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Background: Diabetes mellitus (DM) is a disorder in which blood sugar levels are abnormally high because either absolute or relative insulin deficiency. Treatment of diabetes involves diet, exercise, education and for most people, drugs. Oral antidiabetic drugs and/or insulin doses may be affected by co-administration of many drugs including aspirin. Dose adjustments may be necessary. The pain killer effect of aspirin is best known for its effects on the two cyclooxygenase enzymes (COX1 & COX2), but, recently, aspirin could specifically inhibit the protein I-kappa-β-kinase beta (IKK-beta). This kinase is used for its role in the cascade of signals that activate the nuclear factor kappa-b (NF-kappa-B) family of cellular genes which regulate inflammatory and immune responses. Now, it turns out that IKK-beta also works in another pathway to contribute to insulin resistance by interfering with insulin signaling. Objective: In view of the recent rodent data demonstrating a potentially important role of IKKβ in mediating insulin resistance and the ability of salicylates to inhibit IKKβ activity, we decided to examine the role of different doses of aspirin (low, moderate and high) in experimentally induced diabetic rats. Materials and Methods: DM in rats were induced by administration of nicotinamide (NAD), 15 min prior to the single dose of streptozotocin STZ i.p. Ninety male albino rats were used in this study. They were divided into 6 main groups. The first was served as control which receives no medications. The second group was diabetic induced rats as mentioned above. The third group was controlled by insulin after induction of D.M. Groups from the fourth to the six consist of 20 diabetic induced rats and further subdivided into rats taking either aspirin alone in different doses (low, moderate or high) or aspirin and insulin. At the end of the protocol, fasting blood sugar level (FBS), glycosylated hemoglobin (HBA1c%), total serum proteins, C-peptide, lipid profile and C-reactive proteins were measured. Results: Different doses of aspirin showed that moderate and to a greater extent high dose aspirin administration to diabetic rats have greater impact on fasting blood glucose levels whether treated with insulin or not. Again, HBA1c% in diabetic rats treated with insulin and receiving HDA was lower than diabetic rats treated with insulin only or even taking LDA in addition. On the contrary, different doses of aspirin (LDA, MDA&HDA) administration to diabetic rats have no any influence on HBA1c% as compared to normal non-diabetic rats. TGs in diabetic rats receiving MDA alone was elevated as compared to normal non-diabetic rats. Again, moderate and HDA in diabetic rats not taking insulin had high TGs level as compared to diabetic rats treated with insulin only. Conclusion: The study concluded that the inflammatory pathways hold a substantial part in insulin resistance in type 2 DM. The influence of salicylate compounds on insulin sensitivity is multifactorial especially in high doses, and involves both beneficial a...

Objectives Diabetes mellitus is associated with oxidative stress that leads to inflammation and diabetic nephropathy. This study aimed to determine the possible renoprotective effects of the antioxidants melatonin, vitamin D and vitamin E in diabetic rats. Methods We divided 108 albino rats into 12 groups. G1 group was fed a normal diet and did not receive any medication. G2 to G4 consisted of non-diabetic rats that were treated as follows: G2 with melatonin; G3 with vitamin E; G4 with vitamin D. Groups G5 to G12 consisted of diabetic rats that were treated as follows: G5 received no medication; G6 treated with insulin; G7 treated with melatonin; G8 treated with melatonin and insulin; G9 treated with vitamin E; G10 treated with vitamin E and insulin; G11 treated with vitamin D and G12 treated with vitamin D and insulin. Two months after treatment commenced, histological and biochemical examinations of glucose profile, oxidative stress status, renal function, homocysteine and TNF-α were performed. Results Total antioxidant capacity (TAC) increased significantly in groups G2, 7, 8, 10 and 11. TNF-α significantly increased in G2, but decreased in all other groups. Creatinine increased significantly in groups G5, 6, 7, 8, 9, 11 and 12. In the kidneys of the diabetic rats, thickened capillary basement membrane, diffuse mesangial sclerosis and nodular glomerulosclerosis was observed. Rats treated with melatonin showed marked improvement in these symptoms. However, in those treated with vitamin D and E, thickened capillary basement membrane and mesangial sclerosis was still present. Conclusions Melatonin, administered either with or without insulin had a significant biochemical antioxidant effect and histological renoprotective effect. Conversely, vitamin D and E did not appear to have any effects on the parameters measured.

BackgroundDiabetes mellitus (DM) is a serious chronic disease, with multiple complications including hepatopathy associated with imbalance of the oxidative status. The purpose of this study is to observe possible protective effects of vitamin-D and melatonin on glucose profile, antioxidant-oxidant status, lipid peroxidation, and histopathological protection of the liver in streptozotocin-induced diabetic rats.MethodsEighty three male albino rats were divided into nine groups as follows: G1 (n = 10) Normal control rats; G2 (n = 8) were normal rats treated with melatonin only; G3 (n = 10) were normal rats treated with vitamin D only; G4 (n = 9) were diabetic rats, which received no medications; G5 (n = 8) were diabetic rat treated with insulin only; G6 (n = 10) were diabetic rats treated with melatonin only; G7 (n = 9) were diabetic rats treated with melatonin and insulin; G8 (n = 9) were diabetic rats treated with vitamin D only; G9 (n = 10) were diabetic rats treated with vitamin D and insulin. Two months post treatment, blood was collected to measure: Fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), fructosamine (FA), total antioxidant capacity (TAC), malondialdahyde (MDA). livers were isolated for histopathological study.ResultsAs compared to normal rats, our results demonstrate that glucose, fructosamine and HbA1c levels is increased in diabetic groups and declined to lesser levels in treated groups. TAC level of diabetic rats is not significantly changed. Vitamin D administration significantly increased TAC while it is not changed with melatonin either in treated or non-treated groups. The liver of diabetic rats shows only mild focal microvesicular fatty degeneration. The liver of diabetic rats treated with insulin shows degeneration of cell edema in the stroma. The liver of diabetic rats treated with melatonin with or without insulin, exhibited marked improvement. The liver of diabetic rats treated with vitamin D with or without insulin, shows degeneration of cells and edema in the stroma.ConclusionOur results demonstrated the beneficial antioxidant effect of vitamin D administration to normal and diabetic rats as compared to melatonin. Nevertheless, melatonin still shows more therapeutic effect on liver cell injury induced by induction of diabetes.

