ArticleLiterature Review

Type 2 Diabetes Mellitus, Pandemic in 21st Century

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Abstract

In the second half of the 20th century it became obvious that a relentless increase in Type 2 diabetes mellitus (T2DM), affecting the economically affluent countries, is gradually afflicting also the developing world. This chapter shows the threat that the T2DM epidemic represents to mankind, with the astonishing recent discoveries on the role of obesity and of body fat in this metabolic disorder. Presently, the highest prevalence of T2DM is in Saudi Arabia. T2DM is very high in over 10% of adults in the USA, Switzerland and Austria. Prevalence is low in Norway, China and in Iceland. Predictions of epidemiologists for the first third of the 21st century claim up to 2.5 times increase in the prevalence of T2DM in the Middle East, Sub-Saharan Africa, India, rest of Asia and in the Latin America. In China the number of patients with T2DM will double in 2030. In the economically advanced countries the increase will be about 50% in 2030. Increasing urbanization, aging populations, obesity and falling levels of physical activity are all contributing to the rise of T2DM worldwide. The main cause of T2DM pandemic is growing prevalence of obesity in Europe and USA. In the North America and European Union countries obesity is considered to be responsible for up to 70-90% of T2DM in adult population. The precise mechanism by which obesity leads to insulin resistance and to T2DM is not completely known but it may be related to several biochemical factors such as abnormalities in free fatty acids, adipokines, leptin and other substances.

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... Alternative way of assessing weight bearing asymmetries, the measures obtained from the digital scales has been used as the index to classify weight bearing distribution. It describes the intra test and the test /retest reliability of measures in subjects with or without hemiparesis during quiet stance 31 Subjects with or without hemiparesis 29 to 81 years old It was supporting the use of digital scales. The behavior Of the measurements analyzed by repetition intra-test could reveal important features of the weight bearing distribution calculated from digit scales. ...
... Abnormal weight distribution in the bipedal stance laid foundation to various assessment tools; the frontier of all of them is electronic foot screening protocol used by the optical method. 31 The total body weighing is simple method, standing straight on the foot displays consistent weighing difference in bipedal stance. 31 An alternative way of assessing weight bearing asymmetries is bilateral digital scales usage where the index of classifying weight bearing distribution is identified. ...
... 31 The total body weighing is simple method, standing straight on the foot displays consistent weighing difference in bipedal stance. 31 An alternative way of assessing weight bearing asymmetries is bilateral digital scales usage where the index of classifying weight bearing distribution is identified. 32 In their normal standing or supported position relative left and right weight bearing showed variations both in supported and unsupported weighing system. ...
Article
Background: Type 2 Diabetes mellitus is a common metabolic condition increasing in the elderly population which leads to various disabilities and in longtime can cause chronic complications like diabetic neuropathy, diabetic nephropathy, diabetic retinopathy and diabetic cardiopathy. Objective: The aim of this narrative review is to identify the sway in posture and distribution of weight in bilateral stance in diabetic neuropathy patients. Methods: The articles are taken from Google Scholar, PUBMED, and EMBASE MEDLINE. Results: Increased anterior displacement than medial, lateral and posterior displacement in postural sway both in eye closed and eyes open, center of pressure and center of mass also changes in postural stability which will aid to identify risk of fall. In weight distribution there is an increased plantar pressure in anterior direction and higher plantar pressures were obtained in long standing phase. Discussion and Conclusion: Early detection of postural sway in diabetic patients may decrease in risk of fall, identifying the muscle strengthening and balance impairment. Even early detection of improper weight distribution over the lower limbs mainly over the foot can reduced the presence of plantar pressure sores, risk of falls and balance instability, or diabetic foot. Postural sway and weight distribution is measured in stance phase than dynamic phase, increase in postural sway can cause to risk of fall and increase in weight distribution on limb can cause wear and tear of the structure. Keyword: Postural Sway, Diabetic Neuropathy and Diabetic Nephropathy, weight distribution, plantar pressure, diabetes mellitus, diabetic foot.
... Aujourd'hui, des médicaments peuvent être administrés par de nombreuses voies, comme la voie buccale, orale, rectale, parentérale et des muqueuses. Une autre voie d'administration de médicaments extrêmement pertinente pour la MP du diabète est la voie 6 ...
... Type 2 diabetes (T2D) is the most prominent form with more than 90% of diagnosed cases. [5][6][7] As obesity itself causes some degree of insulin resistance [8][9] , most patients with this form of diabetes are obese or have an increased percentage of body fat distributed predominantly in the abdominal region. In T2D, hyperglycaemia ensues as pancreatic β-cells fail to produce enough insulin to compensate for insulin resistance. ...
... S2.6.1. CQD-1 (carboxylated carbon quantum dots) ....................................................... 80 S2.6.2. ...
Thesis
Advances in materials science and nanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine (PM). Nanotechnology is the foundation of new generations of nano- andmicro-electromechanical systems for controlled antidiabetic drug delivery. Today, drugs can be administered by many routes, such as buccal, oral, rectal, parenteral, and mucous membranes. Another highly relevant route of drug administration for diabetic personalized medicine is the transdermal route. This route offers the advantage of being able to administer drugs which are little or not tolerated when ingested or inhaled, and also of avoiding their degradation by the gastrointestinal system. Transdermal delivery systems (TDS) using nanotechnology are realistically becoming a key delivery mode for implementing PM. Additionally, TDS, if non-invasive, may ameliorate the therapeutic efficacy of the drug by improving patient adherence. However, the administration of drugs by TDS, in a controlled manner and on demand, remains a technological barrier to be overcome. In this thesis, we investigated different approaches to control the non-invasive TDS delivery of insulin, metformin and ramipril, such as the use of heat in combination with graphene oxide matrices. In vitro and in vivo tests were carried out to evaluate the effectiveness of the proposed concepts. In addition, mats of electrospun fibers with incorporated graphene have been investigated for oral rather than transdermal drug delivery. Furthermore, the use of nanostructures to inhibit the aggregation of IAPP (Islet Amyloid Polypeptide) and the first promising results will be discussed.
... In diabetes mellitus the increases level of glucose in blood and resistance to insulin 1 . Primarily it is identified as insulin independent diabetes mellitus. ...
... Primarily it is identified as insulin independent diabetes mellitus. 1 In 2013, 382 million population of the world about 8.3% of young people were affected by diabetes mellitus. 2,3 Diabetes is strongly related to genetics and have six times more chances than normal or non-diabetic family history. ...
... 8 The use of metformin reduces body weight in people with type 2 diabetes mellitus. 9 Chronic liver disease is a side effect associated with metformin intake. Hypoglycemia and other side effects are possible when metformin is combined with other drugs (combination therapy). ...
... 10,11 Metformin is associated with a very low incidence of lactic acidosis because it does not undergo liver metabolism and, as a result, there are no high-risk groups with impaired metabolic handling. 9 Nanoscience has revealed a distinct and effective treatment behavior in medicine, particularly for the treatment of cancer cells. Hence, it has been highly applied in the area of drug delivery systems and tissue engineering. ...
Article
Nanostructures such as nanosheets, nanotubes, nanocages, and fullerenes have been extensively studied as potential candidates in various fields since the advancement of nanoscience. Herein, the interaction between biguanides (BGN) and metformin (MET) on the modified covalent organic framework (COF), COF-B, and COF-Al was investigated using density functional theory at the ωB97XD/6-311+G (d, p) level of computation to explore a new drug delivery system. The electronic properties evaluation reveals that the studied surfaces are suited for the delivery of both drug molecules. The calculated adsorption energies and basis set superposition errors (BSSE) ranged between -21.20 and -65.86 kJ/mol. The negative values obtained are an indication of excellent interaction between the drug molecules and the COF surfaces. Moreover, BGN is better adsorbed on COF-B with Eads of -65.86 kJ/mol, while MET is better adsorbed on COF-Al with Eads = -47.30 kJ/mol. The analysis of the quantum theory of atom in molecules (QTAIM) explained the nature and strength of intermolecular interaction existing between the drug molecules BGN and MET with the adsorbing surfaces. The analysis of noncovalent interaction (NCI) shows a weak hydrogen-bond interaction. Other properties such as quantum chemical descriptors and natural bond orbital (NBO) analysis also agree with the potential of COF surfaces as drug delivery systems. The electron localization function (ELF) is discussed, and it confirms the transitions occurring in the NBO analysis of the complexes. In conclusion, COF-B and COF-Al are suitable candidates for the effective delivery of BGN and MET.
