COVID-19-Induced Diabetes Mellitus: Comprehensive Cellular and Molecular Mechanistic Insights.

Despite evidence demonstrating the risks of developing diabetes mellitus because of SARS-CoV-2, there is, however, insufficient scientific data available to elucidate the relationship between diabetes mellitus and COVID-19. Research indicates that SARS-CoV-2 infection is associated with persistent damage to organ systems due to the systemic inflammatory response. Since COVID-19 is known to induce these conditions, further investigation is necessary to fully understand its long-term effects on human health. Consequently, it is essential to consider the effect of the COVID-19 pandemic when predicting the prevalence of diabetes mellitus in the future, especially since the incidence of diabetes mellitus was already on the rise before the pandemic. Additional research is required to fully comprehend the impact of SARS-CoV-2 infection on glucose tolerance and insulin sensitivity. Therefore, this article delves deeper into the current literature and links the perceived relationship between SARS-CoV-2 and diabetes. In addition, the article highlights the necessity for further research to fully grasp the mechanisms that SARS-CoV-2 utilises to induce new-onset diabetes. Where understanding and consensus are reached, therapeutic interventions to prevent the onset of diabetes could be proposed. Lastly, we propose advocating for the regular screening of diabetes and pre-diabetes, particularly for the high-risk population with a history of COVID-19 infection.

Preventing the onset of diabetes-induced chronic kidney disease during prediabetes: The effects of oleanolic acid on selected markers of chronic kidney disease in a diet-induced prediabetic rat model.

BACKGROUND: The prevalence of prediabetes correlates with increased incidence of chronic kidney disease (CKD). This study was aimed at investigating the effects of oleanolic acid (OA) on markers associated with CKD in the prediabetic rat model. METHODS: Prediabetes was induced by exposing male Sprague Dawley rats (150-180 g) to high-fat high- carbohydrate (HFHC) diet for 20 weeks. The prediabetic animals were further subdivided according to their treatment and treated for 12 weeks with either OA (80 mg/kg p.o) or metformin (500 mg/kg p.o) both with and without dietary intervention. 24 h fluid intake and urine output were measured every fourth week of the treatment period while the urine samples were also used for podocin quantification through PCR. The animals were then sacrificed with urine, plasma and kidneys being harvested for biochemical analysis including the measurement of aldosterone, kidney-injury-molecule-1(KIM-1), blood and urine electrolytes, estimated glomerular filtration rate (eGFR), and albumin/creatinine (Alb/Cr) ratio. RESULTS: This study observed that OA could reduce oxidative stress in the kidney while restoring plasma aldosterone and KIM-1 as well as urine electrolytes which were found to be augmented in prediabetic animals. This also correlated with normalization of GFR and Alb/Cr ratio in the OA-treated groups in both the absence and presence of dietary intervention. CONCLUSIONS: These findings suggest that OA can ameliorate renal complications in a prediabetic rat model. However, more research is needed for the elucidation of molecular mechanisms behind these effects.

Plant-derived oleanolic acid ameliorates markers of subclinical inflammation and innate immunity activation in diet-induced pre-diabetic rats.

AIMS: Sub-clinical inflammation during pre-diabetes is one of the predisposing factors that facilitates the progression of pre-diabetes to type 2 diabetes. The administration of oleanolic acid (OA) with or without dietary intervention ameliorates the metabolic and cardiovascular complications in diet-induced pre-diabetes animal models of pre-diabetes. This study aimed to investigate whether OA can also suppress immune activation and ameliorate pro-inflammatory markers. METHODS: Pre-diabetes was induced by feeding Sprague Dawley rats 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 or absence of dietary interventions for a period of 12 weeks. At the end of the treatment period, the animals were euthanised and whole blood was used for platelet and immune cell count while plasma was used for fibrinogen, cluster differentiation 40 ligand and pro-inflammatory cytokine evaluation. RESULTS: The results of this study revealed that OA, with or without dietary intervention, improved lipid metabolism by restoring high-density lipoprotein (HDL) and low-density lipoproteins (LDLs) as well as reducing platelets and immune cell counts. Furthermore, OA also decreased plasma proinflammatory cytokines, including tumour necrosis factor-α and -1ß. Markers of immune activation such as C-reactive protein, fibrinogen, and CD40L were also decreased upon administration of OA with or without dietary intervention. CONCLUSION: The findings of this study suggest that OA may provide an alternative to prevent the progression of pre-diabetes to overt diabetes. This was evident by the reduction of differential white blood cell count and proinflammatory cytokines that exercebate insulin resistance. However, more studies are needed to elucidate the molecular mechanisms and to improve efficacy.

Amelioration of risk factors associated with diabetic nephropathy in diet-induced pre-diabetic rats by an uracil-derived diimine ruthenium(II) compound.

