Changes in Waist Circumference and the Incidence of Diabetes in Middle-Aged Men and Women

Waist circumference (WC) is positively associated with diabetes, but the association with changes in WC (DWC) is less clear. We investigated the association between DWC and the subsequent risk of diabetes in middle-aged men and women, and evaluated the influence from concurrent changes in body mass index (DBMI).Data on 15,577 men and 20,066 women from the Danish Diet, Cancer and Health study were analyzed. Anthropometry was assessed in 1993–97 and 1999–02. Information on diabetes was obtained from The Danish National Diabetes Register. Hazard ratios (HR) were calculated from Cox' proportional hazard models with individuals considered at risk from 1999–02 until December 31 2006. During 5.4 years of follow-up, 1,027 and 876 new cases of diabetes occurred among men and women, respectively. WC was positively associated with diabetes in both sexes also with adjustment for covariates and BMI. DWC was positively associated with diabetes in women, but not in men (HR per 5 cm change = 1.09 (1.04∶1.15) in women, and 1.00 (0.94, 1.07) in men with adjustment for covariates, baseline WC, BMI and DBMI). Associations with DWC were not notably different in sub-groups stratified according to baseline WC or DBMI, or when individuals with diseases or diabetes occurring within the first years of follow-up were excluded.While this study confirmed that WC is positively associated with the risk of diabetes in middle-aged men and women, it surprisingly showed that changes in WC were not associated with the subsequent risk of diabetes in men, and only weakly positively associated with the risk of diabetes in women. Accordingly, these findings suggest that a reduction in WC may be a weak or insufficient or target for prevention of diabetes in middle-aged men and women

Changes in Waist Circumference and Mortality in Middle-Aged Men and Women

BACKGROUND: Waist circumference (WC) adjusted for body mass index (BMI) is positively associated with mortality, but the association with changes in WC is less clear. We investigated the association between changes in WC and mortality in middle-aged men and women, and evaluated the influence from concurrent changes in BMI. METHODOLOGY/PRINCIPAL FINDINGS: Data on 26,625 healthy men and women from the Danish Diet, Cancer and Health study was analyzed. WC and BMI were assessed in 1993-97 and in 1999-02. Information on mortality was obtained by linkage to the Danish central Person Register. Hazard ratios (HR) were estimated with Cox regression models. During 6.7 years of follow-up, 568 and 361 deaths occurred among men and women, respectively. Changes in WC were positively associated with mortality (HR per 5 cm for the sexes combined  = 1.09 (1.02 : 1.16) with adjustment for covariates, baseline WC, BMI and changes in BMI), whereas changes in BMI were inversely associated with mortality (HR per kg/m2 for the sexes combined  = 0.91 (0.86, 0.97) with adjustment for covariates, baseline WC, BMI and changes in WC). Associations between changes in WC and mortality were not notably different in sub-groups stratified according to changes in BMI, baseline WC or when smokers or deaths occurring within the first years of follow-up were excluded. CONCLUSIONS/SIGNIFICANCE: Changes in WC were positively associated with mortality in healthy middle-aged men and women throughout the range of concurrent changes in BMI. These findings suggest a need for development of prevention and treatment strategies targeted against redistribution of fat mass towards the abdominal region

Interaction between Obesity and the NFKB1 - 94ins/delATTG Promoter Polymorphism in Relation to Incident Acute Coronary Syndrome: A Follow Up Study in Three Independent Cohorts

