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Original Article

Physical Activity and Reduced Occurrence of Non-Insulin-Dependent Diabetes Mellitus

Susan P. Helmrich, Ph.D., David R. Ragland, Ph.D., M.P.H., Rita W. Leung, A.B., and Ralph S. Paffenbarger, Jr., M.D., Dr.P.H.

N Engl J Med 1991; 325:147-152July 18, 1991

Abstract

Background.

Physical activity is recommended by physicians to patients with non-insulin-dependent diabetes mellitus (NIDDM), because it increases sensitivity to insulin. Whether physical activity is effective in preventing this disease is not known.

Methods.

We used questionnaires to examine patterns of physical activity and other personal characteristics in relation to the subsequent development of NIDDM in 5990 male alumni of the University of Pennsylvania. The disease developed in a total of 202 men during 98,524 man-years of follow-up from 1962 to 1976.

Results.

Leisure-time physical activity, expressed in kilocalories expended per week in walking, stair climbing, and sports, was inversely related to the development of NIDDM. The incidence rates declined as energy expenditure increased from less than 500 kcal to 3500 kcal. For each 500-kcal increment in energy expenditure, the age-adjusted risk of NIDDM was reduced by 6 percent (relative risk, 0.94; 95 percent confidence interval, 0.90 to 0.98). This association remained the same when the data were adjusted for obesity, hypertension, and a parental history of diabetes. The association was weaker when we considered weight gain between the time of college attendance and 1962 (relative risk, 0.95; 95 percent confidence interval, 0.90 to 1.00). The protective effect of physical activity was strongest in persons at highest risk for NIDDM, defined as those with a high body-mass index, a history of hypertension, or a parental history of diabetes. These factors, in addition to weight gain since college, were also independent predictors of the disease.

Conclusions.

Increased physical activity is effective in preventing NIDDM, and the protective benefit is especially pronounced in persons at the highest risk for the disease. (N Engl J Med 1991; 325:147–52.)

Media in This Article

Figure 1Age-Adjusted Incidence Rates and Relative Risks of NIDDM among 5990 Men, Based on 1962 Data for the Physical-Activity Index in Relation to the Body-Mass Index (Panel A) and Any History of Hypertension (Panel B).
Figure 2Age-Adjusted Incidence Rates and Relative Risks of NIDDM among 5990 Men, According to High-Risk (Solid Line) and Low-Risk (Dashed Line) Subgroups and Physical-Activity Index.
Article

NON-INSULIN-DEPENDENT diabetes mellitus (NIDDM), which affects 10 to 12 million Americans over the age of 20 years,1 2 3 is a complex disorder characterized by increased resistance to insulin and impaired secretion of insulin4 and associated with an increased risk of coronary heart disease, peripheral vascular disease, kidney failure, and blindness. The strongest predisposing factors for NIDDM are obesity5 6 7 8 and a family history of diabetes.9 , 10

Along with proper diet and weight reduction, exercise has been advocated for the management of NIDDM.2 , 11 Whether physical activity is effective in preventing diabetes is unknown, but several indirect lines of evidence support the concept that increased physical activity has a protective effect. First, physically active societies have less NIDDM than less active societies,5 and as populations have become more sedentary the incidence of NIDDM has increased. Second, physical activity increases sensitivity to insulin,12 and regular endurance exercise induces weight loss and improves glucose tolerance.13 Third, greater physical activity has been associated inversely with the prevalence of NIDDM in several cross-sectional studies.14 , 15 Understanding the relation of physical activity to the occurrence of NIDDM is complicated further by the fact that high levels of physical activity are often associated with a low prevalence of other risk factors for the disease, particularly obesity.

We used data from the University of Pennsylvania Alumni Health Study9 , 16 to determine whether higher levels of physical activity are associated with a lower incidence of NIDDM.

Methods

The original study included men who matriculated at the University of Pennsylvania between 1928 and 1947. In 1962, 80 percent of the surviving alumni from this population responded to a questionnaire on lifestyle habits and health. Seventy-two percent responded to a similar questionnaire in 1976; 858 men had died between 1962 and 1976, leaving 65 percent who responded to both questionnaires. Here we report on the subgroup of 5990 men who answered both the 1962 and 1976 questionnaires and who had not been given a diagnosis of diabetes by a physician before 1962. Of the 5990 men who met these conditions, NIDDM developed in 202 during 98,524 man-years of follow-up, through the end of 1976. The sensitivity of the questionnaires in identifying patients with NIDDM was 85 percent, and the specificity was 97 percent, as estimated on the basis of mail or telephone surveys of the physicians of 2200 alumni.

