We proposed that exercise training would reduce insulin resistance in older obese adults, and that this response would be modulated by the glycemic content of the diet. After 12 weeks of aerobic exercise, obese men and women demonstrated a 47 ± 9% improvement in insulin sensitivity and reduced the glycemic load in their diet by 25 ± 10% without any significant change in energy intake. The decrease in insulin resistance correlated with the reduction in glycemic load. Additionally, those who made the greatest change in the glycemic content of their diet (decreased by 61 ± 8%) experienced significantly greater improvements in insulin sensitivity (78 ± 11%). These data suggest that insulin resistance can be reversed with a relatively short-term aerobic exercise-training program, but that the improvement in insulin sensitivity may be further enhanced by consuming a low-glycemic diet. The data point to a potential synergy between exercise and a low-glycemic diet as an integral treatment modality for insulin resistance and type 2 diabetes.
The prevalence of obesity, insulin resistance and type 2 diabetes has dramatically increased in older adults in the past 3 decades. Furthermore, diabetes is associated with excess morbidity and mortality across all age groups, but this is seen most frequently in the elderly [27
]. The Diabetes Prevention Program provides some of the strongest data to support the role of exercise and diet in reducing the risk of developing type 2 diabetes [2
]. A systematic lifestyle intervention was more than twice as effective as metformin in attenuating risk in those over the age of 60 years. The effect of exercise training alone on insulin sensitivity is well established in young obese and type 2 diabetic populations [9
] although this observation is not universal [28
]. Older subjects also show positive adaptations to exercise training, but these observations were not made in all studies [11
]. Indeed, it was recently shown that nonobese older women only improved insulin sensitivity after high-intensity (about 80% VO2peak
) exercise training [29
]. In the present study, exercise intensity was set at a more modest level (about 70% VO2max
) yet these older obese individuals showed positive adaptations demonstrating significant improvements in insulin sensitivity, increases in fitness, and decreases in body weight. The magnitude of the improvement in insulin sensitivity for the higher glycemic-load subgroup alone was approximately 28%, which compares favorably to other exercise studies that have demonstrated improved insulin sensitivity in overweight and obese adults [9
]. However, one of the most novel observations from our current study was the superior response among 4 of the subjects who increased their insulin sensitivity by 78%, i.e. almost 3 times what is normally seen after similar exercise interventions. These ‘super-responders’ prompted us to probe for potential factors that might contribute to the greater increase in insulin sensitivity. While others have identified differences in gene expression profiles between those who respond and do not respond to exercise [31
], we elected to examine the possibility that diet composition may have played a role.
While lifestyle interventions are now widely accepted as the first-line treatment for obesity, diabetes, and related metabolic problems, there is no consensus on the most appropriate diet composition for managing these conditions. Low-fat, high-carbohydrate diets have traditionally been the dietary recommendation of choice [33
]. However, Hughes et al. [35
] have shown that high-carbohydrate diets do not improve insulin sensitivity in older adults. However, this does not take into account that the metabolic response varies substantially between carbohydrates, as evidenced by different glycemic and insulinemic responses [3
]. Diets that include carbohydrates with a low-glycemic response result in lower glucose and lipid levels when compared to high-glycemic diets [8
]. While there are no long-term clinical trials examining the effects of high- or low-glycemic diets on insulin resistance or obesity in the elderly, two small clinical trials report greater weight loss utilizing a low-glycemic approach [8
]. Studies conducted by our group observed improvements in insulin and glucose metabolism in insulin-resistant cirrhotic patients after a low-glycemic diet [39
]. In addition, two epidemiological studies indicate that eating a high-glycemic diet is a significant independent predictor of diabetes risk [40
]. These data suggest that low-glycemic diets may be more advantageous than high-glycemic diets in reducing obesity and insulin resistance. Data from the present study support these observations. While our subjects were not provided a specific diet, there is evidence that the subjects who selected lower-glycemic foods experienced greater improvements in insulin sensitivity. Importantly, this was achieved without significantly changing energy intake. While the glycemic content of the diet may not be the sole determinant of the markedly improved insulin sensitivity in these individuals, the data strongly suggest that reducing the glycemic load may provide a way to optimize the reversal of insulin resistance in obese subjects.
There are good reasons to think that the combined effect of exercise and reduced glycemic load might synergistically affect insulin resistance. Obesity, lipotoxicity, and low levels of chronic inflammation are among the factors that contribute to insulin resistance. Studies show that low-glycemic diets are highly effective in reducing body weight [8
]. Likewise, exercise is effective in lowering body weight, particularly when performed at the level prescribed for the subjects in the current study [11
]. Both exercise and low-glycemic diets have been shown separately to be highly effective in reducing circulating lipids, including low-density lipoproteins [38
]. Exercise and low-glycemic diets have also been shown to separately reduce inflammation in obese and insulin-resistant adults [43
]. Further support may be gleaned indirectly from studies that have combined acute exercise and low- or moderate-glycemic meals, resulting in enhanced performance and hepatic glucose regulation [19
]. While these data suggest that the two interventions may be metabolically compatible during exercise, there are no data to show how the two might interact over an extended period of time. Compared to the rest of the study subjects, the subgroup of ‘super-responders’ in the current study reported a change in food choices that resulted in a shift from a high- to a low-glycemic diet. These subjects experienced substantial improvements in insulin sensitivity that were accompanied by greater weight loss, and greater improvements in circulating lipids, particularly triglycerides. In contrast, plasma tumor necrosis factor-α levels were similar for the main group and the subgroup after the intervention. The latter observation suggests that reversal of inflammation does not explain the improved insulin resistance, at least based on the limited evaluation of this outcome, while greater reductions in body weight and lowering of lipids may play a role and contribute to how a low-glycemic diet coupled with exercise can have such a dramatic effect on insulin resistance.
In summary, we have demonstrated that insulin resistance is reduced following 12 weeks of supervised aerobic exercise. These data also show that in a limited subset of subjects consuming a low-glycemic diet during the exercise intervention there is an even greater improvement in insulin sensitivity than when subjects maintain their normal moderate/high-glycemic diet. Such improvements in insulin sensitivity suggest a possible synergism between exercise and a low-glycemic diet that can be used to treat insulin resistance and type 2 diabetes in obese adults more effectively. Larger-scale clinical trials are needed to determine whether a lifestyle intervention that includes exercise and a low-glycemic diet is capable of effectively reducing the morbidity and mortality associated with insulin resistance and diabetes.