... Therefore, monitoring blood Glu levels is crucial. 66,67 Similar to Alzheimer's disease (AD), type 2 diabetes mellitus (2 DM) is another widespread condition oen linked to obesity and aging. In the U.S., approximately 24 million people exhibit clinical symptoms of 2 DM. ...
Article
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The study on the synthesis of carbon dots, sensing mechanisms, conditions associated with glucose imbalance, and potential applications as promising materials for glucose sensors.
... Maintaining a healthy weight reduces the risk of a variety of chronic diseases, including heart disease, T2DM, and osteoarthritis. At the same time, an adapted diet low in saturated fat and rich in fiber has a favorable effect on glucose metabolism and insulin sensitivity [71,72]. ...
Article
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The aim of the research was to collect and to examine the positive effects of various physical activity (PA) programs on individuals with type 2 diabetes mellitus (T2DM). This included a combination of aerobic exercises and resistance training, with varying intensities, in order to compare which approach yielded better outcomes for T2DM management; This systematic review was conducted in line with PRISMA guidelines, focusing on the period from 1991 to 2024. Studies included in this review involved both experimental procedures and questionnaire-based surveys to assess the impact of PA on T2DM patients. The primary outcome was the effect of PA on T2DM, with secondary outcomes including changes in blood pressure, cholesterol levels, and glycemic control; A total of 23 studies, encompassing 1752 participants (515 men, 546 women, and 691 unspecified), met the inclusion criteria. The studies highlighted the positive effects of exercise, such as improvements in glycemic control, insulin sensitivity, and lipid profiles. Most studies recommended a combination of aerobic and resistance exercises performed 3-4 times per week for 30-60 minutes per session; This systematic review confirms that regular PA is instrumental in managing T2DM. Health care providers should integrate PA programs into treatment plans for T2DM patients to optimize glycemic control and overall health outcomes.
... The most prevalent diabetes type is type 2 (T2DM), which accounts for about 96% of the total incidence of diabetes [1,2]. T2DM was earlier known as insulin-independent diabetes mellitus or adult-onset diabetes because it most frequently occurs in people over the age of 45 and is characterized by a lack of insulin requirements to prevent ketoacidosis [3][4][5]. T2DM is caused by a combination of genetic factors and lifestyle. A major lifestyle risk factor is a high body mass index (BMI). ...
Article
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Type 2 diabetes (T2DM) is a chronic metabolic disease with a steadily increasing prevalence worldwide. Diabetes affects the function of many organs, including the skin. Pharmacotherapy for T2DM is mainly based on oral hypoglycemic drugs. The therapeutic strategy is chosen taking into account the individual patient’s characteristics, among other comorbidities. Antidiabetic drugs can induce cutaneous adverse reactions (CADRs) ranging in severity from mild erythema to serious disorders such as DRESS or Stevens–Johnson syndrome. CADRs can result from hypersensitivity to the drug but can also be related to the mechanism of action of the drug or cross-reactivity with drugs of similar structure. This paper reviews CADRs induced by oral antidiabetic drugs, considering their dermatological manifestations and possible pathomechanisms. Particular attention was paid to specific dermatological conditions such as dipeptidylpeptidase 4 inhibitor-associated bullous pemphigoid or Fournier’s gangrene associated with sodium-glucose cotransporter 2 inhibitor therapy. Knowledge of the dermatological manifestations of CADRs is important in clinical practice. Recognition of a skin lesion resulting from an adverse drug reaction allows for appropriate management, which in this case is primarily related to drug discontinuation. This is particularly important in the treatment of T2DM since this disease has a high prevalence in the elderly, who are at higher risk of adverse drug reactions.
... The four major NCDs, cardiovascular disease (CVD), cancers, chronic respiratory diseases, and diabetes, accounted for 12 million deaths in the Western Pacific region in 2019 [1]. Type-2 diabetes mellitus (T2DM), a major NCD, has been considered an epidemic of the 21st century [2]. According to the latest report of the International Diabetes Federation (IDF) released in 2021, the prevalence of diabetes mellitus (DM) around the globe was 10.5% of the adult population (536.6 million) and is projected to increase up to 12.2% (783.2 million) in 2045 [3]. ...
... Of all the T2DM cases, T2DM cases are over 90% [8]. Previously, T2DM was referred to as adult-onset diabetes or non-insulin dependent T2DM and is identified by deficiency of insulin and insulin resistance, which causes high levels of blood glucose [9]. Rise in urbanization, rise in obesity, aging citizens, and reduced physical activities help in increasing T2DM worldwide [10]. ...
Article
Background Diabetes is a serious and chronic metabolic disorder that is a result of a complex interaction of genetic and environmental factors. Diabetes mellitus has become a worldwide pandemic. Drug discovery has been complicated by the high cost and time required for developing new drugs/agents. In the last 30 years, the number of FDA-approved medications has declined, boosting interest in drug repositioning or repurposing. Repurposing existing drugs may be a significant tool for lowering the financial burden that most nations bear while treating diabetic mellitus. Objective This comprehensive review aims to elucidate the repurposed pharmaceutical agents for the treatment of Diabetes Mellitus along with the diverse array of validation techniques employed in the process. Methods For this review purpose, the authors have gone through a vast number of article sources from various scientific databases like Google Scholar, PubMed, and Web of Science. Results Drug repurposing led to the discovery of a few anti-diabetic drugs which has been widely used for other pharmacological effects. Several medications, including celecoxib, buspirone, berberine, diacerein, methazolamide, and bromocriptine, have been effective in treating diabetic mellitus by various mechanisms like decreasing insulin resistance, hyperglycemia, inhibiting glucagon secretion and improving insulin sensitivity. Conclusion The field of drug repurposing exhibits significant potential in tackling the obstacles presented by T2DM and other complex diseases. The conventional approaches to drug development have often been characterized by prolonged durations and high costs, resulting in significant delays in the discovery of effective medicines for conditions like T2DM. However, the strategy of drug repurposing presents a more streamlined and economically advantageous method for drug development.
... Diabetes mellitus (DM) is a chronic disorder characterized by impaired production and/or unresponsiveness to insulin, leading to both, short-and long-term serious complications [1]. It is one of the most common endocrine chronic diseases worldwide [2]. ...
... Diabetes mellitus (DM) is a chronic disorder characterized by impaired production and/or unresponsiveness to insulin, leading to both, short-and long-term serious complications [1]. It is one of the most common endocrine chronic diseases worldwide [2]. ...
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How to cite this article: Almterin M, Aboalhaıja N, Zıhlıf M, Afıfı F. Effects of Ononis natrix on glucose and lipid metabolism: An in vivo study. J Res Pharm. 2024; 28(1): 278-288. ABSTRACT: Several medicinal plants have been used historically and are claimed to be effective in either preventing or treating diabetes. This study aimed to evaluate the effect and the mechanism of O. natrix extract (ONE) as an antihyperglycemic and antihyperlipidemic agents in in vivo experiments. Lipid profile was analyzed using fully automated chemistry analyzer. Blood serum samples were used to measure high-density lipoprotein (HDL), triglycerides (TG), total cholesterol (TC) and Low-density lipoprotein (LDL). The expression levels of AMPK alpha-2 and Glut-4 receptors in diabetic rats were investigated using Western blotting. Oral starch tolerance test (OSTT) and oral glucose tolerance test (OGTT) were determined for the plant extracts at three concentrations on Wistar rats. Acarbose or metformin and glipizide were used as positive controls. Blood glucose levels were measured at −30, 0, 45, 90 and 135 min.ONE (250mg/kg and 125 mg/kg), administered before or after induction of diabetes using streptozotocin (STZ), significantly (p<0.05) reduced the blood glucose level by applying preventive and treatment protocols. The expression levels of Glut-4 receptors were significantly increased in rats given ONE (250 mg and 125 mg/kg) compared to the diabetic rats after 8 days of treatment. ONE (250 mg/kg) enhanced significantly (p<0.05) starch tolerance area under the curve (AUC) and glucose tolerance AUC. O. natrix extracts can activate the Glut-4 receptor, and enhance the glucose and starch tolerance in experimental rats. Hence, this widely distributed species in Jordan can be considered as a potential candidate for management of diabetes.
