Artesunate Combined With Metformin Ameliorate on Diabetes-Induced Xerostomia by Mitigating Superior Salivatory Nucleus and Salivary Glands Injury in Type 2 Diabetic Rats via the PI3K/AKT Pathway

Polydipsia and xerostomia are the most common complications that seriously affect oral health in patients with diabetes. However, to date, there is no effective treatment for diabetic xerostomia. Recent studies have reported that artesunate (ART) and metformin (Met) improve salivary gland (SG) hypofunction in murine Sjögren’s syndrome. Therefore, aim of this study was to investigate the effect and underlying mechanism of artesunate (ART) alone and in combination with metformin (Met) on hyposalivation in type 2 diabetes mellitus (T2DM) rats. T2DM rats were induced using a high-fat diet and streptozotocin. SPF male Sprague–Dawley rats were divided into the following five groups: normal control group, untreated diabetic group, ART-treated diabetic group (50 mg/kg), Met-treated diabetic group (150 mg/kg), and ART/Met co-treated diabetic group (50 mg/kg ART and 150 mg/kg Met). ART and Met were intragastrically administered daily for 4 weeks. The general conditions, diabetes parameters and serum lipids were evaluated after drug treatment. Furthermore, we observed changes in the central superior salivatory nucleus (SSN) and SG, and changes in the AQP5 expression, parasympathetic innervation (AChE and BDNF expression), and PI3K/AKT pathway- (p-AKT, and p-PI3K), apoptosis- (Bax, Bcl-2, and Caspase3), and autophagy- (LC3 and P62) related markers expression in T2DM rats after treatment. Our results showed that ART or Met alone and ART/Met combination attenuated a range of diabetic symptoms, including weight loss, urine volume increase, water consumption increase, hyperglycemia, insulin resistance, glucose intolerance and dyslipidemia. More importantly, we found that these three treatments, especially ART/Met combination, mitigated hyposalivation in the T2DM rats via improving the central SSN and SGs damage in hyperglycemia. Our data also indicated that ART/Met attenuated SG damage though regulating the PI3K/Akt pathway to inhibit apoptosis and autophagy of SGs in the T2DM rats. Moreover, ART/Met preserved parasympathetic innervation (AChE and BDNF expression) in SGs to alleviate diabetes-induced hyposalivation likely through rescuing central SSN damage. Taken together, these findings might provide a novel rationale and treatment strategy for future treatment of diabetes-induced xerostomia in the clinic.

Impact of Diabetes Mellitus on in Hospital Adverse Outcomes after First Episode of Acute Coronary Syndrome

Objective: To determine the impact of diabetes on adverse outcomes amongst patients presenting for the first time with acute coronary syndrome. Study design: Cohort Study Methodology: A total of 340 patients were enrolled in this study. At presentation patients were divided in two equal age and gender matched groups with 170 patients in Group-A having diabetes and another 170 being non-diabetics in Group-B. Patients were followed up for period of index hospitalization and all adverse outcomes were noted in both groups as per operational definition. Results: Mean age in Group-A with diabetes was 54±12.7 years whereas in non diabetics it was56±13.12 years. In both groups there was male predominance with approximately 60% males and 40% females. In diabetic group, 38% patients had typical chest pain, 62% patients had dyspnea, 20% patients had cardiogenic shock while in non diabetic group, 20% patients had typical chest pain, 40% patients had dyspnea, 10% patients had cardiogenic shock. In diabetic group, 38% patients had heart failure, 10% patients died while in non diabetics 20% had heart failure and 5% patients died. Conclusion: This study concluded that in hospital adverse outcomes after first episode of acute coronary syndrome were more frequent in diabetic patients as compare to non diabetic patients. Keywords: Acute coronary syndrome, Adverse outcomes, First attack