Variables Examined

Information on lifestyle and personal characteristics that were considered possible risk factors for the development of NIDDM (such as body-mass index, parental history of diabetes, and hypertension) was obtained from the 1962 questionnaire. The physical-activity variable was an indicator of a person's weekly expenditure of energy, largely during leisure time. Using methods described elsewhere,17 , 18 we assigned a specific number of kilocalories of energy expenditure to each activity reported on the 1962 questionnaire in order to compute a physical-activity index. For example, walking seven city blocks (0.94 km or 7/12 mile) was assigned a value of 56 kcal, and climbing and descending 70 steps a value of 28 kcal; sports activity was classified as moderate (5 kcal per minute) or vigorous (10 kcal per minute). In addition to the index of total energy expenditure during leisure time, we computed separate indexes for vigorous sports, moderate sports, and the number of flights of stairs climbed and city blocks walked each week.

Body-mass index in 1962 was computed in metric units (the weight in kilograms divided by the square of the height in meters) from the men's reports of their own heights in inches and weights in pounds. For the stratified analyses, the body-mass index was divided into three categories (<24.00, 24.00 to 25.99, and ≥=26.00). Information from physical examinations during the college years (the period from 1928 through 1947) was available for 4965 alumni, and height and weight records from those examinations were used to determine changes in the body-mass index between college and 1962.

The presence of a history of hypertension that was diagnosed by a physician or a parental history of diabetes was determined from the responses to the 1962 questionnaire. Similarly, the men were asked on both the 1962 and 1976 questionnaires whether they had a history of diabetes. Men in whom diabetes had already developed by 1962 were excluded from the study. Since insulin-dependent diabetes rarely develops in adults,8 all cases of diabetes diagnosed after 1962 and reported on the 1976 questionnaire were considered to be cases of NIDDM. The men reporting this condition ranged from 45 through 68 years of age at the time of diagnosis.

Statistical Analysis

We determined the relation between the predictor variables (age, physical-activity index, body-mass index, parental history of diabetes, and hypertension) in 1962 and the incidence of diabetes during the 14-year follow-up period. For the descriptive analyses, we classified the men according to their 1962 levels of physical activity and suspected risk factors for diabetes, and we computed age-adjusted rates of diabetes per 10,000 man-years of observation for each level of the risk variables studied. Relative risks and significance values for linear trend were computed with the Mantel extension of the MantelHaenszel test.19

To test for the independence of the association between physical activity and the development of NIDDM, we used the proportional-hazards regression model.20 The number of years from the response to the questionnaire in 1962 to the reported year of diagnosis of diabetes was used as the time variable; age, body-mass index at base line (1962), history of hypertension, and parental history of diabetes were evaluated as potential confounding variables. Except for history of hypertension and parental history of diabetes, each potential predictor was entered into the model as a continuous variable. In a supplementary analysis, we added the change in weight from the time of the college physical examination to 1962. Statistical levels of probability were calculated with two-tailed tests.

Results

In 1962, the men in the study population were 39 to 68 years old, and their body-mass indexes ranged from 14.1 to 46.0. The scores on the physical-activity index ranged from 0 to 14,700 kcal per week, with a mean (±SD) score of 1950±1834; approximately half the men had scores under 1200 kcal per week.

Physical Activity and NIDDM

Table 1Table 1Age-Adjusted Rates of NIDDM among 5990 Men, 1962 to 1976, According to Measures of Physical Activity in 1962. shows the age-adjusted incidence rates of NIDDM corresponding to the levels of physical activity in 1962. The incidence rate of diabetes decreased by nearly half (from 26.3 to 13.7 cases per 10,000 man-years of observation) as the total index of physical activity during leisure time increased from the lowest level (<500 kcal per week) to the highest level (≥3500 kcal per week) (P<0.01). The energy expenditure in kilocalories per week in both vigorous sports activity alone and all activities except vigorous sports was inversely associated with the incidence of NIDDM, with a somewhat stronger inverse association for vigorous sports.

We also examined this relation by using vigorous and moderate sports as dichotomous variables (Table 2Table 2Age-Adjusted Rates of NIDDM among 5990 Men, 1962 to 1976, According to Type of Physical Activity in 1962.). When we examined the continuum from no sports to moderate sports only, to vigorous sports only, and finally to a combination of moderate and vigorous sports, the associated rates of NIDDM decreased significantly, with relative risks of 1.00, 0.90, 0.69, and 0.65, respectively. For the number of flights of stairs climbed, there was a slight inverse association with the incidence of NIDDM, but the incidence of the disease was not related to the number of city blocks walked.

Other Risk Factors and NIDDM

Both age and body-mass index were positively associated with the development of NIDDM (Table 3Table 3Age-Specific and Age-Adjusted Rates of NIDDM among 5990 Men, 1962 to 1976, According to Selected Risk Factors in 1962.). The risk of diabetes in men 55 years old or older was more than twice that in men under 45 years of age. For men in the highest category of body-mass index, the risk of diabetes was more than three times that for men in the lowest category.

