of combining both group- and individual-level data to enhance lapse prediction. METHODS The current study trained and tested a machine learning algorithm capable of predicting dietary lapses from a behavioral weight loss program among adults with overweight/obesity (n = 12). Participants were asked to follow a weight control diet for 6 weeks and complete ecological momentary assessment (EMA; repeated brief surveys delivered via smartphone) regarding dietary lapses and relevant triggers. RESULTS WEKA decision trees were used to predict lapses with an accuracy of 0.72 for the group of participants. However, generalization of the group algorithm to each individual was poor, and as such, group- and individual-level data were combined to improve prediction. The findings suggest that 4 weeks of individual data collection is recommended to attain optimal model performance. CONCLUSIONS The predictive algorithm could be utilized to provide in-the-moment interventions to prevent dietary lapses and therefore enhance weight losses. Furthermore, methods in the current study could be translated to other types of health behavior lapses.
-
9.
A randomised, double-blind, placebo-controlled phase 1 study of the safety, tolerability and pharmacodynamics of volixibat in overweight and obese but otherwise healthy adults: implications for treatment of non-alcoholic steatohepatitis.
Palmer, M, Jennings, L, Silberg, DG, Bliss, C, Martin, P
BMC pharmacology & toxicology. 2018;(1):10
Abstract
BACKGROUND Accumulation of toxic free cholesterol in hepatocytes may cause hepatic inflammation and fibrosis. Volixibat inhibits bile acid reuptake via the apical sodium bile acid transporter located on the luminal surface of the ileum. The resulting increase in bile acid synthesis from cholesterol could be beneficial in patients with non-alcoholic steatohepatitis. This adaptive dose-finding study investigated the safety, tolerability, pharmacodynamics, and pharmacokinetics of volixibat. METHODS Overweight and obese adults were randomised 3:1 to double-blind volixibat or placebo, respectively, for 12 days. Volixibat was initiated at a once-daily dose of 20 mg, 40 mg or 80 mg. Based on the assessment of predefined safety events, volixibat dosing was either escalated or reduced. Other dose regimens (titrations and twice-daily dosing) were also evaluated. Assessments included safety, tolerability, stool hardness, faecal bile acid (FBA) excretion, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and lipids. RESULTS All 84 randomised participants (volixibat, 63; placebo, 21) completed the study, with no serious adverse events at doses of up to 80 mg per day (maximum assessed dose). The median number of daily bowel evacuations increased from 1 (range 0-4) to 2 (0-8) during volixibat treatment, and stool was looser with volixibat than placebo. Volixibat was minimally absorbed; serum levels were rarely quantifiable at any dose or sampling time point, thereby precluding pharmacokinetic analyses. Mean daily FBA excretion was 930.61 μmol (standard deviation [SD] 468.965) with volixibat and 224.75 μmol (195.403) with placebo; effects were maximal at volixibat doses ≥20 mg/day. Mean serum C4 concentrations at day 12 were 98.767 ng/mL (standard deviation, 61.5841) with volixibat and 16.497 ng/mL (12.9150) with placebo. Total and low-density lipoprotein cholesterol levels decreased in the volixibat group, with median changes of - 0.70 mmol/L (range - 2.8 to 0.4) and - 0.6990 mmol/L (- 3.341 to 0.570), respectively. CONCLUSIONS This study indicates that maximal inhibition of bile acid reabsorption, as assessed by FBA excretion, occurs at volixibat doses of ≥20 mg/day in obese and overweight adults, without appreciable change in gastrointestinal tolerability. These findings guided dose selection for an ongoing phase 2 study in patients with non-alcoholic steatohepatitis. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02287779 (registration first received 6 November 2014).
-
10.
Phase II prospective randomized trial of weight loss prior to radical prostatectomy.
Henning, SM, Galet, C, Gollapudi, K, Byrd, JB, Liang, P, Li, Z, Grogan, T, Elashoff, D, Magyar, CE, Said, J, et al
Prostate cancer and prostatic diseases. 2018;(2):212-220
-
-
Free full text
-
Abstract
BACKGROUND Obesity is associated with poorly differentiated and advanced prostate cancer and increased mortality. In preclinical models, caloric restriction delays prostate cancer progression and prolongs survival. We sought to determine if weight loss (WL) in men with prostate cancer prior to radical prostatectomy affects tumor apoptosis and proliferation, and if WL effects other metabolic biomarkers. METHODS In this Phase II prospective trial, overweight and obese men scheduled for radical prostatectomy were randomized to a 5-8 week WL program consisting of standard structured energy-restricted meal plans (1200-1500 Kcal/day) and physical activity or to a control group. The primary endpoint was apoptotic index in the radical prostatectomy malignant epithelium. Secondary endpoints were proliferation (Ki67) in the radical prostatectomy tissue, body weight, body mass index (BMI), waist to hip ratio, body composition, and serum PSA, insulin, triglyceride, cholesterol, testosterone, estradiol, leptin, adiponectin, interleukin 6, interleukin 8, insulin-like growth factor 1, and IGF binding protein 1. RESULTS In total 23 patients were randomized to the WL intervention and 21 patients to the control group. Subjects in the intervention group had significantly more weight loss (WL:-3.7 ± 0.5 kg; Control:-1.6 ± 0.5 kg; p = 0.007) than the control group and total fat mass was significantly reduced (WL:-2.1 ± 0.4; Control: 0.1 ± 0.3; p = 0.015). There was no significant difference in apoptotic or proliferation index between the groups. Among the other biomarkers, triglyceride, and insulin levels were significantly decreased in the WL compared with the control group. CONCLUSIONS In summary, this short-term WL program prior to radical prostatectomy resulted in significantly more WL in the intervention vs. the control group and was accompanied by significant reductions in body fat mass, circulating triglycerides, and insulin. However, no significant changes were observed in malignant epithelium apoptosis or proliferation. Future studies should consider a longer term or more intensive weight loss intervention.