Waist circumference and body shape -
Zhang C, Rexrode KM, van Dam RM, Li TY, Hu FB. Abdominal obesity and the risk of all-cause, cardiovascular, and cancer mortality: sixteen years of follow-up in US women.
Zhang X, Shu XO, Yang G, et al. Abdominal adiposity and mortality in Chinese women. Arch Intern Med. Despres JP. Health consequences of visceral obesity.
Ann Med. de Koning L, Merchant AT, Pogue J, Anand SS. Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies. Heart J. Vazquez G, Duval S, Jacobs DR, Jr. Qiao Q, Nyamdorj R. Is the association of type II diabetes with waist circumference or waist-to-hip ratio stronger than that with body mass index?
Eur J Clin Nutr. Grundy SM, Cleeman JI, Daniels SR, et al. International Diabetes Federation. The IDF consensus worldwide definition of metabolic syndrome. World Health Organization. Definition, Diagnosis, and Classification of Diabetes Mellitus and its Complications: Report of a WHO Consultation.
Part I: Diagnosis and Classification of Diabetes Mellitus. Geneva: World Health Organization. Assessed on January 26, Skip to content Obesity Prevention Source. Obesity Prevention Source Menu. Search for:. The similarities in the association patterns of ALT and GGT noted in our and previous studies would likely be related to their shared genetic background and the differences between obese men and women reported in our study would likely be related to the sexually dimorphic relative contribution of individual genes Physiologically, ALT participates in the glucose-alanine cycle, transferring ammonium groups from amino acids to pyruvate released from glycolysis in the muscle, thus producing alanine, which in the liver is converted back to pyruvate and is used to generate glucose in gluconeogenesis Correspondingly, intervention studies in humans support a more important role of insulin than lipids for ALT regulation, as carbohydrate restriction contributes to a greater reduction in ALT compared to fat restriction, despite similar weight reductions with alternative low-energy diets Nevertheless, statin administration in humans reduces ALT and GGT levels 36 , and in animal models, cholesterol-depleted but not cholesterol-loaded HDL particles induce ALT release from the liver to the circulation 37 , which is in agreement with the association patterns of ALT matching more closely lipid-related than glucose-related biomarkers in our study.
GGT, on the other hand, is a membrane-bound ectoenzyme, hydrolysing gamma-glutamyl bonds of glutathione and its S-conjugates with xenobiotics, and as such represents part of the cellular antioxidant system but can also have a pro-oxidative action and has been implicated in the pathogenesis of atherosclerosis via oxidation of LDL-C , inflammatory conditions, and cancer This suggests that in addition to factors related to or originating from VAT, there is also an involvement, at least in men, of a factor that either originates from gluteofemoral fat or determines its accumulation.
One such factor could be oestradiol originating from peripheral aromatisation in adipose tissue. This would be compatible with the sexual dimorphism of lipids described in our and other studies, with lower levels of triglycerides and ALT and higher HDL-C and ApoA1 in women compared to men Chronic low-grade inflammation is characteristic of obesity and can contribute to the generation for dysfunctional HDL particles 40 , In our study, however, hip size was associated only with glucose-related and lipid-related factors but not with CRP or neutrophils, highlighting differences in the underlying mechanisms.
Low-grade inflammation is mediated by macrophage infiltration of the adipose tissue Nevertheless, macrophages play a complex role, as their classical activation contributes to a pro-inflammatory phenotype, promoting the development of insulin resistance and type 2 diabetes, while their alternative activation improves insulin sensitivity The classical activation of macrophages can also be triggered by tissue infiltration with neutrophils, which thus contribute to the maintenance of chronic low-grade inflammation, in addition to their key role in the acute inflammatory response Correspondingly, mice with neutropenia have reduced liver lipogenesis and steatosis In humans, neutrophil counts are higher in hyperlipidaemia, hyperglycaemia, and insulin resistance even in healthy individuals 28 , 44 , and are accompanied with higher lymphocyte and monocyte counts and higher CRP levels in obesity and the metabolic syndrome 46 , An upregulation of genes related to neutrophil degranulation has also been reported in patients with cardiovascular diseases Neutrophil counts, however, are reduced after bariatric surgery proportional to the changes in BMI and insulin resistance, while lymphocyte counts are not affected materially and the response of monocytes varies according to the surgical technique The latter is in agreement with the similar associations with body shape for CRP, neutrophils, and partially for monocytes but not for lymphocytes observed in our study.
