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QSAR (Quantitative Structure Activity Relationship) modelling was performed on a dataset of 90 sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The quantitative and explicative evaluations revealed some of the subtle a...
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QSAR (Quantitative Structure Activity Relationship) modelling was performed on a dataset of 90 sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The quantitative and explicative evaluations revealed some of the subtle and distinguished structural features that are responsible for the inhibitory potency of these compounds against SGLT2, such as less possible number of ring carbons at 8 angstrom from the lipophilic atoms in the molecule (fringClipo8A) and more possible value for the sum of the partial charges of the lipophilic atoms present within seven bonds from the donor atoms (lipo_don_7Bc). Multivariate GA-MLR (genetic algorithm-multi linear regression) and thorough validation methodology out-turned a statistically robust QSAR model with a very high predictability shown from various statistical parameters. A QSAR model with r (2) = 0.83, F = 51.54, Q (2) (LOO) = 0.79, Q (2) (LMO) = 0.79, CCC (cv) = 0.88, Q F-2(n) = 0.76-0.81, r (2) (ext) = 0.77, CCC (ext) = 0.85, and with RMSEtr < RMSEcv was proposed. This QSAR model will assist synthetic chemists in the development of the SGLT2 inhibitors as the antidiabetic leads.
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Background & Method: The aim of this study is to compare the prevalence of various thyroid disorders between T1DM and T2DM populations. Present study is conducted at Amaltas Institute of Medical Sciences, Dewas, M.P. Result: Out of 132 diabetic patients, 8.33% (11/132) were suffering from T1DM and 91.67% (121/132) from T2DM.Hyperthyroidism was the most prevalent disorder in T1DM patients, occurring in up to 18.18% of the total T1DM population [9.09% were having primary hyperthyroidism and 9.09% were having T3 toxicosis syndromes]. Males and females are equally affected (Both 9.09%). In T2DM patients, primary hypothyroidism was the most prevalent disorder, occurring in up to 7.44% of the total diabetic population, followed by subclinical hypothyroidism in 5.79%, subclinical hyperthyroidism in 4.13%, hyperthyroidism in 0.83%, and nonthyroid dysfunction in 0.83% patients....
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Background & Method: The aim of this study is to compare the prevalence of various thyroid disorders between T1DM and T2DM populations. Present study is conducted at Amaltas Institute of Medical Sciences, Dewas, M.P. Result: Out of 132 diabetic patients, 8.33% (11/132) were suffering from T1DM and 91.67% (121/132) from T2DM.Hyperthyroidism was the most prevalent disorder in T1DM patients, occurring in up to 18.18% of the total T1DM population [9.09% were having primary hyperthyroidism and 9.09% were having T3 toxicosis syndromes]. Males and females are equally affected (Both 9.09%). In T2DM patients, primary hypothyroidism was the most prevalent disorder, occurring in up to 7.44% of the total diabetic population, followed by subclinical hypothyroidism in 5.79%, subclinical hyperthyroidism in 4.13%, hyperthyroidism in 0.83%, and nonthyroid dysfunction in 0.83% patients.
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Background: Type 2 diabetes mellitus describes a metabolic disorder characterised by prolonged elevated blood glucose that brings a risk of developing microvascular and macrovascular disease. Several factors, such as dysregulation...
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Background: Type 2 diabetes mellitus describes a metabolic disorder characterised by prolonged elevated blood glucose that brings a risk of developing microvascular and macrovascular disease. Several factors, such as dysregulation of the Toll-like receptor 4 (TLR-4), are reputed to contribute to the multiple pathophysiological disturbances responsible for impaired glucose homeostasis. We hypothesised that variants rs5030717 and rs5030718 of TLR4 are associated with diabetic nephropathy, hypertension and dyslipidaemia.
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Background: The prevalence of diabetes is increasing in the United States and worldwide. Insulin injection pens are preferred over vial/syringe methods, and are designed to facilitate use, improve adherence, and provide accurate i...
