Jennifer Logue

Association between general and central adiposity in childhood, and change in these, with cardiovascular risk factors in adolescence: prospective cohort study.

Objectives To examine the prospective associations between body mass index (BMI), waist circumference, and fat mass in childhood and cardiovascular risk factors at age 15-16. Design Prospective cohort study. Setting Avon Longitudinal Study of Parents and Children. Participants 5235 children aged 9-12 at start of study. Main exposures BMI, waist circumference, and fat mass determined by dual energy x ray absorptiometry, assessed at age 9-12 and at age 15-16. Main outcome measures Systolic and diastolic blood pressure and concentrations of fasting glucose, insulin, triglycerides, low density lipoprotein cholesterol, and high density lipoprotein cholesterol assessed at age 15-16. Results In girls a 1 SD greater BMI at age 9-12 was associated with cardiovascular risk factors at age 15-16 in fully adjusted models: odds ratio 1.23 (95% confidence interval 1.10 to 1.38) for high systolic blood pressure (≥130 mm Hg); 1.19 (1.03 to 1.38) for high concentration of low density lipoprotein cholesterol (≥2.79 mmol/l); 1.43 (1.06 to 1.92) for high concentration of triglycerides (≥1.7 mmol/l); 1.25 (1.08 to 1.46) for low concentration of high density lipoprotein cholesterol (<1.03 mmol/l); and 1.45 (1.22 to 1.73) for high concentration of insulin (≥16.95 IU/l). Equivalent results in boys were 1.24 (1.13 to 1.37) for systolic blood pressure; 1.30 (1.07 to 1.59) for low density lipoprotein cholesterol; 1.96 (1.51 to 2.55) for triglycerides; 1.39 (1.22 to 1.57) for high density lipoprotein cholesterol, and 1.84 (1.56 to 2.17) for insulin. BMI was associated with high fasting glucose (≥5.6 mmol/l) only in boys (1.18, 1.03 to 1.36). With these binary outcomes there was statistical evidence that associations differed between girls and boys for fasting glucose (P=0.03) and insulin (P<0.001). When risk factors were examined as continuous outcomes there was evidence for stronger associations of BMI with more adverse levels in boys than girls for fasting insulin, glucose, and triglyceride concentrations (all interaction P≤0.03). BMI, waist circumference, and fat mass were all strongly correlated with each other (r=0.89-0.94), and associations of the three with cardiovascular outcomes were of similar magnitude with statistical evidence of consistency in associations (all P>0.2 for heterogeneity). When waist circumference or fat mass or both were added to models including BMI they did not increase the variation in cardiovascular risk factors already explained by BMI and confounders alone. Girls who were overweight/obese at age 9-12 but were normal weight by 15-16 had similar odds of adverse levels of risk factors to those who were normal weight at both ages. In boys odds of high systolic blood pressure, high concentrations of triglycerides and insulin, and low concentrations of high density lipoprotein cholesterol remained higher in this group compared with those who were normal weight at both ages but were lower than in those who remained overweight/obese at both ages. Conclusions Measurements of waist circumference or directly assessed fat mass in childhood do not seem to be associated with cardiovascular risk factors in adolescence any more strongly than BMI. Girls who favourably alter their overweight status between childhood and adolescence have cardiovascular risk profiles broadly similar to those who were normal weight at both time points, but boys who change from overweight to normal show risk factor profiles intermediate between those seen in boys who are normal weight at both ages or overweight at both ages.

Obesity is associated with fatal coronary heart disease independently of traditional risk factors and deprivation

Background The effect of body mass index (BMI) on coronary heart disease (CHD) risk is attenuated when mediators of this risk (such as diabetes, hypertension and hyperlipidaemia) are accounted for. However, there is now evidence of a differential effect of risk factors on fatal and non-fatal CHD events, with markers of inflammation more strongly associated with fatal than non-fatal events. Objective To describe the association with BMI separately for both fatal and non-fatal CHD risk after accounting for classical risk factors and to assess any independent effects of obesity on CHD risk. Methods and results In the West of Scotland Coronary Prevention Study BMI in 6082 men (mean age 55 years) with hypercholesterolaemia, but no history of diabetes or CVD, was related to the risk of fatal and non-fatal CHD events. After excluding participants with any event in the first 2 years, 1027 non-fatal and 214 fatal CHD events occurred during 14.7 years of follow-up. A minimally adjusted model (age, sex, statin treatment) and a maximally adjusted model (including known CVD risk factors and deprivation) were compared, with BMI 25–27.4 kg/m2 as referent. The risk of non-fatal events was similar across all BMI categories in both models. The risk of fatal CHD events was increased in men with BMI 30.0–39.9 kg/m2 in both the minimally adjusted model (HR=1.75 (95% CI 1.12 to 2.74)) and the maximally adjusted model (HR=1.60 (95% CI 1.02 to 2.53)). Conclusions These hypothesis generating data suggest that obesity is associated with fatal, but not non-fatal, CHD after accounting for known cardiovascular risk factors and deprivation. Clinical trial registration WOSCOPS was carried out and completed before the requirement for clinical trial registration.

