Kari Johansson

Effect of a very low energy diet on moderate and severe obstructive sleep apnoea in obese men: a randomised controlled trial.

Objective To assess the effect of weight loss induced by a very low energy diet on moderate and severe obstructive sleep apnoea in obese men. Design Single centre, two arm, parallel, randomised, controlled, open label trial. Blocked randomisation procedure used for treatment allocation. Setting Outpatient obesity clinic in a university hospital in Stockholm, Sweden. Participants 63 obese men (body mass index 30-40, age 30-65 years) with moderate to severe obstructive sleep apnoea (apnoea-hypopnoea index (AHI) ≥15), treated with continuous positive airway pressure. Interventions The intervention group received a liquid very low energy diet (2.3 MJ/day) for seven weeks to promote weight loss, followed by two weeks of gradual introduction of normal food, reaching 6.3 MJ/day at week 9. The control group adhered to their usual diet during the nine weeks of follow-up. Main outcome measure AHI, the major disease severity index for obstructive sleep apnoea. Data from all randomised patients were included in an intention to treat analysis (baseline carried forward for missing data). Results Of the 63 eligible patients, 30 were randomised to intervention and 33 to control. Two patients in the control group were dissatisfied with allocation and immediately discontinued. All other patients completed the trial. Both groups had a mean AHI of 37 events/h (SD 15) at baseline. At week 9, the intervention group’s mean body weight was 20 kg (95% confidence interval 18 to 21) lower than that of the control group, while its mean AHI was 23 events/h (15 to 30) lower. In the intervention group, five of 30 (17%) were disease free after the energy restricted diet (AHI <5), with 15 of 30 (50%) having mild disease (AHI 5-14.9), whereas the AHI of all patients in the control group except one remained at 15 or higher. In a subgroup analysis of the intervention group, baseline AHI significantly modified the effectiveness of treatment, with a greater improvement in AHI in patients with severe obstructive sleep apnoea (AHI >30) at baseline compared with those with moderate (AHI 15-30) sleep apnoea (AHI −38 v −12, P<0.001), despite similar weight loss (−19.2 v −18.2 kg, P=0.55). Conclusion Treatment with a low energy diet improved obstructive sleep apnoea in obese men, with the greatest effect in patients with severe disease. Long term treatment studies are needed to validate weight loss as a primary treatment strategy for obstructive sleep apnoea. Trial registration Current Controlled Trials ISRCTN70090382.

Outcomes of Pregnancy after Bariatric Surgery

BACKGROUND Maternal obesity is associated with increased risks of gestational diabetes, large-for-gestational-age infants, preterm birth, congenital malformations, and stillbirth. The risks of these outcomes among women who have undergone bariatric surgery are unclear. METHODS We identified 627,693 singleton pregnancies in the Swedish Medical Birth Register from 2006 through 2011, of which 670 occurred in women who had previously undergone bariatric surgery and for whom presurgery weight was documented. For each pregnancy after bariatric surgery, up to five control pregnancies were matched for the mothers presurgery body-mass index (BMI; we used early-pregnancy BMI in the controls), age, parity, smoking history, educational level, and delivery year. We assessed the risks of gestational diabetes, large-for-gestational-age and small-for-gestational-age infants, preterm birth, stillbirth, neonatal death, and major congenital malformations. RESULTS Pregnancies after bariatric surgery, as compared with matched control pregnancies, were associated with lower risks of gestational diabetes (1.9% vs. 6.8%; odds ratio, 0.25; 95% confidence interval [CI], 0.13 to 0.47; P<0.001) and large-for-gestational-age infants (8.6% vs. 22.4%; odds ratio, 0.33; 95% CI, 0.24 to 0.44; P<0.001). In contrast, they were associated with a higher risk of small-for-gestational-age infants (15.6% vs. 7.6%; odds ratio, 2.20; 95% CI, 1.64 to 2.95; P<0.001) and shorter gestation (273.0 vs. 277.5 days; mean difference -4.5 days; 95% CI, -2.9 to -6.0; P<0.001), although the risk of preterm birth was not significantly different (10.0% vs. 7.5%; odds ratio, 1.28; 95% CI, 0.92 to 1.78; P=0.15). The risk of stillbirth or neonatal death was 1.7% versus 0.7% (odds ratio, 2.39; 95% CI, 0.98 to 5.85; P=0.06). There was no significant between-group difference in the frequency of congenital malformations. CONCLUSIONS Bariatric surgery was associated with reduced risks of gestational diabetes and excessive fetal growth, shorter gestation, an increased risk of small-for-gestational-age infants, and possibly increased mortality. (Funded by the Swedish Research Council and others.).

