The association between incretin hormones concentrations and the development of diet-induced Prediabetes.
Loading...
Date
2023
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
The increase in the prevalence of type two diabetes mellitus(T2DM) is attributed to unhealthy lifestyles
and high-calorie diets. T2DM is a chronic metabolic condition characterised by impaired insulin
function and high blood glucose concentration. Prediabetes is an intermediate hyperglycemic condition
that frequently occurs before the onset of T2DM. This condition is characterised by a gradual reduction
of insulin sensitivity by insulin receptors in insulin-dependent cells, frequently followed by significantly
high plasma glucose levels. In this condition, the blood glucose concentration is insufficient to diagnose
T2DM. Studies have looked at how incretin peptides affect the pathology of T2DM. However, the link
between incretin peptide levels and the onset of prediabetes remains unknown. Additionally, the effect
of a low carbohydrate, high unsaturated fat diet on incretin levels during the reversal of prediabetes has
not been established. Thus, this study aimed to assess the role of incretin levels in the emergence of
prediabetes and the effect of a low carbohydrate, high unsaturated fat diet on incretin levels during the
reversal of prediabetes.
Methods
The first study was conducted using 24 male Sprague-Dawley rats, divided into two groups given a
standard rat diet (NPD) (=12), while the other group was given a high-fat high carbohydrate (HFHC)
(n=12) diet. Six animals from each group were sacrificed at week 10 and week 20, and blood was
collected for biochemical analysis at each time interval. After 20 weeks, the HFHC fed group was found
to be prediabetic and were therefore named the prediabetic group (PD). At week 10, the NPD group had
the following mean measurements for the NPD and HFHC groups respectively: Glucose (4.3mmol/L
and 5.9mmol/L), Insulin (40.26 and 118.32pmol/L), HbAc1 (4.9 and 5.15%), GIP (9.308 and
12.91pmol/L),GLP-1 (18.53 and 15.73pmol/L), Leptin(1.92 and 1.08mmol/L), and Ghrelin (122.1 and
186.5pmol/L ). At week 20, the PD group had the following mean measurements for the NPD and PD
groups: Glucose (4.4mmol/L and 7.35mmol/L), Insulin (41.18 and 159.42pmol/L), HbAc1 (4.7 and
6.65%), GIP (10.03 and15.1pmol/L),GLP-1 (21.52 and 6.73pmol/L), Leptin (2.16 and 0.78mmol/L ),
Ghrelin (124.2and 210.63pmol/L).
After 20 weeks of pre-diabetes induction, the second study began with 18 male Sprague-Dawley rats.
Group A continued with the standard diet and was used as a non-prediabetic control (NPDC) (n=6).
The pre-diabetic group B (n=12) was split into two experimental groups. One of the groups continued
a HFHC diet and served as the pre-diabetic control group (PD)(n=6). In contrast, the other group had a
diet intervention where the diet was changed to a low carbohydrate-high unsaturated fats diet (PD+DI)
(n=6). All groups were then maintained on their respective diets for a further 12 weeks. At week 32, the
PD+DI group had the following mean measurements: Glucose (5.367mmol/L), Insulin (188.5ng/ml),
HbAc1 (4.62%), GIP (24.08pg/ml) , GLP-1, Leptin (1.267ng/ml) , and Ghrelin (17.09pg/ml).
XVI
Results
In the first study, after 20 weeks, the HFHC diet resulted in moderate hyperglycaemia, elevated plasma
insulin, elevated HbA1c and insulin resistance in the PD group compared to the NPD group. There were
also significantly increased GIP and ghrelin concentrations with significantly low GLP-1 and leptin
concentrations in the PD group compared to the NPD group. Interestingly, at week 10, there was
moderate hyperglycaemia, elevated plasma insulin, elevated HbA1c and insulin resistance in the HFHC
group. There were also significant GIP and ghrelin levels with significantly low GLP-1 and leptin
concentrations, but there was no prediabetes.
In the second study, there were significantly reduced blood glucose levels, plasma insulin levels,
HOMA-IR index, and HbA1c in the PD+DI group compared to the PD group. In the PD+DI group,
there are significantly reduced GIP and ghrelin levels with significantly increased GLP-1 and leptin
concentrations compared to the PD group. However, when the PD-DI group is compared to the NPDC
group, there is no significant difference in all measured parameters.
Conclusion
The first study's findings show that chronic ingestion of a HFHC diet causes dysregulation of incretin
hormones from week 10, while prediabetes was only diagnosed at week 20. This dysregulation of
incretin hormones precedes the onset of prediabetes and may trigger chronic insulin stimulation, leading
to prediabetes development. In the second study, we observed the effect of diet on incretins as they play
a significant role in developing and reversing pre-diabetes. Chronic consumption of a HFHC diet led to
elevated blood glucose and insulin concentration, resulting in abnormal concentrations of incretins. The
abnormal incretins then maintained this state of hyperglycemia and hyperinsulinemia, resulting in
prediabetes. Chronic consumption of a LCHF by the pre-diabetic rats led to reduced concentrations of
incretins, which could have led to a reduced HbA1c and eventually to the reversal of pre-diabetes. The
results of this study suggest that incretin concentrations preceded the development of prediabetes and
may even have a role in its development as well as its reversal.
Description
Masters Degree. University of KwaZulu-Natal, Durban.