The association between incretin hormones concentrations and the development of diet-induced Prediabetes.

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.