Very‐low‐energy diets (VLEDs) and ketogenic low‐carbohydrate diets (KLCDs) are two dietary strategies that have been associated with a suppression of appetite. However, the results of clinical trials ...investigating the effect of ketogenic diets on appetite are inconsistent. To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, we conducted a systematic literature search and meta‐analysis of studies that assessed appetite with visual analogue scales before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD. Individuals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and individuals adhering to KLCD were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people. Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although individuals may indeed feel slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite. Future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate‐containing foods into the diet.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective
To distinguish the effects of dietary fat profile on gut parameters and their relationships with metabolic changes and to determine the capacity of n‐3 fatty acids to modify gut variables ...in the context of diet‐induced metabolic dysfunctions.
Methods
Mice received control or high‐fat diets emphasizing saturated (HFD‐sat), n‐6 (HFD‐n6), or n‐3 (HFD‐n3) fatty acids for 8 weeks. In another cohort, mice that were maintained on HFD‐sat received n‐3‐rich fish oil or resolvin D1 supplementation.
Results
HFD‐sat and HFD‐n6 induced similar weight gain, but only HFD‐sat increased index of insulin resistance (HOMA‐IR), colonic permeability, and mesenteric fat inflammation. Hydrogen sulfide‐producing bacteria were one of the major groups driving the diet‐specific changes in gut microbiome, with the overall microbial profile being associated with changes in body weight, HOMA‐IR, and gut permeability. In mice maintained on HFD‐sat, fish oil and resolvin D1 restored barrier function and reduced inflammation in the colon but were unable to normalize HOMA‐IR.
Conclusions
Different dietary fat profiles led to distinct intestinal and metabolic outcomes that are independent of obesity. Interventions targeting inflammation successfully restored gut health but did not reverse systemic aspects of diet‐induced metabolic dysfunction, implicating separation between gut dysfunctions and disease‐initiating and/or ‐maintaining processes.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Because of the high prevalence of overweight and obesity, there is a need to identify cost-effective approaches for weight loss in primary care and community settings.
To evaluate the long-term cost ...effectiveness of a commercial weight loss programme (Weight Watchers) (CP) compared with standard care (SC), as defined by national guidelines.
A Markov model was developed to calculate the incremental cost-effectiveness ratio (ICER), expressed as the cost per quality-adjusted life year (QALY) over the lifetime. The probabilities and quality-of-life utilities of outcomes were extrapolated from trial data using estimates from the published literature. A health sector perspective was adopted.
Over a patient's lifetime, the CP resulted in an incremental cost saving of AUD 70 per patient, and an incremental 0.03 QALYs gained per patient. As such, the CP was found to be the dominant treatment, being more effective and less costly than SC (95% confidence interval: dominant to 6225 per QALY). Despite the CP delaying the onset of diabetes by ∼10 months, there was no significant difference in the incidence of type 2 diabetes, with the CP achieving <0.1% fewer cases than SC over the lifetime.
The modelled results suggest that referral to community-based interventions may provide a highly cost-effective approach for those at high risk of weight-related comorbidities.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We evaluated the frequency of moderate and severe adverse events following coadministration of seasonal influenza vaccine (SIV) versus placebo with COVID-19 vaccines among adults to support practice ...guidelines.
FluVID is a participant-blinded, phase IV, randomised control trial. On the same day as the participant's scheduled COVID-19 vaccine, participants were randomised to receive SIV or saline placebo; those assigned placebo at visit one then received SIV a week later, and vice versa. Self-reported adverse events were collected daily for seven days following each visit. The primary endpoint was any solicited adverse event of at least moderate severity occurring up to seven days following receipt of SIV or placebo. This was modelled using a Bayesian logistic regression model. Analyses were performed by COVID-19 vaccine type and dose number.
Overall, 248 participants were enrolled; of these, 195 had received BNT162b2 and 53 had received mRNA1273 COVID-19 vaccines according to national guidelines. After randomisation, 119 were assigned to receive SIV and 129 were assigned to receive placebo at visit one. Adverse events were most frequently reported as mild (grade 1) in nature. Among 142 BNT162b2 booster dose one and 43 BNT162b2 booster dose two recipients, the posterior median risk difference for moderate/severe adverse events following SIV versus placebo was 13% (95% credible interval CrI -0.03 to 0.27) and 13% (95%CrI -0.37 to 0.12), respectively. Among 18 mRNA1273 booster dose one and 35 mRNA1273 booster dose two recipients, the posterior median risk difference of moderate/severe adverse events following influenza vaccine versus placebo was 6% (95%CrI -0.29 to 0.41) and -4% (95%CrI -0.30 to 0.23), respectively.