Effects of anti-obesity drugs, diet, and exercise on weight-loss maintenance after a very-low-calorie diet or low-calorie diet: a systematic review and meta-analysis of randomized controlled trials

Background: Weight-loss maintenance remains a major challenge in obesity treatment. Objective: The objective was to evaluate the effects of anti-obesity drugs, diet, or exercise on weight-loss maintenance after an initial very-low-calorie diet (VLCD)/low-calorie diet (LCD) period (<1000 kcal/d). Design: We conducted a systematic review by using MEDLINE, the Cochrane Controlled Trial Register, and EMBASE from January 1981 to February 2013. We included randomized controlled trials that evaluated weight-loss maintenance strategies after a VLCD/LCD period. Two authors performed independent data extraction by using a predefined data template. All pooled analyses were based on random-effects models. Results: Twenty studies with a total of 27 intervention arms and 3017 participants were included with the following treatment categories: anti-obesity drugs (3 arms; n = 658), meal replacements (4 arms; n = 322), high-protein diets (6 arms; n = 865), dietary supplements (6 arms; n = 261), other diets (3 arms; n = 564), and exercise (5 arms; n = 347). During the VLCD/LCD period, the pooled mean weight change was −12.3 kg (median duration: 8 wk; range 3–16 wk). Compared with controls, anti-obesity drugs improved weight-loss maintenance by 3.5 kg [95% CI: 1.5, 5.5 kg; median duration: 18 mo (12–36 mo)], meal replacements by 3.9 kg [95% CI: 2.8, 5.0 kg; median duration: 12 mo (10–26 mo)], and high-protein diets by 1.5 kg [95% CI: 0.8, 2.1 kg; median duration: 5 mo (3–12 mo)]. Exercise [0.8 kg; 95% CI: −1.2, 2.8 kg; median duration: 10 mo (6–12 mo)] and dietary supplements [0.0 kg; 95% CI: −1.4, 1.4 kg; median duration: 3 mo (3–14 mo)] did not significantly improve weight-loss maintenance compared with control. Conclusion: Anti-obesity drugs, meal replacements, and high-protein diets were associated with improved weight-loss maintenance after a VLCD/LCD period, whereas no significant improvements were seen for dietary supplements and exercise.

Longer term effects of very low energy diet on obstructive sleep apnoea in cohort derived from randomised controlled trial: prospective observational follow-up study

Objective To determine whether initial improvements in obstructive sleep apnoea after a very low energy diet were maintained after one year in patients with moderate to severe obstructive sleep apnoea. Design Single centre, prospective observational follow-up study. Setting Outpatient obesity clinic in a university hospital in Stockholm, Sweden. Participants 63 men aged 30-65 with body mass index (BMI) 30-40 and moderate to severe obstructive sleep apnoea defined as an apnoea-hypopnoea index ≥15 (events/hour), all treated with continuous positive airway pressure. Intervention A one year weight loss programme, consisting of an initial very low energy diet for nine weeks (seven weeks of 2.3 MJ/day and two weeks of gradual introduction of normal food) followed by a weight loss maintenance programme. Main outcome measure Apnoea-hypopnoea index, the main index for severity of obstructive sleep apnoea. Data from all patients were analysed (baseline carried forward for missing data). Results Of 63 eligible patients, 58 completed the very low energy diet period and started the weight maintenance programme and 44 completed the full programme; 49 had complete measurements at one year. At baseline the mean apnoea-hypopnoea index was 36 events/hour. After the very low energy diet period, apnoea-hypopnoea index was improved by −21 events/hour (95% confidence interval −17 to −25) and weight by −18 kg (−16 to −19; both P<0.001). After one year the apnoea-hypopnoea index had improved by −17 events/hour (−13 to −21) and body weight by −12 kg (−10 to −14) compared with baseline (both P<0.001). Patients with severe obstructive sleep apnoea at baseline had greater improvements in apnoea-hypopnoea index (−25 events/hour) compared with patients with moderate disease (−7 events/hour, P<0.001). At one year, 30/63 (48%, 95% confidence interval 35% to 60%) no longer required continuous positive airway pressure and 6/63 (10%, 2% to 17%) had total remission of obstructive sleep apnoea (apnoea-hypopnoea index <5 events/hour). There was a dose-response association between weight loss and apnoea-hypopnoea index at follow-up (β=0.50 events/kg, 0.11 to 0.88; P=0.013). Conclusion Initial improvements in obstructive sleep apnoea after treatment with a very low energy diet can be maintained after one year in obese men with moderate to severe disease. Those who lose the most weight or have severe sleep apnoea at baseline benefit most. Trial registration Current Controlled Trials 70090382.