The impact of vitamin D level on serum lipids in type 2 diabetes mellitus

Background: Vitamin D is considered an important regulator of many metabolic processes in the body. Its deficiency was reported to associate with many pathological conditions, with contradicting reports on its role in dyslipidemia. Objectives: To evaluate the role of vitamin D (total and/or free) in improving dyslipidemia of type 2 diabetes mellitus (T2DM). Methods: Sixty-four patients with T2DM, and 73 apparently healthy normal subjects were enrolled in the study from March to October 2020. Their fasting blood glucose, glycated hemoglobin, HbA1c, and serum lipids (cholesterol, its fractions and triglycerides) were measured in addition to total and free vitamin D. Results: There was a significant negative correlation between total vitamin D and each of cholesterol and LDL-C in the diabetic group. The correlations between serum vitamin D and all other lipid parameters (HDL-C, VLDL-C and triglycerides) were non-significant in the diabetic group, while in the control groups none of serum lipids showed significant correlations with vitamin D. Conclusions: The significant negative association of vitamin D with total cholesterol and LDLC in the diabetics reveals the important action of vitamin D in reducing the atherogenic indices, and consequent reduction in the rate of atherosclerosis and cardiovascular disease or stroke.

A comparative study on echocardiographic evaluation of left ventricular mass and function in normotensive diabetic and non-diabetic patient

Background: Cardiovascular complications account for the highest mortality in diabetic patients, mainly due to coronary artery disease and congestive heart failure. Left ventricular hypertrophy (LVH) is an ominous prognostic sign and an independent risk factor for cardiac events which is frequently present in patients living with diabetes. Aims and Objectives: The aim of the study was to evaluate the LV mass and function in normotensive diabetes patients without antihypertensive medication. Materials and Methods: 100 normotensive diabetic patients were in study group and 100 control patients were studied. Hypertension and other known causes of LVH were excluded from the study. Data were analyzed using proper statistical method. Results: Left ventricular mass index (LVMI) is significantly higher in diabetic patients as compared to control population (P<0.001). It was also observed that the means of the left ventricular posterior wall thickness, interventricular septal thickness, and the left ventricular internal diameter during diastole (in all cases P<0.001) were statistically significantly high in diabetic patients in comparison to healthy control subjects. We have found that a significant systolic dysfunction in diabetic group and diastolic dysfunction also very common in diabetic group than the control group. The LVMI also increased in patients who have longer duration of diabetes and poor glycemic control. Conclusion: LVM is significantly higher in patients of type 2 diabetic without having hypertension, albuminuria, and apparent ischemic heart disease as compared to healthy controls. LVM in diabetic patients increases with duration of diabetes and is positively correlated with HbA1c and blood sugar level.

Type I Diabetes Mellitus and Insulin Therapy on Bone Microarchitecture, Composition and Mechanical Properties

Background: The aim of this study was to evaluate the microarchitecture, composition and mechanical properties of cortical bone of rats with type I diabetes mellitus (TIDM) and submitted to insulin therapy (IT). Methods: Thirty rats were divided into three groups (n=10): non-diabetic, diabetic and diabetic+insulin. TIDM was induced by intravenous injection of streptozotocin. In diabetic+insulin group, 4IU insulin was administered twice per day (1IU at 7am and 3IU at 7pm). The animals were euthanized five weeks after TIDM induction; the tibiae were removed and submitted to microcomputed tomography (micro-CT, 8µm), fourier transform infrared spectroscopy (FTIR) and dynamic microhardness indentation. Results: Micro-CT analysis showed that diabetic group had lower bone surface/tissue volume ratio (BS/BV) (p=0.018), cortical thickness (Ct.Th) (p<0.001) and degree of anisotropy (Ct.DA) (p=0.034) values compared to non-diabetic group. The diabetic group showed lower Ct.Th than diabetic + insulin group (p=0.018). The non-diabetic group had lower fractal dimension (Ct.FD) values compared to diabetic groups (p<0.001). The ATR-FTIR analyses showed lower values for all measured parameters in the diabetic group than non-diabetic group (amide I ratio: p=0.046; crystallinity index: p=0.038; matrix:mineral ratios - M:MI: p=0.006; M:MIII: p=0.028). The diabetic+insulin group showed a lower crystallinity index (p=0.022) and M:MI ratio (p=0.002) than non-diabetic and diabetic groups, respectively. The diabetic group showed lower Vickers hardness values than non-diabetic (p<0.001) and diabetic+insulin (p=0.003) groups. Conclusion: TIDM negatively affect bone microarchitecture, collagen maturation, mineralization and bone microhardness. Moreover, insulin minimized the effect of TIDM on cortical thickness and organic/mineral matrix.

