Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological and dietary interventions is used to prevent the progression of pre-diabetes to T2DM. However, poor patient compliance leads to negligence of the dietary intervention and thus reduced drug efficiency. Oleanolic acid (OA) has been reported to possess anti-diabetic effects in type 1 diabetic rats. However, the effects of this compound on pre-diabetes have not yet been established. Consequently, this study sought to evaluate the effects OA on a diet-induced pre-diabetes rat model. Pre-diabetic male Sprague Dawley rats were treated with OA in both the presence and absence of dietary intervention for a period of 12 weeks. The administration of OA with and without dietary intervention resulted in significantly improved glucose homeostasis through reduced caloric intake, body weights, plasma ghrelin concentration and glycated haemoglobin by comparison to the pre-diabetic control. These results suggest that OA may be used to manage pre-diabetes as it was able to restore glucose homeostasis and prevented the progression to overt type 2 diabetes.

Pre-diabetes is a long-lasting condition that precedes type 2 diabetes (T2D). T2D has been shown to suppress the immune response. However, it remains unclear if immune activation occurs before the onset of T2D during the progression of the pre-diabetic state. This study sought to characterize the changes in general immunity occurring during the progression from pre-diabetes to T2D. Male rats were fed a high-fat high-carbohydrate diet for 20 weeks (pre-diabetes induction period) and kept on the same diet being monitored for a further 12 weeks (experimental period). Blood was collected for haemocytometer analysis on week 0, 4, 8, and 12 of the experimental period after which the animals were sacrificed. Plasma was collected from centrifuged blood for ELISA (TNF-α, CRP, P-selectin, CD40 L, fibrinogen, and IL-6). Blood neutrophils percentage significantly decreased at week 12 possibly due to recruited neutrophils migrating to an inflamed area such as visceral adipose tissue as further observed. Due to hyperglycaemia, there was significant increase in blood lymphocytes percentage at week 12. Blood monocytes percentage significantly increased at week 12. Monocytes recruited and circulated in blood due to hyperglycaemia for glucose uptake to decrease it from circulation. Blood eosinophils percentage significantly decreased at week 12. Eosinophils migrated to inflamed areas such as visceral adipose tissue as further observed. Blood basophils percentage significantly increased due to their recruitment and activation. TNF-α, CRP, and IL-6 increased significantly after 12 weeks. There was also upregulation of fibrinogen, P-selectin, and CD40L. The results of this study show that there are changes in immune cells concentration and that immune cells such as neutrophils and eosinophils migrate to inflamed areas such as adipose tissue. There is also upregulation of various inflammatory cytokines. Based on these findings, immune activation begins during the pre-diabetic state as there is upregulation of inflammatory markers.

The pathogenesis of prediabetes is associated with risk factors such as chronic consumption of an unhealthy diet. Recent studies have reported that diet-induced pre-diabetes is also associated with risk factors of cardiovascular complications, hence this study was aimed at evaluating the effects of oleanolic acid (OA) on pre-diabetes rats. Pre-diabetes was induced by chronic exposure of Sprague Dawley rats (SD) to high-fat high-carbohydrate diet (20 weeks), whereas the non-pre-diabetes control (NC) was given standard rat chow. Pre-diabetes animals were grouped into five groups namely prediabetes control (PC), metformin treated (Met), metformin with diet intervention (Met + DI), oleanolic acid treated (OA), and oleanolic acid with diet intervention (OA + DI) then treated for 12 weeks. At the end of treatment, all animals were sacrificed where organs and tissues were harvested for biochemical analysis and histological studies. The results showed that PC had a significantly higher triglycerides (TGs), low density lipoprotein cholesterol (LDL-C, interleukin-6(IL-6), tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), mean arterial pressure (MAP) and hearts weights in comparison to NC (p < 0.05). However, the administration of OA, in both the presence and absence of dietary intervention showed a significant decrease in TGs, LDL-C, IL-6, TNFα, CRP, MAP, hearts weights (p < 0.05). In conclusion, the administration of OA was able to lower the risks of developing CVDs in pre-diabetes rat model through ameliorating dyslipidaemia, oxidative stress, hypertension, and low-grade inflammation. Therefore OA has the potential to be used as an alternative treatment to prevent the onset of CVDs during pre-diabetes stage even in the absence of dietary and lifestyle intervention.