... This is another argument for designated halal parks, where these complex processes could be better linked (Transforum, 2007). Second, it is important to focus on healthy food production that supports the basic dietary requirements, instead of ultra-processed and fast foods that contain high levels of salt, sugar and fat (Moss, 2013), resulting in our current epidemic in obesity (WHO, 2014;Popkin et al., 2012), type 2 diabetes (Ginter and Simko, 2013;Verburgh, 2012) and cancers (Zappia et al., 2013;Lelièvre and Weaver, 2013). ...
Article
The increasing awareness of the Muslim community in Indonesia towards the halalness of every product eaten causes an increasing demand for halal food. The development of the halal industry must be supported by the development of the right halal supply chain. Halal supply chain as a process of managing halal food products from various supplier points to various consumer points, involving various parties, located in different places, which may be at the same time, involved with managing halal food products, with the aim of meeting the needs and requirements of customers. To ensure the availability and access of halal food, a new paradigm is needed in better structuring halal food production and trade through halal clusters. This study aims to determine the development map and trend of the Halal Cluster published by reputable journals in the field of Halal Economics. The data analyzed were 30 Dimensions indexed research publications. The export data is then processed and analyzed using the R Biblioshiny application program to find out the bibliometric map of the development of the Halal Cluster. This research will also analyze thematic maps that appear based on density and centrality which are analyzed based on document titles with the research theme of Halal Cluster which is divided into 4 quadrants. These results are obtained from a semi-automatic algorithm by reviewing the titles of all references to the object of research
... Diabetic retinopathy is a progressive condition and is potentially vision t h rea te ni ng [18] . The underl yi ng p a t h o g e n e s i s h a s t o d o w i t h microangiopathy and capillary occlusion [19].Diabetic retinopathy is the commonest cause of blindness amongst the working population in the USA [8] and has become an important cause of blindness in the developing world with the near pandemic situation of diabetes mellitus in the world [20].Diabetic retinopathy has few ophthalmic symptoms until visual loss occurs. Up to 21% of DM patients develop DR at the time of diagnosis. ...
Article
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Diabetes retinopathy is the most serious eye complication of diabetes mellitus. Ocular complications from diabetes mellitus could result from microangiopathy and changes in the lens largely from poor gylcaemic control. Ocular complications also depend on duration of diabetes and presence or absence of other co-morbid conditions like hypertension. Since onset of diabetic retinopathy is without symptoms and may even occur several years prior to first diagnosis of diabetes mellitus, there is the need for improved level of awareness in the community about this potentially blinding condition. This can only occur from the background of knowledge, hence this study.Interviewer administered questionnaire was administered to 218 consenting diabetic patients who were previously diagnosed or diagnosed in the eye clinic between January 2009 and December 2010. Ocular examination was carried out by the investigator. Result so obtained was analysed using SPSS17.0 statistical package. Result obtained presented as simple frequency tables of the 218 diabetic patients examined 115 (52.7%) had diabetic retinopathy and commonest wasnon-proliferative diabetic retinopathy (63.3%)while proliferative diabetic retinopathy accounted for only1.7% and 2.6% had DR coexisting with other retinopathies.
... The prevalence of obesity and type 2 diabetes mellitus (T2DM) continue to escalate, largely attributed to the effects of urbanisation, which, in turn, results in notably reduced levels of physical activity [1]. Studies found that people living in urban areas have higher body mass index (BMI) than those living in rural areas [2,3]. ...
Article
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Background Lifestyle modifications involving diet and exercise are recommended for patients diagnosed with obesity and type 2 diabetes mellitus (T2DM). The purpose of this review was to systematically evaluate the effects of combined aerobic exercise and diet (AEDT) on various cardiometabolic health-related indicators among individuals with obesity and T2DM. Methodology A comprehensive search of the PubMed/Medline, Web of Science, Scopus, Science Direct, Cochrane, and Google Scholar databases was conducted for this meta-analysis. The Cochrane risk of bias tool was used to evaluate eligible studies, and the GRADE tool was used to rate the certainty of evidence. A random-effects model for continuous variables was used, and the results were presented as mean differences or standardised mean differences with 95% confidence intervals. Results A total of 16,129 studies were retrieved; 20 studies were included, and data were extracted from 1,192 participants. The findings revealed significant improvements in body mass index, body weight, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, fasting blood glucose, fasting plasma insulin, glycated hemoglobin, leptin, interleukin-6, C-reactive protein, and adiponectin (p < 0.05) compared to the standard treatment (ST) group. No significant differences were observed between the AEDT and ST groups in fat mass, hip circumference, waist-to-hip ratio, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and tumor necrosis factor-alpha. The present findings are based on low- to moderate-quality evidence. Conclusions AEDT may be a critical behavior for holistic cardiometabolic health-related benefits as a contemporary anti-obesity medication due to its significant positive impact on patients with obesity and T2DM. Nevertheless, further robust evidence is necessary to determine whether AEDT is an effective intervention for lowering cardiovascular and metabolic risk factors among individuals with obesity and T2DM.
... Globally, about one in eleven adults have diabetes mellitus, from this 90% have type 2 diabetes mellitus. The main drivers of the T2DM epidemic are the global rise in obesity, sedentary lifestyles, high caloric diets and population aging, which have quadrupled the incidence and prevalence of T2DM [6][7][8].The estimated global prevalence of diabetes in 2015 was 415 million; by 2040, it is expected to rise to 642 million, with more increase in low-and middle-income nations [9]. DM patients have uncontrolled blood sugar levels and a longer duration of diabetes were considered as independent risk factors of CKD [10]. ...
Article
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Background Diabetes is a complicated, chronic condition that requires ongoing medical attention as well as multiple risk-reduction measures beyond glucose control. The prevalence of chronic kidney disease (CKD) is highly variable in different parts of the world due to various environmental, ethnic, socioeconomic, and rural-urban differences. Diabetes is the leading cause of CKD. This study aimed to estimate the global prevalence of CKD and its associated factors among type 2 diabetes(T2DM) patients, provide scientific evidence for a better understanding of the burden of CKD among diabetes mellitus type 2 patients, and design interventional strategies. Methods Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist guideline was followed for this review and meta-analysis. The electronic databases (Pub Med, Cochrane Library, Google Scholar, and grey literature) were searched to retrieve articles by using keywords. Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument was used to assess the quality of studies. The meta-analysis was conducted using STATA 17 software. The Meta logistic regression was computed to present the pooled prevalence and Odds ratio (OR) of the determinate factors with a 95% confidence interval (CI). Results In this systematic review and meta-analysis 20 studies were done in 13 different countries. The pooled magnitude of chronic kidney disease among type 2 DM patients was 27% (95% CI 21%, 33%). The prevalence of chronic kidney disease differs across countries, with the maximum in the USA and the lowest in the United Arab Emirates. Patients with CKD have an elevated risk of severe renal and cardiovascular morbidity and mortality. Renin-angiotensin system inhibitors, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide 1 receptor agonists, and, more recently, non-steroidal mineralocorticoid receptor antagonists are among the medications that have been demonstrated to slow the progression of CKD. In this systematic review and meta-analysis increased age, obesity, having a history of type 2 diabetes mellitus, smoking history, presence of hypertension, and cardiac heart disease were factors significantly associated with the presence of chronic kidney disease among type 2 diabetic patients. Conclusions The prevalence of chronic kidney disease among type 2 diabetes mellitus patients was high based on the included 20 articles. The review reported that old age, hypertension, cardiac disease, smoking, obesity, and duration of diabetes mellitus was predictor variable for chronic kidney disease among type 2 diabetic patients. Therefore, in order to lower the morbidity and mortality from chronic kidney disease among type 2 diabetic patients, it is advised to develop both preventive and curative intervention strategies, such as raising awareness, creating a supportive environment, and prescribing appropriate medication at an early stage.
... The prevalence of T2DM in China was high and brought an enormous health burden. It has been estimated that there were about 20.8 million people in China who had T2DM in the year 2000, and the number of patients with T2DM will double in 2030 [3]. The direct medical costs of T2DM and its complications in China were estimated to be 47.2 billion USD in 2030 [4]. ...
