PLoS One. 2014 Jun 6;9(6):e99062.

Oxidative stress in patients with type 1 diabetes mellitus: is it affected by a single bout of prolonged exercise?

Francescato MP, Stel G, Geat M, Cauci S.

Department of Medical and Biological Sciences, University of Udine, Udine, Italy.



Presently, no clear-cut guidelines are available to suggest the more appropriate physical activity for patients with type 1 diabetes mellitus due to paucity of experimental data obtained under patients’ usual life conditions. Accordingly, we explored the oxidative stress levels associated with a prolonged moderate intensity, but fatiguing, exercise performed under usual therapy in patients with type 1 diabetes mellitus and matched healthy controls. Eight patients (4 men, 4 women; 49±11 years; Body Mass Index 25.0±3.2 kg·m(-2); HbA1c 57±10 mmol·mol(-1)) and 14 controls (8 men, 6 women; 47±11 years; Body Mass Index 24.3±3.3 kg·m(-2)) performed a 3-h walk at 30% of their heart rate reserve. Venous blood samples were obtained before and at the end of the exercise for clinical chemistry analysis and antioxidant capacity. Capillary blood samples were taken at the start and thereafter every 30 min to determine lipid peroxidation. Patients showed higher oxidative stress values as compared to controls (95.9±9.7 vs. 74.1±12.2 mg·L(-1) H2O2; p<0.001). In both groups, oxidative stress remained constant throughout the exercise (p = NS), while oxidative defence increased significantly at the end of exercise (p<0.02) from 1.16±0.13 to 1.19±0.10 mmol·L(-1) Trolox in patients and from 1.09±0.21 to 1.22±0.14 mmol·L(-1) Trolox in controls, without any significant difference between the two groups. Oxidative stress was positively correlated to HbA1c (p<0.005) and negatively related with uric acid (p<0.005). In conclusion, we were the first to evaluate the oxidative stress in patients with type 1 diabetes exercising under their usual life conditions (i.e. usual therapy and diet). Specifically, we found that the oxidative stress was not exacerbated due to a single bout of prolonged moderate intensity aerobic exercise, a condition simulating several outdoor leisure time physical activities. Oxidative defence increased in both patients and controls, suggesting beneficial effects of prolonged aerobic fatiguing exercise.

PMID: 24905823



Oxidative stress is a condition where the increased formation of free radicals overwhelms the available antioxidant capacity. It is involved in many human diseases (e.g. atherosclerosis, cardiovascular and neurological disease) as well as in aging. Oxidative stress is involved in the development and progression of diabetes mellitus and its complications. Regulated production of free radicals, however, participates in several beneficial physiological processes, e.g. it is required for insulin to exert its physiological action (1). In patients with type 1 diabetes mellitus (T1DM) both increases in oxidative stress, as well as unchanged levels compared to healthy controls were reported.

Regular physical activity can reduce the risk of several chronic diseases such as cardiovascular disease, cancer, hypertension, obesity, and premature death, even in patients with diabetes mellitus (2). Nevertheless, there is indirect evidence, on healthy subjects, that exercise may promote oxidative stress (3). Patients with diabetes might be engaged, like healthy subjects, in occasional outdoors leisure time physical activities (e.g., hiking, hill walking, biking, cross-country skiing), which tend to be prolonged in time, while being light to moderate in intensity. The effects of such prolonged fatiguing physical activity in T1DM patients were largely unexplored, in particular in patients exercising without modifying their usual insulin therapy.

In the present investigation, 8 patients with T1DM (4 men and 4 women) and 14 age- and gender-matched healthy subjects (8 men and 6 women) performed a 3-h (from 10:00 AM to 1:00 PM) walk on a treadmill (Saturn, H-P Cosmos, Traunstein, Germany). Venous blood samples were drawn at regular intervals for clinical chemistry analysis and capillary samples (50 mL) were obtained to determine oxidative stress (FORT tests; Calligari, IT) and the free total oxidant defense (FORD tests; Calligari, IT).

