Marieke B. Snijder

Independent and opposite associations of waist and hip circumferences with diabetes, hypertension and dyslipidemia: the AusDiab Study

OBJECTIVE: Fat distribution as measured by waist-to-hip ratio has been shown to be an important independent predictor of glucose intolerance. Few studies, however, have considered the contributions of the waist and hip circumferences independently. The aim of this study was to investigate the independent associations of waist and hip circumference with diabetes in a large population-based study, and to investigate whether they also apply to other major components of the metabolic syndrome (hypertension and dyslipidemia). In addition, as previous studies were performed in older persons, we investigated whether these associations were present across adult age groups.METHODS: Weight, height, waist and hip circumferences were measured in 11 247 participants of the nationally representative Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. HDL-cholesterol, triglycerides, fasting and 2-h postload glucose were determined, and diastolic and systolic blood pressure was measured. After exclusion of persons already known to have diabetes, hypertension or dyslipidemia, logistic and linear regression were used to study cross-sectional associations of anthropometric variables with newly diagnosed diabetes, hypertension and dyslipidemia, and with continuous metabolic measures, all separately for men (n=3818) and women (n=4582). Analyses were repeated in the same population stratified for age.RESULTS: After adjustment for age, body mass index and waist, a larger hip circumference was associated with a lower prevalence of undiagnosed diabetes (odds ratio (OR) per one s.d. increase in hip circumference 0.55 (95% CI 0.41–0.73) in men and 0.42 (0.27–0.65) in women) and undiagnosed dyslipidemia (OR 0.58 (0.50–0.67) in men and 0.37 (0.30–0.45) in women). Associations with undiagnosed hypertension were weaker (OR 0.80 (0.69–0.93) in men and 0.88 (0.70–1.11) in women). As expected, larger waist circumference was associated with higher prevalence of these conditions. Similar associations were found using continuous metabolic variables as outcomes in linear regression analyses. Height partly explained the negative associations with hip circumference. When these analyses were performed stratified for age, associations became weaker or disappeared in the oldest age groups (age ≥75 y in particular), except for HDL-cholesterol.CONCLUSION: We found independent and opposite associations of waist and hip circumference with diabetes, dyslipidemia and less strongly with hypertension in a large population-based survey. These results emphasize that waist and hip circumference are important predictors for the metabolic syndrome and should both be considered in epidemiological studies. The associations were consistent in all age groups, except in age ≥75 y. Further research should be aimed at verifying hypotheses explaining the ‘protective’ effect of larger hips.

Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and women : the hoorn study

OBJECTIVE—Adiponectin is an adipose tissue–derived protein. Low levels are associated with obesity, insulin resistance, and type 2 diabetes. Our objective was to investigate the prospective association between adiponectin levels and the 6.4-year risk of type 2 diabetes and of impaired glucose metabolism (IGM). RESEARCH DESIGN AND METHODS—The Hoorn Study is a cohort study among Caucasians, aged 50–75 years. BMI, waist-to-hip ratio (WHR), fasting glucose, 2-h glucose, triglycerides, HDL cholesterol, LDL cholesterol, alanine aminotransferase, leptin, and adiponectin were measured at baseline. Lifestyle (alcohol intake, smoking, and physical activity) was assessed by questionnaires. After a mean follow-up of 6.4 years, glucose tolerance was assessed by a 75-g oral glucose tolerance test. Analyses were performed in 1,264 subjects (584 men and 680 women) without type 2 diabetes at baseline. For analyses of incident IGM, 239 subjects with IGM at baseline and/or type 2 diabetes at follow-up were excluded. RESULTS—Age- and lifestyle-adjusted odds ratios and 95% CIs comparing highest with lowest adiponectin quartile were 0.52 (0.23–1.18) in men and 0.15 (0.06–0.39) in women for type 2 diabetes and 0.90 (0.51–1.61) and 0.28 (0.16–0.48) for IGM, respectively. The risks were only slightly reduced after adjustment for WHR and leptin as markers of (abdominal) adiposity. Adjustment for baseline fasting and postload glucose levels (potential mediators) substantially diminished these inverse associations with type 2 diabetes (0.79 [0.32–1.91] and 0.62 [0.21–1.81]) and with IGM (1.20 [0.61–2.35] and 0.48 [0.26–0.90]), respectively. CONCLUSIONS—A high adiponectin level was strongly associated with a lower risk of IGM and type 2 diabetes, particularly in women. These results suggest that adiponectin is involved in the pathophysiology linking obesity to type 2 diabetes.

Prognostic value of adiponectin for cardiovascular disease and mortality.