A likely mechanistic factor explaining the positive association of waist size with metabolic and inflammatory biomarkers would be cortisol, as glucocorticoids play a key role in the regulation of the anti-inflammatory response and the hypothalamus—pituitary—adrenal axis is dysfunctional in obesity, favouring VAT accumulation, metabolic alterations, and abdominal obesity In animal models, neutrophil infiltration of mouse liver and secretion of neutrophil elastase is accompanied with activation of clock genes and follows a circadian rhythm, with the lowest neutrophil counts in liver at lights-off time and the highest at lights-on time, corresponding to the circulating corticosterone levels 45 , In humans, glucocorticoids contribute to higher circulating neutrophil counts via increased release of polymorphonuclear cells from the bone marrow and from the marginalised pool cells attached to the endothelial surface , as well as by delayed apoptosis It remains unclear, however, what is the contribution of glucocorticoids to associations with hip size and how they interact with other factors related to body shape.
Bilirubin and ALP, similarly to inflammatory biomarkers, were associated only with BMI and waist and not with hip size, but unlike their concomitant increase in obstructions of the biliary tract, their associations with anthropometric indices were discordant.
In agreement with our findings, higher levels of the total and liver fraction of ALP in serum have been reported in obesity and it has been shown that tissue ALP is involved in lipid metabolism and adipokine synthesis 53 , Obesity is also associated with higher expression of leucocyte ALP ALPL gene in neutrophils, a marker of neutrophil activation 55 , which is compatible with an involvement of ALP in the inflammatory response, in agreement with the positive correlation of ALP with CRP and neutrophil counts observed in our study.
Further in agreement with our findings, lower bilirubin levels have been reported in obesity without metabolic complications 56 , as well as in type 2 diabetes and the metabolic syndrome Bilirubin also plays a protective role against liver lipid infiltration and the development of NAFLD 58 , and animal models have shown that biliverdin, a bilirubin precursor in the haem catabolic pathway, contributes to smaller adipocyte size and suppresses inflammatory factors, thus reducing insulin resistance Our study has shown that associations with body size and body shape related to obesity hold within the clinical reference ranges of biomarker levels, while for lower or higher levels, pathological conditions other than obesity would likely gain leverage.
Thus, severe chronic inflammatory conditions and liver damage can contribute to skeletal muscle wasting and cachexia 60 , potentially explaining the inverse associations of BMI with high ALT and CRP observed in our study in men and for high CRP, also in women.
Further, the inverse associations of BMI with low neutrophil counts, most prominent in our study for women, could be related to a secondary autoimmune type neutropenia accompanying chronic inflammatory or autoimmune conditions Although high HDL-C is generally considered beneficial, U-shaped associations have been reported for HDL-C, with a positive association with ALT and AST at high HDL-C This, together with the positive association of high HDL-C and ApoA1 with ABSI observed in our study in men, suggests un underlying pathological condition for very high HDL-C levels, which merits further investigation.
Our study benefited from a very large sample size, which enabled us to examine in more detail some relatively small subgroups. There was also a detailed information for covariates, which permitted adjustment for major lifestyle and reproductive factors and minimised confounding.
The standardised anthropometric measurements, obtained by trained personnel, avoided bias from self-reported values. The standardised approach to biomarker measurements, with a unified and systematic quality control for all samples, minimised measurement errors.
Due to limited numbers, however, we could not examine underweight or severe obesity, or ethnic variations, or pre-menopausal women, or younger men, or longitudinal associations, or association of biomarkers with imaging measurement of body composition, which were obtained a few years later for a small part of the UK Biobank cohort.
A misclassification of medication use is also possible, as the information was self-reported and was assembled from several questions.
Importantly, our study was cross-sectional, and as such could not assess temporality or provide strong insights for potential causality.
Although we have removed participants with known underlying conditions potentially influencing body composition or contributing to weight change prevalent cancer and non-cancer illness or medication use at enrolment, or incident cancer and death within the first two years after enrolment , thus retaining only half of the original UK Biobank dataset, some possibility for reverse causality from subclinical or unreported conditions remains.
Nevertheless, body size and body shape and the underlying body composition, as well as biomarker levels, are endogenous factors. As such, they are likely interrelated in complex causal networks, rather than in linear causal pathways, with each other and with other endogenous factors such as sex steroids and glucocorticoids, as well as with exogenous and genetic factors.
In this context, our findings suggest that body size and body shape and their determining factors are more likely to be leading a direct association within the central part of the biomarker distributions. Towards the tails of the biomarker distributions, however, biomarkers and their determining factors and associated diseases are more likely to be contributing to reverse causality.
Finally, UK Biobank participants are not only relatively older, but have a healthier lifestyle and are not representative of the overall UK population This discrepancy would be aggravated further by the removal of participants with prevalent illnesses at enrolment or using medications.
In conclusion, glucose-related and lipid-related biomarkers are associated in opposite directions with waist and hip size, independent of overall body size, while inflammatory biomarkers are associated only with waist size, suggesting differences in the underlying mechanisms. Associations with body size and body shape related to obesity remain consistent within the clinical reference ranges of biomarker levels, but are lost or change direction for low or high levels, potentially reflecting the influence of chronic inflammatory or autoimmune conditions.