Background: The increased prevalence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) patients is becoming a worldwide health burden. Studies have indicated, however, that the onset of NAFLD occurs during pre-diabetes, a condition that often precedes the onset of T2DM. Oleanolic acid has been reported to improve glucose homeostasis in diet-induced pre-diabetes; however, the effects of this triterpene on liver function have not been evaluated. Purpose: This study was aimed at evaluating the therapeutic effects of oleanolic acid (OA) on selected markers of NAFLD in a pre-diabetes rat model. Methods and materials: Pre-diabetes was induced by exposing Sprague Dawley rats to a high-fat high-carbohydrate diet for 20 weeks. The pre-diabetic rats were then treated with OA (80 mg/kg) or metformin (500 mg/kg) in the presence and absence of dietary interventions for a period of 12 weeks. The effects of OA were evaluated on parameters including plasma triglycerides (TGs), very low-density lipoprotein (VLDL) particles, bilirubin, AST, ALT, SREBP and antioxidant profile while the livers were collected for histological analysis. Results: The findings of this study showed that the administration of OA to pre-diabetic rats ameliorated body/liver weights ratio and significantly decreased plasma triglycerides (TGs) and VLDL. Furthermore, OA also ameliorated hepatic oxidative stress, lowered the SREBP expression and intrahepatic TGs. In addition, OA administration decreased plasma concentrations of bilirubin and liver damage enzyme biomarkers. Conclusion: The findings of the study suggest that OA ameliorates the risk of developing pre-diabetes-related NAFLD through the prevention of intrahepatic fat accumulation while also lowering hepatic inflammation.

Background. Studies suggest thatMomordica balsamina(intshungu) possesses hypoglycaemic effects. The effects ofMomordica balsaminaon diabetic complications such as DN, however, have not been established. Accordingly, this study seeks to investigate the effects ofM. balsaminaon kidney function in STZ-induced diabetic rats.Methods. Methanolic extracts (ME) ofM. balsamina’s leaves were used in this study. Short-term effects ofM. balsaminamethanolic extract on kidney function and MAP were studied in STZ-induced diabetic rats treated twice daily withM. balsaminamethanolic extract (250 mg/kg), insulin (175 μg/kg, s.c.), and metformin (500 mg/kg) for 5 weeks.Results.M. balsaminamethanolic extract significantly increased Na⁺excretion outputs in STZ-induced diabetic rats by comparison to STZ-diabetic control rats.M. balsaminamethanolic extract significantly increased GFR in STZ-diabetic rats with a concomitant decrease in creatinine concentration and also reduced kidney-to-body ratio, albumin excretion rate (AER), and albumin creatinine ratio (ACR).M. balsaminamethanolic extract significantly reduced MAP in STZ-diabetic animals by comparison with STZ-diabetic control animals. These results suggest thatM. balsaminamethanolic extract not only lowers blood glucose but also has beneficial effects on kidney function and blood pressure.Conclusion. These findings suggest thatM. balsaminamay have beneficial effects on some processes that are associated with renal derangement in STZ-induced diabetic rats.

Pre-diabetes is a condition that precedes type 2 diabetes mellitus (T2DM) that is characterised by elevated glycated haemoglobin (HbA1c). The management of pre-diabetes includes the combination of dietary and pharmacological interventions to increase insulin sensitivity. However, poor patient compliance has been reported with regard to dietary interventions, therefore, new alternative drugs are required that can be effective even without the dietary intervention. In our laboratory, we have synthesised a novel ruthenium complex that has been shown to have elevated biological activity. This study investigated the effects of this complex in both the presence and absence of dietary intervention on glucose handling in a diet-induced pre-diabetes rat model. Pre-diabetic animals were randomly assigned to respective treatment groups. The ruthenium complex was administered to pre-diabetic rats once a day every third day for 12 weeks. The administration of the ruthenium complex resulted in reduced fasting blood glucose, food intake, and body weight gain which was associated with decreased plasma ghrelin, insulin, and HbA1c levels in both the presence and absence of dietary intervention. The administration of the ruthenium complex ameliorated glycaemic control and insulin sensitivity in pre-diabetic rats. The results of this study warrant further investigations as this compound could potentially be able to re-sensitize insulin resistant cells and reduce the incidence of T2DM.