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1 From the US Department of Agriculture Human Nutrition Research Center at Tufts University, Boston.
2 Supported by the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University (agreement 58-950-9-001), the US Department of Agriculture (grant 98l-35200-6057), and the National Institutes of Health (grant T32AG00209).
3 Address reprint requests to A Taylor, USDA Human Nutrition Research Center at Tufts University, 711 Washington Street, Boston, MA 02111. E-mail: ataylor{at}hnrc.tufts.edu.
See corresponding article on page1495.
Age-related cataract is a major public health problem, accounting for the largest line item (>$5 billion, or 12%) in the US Medicare budget (1). It is also the leading cause of preventable blindness in the world. In the United States, 20% and 50% of persons aged 65–74 and >75 y, respectively, have age-related cataract, which results in visual impairment. Cataract appears in the posterior subcapsular (PSC), cortical, and nuclear portions of the lens. It was estimated that delaying cataract by only 10 y would diminish by 50% the number of cataract extractions required in the United States (2). Clearly, the compromises in quality of life of our elderly population and the burden to our public health budgets provide major incentives to elucidate the cause of cataract and discover means to delay the onset and or progress of the disease.
Given the high prevalence of cataract, many people assume that cataract is part of "normal aging." This implies an acceptance of the status quo. However, many persons do not have vision-impairing cataract and recent research indicates that there are many societal, disease, dietary, behavioral, and environmental correlates of cataract (3). Several studies indicated that body composition is also related to the risk of cataract (4–17).
A growing body of information indicates that sites of fat deposition have profound effects on the risk of debilities and the mechanisms of alteration of metabolism and homeostasis (4). The waist-to-hip ratio (WHR) is thought to indicate fat distribution. Elevated WHRs are indicative of abdominal adiposity and visceral fat. Studies have positively related abdominal obesity to premature mortality, hypertension, and type 2 diabetes mellitus. Prospective epidemiologic studies showed the predictive power of elevated insulin concentrations, hypertension, and smoking in relation to abdominal obesity, type 2 diabetes, cardiovascular disease, and, perhaps, cataract. Accordingly, it is reasonable to ask whether abdominal adiposity is related to or predictive of cataract, whether each of these diseases shares a common etiology induced by or related to adiposity, and whether the information can be exploited to alleviate the burden imposed by cataract.
An inverse association between body mass index (BMI; in kg/m2) and cataract was found in 2 case-control studies (5, 6), whereas a direct relation was observed in a third case-control study (7) and in 3 prospective studies (8–10). In a fourth prospective study, an association between BMI and cataract was not found (11), although BMI was found to be directly associated with PSC cataract in persons without diabetes (12). BMI was not related to risk of cataract in a cross-sectional study of a disproportionately overweight black population (13).
In this issue of the Journal, Schaumberg et al (14) revisit the relation between body composition and size and cataract risk. Useful aspects of their study include the confirmation of cataract by a cataract-related decrease in visual acuity of 20/30 or worse and the inclusion of only physicians (all male), thus avoiding confounding due to differences in socioeconomic status, which is related to risk of cataract. During 245000 person-years, 2007 volunteers developed a confirmed incident cataract. This study indicated that after an average of 12 y of follow-up, both baseline BMI and nearest past BMI were positively related to the risk of incident cataract [rate ratio (RR): 1.4; 95% CI: 1.13, 1.74 for obesity, BMI 30 compared with BMI < 22] and corroborates data from a prior study that were recorded at the 5-y follow-up (8). Incident cataract surgery was performed in 1157 of the men and was also positively correlated to BMI.
Schaumberg et al also noted positive associations between WHR [RR: 1.31 for top compared with bottom quintile (WHR 0.986 and <0.897, respectively)] after corrections were made for BMI; use of carotene, aspirin, vitamin E, vitamin C, and multivitamin supplements; fruit, vegetable, and breakfast cereal consumption; cigarette smoking; daily alcohol intake; and vigorous exercise, but not for carbohydrate compared with fat intake, glycated hemoglobin or other major sources of lutein and zeaxanthin (14). These findings are consistent with the observations of Leske et al (13), who found a higher risk [odds ratio (OR) = 1.36; 95% CI: 1.0, 1.84] of cortical cataract in black persons in the highest WHR category than in those in the lowest category.
The relation between adult height and cataract was examined in 3 cross-sectional studies. Although 1 of these studies showed a greater prevalence of nuclear cataract in taller than in shorter persons (15), the other 2 studies showed inverse associations (16, 17). As with BMI and WHR, Schaumberg et al found that height was also positively associated with risk of cataract (RR = 1.3; 95% CI: 1.05, 1.63 after all corrections) at a height of 184 compared with 170 cm (6 feet and 5 feet 7 inches, respectively). The association was independent of BMI. The influences of genetics (18), nutrition, and other potential confounders should be evaluated fully in future studies. These data are consistent with results from laboratory animal models in which cataract and many age-related debilities were delayed and life extended in animals fed energy-restricted diets (19).
The inconsistent observations between studies may be explained in part by differences in the characteristics of study participants, method of body size measurement, or outcome definition. The studies were conducted in varied geographic locations, including the United States (5, 8–12,15), the United Kingdom (16), Italy (7), India (6, 17), and Barbados (13). The study participants varied in age or nutritional status and different methods were used to adjust for these variables. In addition, some studies relied on self-reported body measurements (7–9), whereas weight and height were measured directly in other studies (5, 6, 10, 11, 13, 15, 16).Also, cataract was variously defined as cataract extraction surgery (7–9, 11), cataract resulting in a specific amount of visual loss (6, 8, 17), or a graded lens opacity (5, 10, 12, 13, 15, 16). Most of the associations were weak to moderate. However, given that they represent an opportunity to diminish the large public health burden, these hypotheses should be pursued in both sexes in studies that show detailed body-composition information.
What mechanisms might explain the elevated risk of cataract in persons with high BMI or WHR? Obesity is known to be associated with diabetic conditions that are causally related to cataract. The independent relation between abdominal obesity and cataract (14) and their endpoints and risk factors might be explained in principle either by a direct causal relation or by an unkown factor, causing abdominal distribution of body fat as a parallel phenomenon to related diseases, including cataract. Evidence suggests that endocrine dysfunction is causally related to elevation of WHR and other sequelae (4). Unique metabolic characteristics of intraabdominal adipose tissue include an exceedingly sensitive system for the mobilization of fatty acid as seen in healthy men and abdominally obese women. Thus, there might be high portal fatty acid concentrations in situations in which fatty acid mobilization is triggered, such as stress and smoking (4). These factors are related to the risk of cataract in animals and humans (3). Elevation of portal fatty acids is associated with hyperinsulinemia due to a decreased rate of degradation and with increased splanchic production of glucose. Therefore, a cataractogenic pathway might include steroid-induced accumulation of diabetic-type modifications to lens proteins, including protein glycation, direct protein-steroid adduct formation, and sorbitol accumulation. In support of a diabetes-related cause of WHR-associated cataract is the positive correlation between glycated hemoglobin concentrations and cataract (13) and the independence (of BMI) of the WHR-PSC (more common in diabetic subjects) cataract relation. Implicit in this hypothesis is that, in persons with high WHRs, more glucose is available within lens cells. If redox potential is compromised, that would also be cataractogenic (3). These are testable hypotheses but currently the data are not available.
ACKNOWLEDGMENTS
We thank G Bray, P Bjorntorp, F Shang, and M Obin for their helpful discussions.
REFERENCES