Adverse events following SIV and COVID-19 co-administration were generally mild and occurred with similar frequency to events following COVID-19 vaccine alone. We found no evidence to justify routine separation of SIV and COVID-19 vaccine doses.
ACTRN12621001063808.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this clinical trial, the appetite suppressant sibutramine as compared with placebo resulted in modest weight loss but also in an unexpected increase in the risk of nonfatal myocardial infarction ...and stroke (a finding limited to patients with preexisting cardiovascular disease). Sibutramine should not be used in patients with cardiovascular disease.
Obesity and excess weight are escalating public health concerns because they increase the prevalence of associated conditions such as diabetes mellitus and the risk of premature death.
1
,
2
More than 80% of even highly motivated patients are unable to achieve weight loss with dietary and lifestyle modifications alone.
3
Sibutramine is a norepinephrine and serotonin reuptake inhibitor that was approved for weight management in patients who are unable to lose weight by means of diet and exercise alone. Sibutramine induces satiety (resulting in reduced food intake) and an increase in energy expenditure.
4
,
5
In some patients, sibutramine increases blood pressure, pulse . . .
Many weight loss programmes show short-term success, but long-term data in larger studies are scarce, especially in community settings. Attrition is common and complicates the interpretation of ...long-term outcomes.
To investigate 2-year outcomes and explore issues of attrition and missing data.
A total of 772 overweight and obese adults recruited by primary care practices in Australia, Germany and the UK and randomised to a 12-month weight loss intervention delivered in a commercial programme (CP) or in standard care (SC).
Weight change from 0-24 and 12-24 months including measured weights only and measured and self-reported weights, using last observation carried forward (LOCF), baseline observation carried forward (BOCF), completers-only and missing-at-random (MAR) analyses.
A total of 203 participants completed the 24-month visit. Using measured weights only, there was a trend for greater 24-month weight loss in CP than in SC, but the difference was only statistically significant in the LOCF and BOCF analyses: LOCF: -4.14 vs -1.99 kg, difference adjusted for centre -2.08 kg, P<0.001; BOCF: -1.33 vs -0.74 kg, adjusted difference -0.60 kg, P=0.032; completers: -4.76 vs -2.99 kg, adjusted difference -1.53 kg, P=0.113; missing at random: -3.00 vs -1.94 kg, adjusted difference -1.04 kg, P=0.150. Both groups gained weight from 12-24 months and weight regain was significantly (P<0.001) greater for CP than for SC in all analysis approaches. Inclusion of self-reported weights from a further 138 participants did not change the interpretation of the findings.
Initial weight loss was poorly maintained during the no-intervention follow-up, but both groups did have lower weight over the 24 months. Attrition was high in both groups, and assumptions about missing data had considerable impact on the magnitude and statistical significance of treatment effects. It is vital that trials on weight loss interventions consider the plausibility of these differences in an analytical approach when interpreting research findings and comparing data between studies.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Due to the high prevalence of overweight and obesity there is a need to identify cost-effective approaches for weight loss in primary care and community settings.
We evaluated the cost effectiveness ...of two weight loss programmes of 1-year duration, either standard care (SC) as defined by national guidelines, or a commercial provider (Weight Watchers) (CP).
This analysis was based on a randomised controlled trial of 772 adults (87% female; age 47.4±12.9 years; body mass index 31.4±2.6 kg m(-2)) recruited by health professionals in primary care in Australia, United Kingdom and Germany. Both a health sector and societal perspective were adopted to calculate the cost per kilogram of weight loss and the ICER, expressed as the cost per quality adjusted life year (QALY).
The cost per kilogram of weight loss was USD122, 90 and 180 for the CP in Australia, the United Kingdom and Germany, respectively. For SC the cost was USD138, 151 and 133, respectively. From a health-sector perspective, the ICER for the CP relative to SC was USD18 266, 12 100 and 40 933 for Australia, the United Kingdom and Germany, respectively. Corresponding societal ICER figures were USD31,663, 24,996 and 51,571.
The CP was a cost-effective approach from a health funder and societal perspective. Despite participants in the CP group attending two to three times more meetings than the SC group, the CP was still cost effective even including these added patient travel costs. This study indicates that it is cost effective for general practitioners (GPs) to refer overweight and obese patients to a CP, which may be better value than expending public funds on GP visits to manage this problem.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving ...long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in body weight and blood pressure, and the impact of these changes on subsequent cardiovascular outcome events.