Article
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Background: Type 2 diabetes mellitus (T2DM) and thyroid dysfunction (TD) are two common chronic endocrine disorders that often coexist. Folate deficiency has been reported to be related with the onset and development of T2DM. However, the relationship between folate deficiency and TD remains unclear. This study aims to investigate the association of serum folate with TD in patients with T2DM. Methods: The study used data on 268 inpatients with T2DM in the Beijing Chao-yang Hospital, Capital Medical University from October 2020 to February 2021. Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and serum folate were measured with chemiluminescence immunoassay (CLIA), and folate deficiency was defined as a serum folate concentration < 4.4 ng/mL. Ordinary least squares regression models were used to assess the association of serum folate with TSH concentration. Multivariable logistic regression models were performed to explore the correlation of folate deficiency and the risk for elevated TSH. Results: 15.3% of T2DM patients had TD. Among those patients with TD, 80.5% had elevated TSH. Compared with the normal-TSH and low-TSH groups, the prevalence of folate deficiency was significantly higher in the elevated-TSH group (P < 0.001). Serum folate level was negatively associated with TSH (β=-0.062, 95%CI: -0.112, -0.012). Folate deficiency was associated with the higher risk for elevated TSH in patients with T2DM (OR = 8.562, 95%CI: 3.108, 23.588). Conclusions: A low serum folate concentration was significantly associated with a higher risk for elevated TSH among T2DM patients.
... [2] Increasing urbanization, an aging population, obesity, and physical inactivity are all factors contributing to the global rise in diabetes. [4] Individuals with impaired fasting glucose (IFG) have been labeled as having prediabetes, indicating a relatively high risk of developing diabetes in future. IFG should not be regarded as a separate clinical entity, but rather as a risk factor for diabetes and cardiovascular disease (CVD). ...
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Background Diabetes is a major health concern that has grown to alarming proportions. With more than 500 million sufferers globally, diabetes is one of the most prevalent metabolic diseases. The aim of the study is to find the prevalence of impaired fasting glucose (IFG) and undiagnosed diabetes mellitus (DM) in patients presented to our outpatient department at Mogadishu Somali Turkey Training and Research Hospital. Methods In this cross-sectional study conducted in the largest referral hospital in Mogadishu Somalia, all adult patients who volunteered to give consent have participated in the study. We excluded pregnant women, individuals taking medications that could affect glucose metabolism (e.g., steroids, beta-blockers, and thiazide diuretics), and confirmed diabetic patients from our study. Results Seven hundred and twenty-two adults with a mean age of 42.85 ± 18.23 years were included. Most of the participants were female 432 (59.8%), aged 20–40 years 329 (45.6%). The prevalence of IFG was common among males (22.4%) and those 60 years and above (30.6%), while the prevalence of undiagnosed DM was high among males (9.7%), aged 40–60 years (13.4%). In the bivariate analysis, total cholesterol, high-density lipoprotein, triglycerides, systolic blood pressure, and comorbidities were found to be significantly associated with the prevalence of IFG in all age groups. Conclusions IFG was common among outpatient adults. Increased urbanization, the rise of the middle class, and population aging will lead to considerable rises in IFG, undiagnosed diabetes, and diabetes in Somalia in the next years. To limit the growth of diabetes in Somalia, public health interventions must be implemented soon. Promoting the health system and providing education can help.
... Diabetes is a chronic disease with an inadequate ability to regulate blood glucose levels. Long-term hyperglycemia can cause severe damage to organs, such as the heart, blood vessels, eyes, kidneys, and nerves, leading to a higher risk of premature death [1][2][3][4][5]. While there is no cure for diabetes, blood glucose level management can significantly reduce the health risks [6]. ...
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Non-enzymatic sensors with the capability of long-term stability and low cost are promising in glucose monitoring applications. Boronic acid (BA) derivatives offer a reversible and covalent binding mechanism for glucose recognition, which enables continuous glucose monitoring and responsive insulin release. To improve selectivity to glucose, a diboronic acid (DBA) structure design has been explored and has become a hot research topic for real-time glucose sensing in recent decades. This paper reviews the glucose recognition mechanism of boronic acids and discusses different glucose sensing strategies based on DBA-derivatives-based sensors reported in the past 10 years. The tunable pKa, electron-withdrawing properties, and modifiable group of phenylboronic acids were explored to develop various sensing strategies, including optical, electrochemical, and other methods. However, compared to the numerous monoboronic acid molecules and methods developed for glucose monitoring, the diversity of DBA molecules and applied sensing strategies remains limited. The challenges and opportunities are also highlighted for the future of glucose sensing strategies, which need to consider practicability, advanced medical equipment fitment, patient compliance, as well as better selectivity and tolerance to interferences.
... Type-2 Diabetes Mellitus (T2DM) is an ever-growing issue globally and is considered to have reached the status of a global pandemic in the 21st century (Poznyak et al., 2020). Associated CVDs is the primary contributor to mortality amongst diabetes patients (Ginter and Simko, 2012). There is a mutual 'Casual-Effect' relationship between ACVD and T2DM: on one side, the establishment of diabetes leads to a number of microvascular complications (such as nephropathy, retinopathy, and neuropathy), as well as contributing to greater macrovascular complications (including atherosclerosis, which may ultimately lead to the forementioned CVDs). ...
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Atherosclerosis is a progressive, multifactorial inflammatory, and dyslipidaemic disease, responsible for the majority of cardiovascular diseases globally. The chronic inflammation is the main driver of the initiation and progression of such disease, as a result of an imbalanced lipid metabolism and an ineffective immune response to attenuate the inflammatory component. The importance of inflammation resolution is being increasingly recognised in atherosclerosis and cardiovascular disease. It has a complex mechanism consisting of multiple stages, including restoring an effective removal of apoptotic bodies (efferocytosis) and their degradation (effero-metabolism), a macrophage phenotype switching towards resolving phenotypes, and the promotion of tissue healing and regeneration. The low-grade inflammation associated with atherosclerosis development is a driving force in disease exacerbation, and hence inflammation resolution is a key area of research. In this review, we explore the complex disease pathogenesis and its many contributing factors to gain a greater understanding of the disease and identify the current and potential therapeutic targets. First-line treatments and their efficacy will also be discussed in detail, to highlight the emerging field of resolution pharmacology. Despite the great efforts made by current gold-standard treatments, such as lipid-lowering and glucose-lowering drugs, they remain ineffective at tackling residual inflammatory risk and residual cholesterol risk. Resolution pharmacology represents a new era of atherosclerosis therapy, as endogenous ligands associated with inflammation resolution are exploited for their pharmacological benefits in a more potent and longer-acting manner. Novel FPR2-agonists, such as synthetic lipoxin analogues, provide an exciting new approach to enhance the pro-resolving response of the immune system and subsequently end the pro-inflammatory response to allow for an anti-inflammatory and pro-resolving environment for tissue healing, regeneration, and return to homeostasis.
... Being overweight, a lack of physical activity, and a vitamin D deficiency are all the main risk factors for the initiation and progression of T2DM [8]. ...
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Diabetes mellitus (DM) is a metabolic disorder majorly arising from the pathophysiology of the pancreas manifested as a decline in the insulin production or the tissue’s resistance to the insulin. In this research, we have rationally designed and synthesized new succinimide–thiazolidinedione hybrids for the management of DM. In a multistep reaction, we were able to synthesize five new derivatives (10a–e). All the compounds were new containing a different substitution pattern on the N-atom of the succinimide ring. Initially, all the compounds were tested against the in vitro α-glucosidase, α-amylase, PTP1B, and DPP4 targets. In all of these targets, the compound 10d was observed to be the most potential antidiabetic agent. Based on this, the antidiabetic activity of the compound 10d was further investigated in experimental animals, which overall gave us encouraging results. The molecular docking studies of the compound 10d was also performed against the target enzymes α-glucosidase, α-amylase, PTP1B, and DPP4 using MOE. Overall, we observed that we have explored a new class of compounds as potential antidiabetic agents.
... Diabetes is considered one of the major global epidemics of the 21st century and a public health issue 1,2 . According to the Brazilian Diabetes Society (Sociedade Brasileira de Diabetes, SBD), more than 13 million people live with the disease in Brazil, which corresponds to 6.9% of the population 3 . ...