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Background: The prevalence of diabetes is increasing in the United States and worldwide. Insulin injection pens are preferred over vial/syringe methods, and are designed to facilitate use, improve adherence, and provide accurate insulin delivery. Objective: This study compares the efficacy, safety profile, and patient preference of the new prefilled insulin pen FT** *FlexTouch is a registered trade name of Novo Nordisk A/S, Bagsvaerd, Denmark. versus the original insulin pen FP.? ?FlexPen is a registered trade name of Novo Nordisk A/S, Bagsvaerd, Denmark. Methods: This randomized, multicenter, open-label, crossover study was conducted in insulin-treated pen-nave patients with type 1 or type 2 diabetes mellitus (n=242, mean age 58 years, mean body mass index (BMI) 31.4kg/m 2, baseline glycosylated hemoglobin [HbA1c] 7.3%). Patients were randomized 1:1 to either FT or FP for 12 weeks and then switched to the alternate insulin device for 12 weeks, while the insulin regimen was kept the same. All subjects were on either insulin detemir alone or in combination with insulin aspart treatment during the trial. HbA1c was assessed at screening, randomization, cross-over period, and end of trial. The safety profile was evaluated based on adverse events (AEs), adverse device effects (ADEs), and hypoglycemic episodes. Patient-reported outcome (PRO) questionnaires assessed at randomization, crossover period, and end of trial were used to investigate the subjects' preference of the two prefilled devices. Results: A total of 400 subjects were screened, 242 subjects were randomized and exposed to the prefilled pen devices, and 222 subjects completed the trial. Twenty subjects discontinued the study. Four subjects discontinued due to adverse events. Subject default (withdrawal of consent and loss to follow up) was the most common reason for discontinuation (10 subjects), Glycemic control achieved with FT was comparable to that with FP (FTFP: difference -0.047 [95% CI -0.127; 0.032%]). The majority of subjects (68%) indicated a preference for the FT device over FP. In addition, the majority of subjects found FT easier to use (64% [144/226]), easier to inject the insulin dose (65% [148/227]) and easier to push for injection (69% [155/226]). The Treatment Related Impact MeasureDiabetes (TRIM-D) ratings of FT were significantly higher for diabetes management facilitation (P<0.001), and treatment burden (P<0.001). The safety profiles were comparable for FT and FP. Conclusions: FT was found to be comparable to FP with respect to the efficacy and safety profile. Significantly more subjects favored the FT device in terms of ease of use, insulin injection, diabetes management, and overall preference. A limitation of the present study was its open-label design because the pen devices used to administer the insulin were distinctively different and the use of a double-dummy design was precluded by the absence of placebo pen devices. The questionnaires about treatment were related to the use of the device and therefore a blinded study was not possible.
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Aims: This study investigates whether diabetes patients visiting a primary care setting are interested in using a telemonitoring platform and if so, whether characteristics of interested users could be distinguished. Methods: Thre...
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Aims: This study investigates whether diabetes patients visiting a primary care setting are interested in using a telemonitoring platform and if so, whether characteristics of interested users could be distinguished. Methods: Three questionnaires were administered by 92 diabetes persons recruited between May and September 2011. Descriptive statistics and logistic regression analysis were performed. Special attention was drawn to include patients with low educational levels. Results: Patients with middle or high educational levels show quite some interest in the use of a telemonitoring platform, especially for the transmission of glycaemic data or for asking questions. Patients with low educational levels only show a minor interest in using such a platform. Conclusions: It is possibly worthwhile to implement a telemonitoring platform in a primary care setting; however this study did not show immediate profit for implementation in a CHC that organises diabetes clinics on regular basis. In primary care settings where it will be implemented, even if there is a social-digital divide today, the use of a telemonitoring platform could possibly reduce inequity in health care as time could become available for those most in need for face-to-face contact with their physician.
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Sirtuins are the protein deacetylases, which are linked to metabolic diseases and aging. There are seven sirtuins present in cell, whose regulation in diabetic heart is yet to be explored. Resveratrol is a well-known activator of ...
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Sirtuins are the protein deacetylases, which are linked to metabolic diseases and aging. There are seven sirtuins present in cell, whose regulation in diabetic heart is yet to be explored. Resveratrol is a well-known activator of SIRT-1, but its effect on other sirtuins is not yet clear. In the present study, we focused to find out the expression and regulation of all sirtuins in diabetic heart with the effect of resveratrol administration on them. We have induced T1DM rat model using steptozotocin and T2DM rat model by feeding high fructose diet for a period of eight weeks and analyzed the myocardial changes. Resveratrol was administrated to both the models simultaneously. Increased oxidative stress and cardiac phenotype alterations shows the induction of cardiac abnormalities in both models. We have observed decreased SIRT-1 and increased SIRT-3 activity in the T2DM rat heart. Moreover, in case of T1DM, gene and protein expression of all sirtuins was down, except SIRT-2 whose protein levels were increased. Administration of resveratrol prevented the alteration in SIRT-1 in T2DM and SIRT-1, 2, 3 and SIRT-5 in T1DM rat heart. Altered level of protein acetylation was observed corresponding to the changes in sirtuins. In conclusion, sirtuins are perturbed in both types of diabetic heart and can be considered as druggable target for therapeutic intervention. (C) 2015 Elsevier Inc. All rights reserved.
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The antihyperglycemic actions of caffeamide derivatives, especially KS370G, in normal ICR, streptozotocin-induced diabetic (T1DM) and diet-induced diabetic (T2DM) mice were investigated in this study. Oral administration of the co...