A total of 9804 male and female subjects, aged 55 years or older, with a body mass index of 27-45 kg m(-2) were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor (hypertension, dyslipidemia, current smoking or diabetic nephropathy) to assess cardiovascular outcomes. Post hoc subgroup analyses of weight change (categories) and blood pressure were performed overall and by treatment group (6-week sibutramine followed by randomized placebo or continued sibutramine). The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models with factors for treatment, subgroups and interactions.
During the initial 6-week sibutramine treatment period, systolic blood pressure decreased progressively with increasing weight loss in hypertensive subjects (-8.1±10.5 mm Hg with <5 kg weight loss to -10.8±11.0 mm Hg with ⩾5 kg weight loss). The highest POE incidence occurred mainly in groups with increases in both weight and blood pressure. However, with long-term sibutramine treatment, a markedly lower blood pressure tended to increase POEs.
Modest weight loss and modest lower blood pressure each reduced the incidence of cardiovascular events, as expected. However, the combination of early marked weight loss and rapid blood pressure reduction seems to be harmful in this obese elderly cardiovascular diseased population.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aims/hypothesis
The optimal HbA
1c
concentration for prevention of macrovascular complications and deaths in obese cardiovascular high-risk patients with type 2 diabetes remains to be established and ...was therefore studied in this post hoc analysis of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial, which enrolled overweight and obese patients with type 2 diabetes and/or cardiovascular disease.
Methods
HRs for meeting the primary endpoint (nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death) and all-cause mortality were analysed using Cox regression models.
Results
Of 8,252 patients with type 2 diabetes included in SCOUT, 7,479 had measurements of HbA
1c
available at baseline (i.e. study randomisation). Median age was 62 years (range 51–86 years), median BMI was 34.0 kg/m
2
(24.8–65.1 kg/m
2
) and 44% were women. The median HbA
1c
concentration was 7.2% (3.8–15.9%) (55 mmol/l 18–150 mmol/l) and median diabetes duration was 7 years (0–57 years). For each 1 percentage point HbA
1c
increase, the adjusted HR for the primary endpoint was 1.17 (95% CI 1.11, 1.23); no differential sex effect was observed (
p
= 0.12 for interaction). In contrast, the risk of all-cause mortality was found to be greater in women than in men: HR 1.22 (1.10, 1.34) vs 1.12 (1.04, 1.20) for each 1 percentage point HbA
1c
increase (
p
= 0.02 for interaction). There was no evidence of increased risk associated with HbA
1c
≤6.4% (≤46 mmol/l). Glucose-lowering treatment regimens, diabetes duration or a history of cardiovascular disease did not modify the associations.
Conclusions/interpretation
In overweight, cardiovascular high-risk patients with type 2 diabetes, increasing HbA
1c
concentrations were associated with increasing risks of cardiovascular adverse outcomes and all-cause mortality.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aim: The Sibutramine Cardiovascular OUTcomes trial showed that sibutramine produced greater mean weight loss than placebo but increased cardiovascular morbidity but not mortality. The relationship ...between 12‐month weight loss and subsequent cardiovascular outcomes is explored.
Methods: Overweight/obese subjects (N = 10 744), ≥55 years with cardiovascular disease and/or type 2 diabetes mellitus, received sibutramine plus weight management during a 6‐week Lead‐in Period before randomization to continue sibutramine (N = 4906) or to receive placebo (N = 4898). The primary endpoint was the time from randomization to first occurrence of a primary outcome event (non‐fatal myocardial infarction, non‐fatal stroke, resuscitated cardiac arrest or cardiovascular death).
Results: For the total population, mean weight change during Lead‐in Period (sibutramine) was −2.54 kg. Post‐randomization, mean total weight change to Month 12 was −4.18 kg (sibutramine) or −1.87 kg (placebo). Degree of weight loss during Lead‐in Period or through Month 12 was associated with a progressive reduction in risk for the total population in primary outcome events and cardiovascular mortality over the 5‐year assessment. Although more events occurred in the randomized sibutramine group, on an average, a modest weight loss of approximately 3 kg achieved in the Lead‐in Period appeared to offset this increased event rate. Moderate weight loss (3–10 kg) reduced cardiovascular deaths in those with severe, moderate or mild cardiovascular disease.
Conclusions: Modest weight loss over short‐term (6 weeks) and longer‐term (6–12 months) periods is associated with reduction in subsequent cardiovascular mortality for the following 4–5 years even in those with pre‐existing cardiovascular disease. While the sibutramine group experienced more primary outcome events than the placebo group, greater weight loss reduced overall risk of these occurring in both groups.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
PDF