... 3 In T2D, the body cannot use insulin effectively, and insulin resistance develops as blood glucose levels rise. 4 The insulin injections, and the cost they incur, are very irritating for patients. 1 No exact cause has been found to justify how the disease occurs. ...
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Background: In the realm of diabetes treatment, various strategies have been tried, including islet transplantation and common drug therapies, but the limitations of these procedures and lack of responsive to the high number of patients have prompted researchers to develop a new method. In recent decades, the use of stem cells and three-dimonsional (3D) scaffold to produce insulin-secreting cells is one of the most promising new approaches. Meanwhile, human-induced pluripotent stem cells (iPSCs) propose due to advantages such as autologousness and high pluripotency in cell therapy. This study aimed to evaluate the differentiation of iPSCs into pancreatic islet insuli-producing cells (IPCs) on Silk/PES (polyethersulfone) nanofiber as a 3D scaffold and compare it with a two-dimonsional (2D) cultured group. Methods: Investigating the functional, morphological, molecular, and cellular characteristics of differentiated iPSCs on control cultures (without differentiation medium), 2D and 3D were measured by various methods such as electron microscopy, Q-PCR, immunofluorescence, western blot, and ELISA. Results: This investigation revealed that differentiated cells on the 3D Silk/PES scaffold expressed pancreatic specific-markers such as insulin and pdx1 at higher levels than the control and 2D groups, with a significant difference between the two groups. All results of Q-PCR, immunocytochemistry, and western blot showed that IPCs in the silk/PES 3D group was more efficient than in the 2D group. In the face of these cases, the release of insulin and C-peptide in response to several concentrations of glucose in the 3D group was significantly higher than in the 2D culture. Conclusion: Finally, our findings displayed that optimized Silk/PES 3D scaffolds can enhance the differentiation of IPCs from iPSCs compared to the 2D culture group.
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Diabetes is a chronic health condition affecting millions globally, causing severe complications and burdening healthcare systems. Current machine learning methods for diabetes prediction face challenges such as data imbalance, limited generalizability, and computational inefficiency. This study proposes a novel method that combines K-Nearest Neighbors (KNN), clustering techniques, Synthetic Minority Over- sampling Technique (SMOTE), and Random Forest for outcome classification to address these issues. The PIMA Indian Diabetes Dataset was used to evaluate the approach, achieving accuracy of 87.50%. However, the study has limitations, such as dependency on specific datasets and computational complexity. Future work will focus on validating the method across diverse datasets, optimizing computational efficiency, and developing real-time prediction capabilities.
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Background A pivotal impetus has led to the development of numerous small molecules to develop therapeutic strategies for type 2 diabetes. Novel heterocyclic derivatives are now available with expansive pharmacological activity designed specifically to activate Glucokinase (GK) in the body. This target is of particular significance in antidiabetic drug design since it is a newly validated target. Individuals with type 2 diabetes are unable to maintain blood glucose homeostasis due to impaired glucokinase function. The novel approach to managing type 2 diabetes relies on utilizing heterocyclic derivatives to activate the GK enzyme, also known as a metabolic enzyme. Objective In this research endeavor, the primary objective was to improve drug delivery while minimizing adverse effects by using molecules that activate glucokinase Methods There are 53,000 compounds included in Maybridge's online repository, which has been subjected to rigorous scrutiny. Eight two compounds that encompass the specific oxadiazole core were selectively extracted from this extensive collection. ChemBioDraw Ultra was used for structural drawing, and AutoDock Vina 1.5.6 was used to perform docking analysis. For the online prediction of log P, the SwissADME algorithm was employed. A PKCSM software program was used to predict toxicity for leading compounds. Results Among all of the compounds, AD80 and AD27 displayed the highest affinity for GK receptors. These compounds, by adhering to Lipinski’s Rule of Five, exhibited good absorption and excretion profiles through the gastrointestinal (GI) tract. Lipinski’s Rule of Five refers to physicochemical properties that favor good oral bioavailability, and these specifications are zero to five hydrogen bond donors, zero to ten hydrogen bond acceptors, molecular weight below 500, and log P no more than five. These criteria ensure that the compounds of the invention have acceptable solubility and permeability, which are vital prerequisites when given orally, to be absorbed via the gastrointestinal wall, metabolized, and found in the urine. Therefore, the chance of drug candidates exhibiting favorable pharmacokinetic characteristics is increased, enhancing their chances of being developed for oral administration. In comparison with standard drugs Dorzagliatin as a glucokinase activator (GKA) and MRK (co-crystallized ligand), these compounds exhibit no skin sensitization, AMES toxicity, or hepatotoxicity. Conclusion The recently designed lead molecules exhibit an improved pharmacokinetic profile, enhanced binding affinity, and minimal toxicity based on the computational study, potentially making them suitable candidates for further optimization as glucokinase activators.
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Diabetes mellitus (DM) is a metabolic disorder and is responsible for the death of more than 4.2 million people in 2019. Synthetic drugs for DM like metformin have been reported to induce numerous complications and side effects. Reports suggested that essential plant oil has been used as an herbal remedy to lower blood glucose levels. Essential oils (EOs) are complex combinations of small molecules obtained from plants via the process of steam distillation and several solvents. EOs have already shown great efficacy as antimicrobials, anti-inflammatory, hepatoprotective, and anti-hypertensive. This review aims to summarize some potential EOs that have been reported to have anti-diabetic activity both in preclinical and clinical aspects while summarizing the probable mechanism of action. The authors went through a vast number of articles from various scientific databases like Google Scholar, PubMed, and Web of Science. It was found that EO from a total of 20 plants has been pre-clinically investigated to have anti-diabetic potential. Besides this, clinical studies have reported the antidiabetic efficacy of EOs from Nigella sativa and Cuminum cyminum at different concentrations. Bioactive phytoconstituents like carvacrol, thymol, α- pinene, via . obtained from EOs ameliorate DM by inhibiting α-GLUC, α-amylase, lipase enzymes and increasing GLUT-4 expression, AKT phosphorylation, via . Although fewer in number, EOs from plant sources have demonstrated significant efficacy in DM. Proper elucidation of the anti-diabetic efficacy of the EOs may open up new avenues for drug discovery and development subjected to clinical studies.
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A BSTRACT Background Type 2 diabetes mellitus (T2DM) is a major lifestyle disorder with multiple systemic complications. Although conventional treatments have been able to combat the symptoms and complications, it has not been able to provide long-lasting control, hence yoga is considered more effective and alternate method of controlling diabetes mellitus. Objectives The objective of this study was to evaluate the effect of yoga protocol on heart rate variability (HRV), glycemic control, and anthropometric parameters in T2DM individuals. Materials and Methods This is a randomized, comparative study design. A total of 100 participants who met the inclusion criteria were randomly allocated into two groups, the test group ( n = 50) received yogic protocol along with pharmacological treatment and the control group ( n = 50) was on conventional treatment with regular activities for 90 days. The pre­post assessments of HRV, anthropometric measurements, and blood samples were collected at baseline and after 3 months. Data were analyzed using SPSS version 20.0. Results The experimental group showed significant decrease in blood pressure, heart rate, low frequency (LF), LF/HF, blood glucose, HbA1c and anthropometric parameters as compared to control gorup. However, there was no significant effect of yoga therapy on waist-hip ratio. Conclusion The result of the present study demonstrated that yoga is effective in reducing blood glucose levels in patients with T2DM. Hence, the given specific yogic intervention can be clinically used in the management of T2DM.
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The growing prevalence of diabetes has necessitated the development of effective digestive blueprints to increase blood glucose levels and improve overall well-being. This study aimed to determine the impact of various dietary elements and abstinence from food patterns on glycemic control in diabetic inmates. Specifically, it tests the parts of hydrocarbons, glycemic impact, glycemic load, glycemic index, and the ability of the Mediterranean diet to consume diabetes. The research methodology involved an inclusive composition review and meta�reasoning of the existing studies that concentrated on these factors. Data were obtained from dispassionate tests, practical studies, and digestive directions written inpeer�reviewed journals. The verdicts indicate that diets high in complex carbohydrates and texture, accompanied by a reduced glycemic index and glycemic load, are advantageous in controlling blood glucose levels. The Mediterranean diet, resulting from the extreme use of products that produce whole grains and healthy fats, is specifically productive for reconstructing glycemic control and lowering cardiovascular risk determinants. Furthermore, the study highlights the significance of the individualized ability to consume pieces of advice to establish the glycemic reaction of various cookings, seeing the variability in individual metabolic reactions. The results imply that merging these digestive elements into regular food planning can considerably improve diabetes administration and overall well-being
Chapter
Diabetes is a multifaceted disease characterized by several comorbidities and complications. Patients with lower extremity complications, i.e., peripheral vascular disease and ulcerations, may also suffer from chronic renal disease, cardiac disease, or gastrointestinal disturbances which will all affect the management of their foot problem. For this reason, a multidisciplinary team to manage these comorbid complications is essential even when patients are admitted for seemingly unrelated conditions. This chapter will begin with a historical perspective of the team approach as developed at the New England Deaconess Hospital and will then proceed to the currently prevailing concepts and evidence for the establishment of a successful foot care unit to manage these diabetic lower extremity conditions.