CONTEXT Low adiponectin concentrations are associated with the presence of an adverse cardiovascular disease (CVD) risk profile. OBJECTIVE We studied the predictive value of adiponectin levels for all-cause and CVD mortality and CVD morbidity. DESIGN, SETTING, AND PARTICIPANTS This was a population-based cohort study in Hoorn, The Netherlands, which started in 1989 and included 2484 participants, aged 50-75 yr. MAIN OUTCOME MEASURES Hazard ratios (HRs) with 95% confidence interval per sd change in log-adiponectin for all-cause and CVD mortality and CVD morbidity were calculated. RESULTS Adiponectin was determined for 1077 men and 1248 women. Higher adiponectin reduced the risk of nonfatal CVD in women [HR with 95% confidence interval 0.72 (0.61-0.90) in women and 0.92 (0.79-1.06) in men], but not the risk of all-cause or CVD mortality. In contrast, after adjustment for cardiovascular risk factors, higher adiponectin was a significant predictor of all-cause and CVD mortality [HR for CVD mortality 1.45 (1.10-1.92) in women and 1.30 (1.04-1.63) in men]. Higher adiponectin was associated with an increased risk of CVD mortality in people with prevalent CVD [HR 1.27 (0.98-1.63)] and with reduced risk in people without [HR 0.90 (0.73-1.11)]. After adjustment for cardiovascular risk factors, the HRs for CVD mortality were 1.60 (1.14-2.23) for patients with and 1.38 (1.06-1.80) for patients without prevalent CVD. CONCLUSIONS High levels of adiponectin predict mortality, in particular in patients with prevalent CVD. We hypothesize that adiponectin protects against metabolic and vascular diseases, but in patients already afflicted with CVD, adiponectin is compensatory up-regulated and, therefore, indicates a high mortality risk.

Association between Body Mass Index and Mortality Is Similar in the Hemodialysis Population and the General Population at High Age and Equal Duration of Follow-Up

The association of body mass index (BMI) with mortality in hemodialysis patients has been found to be reversed in comparison with the general population. This study examined the association of BMI with mortality in the hemodialysis population and the general population when age and time of follow-up were made strictly comparable. Hemodialysis patients who were aged 50 to 75 yr at the start of follow-up were selected from the Netherlands Cooperative Study on the Adequacy of Dialysis-2 (NECOSAD), a prospective cohort study in incident dialysis patients in the Netherlands (n = 722; age 66 +/- 7 yr; BMI 25.3 +/- 4.5 kg/m(2)), and compared with adults who were aged 50 to 75 yr and included in the Hoorn Study, a population-based prospective cohort study in the same country (n = 2436; age 62 +/- 7 yr; BMI 26.5 +/- 3.6 kg/m(2)). In both populations, 2- and 7-yr standardized mortality rates were calculated for categories of BMI. Adjusted hazard ratios (HR) of BMI categories were calculated with a BMI of 22.5 to 25 kg/m(2) as the reference category within each population. In 7 yr of follow-up, standardized mortality rates were approximately 10 times higher in the hemodialysis population than those in the general population. Compared with the reference category, the HR of BMI <18.5 kg/m(2) was 2.0 (95% confidence interval [CI]1.2 to 3.4) in the hemodialysis population and 2.3 (95% CI 0.7 to 7.5) in the general population. Obesity (BMI >or=30 kg/m(2)) was associated with a HR of 1.2 (95% CI 0.8 to 1.7) in the hemodialysis population and 1.3 (95% CI 0.9 to 2.0) in the general population. In conclusion, a hemodialysis population and a general population with comparable age and equal duration of follow-up showed similar mortality risk patterns associated with BMI. This suggests that there is no reverse epidemiology of BMI and mortality in hemodialysis patients. The clinical implication of this study is that to improve survival in the hemodialysis population, more attention should be paid to patients who are underweight instead of overweight.

Regional body composition as a determinant of arterial stiffness in the elderly: The Hoorn Study.