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The antihyperglycemic actions of caffeamide derivatives, especially KS370G, in normal ICR, streptozotocin-induced diabetic (T1DM) and diet-induced diabetic (T2DM) mice were investigated in this study. Oral administration of the compound decreased the plasma glucose levels in both normal and diabetic mice, and appeared to be in a dose-dependent manner in normal arid diet-induced type 2 diabetic mice. It was found that KS370G could stimulate the release of insulin in both normal and T2DM mice, and a dose of 1 mg per kg KS370G could significantly attenuate the increase of plasma glucose induced by an intraperitoneal glucose challenge test in normal and diabetic mice. Similar treatment with KS370G significantly increased glycogen content in both liver and skeletal muscle. Hence, the hypoglycemic effect of KS370G in normal and diabetic mice could be attributed to the stimulation of insulin release and the increase of glucose utilization.
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Abstract Objectives: Calcium deregulation in diabetes mellitus (DM) is central to the brain-heart axis pathology. This has led to the use of medical plants in complementary medicine such as Amaranthus hypochondriacus (GA). The obj...
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Abstract Objectives: Calcium deregulation in diabetes mellitus (DM) is central to the brain-heart axis pathology. This has led to the use of medical plants in complementary medicine such as Amaranthus hypochondriacus (GA). The objective of the study was to establish the effects of grain amaranth feed supplementation on calcium, s100al protein and antioxidant levels on the brain-heart axis in diabetic male Wistar rats. Methods: The study involved six groups (n=5) with DM being induced in 20 rats. To the diabetic rats, Group I received mixtard?, Group II was positive control, Groups III and IV received GA feed supplementation at 25 and 50%. In the nondiabetic rats (n=10), Group V received 50% grain amaranth while Group VI was the negative control. The brain and heart tissues were harvested after five weeks and processed using standard methods. Results: Grain amaranth feed supplementation led to improved calcium levels in DM as compared to the positive control. This also led to increased s100a1, antioxidant levels in the brain-heart axis during DM. This then protected the tissues against oxidative damage, thus preserving tissue function and structure. Conclusions: Grain amaranth’s actions on calcium signaling subsequently affected s100a1 protein levels, leading to improved tissue function in diabetes.
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The purpose of this paper is to highlight specific considerations in the medical management of women with type 2 diabetes mellitus (T2DM). T2DM, a significant source of morbidity and mortality, has become an ever growing epidemic ...
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The purpose of this paper is to highlight specific considerations in the medical management of women with type 2 diabetes mellitus (T2DM). T2DM, a significant source of morbidity and mortality, has become an ever growing epidemic within the United States. Although it is well understood that diabetes can significantly increase the risk for microvascular and macrovascular complications, there has been limited research examining the differential impact of these complications on men and women. Women, in particular, are subject to especially high risk for the development of myocardial infarction (MI), claudication, and stroke and are disproportionately afflicted by cardiovascular, cerebrovascular, and peripheral vascular disease. There is new evidence that tight glycemic control and earlier initiation of insulin therapy can improve outcomes and thereby reduce the risk for development of both macrovascular and microvascular complications of the disease. Although there are many commonalities in the treatment of men and women, women with diabetes have several unique issues, including the possible effects of therapy on reproductive health, fetal health, breastfeeding, potential interactions with hormonal contraceptives, and effects on bone health, that should be considered when determining a therapeutic approach. This paper presents evidence-based treatment strategies for reducing the risk of diabetes-associated complications overall and cardiovascular disease in particular through glycemic control. Special attention is paid to the selection of antidiabetic agents that are best suited to the unique needs of women.
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The number of cases of diabetes worldwide has increased significantly in the last decade. Characteristically, the incidence of gestational diabetes (GDM) reflects the incidence of type 2 diabetes mellitus (T2DM) in the background ...
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The number of cases of diabetes worldwide has increased significantly in the last decade. Characteristically, the incidence of gestational diabetes (GDM) reflects the incidence of type 2 diabetes mellitus (T2DM) in the background population, which is a warning that a rapid increase in the incidence is to be expected concomitant with the already observed increase in the incidence of T2DM. Although the majority of all deliveries worldwide take place in the so-called developing world, little is known about the prevalence of diabetes in pregnancy in rural areas of East Africa. Diabetes in pregnancy has effects on prospects for marriage, motherhood, and the role of women in East African society. Furthermore, intrauterine exposure to the metabolic environment of maternal diabetes, or GDM, is associated with increased risk of altered glucose homeostasis in the offspring, beginning in childhood and producing a higher prevalence of GDM in the next generation with all burdens and complications being associated with this disease. It is reasonable to conclude that more newborn infants each year are being exposed to the metabolic environment of diabetes during intrauterine development as a result of changing incidence and demographics of diabetes and pregnancy. We believe that programs and policies have to be established, including organization of the health system to provide care, medicines, and other tools necessary for diabetes in pregnancy management, consideration of accessibility and affordability of care, education for healthcare workers, and education of pregnant and nonpregnant women of reproductive age.
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