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There is growing evidence indicating the substantial contribution of man-made products to an increase in the risk of diseases of civilization. In this article, the Belgian Scientific Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) Committee gives a critical view on the working of REACH. The current regulatory framework needs to further evolve taking into account data generated using modern science and technology. There is a need for improved assessment process not only before but also after entering the market. Objectivity, transparency, and the follow-up after market access can be optimized. Additionally, no guidance documents exist for regulation of mixture effects. Further, the lengthiness before regulatory action is a big concern. Decision-making often takes several years leading to uncertainties for both producers and end users. A first proposed improvement is the implementation of independent toxicity testing, to assure objectivity, transparency, and check and improve compliance. A “no data, no market” principle could prevent access of hazardous chemicals to the market. Additionally, the introduction of novel testing could improve information on endpoints such as endocrine disrupting abilities, neurotoxicity, and immunotoxicity. An adapted regulatory framework that integrates data from different sources and comparing the outputs with estimates of exposure is required. Fast toxicology battery testing and toxicokinetic testing could improve speed of decision-making. Hereby, several improvements have been proposed that could improve the current REACH legislation.
Chapter
This chapter covers the development of closed-loop insulin delivery systems known as artificial pancreas systems (APSs). These systems can be either electronics-based or electronics-free, and there is a continuous drive to make them both wearable and user-friendly. First, we outline the development and validation status of electronics-based APSs. Then, we summarize the growing research effort to develop electronics-free, chemically-controlled APSs, with particular emphasis on ongoing efforts to make them wearable. We also discuss current challenges, possible solutions, and future perspectives based on promising results from a recent clinical trial.
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A BSTRACT Background and Objective The treatment of elderly people who have developed Type II diabetes is a major challenge. Therefore, this study was conducted to ascertain the drug prescription pattern and the adverse effects of drugs in a tertiary care hospital. Methodology This was a cross-sectional, observational study. This study was carried out on 164 elderly patients with diabetes mellitus attending inpatient and outpatient of the institute. This study assesses the prescribing pattern of antidiabetic drugs and adverse drugs reaction to the drugs administered. Naranjo-Algorithm Probability of American depositary receipt (ADR) scale and WHO prescribing indicators were used for assessment. This study also identifies the drug utilization in diabetic patients associated with other co-morbidities. Results Mean age of the patient was 72.5 in both inpatient and outpatient and male:female ratio among inpatient and outpatient 1.5:1 and 1:1.3, respectively. Metformin (biguanide) was the most commonly prescribed antidiabetic drug and was followed by glimepiride. Insulin was used in 65% of inpatient. Potential drug-drug interactions were noted in 71% of inpatient and 50.8% of outpatient. The incidence of ADR observed in this study was3.6%. Conclusion Metformin and glimepiride were the most common drugs used in both inpatient and outpatient groups. Human regular insulin analog was commonly used in both patients group. The poor reporting in pharmacovigilance although mandated by the Indian Council of Medical Research is falling short; in preempting ADR. Effective pharmacovigilance will improve the quality of life in geriatric patients and would help the treating physicians to steer towards safe and effective healthcare.
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The consumption of probiotics protects pancreatic β‐cells from oxidative damage, delaying the onset of type 2 diabetes mellitus (T2DM) and preventing microvascular and macrovascular complications. This study aimed to evaluate the antidiabetic activity of CDE fermented by Lactobacillus casei (ATCC 39539) (LC) in alloxan‐induced diabetic rats. The oxidative stress identified by catalase (CAT), serum AST, ALT, ALP, creatinine, urea, and uric acid were measured. The chemical profiles of the plant extract and the fermented extract were studied using HPLC/MS. The potential of the compounds towards the binding pockets of aldose reductase and PPAR was discovered by molecular docking. A significant reduction in fasting blood glucose in alloxan‐treated rats. The CAT showed a significant decrease in diabetic rats. Also, serum AST, ALT, ALP, creatinine, urea, and uric acid were significantly decreased in the mixture group. Mild histological changes of pancreatic and kidney tissues suggested that the mixture of probiotics and cleome possesses a marked anti‐diabetic effect. Overall, the study suggests that the combination of Cleome droserifolia fermented by Lactobacillus casei exhibits significant antidiabetic activity (p‐value=0.05), reduces oxidative stress, improves lipid profiles, and shows potential for the treatment of diabetes.
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We studied the effect of a dietary supplement on blood glucose. This prospective, single-arm, unblinded clinical interventional study investigated the impact of a nutritional supplement combination on fasting glucose and glycated hemoglobin (A1c) levels, which were measured before and after the intervention. The supplement, which consisted of organic mulberry leaf extract, LactoSpore probiotics, and Fenumannan prebiotic, was given to adult (age ≥21 years) prediabetics and adults with type 2 diabetes (A1c >5.60 mg/dL). The study protocol comprised six phases including initial and final tests for fasting glucose and A1c, and a 12-week period of supplement administration. The statistical analyses were carried out using SPSS and Intellectus Statistics. A total of 24 participants completed the study. A reduction of 0.94% in the A1c level and 40.52% in the fasting glucose level were found. These preliminary findings suggest that the nutritional supplement combination might be clinically effective in reducing fasting glucose and A1c in prediabetic adults and those with type 2 diabetes.
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Background Lifestyle changes involving diet and exercise are recommended for patients diagnosed with obesity and type 2 diabetes mellitus (T2DM). However, the effectiveness of combining aerobic exercise and diet (AEDT) in obese T2DM patients has not been studied in a systematic review and meta-analysis. Therefore, the purpose of this review was to systematically evaluate the effects of AEDT on individuals with obesity and T2DM. Methodology: A comprehensive search of the PubMed, Web of Science, Scopus, Science Direct, Cochrane, and Google Scholar databases was conducted for this meta-analysis. Statistical analysis was performed using the random effects model for continuous variables, and the results were presented as mean differences (MD) or standardized mean difference (SMD) with 95% confidence intervals (CI). Results Out of the 16,129 studies identified, 15 trials involving a total of 2,454 patients were included in the meta-analysis. The findings revealed significant reductions in body mass index, body weight, waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride levels, glycated hemoglobin (HbA1c), fasting blood glucose, fasting plasma insulin, leptin, interleukin-6 (IL-6), and C-reactive protein (CRP) (p < 0.005) compared to the standard treatment (ST) group. On the other hand, there was a significant increase in adiponectin levels in response to AEDT (p < 0.005). However, when evaluating obesity-related factors, no significant differences were observed between the AEDT and ST groups for parameters such as fat mass, hip circumference, waist-to-hip ratio, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and tumor necrosis factor-alpha (TNF-α) (p > 0.05). Conclusions AEDT could be considered an additional therapy in conjunction with conventional clinical treatments due to its significant positive impact on obese T2DM patients. Nevertheless, further robust evidence is necessary to determine whether AEDT is an effective intervention for reducing the need for aggressive pharmacological approaches in individuals with obesity and T2DM.
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Aim: To enrich the pool of α-amylase inhibitors to manage Type 2 diabetes. Methods: Synthesis, conformational study, α-amylase inhibitory action and various in silico studies of novel N'-(arylbenzylidene)-2-(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d]imidazol-1-yl)acetohydrazides carried out. Results: Compound H6 demonstrated the highest activity (IC50 = 0.0437 μmol mL-1) among the tested compounds. Structure-activity relationship study suggested that variable substitution at the aryl ring has a pivotal role in determining the inhibitory action of tested compounds. Docking simulations of the most active compound (H6) confirmed its interaction potential with active site residues of A. oryzae α-amylase. The root-mean-square deviation fluctuations substantiated the stability of protein-ligand complex. Absorption, distribution, metabolism and excretion prediction revealed optimal values for absorption, distribution, metabolism and excretion parameters. Conclusion: The developed molecules could be beneficial for the development of novel α-amylase inhibitors to treat Type 2 diabetes.
