Martin Neovius

Does Excess Pregnancy Weight Gain Constitute a Major Risk for Increasing Long-term BMI?

Objective: The objective was to assess the relevance of the recommendations of the Institute of Medicine (IOM), regarding gestational weight gain (GWG) for long‐term BMI development.

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.

Prevalence of Obesity in Sweden

Although the prevalence of obesity in Sweden still is low in an international perspective, the development during the last decades is alarming in adults, adolescents and children alike. The prevalence of obesity [body mass index (BMI) > 30 kg m−2] in adults has doubled during the last two decades and is now approximately 10% in both men and women, according to estimates based on self‐reported BMI from repeated random samples of the population. However, prevalence estimates based on measured BMI from the WHO MONICA study indicate that the self‐reported data result in underestimates. In military conscripts, the prevalence of obesity (BMI > 30 kg m−2) almost quadrupled to 3.2% from 1971 to 1995, while the overweight fraction (BMI > 25 kg m−2) more than doubled to 16.3%. The development in younger age groups seems to be similar; the prevalence of overweight [International Obesity Task Force (IOTF)/Cole] in children aged 10 years in Gothenburg has doubled to 18% (2.9% obese) during the last decade, and similar figures have been reported in other studies. However, most reports on childhood overweight stem from the larger metropolitan areas, and hence may be underestimates because of the urban–rural influence on obesity‐status. Recent data from non‐urban areas in the northern part of Sweden estimate the prevalence of overweight (BMI > 20 kg m−2) in 10‐year‐olds to above 30%. In the most comprehensive study in children, including both rural and urban areas, BMI was measured among all children aged 10 years (n = 5517; 92.7% of the population) in the county of Ostergotland, and the prevalence of overweight (IOTF/Cole) was 22% in both boys and girls, of which 4% and 5% were obese respectively.

Nationwide prevalence of rheumatoid arthritis and penetration of disease-modifying drugs in Sweden

Objective To provide Swedish nationwide data on the prevalence of rheumatoid arthritis (RA), including variations by age, sex, geography, demography and education level, and assess antirheumatic treatment penetration. Methods Patients ≥16 years assigned an RA diagnosis were identified from inpatient (n=96 560; 1964–2007) and specialist outpatient care (n=56 336; 2001–2007) in the Swedish National Patient Register, and the Swedish Rheumatology Quality Register (n=21 242; 1995–2007). Data on prescriptions, demography, vital status and educational level were retrieved from national registers. Results A total of 58 102 individuals (mean age 66 years; 73% women) assigned an RA diagnosis were alive in Sweden in 2008, corresponding to a cumulative prevalence of 0.77% (women 1.11%, men 0.43%). The 2001–2007 period prevalence was 0.70%. Restriction to patients with ≥2 visits or diagnosis from a rheumatologist/internist reduced the overall cumulative prevalence to 0.68%. Whereas urban/rural differences (crude 0.65–1.00%) were explained by age differences, the age/sex-adjusted prevalence remained higher in patients with ≤9 years education (0.86%) than for those with 10–12 years (0.82%) and >12 years (0.65%). Treatment exposures (76% any disease-modifying antirheumatic drugs (DMARDs) or steroids, 64% any DMARD, 15% biological agents) varied with age; use of biological agents decreased from 22% in 16–59 years olds to 3% in ≥80 years olds. Any DMARD use correspondingly decreased from 71% to 43%. Applying age cut-off points from previous northern European and North American prevalence studies reduced or eliminated between-study differences. Conclusion This nationwide approach yielded a prevalence of RA similar to previous regional assessments. While displaying only modest geographical variation and no urban/rural gradient, prevalence was associated with educational level. Although most patients received antirheumatic drugs, age was a strong treatment determinant.

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.).

BMI, waist-circumference and waist-hip-ratio as diagnostic tests for fatness in adolescents

OBJECTIVE:To evaluate the diagnostic accuracy of body mass index (BMI, kg/m2), waist-circumference (WC) and waist-hip-ratio (WHR) as diagnostic tests for detecting fatness in adolescents.DESIGN:A cross-sectional analysis of 474 healthy adolescents aged 17 y was used. Measurements of height, weight, WC, hip-circumference and body fat percentage (%BF) were obtained. The diagnostic accuracy for detecting excess fatness was evaluated through receiver operating characteristics (ROC) analyses with %BF, measured by densitometry (air-displacement plethysmography), as reference test.RESULTS:BMI and WC showed strong positive correlation (r=0.68–0.73; P<0.0001) with %BF in both sexes, but the correlation was weaker for WHR (r=0.30–0.41; P<0.0001). For overweight and obesity in boys and obesity in girls, the area under the ROC curve was high (0.96–0.99) for BMI and WC. WHR was not significantly better than chance as diagnostic test for obesity in girls. For BMI and WC, highly sensitive and specific cutoffs for obesity could be derived, while larger trade-offs were needed for detecting overweight in girls. The cutoffs producing equal sensitivity and specificity were lower than the ones minimizing the absolute number of misclassifications. The latter approached internationally recommended reference values, but were still several units lower for BMI in girls and several centimeters lower for WC in boys.CONCLUSION:BMI and WC were found to perform well as diagnostic tests for fatness, while WHR was less useful. The discrepancies between cutoffs producing equal sensitivity and specificity, cutoffs minimizing the absolute number of misclassifications and internationally recommended reference values for overweight and obesity highlight the importance of specifying the characteristics of classification systems for different settings.