Piché, M. Obesity phenotypes, diabetes, and cardiovascular diseases. Article PubMed CAS Google Scholar. Saltiel, A. Inflammatory mechanisms linking obesity and metabolic disease. Article PubMed PubMed Central Google Scholar.
Engin, A. Non-alcoholic fatty liver disease. Article CAS PubMed Google Scholar. Lassailly, G. et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients.
Gastroenterology , —; quiz e— Gujral, U. Diabetes among non-overweight individuals: An emerging public health challenge. Honda, Y.
Characteristics of non-obese non-alcoholic fatty liver disease: Effect of genetic and environmental factors.
Karpe, F. Biology of upper-body and lower-body adipose tissue—link to whole-body phenotypes. Nat Rev Endocrinol 11 , 90— Neeland, I. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: A position statement. Lancet Diabetes Endocrinol. Article PubMed Google Scholar.
Cameron, A. A systematic review of the impact of including both waist and hip circumference in risk models for cardiovascular diseases, diabetes and mortality. Christakoudi, S. A Body Shape Index ABSI , hip index and risk of cancer in the UK Biobank cohort.
Cancer Med. A Body Shape Index ABSI achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort.
Krakauer, N. A new body shape index predicts mortality hazard independently of body mass index. PLoS One 7, e An anthropometric risk index based on combining height, weight, waist, and hip measurements.
Association of body-shape phenotypes with imaging measures of body composition in the UK Biobank cohort: relevance to colon cancer risk. BMC Cancer 21 , Corbatón-Anchuelo, A. A body shape index ABSI and Hip Index HI Adjust waist and hip circumferences for body mass index, but only ABSI predicts high cardiovascular risk in the spanish caucasian population.
Lee, D. Comparison of the association of predicted fat mass, body mass index, and other obesity indicators with type 2 diabetes risk: two large prospective studies in US men and women. Sudlow, C. UK biobank: An open access resource for identifying the causes of a wide range of complex diseases of middle and old age.
PLoS Med. UK Biobank Coordinating Centre; UK Biobank: Protocol for a large-scale prospective epidemiological resource. Protocol No: UKBB-PROT—06 Main Phase ; 21 March AMENDMENT ONE FINAL.
R Core Team R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria.
Bertoli, S. Association of Body Shape Index ABSI with cardio-metabolic risk factors: A cross-sectional study of Caucasian adults. Biolo, G.
Gentile, M. Association between body shape index and small dense LDL particles in a cohort of mediterranean women: findings from Progetto ATENA. Clark, D. Sex and Race Differences in the Relationship between Obesity and C-Reactive Protein. Ethn Dis 26 , — Głuszek, S.
Anthropometric indices and cut-off points in the diagnosis of metabolic disorders. Hardy, D. Anthropometric discriminators of type 2 diabetes among White and Black American adults.
J Diabetes 9 , — Chen, S. Anthropometric Indices in Adults: Which Is the best indicator to identify alanine aminotransferase levels?. Public Health 13 , — Article PubMed PubMed Central CAS Google Scholar. Boyer, W. The associations between increasing degrees of homa-ir and measurements of adiposity among euglycemic U.
Caporaso, N. Insulin Resistance in Healthy U. Adults: Findings from the National Health and Nutrition Examination Survey NHANES. Cancer Epidemiol. Clark, J. The prevalence and etiology of elevated aminotransferase levels in the United States. Deboer, M. Severity of metabolic syndrome is greater among nonalcoholic adults with elevated ALT and advanced fibrosis.
Lawlor, D. The associations of physical activity and adiposity with alanine aminotransferase and gamma-glutamyltransferase. Siddiqui, M. Association between high-normal levels of alanine aminotransferase and risk factors for atherogenesis.
Gastroenterology , e Van Beek, J. The genetic architecture of liver enzyme levels: GGT, ALT and AST.
Petersen, K. Regulation of hepatic mitochondrial oxidation by glucose-alanine cycling during starvation in humans.
Article CAS PubMed PubMed Central Google Scholar. Ryan, M. Serum alanine aminotransferase levels decrease further with carbohydrate than fat restriction in insulin-resistant adults. Diabetes Care 30 , — Pastori, D.
Statin liver safety in non-alcoholic fatty liver disease: A systematic review and metanalysis. Herzog, E. Reconstituted high-density lipoprotein can elevate plasma alanine aminotransferase by transient depletion of hepatic cholesterol: role of the phospholipid component.
Corti, A. Free Radic. Wang, X. J Clin Endocrinol Metab 96 , — Rosenson, R. Dysfunctional HDL and atherosclerotic cardiovascular disease. Zhang, T. Interaction between adipocytes and high-density lipoprotein:new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis.