Association Between BMI Measured Within a Year After Diagnosis of Type 2 Diabetes and Mortality

OBJECTIVE To describe the association of BMI with mortality in patients diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS Using records of 106,640 patients in Scotland, we investigated the association between BMI recorded around the diagnosis of type 2 diabetes mellitus (T2DM) and mortality using Cox proportional hazards regression adjusted for age and smoking status, with BMI 25 to <30 kg/m2 as a referent group. Deaths within 2 years of BMI determination were excluded. Mean follow-up to death or the end of 2007 was 4.7 years. RESULTS A total of 9,631 deaths occurred between 2001 and 2007. Compared with the reference group, mortality risk was higher in patients with BMI 20 to <25 kg/m2 (hazard ratio 1.22 [95% CI 1.13–1.32] in men, 1.32 [1.22–1.44] in women) and patients with BMI ≥35 kg/m2 (for example, 1.70 [1.24–2.34] in men and 1.81 [1.46–2.24] in women for BMI 45 to <50 kg/m2). Vascular mortality was higher for each 5-kg/m2 increase in BMI >30 kg/m2 by 24% (15–35%) in men and 23% (14–32%) in women, but was lower below this threshold. The results were similar after further adjustment for HbA1c, year of diagnosis, lipids, blood pressure, and socioeconomic status. CONCLUSIONS Patients categorized as normal weight or obese with T2DM within a year of diagnosis of T2DM exhibit variably higher mortality outcomes compared with the overweight group, confirming a U-shaped association of BMI with mortality. Whether weight loss interventions reduce mortality in all T2DM patients requires study.

Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15.

Background Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15. Methods and Findings Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0–2 years and BMI from 2–10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL- and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0–2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5–10), and were largely mediated by fat mass at age 15. Conclusion Changes in PI/BMI from 0–10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5–10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight.

Management of obesity: summary of SIGN guideline

In Scotland 68.5% of men, 61.8% of women, 36.1% of boys, and 26.9% of girls are classified as overweight or obese.1 The cost of obesity and obesity related illnesses to the NHS in Scotland was estimated to be £171m (€190m;

Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology

273m) in 2001,2 and forecasts in England suggest that NHS expenditure attributable to these conditions could double between 2007 and 2050.3 Being obese at age 40 reduces life expectancy by 7.1 years for women and 5.8 years for men.4 Given the massive detrimental effect of obesity on health and wellbeing, all health professionals should know how obesity should be managed. This article summarises the most recent recommendations from the Scottish Intercollegiate Guidelines Network (SIGN) on the management of obesity.5 SIGN recommendations are based on systematic reviews of best available evidence, and the strength of the evidence is indicated as A, B, C, or D (figure⇓). Recommended best practice (“good practice points”), based on the clinical experience of the guideline development group, is also indicated (as GPP). Explanation of SIGN grades of recommendations ### Classification Use body mass index (BMI) to classify overweight or obesity in adults (B): Waist circumference may be used in addition to BMI to help assess the risk of obesity related comorbidities (C). Waist circumference cut-off values for an increased risk of obesity related health problems are: ### Prevention and identification of high risk groups

Outcomes of a specialist weight management programme in the UK National Health Service: prospective study of 1838 patients.

The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30–40% of patients) and associated with a higher risk of HF hospitalization, all‐cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice. There are no specific limitations to HF treatment in T2DM. Subanalyses of trials addressing HF treatment in the general population have shown that all HF therapies are similarly effective regardless of T2DM. Concerning T2DM treatment in HF patients, most guidelines currently recommend metformin as the first‐line choice. Sulphonylureas and insulin have been the traditional second‐ and third‐line therapies although their safety in HF is equivocal. Neither glucagon‐like preptide‐1 (GLP‐1) receptor agonists, nor dipeptidyl peptidase‐4 (DPP4) inhibitors reduce the risk for HF hospitalization. Indeed, a DPP4 inhibitor, saxagliptin, has been associated with a higher risk of HF hospitalization. Thiazolidinediones (pioglitazone and rosiglitazone) are contraindicated in patients with (or at risk of) HF. In recent trials, sodium–glucose co‐transporter‐2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have both shown a significant reduction in HF hospitalization in patients with established CV disease or at risk of CV disease. Several ongoing trials should provide an insight into the effectiveness of SGLT2 inhibitors in patients with HFrEF and HFpEF in the absence of T2DM.