Diabetic renal injury advances through different stages of structural and functional changes in the glomerulus, therefore treatment during the pre-diabetic state could be used as therapeutic target in the management and prevention of diabetic nephropathy (DN). Once diagnosed, dietary interventions and pharmacological therapy have been recommended to manage DN and pre-diabetic related complications. However, poor patient compliance still results, therefore newer alternative drugs are required. High fat high carbohydrates (HFHC) diet was used to induce pre-diabetes for 20 weeks. After the induction, pre-diabetic rats were randomly allocated to respective treatment groups. Subcutaneous ruthenium(II) Schiff base complex injection (15 mg/kg) was administered to pre-diabetic rats in both the presence and absence of dietary intervention once a day every third day for 12 weeks. The administration of ruthenium(II) complex resulted in reduced blood glucose, aldosterone, fluid intake and urinary output which correlated with a restoration in plasma and urinary electrolytes along with plasma antioxidants concentration. Furthermore, there was a decrease in kidney injury molecule-1 (KIM-1) concentration, albumin excretion rate (AER) albumin creatinine ratio (ACR) and mRNA expression of podocin in urine in ruthenium-treated pre-diabetic rats. Ruthenium(II) Schiff base complex ameliorated renal function while preventing the progression of DN in prediabetic-treated rats.

Hepatoprotective Effects of a Ruthenium(II) Schiff Base Complex in Rats with Diet-Induced Prediabetes.

BACKGROUND: Progressive insulin resistance in a prediabetic state has been reported to be the predominant causative factor for the development of nonalcoholic fatty liver disease. The combination of dietary modification and pharmacotherapy has been recommended to manage diabetic liver complications. However, poor patient compliance and toxicity of current drug therapy on liver function still results; thus, newer alternative drugs are required. OBJECTIVE: This study sought to investigate the hepatoprotective effects of the ruthenium(II) Schiff base complex in the presence and absence of dietary intervention in a diet-induced pre-diabetic rat model. METHODS: Prediabetic rats were randomly allocated to respective treatment groups. The ruthenium-based compound (15 mg/kg) was administered to the prediabetic rats in both the presence and absence of dietary intervention once a day every third day for 12 weeks. RESULTS: The administration of the ruthenium compound in both the presence and absence of dietary intervention resulted in the restoration of liver and body weights. This treatment also reduced liver damage enzyme biomarkers, bilirubin, and sterol regulatory element binding protein 1c concentrations in the plasma. CONCLUSIONS: The ruthenium(II) complex showed beneficial effects as it ameliorated and prevented the progression of diabetes-related liver derangements while eliminating the hepatotoxicity associated with the use of metal compounds. However, further studies are still required to further determine the physiological mechanisms behind this effect.

Plant-derived oleanolic acid ameliorates markers associated with non-alcoholic fatty liver disease in a diet-induced pre-diabetes rat model.

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.

Cardioprotective effects of a ruthenium (II) Schiff base complex in diet-induced prediabetic rats.

BACKGROUND: Prediabetes and the onset of cardiovascular diseases (CVD) are strongly related. Prolonged hyperglycemia has been identified as a major contributing factor in the pathogenesis of CVD and diabetic complications. The management of hyperglycemia and prediabetes-associated vascular complications rely on pharmacotherapy and lifestyle intervention strategies. However, patients still take the conventional drugs and neglect lifestyle intervention; therefore, newer alternative drugs are required. The synthesized ruthenium Schiff base complex has been shown to have elevated biological and antidiabetic activity. Thus, the research investigated the cardio-protective effects of ruthenium (II) Schiff base complex in diet-induced prediabetic (PD) rats. MATERIALS AND METHODS: The rats were randomly allocated to respective groups and treated for 12 weeks. Ruthenium (15 mg/kg) was administered to PD rats once a day every third day. Blood pressure and plasma glucose were monitored throughout the study. Blood and heart tissue were collected for biochemical assays. RESULTS: Ruthenium complex with dietary intervention lead to reduced mean arterial blood pressure which correlated with a restored heart to body weight ratio. Additionally, there was a significant decrease in tissue malondialdehyde and increased superoxide dismutase and glutathione peroxidase concentration in both the plasma and heart tissue. Furthermore, there was a decrease in plasma triglycerides, low-density lipoprotein with an increased high-density lipoprotein concentration in ruthenium-treated rats. This was further evidenced by reduced plasma tumor necrosis factor-α, IL-6, and cardiac C-reactive protein concentrations in ruthenium-treated rats. CONCLUSION: Ruthenium coupled with dietary intervention decreased the risk of developing cardiac injury, thus preventing CVD in prediabetes. Therefore, this complex may be a beneficial therapeutic agent in the prevention of PD cardiovascular complications.

Plant-Derived Oleanolic Acid (OA) Ameliorates Risk Factors of Cardiovascular Diseases in a Diet-Induced Pre-Diabetic Rat Model: Effects on Selected Cardiovascular Risk Factors.

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.

Effects of a Ruthenium Schiff Base Complex on Glucose Homeostasis in Diet-Induced Pre-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.

The Effects of Plant-Derived Oleanolic Acid on Selected Parameters of Glucose Homeostasis in a Diet-Induced Pre-Diabetic Rat Model.

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.