Ever since the U.S. Diabetes Prevention Program (DPP) multicenter trial was completed nearly two decades ago (1), we have known that it is possible to prevent, or at least delay, prediabetes (an insulin resistant state) from progressing into full-blown type 2 diabetes. Why? Diabetes risk was reduced by 58% in the “intensive lifestyle” (ILS) participant group and by 31% in the metformin (an oral glucose-lowering medication) participants compared to no intervention (“placebo” group). For participants who were 60 years or older, lifestyle changes worked much better to prevent diabetes than taking metformin (1,2).
As an exercise physiologist, what I have always disagreed with about the DPP trial is its greater emphasis on weight loss than on physical activity. Admittedly, ILS consisted of a goal of losing 7 percent of body weight (only 14 pounds if you weight 200) by following a low-calorie, low-fat, high fiber diet and doing at least 150 minutes per week of a moderate physical activity (like brisk walking). In a follow-up report (2), for every kilogram (2.2 pounds) of weight loss, type 2 diabetes risk was reduced by 16%.
However, in the DPP, both a lower percent of calories from fat and increased physical activity predicted weight loss. Typically, it is easier for people to lose some weight than to keep it off afterwards, and that study reported that increased physical activity was critical to maintaining a lower weight. Even among the 495 participants who failed to meet the weight loss goal of 7% loss the first year, those who exercised regularly still had a 44% lower diabetes incidence (without weight loss!), and only the regular exercisers kept the weight off (2). In my mind, that means that physical activity is likely more important.
For the 10-year DPP Outcomes Study (DPPOS) and the 15-year follow-up, all original DPP participants were offered intensive lifestyle management training (3,4). During the first 7 years, diabetes incidence rates decreased by 42% in those who had not been doing ILS or taking metformin previously (DPP placebo group) and by 25% in the DPP metformin participants (who had the option to keep taking metformin); by way of comparison, those in ILS during the DPP increased diabetes rates by 31% during follow-up (5). That seems like a horrible outcome for the DPP ILS participants who only had to keep up their lifestyle changes.
On further analysis, no combination of changes in weight, physical activity, diet, smoking, and antidepressant or statin use explained the DPPOS lower rates of diabetes progression in placebo and metformin groups, but…weight gain was associated with higher rates in the ILS group. That also seems like a bad outcome. Did these participants stop exercising or become less active during the follow-up study? Statistically speaking, physical activity was not a factor that accounted for their increased diabetes rates, but in practical terms, even small changes in activity can make a big difference in blood glucose and body weight management. It’s also important to note that the ILS group still had the overall lowest rates of diabetes incidence at the 15-year mark, even though they rose closer to the other groups (4).
Although the DPP established combined lifestyle improvements (diet, activity, and weight loss) as the best way to prevent type 2 diabetes, a more recent study attempted to determine how much exercise alone contributes, along with the optimal intensity of exercise since most DPP participants did brisk walking (6). Three study groups did varying amounts and intensities of exercise while the fourth followed diet and exercise strategies like the DPP to lose 7% of body weight. Interestingly, a higher amount of moderate-intensity exercise by itself (the equivalent of walking about 13.8 miles weekly) was very effective at improving how well people responded to consuming a large amount of glucose (via an oral glucose tolerance test) despite a relatively modest 2-kilogram (4.4-pound) loss of body fat, which suggests that a higher amount of moderate-intensity walking may work as well as combined approaches for preventing the progression to type 2 diabetes. It should be noted, however, that only the diet and exercise group experienced a decrease in fasting blood glucose levels in that study (6).
So, does physical activity matter? I still maintain that it is as important as—if not more important than—losing weight when it comes to preventing diabetes and managing insulin resistance (even if you have type 1 diabetes), especially since most people have trouble keeping the weight off and only regular physical activity is guaranteed to help you do that. Importantly, the latest follow-up study coming from the DPP just confirmed that I (and others) were right all along (7). In that study, cumulative diabetes incidence remained lower in the lifestyle compared with the placebo and metformin randomized groups and this difference could not be explained by changes in body weight. Examining the self-reported physical activity overall revealed that physical activity was inversely related to diabetes, meaning that the more active people were over time, the less likely they were to develop it, regardless of their body weight. Eureka!
Losing the right type of weight matters as well (that is, mostly fat and not much muscle), so if you are dieting, make sure you include regular activity (particularly resistance exercise) to retain more of your insulin-sensitive muscle mass (8).
References:
1. Knowler WC, Barrett-Connor E, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403.
2. Hamman RF, Wing RR, et al. Effect of weight loss with lifestyle intervention on risk of diabetes. Diabetes Care. 2006;29(9):2102-7.
3. Diabetes Prevention Program Research Group, Knowler WC, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677-86.
4. Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015;3(11):866-75.
5. Diabetes Prevention Program (DPP) Research Group, Hamman RF, et al. Factors affecting the decline in incidence of diabetes in the Diabetes Prevention Program Outcomes Study (DPPOS). Diabetes. 2015;64(3):989-98.
6. Slentz CA, Bateman LA, et al. Effects of exercise training alone vs a combined exercise and nutritional lifestyle intervention on glucose homeostasis in prediabetic individuals: a randomised controlled trial. Diabetologia. 2016;59(10):2088-98.
7. Kriska AM, Rockette-Wagner B, Edelstein SL, et al. The Impact of Physical Activity on the Prevention of Type 2 Diabetes: Evidence and Lessons Learned From the Diabetes Prevention Program, a Long-Standing Clinical Trial Incorporating Subjective and Objective Activity Measures. Diabetes Care. 2021;44(1):43-49.
8. Colleluori G, Aguirre L, et al. Aerobic plus resistance exercise in obese older adults improves muscle protein synthesis and preserves myocellular quality despite weight loss. Cell Metab. 2019;30(2):261-273.e6.
The DPP program has a number of issues that may result in poor acceptance and participation on the part of program organizers and those at high risk for diabetes. The focus on weight loss as the primary outcome has left many program administrators and participants dissatisfied with the program. With advances in wearables and other technologies, perhaps we can focus on other measures of success than the scale.