We addressed the single and joint associations of CRF and BMI for the risk of development of type 2 diabetes in women. Low fitness was associated with a significantly higher risk for type 2 diabetes in women, independent of age, smoking, alcohol intake, hypertension, family history of diabetes, and BMI at baseline. Overweight and obese women also had a higher risk of type 2 diabetes. The protective effect of CRF remained in overweight/obese women but not in the normal-weight women.
Previous observational studies have indicated that physical activity (4
) or CRF (13
) is inversely associated with the prevalence and incidence of diabetes. However, studies on the prospective association of CRF, an objective measure of physical activity habits that is less prone to misclassification, with diabetes risk in women are limited (14
). There are only two studies that included women, but separate analyses for women and men were not performed. Carnethon et al. (14
) reported a 15-year follow-up study in 2,478 young adults, during which 56 cases of type 2 diabetes were identified. After adjusting for confounders including BMI, participants with low fitness (<20th percentile) were two times more likely to develop type 2 diabetes than those with high fitness (≥60th percentile). Katzmarzyk et al. (17
) followed 1,543 adults aged 18–69 years for 15 years and found that physical fitness, but not physical activity, was a significant predictor of incident diabetes after adjustment for age, sex, and several covariates. We found 14 and 39% lower risks of diabetes for women in the middle and upper thirds of fitness, compared with women in the lower third of fitness group. The present study extends our previous findings in men (16
) and is the first to report an inverse association between CRF and the risk for diabetes in overweight and obese women.
The protection against the development of type 2 diabetes by physical activity or CRF may be explained by enhanced glucose homeostasis (27
). Structural changes (e.g., increased fiber size, capillary density, and blood flow) and biochemical changes (e.g., increased insulin and noninsulin signaling kinetics, enzymes related to glucose metabolism, and/or myoglobin) in skeletal muscle are two of the several mechanisms involved with the favorable effect that regular physical activity has on glucose (27
). Other suggested mechanisms include systemic influences of physical activity such as improved oxygen uptake and functional capacity, better lipemic control, and lowered excessive hepatic secretion of glucose and VLDL (27
Obesity is an independent risk factor for the development of type 2 diabetes in women (5
). We observed low fitness in 28, 48, and 82% of women across normal-weight, overweight, and obese groups, respectively, and overweight/ obese and low fit women had the highest risk of type 2 diabetes compared with other fitness and BMI combination groups (). Higher fitness was associated with a lower risk of type 2 diabetes in overweight/obese women but not in normal-weight subjects. The latter finding was inconsistent with two previous studies showing that the risk of diabetes could be reduced by higher physical activity in individuals with or without obesity (4
) but was in accordance with another study (5
). In fact, the joint association of physical activity and BMI on diabetes in women has been poorly understood, and the data are very limited (5
). The Women’s Health Study (5
) reported a small and nonsignificant lower risk within the normal-weight, overweight, and obese groups when inactive and active participants were compared. Recently, the Nurses’ Health Study (8
) showed that slower walking pace was associated with higher risk of type 2 diabetes within the same BMI category, and the inverse association between pace and intensity of walking and risk of type 2 diabetes was most evident in overweight and obese women. There are several possible explanations for the differing results when we compare our findings with those of others. First, the measures of CRF used in this study may be a better marker for habitual levels of physical activity than less precise self-reported physical activity exposures, particularly in women (10
). Second, the sample size and small number of events in the current study may not have been adequate to detect a significant effect of CRF in the normal weight individuals. The present study adds useful information, as no previous studies have examined the independent and joint association of CRF and BMI on the incidence of type 2 diabetes in women.
Although CRF has a genetic component (25–40%) (29
), it is clear that usual physical activity habits are the primary determinant of fitness. Recently, Church et al. (31
) reported that an activity level as low as 4 kcal · kg−1
level (~72 min/week of moderate intensity walking) was associated with a significant improvement in CRF compared with women in the nonexercise control group.
The laboratory measurements of CRF and BMI as predictors and fasting blood glucose as the primary source for defining the study outcome are major strengths of the current study. Limitations are mainly those for epidemiological studies in general. The homogeneity of our population sample should not affect the internal validity but may limit the generalizability. Whether our results apply to men, women of other ethnic groups, or individuals of low socioeconomic status remains to be determined; however, our previous report (16
) and other studies in men (15
) on the association of CRF with diabetes are consistent with those reported here. Although women in this cohort tend to be healthier than those in the general population, the biological mechanisms that affect the development of type 2 diabetes are not likely to be different. We did not have sufficient information on hypertension medication usage, menopausal status, or dietary habits to include these in our analysis. We do not have data from an oral glucose tolerance test. Self-report of diabetes was one criterion used to categorize participants, and, consequently, we cannot verify that the participants had type 2 rather than type 1 diabetes. However, based on the current literature, >90% of adults with diabetes are estimated to have type 2 diabetes (32
). Because this study consisted of middle-aged women, we suspect that most of the participants had type 2 diabetes. Therefore, our methods of ascertainment should not be less valid than those of other epidemiologic studies (5
) in which self-reported diabetes was used.
In summary, this study demonstrated that both CRF and BMI are important in the development of diabetes in women. Our finding that high fitness was associated with a lower risk of type 2 diabetes in overweight/obese women further confirms the benefits of engaging in regular physical activity for these high-risk individuals. Our data also support the benefits of maintaining normal weight. Given the rapidly growing population prevalence of diabetes (34
), the small improvement in physical activity over the past decade (34
), and the continuing rise in obesity rates (35
), the public health burden attributed to diabetes continues to be large and is likely to increase in coming years. We therefore believe health professionals should consider the potential benefits of greater CRF and aggressively counsel their sedentary obese patients to become more physically active and improve their CRF as a cornerstone of diabetes prevention.