Association of blood pressure in late adolescence with subsequent mortality: cohort study of Swedish male conscripts

Objective To investigate the nature and magnitude of relations of systolic and diastolic blood pressures in late adolescence to mortality. Design Nationwide cohort study. Setting General community in Sweden. Participants Swedish men (n=1 207 141) who had military conscription examinations between 1969 and 1995 at a mean age of 18.4 years, followed up for a median of 24 (range 0-37) years. Main outcome measures Total mortality, cardiovascular mortality, and non-cardiovascular mortality. Results During follow-up, 28 934 (2.4%) men died. The relation of systolic blood pressure to total mortality was U shaped, with the lowest risk at a systolic blood pressure of about 130 mm Hg. This pattern was driven by the relation to non-cardiovascular mortality, whereas the relation to cardiovascular mortality was monotonically increasing (higher risk with higher blood pressure). The relation of diastolic blood pressure to mortality risk was monotonically increasing and stronger than that of systolic blood pressure, in terms of both relative risk and population attributable fraction (deaths that could be avoided if blood pressure was in the optimal range). Relations to cardiovascular and non-cardiovascular mortality were similar, with an apparent risk threshold at a diastolic blood pressure of about 90 mm Hg, below which diastolic blood pressure and mortality were unrelated, and above which risk increased steeply with higher diastolic blood pressures. Conclusions In adolescent men, the relation of diastolic blood pressure to mortality was more consistent than that of systolic blood pressure. Considering current efforts for earlier detection and prevention of risk, these observations emphasise the risk associated with high diastolic blood pressure in young adulthood.

Combined effects of overweight and smoking in late adolescence on subsequent mortality: nationwide cohort study

Objective To investigate the combined effects on adult mortality of overweight and smoking in late adolescence. Design Record linkage study with Cox proportional hazard ratios adjusted for muscle strength, socioeconomic position, and age. Setting Swedish military service conscription register, cause of death register, and census data. Participants 45 920 Swedish men (mean age 18.7, SD 0.5) followed for 38 years. Main outcome measures Body mass index (underweight (BMI <18.5), normal weight (18.5-24.9), overweight (25-29.9), and obesity (≥30)), muscle strength, and self reported smoking (non-smoker, light smoker (1-10 cigarettes/day), heavy smoker (>10/day)) at mandatory military conscription tests in 1969-70. All cause mortality. Results Over 1.7 million person years, 2897 men died. Compared with normal weight men (incidence rate 17/10 000 person years, 95% confidence interval 16 to 18), risk of mortality was increased in overweight (hazard ratio 1.33, 1.15 to 1.53; incidence rate 23, 20 to 26) and obese men (hazard ratio 2.14, 1.61 to 2.85; incidence rate 38, 27 to 48), with similar relative estimates in separate analyses of smokers and non-smokers. No increased risk was detected in underweight men (hazard ratio 0.97, 0.86 to 1.08; incidence rate 18, 16 to 19), though extreme underweight (BMI <17) was associated with increased mortality (hazard ratio 1.33, 1.07 to 1.64; incidence rate 24, 19 to 29). The relative excess risk due to interaction between BMI and smoking status was not significant in any stratum. Furthermore, all estimates of interaction were of small magnitude, except for the combination of obesity and heavy smoking (relative excess risk 1.5, −0.7 to 3.7). Compared with non-smokers (incidence rate 14, 13 to 15), risk was increased in both light (hazard ratio 1.54, 1.41 to 1.70; incidence rate 15, 14 to 16) and heavy smokers (hazard ratio 2.11, 1.92 to 2.31; incidence rate 26, 24 to 27). Conclusions Regardless of smoking status, overweight and obesity in late adolescence increases the risk of adult mortality. Obesity and overweight were as hazardous as heavy and light smoking, respectively, but there was no interaction between BMI and smoking status. The global obesity epidemic and smoking among adolescents remain important targets for intensified public health initiatives.

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.

Juvenile idiopathic arthritis and risk of cancer: a nationwide cohort study.

OBJECTIVE Reports of therapy-related adverse events suggest an elevated rate of malignancy in patients with juvenile idiopathic arthritis (JIA) treated with biologic therapies. However, the scarcity of data on the underlying risk of malignancy in JIA hampers interpretation of these signals. Therefore, the aim of this study was to determine the risk of cancer in patients with JIA as compared with that in the general population. METHODS Through linkage with a national database, the Swedish Patient Register (comprising inpatient discharges in 1969-2007 and specialist outpatient visits in 2001-2007 in Sweden), a national JIA cohort (n = 9,027) was identified, and each JIA case was matched with 5 general population comparators. Using data from the Swedish Cancer, Census, Death, and Biologics Registers, the occurrence of cancer, vital status, and start of a biologic therapy were identified. The relative risk (RR) of first occurrence of a primary cancer in patients who had not been treated with biologics (biologics-naive patients with JIA) was estimated using Poisson regression, stratified a priori by year of earliest identification of JIA (before 1987 versus 1987 and thereafter). In sensitivity analyses, the data were followed up to 1999, when biologics first became available. RESULTS In this biologics-naive JIA cohort, 60 malignancies were observed during 131,144 person-years of followup, compared with 266 cancers observed during 661,758 person-years in the general population comparator (0.46 cases/1,000 person-years versus 0.40 cases/1,000 person-years; RR 1.1, 95% confidence interval [95% CI] 0.9-1.5). Patients with JIA identified before 1987 were not at increased risk of cancer, whereas JIA identified in 1987 and thereafter was significantly associated with incident lymphoproliferative malignancies (RR 4.2, 95% CI 1.7-10.7) and cancers overall (RR 2.3, 95% CI 1.2-4.4). Sensitivity analyses did not reveal any ready explanation for this heterogeneity. CONCLUSION Although absolute risks were low, an elevated risk of malignancy was observed among biologics-naive patients in whom the diagnosis of JIA was made in the past 20 years, which may have implications for the interpretation of cancer signals in patients with JIA treated with newer therapies.