Introduction: The NF-κB transcription factor family regulates several genes encoding pro-inflammatory and anti-inflammatory proteins in adipose tissues and in atherosclerotic plaques. The deletion variant allele of the NFKB1 - 94ins/delATTG promoter polymorphism leads to lower transcript levels of the p50 subunit, and the variant allele has been associated with the risk of several inflammatory diseases as well as coronary heart disease where inflammation is important in the pathogenesis. The objective of this study was to explore the potential interaction between the NFKB1-94ins/delATTG promoter polymorphism and general, abdominal, and gluteofemoral obesity in relation to the risk of incident acute coronary syndrome (ACS) in three large independent cohorts. Methods and Results: The analyses were conducted in the Danish prospective study Diet, Cancer and Health and the two US based cohorts; Nurses’ Health Study and Health Professionals Follow-up Study. We conducted sex stratified analyses that included 1202 male and 708 female cases of incident ACS. We observed a positive association for general and abdominal obesity with risk of incident ACS, independent of genotype in both genders. Gluteofemoral obesity was negatively associated with ACS risk in women independent of genotype, whereas there was no clear association for men. We calculated the relative excess risk due to interaction (RERI) and observed a statistically significant excess risk among men jointly exposed to general or abdominal obesity and the variant allele of the NFKB1-94ATTG polymorphism, whereas there was a tendency towards sub-additivity for gluteofemoral obesity. The excess risks in all analyses were, however, small and could not clearly be demonstrated in women. Conclusion: The variant allele of the NFKB1-94ins/delATTG promoter polymorphism did not substantially modify the association between obesity and incident ACS

FTO Gene Associated Fatness in Relation to Body Fat Distribution and Metabolic Traits throughout a Broad Range of Fatness

A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already in adolescence.Obese young Danish men (n = 753, BMI > or = 31.0 kg/m(2)) and a randomly selected group (n = 879) from the same population were examined in three surveys (mean age 35, 46 and 49 years, respectively). The traits included anthropometrics, body composition, oral glucose tolerance test, blood lipids, blood pressure, fibrinogen and aspartate aminotransferase. Logistic regression analysis was used to assess the age-adjusted association between the phenotypes and the odds ratios for the FTO rs9939609 (TT and TA genotype versus the AA genotype), for anthropometrics and body composition estimated per unit z-score. BMI was strongly associated with the AA genotype in all three surveys: OR = 1.17, p = 1.1*10(-6), OR = 1.20, p = 1.7*10(-7), OR = 1.17, p = 3.4*10(-3), respectively. Fat body mass index was also associated with the AA genotype (OR = 1.21, p = 4.6*10(-7) and OR = 1.21, p = 1.0*10(-3)). Increased abdominal fatness was associated with the AA genotype when measured as waist circumference (OR = 1.21, p = 2.2*10(-6) and OR = 1.19, p = 5.9*10(-3)), sagittal abdominal diameter (OR = 1.17, p = 1.3*10(-4) and OR = 1.18, p = 0.011) and intra-abdominal adipose tissue (OR = 1.21, p = 0.005). Increased peripheral fatness measured as hip circumference (OR = 1.19, p = 1.3*10(-5) and OR = 1.18, p = 0.004) and lower body fat mass (OR = 1.26, p = 0.002) was associated with the AA genotype. The AA genotype was significantly associated with decreased Stumvoll insulin sensitivity index (OR = 0.93, p = 0.02) and with decreased non-fasting plasma HDL-cholesterol (OR = 0.57, p = 0.037), but not with any other of the metabolic traits. However, all significant results for both body fat distribution and metabolic traits were explained by a mediating effect of total fat mass.The association of the examined FTO SNP to general fatness throughout the range of fatness was confirmed, and this association explains the relation between the SNP and body fat distribution and decreased insulin sensitivity and HDL-cholesterol. The SNP was not significantly associated with other metabolic traits suggesting that they are not derived from the general accumulation of body fat

Changes in Waist Circumference and the Incidence of Acute Myocardial Infarction in Middle-Aged Men and Women

