Overweight and Obesity in Women: Health Risks and Consequences

Frank B. Hu, M.D., Ph.D.

In This Article

Clustering of Obesity and Characteristics of Metabolic Syndrome

In his Banting Award Lecture in 1988,[11] Reaven used the term "syndrome X" to describe the close interrelationship among obesity, hyperinsulinemia, glucose intolerance, and dyslipidemia. Central to Reaven's syndrome X concept is compensatory hyperinsulinemia resulting from resistance to insulin-mediated glucose uptake. In 1989, Kaplan[12] used the term "deadly quartet" to describe the clustering of upper body obesity, hypertriglyceridemia, glucose intolerance, and hypertension. Several other terms have been used to describe the clustering of metabolic disorders, including insulin resistance syndrome,[13] metabolic syndrome,[14] multiple metabolic syndrome,[15] metabolic cardiovascular syndrome,[16] and chronic cardiovascular risk factor clustering syndrome.[17] Essential to all these descriptions is that the co-occurrence of obesity, hypertension, high cholesterol, and insulin resistance is not due to chance alone but rather to a common underlying process.[18] The recently released Third Report of the National Cholesterol Education Program (NCEP) Expert Panel has provided a working definition of metabolic syndrome.[19] According to the Adult Treatment Panel III (ATP III), individuals with three or more of the following characteristics have the metabolic syndrome:

  • Abdominal obesity: waist circumference > 102 cm in men and > 88 cm in women

  • Hypertriglyceridemia: _150 mg/dl (1.69 mmol/L)

  • Low high-density lipoprotein (HDL) cholesterol: <40 mg/dl (1.04 mmol/L) in men and <50 mg/dl (1.29 mmol/L) in women

  • High blood pressure: _130/85 mm Hg

  • High fasting glucose: _110 mg/dl (6.1 mmol/L)

Using data from the third National Health and Nutrition Examination Survey (NHANES III) Ford et al.[20] estimated that approximately one quarter of U.S. adults (47 million) have the metabolic syndrome. Although the overall prevalence of metabolic syndrome was similar for men and women, among African Americans, women had about a 57% higher prevalence than men, and among Mexican Americans, women had about a 26% higher prevalence than men. The prevalence of abdominal obesity exceeds 60% in both African American and Mexican American women and 40% in white and other women. Obesity is central to individual components of the metabolic syndrome as well as to characteristics related to the syndrome, such as increased insulin resistance, thrombogenic tendency, and inflammation.

Overweight and obese people are at substantially elevated risk for developing hypertension.[21,22] Even within relatively lean populations in China, individuals with greater body mass have substantially elevated blood pressure and a higher rate of hypertension.[23,24] The mechanisms for the relation between body weight and blood pressure have not been fully elucidated. Hyperinsulinemia associated with overweight and obesity may play a critical role in the development of hypertension.[22] Other postulated factors include hypercaloric intake, enhanced sympathetic activity, and even the greater lean mass present in obese subjects. In addition, enhanced salt sensitivity among obese people also may be responsible for the development of hypertension.[25]

Dyslipidemia is one of the most common metabolic disorders associated with obesity.[22] In many studies, indices of body size and adiposity, including BMI, WHR, subscapular skinfold measure, and percent body fat are strongly correlated with hypertriglyceridemia, hypercholesterolemia, and low HDL cholesterol. In diabetics, low HDL and high triglycerides are among the most common features of dyslipidemia,[26] and diabetic dyslipidemia appears to more severe in women than in men, which may explain the excess relative risk of CHD in diabetic women.[27] Even among leaner healthy individuals from Chinese populations, there is a strong inverse association of BMI with HDL cholesterol levels.[24,28] The possible mechanisms between overweight and dyslipidemia are complex and not well understood. The reduction in HDL among overweight people may be mediated by direct removal of HDL from the circulation by adipose tissue or through separation of the lipid from its apo A-I transport protein or its cholesterol ester.[22] On the other hand, hypertriglyceridemia associated with obesity is probably caused by overproduction of very low density lipoprotein (VLDL) triglycerides and defective lipolysis of the triglyceride-rich lipoproteins.[22]

Insulin resistance refers to the reduction in insulin-mediated glucose uptake in insulin-sensitive tissue, specifically in skeletal muscle and the liver.[11] Among obese individuals in particular, insulin resistance commonly is present and most closely related to the amount of fat in the central abdominal region.[29,30,31] In normoglycemic subjects, fasting insulin correlated well with whole body glucose uptake (r = -.068), as measured by a euglycemic clamp, although the correlation was lower (r = -.047) in subjects with impaired glucose tolerance (IGT) or type 2 diabetes.[32]

Obesity is strongly related to PCOS in women. Over half of women with PCOS are overweight or obese, and most of them have abdominal obesity.[33] The majority of women with PCOS have various characteristics of the metabolic syndrome and insulin resistance. It is believed that obesity plays an important role in the development of PCOS, although the direction of the causality between obesity and PCOS is still not clear. Abdominal obesity is at least partly responsible for hyperinsulinemia and subsequent hyperandrogenism in women with PCOS.[33]

High concentrations of plasma thrombogenic factors, such as fibrinogen, factor VII, and plasminogen activator inhibitor-1 (PAI-1), predict increased risk of cardiovascular disease (CVD).[34] Fibrinogen contributes to platelet aggregation and a hypercoagulable state that favors the formation of atheromatous plaques.[35] Fibrinogen correlates with BMI, waist and hip circumferences, and WHR among obese individuals, and weight loss substantially lowers fibrinogen levels.[35] The function of PAI-1 is to inhibit the action of tissue plasminogen activator (t-PA), thus contributing to continued thrombus formation.[36] Studies have shown that PAI-1 concentrations are positively associated with visceral adipose tissue and upper body fat distribution in women.[36] Ferguson et al.[37] showed that even in early childhood, adiposity is associated with unfavorable homeostatic factors, such as increased fibrinogen and PAI-1 levels, and there were strong correlations between fasting insulin levels and levels of fibrinogen and PAI-1. In the Cardiovascular Health Study,[38] factor VII concentrations were correlated with blood lipids in men and correlated with obesity, blood lipids, and insulin levels in women. Recently, in the Framingham Offspring Study, Meigs et al.[39] found that hyperinsulinemia was significantly associated with levels of PAI-1 and t-PA.

C-reactive protein (CRP) is a sensitive marker for acute-phase systemic inflammation.[40] Elevated serum CRP concentration significantly predicted future risk of CHD in several prospective cohort studies.[34,41,42,43] Recently, Visser et al.[44] analyzed data from 16,616 men and women from NHANES III and found a strong correlation between obesity and CRP levels, especially among women. After adjustment for potential confounders, the odds ratio (OR) for elevated CRP was 2.13 (95% confidence interval [CI], 1.56-2.91) for obese men and 6.21 (95% CI, 4.94-7.81) for obese women. In addition, BMI was associated with clinically raised CRP levels in women, with an OR of 4.76 (95% CI, 3.42-6.61) for obese women. WHR was positively associated with elevated CRP levels in both men and women, independent of BMI. In the Women's Health Study,[45] elevated CRP and interleukin-6 (IL-6) levels strongly predicted risk of type 2 diabetes.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: