Physical Activity in the Prevention of Type 2 Diabetes

Abstract

Type 2 diabetes is a common chronic disease with multiple complications, most notably car diovascular diseases. In the past decade, the associations of physical activity, physical fit ness, and changes in the lifestyle with the risk of type 2 diabetes have been assessed by a number of prospective studies and clinical tri als. A few studies also evaluated joint associa tions of physical activity, Body Mass Index and glucose levels with the risk of type 2 diabetes. The results based on 21 prospective studies and four clinical trials have shown that mod erate or high levels of physical activity or phys ical fitness, and changes in the lifestyle (di etary modification and increase in physical ac tivity) can prevent type 2 diabetes. Not only leisure-time physical activity, but also occupa tional and commuting physical activities are important components of healthy lifestyle and can protect against type 2 diabetes.

Introduction

Diabetes is one of the fastest growing public health problems in both developed and devel oping countries. It has been estimated that the number of patients with diabetes in the world will double from the current 171 million in 2000 to 366 million in 2030 [1]. Both genetic and environmental factors are important in the etiology of type 2 diabetes [2]. Of lifestyle risk factors for type 2 diabetes most important are physical inactivity and obesity [3]. Results from prospective studies [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24] and clinical trials [25,26,27,28] have shown that moderate or high levels of physical activity or physical fitness, and changes in the lifestyle (dietary modification and increase in physical activity) can prevent type 2 diabetes. In this review, we summarise current evidence about the role of physical activity in the primary prevention of type 2 diabetes.

Physical activity and type 2 diabetes in prospective epidemiological studies

Nineteen prospective epidemiological studies of physical activity on the risk of type 2 dia betes are summarised in

Table 1. Prospective studies of physical activity and the risk for type 2 diabetes.

. The first study investigated the association between leisure time physical activity and the risk of type 2 diabetes in 5990 male alumni of the Uni versity of Pennsylvania [4]. It found that higher levels of leisure time physical activity were effective in the prevention of type 2 dia betes. A 2-year follow-up study in Malta showed that low overall physical activity dur ing work, leisure time and commuting was associated with a 3.7-fold risk of diabetes and impaired glucose tolerance compared with high physical activity among subjects with normal or impaired glucose tolerance at base line [6]. The Nurses’ Health Study involved 87 253 US women aged 34–59 years free of diabetes at baseline [5]. During the 8-year of follow-up (1980 to 1988), 1303 cases of self-reported type 2 diabetes were ascertained. Women who were engaged in vigorous exer cise at least once per week had a 33% reduced aged-adjusted relative risk of type 2 diabetes (p <0.001) compared with women who did not exercise. Multivariate adjustment for age, family history of diabetes, Body Mass Index, and other variables did not alter the observed risk reduction. Another prospective 5-year study of 21 271 US male physicians aged 40–84 years (1982–1988) indicated that men who ex ercised at least once a week had a multivari ate-adjusted relative risk of diabetes of 0.71 (p = 0.015) [7]. After a new follow-up period, the Nurses’ Health Study (1986 to 1994) and the Health Professionals’ Follow-up Study (1986–1996) found a progressive reduction in the multivariate-adjusted relative risk of type 2 diabetes with increasing leisure time physi cal activity [14, 19]. These studies also re ported that walking prevented type 2 diabetes as well as vigorous physical activity [14, 19].

In the Honolulu Heart Program the risk of type 2 diabetes was inversely related to total physical activity during a 2 to 6-year follow-up of 6815 Japanese-American men aged 45–68 years [8]. The result from the British Regional Heart Study indicated that men engaged in moderate levels of physical activity had a substantially reduced risk of type 2 diabetes com pared with the physically inactive men after adjustment for age, Body Mass Index, systolic blood pressure, high density lipoprotein cho lesterol, smoking, alcohol intake, and preva lent coronary heart disease [9]. The Malmö Preventive Trial found that men who devel oped with diabetes during 6-year follow-up had a 16% lower baseline mean value of phys ical activity score compared with men who did not develop diabetes [10]. In the Kuopio Is chemic Heart Disease Risk Factor Study of 897 middle-aged Finnish men, physical activity of moderate intensity (≥5.5 metabolic units) that was undertaken for at least a 40 minutes duration per week protected against the devel opment of type 2 diabetes after adjusting for age, baseline glucose levels and known risk factors [11]. Another Finnish prospective study also examined 891 men and 973 women aged 35–63 years during a 10-years follow-up [12]. Only women with a higher overall activ ity or weekly vigorous activity had a reduced risk of type 2 diabetes. An aged-adjusted rela tive risk of 2.6 for diabetes was found for the lowest third of physical activity compared with the highest third [12]. The Pitt County Study demonstrated that the risk of type 2 diabetes among African-Americans who engaged in moderate physical activity was 65% lower than that of their physically inactive counter parts [13]. The Iowa Women’ Health Study investigated 34 257 postmenopausal women aged 55–69 years without clinical diabetes at baseline [16]. Women who reported any leisure time physical activity had a relative risk of 0.86 compared with sedentary women after ad justment for age, and other confounding fac tors. The Osaka Health Survey included 6013 Japanese men aged 35–60 years who were free of clinical diabetes, impaired fasting gly-caemia, or hypertension at baseline [17]. Men who participated in physical exercise at least once a week or vigorous activity only once a week at weekends had a decreased risk of type 2 diabetes. The result from Pima Indians Com munity Study also indicated that leisure time physical activity plays a significant role in pre venting type 2 diabetes [21]. The Gothenburg BEDA Study found a significant inverse asso ciation between leisure time physical activity and the risk of type 2 diabetes among 2017 Swedish women [23].

Recently, we investigated 6898 Finnish men and 7392 women of 35 to 64 years of age without a history of stroke, coronary heart dis ease, or diabetes at baseline [20]. During a mean follow-up of 12 years, there were 373 in cident cases of type 2 diabetes. Moderate or vigorous activity at work and moderate or high levels of leisure time physical activity were as sociated with a significantly reduced risk of type 2 diabetes (

Table 2. Relative risk of type 2 diabetes according to different levels of occupational, commuting, and leisure time physical activity, with various forms of adjustment among Finns*. Published with permission from: Hu G, Qiao Q, Silventoinen K, Eriksson JG, Jousilahti P, Lindstrom J, et al. Occupational, commuting, and leisure-time physical activity in relation to risk for type 2 diabetes in middle-aged Finnish men and women. Diabetologia 2003, 46, 322–9. © Springer-Verlag GmbH, Heidelberg.

). Walking or cycling to and from work for more than 30 minutes a day was also significantly and inversely associated with the risk of type 2 diabetes. These associ ations were independent of age, systolic blood pressure, smoking, education, the other two types of physical activity, and Body Mass In dex. Simultaneous engagement in two or three types of moderate or high levels of occupa tional, commuting, and leisure time physical activity was independently and significantly associated with a lower risk of type 2 diabetes than doing only one type of moderate or high physical activity.

Figure 1. Relative risk of type 2 dia betes according to different levels of physical activity and Body Mass Index (<30 kg/m2 and ≥30 kg/m2); physical activity and glucose (normal glucose, impaired glucose regula tion). Published with per mission from: Hu G, Lind strom J, Valle TT, Eriksson JG, Jousilahti P, Silventoinen K, et al. Physical activity, body mass index, and risk of type 2 diabetes in patients with normal or impaired glucose regulation. Arch In tern Med 2004, 164, 892–6. Copyrighted © 2004, Ame rican Medical Association. All rights reserved. adjusted for age, sex, study year, systolic blood pressure, smoking status, education and Body Mass Index. IGR = impaired glucose regulation.

Figure 1. Relative risk of type 2 dia betes according to different levels of physical activity and Body Mass Index (<30 kg/m2 and ≥30 kg/m2); physical activity and glucose (normal glucose, impaired glucose regula tion). Published with per mission from: Hu G, Lind strom J, Valle TT, Eriksson JG, Jousilahti P, Silventoinen K, et al. Physical activity, body mass index, and risk of type 2 diabetes in patients with normal or impaired glucose regulation. Arch In tern Med 2004, 164, 892–6. Copyrighted © 2004, Ame rican Medical Association. All rights reserved. adjusted for age, sex, study year, systolic blood pressure, smoking status, education and Body Mass Index. IGR = impaired glucose regulation.

In a sub-sample of 2017 Finnish men and 2352 women who participated in the standard oral glucose tolerance test at baseline, we eval uated the single and joint association of phys ical activity, Body Mass Index, and glucose lev els with the risk of type 2 diabetes [24]. Phys ical activities were merged and regrouped into three categories: (1.) low was defined as sub jects who reported light levels of occupational, commuting (<30 minutes) and leisure time physical activity; (2.) moderate was defined as subjects who reported only one of the all three types of moderate to high physical activity; (3.) high was defined as subjects who reported two or three types of moderate to high physical ac tivity. Higher levels of physical activity were associated with a significantly reduced risk for type 2 diabetes, and this inverse association was persistent in subgroup analyses based on Body Mass Index (<30 and ≥30 kg/m2) and glu cose levels (normal glucose, and impaired glu cose regulation) (fig. 1A and 1B). In the joint analyses of different levels of physical activity, Body Mass Index, and plasma glucose with the risk of type 2 diabetes (fig. 2), the direct asso ciation of Body Mass Index and the inverse association of physical activity were found among both normoglycaemic subjects and sub jects with impaired glucose regulation. In com parison with non-obese persons who reported higher levels of physical activity and had nor mal glucose tolerance/homeostasis, obese sub jects who reported low level of physical activ ity and had impaired glucose regulation showed a 30 times higher risk for the develop ment of type 2 diabetes. Individuals who were inactive, obese and had normal glucose levels had a higher risk of type 2 diabetes compared with those who were physically active, non-obese and had impaired glucose regulation.

Figure 2. Relative risk of type 2 diabetes according to joint levels of physical activity, Body Mass Index, and glucose tolerance status. Adjusted for age, sex, study year, systolic blood pressure, smoking status, and education. Published with permission from: Hu G, Lindstrom J, Valle TT, Eriksson JG, Jousilahti P, Silventoinen K, et al. Physical activity, body mass index, and risk of type 2 diabetes in patients with normal or impaired glucose regulation. Arch Intern Med 2004, 164, 892–6. Copyrighted © 2004, American Medical Association. All rights reserved. IGR = impaired glucose regulation.

Figure 2. Relative risk of type 2 diabetes according to joint levels of physical activity, Body Mass Index, and glucose tolerance status. Adjusted for age, sex, study year, systolic blood pressure, smoking status, and education. Published with permission from: Hu G, Lindstrom J, Valle TT, Eriksson JG, Jousilahti P, Silventoinen K, et al. Physical activity, body mass index, and risk of type 2 diabetes in patients with normal or impaired glucose regulation. Arch Intern Med 2004, 164, 892–6. Copyrighted © 2004, American Medical Association. All rights reserved. IGR = impaired glucose regulation.

Physical fitness and type 2 diabetes in prospective epidemiological studies

Only four prospective epidemiological studies have assessed the association of physical fit ness with the risk of type 2 diabetes (

Table 3. Prospective studies of physical fitness and the risk for type 2 diabetes.

) [10, 11, 15, 22]. The Malmö Preventive Trial found that poor physical fitness, measured by vital capacity and maximal oxygen uptake, was inversely associated with the risk of type 2 diabetes [10]. In the Kuopio Ischemic Heart Disease Risk Factor Study, higher levels of car diorespiratory fitness (≥31.0 ml of oxygen per kilogram per minute) protected against the development of type 2 diabetes after adjusting for age, baseline glucose levels and other risk factors [11]. The Aerobic Center Longitudinal Study involved 8633 men aged 30–79 years without diabetes at baseline [15]. Men in the low cardiorespiratory fitness group (the least fit 20% of the cohort) had a 3.7-fold risk for development of diabetes compared with those in the high fitness group (the most fit 40% of the cohort) [15]. The Tokyo Gas Company Study including 4747 non-diabetic Japanese men aged 20–40 years found a significant in verse association between cardiorespiratory fitness and the risk of type 2 diabetes [22].

Changes in the lifestyle and type 2 diabetes in clinical trials

Two early reports from Sweden and China demonstrated that changes in lifestyle can prevent type 2 diabetes, but a major limitation of these two studies was that the subjects were not randomly assigned to the intervention and control groups [25, 26]. Recently results from two well-designed randomised controlled tri als in Finland and the United States have been reported [27, 28].

The Malmö study from Sweden used in creased physical exercise and weight loss as major intervention strategies to prevent and delay type 2 diabetes [25]. Subjects with im paired glucose tolerance had less than half the risk of developing type 2 diabetes compared with those who chose not to take part in the exercise program during the 5-year follow-up. In the Chinese study from Da Qing, 577 indi viduals with impaired glucose tolerance were randomised by clinic into one of the four groups: exercise only, diet only, diet plus exer cise, and a control group [26]. The cumulative incidence of type 2 diabetes during 6 years was significantly lower in the three intervention groups compared with the control group (41% in the exercise group, 44% in the diet group, 46% in the diet plus exercise group, and 68% in the control group) and remained significant even after adjusting for differences in baseline Body Mass Index and fasting glucose.

In the Finnish Diabetes Prevention Study (DPS), 522 middle-aged (mean age 55 years), overweight (mean Body Mass Index 31 kg/m2) men (33%) and women (67%) with impaired glucose tolerance were randomised either to the intensive lifestyle intervention group or the control group [27, 29]. The five main goals of the lifestyle intervention were based upon available evidence on diabetes risk factors. They were weight reduction 5%, moderate intensity physical activity 30 minutes/day, dietary fat <30 proportion of total energy (en-ergy%), saturated fat <10 energy%, and fiber 15 g/1000 kcal. During the first year of the study the intervention was intensive, includ ing seven individual dietary counselling ses sions with the study nutritionist. After the in tensive intervention period, there was a maintenance phase which included a counselling session every three months. At each of these counselling sessions exercise habits were also discussed and all kinds of physical activity was strongly recommended, and increased physi cal activity was considered as an essential part of successful weight loss program. Endurance exercise (walking, jogging, swimming, aerobic ball games, skiing) was recommended to in crease aerobic capacity and cardiorespiratory fitness. The study subjects were also offered an opportunity to attend supervised, progressive, individually tailored circuit-type resistance training sessions. The moderate intensity and medium to high volume programmes were de signed to improve the functional capacity and strength of the large muscle groups of the up per and lower body. The cumulative incidence of diabetes after four years was 11% in the in tervention group and 23% in the control group. During the entire trial, the risk of diabetes was reduced by 58% (p <0.001) in the intervention group. The reduction in the incidence of dia betes was directly associated with changes in lifestyle, since more of the people who reached four or five of the five lifestyle targets devel oped diabetes.

In the DPS the role of leisure time physi cal activity in preventing type 2 diabetes was assessed by examining the association of the changes in leisure time physical activity during the study with the incidence of diabetes in the combined intervention and control groups [30]. In the combined groups, the change in total leisure time physical activity was more strongly associated with incident diabetes than changes in subcategories of leisure time physical activity (

Table 4. Relative risk (95% confidence intervals) of developing type 2 diabetes during the study according to tertiles of the change in leisure-time physical activity in DPS study* [30].

). Adjusting for age, sex, group, smoking and major risk factors for diabetes at baseline, including Body Mass In dex, fasting and two-hour plasma glucose and insulin levels and family history of diabetes, and baseline total leisure time physical activ ity, participants in the upper third of the change in total leisure time physical activity were 80% less likely to develop diabetes dur ing the trial than those in the lower third (rel ative risk 0.20; 95% CI 0.10–0.41). Partici pants who were in the upper third for a change in moderate-to-vigorous leisure time physical activity were 49 to 65% less likely to develop diabetes than those who were in the lower third after adjustment for confounding factors including low-intensity leisure time physical activity and its changes (Table 4). Changes in low-intensity leisure time physical activity also predicted a 59 to 64% reduction in the risk of incident diabetes, even with simultaneous adjustment for moderate-to-vigorous leisure time physical activity and its changes.

In the U.S. Diabetes Prevention Program (DPP), the 3234 non-diabetic persons with elevated fasting and post-load plasma glucose concentrations were randomised into placebo, metformin, or a lifestyle-modification program with the goals of at least a 7% weight loss and at least 150 minutes of physical activity per week [28, 31]. The mean age of the participants was 51 years, the mean Body Mass Index was 34 kg/m2, 68% of the participants were women, and 45% of them were members of non-Cau-casian ethnic groups. The exercise interven tion emphasized brisk walking, but also other activities with equivalent intensity (aerobic dance, bicycle riding, skating, swimming) were recommended. The participants were advised to distribute the physical exercise throughout the week, with at least 10 minutes per session. Voluntary, supervised physical activity ses sions were offered at least twice per week throughout the study, including group walks, aerobic classes, and one-to-one personal train ing. After an average follow-up of 2.8 years, the incidence of diabetes was 11.0, 7.8 and 4.8 cases per 100 person-years in the placebo, met formin and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58% and metformin by 31%, as compared with placebo; the lifestyle intervention was signifi cantly more effective than metformin in the prevention of type 2 diabetes.

Prevention of cardiovascular disease by physical activity in diabetic patients

In previous years, several studies assessed the association between physical activity and the risk of cardiovascular mortality among dia betic patients [32,33,34,35,36]. The results from the Aerobic Center Longitudinal Study [32], the Nurses’ Health Study [33], the Whitehall Study [34], the National Health Interview Sur vey [35], and the Health Professionals’ Follow up Study [36] have indicated that regular leisure-time physical activity is associated with reduced CVD and total mortality among patients with diabetes. Walking had similar inverse association with the risk of CVD and total mortality to vigorous leisure-time physi cal activity [33,34,35,36]. In the Aerobic Center Lon gitudinal Study, low fitness group had a high relative risk for total mortality compared with the fit group [32]. The analyses from our group also evaluated whether other types of physical activities, such as occupational and daily com muting physical activity on foot or by bicycle, are related to reduced CVD mortality among diabetic patients [37]. We reviewed data on

3316 people age 25 to 74 with type 2 diabetes who participated in surveys of randomly se lected samples from the Finnish population conducted between 1972 and 1997. The data included questionnaires on the level of physi cal activity on the job; on the way to and from work; and during their leisure time. During an average follow-up of 18.4 years, 1410 of the subjects died, including 903 (64%) from cardio vascular disease. After adjusting for age, gen der, Body Mass Index, systolic blood pressure, total cholesterol, smoking and the other two categories of physical activity, we found that moderately active work was associated with a 9% reduction in cardiovascular mortality and active work was associated with a 40% reduc tion in cardiovascular death. High level of leisure-time physical activity was associated with a 33% drop in cardiovascular mortality and moderate activity was linked to a 17% drop in cardiovascular mortality compared to the most sedentary group. Daily walking or cy cling to and from work decreased cardiovascu lar mortality, but this relation was no longer significant after additional adjustment for oc cupational and leisure-time physical activity. Simultaneously doing one, two or three types of moderate or high occupational, commuting, and leisure-time physical activity reduced to tal and CVD mortality [37].

Although the mechanisms of the protec tive effect of regular exercise are not addressed in these studies, the large body of literature demonstrates that regular physical activity can improve insulin sensitivity and other com ponents of the metabolic syndrome, eg de crease blood pressure, increase plasma levels of high-density lipoprotein cholesterol, de crease plasma levels of triglycerides, reduce body weight and maintain healthy weight [18, 38], and also reduce the risk of developing the metabolic syndrome [39]. The Kuopio Ischemic Heart Disease Risk Factor Study suggested that poor cardiorespiratory fitness is not only associated with all components of the meta bolic syndrome but could also be considered a feature of the syndrome [40]. A recent analysis from the Insulin Resistance Atherosclerosis Study showed that both vigorous and non-vig-orous activities were associated with higher insulin sensitivity among 1467 men and women of 40 to 69 years of age [38]. The British Regional Heart Study examined the role of serum insulin concentration and components of the metabolic syndrome in the relation be tween physical activity and the incidence of type 2 diabetes among 5159 men of 40 to 59 years of age [18]. It showed that physical activity was significantly and inversely associ ated with serum insulin concentrations and many components of the metabolic syndrome, and serum insulin concentrations and the com ponents of the metabolic syndrome was a me diating factor in the relation between physical activity and the incidence of type 2 diabetes.

Another critical factor in preventing type 2 diabetes is the prevention or treatment of obesity through dietary energy restriction and increasing physical activity. Epidemiological evidence has shown that physical activity and body weight loss are of medical benefit, not just for preventing diabetes, but also for cardiovas cular health and quality of life [41,42,43,44,45,46,47]. Regu lar physical activity is a crucial component of a healthy lifestyle. Health care professionals and policy makers should more aggressively promote physical activity and weight control.