4.3.1 The effects on insulin resistance in mothers and their offspring
Factors associated with insulin resistance include obesity, particularly abdominal obesity, increased waist circumference, familial history of type 2 diabetes, sedentary lifestyle, hypertension, and fatty liver. Furthermore, is insulin resistance also characterized by hypertriglyceridemia, lower concentrations of high-density lipoprotein (HDL) cholesterol in blood, and increased inflammation. As a result, glucose metabolism deteriorates, resulting in hyperglycemia, impaired glucose tolerance or overt type 2 diabetes mellitus. Weight loss and regular moderate intensity physical activity/exercise are significant factors for insulin resistance prevention and/or treatment (Papakonstantinou et al., 2022). In our work, we used voluntary physical exercise as an intervention and it was observed to improve the glycemic profile in the mothers and their offspring.
The glycemic profile in mothers was altered with FRU and the VPE had the potential to modulate this effect, in different periods. Regarding fasting glycemia and insulin tolerance test, in pre-pregnancy mothers we observed an increase in fasting glycemia and insulin resistance in the FRU group, while in combination with modulation the exercise intervention (FRU+VPE group) there was a decrease in fasting glycemia and modulation of insulin resistance. During pregnancy, we observed a similar change with a decrease in fasting glucose in response to the physical activity interventions (FRU+VPE/Water+VPE and FRU+VPE/Water groups). In contrast, in the post-pregnancy period, an increase in fasting glucose was observed in the Water+VPE group, however we did not observe insulin resistance in any group during this period.
In the female offspring, we did not observe changes in fasting blood glucose in the fructose group, but a possible modulation in the FRU+VPE/Water+VPE group, due to the decrease in blood glucose. However, in males no differences were found, only a decrease in the area under the curve in the insulin tolerance test. With these results, we observed that fructose exposure can cause a glycemic imbalance in the mothers and that physical exercise may have the potential to modulate, but not enough to be a modulator of insulin resistance in offspring.
Similar to our result, Mamikutty et al. (2014) observed that fructose consumption at doses of 20% and 25% for a period of 8 weeks was able to alter food consumption and lead to metabolic disorders such as obesity, dyslipidemia, hypertension and hyperglycemia. This change in the glycemic profile and insulin resistance is due to the fact that, unlike glucose, fructose does not stimulate insulin secretion from pancreatic β cells. Furthermore, reduced insulin sensitivity in the state of hypertriglyceridemia can lead to the formation of hyperglycemia (Bray et al., 2004). Furthermore, excess fructose can increase the production of its triosis phosphate metabolites and enter the Krebs cycle for intrahepatic oxidation or synthesis of glucose, lactate and/or lipids (Horst and Serlie, 2017). The change in the gestational period, on the other hand, corroborates the results found in the study by Magenis et al. 2020 and 2022, where the consumption of fructose during the gestational period in mice was able to increase the fasting glucose of the females and offspring. However, we did not observe insulin resistance in the post-pregnancy period and in the offspring, and the same was found in previous studies (Magenis et al., 2020; Magenis et al., 2022).
Pregnancy is characterized by myriad metabolic adaptations that affect glucose levels and may also alter the effects of exercise on glycemic control. Glucose is the primary source of fetal energy and is required for optimal fetal growth and development. Accordingly, hormonal changes during pregnancy and in the placenta drive preferential feto-placental glucose delivery, since maternal glucose production increases and maternal insulin sensitivity is reduced as pregnancy progresses, particularly at the level of skeletal muscle, in order to shift glucose to the developing fetus (Motola and Artal, 2016; Barbour et al. 2007). We believe that the mechanisms of fructose metabolic disorders are more associated with an increase in free fatty acid, so there is an increase in lipotoxicity and, consequently, oxidative stress and inflammation, often not causing type 2 diabetes mellitus initially, only a glycemic imbalance (Lipke et al. al., 2022).
Based on this assumption, physical exercise is necessary as an adjuvant for the prevention and treatment of obesity and associated comorbidities. To date, studies show that resistance and aerobic exercises are recommended as effective treatments for people with obesity and type 2 diabetes mellitus (Yang et al., 2014; Xiao and Fu, 2015; Villareal et al., 2017; García-Hermoso et al., 2018). Furthermore, the ACOG recommends the practice of physical exercise during the pre- and gestational period in order to prevent gestational diabetes (ACOG, 2018). Among healthy pregnant women, regular exercise during pregnancy reduces insulin resistance and upregulates skeletal muscle glucose transporter GLUT4, (Davenport et al., 2018). Although our glycemic results are not conclusive regarding insulin resistance, we suggest that physical exercise has the potential to control the mother’s fasting glucose and can bring benefits to her offspring, as described in the literature.