Alzheimer's disease (AD) is a complex neurodegenerative disease. There is epidemiological evidence that heart failure (HF) patients are at higher risk of developing AD, and the impact of sacubitril/valsartan, the first angiotensin receptor-neprilysin inhibitor (ARNI) approved for HF, on cognitive functions is still controversial. To investigate the effect of sacubitril/valsartan on cognitive functions in colchicine-induced AD rat model. Forty adult male Wistar rats were equally allocated into four groups (each of 10 rats): Group I: normal control, Group II: intracerebroventricular injection of colchicine (15 μg/5 μl/bilaterally), Group III: colchicine (15 μg/5 μl/bilaterally, icv) + oral sacubitril/valsartan (100 mg/kg/day) for 25 days, and Group IV: colchicine (15 μg/5 μl/bilaterally, icv) + oral valsartan (50 mg/kg/day) for 25 days. Behavioral assessment was done using Morris water maze and passive avoidance tasks. Biochemically, β-amyloid (1-40 and 1-42) peptides, oxidative stress (malondialdehyde and superoxide dismutase) and inflammatory (tumor necrosis factor-alpha) parameters were measured in hippocampus and prefrontal cortex. Sacubitril/valsartan exaggerated colchicine-induced cognitive impairment in both Morris water maze and passive avoidance tasks and was associated with significant increase in β-amyloid accumulation, oxidative stress, and inflammation versus valsartan. Sacubitril/ valsartan caused deleterious effect on cognitive impairment and biochemical alterations in colchicine-induced AD rat model. Hence, special caution should be taken following long-term intake of ARNI on cognitive functions.

Diabetic dyslipidemia is a significant contributor in the pathogenesis of type 2 diabetes (T2D). The study aimed at comparing the effect of dapagliflozin, liraglutide, and atorvastatin alone or their combinations on lipids and inflammatory markers and their vascular impact in T2D rats. There were 56 male albino rats included in the study and divided into two main groups. Group A (8 rats) served as normal control. Group B (48 rats) were streptozotocin-nicotinamide-induced diabetic rats. Subgroups (B-1, B-2, B-3, B-4, B-5, and B-6) received (no medications, dapagliflozin, liraglutide, atorvastatin, dapagliflozin + atorvastatin, and liraglutide + atorvastatin), respectively. Urine albumin/creatinine ratio (UACR), glycosylated hemoglobin (HBA1c), fasting serum glucose (FSG), serum low-density lipoproteincholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), TGs, lipoprotein(a) Lp (a), serum thyrotropin (TSH), highly sensitive C-reactive protein (hs-CRP) and advanced glycation end products (AGEs), were assessed. Qualitative and quantitative histological examination of kidneys focused on renal corpuscles. Dapagliflozin improved the studied parameters but with statistically insignificant increase in LDL-C, Lp (a) and significant increase in UACR. Atorvastatin improved the studied parameters but with statistically insignificant increase in FSG and HbA1C. Liraglutide and the combination groups significantly improved all studied parameters. Histologically, liraglutide and atorvastatin produced therapeutic effect, while dapagliflozin depicted nephrotoxic effect. Combination groups resulted in better effects with normalization of most of renal corpuscles. There were positive correlations between LDL-C and hs-CRP, AGEs, TSH and mesangial expansion. Combination of atorvastatin with liraglutide can improve its vasculoprotective effect. Moreover, combination of atorvastatin with dapagliflozin can ameliorate its possible nephrotoxic effect.

Background: The association between diabetes mellitus (DM) and thyroid dysfunction is well known. However, the prevalence of having DM with thyroid dysfunction is extremely variable from one study to another. Clinical relevance of thyroid disorders in diabetic patients leads to serious consequences with metabolic compensation of diabetes. Objectives: to find the prevalence of thyroid dysfunction in T2D retrospectively through the data available in our diabetic centers among those who attended the diabetic clinics for routine checkup. Patients and methods: This is a retrospective cohort study conducted from January to August 2017 at three diabetic centers in Makkah and Jeddah, Kingdom of Saudi Arabia. Nine hundred and seventy-nine patients aged between 30 and 65years, of both genders with T2D were randomly selected. The participants` data were collected from their files, using a data collection checklist prepared for the study. Results: The study included 979 T2D patients. The prevalence of thyroid dysfunction among T2D patients was 13.1%. Mean age amongT2D patients with thyroid dysfunction was 48.8 years whereas the mean age among T2D patients with hypertension was 58.5 years. Females were significantly more presented with T2D and thyroid dysfunction. Again, T2D associated with thyroid dysfunction and hypertension was significantly more in females than males. Duration of diabetes was significantly more among patients having T2D, thyroid dysfunction and hypertension than those with only T2D and thyroid dysfunction. Oral antidiabetics (OADs) were more frequently used than combination of OADs and insulin while diet and exercise only were less, however thyroid dysfunction was more among them. Majority of our participants with T2D and thyroid dysfunction reported the occurrence of T2D first Conclusion: The prevalence of thyroid disorder is quite high amongT2D patients. Prevalence was higher in female patients and relatively younger ages. Early detection of thyroid dysfunction in patients with T2Dis of great importance and consequences.

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