Actual exercise intensity during the walks, expressed as percentage of maximal individual’s heart rate, amounted on average to about 30% of maximal heart rate (i.e. about 101 bpm). As expected, glycemia was higher in patients than in controls in all the tested conditions (p<0.01). In healthy subjects, glycemia did not change significantly throughout the exercise amounting on average 4.6 mmol·L-1, whereas in patients glycemia fell from about 8.0 mmol·L-1 at the start to about 5.9 mmol·L-1 at the end of the exercise (p<0.05). Also insulin concentrations were higher in patients as compared to controls (p<0.005), although in both groups it decreased by the end of the exercise (p<0.001). Oxidative stress values (evaluated by FORT test) remained constant in both groups of volunteers throughout the 3-h walk (Figure 1), being higher in patients than in controls at each time point (p<0.001). On the opposite, total oxidant defense (evaluated by FORD test) increased in a similar way in both groups from the start to the end of the exercise (p<0.02). Interestingly, oxidative stress was positively related to the HbA1c values (p<0.005), and inversely related to the serum concentration of uric acid (p<0.005).



Fig1Col  Fig 1. Oxidative stress values throughout the 3-h walks. Red dots are T1DM patients and green dots are healthy control subjects.


The present study showed that a single bout of prolonged moderate intensity aerobic exercise did not increase the oxidative stress, in both T1DM patients and healthy subjects, despite patients showed higher oxidative stress levels throughout. In contrast, an increase in the anti-oxidant defense was observed at the end of the exercise in all volunteers.

Physical exercise is strongly recommended in T1DM patients because of its numerous health benefits (2), but it might also cause oxidative stress (3), resulting in a potentially harmful condition. Our results suggest that a 3-h walk, simulating several outdoor leisure time physical activities, although fatiguing, was not able to provoke a large enough increase in free radical production to overwhelm the antioxidant defenses. Notably, the serum antioxidant capacity was augmented by exercise, suggesting that the pathways that generate free radicals and those stimulating the antioxidant defense are quite unrelated. Indeed, reactive oxygen species produced by increased muscular activity may act as signals resulting in upregulation of powerful antioxidant enzymes. Thus, moderate exercise can be considered also an antioxidant with beneficial effects (4).

It should be pointed out here that patients with T1DM often require some extra carbohydrates before/during the effort to prevent an excessive fall of glycemia. This extra amount of carbohydrates might be considered a caloric load that will be oxidized in mitochondria, resulting in a potential higher production of free radicals. Nevertheless, there is evidence that the whole-body carbohydrates oxidation rate is not different between T1DM patients receiving appropriate amounts of carbohydrates as compared to control subjects, who did not receive carbohydrates supplementation during exercise.

The relationship we observed between oxidative stress and glycated hemoglobin (HbA1c) levels agrees with a similar relationship reported by others. Indeed, prolonged periods of improved glycemic control result in a reduction of the oxidative stress in patients with diabetes.

We unexpectedly found an inverse relationship between oxidative stress and serum uric acid levels. Indeed, uric acid is a powerful antioxidant and scavenger of singlet oxygen and radicals. The lower uric acid levels in T1DM patients in comparison to controls were consistent with few previous findings where a significantly reduced level of plasma uric acid amongst subjects with T1DM was reported. It remains to be clarified whether the low uric acid concentration observed in patients is a consequence or a cause of the high oxidative stress levels observed in these subjects. Although future research is warranted to better evaluate this relationship on a larger group of patients, clinicians should carefully monitor uric acid, due to its association with the oxidative stress, in particular in patients with T1DM.

In conclusion, a 3-h walking exercise did not worse the oxidative stress levels, while it increased the oxidative defense, thus suggesting that a single bout of even prolonged moderate intensity aerobic exercise can be safely performed as leisure time outdoors activity also by patients with type 1 diabetes.



1. Bashan N, Kovsan J, Kachko I, Ovadia H, Rudich A (2009) Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species. Physiol Rev 89: 27-71.
2. Chimen M, Kennedy A, Nirantharakumar K, Pang T, Andrews R, et al. (2012) What are the health benefits of physical activity in type 1 diabetes mellitus? A literature review. Diabetologia 55: 542-551.
3. Powers SK, Nelson WB, Hudson MB (2011) Exercise-induced oxidative stress in humans: Cause and consequences. Free Radic Biol Med 51: 942-950.
4. Viña J, Sanchis-Gomar F, Martinez-Bello V, Gomez-Cabrera M (2012) Exercise acts as a drug; the pharmacological benefits of exercise. Br J Pharmacol 167: 1-12.

Contact Information:

Dr. Maria Pia Francescato
Department of Medical and Biological Sciences
University of Udine
p.le M. Kolbe 4
33100 – Udine (Italy)
phone: +39 0432494336
fax: +39 0432494301

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