Contributions of maternal and paternal adiposity and smoking to adult offspring adiposity and cardiovascular risk: the Midspan Family Study

Objectives There is limited evidence on the effectiveness of weight management programmes provided within routine healthcare and inconsistent use of outcome measures. Our aim was to evaluate a large National Health Service (NHS) weight management service and report absolute and proportional weight losses over 12 months. Design Prospective observational study. Setting Glasgow and Clyde Weight Management Service (GCWMS), which provides care for residents of NHS Greater Glasgow and Clyde area (population 1.2 million). Participants All patients who began GCWMS between 1 October 2008 and 30 September 2009. Interventions Structured educational lifestyle programme employing cognitive behavioural therapy, 600 kcal deficit diet, physical activity advice, lower calorie diet and pharmacotherapy. Primary and secondary outcomes measures Baseline observation carried forward (BOCF), last observation carried forward (LOCF) and changes in programme completers reported using outcomes of absolute 5 kg and 5% weight losses and mean weight changes at a variety of time points. Results 6505 referrals were made to GCWMS, 5637 were eligible, 3460 opted in and 1916 (34%) attended a first session. 78 patients were excluded from our analysis on 1838 patients. 72.9% of patients were women, mean age of all patients at baseline was 49.1 years, 43.3% lived in highly socioeconomically deprived areas and mean weights and body mass indices at baseline were 118.1 kg and 43.3 kg/m2, respectively. 26% lost ≥5 kg by the end of phase 1, 30% by the end of phase 2 and 28% by the end of phase 3 (all LOCF). Weight loss was more successful among men, particularly those ≤29 years old. Conclusions Routine NHS weight management services may achieve moderate weight losses through a comprehensive evidence-based dietary, activity and behavioural approach including psychological care. Weight losses should be reported using a range of outcome measures so that the effectiveness of different services can be compared.

Effect of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

Objective Obesity has some genetic basis but requires interaction with environmental factors for phenotypic expression. We examined contributions of gender-specific parental adiposity and smoking to adiposity and related cardiovascular risk in adult offspring. Design Cross-sectional general population survey. Setting Scotland. Participants 1456 of the 1477 first generation families in the Midspan Family Study: 2912 parents (aged 45–64 years surveyed between 1972 and 1976) who had 1025 sons and 1283 daughters, aged 30–59 years surveyed in 1996. Main measures Offspring body mass index (BMI), waist circumference (WC), cardiometabolic risk (lipids, blood pressure and glucose) and cardiovascular disease as outcome measures, and parental BMI and smoking as determinants. All analyses adjusted for age, socioeconomic status and family clustering and offspring birth weight. Results Regression coefficients for BMI associations between father–son (0.30) and mother–daughter (0.33) were greater than father–daughter (0.23) or mother–son (0.22). Regression coefficient for the non-genetic, shared-environment or assortative-mating relationship between BMIs of fathers and mothers was 0.19. Heritability estimates for BMI were greatest among women with mothers who had BMI either <25 or ≥30 kg/m2. Compared with offspring without obese parents, offspring with two obese parents had adjusted OR of 10.25 (95% CI 6.56 to 13.93) for having WC ≥102 cm for men, ≥88 cm women, 2.46 (95% CI 1.33 to 4.57) for metabolic syndrome and 3.03 (95% CI 1.55 to 5.91) for angina and/or myocardial infarct (p<0.001). Neither parental adiposity nor smoking history determined adjusted offspring individual cardiometabolic risk factors, diabetes or stroke. Maternal, but not paternal, smoking had significant effects on WC in sons (OR=1.50; 95% CI 1.13 to 2.01) and daughters (OR=1.42; 95% CI 1.10 to 1.84) and metabolic syndrome OR=1.68; 95% CI 1.17 to 2.40) in sons. Conclusions There are modest genetic/epigenetic influences on the environmental factors behind adverse adiposity. Maternal smoking appears a specific hazard on obesity and metabolic syndrome. A possible epigenetic mechanism linking maternal smoking to obesity and metabolic syndrome in offspring is proposed. Individuals with family histories of obesity should be targeted from an early age to prevent obesity and complications.

Childhood Obesity: A Ticking Time Bomb for Cardiovascular Disease?

Orlistat is an effective adjunctive treatment to lifestyle modifications in the treatment of obesity. While the majority of current evidence is on the effect of orlistat in obese patients without diabetes, some studies suggest that patients who are obese and have diabetes mellitus lose more weight and have greater improvements in diabetic outcomes when treated with orlistat plus a lifestyle intervention than when treated by lifestyle interventions alone. The aim of this study was to review the evidence of the effects of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes. A systematic review of randomized controlled trials of orlistat in people with type 2 diabetes reporting diabetes outcomes in studies published between January 1990 and September 2013 was conducted. We searched for articles published in English in MEDLINE and EMBASE. Inclusion criteria included all randomized controlled trials of orlistat carried out on adult participants with a body mass index of 25 kg m−2 or over diagnosed with type 2 diabetes, which reported weight change and at least one diabetic outcome. A total of 765 articles were identified out of which 12 fulfilled the inclusion criteria. The overall mean weight reduction (3, 6 and 12 months) in the orlistat group was −4.25 kg (95% CI: −4.5 to −3.9 kg). The mean weight difference between treatment and control groups was −2.10 kg (95% CI: −2.3 to −1.8 kg, P < 0.001), the mean HbA1c difference was −6.12 mmol mol−1 (95% CI: −10.3 to −1.9 mmol mol−1, P < 0.004) and the mean fasting blood glucose difference was −1.16 mmol L−1 (95% CI: −1.4 to −0.8 mmol L−1, P < 0.001). Treatment with orlistat plus lifestyle intervention resulted in significantly greater weight loss and improved glycaemic control in overweight and obese patients with type 2 diabetes compared with lifestyle intervention alone.