Lipids Health Dis. Esser, N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res. Odegaard, J. Mechanisms of macrophage activation in obesity-induced insulin resistance. Mantovani, A.
Neutrophils in the activation and regulation of innate and adaptive immunity. Crespo, M. Neutrophil infiltration regulates clock-gene expression to organize daily hepatic metabolism. Bahadır, A. Is the neutrophil-to-lymphocyte ratio indicative of inflammatory state in patients with obesity and metabolic syndrome?.
Lao, X. White blood cell count and the metabolic syndrome in older Chinese: The Guangzhou Biobank Cohort Study. Atherosclerosis , — Article ADS CAS PubMed Google Scholar.
Kvist-Hansen, A. Neutrophil pathways of inflammation characterize the blood transcriptomic signature of patients with psoriasis and cardiovascular disease.
Cunha, F. Effect of different bariatric surgery type on the leukocyte formula. Pasquali, R. The hypothalamic-pituitary-adrenal axis and sex hormones in chronic stress and obesity: Pathophysiological and clinical aspects.
N Y Acad. Article ADS CAS PubMed PubMed Central Google Scholar. Sundar, I. Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD: Implication for COPD-associated neuropathogenesis.
Nakagawa, M. Glucocorticoid-induced granulocytosis: contribution of marrow release and demargination of intravascular granulocytes.
Circulation 98 , — Ali, A. The relationship between anthropometry and serum concentrations of alkaline phosphatase isoenzymes, liver-enzymes, albumin, and bilirubin.
Am J Clin Pathol , — Hernández-Mosqueira, C. Tissue alkaline phosphatase is involved in lipid metabolism and gene expression and secretion of adipokines in adipocytes. Acta , — Pan, Y.
Discovery and validation of a novel neutrophil activation marker associated with obesity. Jenko-Pražnikar, Z. Serum bilirubin levels are lower in overweight asymptomatic middle-aged adults: an early indicator of metabolic syndrome?. Metabolism 62 , — Nano, J.
Association of circulating total bilirubin with the metabolic syndrome and type 2 diabetes: A systematic review and meta-analysis of observational evidence. Diabetes Metab. Weaver, L. Biliverdin reductase and bilirubin in hepatic disease. Liver Physiol. Takei, R. Bilirubin reduces visceral obesity and insulin resistance by suppression of inflammatory cytokines.
Webster, J. Inflammation and skeletal muscle wasting during Cachexia. Akhtari, M. Autoimmune neutropenia in adults. Jiang, Z. Low LDL-C and high HDL-C levels are associated with elevated serum transaminases amongst adults in the United States: A cross-sectional study.
Fry, A. Comparison of sociodemographic and health-related characteristics of UK biobank participants with those of the general population. Download references. This work was supported by the National Institute for Health Research NIHR Imperial Biomedical Research Centre BRC , which provided infrastructure support for the Department of Epidemiology and Biostatistics at Imperial College London UK.
The funders had no role in the design and conduct of the study, the collection, analysis, and interpretation of the data, or the preparation, review, and approval of the manuscript, or in the decision to submit the manuscript for publication.
Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. You can also search for this author in PubMed Google Scholar. and E. conceived and designed the study. provided statistical advice. led the research and performed the statistical analysis.
had full access to all of the data in this study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
drafted the paper with contributions from K. All authors: S. were involved in the interpretation of the results, the critical revisions of the paper, and the approval of the final version of the manuscript.
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Waist circumference and body shape more information about PLOS Subject Circumfegence, click here. Obesity, typically quantified in Waist circumference and body shape of Body Homestyle cooking Index BMI exceeding circunference values, shwpe Green building materials a leading cause of premature death worldwide. Wasit given body size BMIit is recognized that risk is also affected by body shape, particularly as a marker of abdominal fat deposits. Waist circumference WC is used as a risk indicator supplementary to BMI, but the high correlation of WC with BMI makes it hard to isolate the added value of WC. We considered a USA population sample of 14, non-pregnant adults from the National Health and Nutrition Examination Survey NHANES — with follow-up for mortality averaging 5 yr deaths. We developed A Body Shape Index ABSI based on WC adjusted for height and weight:. Food Assistance and Food Antioxidant protection against diseases Resources. Adult BMI Wist. A high amount of body circumfeerence can Green building materials to weight-related diseases cirucmference Green building materials health anx. Being underweight is also a health risk. Body Mass Index BMI and waist circumference are screening tools to estimate weight status in relation to potential disease risk. However, BMI and waist circumference are not diagnostic tools for disease risks. A trained healthcare provider should perform other health assessments to evaluate disease risk and diagnose disease status.
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