Objective To estimate the relation of precisely measured regional body composition with peripheral and central arterial stiffness in the elderly. Methods We investigated 648 participants (mean age 69.0 ± 6.0 years) of the Hoorn Study, a population-based cohort study. Trunk fat, leg fat, trunk lean and leg lean mass were distinguished by dual-energy X-ray absorptiometry. We used ultrasound to measure the distensibility and compliance of the carotid, femoral and brachial arteries, and carotid Youngs elastic modulus, as estimates of peripheral stiffness. As estimates of central stiffness we measured carotid–femoral transit time, aortic augmentation index and systemic arterial compliance. Results After adjustment for sex, age, height, mean arterial pressure, leg lean and leg fat mass, a larger trunk fat mass was consistently associated with higher peripheral arterial stiffness (standardized beta (β) of mean Z-scores of all three large arteries −0.24, P < 0.001). In contrast, larger leg fat mass (β = 0.15, P = 0.009) and leg lean mass (β = 0.09, P = 0.20) were associated with lower peripheral arterial stiffness. Trunk or leg fat mass were not associated with central arterial stiffness. Leg lean mass, however, was consistently associated with lower central arterial stiffness (β = 0.29, P < 0.001). Conclusions Trunk fat mass may have adverse effects on peripheral, but not on central arterial stiffness, while leg fat was not harmful and may have a slight protective effect. Larger leg lean mass was the most important determinant of lower central arterial stiffness. These results provide a pathophysiological framework to explain not only the higher cardiovascular risk in individuals with larger trunk fat mass, but also the reduced cardiovascular risk in individuals with larger leg lean and fat mass.

Unravelling the impact of ethnicity on health in Europe: the HELIUS study

BackgroundPopulations in Europe are becoming increasingly ethnically diverse, and health risks differ between ethnic groups. The aim of the HELIUS (HEalthy LIfe in an Urban Setting) study is to unravel the mechanisms underlying the impact of ethnicity on communicable and non-communicable diseases.Methods/designHELIUS is a large-scale prospective cohort study being carried out in Amsterdam, the Netherlands. The sample is made up of Amsterdam residents of Surinamese (with Afro-Caribbean Surinamese and South Asian-Surinamese as the main ethnic groups), Turkish, Moroccan, Ghanaian, and ethnic Dutch origin. HELIUS focuses on three disease categories: cardiovascular disease (including diabetes), mental health (depressive disorders and substance use disorders), and infectious diseases. The explanatory mechanisms being studied include genetic profile, culture, migration history, ethnic identity, socio-economic factors and discrimination. These might affect disease risks through specific risk factors including health-related behaviour and living and working conditions. Every five years, participants complete a standardized questionnaire and undergo a medical examination. Biological samples are obtained for diagnostic tests and storage. Participants’ data are linked to morbidity and mortality registries. The aim is to recruit a minimum of 5,000 respondents per ethnic group, to a total of 30,000 participants.DiscussionThis paper describes the rationale, conceptual framework, and design and methods of the HELIUS study. HELIUS will contribute to an understanding of inequalities in health between ethnic groups and the mechanisms that link ethnicity to health in Europe.

Relationship of adiposity with arterial stiffness as mediated by adiponectin in older men and women: the Hoorn Study

OBJECTIVE To investigate whether adiponectin is associated with arterial stiffness, and whether adiponectin explains the association between body composition and arterial stiffness. DESIGN Cross-sectional cohort study. METHODS Subjects were participants (n=456, mean age 68.9+/-6.1 years; age range 60-86 years) of the third follow-up examination of the Hoorn Study. Trunk fat, leg fat, trunk lean, and leg lean mass were measured by dual-energy X-ray absorptiometry. Ultrasound was used to measure distensibility and compliance of the carotid, femoral, and brachial arteries, and carotid Youngs elastic modulus (as estimates of peripheral arterial stiffness). Results Trunk fat mass was negatively associated with (ln-transformed) adiponectin (standardized beta=-0.49, P<0.001), while leg fat mass was positively associated with adiponectin (beta=0.44, P<0.001), after adjustment for each other, age, and lean mass. After adjustment for age, sex, mean arterial pressure, and estimated glomerular filtration rate, higher adiponectin was associated with decreased peripheral arterial stiffness (beta of mean Z-scores of all three arteries=0.14, P=0.001). However, the associations of trunk fat (beta=-0.26, P<0.001) and leg fat (beta=0.16, P=0.006) with peripheral arterial stiffness were only minimally explained by adiponectin levels. CONCLUSION Trunk fat and leg fat are oppositely associated with adiponectin. Although low adiponectin was a determinant of increased peripheral arterial stiffness, it only explained a small part of the association between body fat and peripheral arterial stiffness. This indicated that factors other than adiponectin may be more important in the pathophysiological mechanisms by which abdominal obesity leads to arterial stiffness.

Obesity in older adults is associated with an increased prevalence and incidence of pain.

