Lisanne L. Blauw

Smoking is associated with increased resting energy expenditure in the general population: The NEO study

OBJECTIVE Animal studies and human studies in small selected populations have shown a positive association between nicotine smoking and resting energy expenditure (REE), but data in large cohorts are lacking. We aimed to investigate the association between smoking behavior and REE in a large, population-based study. DESIGN Population-based cross-sectional study. METHODS In this cross-sectional analysis of baseline measurements from the Netherlands Epidemiology of Obesity (NEO) study (n=6673), we included participants with REE measurement by indirect calorimetry who were not using lipid or glucose lowering drugs (n=1189). We used linear regression analysis to examine the association of smoking status (never, former, occasional, current smoker) and smoking quantity (pack years) with REE per kilogram (kg) fat free mass (FFM) and with REE adjusted for FFM. Models were adjusted for age, sex, ethnicity, educational level, physical activity, energy intake and body mass index (BMI). RESULTS Mean (standard deviation, SD) age was 55.2 (5.9) years and BMI was 26.3 (4.4) kg/m(2). 60% of the participants were women. Mean (SD) REE/FFM (kcal/day/kg FFM) was for male never smokers 25.1 (2.0), male current smokers 26.4 (2.8), female never smokers 28.9 (2.5) and female current smokers 30.1 (3.7). After adjustment, only current smokers had a higher REE/FFM (mean difference 1.28, 95% CI 0.64, 1.92), and a higher REE adjusted for FFM (mean difference 60.3 kcal/day, 95% CI 29.1, 91.5), compared with never smokers. There was no association between pack years and REE/FFM (mean difference -0.01, 95% CI -0.06, 0.04) or REE adjusted for FFM (mean difference 0.2, 95% CI -2.4, 2.8) in current smokers. CONCLUSION Current smoking is associated with a higher resting energy expenditure compared with never smoking in a large population-based cohort.

Diabetes incidence and glucose intolerance prevalence increase with higher outdoor temperature

Objective Rising global temperatures might contribute to the current worldwide diabetes epidemic, as higher ambient temperature can negatively impact glucose metabolism via a reduction in brown adipose tissue activity. Therefore, we examined the association between outdoor temperature and diabetes incidence in the USA as well as the prevalence of glucose intolerance worldwide. Research design and methods Using meta-regression, we determined the association between mean annual temperature and diabetes incidence during 1996–2009 for each US state separately. Subsequently, results were pooled in a meta-analysis. On a global scale, we performed a meta-regression analysis to assess the association between mean annual temperature and the prevalence of glucose intolerance. Results We demonstrated that, on average, per 1°C increase in temperature, age-adjusted diabetes incidence increased with 0.314 (95% CI 0.194 to 0.434) per 1000. Similarly, the worldwide prevalence of glucose intolerance increased by 0.170% (95% CI 0.107% to 0.234%) per 1°C rise in temperature. These associations persisted after adjustment for obesity. Conclusions Our findings indicate that the diabetes incidence rate in the USA and prevalence of glucose intolerance worldwide increase with higher outdoor temperature.

Serum CETP concentration is not associated with measures of body fat: The NEO study.

INTRODUCTION Adipose tissue has been postulated to contribute substantially to the serum cholesteryl ester transfer protein (CETP) pool. However, in a recent large cohort study waist circumference was not associated with plasma CETP. The aim of the present study was to further examine associations of accurate measures of body fat and body fat distribution with serum CETP concentration. METHODS In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, we examined in 6606 participants (aged 45-65 years) the associations of total body fat, body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), abdominal subcutaneous (aSAT) and visceral adipose tissue (VAT) assessed with magnetic resonance imaging (n = 2547) and total and trunk fat mass assessed with dual-energy X-ray absorptiometry (n = 909) with serum CETP concentration. Regression models were adjusted for age, ethnicity, sex, dietary intake of fat and cholesterol, physical activity, smoking and menopausal status. RESULTS Mean (SD) age was 56 (6) years and BMI 26.3 (4.4) kg/m(2), 56% were women. Mean serum CETP concentration was 2.47 μg/mL. The difference in serum CETP was 0.02 μg/mL (95%CI: -0.01, 0.05) per SD total body fat (8.7%), and 0.02 μg/mL (0.00, 0.04) per SD BMI (4.4 kg/m(2)). Similar associations around the null were observed for waist circumference, WHR, aSAT, VAT, total and trunk fat mass. CONCLUSION In this population-based study, there was no evidence for clinically relevant associations between several measures of body fat and serum CETP concentration. This finding implies that adipose tissue does not contribute to the CETP pool in serum.

CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease

Background: We aimed to identify independent genetic determinants of circulating CETP (cholesteryl ester transfer protein) to assess causal effects of variation in CETP concentration on circulating lipid concentrations and cardiovascular disease risk. Methods: A genome-wide association discovery and replication study on serum CETP concentration were embedded in the NEO study (Netherlands Epidemiology of Obesity). Based on the independent identified variants, Mendelian randomization was conducted on serum lipids (NEO study) and coronary artery disease (CAD; CARDIoGRAMplusC4D consortium). RESULTS: In the discovery analysis (n=4248), we identified 3 independent variants (P<5×10−8) that determine CETP concentration. These single-nucleotide polymorphisms were mapped to CETP and replicated in a separate subpopulation (n=1458). Per-allele increase (SE) in serum CETP was 0.32 (0.02) µg/mL for rs247616-C, 0.35 (0.02) µg/mL for rs12720922-A, and 0.12 (0.02) µg/mL for rs1968905-G. Combined, these 3 variants explained 16.4% of the total variation in CETP concentration. One microgram per milliliter increase in genetically determined CETP concentration strongly decreased high-density lipoprotein cholesterol (−0.23 mmol/L; 95% confidence interval, −0.26 to −0.20), moderately increased low-density lipoprotein cholesterol (0.08 mmol/L; 95% confidence interval, 0.00–0.16), and was associated with an odds ratio of 1.08 (95% confidence interval, 0.94–1.23) for CAD risk. Conclusions: This is the first genome-wide association study identifying independent variants that largely determine CETP concentration. Although high-density lipoprotein cholesterol is not a causal risk factor for CAD, it has been unequivocally demonstrated that low-density lipoprotein cholesterol lowering is proportionally associated with a lower CAD risk. Therefore, the results of our study are fully consistent with the notion that CETP concentration is causally associated with CAD through low-density lipoprotein cholesterol.

Genetic variation in the obesity gene FTO is not associated with decreased fat oxidation: the NEO study

Background:The fat mass and obesity-associated (FTO) gene harbors the strongest common genetic variant associated with obesity. Recently, rs1421085-T to -C substitution mapped in FTO was shown to induce a developmental shift of human adipocytes from an energy-combusting beige to an energy-storing white phenotype in vitro. As browning of adipocytes selectively enhances fat oxidation (FatOx), we hypothesized that rs1421085-C in FTO is associated with deceased FatOx compared with carbohydrate oxidation (CarbOx) and an increased respiratory quotient (RQ).Methods:In the Netherlands Epidemiology of Obesity study, a population-based cohort study of middle-aged individuals (45–65 years), anthropometry and genotyping was performed (n=5744), in addition to indirect calorimetry (n=1246). With linear regression analyses, we examined associations of rs1421085 genotype with FatOx, CarbOx and RQ.Results:In the total study population, 36.7% carried the rs1421085-TT genotype, 47.6% rs1421085-CT and 15.7% rs1421085-CC. Mean (s.d.) age was 56 (6) years, mean (s.d.), body mass index (BMI) was 26.3 (4.4) kg m−2 and 56% of the total population were women. Measures of adiposity (difference, 95% confidence interval) were higher in CC carriers compared with that in rs1421085-TT carriers: BMI +0.56 (0.15, 0.98) kg m−2, waist circumference +1.25 (0.02, 2.49) cm and total body fat mass +1.21 (0.28, 2.14) kg. However, no differences in mean FatOx (+2.5 (−2.4, 7.4) mg min−1), CarbOx (−6.1 (−17.4, 5.2) mg min−1) or RQ (−0.01 (−0.02, 0.01)) were observed between the two genotypes.Conclusions:We observed no evidence for associations of rs1421085 in FTO with FatOx and RQ. This indicates that the rs1421085-C allele in FTO induces obesity likely via other pathways than via reduced FatOx.