Article
PurposeThis current research study was designed to investigate beneficial effects of R. humilis (Rivina humilis) against streptozotocin-induced diabetic rats.Methods The R. humilis ethanol extract was prepared using soxhlet and its phenol content was determined. The type-2 diabetes was induced in rats by giving fructose mixed drinking water and single dose of streptozotocin. Oral glucose tolerance test (OGTT) was performed after 72 h of streptozotocin to check ability of extract to utilize oral glucose load with 2 h. The extract was also tested for its potentials to reduce blood glucose (BGL) and diabetic complications by administering to diabetic rats for 21 days. Blood glucose was determined on day 1, 7, 14 and 21. At 21st day, blood samples were collected from experimental rats were euthanized to collect pancreas and liver. Liver and kidney function tests, HbAc1 and lipid profile was established from blood samples. Pancreas was subjected to histopathological examination and liver was used to determine antioxidant enzymes. In vitro study was done to investigate the effect of extract on glucose utilization by rat hemidiaphragm.ResultsIn OGTT, administration of extract could stimulate glucose utilization which was witnessed by significant BGL reduction at 90 and 120 min in therapeutic groups compare to diabetics. In chronic study, we observed significant reduction in BGL on 21st day and all tests performed to determine liver and kidney function, HbAc1, vitamin E were normal in extract treated groups. There was significant increase in liver antioxidant enzymes in therapeutic groups which revealed regeneration of β-cells in therapeutic groups.Conclusion The results of research demonstrated significant antidiabetic potentials in R. humilis.
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Oxadiazoles, a class of five membered heterocyclic azoles, are considered to be a versatile scaffold and is found to be a core moiety of various pharmaceutically active agents.Oxadiazoles are known to inhibit alpha-amylase and alpha-glucosidase enzyme which is rational approach for selecting oxadiazole as antidiabetic agents in controlling postprandial hyperglycemia in type II diabetes mellitus. They are found to exist in 4 different regioisomeric forms namely 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole and 1,3,4-oxadiazole. Oxadiazoles are known to exhibit a wide range of biological activities and many mono and di-substituted oxadiazoles have been studied for their antihyperglycemic potential. Oxadiazoles have been found to act on various potential targets of the antidiabetic therapy. They are found to elicit hypoglycemic action by different mechanisms like inhibition of digestive enzymes, insulin sensitization, reduction of renal glucose reabsorption, etc. The results of various substituted oxadiazoles studied for their anti-diabetic activity has been reviewed in this article.
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Background: Diabetes mellitus (DM) is a metabolic condition defined by persistent hyperglycemia caused by either insufficient insulin production by the pancreas or inability of peripheral target tissues to respond to normal insulin concentrations. The present study was designed to find the bioactive compounds from the Indian medicinal plants for the treatment of Diabetes mellitus using Virtual screening, Docking and ADMET studies. The 3D structure of phytocompounds was obtained using IMPPAT and PubChem database. The Lipinski rule of five for all the phytocompounds was tested using SwissADME. The sequence of the target protein was retrieved from the UniProt database and modelled using Swiss-Model. The docking studies were performed using PyRx and the results were analyzed using Discovery Studio 2021. Results: The phytocompounds Taraxerol, Obtusifoliol and Kulactone showed very good binding affinity like -9.7, -9.7 and -9.4 Kcal/mol, respectively. Toxicity studies were done for the best-interacted phytocompounds and the results showed that the compounds had very less toxicity. Conclusion: The present study concludes that Taraxerol from Coccinia grandis, Obtusifoliol and Kulactone from Azadirachta indica and may have a potential ability in the treatment of Diabetes Mellitus.
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While epigenetic modifications of DNA and histones play main roles in gene transcription regulation, recently discovered post-transcriptional RNA modifications, known as epitranscriptomic modifications, have been found to have a profound impact on gene expression by regulating RNA stability, localization and decoding efficiency. Importantly, genetic variations or environmental perturbations of epitranscriptome modifiers (that is, writers, erasers and readers) are associated with obesity and metabolic diseases, such as type 2 diabetes. The epitranscriptome is closely coupled to epigenetic signalling, adding complexity to our understanding of gene expression in both health and disease. Moreover, the epitranscriptome in the parental generation can affect organismal phenotypes in the next generation. In this Review, we discuss the relationship between epitranscriptomic modifications and metabolic diseases, their relationship with the epigenome and possible therapeutic strategies.
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Osteocalcin is one of the main organic components of the bone matrix and consists of 49 amino acids excreted from osteoblastic cells in carboxylated and uncarboxylated forms. Carboxylated Osteocalcin belongs to the bone matrix, whereas uncarboxylated osteocalcin (ucOC) is an important enzyme of osteocalcin in the circulatory system. It is an essential protein for balancing the minerals in bones, binding with calcium, and regulating body glucose levels. In this review, we point out the assessment of ucOC levels in type 2 diabetes mellitus. The experimental results that show ucOC controls glucose metabolism are significant because they relate to the current obesity, diabetes, and cardiovascular disease. To confirm that, low serum levels of ucOC were a risk factor for poor glucose metabolism, and further clinical studies are required.
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Background Diabetes type II is one of the most serious metabolic diseases in the world attracting the attention of many researchers who predict that diabetes will be one of the top major causes of disability or death in the coming few decades. To tackle this disease several classes of synthetic molecules were developed to target certain enzymes that are involved in sugar metabolism. Herbal extracts targeting diabetes have witnessed renascence in the last few decades with the introduction of highly effective herbal remedies that effectively regulate sugar levels in the blood. Methods In this work, we studied the interaction of molecules from the Zygophyllum sp. with the main enzymes involved in sugar metabolism (alpha-amylase and DPP-4) using Molecular Operating Environment (MOE) as a molecular docking technique. The choice of Zygophyllum sp. was based on an ethnopharmacological local survey. Results The obtained results showed that myristic acid gave the best score equal to -7.5471 Kcal/mol for alpha-amylase and -9.0457 Kcal/mol for DPP-4. Palmitic acid also gave a good score equal to -7.4528 Kcal/mol with DPP-4. Conclusion Conclusion: The calculated scores of molecules from Zygophyllum sp. were better than those calculated with the known inhibitors. The results demonstrated that many molecules showed good affinity to two important enzymes involved in type II diabetes, suggesting that these molecules may possess potential hypoglycemic and antidiabetic effects. These results added further scientific evidence supporting the folk use of Zygophyllum sp. in targeting diabetes and suggested its potential as a valuable source of antidiabetic drug leads. Result The obtained results showed that myristic acid gave the best score equal to -7.5471 Kcal/mol for alpha-amylase and -9.0457 Kcal/mol for DPP-4. Palmitic acid gave also a good score equal to -7.4528 Kcal/mol with DPP-4.
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The purpose of this study was to examine the association between dietary protein intake and the risk of type 2 diabetes mellitus (T2DM) among a Chinese rural elderly population. We used the demographic and dietary information of adults over age 65 in the Henan Rural Cohort Study to identify and pair 950 T2DM patients with healthy controls in a 1 : 1 matched case-control study. Dietary data was collected through a Food Frequency Questionnaire. A multivariate logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) of T2DM risk according to protein intake. After adjustment for confounding factors, higher intake of total protein was negatively associated with T2DM risk in the total population (extreme-tertile OR=0.75, 95% CI: 0.58-0.93) and women (extreme-tertile OR=0.84, 95% CI: 0.47-0.93). Multivariate-adjusted ORs for the risk of T2DM in the highest compared with lowest tertile of plant protein intake in the total population and in women were 0.86 (95% CI: 0.60-0.84) and 0.58 (95% CI: 0.36-0.95), respectively. Our results suggest that the protein intake, especially plant protein, has a significant association with the risk of T2DM in rural elderly populations, and the sources of protein may be also important in future guidelines.