Swimming training and Plantago psyllium ameliorate cognitive impairment and glucose tolerance in streptozotocin–nicotinamide-induced type 2 diabetic rats

Brain malfunction is common in diabetic patients. On the other hand, a growing body of research points to the beneficial effect of medicinal plants and exercise training on insulin sensitivity and brain function. Therefore, the aim of the present study was to investigate the effect of co-administration of swimming training and Plantago psyllium (mixed with standard pelleted food at a weight ratio of 5%) on learning and memory impairment and glucose tolerance in type 2 diabetic rats. For this purpose, 10 healthy and 40 rats with type 2 diabetes were randomly allocated to five groups: healthy sedentary control group (Con), sedentary diabetic group (D), diabetic group subjected to swimming training (D + Tr), diabetic group receiving P. psyllium (D + Ps), and diabetic group subjected to swimming training and receiving P. psyllium (D + Ps + Tr). Diabetes was induced by a single intraperitoneal injection of nicotinamide (120 mg/kg) and streptozotocin (65 mg/kg) separately with 15 min intervals. Experimental groups were treated with swimming training and P. psyllium independently and simultaneously for 12 weeks. Lipid profile and food intake were measured and also, glucose tolerance was evaluated by glucose area under the curve (AUCg) using an oral glucose tolerance test. Passive avoidance learning (PAL) and memory were evaluated by shuttle box test and cognitive memory was assessed by novel object recognition (NOR) and elevated plus-maze (EPM) tests. Diabetic rats exhibited a significant increase in food intake, lipid profile, and AUCg compared to healthy rats. Step-through latency in the PAL acquisition trial (STL-a) and retention test (STL-r) were significantly lower in diabetic rats than in the control group. In the diabetic group without treatment, time spent in the dark compartment increased compared to the control group in the shuttle box test. Discrimination index and distance traveled reduced in diabetic rats. On the other hand, swimming training and P. psyllium alleviated food intake, lipid profile, and glucose tolerance in diabetic rats. Also, the STL-a, STL-r, discrimination index, and distance travelled in the D + Ps + Tr group were significantly more than the diabetic group. Results showed that 12 weeks of swimming training and receiving P. psyllium improved memory deficit in streptozotocin–nicotinamide-induced type 2 diabetic rats possibly through hypolipidemic and hypoglycemic effects. These results suggest that the administration of swimming training and P. psyllium simultaneously might be an effective intervention for the treatment of diabetes-induced behavioral deficits.

Estimation of vitamin D receptor gene polymorphism in Type 2 Diabetes Mellitus patients in Erbil city

Type 2 diabetes mellitus (T2DM) is a global problem. Recent studies confirmed the association of genes and different single nucleotide polymorphisms with T2DM occurrence and progress. This study was aimed to estimate the vitamin D receptor (VDR) gene polymorphism in Type 2 Diabetes Mellitus patients in Erbil city. The results showed that the Body mass index (BMI), Systolic blood pressure and Diastolic blood pressure were significantly higher in the diabetic group compared to the control group (P<0.05). In addition, the percent of Glycated hemoglobin (HbA1c), Fasting blood glucose (FBG), and Homeostatic model assessment for insulin resistance (HOMA-IR) were significantly higher in the diabetic group compared to the control group (P<0.05). Among different parameters of lipid profile, only Low-density lipoprotein (LDL) was significantly higher in the diabetic group compared to the control group. It was found that FBG value was significantly higher in patients with GA and AA genotypes of BsmI compared with healthy controls. Patients with the GA genotype of BsmI had a higher value of triglyceride compared to healthy individuals. Patients with all ApaI genotypes had higher FBS values than controls. There were not observed any signi?cant associations among the BsmI and ApaI polymorphisms and the risk of T2DM. In conclusion, no evidence was found for the association between two VDR polymorphisms and T2DM patients in Erbil city.

Diabetes is not associated with greater pain and worse patient-reported outcome measures one year after laminoplasty for cervical spondylotic myelopathy