Cross‐sectional studies suggest an association between BMI and pain. This prospective study investigated the associations of measured BMI and waist circumference with prevalent and incident pain in older adults. The study included participants of the Longitudinal Aging Study Amsterdam, aged 55–85 years at baseline (1992–1993). Pain was assessed using a subscale of the Nottingham Health Profile at baseline (N = 2,000), after 3 years (N = 1,478) and 6 years (N = 1,271) of follow‐up. The overall prevalence of pain was 32.7% at baseline and increased significantly with higher quartiles of BMI or waist circumference. After adjustment for age, education, depression, smoking, physical activity, and chronic diseases, multiple logistic regression analyses showed odds ratios (ORs (95% confidence interval)) for prevalent pain of 2.16 (1.32–3.54) in men and 1.93 (1.26–2.95) in women comparing the highest with the lowest quartile of BMI. Of the participants without pain at baseline, those in the highest quartile of BMI had a twofold increased odds for incident pain after 3 years of follow‐up. After 6 years of follow‐up, ORs for incident pain were 2.34 (1.17–4.72) in men and 2.78 (1.36–5.70) in women. Additional adjustment for weight change did not change these associations. Similar results were found for the associations between waist circumference and pain. Exploring the reversed causal relation, analyses showed no significant associations between prevalent pain and weight gain. In conclusion, the prevalence of pain is higher among obese older men and women compared to their normal‐weight peers. Furthermore, obese older adults are at increased odds to develop pain.

Hypertension control in a large multi-ethnic cohort in Amsterdam, The Netherlands: The HELIUS study

OBJECTIVE Hypertension is a major problem among European ethnic minority groups. We assessed the current situation of hypertension prevalence and its management among a multi-ethnic population in Amsterdam, The Netherlands. METHODS Data from the HELIUS study were used including 12,974 participants (1871 Ghanaian, 2184 African Surinamese, 2278 South-Asian Surinamese, 2277 Turkish, 2222 Moroccan and 2142 Dutch origin people), aged 18-70 years. Comparisons among groups were made using proportions and age-adjusted prevalence ratios (PRs). RESULTS Hypertension prevalence ranged from 24% and 16% in Moroccan men and women to 52% and 62% in Ghanaian men and women. Except for Moroccan women, age-adjusted PR of hypertension was higher in all the ethnic minority groups than in Dutch. Among hypertensives, ethnic minority groups generally had higher levels of hypertension awareness and BP lowering treatment than Dutch. Moreover, prevalence rates for the prescription of more than one BP lowering drug were generally higher in African and South-Asian origin groups compared with Dutch origin people. By contrast, BP control levels were lower in all the ethnic groups than in Dutch, with control rates being significantly lower in Ghanaian men (26%, PR=0.49; 95% CI, 0.37-0.66) and women (45%, PR=0.64; 0.52-0.77), African-Surinamese men (30%, PR=0.61; 0.46-0.81) and women (45%, PR=0.72; 0.51-0.77), and South-Asian Surinamese men (43%, PR=0.77; 0.61-0.97) and women (47%, PR=0.76; 0.63-0.92) compared with Dutch men (53%) and women (61%). CONCLUSION Our findings indicate poor BP control in ethnic minority groups despite the high treatment levels. More work is needed to unravel the potential factors contributing to the poor control in order to improve BP control in ethnic minority groups, particularly among African and South-Asian origin groups.

Vitamin D in Relation to Myocardial Structure and Function after Eight Years of Follow-Up: The Hoorn Study

Background and Aims: To investigate associations between baseline serum 25-hydroxyvitamin D [25(OH)D] levels and myocardial structure and function after 8 years of follow-up in older Dutch subjects. Methods: We included 256 subjects of the Hoorn Study, a population-based cohort. They underwent a standardized 2-dimensional echocardiogram at baseline between 2000 and 2001, and again between 2007 and 2009. We studied the association of 25(OH)D quartiles with echocardiographic measures of the left ventricular mass index (LVMI), left ventricular systolic function and markers of diastolic function using linear regression analyses. Results: At baseline, subjects had a mean age of 67.4 ± 5.2 years and 41.4% had prior cardiovascular disease (CVD). Low serum 25(OH)D levels were only associated with higher LVMI at 8-year follow-up in subjects without prior CVD and in subjects with low kidney function (median estimated glomerular filtration rate ≤77.5 ml/min/1.73m2). The associations attenuated after adjustments for parathyroid hormone (PTH), which was associated with higher LVMI (g/m2.7) in subjects with low kidney function (regression coefficient highest quartile 6.3, 95% CI: 0.2, 12.5). Conclusion: This study showed no strong associations of 25(OH)D with myocardial structure and function. However, PTH - a possible modifiable mediator in the relation between 25(OH)D and myocardial structure - was positively associated with LVMI in subjects with low kidney function.