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.