Although patients with diabetes reportedly have more peripheral neuropathy, the impacts of diabetes on postoperative recovery in pain and patient-reported outcome measures (PROMs) after laminoplasty for cervical spondylotic myelopathy (CSM) is not well characterized. The authors aimed to elucidate the effects of diabetes on neck/arm/hand/leg/foot pain and PROMs after laminoplasty CSM. The authors retrospectively reviewed 339 patients (82 with diabetes and 257 without) who underwent laminoplasty between C3 and C7 in 11 hospitals during April 2017−October 2019. Preoperative Numerical Rating Scale (NRS) scores in all five areas, the Short Form-12 Mental Component Summary, Euro quality of life 5-dimension, Neck Disability Index, and the Core Outcome Measures Index-Neck) were comparable between the groups. The between-group differences were also not significant in NRS scores and PROMs one after surgery. The change score of NRS hand pain was larger in the diabetic group than the nondiabetic group. The diabetic group showed worse preoperative score but greater improvement in the Short Form-12 Physical Component Summary than the nondiabetic group, following comparable score one year after surgery. These data indicated that the preoperative presence of diabetes, at least, did not adversely affect pain or PROMs one year after laminoplasty for CSM.

Cadmium Exposure Decreases Fasting Blood Glucose Levels and Exacerbates Type-2 Diabetes in a Mouse Model

Purpose Although the effects of cadmium (Cd) on the development of diabetes have been extensively investigated, the relationship between Cd exposure and the severity of established diabetes is unclear. Herein, we investigate the effects of long-term exposure to Cd in a streptozotocin-induced mouse model of type 2 diabetes and the underlying mechanism. Methods C57BL/6 Mice were divided into the following four groups: 1) control group; 2) Cd-exposed group; 3) diabetic group; 4) Cd-exposed diabetic group. Cd exposure was established by the administration of 155 ppm CdCl2 in drinking water. After 25 weeks of treatment, serum fasting glucose and insulin were measured. Meanwhile, the liver and pancreas specimens were sectioned and stained with Hematoxylin and eosin. Gluconeogenesis, glycolysis, lactate concentration and fibrosis in liver were evaluated. Results Clinical signs attributable to diabetes were more apparent in Cd-exposed diabetic mice. Interestingly, Cd exposure significantly decreased fasting blood glucose levels in diabetic group. We further demonstrated that the glycolysis related hepatic enzymes, pyruvate kinase M2 (PKM-2) and lactic dehydrogenase A (LDHA) were both increased, while the gluconeogenesis related hepatic enzymes, phosphoenolpyruvate-1 (PCK-1) and glucose-6-phosphatase (G6Pase) were both decreased in Cd exposed diabetic mice, indicating that Cd increased glycolysis and inhibited gluconeogenesis in diabetic model. Moreover, lactate accumulation was noted accompanied by the increased inflammation and fibrosis in the livers of diabetic mice following Cd exposure. Conclusions Cd exposure disturbed glucose metabolism and exacerbated diabetes, providing a biological relevance that DM patients are at greater risk when exposed to Cd.

Synergistic effects of sinapic acid and ellagic acid ameliorate streptozotocin-induced diabetic nephropathy by inhibiting apoptosis, DNA damage, and structural deterioration in rats

Introduction Diabetic nephropathy (DN), a global problem that threatens human health, is an important reason for chronic kidney disease and kidney failure. In our study, it was aimed to investigate the individual and combined effects of SA and EA in streptozotocin (STZ)-induced rats. Methods The groups are as follows: Control, untreated diabetic, diabetic treated with Sinapic acid (SA), diabetic treated with Ellagic acid (EA), diabetic treated with SA and EA, treated with SA, treated with EA, and treated with SA and EA. Total kidney volume, total glomerulus volume, total filtration space volume, caspase-3, and 8-OHdG immunoreactivity, Malondialdehyde (MDA), Glutathione (GSH), Catalase (CAT), serum urea, and creatinine levels were evaluated by stereological, immunohistochemical, and biochemical methods. Results The findings of the study showed that total kidney volume, total glomerulus volume, total filtration gap volume, caspase-3, and 8-OHdG immunoreactivity, MDA, serum urea, and creatinine levels significantly increased in the untreated diabetic group compared to the control group. Also, severe mesangial and glomerular enlargement, extracellular matrix accumulation, and glomerular and tubular basal membrane thickness were observed in the tubulointerstitial and glomerular of the diabetic rats. However, individual and combined treatments of SA and EA ameliorated these histological changes. Additionally, decreased GSH and CAT in the untreated diabetic group increased by SA and EA treatment. Conclusions The findings suggest that treatment of SA and EA prevent apoptosis and DNA damage and structural changes in STZ-induced DN. However, the combined treatment of SA and EA were more effective than their individual treatments in all parameters except serum urea and creatinine.