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Adipose tissue is increasingly recognized as an active endocrine organ with many secretory products and part of the innate immune system. With obesity, macrophages infiltrate adipose tissue, and numerous adipocytokines are released by both macrophages and adipocytes. Adipocytokines play important roles in the pathogenesis of insulin resistance and associated metabolic complications such as dyslipidemia, hypertension, and premature heart disease. Published literature was analyzed with the intent of addressing the role of the major adipose secretory proteins in human obesity, insulin resistance, and type 2 diabetes. This review analyzes the characteristics of different adipocytokines, including leptin, adiponectin, pro-inflammatory cytokines, resistin, retinol binding protein 4, visfatin, and others, and their roles in the pathogenesis of insulin resistance. Inflamed fat in obesity secretes an array of proteins implicated in the impairment of insulin signaling. Further studies are needed to understand the triggers that initiate inflammation in adipose tissue and the role of each adipokine in the pathogenesis of insulin resistance.
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The AMP-activated protein kinase (AMPK) system is a key player in regulating energy balance at both the cellular and whole-body levels, placing it at centre stage in studies of obesity, diabetes and the metabolic syndrome. It is switched on in response to metabolic stresses such as muscle contraction or hypoxia, and modulated by hormones and cytokines affecting whole-body energy balance such as leptin, adiponectin, resistin, ghrelin and cannabinoids. Once activated, it switches on catabolic pathways that generate adenosine triphosphate (ATP), while switching off ATP-consuming anabolic processes. AMPK exists as heterotrimeric complexes comprising a catalytic alpha-subunit and regulatory beta- and gamma-subunits. Binding of AMP to the gamma-subunit, which is antagonized by high ATP, causes activation of the kinase by promoting phosphorylation at threonine (Thr-172) on the alpha-subunit by the upstream kinase LKB1, allowing the system to act as a sensor of cellular energy status. In certain cells, AMPK is activated in response to elevation of cytosolic Ca2+ via phosphorylation of Thr-172 by calmodulin-dependent kinase kinase-beta (CaMKKbeta). Activation of AMPK, either in response to exercise or to pharmacological agents, has considerable potential to reverse the metabolic abnormalities associated with type 2 diabetes and the metabolic syndrome. Two existing classes of antidiabetic drugs, that is, biguanides (for example, metformin) and the thiazolidinediones (for example, rosiglitazone), both act (at least in part) by activation of AMPK. Novel drugs activating AMPK may also have potential for the treatment of obesity.
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There is little research on the association of lifestyle exercise, such as active commuting (walking or biking to work), with obesity, fitness, and cardiovascular disease (CVD) risk factors. This cross-sectional study included 2364 participants enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who worked outside the home during year 20 of the study (2005-2006). Associations between walking or biking to work (self-reported time, distance, and mode of commuting) with body weight (measured height and weight); obesity (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, >or= 30); fitness (symptom-limited exercise stress testing); objective moderate-vigorous physical activity (accelerometry); CVD risk factors (blood pressure [oscillometric systolic and diastolic]); and serum measures (fasting measures of lipid, glucose, and insulin levels) were separately assessed by sex-stratified multivariable linear (or logistic) regression modeling. A total of 16.7% of participants used any means of active commuting to work. Controlling for age, race, income, education, smoking, examination center, and physical activity index excluding walking, men with any active commuting (vs none) had reduced likelihood of obesity (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.33-0.76), reduced CVD risk: ratio of geometric mean triglyceride levels (trig(active))/(trig(nonactive)) = 0.88 (95% CI, 0.80 to 0.98); ratio of geometric mean fasting insulin (FI(active))/(FI(nonactive)) = 0.86 (95% CI, 0.78 to 0.93); difference in mean diastolic blood pressure (millimeters of mercury) (DBP(active)) - (DBP(nonactive)) = -1.67 (95% CI, -3.20 to -0.15); and higher fitness: mean difference in treadmill test duration (in seconds) in men (TT(active)) - (TT(nonactive)) = 50.0 (95% CI, 31.45 to 68.59) and women (TT(active)) - (TT(nonactive)) = 28.77 (95% CI, 11.61 to 45.92). Active commuting was positively associated with fitness in men and women and inversely associated with BMI, obesity, triglyceride levels, blood pressure, and insulin level in men. Active commuting should be investigated as a modality for maintaining or improving health.
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Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. We analyzed 3640 consecutive (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of (18)F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery. Substantial depots of brown adipose tissue were identified by PET-CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher (18)F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P=0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P=0.007). Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.
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The prevalence of obesity has been increasing dramatically in the last decades in the whole world, not only in industrialized countries but also in developing areas. A major complication of obesity is insulin resistance and type 2 diabetes. Diabetes is also rapidly increasing world-wide--reaching a prevalence in adults of approx. 5-6% in Central Europe and in the US, and more than 50% in specific, genetically prone populations. This article reviews pathogenetic mechanisms linking obesity and type 2 diabetes. Emphasis is placed on the observation that excessive amounts of adipocytes are associated with an impairment of insulin sensitivity, a key feature of the "metabolic syndrome". This is a cluster of metabolic abnormalities such as type 2 diabetes, hypertension and dyslipidemia; all of them are enhanced by the presence of visceral (abdominal) obesity and all contribute to the increased cardiovascular risk observed in these patients. Besides release of free fatty acids, adipocytes secrete substances that contribute to peripheral insulin resistance, including adiponectin, resistin, TNF-alpha and interleukin 6. Increased turnover of free fatty acids interferes with intracellular metabolism of glucose in the muscle, and they exert lipotoxic effect on pancreatic beta-cells. The pre-receptor metabolism of cortisol is enhanced in visceral adipose tissue by activation of 11 beta-hydroxysteroid dehydrogenase type 1. A new class of anti-diabetic drugs (thiazolidinediones, or glitazones) bind to peroxisome proliferator activated receptor (PPAR-gamma) and lower thereby plasma free fatty acids and cytokine production in adipocytes, in addition to a decrease of resistin and an increase in adiponectin observed in animals, resulting in an overall increase in insulin sensitivity and in an improvement of glucose homeostasis. However, the first step to avoid insulin resistance and prevent the development of diabetes should be a reduction in body weight in overweight subjects, and an increase in physical activity. There are now three published randomized controlled trials demonstrating that in high risk individuals, life style changes with modest weight lost, associated with diminished fat intake and an increase in fruit and vegetable consumption result in marked inhibition of the transition from the prediabetic state to manifest type 2 diabetes.
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The recent increase in the prevalence of obesity has been associated with a coincident rise in the prevalence of Type 2 diabetes, whereas weight loss has been shown to decrease the risk of Type 2 diabetes. The pathophysiological mechanisms that have been proposed to explain this link are fundamentally concerned with insulin resistance and the decline in pancreatic B-cell function that accompanies an increase in visceral obesity. They involve the rise in the plasma concentrations of free fatty acids (FFAs) that are associated with an increase in fat mass. Elevated levels of FFAs can lead to insulin resistance, and evidence is growing that B-cell function is impaired through lipotoxicity. Factors such as tumour necrosis factor-alpha (TNF-alpha) and adiponectin, released from adipose tissue, can also modulate insulin resistance. Many interventions that are helpful in treating or preventing Type 2 diabetes, such as weight loss and certain pharmacological interventions, reduce circulating FFA concentrations to a greater or lesser extent. Recent study results suggest that peroxisome proliferator-activated receptor (PPAR)gamma agonists have an effect on the development of Type 2 diabetes. However, in light of concerns over the apparent increase in congestive heart failure with PPARgamma agonists, their place in the prevention of Type 2 diabetes remains to be determined.
Overweight and obesity
  • Wpt James
  • R Jackson-Leach
  • C N Mhurdu
  • W.P.T. James
Obesity, fatty tissue and inflammation
  • M Ferencik
  • I Hulin
  • M. Ferencik
AMP-activated protein kinase signaling in metabolic regulation
  • Y C Long
  • J R Zierath
  • Y.C. Long
AMPK: neglected players in type 2 diabetes mellitus
  • R D Pro-Insulin
  • R.D. lele
Prevalence of diabetes. Estimates for the year 2000 and projection for 2030
  • G Roglic
  • A Green
  • G. Roglic
Incretin therapies: Effects beyond glycemic control
  • S Mudaliar
  • S. Mudaliar
Global prevalence of diabetes: estimates for the year 2000 and projections for 2030
  • Who