Michael E. J. Lean

Waist circumference as a measure for indicating need for weight management

Abstract Objective: To test the hypothesis that a single measurement, waist circumference, might be used to identify people at health risk both from being overweight and from having a central fat distribution. Design: A community derived random sample of men and women and a second, validation sample. Setting: North Glasgow. Subjects: 904 men and 1014 women (first sample); 86 men and 202 women (validation sample). Main outcome measures: Waist circumference, body mass index, waist:hip ratio. Results: Waist circumference >/=94 cm for men and >/=80 cm for women identified subjects with high body mass index (>/=25 kg/m2) and those with lower body mass index but high waist:hip ratio (>/=0.95 for men, >/=0.80 women) with a sensitivity of >96% and specificity >97.5%. Waist circumference >/=102 cm for men or >/=88 cm for women identified subjects with body mass index >/=30 and those with lower body mass index but high waist:hip ratio with a sensitivity of >96% and specificity >98%, with only about 2% of the sample being misclassified. Conclusions: Waist circumference could be used in health promotion programmes to identify individuals who should seek and be offered weight management. Men with waist circumference >/=94 cm and women with waist circumference >/=80 cm should gain no further weight; men with waist circumference >/=102 cm and women with waist circumference >/=88 cm should reduce their weight.

Waist circumference action levels in the identification of cardiovascular risk factors: prevalence study in a random sample

Abstract Objective: To determine the frequency of cardiovascular risk factors in people categorised by previously defined “action g126 levels” of waist circumference. Design: Prevalence study in a random population sample. Setting: Netherlands. Subjects: 2183 men and 2698 women aged 20-59 years selected at random from the civil registry of Amsterdam and Maastricht. Main outcome measures: Waist circumference, waist to hip ratio, body mass index (weight (kg)/height (m2)), total plasma cholesterol concentration, high density lipoprotein cholesterol concentration, blood pressure, age, and lifestyle. Results: A waist circumference exceeding 94 cm in men and 80 cm in women correctly identified subjects with body mass index of >/=25 and waist to hip ratios >/=0.95 in men and >/=0.80 in women with a sensitivity and specificity of >/=96%. Men and women with at least one cardiovascular risk factor (total cholesterol >/=6.5 mmol/l, high density lipoprotein cholesterol </=0.9 mmol/l, systolic blood pressure >/=160 mm Hg, diastolic blood pressure >/=95 mm Hg) were identified with sensitivities of 57% and 67% and specificities of 72% and 62% respectively. Compared with those with waist measurements below action levels, age and lifestyle adjusted odds ratios for having at least one risk factor were 2.2 (95% confidence interval 1.8 to 2.8) in men with a waist measurement of 94-102 cm and 1.6 (1.3 to 2.1) in women with a waist measurement of 80-88 cm. In men and women with larger waist measurements these age and lifestyle adjusted odds ratios were 4.6 (3.5 to 6.0) and 2.6 (2.0 to 3.2) respectively. Conclusions: Larger waist circumference identifies people at increased cardiovascular risks.

Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study

BACKGROUND The frequency of obesity has risen dramatically in recent years but only few safe and effective drugs are currently available. We assessed the effect of liraglutide on bodyweight and tolerability in obese individuals without type 2 diabetes. METHODS We did a double-blind, placebo-controlled 20-week trial, with open-label orlistat comparator in 19 sites in Europe. 564 individuals (18-65 years of age, body-mass index 30-40 kg/m2) were randomly assigned, with a telephone or web-based system, to one of four liraglutide doses (1.2 mg, 1.8 mg, 2.4 mg, or 3.0 mg, n=90-95) or to placebo (n=98) administered once a day subcutaneously, or orlistat (120 mg, n=95) three times a day orally. All individuals had a 500 kcal per day energy-deficit diet and increased their physical activity throughout the trial, including the 2-week run-in. Weight change analysed by intention to treat was the primary endpoint. An 84-week open-label extension followed. This study is registered with ClinicalTrials.gov, number NCT00422058. FINDINGS Participants on liraglutide lost significantly more weight than did those on placebo (p=0.003 for liraglutide 1.2 mg and p<0.0001 for liraglutide 1.8-3.0 mg) and orlistat (p=0.003 for liraglutide 2.4 mg and p<0.0001 for liraglutide 3.0 mg). Mean weight loss with liraglutide 1.2-3.0 mg was 4.8 kg, 5.5 kg, 6.3 kg, and 7.2 kg compared with 2.8 kg with placebo and 4.1 kg with orlistat, and was 2.1 kg (95% CI 0.6-3.6) to 4.4 kg (2.9-6.0) greater than that with placebo. More individuals (76%, n=70) lost more than 5% weight with liraglutide 3.0 mg that with placebo (30%, n=29) or orlistat (44%, n=42). Liraglutide reduced blood pressure at all doses, and reduced the prevalence of prediabetes (84-96% reduction) with 1.8-3.0 mg per day. Nausea and vomiting occurred more often in individuals on liraglutide than in those on placebo, but adverse events were mainly transient and rarely led to discontinuation of treatment. INTERPRETATION Liraglutide treatment over 20 weeks is well tolerated, induces weight loss, improves certain obesity-related risk factors, and reduces prediabetes. FUNDING Novo Nordisk A/S, Bagsvaerd, Denmark.

Impairment of health and quality of life in people with large waist circumference

BACKGROUND Symptoms and secondary disorders associated with excess central fat distribution are being increasingly recognised. We aimed to define the symptoms and assess risks of chronic disorders in people with large waist circumferences. METHODS We did a cross-sectional study of 5887 men and 7018 women aged 20-59 years from the general population of Maastricht, Amsterdam, and Doetinchem, Netherlands. We assessed in health centres respiratory insufficiency, low back pain, degree of physical function, presence of non-insulin-dependent diabetes, and cardiovascular risk factors. We measured bodyweight, body-mass index, and waist circumference by action levels (men: less than action level 1 <94.0 cm, action levels 1-2 94.0-101.9 cm, more than action level 2 > or =102.0 cm; women: less than action level 1 <80.0 cm, action levels 1-2 80.0-87.9 cm) more than action level 2 > or =88.0 cm). The reference group were people with waist circumferences lower than action level 1. FINDINGS All symptoms and risks increased among participants higher than action level 2, after adjustment for age and lifestyle, by 3.1 (95% CI 2.5-3.7) in men and 2.7 (2.3-3.1) in women for shortness of breath when walking upstairs; 4.5 (2.5-7.8) and 3.8 (1.9-7.3) for non-insulin-dependent diabetes; and 4.2 (3.6-5.0) and 2.8 (2.4-3.2) for at least one major cardiovascular risk factor. Above action level 2, compared with the reference group, men and women were at twice the risk of difficulties in everyday activities, women were 1.5 times more likely to have low back pain or symptoms of intervertebral disc herniation, with secondary problems including hindrance to daily activities. INTERPRETATION People with large waist circumferences have excess burden of ill health. Waist action levels could be useful for health promotion to raise awareness of the need for weight management.

Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide

Objective:Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years.Design:A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers.Subjects:A total of 564 adults (n=90–98 per group; body mass index 30–40 kg m−2) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n=90–95), placebo (n=98) or open-label orlistat (120 mg × 3, n=95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007–April 2009 and is registered with Clinicaltrials.gov, number NCT00480909.Results:From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7–8.0) more weight than those on placebo and 3.8 kg (1.6–6.0) more than those on orlistat (P⩽0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n=184) lost 3.0 kg (1.3–4.7) more weight than those on orlistat (n=95; P<0.001). Completers on liraglutide 2.4/3.0 mg (n=92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids.Conclusion:Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors.