BACKGROUND: Waist circumference (WC) measured at one point in time is positively associated with the risk of acute myocardial infarction (MI), but the association with changes in WC (DWC) is not clear. We investigated the association between DWC and the risk of MI in middle-aged men and women, and evaluated the influence from concurrent changes in BMI (DBMI). METHODOLOGY/PRINCIPAL FINDINGS: Data on 38,593 participants from the Danish Diet, Cancer and Health study was analysed. Anthropometry was assessed in 1993-97 and 1999-02. Information on fatal and non-fatal MI was obtained from National Registers. Cases were validated by review of the medical records. Hazard ratios (HR) were calculated from Cox proportional hazard models with individuals considered at risk from 1999-02 until December 30 2009. During 8.4 years of follow-up, 1,041 incident cases of MI occurred. WC was positively associated with the risk of MI, but weakly after adjustment for BMI. DWC was not associated with the risk of MI (HR per 5 cm change = 1.01 (0.95, 1.09) with adjustment for covariates, baseline WC, BMI and DBMI). Associations with DWC were not notably different in sub-groups stratified according to baseline WC or DBMI, or when individuals with MI occurring within the first years of follow-up were excluded. CONCLUSIONS/SIGNIFICANCE: WC was positively associated with the risk of MI in middle-aged men and women, but changes in WC were not. These findings suggest that a reduction in WC may be an insufficient target for prevention of MI in middle-aged men and women

Waist Circumference Adjusted for Body Mass Index and Intra-Abdominal Fat Mass

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associations between general and abdominal adiposity and mortality in individuals with diabetes mellitus

Individuals with diabetes mellitus are advised to achieve a healthy weight to prevent complications. However, fat mass distribution has hardly been investigated as a risk factor for diabetes complications. The authors studied associations between body mass index, waist circumference, waist/hip ratio, and waist/height ratio and mortality among individuals with diabetes mellitus. Within the European Prospective Investigation into Cancer and Nutrition, a subcohort was defined as 5,435 individuals with a confirmed self-report of diabetes mellitus at baseline in 1992-2000. Participants were aged 57.3 (standard deviation, 6.3) years, 54% were men, the median diabetes duration was 4.6 (interquartile range, 2.0-9.8) years, and 22% of the participants used insulin. Body mass index, as indicator of general obesity, was not associated with higher mortality, whereas all measurements of abdominal obesity showed a positive association. Associations generally were slightly weaker in women. The strongest association was observed for waist/height ratio: In the fifth quintile, the hazard rate ratio was 1.88 (95% confidence interval: 1.33, 2.65) for men and 2.46 (95% confidence interval: 1.46, 4.14) for women. Measurements of abdominal, but not general, adiposity were associated with higher mortality in diabetic individuals. The waist/height ratio showed the strongest association. Respective indicators might be investigated in risk prediction models

Fatness-Associated FTO Gene Variant Increases Mortality Independent of Fatness – in Cohorts of Danish Men

The A-allele of the single nucleotide polymorphism (SNP), rs9939609, in the FTO gene is associated with increased fatness. We hypothesized that the SNP is associated with morbidity and mortality through the effect on fatness.In a population of 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (BMI>or=31.0 kg/m(2)) and a random 1% sample of the others were identified. In 1992-94, at an average age of 46 years, 752 of the obese and 876 of the others were re-examined, including measurements of weight, fat mass, height, and waist circumference, and DNA sampling. Hospitalization and death occurring during the following median 13.5 years were ascertained by linkage to national registers. Cox regression analyses were performed using a dominant effect model (TT vs. TA or AA). In total 205 men died. Mortality was 42% lower (p = 0.001) with the TT genotype than in A-allele carriers. This phenomenon was observed in both the obese and the randomly sampled cohort when analysed separately. Adjustment for fatness covariates attenuated the association only slightly. Exploratory analyses of cause-specific mortality and morbidity prior to death suggested a general protective effect of the TT genotype, whereas there were only weak associations with disease incidence, except for diseases of the nervous system.Independent of fatness, the A-allele of the FTO SNP appears to increase mortality of a magnitude similar to smoking, but without a particular underlying disease pattern barring an increase in the risk of diseases of the nervous system