A history of hypertension before 1962 and a parental history of diabetes were also significant predictors of NIDDM. Men with physician-diagnosed hypertension had almost twice the incidence of diabetes during the 14-year follow-up period, as compared with the normotensive men. For men with a history of diabetes in one or both parents, the risk of having the disease was almost three time higher than in men whose parents did not have diabetes.

Physical Activity in Relation to Body-Mass Index and History of Hypertension

Figure 1Figure 1Age-Adjusted Incidence Rates and Relative Risks of NIDDM among 5990 Men, Based on 1962 Data for the Physical-Activity Index in Relation to the Body-Mass Index (Panel A) and Any History of Hypertension (Panel B). is a stereographic presentation of cross-tabulations of the physical-activity index with the body-mass index and the history of hypertension of the alumni in 1962. In the two highest categories of body-mass index (Fig. 1A), the most active men had a risk of NIDDM that was two thirds that of the least active men. Among the men in the lowest category of body-mass index, the risks were similar among the levels of activity and were one quarter to one third the risks for men in the group with the highest body-mass index. Thus, the protective effect of an increased energy expenditure during leisure time in lowering the risk of NIDDM was both strong and independent of the even stronger influence of the body-mass index.

There was a steady decline in the risk of NIDDM with increasing levels of energy expenditure, whether or not the men had a history of hypertension (Fig. 1B). Conversely, at each level of physical activity, the normotensive men had a substantially lower risk (by approximately half) than the hypertensive men. These data indicate that physical activity and hypertension contribute independently to the incidence of diabetes.

Predictor Variables and NIDDM

The proportional-hazards model20 was used to estimate the relative risk (estimated from the relative hazard) of NIDDM for each variable, and the model was standardized to reflect a specified increment for that variable. Table 4Table 4Relative Risks of NIDDM among 5990 Men, 1962 to 1976, According to Selected Risk Factors in 1962.* shows that the physical-activity index had a significant inverse association with NIDDM after adjustment for age, body-mass index, history of hypertension as reported in 1962, and parental history of diabetes. An increment of 500 kcal per week in the physical-activity index was associated with a relative risk of 0.94; stated otherwise, each increase of 500 kcal in the physical-activity index was associated with a 6 percent decrease in the risk of NIDDM. Moderate and vigorous sports activity were then entered into the model as separate variables. Each had marginal statistical significance, but the protective effect of vigorous activity was greater than that of moderate activity.

For body-mass index, each two-unit increment was associated with a relative risk of 1.21, or a 21 percent increase in the risk of NIDDM. Men who had hypertension in 1962 had a relative risk for NIDDM of 1.75, as compared with those with no such history. The adjusted relative risk of NIDDM that was associated with having at least one parent with a history of diabetes was 3.10.

Physical Activity, Gain in Body-Mass Index, and NIDDM

To search for a mechanism whereby physical activity may protect against NIDDM, we added another variable to the model: gain in the body-mass index since college. The addition of this variable, an independent predictor of NIDDM (relative risk, 1.18; P = 0.03), changed the relative risk associated with an increase in physical activity of 500 kcal per week from 0.94 to 0.95, indicating that some of the association between physical activity and diabetes was accounted for by the association of smaller gain in the body-mass index with greater physical activity. However, active men continued to have a reduced risk even after the change in body mass was taken into account.

Physical Activity and NIDDM in Subgroups at High and Low Risk

We classified the men as being at high or low risk on the basis of three risk factors identified in this study. Men at high risk were defined as those with a body-mass index of 25 or more, a history of hypertension, a positive parental history of diabetes, or any combination of these factors. We analyzed the association between the physical-activity index (divided into the three categories of <500, 500 to 1999, and ≥2000 kcal per week) and NIDDM for the high- and low-risk subgroups (Fig. 2Figure 2Age-Adjusted Incidence Rates and Relative Risks of NIDDM among 5990 Men, According to High-Risk (Solid Line) and Low-Risk (Dashed Line) Subgroups and Physical-Activity Index.). Of 2634 men in the high-risk subgroup, 135 had diabetes, representing 67 percent of the cases of diabetes. Among the men at high risk, the incidence of NIDDM declined by 41 percent from the lowest to the highest levels of energy expenditure (P = 0.03). In contrast, the incidence rates in the low-risk group were not altered by the level of physical activity (P = 0.97).