Characteristics of Secondary, Primary, and Compensated Hypogonadism in Aging Men: Evidence from the European Male Ageing Study

CONTEXT The diagnosis of late-onset hypogonadism (LOH) in older men with age-related declines in testosterone (T) is currently not well characterized. OBJECTIVE Our objective was to investigate whether different forms of hypogonadism can be distinguished among aging men. DESIGN The study was a cross-sectional survey on 3369 community-dwelling men aged 40-79 yr in eight European centers. METHODS Four groups of subjects were defined: eugonadal (normal T and normal LH), secondary (low T and low/normal LH), primary (low T and elevated LH), and compensated (normal T and elevated LH) hypogonadism. Relationships between the defined gonadal status with potential risk factors and clinical symptoms were investigated by multilevel regression models. RESULTS Among the men, 11.8, 2.0, and 9.5% were classified into the secondary, primary, and compensated hypogonadism categories, respectively. Older men were more likely to have primary [relative risk ratio (RRR) = 3.04; P < 0.001] and compensated (RRR = 2.41; P < 0.001) hypogonadism. Body mass index of 30 kg/m(2) or higher was associated with secondary hypogonadism (RRR = 8.74; P < 0.001). Comorbidity was associated with both secondary and primary hypogonadism. Sexual symptoms were more prevalent in secondary and primary hypogonadism, whereas physical symptoms were more likely in compensated hypogonadism. CONCLUSIONS Symptomatic elderly men considered to have LOH can be differentiated on the basis of endocrine and clinical features and predisposing risk factors. Secondary hypogonadism is associated with obesity and primary hypogonadism predominately with age. Compensated hypogonadism can be considered a distinct clinical state associated with aging. Classification of LOH into different categories by combining LH with T may improve the diagnosis and management of LOH.

One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor.

OBJECTIVE: To assess the efficacy and tolerability of orlistat (Xenical®) in producing and maintaining weight loss over a 12-month period.DESIGN: Patients were randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with a low-energy diet, for 12 months.SETTING: Five centres in the UK.SUBJECTS: 228 obese adult patients with body mass index between 30 and 43 kg/m2 and mean weight 97 kg (range 74–144 kg).INTERVENTIONS: All patients were prescribed a low-energy diet, providing 30% of energy from fat, designed to produce an individually tailored energy deficit of approximately 600 kcal/day, for a run-in period of 4 weeks and then 12 months, plus orlistat 120 mg or placebo three times daily.MAIN OUTCOME MEASURES: Change in body weight (the primary efficacy parameter), waist circumference and adverse events were reviewed regularly, together with serum lipids, insulin, glucose and plasma levels of fat-soluble vitamins and β carotene.RESULTS: Based on an intent-to-treat analysis, after 1 y of treatment patients receiving orlistat had lost an average of 8.5% of their initial body weight compared with 5.4% for placebo-treated patients; 35% of the orlistat group lost at least 5% of body weight compared with 21% of the placebo group (P<0.05), and 28% and 17%, respectively (P=0.04) lost at least 10% of body weight. Orlistat-treated patients showed significant decreases (P<0.05) in serum levels of total cholesterol, low density lipoprotein cholesterol, and in the low density lipoprotein:high density lipoprotein ratio in comparison with placebo. Both groups had similar adverse-event profiles, except for gastrointestinal events, which were 26% more frequent in the orlistat group but were mostly mild and transient. To maintain normal plasma levels of fat-soluble vitamins, supplements of vitamins A, D and E were given to 1.8%, 8.0% and 3.6%, respectively, of orlistat-treated patients, compared with 0.9% of placebo-treated patients for each vitamin type. After 1 y, the decrease in vitamin E and β carotene was significantly greater in orlistat-treated patients compared with those receiving placebo (P<0.001). No significant change was found in the mean vitamin E:total cholesterol ratio in either group after 52 weeks.Conclusions: Orlistat, in conjunction with a low-energy diet, produced greater and more frequent significant weight loss than placebo during 1 y of treatment. One-third of orlistat-treated patients achieved clinically relevant weight loss (≥5% initial body weight). There was also an improvement in relevant serum lipid parameters. Fat-soluble vitamin supplements may be required during chronic therapy. Orlistat was well tolerated and offers a promising new approach to the long-term management of obesity.

Obesity, Weight Loss and Prognosis in Type 2 Diabetes

Medical records were reviewed of all 263 Type 2 diabetic patients from the Aberdeen diabetic clinic who were known to have died in 1985 or 1986. Mean age was 65 years (interquartile range 57–75 years) at diagnosis and 72 (66–80) years for men, 75 (72–83) years for women, at death. Life expectancy at age 65 was 35% less than published figures for the general population. Analysis of survival in 233 patients who lived more than 1 year (189 overweight) using stepwise multiple regression indicated as significant (p < 0.05) adverse independent variables: age at diagnosis, presence of clinical ischaemic heart disease at diagnosis, plasma glucose at diagnosis; and as significant favourable variables: oral hypoglycaemic drug therapy, weight loss in the first year, and an interaction between weight loss and BMI for patients with BMI > 25 kg m−2. Changes in fashions over the years are likely to have biased these results towards including oral hypoglycaemic therapy and excluding the expected adverse effect of smoking. Mean weight loss at 1 year was 2.6 kg for those with BMI 25–30 kg m−2, 6.8 kg with BMI > 30 kg m−2, following standard dietetic advice. For the average patient each 1 kg weight loss was associated with 3–4 months prolonged survival.

Polyphenols and health: What compounds are involved?

On the basis of prospective, cross-sectional and intervention studies linking polyphenols to human health, several experimental papers in the literature have tried to evaluate the molecular mechanisms involved in their bioactivity. Polyphenols are reported to in vitro inhibit cancer cell proliferation, reduce vascularisation, protect neurons, stimulate vasodilation and improve insulin secretion, but are often studied as aglycones or as sugar conjugates and at non-physiological concentration. However, it is now well established that polyphenols undergo substantial metabolism after being ingested by humans in dietary relevant amount and that concentrations of plasma metabolites after a normal dietary intake rarely exceed nmol/L. This viewpoint intends to highlight that uncritical judgements made on the basis of the published literature, particularly about toxicity and bioactivity, may sometimes have been misled and misleading and to conclude that i) bioavailability values reported in the literature for phenolic compounds should be strongly reconsidered in the light of the large number of newly identified circulating and excreted metabolites, with particular attention to colonic ring-fission products which are obviously contributing much more than expected to the percentage of their absorption; ii) it is phenolic metabolites, formed in the small intestine and hepatic cells, and low molecular weight catabolic products of the colonic microflora to travel around the human body in the circulatory system or reach body tissues to elicit bioactive effects. Understanding these compounds certainly carries interest for drug-discovery but also for dietary prevention of disease.

Age‐Related Changes in General and Sexual Health in Middle‐Aged and Older Men: Results from the European Male Ageing Study (EMAS)

INTRODUCTION Limited information is available concerning the general and sexual health status of European men. AIM To investigate the age-related changes in general and sexual health in middle-aged and older men from different countries of the European Union. METHODS This is a cross-sectional multicenter survey performed on a sample of 3,369 community-dwelling men aged 40-79 years old (mean 60 + or - 11 years). Subjects were randomly selected from eight European centers including centers from nontransitional (Florence [Italy], Leuven [Belgium], Malmö[Sweden], Manchester [United Kingdom], Santiago de Compostela [Spain]) and transitional countries (Lodz [Poland], Szeged [Hungary], Tartu [Estonia]). MAIN OUTCOME MEASURES Different parameters were evaluated including the Becks Depression Inventory for the quantification of depressive symptoms, the Short Form-36 Health Survey for the assessment of the quality of life (QoL), the International Prostate Symptom Score for the evaluation of lower urinary tract symptoms, and the European Male Ageing Study sexual function questionnaire for the study of sexual function. RESULTS More than 50% of subjects reported the presence of one or more common morbidities. Overall, hypertension (29%), obesity (24%), and heart diseases (16%) were the most prevalent conditions. Around 30% of men reported erectile dysfunction (ED) and 6% reported severe orgasmic impairment, both of which were closely associated with age and concomitant morbidities. Only 38% of men reporting ED were concerned about it. Furthermore, concern about ED increased with age, peaking in the 50-59 years age band, but decreased thereafter. Men in transitional countries reported a higher prevalence of morbidities and impairment of sexual function as well as a lower QoL. CONCLUSION Sexual health declined while concomitant morbidities increased in European men as a function of age. The burden of general and sexual health is higher in transitional countries, emphasizing the need to develop more effective strategies to promote healthy aging for men in these countries.