Effects of childhood abuse on adult obesity: a systematic review and meta-analysis

Controversy exists surrounding the role of childhood abuse in obesity development. This is a meta‐analysis of observational studies on the role of childhood abuse in adult obesity. Systematic searches of PubMed, PsycInfo, Medline and CINAHL resulted in 23 cohort studies (4 prospective, 19 retrospective) with n = 112,708 participants, containing four abuse types (physical, emotional, sexual, general). Four studies reported dose–response effects. A random effects model was used to quantify effect sizes, meta‐regression/subgroup analysis for identifying potential moderating variables and Eggers test for publication bias. Adults who reported childhood abuse were significantly more likely to be obese (odds ratio [OR]: 1.34, 95% confidence interval [CI]: 1.24–1.45, P < 0.001). All four types of abuse were significantly associated with adult obesity: physical (OR: 1.28, 95% CI: 1.13–1.46), emotional (OR: 1.36, 95% CI: 1.08–1.71), sexual (OR: 1.31, 95% CI: 1.13–1.53) and general abuse (OR: 1.45, 95% CI: 1.25–1.69). Severe abuse (OR: 1.50, 95% CI: 1.27–1.77) was significantly more associated with adult obesity (P = 0.043) compared with light/moderate abuse (OR: 1.13, 95% CI: 0.91–1.41). We found no significant effects of study design (prospective vs. retrospective, P = 0.07), age (P = 0.96) or gender (P = 0.92). Publication bias was evident (Eggers test P = 0.007), but effect sizes remained statistically significant in sensitivity analyses. Childhood abuse was clearly associated with being obese as an adult, including a positive dose–response association. This suggests that adverse life experiences during childhood plays a major role in obesity development, potentially by inducing mental and emotional perturbations, maladaptive coping responses, stress, inflammation and metabolic disturbances.

Discontinuation due to adverse events in randomized trials of orlistat, sibutramine and rimonabant: a meta‐analysis

The objective of this article was to estimate the risk of discontinuation due to adverse events in trials of orlistat, sibutramine and rimonabant. Medline, EMBASE, the Cochrane controlled trials register and reference lists of identified articles were searched from 1990 to May 2008. All randomized placebo‐controlled trials of 12–24 months of duration on adults using licensed doses were included. Studies/study arms were excluded if they evaluated weight maintenance after weight loss. Trials were identified, subjected to inclusion and exclusion criteria and reviewed. Data on participants, interventions and discontinuation were extracted and trials rated for quality based on established criteria. A random effects model was used to estimate pooled risk ratios, risk differences and number needed to harm (NNH). A total of 28 trials met the inclusion criteria (16 orlistat, 7 sibutramine and 5 rimonabant). The risk ratios for discontinuation due to adverse events were significantly elevated for rimonabant (2.00; 1.66–2.41) and orlistat (1.59; 1.21–2.08), but not sibutramine (0.98, 0.68–1.41). Compared with placebo, the risk difference was the largest for rimonabant (7%, 5–9%; NNH 14, 11–19), followed by orlistat (3%, 1–4%; NNH 39, 25–83), while no significant difference was seen for sibutramine (0.2%, −3 to 4%; NNH 500). The most common adverse events leading to withdrawal were gastrointestinal for orlistat (40%) and psychiatric for rimonabant (47%). Corresponding information was unavailable for sibutramine. In conclusion, available weight loss drugs differ markedly regarding risk of discontinuation due to adverse events, as well as in underlying causes of these events. Given the large number of patients eligible for treatment, the low NNH for rimonabant is a concern.

Weight loss and dropout during a commercial weight-loss program including a very-low-calorie diet, a low-calorie diet, or restricted normal food: observational cohort study

Background: The effectiveness of commercial weight-loss programs consisting of very-low-calorie diets (VLCDs) and low-calorie diets (LCDs) is unclear. Objective: The aim of the study was to quantify weight loss and dropout during a commercial weight-loss program in Sweden (Itrim; cost:

Long‐term weight loss and weight‐loss maintenance strategies

1300/€1000; all participants paid their own fee). Design: This observational cohort study linked commercial weight-loss data with National Health Care Registers. Weight loss was induced with a 500-kcal liquid-formula VLCD [n = 3773; BMI (in kg/m2): 34 ± 5 (mean ± SD); 80% women; 45 ± 12 y of age (mean ± SD)], a 1200–1500-kcal formula and food-combination LCD (n = 4588; BMI: 30 ± 4; 86% women; 50 ± 11 y of age), and a 1500–1800-kcal/d restricted normal-food diet (n = 676; BMI: 29 ± 5; 81% women; 51 ± 12 y of age). Maintenance strategies included exercise and a calorie-restricted diet. Weight loss was analyzed by using an intention-to-treat analysis (baseline substitution). Results: After 1 y, mean (±SD) weight changes were −11.4 ± 9.1 kg with the VLCD (18% dropout), −6.8 ± 6.4 kg with the LCD (23% dropout), and −5.1 ± 5.9 kg with the restricted normal-food diet (26% dropout). In an adjusted analysis, the VLCD group lost 2.8 kg (95% CI: 2.5, 3.2) and 3.8 kg (95% CI: 3.2, 4.5) more than did the LCD and restricted normal-food groups, respectively. A high baseline BMI and rapid initial weight loss were both independently associated with greater 1-y weight loss (P < 0.001). Younger age and low initial weight loss predicted an increased dropout rate (P < 0.001). Treatment of depression (OR: 1.4; 95% CI: 1.1, 1.9) and psychosis (OR: 2.6; 95% CI: 1.1, 6.3) were associated with an increased dropout rate in the VLCD group. Conclusion: A commercial weight-loss program, particularly one using a VLCD, was effective at reducing body weight in self-selected, self-paying adults.

Trends in self-reported BMI and prevalence of obesity 2002-10 in Stockholm County, Sweden.

It has been suggested that about 20% of subjects undergoing weight‐loss programmes can achieve a certain degree of long‐term success. At present, surgery remains the only method resulting in long‐term sustained weight loss, but access remains restricted. Hence it is important to analyse, in addition to pharmacotherapy, the methods to improve the effects of diet, exercise and behavioural modification. Since these techniques are less spectacular than others, there is a risk that their potential will be overlooked, in spite of the fact that they remain the main alternative for most subjects undergoing weight‐loss therapy. This review summarizes realistic treatment alternatives and also provides data from a day care treatment, a strategy not much reported in the literature. This is a standard treatment modality for diabetes but less common in obesity treatment.

Risk of symptomatic gallstones and cholecystectomy after a very-low-calorie diet or low-calorie diet in a commercial weight loss program: 1-year matched cohort study

BACKGROUND Trends in obesity have been reported to level off in several Western countries. The aim of this study was to investigate trends in body mass index (BMI) and prevalence of obesity between 2002 and 2010 in Stockholm County, Sweden. METHODS Three cross-sectional questionnaires from the Stockholm Health Surveys were used for this study. A total of 31 182, 34 707 and 30 767 men and women aged between 18 and 64 years completed the questionnaire regarding sociodemographic factors, health parameters, physical activity, smoking habits and anthropometry in 2002, 2006 and 2010, respectively (response rate: 62.5, 61.3 and 55.6%, respectively). Linear regression was used to investigate changes in mean BMI. Relative risk regression models were used to investigate changes in prevalence of obesity, defined as BMI ≥ 30 kg/m(2). All analyses were stratified on age and further adjusted for smoking, education and socioeconomic position. RESULTS Between 2002 and 2006, a stabilization was found in BMI and prevalence of obesity in both men and women. But from 2006 to 2010, BMI and prevalence of obesity had increased, also among the young. In 2010, the prevalence of obesity was 12.2% among men and 10.3% among women. CONCLUSION After a period of stabilization in 2002-06, BMI and prevalence of obesity are increasing in Stockholm County, Sweden.