Discussion

Total expenditure of energy during leisure time had a protective effect against the development of NIDDM in middle-aged men. This effect was independent of obesity, age, history of hypertension, and parental history of diabetes. The occurrence of NIDDM was reduced by 6 percent for every increment of 500 kcal per week in leisure-time physical activity. For the average (75-kg) man, this energy expenditure can be achieved by engaging in regular, sustained body movement — jogging at approximately 5 miles per hour, bicycling at 10 miles per hour, swimming laps with light-to-moderate effort, or the like — for approximately one hour.21 Vigorous sports activity was most effective in decreasing the risk of NIDDM, but moderate sports activity was also effective.

Physical activity may protect against the development of NIDDM by helping to maintain a proper lean-to-fat balance with respect to body mass. Such a mechanism is plausible, since physical activity is associated with weight loss or the prevention of weight gain.22 The men's level of physical activity in 1962 was inversely correlated with their weight gain since matriculation at college (r = 0.1, P<0.001), and weight gain was a strong independent predictor of NIDDM. The inclusion of change in the body-mass index in the multivariate model slightly reduced the association between physical activity and NIDDM. Adipose tissue is a major site for insulin insensitivity, and most obese persons have increased insulin resistance, some degree of glucose intolerance, or both.7 , 8 In addition, approximately 80 percent of all patients with non-insulin-dependent diabetes are obese.2

Alternatively, physical activity may influence glucose metabolism. Among patients with diabetes, short periods of exercise can lower plasma glucose levels by enhancing the effect of insulin,23 , 24 and more extended exercise training may improve the action of insulin and glucose tolerance.25 In healthy subjects, studies of the effects of exercise on insulin sensitivity and glucose tolerance have been limited to short periods of follow-up.23 , 24 However, long-distance runners and physically trained middle-aged men have lower plasma insulin levels than healthy sedentary men,26 and an increase in sensitivity to insulin is characteristic of well-trained athletes.27 , 28

The protective effect of physical activity was particularly apparent in the subjects at high risk for NIDDM. This protective effect was especially strong among the heaviest persons, a finding consistent with the improvement in glucose tolerance in obese subjects after physical training.29 , 30 In addition, glucose intolerance that is related to obesity diminishes with exercise, whether or not there are changes in body weight.30 , 31

Although this study was prospective, thus avoiding problems of interpretation associated with previous cross-sectional studies,14 , 15 , 32 , 33 physical activity may have appeared to prevent NIDDM because the healthier men were more able to exercise. However, an analysis excluding subjects with coronary heart disease, hypertension, stroke before 1962, or a combination of these factors yielded virtually the same findings. Thus, activity would seem to provide protection from NIDDM independently of the subject's general health status.

Gains in the body-mass index before the base-line examination in 1962 may have played an important part in the development of NIDDM. One previous study found that obesity 10 years before the base line, but not more recent weight change, was an important predictor of NIDDM.34 It is likely that the biologic mechanism of weight gain is related to NIDDM, perhaps involving abnormalities of lipid metabolism or high levels of low-density lipoproteins. Whatever the mechanism, it appears to be partly mitigated by increased physical activity. If an increased body-mass index is a true predictor of NIDDM, then the protective effect of increased physical activity seen in this study may be partly due to its effect on body weight.

Many studies have examined hypertension in persons with diabetes in relation to coronary heart disease,35 36 37 but not specifically as a risk factor for diabetes itself. In this study we demonstrated that a history of hypertension increased the risk of NIDDM independently of other known risk factors, including obesity. An earlier study of the same alumni of the University of Pennsylvania showed that higher levels of blood pressure in college were associated with an increased risk of adult-onset diabetes.9 In addition, the higher rate of NIDDM among men with a parental history of diabetes is consistent with the results of previous studies.9 , 38 , 39 Whether a parental history of diabetes operates through genetic or environmental mechanisms is not known.

The data reported here support the concept that diabetes may be prevented by increasing overall activity and that vigorous activities, including swimming, tennis, and running, may have an even stronger protective effect than less vigorous activities. Furthermore, the data suggest that increased energy expenditure should be encouraged in subgroups of the population that are otherwise at high risk of diabetes, such as obese persons, persons with hypertension, and children of diabetics. We believe that exercise should be recommended as an adjunct to proper diet and weight control for the prevention of NIDDM.

Supported by grants (T32 HL07365 and R01 HL34174) from the National Heart, Lung and Blood Institute and by a grant from the Diabetes Research and Education Foundation.

We are indebted to Drs. Joseph V. Selby, Richard A. Levine, Dexter L. Jung, Andrea M. Kriska, Lynn Rosenberg, Sally L. Glaser, Mary C. White, and S. Leonard Syme for their comments.

Source Information

From the School of Public Health, University of California, Berkeley (S.P.H., D.R.R.), and the Department of Health Research and Policy, Stanford University School of Medicine, Stanford, Calif. (R.W.L., R.S.P.). Address reprint requests to Dr. Paffenbarger at the Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305.

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